U0) {U.S CONGRESS. sowie, SE GE AA A RN "QUALITY OF HEALTH CARE—HUMAN EXPERIMENTATION, 1973 HEARINGS BEFORE THE SUBCOMMITTEE ON HEALTH OF THE COMMITTEE ON LABOR AND PUBLIC WELFARE UNITED STATES SENATE ° NINETY-THIRD CONGRESS FIRST SESSION ON S. 974 To amend the Public Health Service Act to provide, in the training of health professionals, for an increased emphasis on the ethical, social, legal, and moral implications of advances in biomedical research and technology S. 878 To amend the Public Health Service Act to provide for restrictions on funds for experimental use S.J. Res. 71 To provide for a study and evaluation of the ethical, social, and legal implications of advances in biomedical research and technology FEBRUARY 23 AND MARCH 6, 1973 DOCUMENTS DEPARTMENT] ~~ PART 2 AUG 2 4 1373 LIBRARY 32 HNIVERSITY OF CALIFORNIA | am fe Printed for the use of the Committee on Labor and Public Welfare _ QUALITY OF HEALTH oa EXPERIMENTATION, 1973 | HEARINGS I BEFORE THE SUBCOMMITTEE ON HEALTH OF THE COMMITTEE ON LABOR AND PUBLIC WELFARE UNITED STATES SENATE NINETY-THIRD CONGRESS FIRST SESSION ON S. 974 To amend the Public Health Service Act to provide, in the training of health professionals, for an increased emphasis on the ethical, social, legal, and moral implications of advances in biomedical research and technology S. 878 To amend the Public Health Service Act to provide for restrictions on funds for experimental use S.J. Res. 71 To provide for a study and evaluation of the ethical, social, and legal implications of advances in biomedical research and technology FEBRUARY 23 AND MARCH 6, 1973 PART 2 2 Printed for the use of the Committee on Labor and Public Welfare U.S. GOVERNMENT PRINTING OFFICE 93-999 O WASHINGTON : 1973 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, D.C. 20402 - Price $2.60 domestic postpaid $2.25 GPO Bookstore COMMITTEE ON LABOR AND PUBLIC WELFARE HARRISON A. WILLIAMS, Jr., New Jersey, Chairman JENNINGS RANDOLPH, West Virginia JACOB K. JAVITS, New York CLAIBORNE, PELL, Rhode Island PETER H. DOMINICK, Colorado EDWARD M. KENNEDY, Massachusetts RICHARD S. SCHWEIKER, Pennsylvania GAYLORD NELSON, Wisconsin ROBERT TAFT, Jk., Ohio WALTER I. MONDALE, Minnesota J. GLENN BEALL, Jg., Maryland THOMAS FF. EAGLIEITON, Missouri ROBERT T. STAFFORD, Vermont ALAN CRANSTON, California HAROLD E. HUGHES, Towa WILLIAM D. HATHAWAY, Maine STEWART LE. MCCLURE, Chief Clerk RoBeRT IX. NAGLE, General Counsel Roy H. MILLENSON, Minority Chief Clerk EUGENE MITTELMAN, Minority Counsel SUBCOMMITTEE ON HEALTH EDWARD M. KENNEDY, Massachusetts, Chairman HARRISON A. WILLIAMS, Ji, New Jersey RICHARD 8S, SCHWEIKER, Pennsylvania GAYLORD NELSON, Wisconsin JACOB K. JAVITS, New York THOMAS I. EAGLETON, Missouri PETER H. DOMINICK, Colorado ALAN CRANNTON, California J. GLENN BEALL, Jr, Maryland HAROLD E. HUGHES, Iowa ROBERT TAFT, Jk., Ohio CLAIBORNE PELL, Rhode Island WALTER FF. MONDALILL, Minnesota LEROY G. GorLbMan, Professional Staff Member Jay B. Currier, Minority Counsel (11) KFae L 35Y¢/ 1973 CONTENTS v. PuBtL CHRONOLOGICAL LIST OF WITNESSES FripAY, FEBRUARY 23, 1973 Brown, Dr. Bertram S., Director, National Institute of Mental Health, accompanied by Dr. John Sherman, Acting Director, National Institutes of Health; Dr. Murray Goldstein, Associate Director, Extramural Pro- grams, National Institute of Neurological Diseases and Stroke (NIH) ; David Kefauver, Assistant Director for Extramural Programs, NIMH; and Dr. Lyle Bivens, Chief, Neuropsychology Section Behavioral Sci- ences Research Branch, NIMH... coo osm moi om me hm sn td rom Andy, Dr. Orlando J., Department of Neurosurgery, University of Mis- BIBRIDDT roi movin coms oi sn 5 ft eet 5 Breggin, Peter R., M.D., Washington, D.C. Heath, Robert G., M.D., professor and chairman, Department of Psy- chiatry /Neurology, Tulane University School of Medicine, New Orleans, TUB mis soo em e Skinner, Prof. B. F., Harvard University Cambridge, Mass______________ Gaylin, Willard, M.D., president, Hastings Institute, Hastings-on-Hud- TUESDAY, MARCH 6, 1973 Kennedy, Hon. Edward M., a U.S. Senator from the State of Massachu- setts, chariman of the Senate Subcommittee on Health, opening state- TIVOTIE ccs sarmmmrmamme mime onto mg gm mm ee, a i Callahan, Daniel, Ph.D. Institute of Society, Ethics, and the Life Sciences, Hastings-on-Hudson, N.Y_____________ Sherman, John, M.D., Acting Director, National Institutes of Health, accompanied by Robert W. Berliner, M.D., Deputy Director of Science, Department of Health, Education, and Welfare _____________________ Thomas, Lewis, M.D., dean and professor of pathology Yale University SCHOOL OF NBIC ITIO reco ce mm mss eo son mm sm om os ts i 0 8 EE tt DeBakey, Michael E., M.D., president, Baylor College of Medicine, Hous- BONY, DR com i oi i i 8 Watson, James D., professor of molecular biology, Harvard University___ STATEMENTS Andy, Dr. Orlando J., Department of Neurosurgery, University of Mis- SHORTING ot SS Sa te a 55 Breggin, Peter R., M.D., Washington, D.C carn nvncanimencmnmmmmn we Brown, Dr. Bertram S., Director, National Institute of Mental Health, ac- companied by Dr. John Sherman, Acting Director, National Institutes of Health; Dr. Murray Goldstein, Associate Director, Extramural Pro- grams, National Institute of Neurological Diseases and Stroke (NTH) : David Kefauver, Assistant Director for Extramural Programs, NIMH ; and Dr. Lyle Bivens, Chief, Neuropsychology Section, Behavioral Sci- ences ResearCh Brafch, NIMH . . owe wm cms mm imo sw mo ————— Callahan, Daniel, Ph. D., Institute of Society, Ethics, and the Life Sciences, BASING RONTTURABON. INV mre mmm msi ois m5 mm 5058 56 i DeBakey, Michael E., M.D., president, Baylor College of Medicine, Hous- BON, TLIO... cc iri cme isos iio si So se et pe ee ee 0 0 0 Gaylin, Willard, M.D., president, Hastings Institute, Hastings-on-Hud- IE NN ee oe, i 0 Se Heath, Robert G., M.D., professor and chairman, Department of Psy- chiatry/Neurology, Tulane University, School of Medicine, New Orleans, La em Page 338 348 357 363 369 373 481 482 504 511 348 357 338 482 504 373 363 Iv Kennedy. Hon. Edward M., a U.S. Senator from the State of Massachu- setts, chairman of the Senate Subcommittee on Health, opening state- Page NOME cone ao oso eo SE EE BTR i te ER 481 Sherman, John, M.D., Acting Director, National Institutes of Health, accompanied by Robert W. Berliner, M.D., Deputy Director of Science, Department of Health, Education, and Welfare______________________ 487 Skinner, Prof. B. F., Harvard University, Cambridge, Mass____________ 369 Thomas, Lewis, M.D., dean and professor of pathology, Yale University School of Medicine 496 Watson, James D., professor of molecular biology, Harvard University__ 511 Prepared statement (with additional information) _______________ 516-791 ADDITIONAL INFORMATION Articles, publications, ete. : “A Law To Prohibit Nonmedical Brain Surgery,” by Peter Rober Breggin 435 “Lobotomies Are Still Bad Medicine,” by Peter R. Breggin, M.D. published in Medical Opinion, March 1972....cocvmmmemmmesmmmmins 387 “Medical Research Is Hurting,” by Michael E. DeBakey and Lois DeBakey, from Saturday Review, October 16, 1971______________ 430 “New Information in the Debate Over Psychosurgery,” by Peter Breggin, from the Congressional Record, Extensions of Remarks, ON ATR BO, NT. oe comm com mm ln, i io 437 “Progress of Medical Science,” from the American Journal of the Medical Sciences, August 1966 _____ 417 “Project To Examine Psychiatric Technology,” the, by the Washington School of Psychiatry, Washington, D.Cacauuccvnsnnacanwannens 383 “Psychological Aspects of Diencephalotomy,” by M. F. Jurko, Ph. D., and O. J. Andy, M.D., from the Department of Neurosurgery, Univer- sity of Mississippi Medical Center, Jackson, Miss________________ 402 “Return of Lobotomy and Psychosurgery" : Article by Hon. Cornelius E. Gallagher, of New Jersey, in the House of Representatives (from the Congressional Record, February 24. 1972) ___ 454 Copyright 1972, by Peter Breggin___________ __________________ 455 “Rorschach Study of Perceptual Changes Following Diencephalotomy,” by Marion F. Jurko, I’h. D., and Orlando J. Andy, M.D., from the American Journal of Psychiatry 121: 487490, 1964 _____________ 394 “Senate Urged To Kill ‘Brain’ Study,” by Jean Dietz, Globe staff, from the Boston Sunday Globe, September 24, 1972____________________ 436 “Thalamotomy in Hyperactive and Aggressive Behavior,” by O. J. Andy, M.D., Department of Neurosurgery, University of Mississippi Medical Center, Jackson, Miss. _____ 398 “Thalamotomy for Hyperresponsive Syndrome,” by Orlando J. Andy, M.D. and Marion EF. Jurko. Ph. D., from Psychosurgery, 1972_____ 408 “Second Wave,” by Peter Roger Breggin, M.D. from Mental Hygiene, NA El FT Dn oc mee ccsmmmcomm mm mcm gm om cm tc 2 em 390 “Treatable Violence,” by Barry M. Maletzky, M.D., chief, Department of Neuropsychiatry, U.S. Lyster Army Hospital, Fort Rucker, Ala., from Resident and Staff Physician, February 1973. ccemcccnnauaa 424 Memorandum to: Leonard, Jerris, Director of the Law Enforcement Assistance Adminis- tration of Justice, from Ann Sadowsky. National Institute for Law Enforcement and Criminal Justiee cova cinco csi woman 385 QUALITY OF HEALTH CARE—HUMAN EXPERIMENTATION, 1973 FRIDAY, FEBRUARY 23, 1973 U.S. SENATE, SuBcoMMITTEE ON HEALTH oF THE CoMMITTEE ON LABOR AND PUBLIC WELFARE, Washington, D.C. The subcommittee met, pursuant to notice, at 10 a.m. in room 4232, Dirksen Senate Office Building, Senator Edward M. Kennedy (chair- man of the subcommittee) presiding. Present : Senator Kennedy. Committee staff members present: LeRoy G. Goldman, professional staff member and Jay B. Cutler, minority counsel. Senator KenNepy. The subcommittee will come to order. The nature and functioning of the human mind has fascinated scientists for centuries. In recent years they have begun to understand that this is the basis of behavior and have developed tools and tech- niques to modify and control it. There are those who say the new behavioral research will enable us to realize our full potential as a nation and as a people. There are others who believe that the new technology is a threat to our most cherished freedoms. It is important for the people of this Nation to begin to understand the nature and implications of behavioral research. Scientists have developed some very powerful tools, tools that have the potential to affect, and perhaps even alter, each of our lives. We must as a society decide how these tools are to be used. Few areas of biomedical research have been as controversial as the behavioral research we are to hear about today. Some Federal scien- tists recently circulated a petition urging the National Institutes of Health and the National Institute of Mental Health, to refuse to sponsor research into psychosurgery. It is our hope that today’s hearing will air both sides of the contro- versy and help us as a society come to understand and master this new technology so as not to become the victims of it. Our first witnesses this morning are Dr. Bertram S. Brown, Direc- tor of the National Institute of Mental Health, accompanied by John Sherman, Acting Director of the National Institutes of Health, and a group of other gentlemen. (337) 338 STATEMENT OF DR. BERTRAM S. BROWN, DIRECTOR, NATIONAL INSTITUTE OF MENTAL HEALTH, ACCOMPANIED BY DR. JOHN SHERMAN, ACTING DIRECTOR, NATIONAL INSTITUTES OF HEALTH; DR. MURRAY GOLDSTEIN, ASSOCIATE DIRECTOR, EXTRAMURAL PROGRAMS, NATIONAL INSTITUTE OF NEURO- LOGICAL DISEASES AND STROKE (NIH): DAVID KEFAUVER, ASSISTANT DIRECTOR FOR EXTRAMURAL PROGRAMS, NIMH; AND DR. LYLE BIVENS, CHIEF, NEUROPSYCHOLOGY SECTION, BEHAVIORAL SCIENCES RESEARCH BRANCH, NIMH Dr. Browx. Good morning, Senator. It is a pleasure to see you for the second time. since I began my day at 7 a.m., hearing that you would be on morning television discussing the issues we have before us today. I welcome this opportunity to discuss with you. in what I hope 1s a balanced and rational manner, an issue which has served as a lightning rod for highly emotional responses on both sides of the issue: Should psychosurgery be encouraged or even permitted as a technique to bring about desired therapeutic changes in a patient's behavior. Dr. John Sherman. Acting Director of the National Institutes of Health, is with me. To his left is Dr. Murray Goldstein, Associate Director for Extramural Programs at the National Institute of Neuro- logical Diseases and Stroke at NII : to my immediate right is Dr. Lyle Bivens. who is Chief of the Neuropsychology section of the Be- havioral Sciences Research Branch of NIMIT: and to his right is Mr. David Kefauver, who is Assistant Director for Extramural Pro- grams at NTMI: and with us is Dr. Donald Chalkley. who is the head of the Institutional Relations Branch at NTH. the branch that is charged with protecting patients’ rights in DIHEW-supported re- search. These gentlemen have a long-standing concern with the topics we will be discussing today and will be glad to answer any questions vou may have from the perspective of their programs. Let me start by placing our dilemma in context. Medical science is a dynamic. ever-changing body of substantive knowledge, Sometimes. new information descends on the scientific community like the raisins in a Christmas pinata, or the snow in this morning's traflic. in a form and at a pace that defies judicious contem- plation and leisurely digestion. This is not entirely a modern phenom- enon. The Emperor Napoleon Bonaparte is reputed to have turned down an offer of a newly discovered medical treatment with the pointed comment: 1 do not want two discases—one nature-made. one doctor-made.™ In the intervening vears. the march of medical knowl- edge has certainly expanded the possibilities of “doctor-made” disease. Every medical man has been indoerinated carly in the course of his training with the maxim. “Above all. do no harm.” The Declaration of Geneva of the World Medical Association in 1964 further binds the doctor with the words: “The health of ny patient will be my first consideration.” } On the other hand. the World Medical Association recognized that it may be equally immoral to withhold from human subjects the re- 339 sults of laboratory experiments with high potential for the further- ance of scientific knowledge to “help suffering humanity.” Let us be clear about the kind of procedure we are talking about— and what is not properly encompassed by the term “psychosurgery.” Psychosurgery can best be defined as a surgical removal or destruc- tion of brain tissue or the cutting of brain tissue to disconnect one part of the brain from another, with the intent of altering behavior, even though there may be no direct evidence of structural disease or damage mn the brain. The surgical treatment of epilepsy, while in one sense a form of psychosurgery since behavioral symptoms are altered, should be ex- cluded from this discussion when the disease can be clearly diagnosed and there is convincing evidence that epilepsy is caused by organic pathology in the brain. Some investigators have suggested that certain episodic behavioral manifestations may appear as a symptom of epilepsy. The ethical as- pects of work in this borderline area are obviously troublesome, and I will return to this subject later. Psychosurgery is based on the theory that the mental states of man—including the emotions of love, fear, and hate—are related to chemical and electrical activities in the billions of nerve cells that comprise the central nervous system. If normal behaviors are produced or controlled by physical events occurring within the brain, then, reason the scientists, pathological behaviors must also be the result of these same physical processes operating in pathological ways. If one could pinpoint accurately the precise locus of the center in the brain that stimulates the abnormal behavior or the tract through which it is disseminated and then remove or destroy only that portion of the brain, the patient could be relieved of his pathology over which he had no control and be returned to the community as a functioning, respon- sible member of society. Senator KenNEepy. Can you do that accurately ? Dr. Brown. That is the basic issue Senator Kexnyepy. Well, that is your conclusion ? Dr. Brow~. In many situations, it can. In the majority of situa- tions, the very nature of the research is to determine 1f there is such a locus; and this is the dilemma we are faced with. It is not yet clear In a majority of instances that this can be accurately done for all cases. Senator Kexnepy. Well, your testimony is that in a majority of cases, it cannot be ? Dr. Brown. In the majority of cases where you have abnormal behavior without obvious brain pathology, you cannot accurately locate the brain locus responsible. Early psychosurgery efforts did not face this dilemma, since they destroyed such a wide area of the brain. The technique known as lobotomy or leucotomy was first developed by a Portuguese neurologist. Dr. Egas Moniz, in 1935, and was introduced in this country by Dr, Walter Freeman and Dr. James Watts in 1936. } This procedure, as commonly performed by individual practitioners during those early years, severed virtually all of the subcortical con- nections of the frontal lobes of the brain. Some dramatic results were achieved. ‘ 340 It is reported that a number of violently disturbed schizophrenics, many of them homicidal or suicidal. were sufliciently improved so that they could be released from constraints and integrated into the ordinary routine of the hospital. On the other hand. this drastic procedure also resulted in striking changes of personality. emotional disturbances, and impairment of judgment with lack of control of impulses. But lobotomy was only a beginning. There were continual efforts, over many years. to limit the destruction of brain tissue, and the result- ing adverse side effects, culminating in modern stereotaxic techniques in which a small electrode is positioned in the brain, using geometric coordinates and N-ray inspection to place the electrode in a precise location, and then destroying the tissue at the electrode tip by passing an electrical current through the electrode. Unfortunately. it is lobotomy that the public associates with psycho- surgery-—a procedure in which the “cure” was sometimes worse than the disease. And T think I can state unequivocally that no responsible scientist today would condone a classical Tobotomy operation. The Federal Government has contributed extensively to research in the structure and function of the brain. Senator KexNepy. Do you remember how many were performed ? Dr. Browx. The estimates T have seen range anywhere from 20,000 to 50,000 in the United States. T don’t know the exact figure, I do know that during my training period during the late 1950°s and early 1960's in Boston, it had been quite a common procedure ; and during mv train- mg period. T saw many such patients myself. T did note the two sides of the coin, Senator. IT did note patients who had been difficult and trouble- some for months and years on end went out into the community, lived with their families and often functioned well. But T did note, even as an early student and young psychiatrist, that there were changes in personality that were quite dramatic: and the dilemma posed by assess- ing the cost and the benefit was indeed troubling in that early period. While this research is fundamental to psychosurgery. the Federal role in the practice of psychosurgery has been largely indirect. The NIMH extramural grants program and those of the National Institute of Neurological Disease and Stroke have long provided sup- port for basic brain-behavior research in order to develop the theo- retical framework for any future applications of new knowledge of brain functions to human clinical practice. We have been supporting the exploration of a myriad of pressine and important problems regarding brain behavior relations in research laboratories around the country. For example, we need to know the answers to such questions as: What chemicals are responsible for transmission of nerve impulses within the brain and how do these chemicals control different forms of behavior? What chemical or physical changes occur when learning takes place, or when memory is recovered from the brain? What anatomical systems and what chemicals are responsible for aggressive behavior, sexual behavior, eating behavior, drinking be- havior, and the common state of sleep and dreaming? Senator Kexxeny. How much of this do we know at the present time? 341 Dr. Brown. There are two answers to that question : one is “a great deal,” and the other is “very little.” Animal research has revealed many facts about brain regions controlling a variety of behaviors, and the biochemical transmitters responsible for neural transmission, but the complex physiological processes that produce integrated and mean- ingful behavior, and the uniquely human cognitive and intellectual functions, are very poorly understood. We also want to know what happens to the behavior, thinking, or cognitive processes of man when portions of the brain are damaged through accident, birth injury, malnutrition or disease. Can functions that have been lost through such disruption of the brain be recovered, or taken over, by other portions of the brain ? As each specific question is answered, several other questions arise, growing more and more specific and amenable to experimental tests as we increase our basic information in this area. We are thus well on our way to building a solid framework for understanding mental processes. Although most of the brain behavior research supported by the two institutes, NIMH and NINDS, involve experiments with animal sub- jects, some studies do involve human subjects. However, with a single exception, I will mention in a moment, none of the human studies involve any form of experimental psychosurgery. Most of the human studies are aimed at understanding the behavioral consequences of altered brain function as a result of war injury, ac- cident, disease, or surgery performed because of clinical necessity, such as removal of malignant brain tumors. Thus, neurological patients are studied with behavioral tests in or- der to define and understand the sometimes subtle effects of injury to the brain. In these cases, there is no experimental manipulation of the brain itself, the subjects being selected on the basis of pre-existing brain dysfunction, damage, or clinical surgery. Unlike the old-fashioned Western, there is no clearly identifiable hero and villain in this controversy. Inevitably, complex ethical issues must arise in developing a sound scientific base for clinical modification of human behavior. The issue is whether to use psychosurgical procedures on human subjects either in research or in practice: if so, when and under what circumstances—if any—is it justified? Where do we draw the line? As with any controversial issue, there are extreme opinions pro and con psychosurgery. Some opponents argue that psychosurgery in any form and for any mental or behavioral disturbance—regardless of its severity—should be outlawed. At the other extreme, some proponents argue that psychosurgical procedures should no longer be considered research but constitute routine and accepted treatment for a wide range of behavioral disorders ranging from childhood hyperkinesis— or overactivity—to homosexuality. A middle stance would hold that psychosurgery might be of po- tential benefit and should be studied only for its use in cases of ex- treme mental illness, especially those that are life-threatening to the patient or those around him and that psychosurgery should be per- formed only after extensive attempts at alternate modes of therapy had failed. 342 We believe that knowledge and understanding of the relationship between the brain and behavioral abnormality and of the optimal treatment of such abnormalities are still in very early stages. It is in the area of clinical experimentation in this controversial frontier be- tween the neurological and behavioral sciences that complex ethical issues arise. Senator Kex~epy. You are suggesting that the psychosurgery be well controlled, set up as a specific experiment ? Dr. Browx. I would say that is a minimum condition. 1 should also mention one of the phenomena that makes this kind of research so difficult. Researchers have found that in some instances the mere fact that a person exhibiting violent behavior is removed from his environ- ment and placed in a treatment setting—without any other niedical or drug regimen—is enough to reduce the frequency and/or the severity of the violent symptoms. What one is trying to study literally disappears: to study that phenomenon itself becomes critically im- portant. You can appreciate how dificult it is to study this kind of situation scientifically. I have been attempting to present a balanced picture of the pros and cons of psychosurgery; and we come to the basic ethical issue with which we started. Despite the marked contrast between lobotomy and current practices of localized tissue destruction. is any form of irreversible damage to even a small part of the human brain ever justified ¢ There are some who would also criticize, with some reason, the changing of behavior by stimulating the brain through implanted electrodes, even though this is a less drastic treatment because it does not rause irreversible damage to the brain. And lurking just beneath the surface is the fear of many thoughtful people that the sanctioning of such procedures may eventually lead to thought control, ala “19847 or “Clockwork Orange.” Senator Kex~epy. Is there any validity to those fears? Dr. Browx. I think there is great validity in the sense that there is something special indeed about the brain. There is something very special about experimenting on the brain. And the anxiety of course 1s very deep in terms of the control of feelings, thought and behavior. There is validity in the depth of concern with taking cognizance of the need of troubled people to receive help, of the need for us to develop more knowledge in order to treat these people; and in order to treat people with these difficulties, we must deal with that valid set of anxieties. . The next issue is how much clinical psychosurgery is done. We do not have reliable data in this country on the types of patients subjected to this technique, or the after-effects on patient behavior. The most systematic attempt to assess the effects of psychosurgery on patient behavior and intellectual capacity was the Columbia-Grey- stone project, which was conducted in 1947—and I would be glad to submit for the record the facts on this. But it is a study that involves only 48 cases: 24 who had received lobotomies and 24 who had not. Since then. of course, many changes in psychiatric and medical practice have taken place: chemotherapy has dramatically changed the nature of the patient population in mental hospitals, and new 343 surgical procedures have been introduced which are quite different from those studied in the Columbia-Greystone project. In order to make any specific recommendations for overseeing or controlling the clinical practice of psychosurgery, a systematic survey of the field must be conducted by one of the many professional societies and private foundations that have begun to focus on ethical issues in life sciences. We need to gather existing data available from patient histories and other sources which never come to our attention because they are not federally funded. We must find out what is going on if we are to accurately answer these hard questions. I have been asked quite often about how many psycho-surgical clin- ical operations are going on in the country right now, Senator. I don’t know the answer. I have heard estimates as high as several hundred to several thousand. My own guess would be that perhaps several hundred of such procedures are taking place in the United States each year at the present time. The fact that we don’t know is a troublesome one and one that we intend to encourage the responsible societies to respond to. Senator Kex~epy. It should be a more than troublesome one. We asked you before about minimum standards: the fact is that any kind of experiment ought to be very carefully controlled and very well thought out. Let me ask you this: If a private doctor wants to practice psychosurgery is there any way that you can prohibit it? Dr. Brown. No. We only have direct control over those clinical and experimental procedures that are done under our research grant funds. Senator Kex~epy. Do you know of every case, or every place where psychosurgery is performed in the country today? Dr. BrowN. No; I do not. I would guess that somewhere from several hundred to perhaps a few thousand are performed. We do not have an overview or purview of all the clinical practice that is now taking place. Senator KENNEDY. So these procedures are taking place in the numbers that you have mentioned and you have no way of knowing whether those are under the very carefully controlled conditions that you have outlined as being absolutely minimal at best ? Dr. Brown. That is correct. We have no direct knowledge. Senator KexNepy. What can we do about this? How is the patient to be protected ? Dr. Brown. I think there are several ways of making sure that the patient’s interests are being served in this difficult situation. One is to make the general citizenry and consumer aware of the critical issues, through hearings such as this. They serve a useful purpose in bringing to public awareness the difficulties and the pros and the cons of such a procedure. The second would be through dealing with the medically respon- sible groups—and I refer to the AMA, the neurosurgeons, the psychia- trists, the psychologists, and others who are directly involved in clinical care. Senator Kex~epy. Much stronger peer review, and much stronger institutional quality control ? 344 Dr. Brows. I think the issue here in psychosurgery while more charged and emotional and sharper, is not different than the issue of when heart transplant, or kidney transplant. or other on-the-forefront types of medical procedures should be done. I think one might well ask how we insure the interest of the patient in these different areas. In this sense, the issue is, how do we develop consumer protection for very dramatic. often life-saving procedures? Senator Kexxeoy. What has been the record of the AMMA on psyvehosurgery 4 Have they supported it or opposed it Dr. Brows. I think you should get that more directly from them. Senator Kexxepy. We will solicit their opinion directly. but what kind of impact have they had. in your own opinion? Dr. Brow. 1 think they are concerned: I think they have been cooperative with an effort that, vou may be aware: is discribed in the latter part of my testimony: that the two institutes, NIMH and NINDS. have set up working groups to carefully look at the range of issues. I don’t think I could say anything more than that—- Senator Kexxepy. We are going to hear from then. Dr. Brows. That would make it a lot more comfortable for me. Senator Kexxeny. Very well. Dr. Brow~. A few minutes ago, I stated that the goal of respon- sible researchers in psychosurgery is to pinpoint the exact locus of the undesirable behavior in the brain and destroy only those tissues and nerve cells. leaving other functions and behaviors of the patient unaffected. Frankly, the current practices of psyehosurgery fall short of this coal. And even the best research in this field is not able to achieve such precision. My own view is that more knowledge and more refined techniques would be needed before one could determine unequivocal clinical indications for psychosurgical interventions. I am. in fact. too painfully aware of how much more there 1s to learn about this incredibly complex structure we call the brain. I mentioned earbier a single exception to the statement that none of the NIMIT or NINDS studies on humans mvolve any form of experimental psyehosurgery. The exception is a contract in the amount of £500,000 to the Neuro-Research Foundation in Boston. Massa- chusetts, which began on June 25, 1971, and will terminate on March 31, 1973. The contract involves an attempt to understand and control violent and destructive behavior that is presumed to he a direct result of brain dysfunction. Rather than take your time to recount the background and details of this contract. I would like. with your permission, to provide this documentation for the record. I also know that Dr. Horowitz has either received or there is now in the math a rather detailed letter on this subject. Senator Kexyepy. We have received it. It is a very useful one. One part of it is. I think. probably the only amusing part of our own hearing. This is the part that says that the decision about the program in support of psvehosurgery is made primarily on the basis that not to have awarded the contract would have been to thwart the intent of Congress. 345 We hear so much about what the intent of Congress is on different matters, and about how important it is to assure that the intent of Congress is carried through; and this question is of interest. Senator Magnuson tells me that his intent was to get further information on this subject. Dr. Brown. Thank you, Senator Kennedy. It is always a pleasure to follow the intent of Congress. [ Laughter.] I should like to stress that no actual lesion ; that is, no actual psycho- surgical procedures have been carried out to date on that contract. Nor are any scheduled for the remainder of the project. The investigators have found encouraging indications that at least some patients exhibiting uncontrollable violent behavior can be helped through nonsurgical and psychiatric treatment without resorting to irreversible surgery. The last topic that we have to cover is the Department of Health, Education, and Welfare policy; and I know the subcommittee is quite familiar with the three cardinal principles of the DHEW guidelines for the protection of human research subjects. They are, briefly: that the rights and welfare of the subjects in- volved are adequately protected, that the risks to the individual are outweighed by the potential benefit to him, or by the importance of the knowledge to be gained; and that informed consent is obtained in an adequate and an appropriate manner. The securing of informed consent poses a difficult problem even when human subjects are of normal intelligence and are emotionally healthy and mature. It becomes infinitely more complicated when the subjects are seriously disturbed, below normal intelligence, or chil- dren, and when the proposed procedures involve serious risks and irre- versible consequences. But a clinical investigator may not avoid the solemn responsibility of securing informed consent merely because it is difficult. The DHEW guidelines describe the basic elements of an informed consent as follows: One, a fair explanation of the procedures to be followed, including an identification of those which are experimental; Two, a description of the attendant discomforts and risks; Three, a description of the benefits to be expected ; Four, a disclosure of appropriate alternative procedures that would be advantageous for the subjects; Five; an offer to answer any inquiries concerning the procedures; and Six, an instruction that the subject is free to withdraw his consent and to discontinue participation in the project or activity at any time. In other words, the clinical investigator may not withhold from the subject any facts which are necessary to form the basis of an intelli- gent consent to the proposed investigation. In addition, it forbids the inclusion of any exculpatory language in the consent form Senator KexnNepy. Now, let me ask you this: the doctors are not really required to follow those regulations in their clinical practice; are they? 346 Dr. Browx. No. As I mentioned. the heart of the matter is that in terms of these things. these demands are required to be met only when Federal research grants are involved. Senator Kexxeny. Everyone in such an experiment must be noti- fied; but in regard to the 600 other such operations that are taking place: Unless a doctor wants to use the IEW guidelines. there is very little that could be required of him. This testimony is enormously useful. There has been tremendous development in this area. and I am not in any way implying a eriti- cism of your shop. which is extremely able and helpful. But again, in terms of the patient's interest. the only procedures you have control over are the ones that are actually funded by HEW. and not any of the several hundred others. Dr. Brow. I think that is correct. ITowever, there is an interaction, a spillover. if T could use that word, into general clinical practice in the sense that the DITEW guidelines apply to research grants at many institutions also involved in general clinical practice. And 1 think it pervades the institution and thus influences the conduct of medical practice in general. Senator Kux~xepy. Do you want to just summarize the rest of these points. Dr. Browx. I think that by the questions you have asked, we have substantially covered most of the important issues. The last point T would like to make is that we have to combine two sides of the coin of knowledge; when we create new knowledge we can also create the potential for abuse of that knowledge. We must combine new information with a sensible, rational and humanitarian perspective on the applications of that knowledge. As a last point. T would Tike to say that psychosurgery is to me now what marijuana was in 1969. Senator. Marijuana as an issue is a terribly important one. But in addition to the intrinsic importance of marijuana. it also became a lightning rod for other issues—the generation gap, who shall set the laws. what shall be done—a whole complex of values of concern to the society as a whole were discharged on the lightning rod of marijuana. Tn 1973. psychosurgery has become such an issue. As a biomedical technique with both treatment and abuse potential, it is mtrinsically important. But im addition, it also has become the lightning rod for such things as the control of behavior, political intent, the rights of op- pressed minorities. and the like. And I think there is much to be dis- tinguished between the lightning rod aura of the terribly important issues and the intrinsic problems of psychosurgery. Senator Kexzeoy. But with psvehosurgicals operations, the per- manent damage seems to be much greater. In spite of all the emotion that surrounds the marijuana issue. the issues surrounding psycho- surgery are much deeper. and much more in need of investigation. Certainly your own testimony on lobotomy and the other kinds of surgery is enormously alarming. Let me ask vou this. Do vou think psychosurgery is a valid tech- nique to treat behavioral disorders: and if so, under what conditions? 347 Dr. Brown. Do I think it is a valid technique for behavioral dis- orders? My answer is a crisp “maybe.” And under what conditions? I would say only when extensive attempts at other treatments have failed and the situation is very equal or desperate, and only under the most carefully controlled conditions. Senator Kenxepy. Is it being performed today? Dr. Browx. If it is not performed in such a way, I would be ter- ribly concerned. Senator KEx~epy. Would you give that to me again ? Dr. Brown. I don’t know, in fact, how well it is being performed. Senator Kex~epy. Well, how extensively is it being performed? Dr. Brown. It is extensively performed qualitatively well, by which I mean under the most careful circumstances and as a course of last resort. Senator KEn~Nepy. What consequences would it have if it were not performed correctly ? Dr. Brown. The consequences are clear in that insofar as a proce- dure has been done, the effects are largely irreversible. But again, the issue is the same as that when an inappropriate or a poorly done heart [Snsplant is performed. Again the situation may be just as irrevers- ible. Senator Ken~epy. How important is the application of this tech- nique for mass behavioral control ? Dr. Brown. I think it has no role at all in mass behavioral control. I think that would be an abuse of the highest order. Senator Ken~epy. Could it be used for that frightening purpose ? Dr. Brown. Yes. I can picture scenarios under certain kinds of au- thoritarian or totalitarian situations where it could be used for such purposes. I think they would be dreadful-—and un-American. Senator Ken~epy. Senator Javits has requested that we discuss the HEW guidelines in respect to the human research subject. In regard to all federally supported research, should all research, at a minimum, be subject to the guidelines and the scope of S. 78? Dr. Brown. I would like to ask Dr. Sherman to comment on that. That is an issue with which we are concerned and familiar. Dr. Sherman? Dr. Suerman. Mr. Chairman, the Acting Assistant Secretary for Health at HEW has already asked us to undertake exploration with other government agencies, including those outside the department, with this possibility in mind. Senator Kexxepy. Could Senator Javits submit in writing some questions in this area? I want to thank you very much, Dr. Sherman; you and Dr. Brown have been enormously responsive. These are terribly complex and difficult questions; and I think you have been very frank. Our next witness is Dr. Orlando Andy. Dr. Andy has been a professor and head of the department of neurosurgery at the University of Mississippi Medical Center since 1960, and associate professor of psychology, physiology, and bio- physics. We want to welcome you today. 348 STATEMENT OF DR. ORLANDO J. ANDY, DEPARTMENT OF NEUROSURGERY, UNIVERSITY OF MISSISSIPPI Dr. Axpy. Thank you. 1t is good to be here, Senator Kennedy, to testify on the subject of psychosurgery ; ; and 1 would like to start by giving a few brief case reports. A 33-year-old man had violent aggressive behavior since childhood. He was an alcoholic, addicted, had seizures, attempted suicide six times, and was in jail one yea P sychosur gery was done ht years ago. He started an up holstery and ¢ abinetmaking business seven years ago ad presently has tive employees under his care and is happily marr Tried. A 24-year-old man had attacks of nervousness and aggression since childhood. The patient suddenly attacked a fellow worker st; wmding by, and broke his nose. Within a week after joining the Army, he was S dis- charged because of behavioral instability. He attempted suicide with a gun, resulting in his losing one-third of his liver and almost dying. Psy chosurgery was per formed 12 years ago. He no longer has out- bursts of aggression, is happily married and supervises five other workers at his place of employment. An 11-year-old boy, mentally retarded and institutionalized had to be tied to a chair and to a bed because he constantly beat himself. He had a cauliflower car and ulcerated scalp because of the selt-matila- tion. Following psychosurgery nine years ago, the patient became re- habilitated and has been playing with other institutionalized patients. A seven-year-old mentally retarded child had sudden attacks of screaming, yelling, running and beating the head against the wall. The walls were actually indented by the blows. Following thalamotomy three years ago, the patient did not dis- play the wild, aggressive and screaming behavior. The improved be- havior was an enjoyment for both the Child and the parents. What is psychosurgery ? Psychosurgery is a term which has been loosely used to identify brain operations performed for the treatment of behavioral and related neurological disorders. Rationale for “psychosurgery. In order to understand the rationale for psychosurgery, one must first recognize that behavior emanates from that vital organ called the brain. There are two major factors which determine how that brain functions. These two factors are: (1) the structural organization of the brain which is genetically determined and may be altered by brain damage: and (2) the environmental influence. For the treatment of abnormal behavior it thus is rational to utilize either surgical or psychological techniques to alter the brain function. The surgical technique is a direct approach to the structural and functional organization of the brain, whereas the psychological technique is indirect. 349 PSYCHOSURGICAL VERSUS PSYCHIATRIC TREATMENT OF BEHAVIORAL DISORDERS DUE TO BRAIN PATHOLOGY There are a group of behavioral disorders such as psychomotor seizures and the hyper-responsive syndrome which emanate from anatomically deranged and pathological brain tissues. Psychiatric and psychologic therapy have not been successful in treatment of most of those pathologic conditions. It is, however, well established that surgery is one of the most effective methods of treating structural pathology of the brain. For example, in our i Sr institutions there are cases of un- successful psychiatric treatment of behavioral problems due to brain tumors. After the correct diagnosis is made, they are successfully treated by brain surgery. Such cases serve to emphasize three points: First, abnormal be- havior does result from structurally abnormal brain tissue, a fact Thich some psychiatrists and psychologists do not know or tend to orget. Second, psychiatric techniques in dealing with abnormal anatomi- cal changes of the brain in most instances are futile; and, Third, adequate therapy can be obtained only by techniques such as surgery which deal directly with the structural abnormality. PSYCHOSURGERY VERSUS DRUG THERAPY It can be argued that drug or chemotherapy will alter anatomical structures and thus favorably influence behavior without necessitating surgery. There are many patients with seizure and various behavioral problems who are well controlled by drug therapy and do not need surgical treatment. On the other hand, there are patients who do not respond to drug therapy, and surgery is performed with beneficial results. It must be noted that some drugs may have detrimental side effects. Some drugs used to treat behavioral disorders lack specificity for the pathologic process and cause irreversible anatomical changes. For example, there are patients on phenothiazines who have devel- oped permanent and incapacitating motor disorders such as Tardive Dyskinesia. Consequently, the psychiatrist contemplating the use of these and other dangerous drugs should consider surgery as a possible alternative, especially in patients with pathology. The behavioral population treated by psychosurgery versus the population treated by psychiatry: Behavior is a continuum. In the treatment of behavioral disorders, it must be recognized that there is a continuum between the extreme states of behavioral abnormality and behavioral normality. Between those two extremes, there is a gray zone in which it would be impossible to distinguish between abnormal and normal behaviors. It must be stressed that the psychosurgery which has been per- formed by me and others has dealt with those abnormal behaviors which are at the extreme pathologic end of the scale. We are not oper- ating on patients in the gray and normal zones, which are successfully treated by psychiatrists and psychologists. We are dealing with those patients by far who have been abandoned by the psychiatrists and in many instances have been institutionalized. 93-999 (Pt. I) 0-73 -2 350 DEVELOPMENT OF PSYCHOSURGERY Psychosurgical procedures for the treatment of behavioral abnor- malities have developed as a result of empirical clinical observations and experience. These observations have been based on correlating behavioral changes with the locus of brain tumors and other brain lesions being treated by brain surgery. Psychosurgical procedures are not experimental. as implied by some critics. However, experimental neuropsychologic. neuroanatomice and neurophysiologic observations in animals have supported these devel- opments. My own clinical interests have been in the realm of tr ating ageres- sive, uncontrollable. violent, and hyperactive behavior which does not respond to various other medical forms of therapy. Based upon empirical observations during the course of performing neurosurgery for motor, pain and seizure disorders in adult patients, my colleagues and T have observed an amelioration of coexisting be- havioral disorders. In children suffering from cerebral palsy and intractable motor dis- orders with associated behavioral abnormalities, it also was observed that operations in the thalamus of the brain—thalmotomy—improved the behavioral abnormalities, in addition to the motor disorder. An analysis of these eases revealed one common finding in relation to the clinical manifestations of the behavior. The common finding was a state of hyperactivity to hoth external and internal originating stimuli. HYPERRESPONSIVE SYNDROME The term “hyperresponsive syndrome” was given to these disorders to identify them as representing a clinical entity. Its use may be con- sidered analogous to the use of the term “epilepsy” which serves to identify a clinical entity resulting from a variety of brain pathol- ogies. The hyperresponsive syndrome may be defined as representing er- ratic. aggressive, hyperactive and emotional instability of an episodic character which. in its full blown expression. terminates with attack. The existence of this form of behavior has been very well demon- strated following electrical stimulation and ablation of various limbic, diencephalic, and mesencephalic structures in the experimental animal. The lesions which T and others have been placing in the thalamus. hypothalamus and amygdala for the treatment of such behavior is thus well grounded both on the basis of clinical observations and neuro- physiologic and anatomic experimentation. In relation to this behavior, one may question the application of animal observations to human behavior. Tt should be observed that one of the main differences in phylogenetic development between the animal brain and the human brain is the very marked and advanced neocortical development in the human in contrast to the animal. It is this neocorticalization which provides for the control which the human exerts upon these phylogenetically less well-developed subcor- tical structures. In reality, one may consider the phylogenetic development of limbic and brain stem diencephalic structures as being just as barbaric or crude in the human as it is in the lower animal forms. 351 MULTIPLE LESIONS IN PSYCHOSURGICAL THERAPY The mere fact that a lesion must be bilateral or be enlarged in order to attain satisfactory results does not mean that the procedure is ineffective as suggested by some critics. It is rational to expect lesions of varying size and location to be necessary in the treat- ment of behavioral disorders of varying complexities. This is especially true in those brains which have extensive bilateral brain damage. It de been very well established by my observations and those of many other neurosurgeons that relatively better results are obtained with bilateral lesions than with unilateral lesions. This is ‘due to the fact that the pathology in most instances is diffuse. Widespread involvement is often evident from the diffuse abnormalities demonstrated by radiologic, neurologic and electroen- cephalographic findings. For whom is psychosurgery proposed ? Behavioral problems which do not respond adequately to medical, psychiatric, psychologic and sociologic methods should be treated by surgery, provided the probability of gain outweighs the risks. It should be performed on patients who are a detriment to them- selves and to society. It should be used for custodial purposes when a patient requires constant attention, supervision, and an inordinate amount of institutional care. It should be used when patients require so much medication that it makes them non-responsive and non-communicative. Finally, it should be used in the adolescent and pediatric age group in order to allow the developing brain to mature with as normal a reaction to its environment as possible. It should be emphasized that during early development, the inter- action between the brain and its environment provide the very im- portant basis and background for the behaviors in adult life. Psychosurgery is thus preferable to that of having a child with abnormal behavior continue under inadequate control during the formative and developmental years of his life. It finally must be made clear that psychosurgery is proposed irre- spective of patient’s color, religion, nationality, and financial status. Psychosurgery is not recommended for individuals who are in con- trol of their aggressive behavior. It also must be emphasized that psychosurgery is recommended only for patients who previously un- derwent medical and psychiatric treatment without success. Psycho- surgery thus is a treatment of last resort. THE ETHICS OF PSYCHOSURGERY It is unfortunate that our institutions are constantly filled with patients who have behavioral disorders which do not respond to psy- chiatric and medical therapy and which, in some instances, would re- spond to psychosurgery but are denied treatment for a variety of rational and irrational reasons. In such instances, to deny psychosurgical treatment is unethical. The ethics involved in the treatment of behavioral disorders is no different than the ethics involved in the treatment of all medical problems. 352 The medical problem concerning behavior may have a more direct impact upon society than other medical problems such as cardiac and Kidney dysfunction. Although behavioral abnormalities often result in legal involvement, it should be the moral and not the legal responsibility of society to determine whether or not the patient should undergo medical treatment. However, if treatment is desired, it is neither the moral or the legal responsibility of society to decide what type of treatment should be administered. The ethics for the diagnosis and treatment of the be- havioral illness should remain in the hands of the treating physicians who are qualified to treat the illness, and the patient, the relatives and designated friends who ave vitally interested in the pateint’s illness and well being. Before the intended surgery, the patient and relatives should be in- formed of the recommended procedure in relation to the benefits, risks. complications, and any other facets of the problem which they mu- tually feel should be discussed. Needless to say, it 1s impossible for the patient to ever become as thoroughly familiar with the medical problem as the physician. Consequently, the patient must have confidence and trust in the physician or physician's recommendation. The final decision, however, to have an operation should be left to the patient and relatives. I do not operate without their support. consent and request. The problem of ethics between physicians also is important in the treatment of these disorders. The physicians among themselves must have a certain amount of trust and faith in the knowledge, background, and experience of ach other, since it is presently mmpossible for any one physician to be thoroughly acquainted with all of the medical problems and methods of therapy which may relate to a given problem. One must deal with these problems with intelligence and not with ignorance, with logic and not with illogic, with experience and not in- experience: and, finally, with an open mind and not a bias. Think and act in terms of the patient's welfare—this is the ethics of medicine. Future of psychosurgery : The lobotomy era of psychosurgery is in the past and the advent of stereotaxic surgery has brought about a new era in this field of medi- cine. With stereotaxic techniques. needle-sized electrodes can be in- serted into the depths of the brain with a precision which previously was unattainable. Chronic brain stimulation, somewhat similar to the techniques used for cardiac pacemakers, and chemical brain implants, are anticipated future developments in the treatment of brain damage patients. These are possible methods of treating patients who do not respond to the presently available therapies. One of the major needs in psychosurgery is to develop new methods of identifying and quantifying behavior. Finally, we must develop a new classification of behavior, one which takes into consideration the anatomy and physiology of the brain. Thank you. Senator Kexxepy. Thank you very much, Dr. Andy. On how many patients have you practiced psychosurgery / 353 Dr. Axpy. Between 30 and 40. Senator Kex~NEpY. Between 30 and 40 patients. Over how long a period ? Dr. Axpy. Since 1955. Senator KexNepy. How many of those Dr. Anpy. I am sorry. It probably goes back to 19—early ‘50s. Senator Ken~epY. And how many of those operations have you performed on children ? Dr. Axpy. Oh, 13 or 14. Senator Kex~epy. What ages? Dr. Axpy. Six and 7 through 19. Senator KeN~NEpy. What was the youngest person ? Dr. Axpy. About 6 or 7. Senator Kexxepy. Did you have the consent of the parents? Dr. Anpy. Yes. Senator KENNEDY. You have had up to 30 or 40 patients in psycho- surgery, and the youngest is 7 years of age ? Dr. Axpy. Yes. Senator KENNEDY. Approximately 13 or 14 of them were children? Dr. ANpy. Yes. Senator KenNEpY. What was the oldest ? Dr. Anpy. 40. Senator KENNEDY. 40. Dr. Axpy. Approximately 40. Senator KENNEDY. In some of your writings, you have indicated the three different classifications of results. You indicate there is a good result group; there is a fair result group, and a poor result group; ten in the poor result group; six in the good, and about 16, 18, in the fair. Do you remember that compilation ? Dr. Anpy. Yes. Senator Ken~epy. What are these—what does it mean to patients who fall into the poor results group? To have part of their brain destroyed, or changed, or altered, and then you get poor results. What is the impact on that patient ? Dr. Axpy. Usually, before one operates on such a patient, one can anticipate the probabilities of being good or bad or fair as to results and possibly what can be attained; and in most instances, when one foresees this, that the probability 1s not very good, one informs the patient of that situation and, under those instances, if the patient does not turn out to have an excellent result, or a fair result, or it doesn’t change at all, then the patient is not disturbed over the situation be- cause, even if they do not improve, they do not have any detrimental effects as far as we can tell by such an operation. So the overall observation— Senatar KenNepy. You mean they are in poor shape to begin wit Dr. Axpy. Yes. In other words, we have Senator Ken~epy. Are they in poor Dr. Axpy. I am sorry. Senator KENNEDY. Aren’t they in poor shape afterwards if they have had their brain altered ? Dr. Axpy. No, sir. Senator KenNEpy. They are not ? 354 Well, then, why do you indicate that they are in poor shape before they go in; when they come out, they are in about the same shape? Dr. Axpy. Yes. For example, most of these patients have bilateral pathclogy—that nieans of the brain—and what we do is perform an oper ration on both sides; in most instances in these advanced cases, there are patients who will have an operation on one side and then will not have the operation on the opposite side and, in that instance, I will categorize them as a poor result if they haven't shown improvements of over 50 or more percent. Senator Kex~epy. What kind of review procedure is required before you operate on one of these patients, say a child? Dr. A~xoy. Well, these patients are always referred to ne, first of all, by other physicians, or pediatricians, psychiatrists and psycholo- gists. The a have gone through quite an extensive gamut of treatment by these other “physic tans. The physicians have by then ahead at the conclusion that here isn’t very much more that they ‘an offer this patient. Meanwhile, the parents or the child. or the pa- Trt himself, if he is an adult, proceed to seek more treatment, and they then ask for a neurosurgery consultation in order to get an opin- ion as to whether or not we think something can or cannot be done from the psychosurgical standpoint. Senator KexNEpY. Do vou make an independent judgment as to whether to go forward with an operation? Dr. Axpy. Yes. I will then see the patient and have the patient worked up from our standpoint by doing a variety of studies in order to determine the degree of brain damage that may or may not be present in that patient, and the locus of it, as much as possible. After I have worked him up in that fashion, we relate this information and decide whether or not it. would be worthwhile or whether or not, with surgery there is a probability of helping this patient. After discussing this with the physician. we then approach the patient and the f family and even the relatives. Senator Kexxepy. Basically, then you make an independent judg- ment whether to move ahead on this’ kind of operation. Dr. A~xpy. Yes. The final decision is always mine in terms of whether or not an operation will or will not be done, but —they have to make the decision themselves; I don’t push them into it, in other words. But the recommendation is ke by me. Senator Kexxepy. Do you have any board or panel that continues to review the various bases for the psychosurgery in which you have been involved ? Dr. Axpy. No. We don’t have a board of supervisors or investigators or peer review type of activity, over what we are doing. The only method that we have of checking out on ourselves is through meetings and organizations that we belong to at which we give reports and discuss our observations and findings and treatment. Senator Kexxepy., This is done on a case- by-case basis, bon are involved with different doctors and general surgeons on every case: but you are the one who makes the “independent decision to do the psychosurgery / Dr. Axpy. Yes. 355 We have conferences with respect to certain cases. The only other contact we have is related to exchange of information with other neurosurgeons. Monitoring of what is being done, it is through the neurosurgical meetings at which we present case reports. Cases such as we are discussing are presented at meetings where surgeons who are in- volved with this problem get together and discuss the various aspects of it. Senator KexNepy. Do you know how much psychosurgery is being done today ? Dr. Axpy. I really don’t know. But I would give a rough guess, 1 would be surprised if it is more than 500 cases a year right now. That would be a very rough guess. I really don’t know. But I doubt that it is 1,000 or above. I give that more from the point of view of having attended and participated in meetings in which psychosurgeons have mutual interest and present cases and Fo cases. Senator KENNEDY. Is there more or less taking place today than a few wears ago? Dr. Axpy. I believe there is probably a little more now than there was a few years ago. Senator Kennepy. How do you account for that? Dr. Axpy. I believe that in the past, we will say, several years, we have had a much more refinement in our techniques; and in addition, we have had additional information relative to the correlation of the behavioral problems with brain pathology. So that we have more information upon which to operate. Senator Kex~epy. I think you were probably here when Dr. Brown outlined some procedures—HEW guidelines—to be followed—includ- ing the identification of experimental restrictions, the discomfort and risk, the benefit, and various other procedures. Do you follow those? Dr. Anpy. Yes. I even go further than that. For example, as I mentioned, in the Senator KeNnepy. Do you have any written material on these pro- goflvnts. Do you explain them to patients orally, or do you have a orm? Dr. Axpy. No. I doit orally. Senator KENNEDY. And you go over this with the individual, or with the guardian or the parent? Dr. Axpy. As I was going to say, my approach is this: for example, a behavioral problem is somewhat different from some other mental problems in that that patient goes out into society and there are more than just the patient himself and the parents involved and the relatives involved ; and if there is this potential involvement, what I do is ad- vise the parents of the patient to bring in whoever is involved and con- cerned about this problem so that I may discuss it with them and answer whatever questions may be brought up and then, before the surgery is performed or assigned, I always want to be sure that they all agree that it is desired. If, say, there are three or four involved, and three say yes, we want it, and one says no; then I will not perform it; and if everyone desires it except the patient, again, I will not perform it. Senator Ken~epy. Is your facility a research center or a clinical facility ? Dr. Anxpy. It’s clinical. 356 Senator Kex~xepy. Clinical. Are you aware that the Director of the National Institute of Mental Health stated. and T quote. “The National Institute of Mental Health staff believes that our knowledge of brain function is inadequate to justify any psychosurgical procedure unless there is a very strong evidence of organic pathology of the brain.” They don’t think that the decision to perform psychosurgery should be hased totally on the be- havioral function. unless there is evidence of organic brain damage, and that psychosurgery should be performed only as a last resort. What is your reaction to that / Dr. A~xoy. Well. as IT have stated, I don’t believe that one ought to do psychosurgery. even in brain pathology. without having the patient co through the medical therapies that ave available. including drug therapy. Senator Kexyeny. Well, would you agree to that statement ? Dr. Axoyv. © disagree with the first part in which he says we don’t know enough | it. T think we know quite a bit about this brain physiology. and I think we know quite a bit about the anatomy of behavior. For example. we have quite a bit of knowledge on ageression. And there is literature—— Senator Kexxeny. Well. do you have knowledge that the National Institute of Mental Health does not have? Dr. Axpy. The fact that T am a little more closely involved with it than probably the members of the National Institute of Mental ITealth who are not involved with it, except from an administrative stand- point. Senator Kexxepy. So vou feel that vou can continue to practice this kind of surgery based upon your own information / Dr. A~xpy. I believe that the information that we presently have is adequate to justify performing surgery in several brain parts for the treatment of behavorial disorders that are pathologically based. without question. Senator KenN~Nepy. So vou can continue to practice without notify- ing the National Institute of Mental Health. even though they have very grave and serious reservations about this kind of procedure? Dr. Axpy. 1 believe that if anv responsible institute has grave con- cern over a situation, that they could make themselves acquainted with that particular problem: oot a hetter understanding of it and ar- rive at some decision where, in the final analysis, the patient does benefit from the treatment that is given to hin. ¢ Senator Kex~yeny. Let us refer to vour own witness, in particular a report that dealt with one procedure. It notes that a “decrease in = ve hal [Q was apparent at testing intervals of one half to two years. oo this represents a loss of 8 to 14 points. out of eight patients, 75 percent of the subjects. We noted that the decrease in verbal TQ was mainly due to the poor performance on—test similarity. And in a report on a boy of nine years old. labeled JM. vour report says again, “intellectually, however, the patient is deteriorating.” Two of your own reports show that one patient had a lowering of IQ and in another case, ntellectunlly the patient is deteriorating. Why do vou think results suc! as these justify vour performing this surgery? 357 Dr. Axpy. Unfortunately, that information is not really revealing of performance of these patients. Se or KexNepy. Well Dr. Axpy. And may I just say, as relates to the second patient, the patient’s IQ would deteriorate. This was a result of an evaluation of this patient several years after he had surgery. Meanwhile, the pa- tient is one whose original preoperative IQ was not within a normal range; it was below normal. Several years post operatively, with the test based on patients of older age groups, the result was down several points. But 1f one were to evaluate that patient in relation to the tests that he had, at the time he was operated on, it would not have been down; it would have been up. And that patient, for example, the one I just mentioned, who was operated on quite a few years ago, is working with a trucking firm, is very productive and is getting along very well, has no difficulty, lives with his family, is quite happy and the family is quite happy. And I would say today that if he had not had an operation that mentally, he would have gone down much greater because he would not have had the ability to acquire the experience that is necessary for IQ develop- ment. As it was—for example, he could not feel pain. He never felt pain. And after the operation, he started to feel it. Senator KENNEDY. Given the kind of concern we have heard evidence from the NIMH, do you think we should have a formal peer review of these areas of surgical procedures? Dr. Axpy. Yes. But may I go back to answer another question that was asked before in terms of 1Q, in terms of similarity for a specific test. I might say that we have analyzed all aspects, we have tried to analyze all aspects of the changes that take place. Relatively speaking, the impairment of that specific subtest is really not a major detriment to the patient in his overall post-operative functioning. And relative to the benefits that the patient derives from the surgery, this is very, very minimal. Senator Kex~epy. But still, given the concerns of the department, shouldn’t we have a form of peer review of the various psychosurgery that is performed today ? Dr. Axpy. I think it would be very good to have peer review tech- niques. We have, through the dean of our medical center, appointed a group to review all patients who go through psychosurgery treatment. Senator Kex~Nepy. We want to thank you very much, Dr. Andy. Our next witness is Dr. Peter Breggin. Dr. Breggin has been in private practice since 1968, has been asso- ciated with the Washington School of Psychiatry, has served as a faculty member from April, 72 in research psychiatry, and is Di- rector of the Project to Examine Psychiatric Technology. He has pub- lished many cases on scientific, ethical and political, cases, and on psychiatric techniques. STATEMENT OF PETER R. BREGGIN, M.D., WASHINGTON, D.C. Dr. Bregein. During my testimony, IT have to cover in a sense, three topics: my own; and then I wish to develop some data on Dr. Andy that he has not given you, some statements which I believe are out- 358 right false. And also to fill in on some of the data for you that NIMH said is not available. Actually. we know a great deal more on that topic. Senator Kex~zepy. I would like to tell Dr. Andy that if his name is going to be mentioned, we will give him a chance for rebuttal. Dr. Axpy. Thank you. Senator Kexzeny. Or if you want to file a statement. we will pat it in the record, whichever way you want. Dr. Brecain. T have also done a great deal of research on the role of the National Institute of Mental Health. a good deal more than they have indicated here. But first T want to go through my own testimony and summarize the first ten pages to give you an idea of what I believe are the real prob- lems that we are facing today. The theory and practice of behavioral modification is really at the root of psychosurgery. and whether or not Skinner himself supports psychosurgery, his mechanistic, anti-individual, antispiritual view, which T call totalitarian. is what gives justification to the mutilation of the brain and the mind. in the interest of controlling the individual. Jose Delgado. who is one T also examine in my testimony but won’t cover here. is the chief apologist for psychosurgery politically. and his totalitarian views are very similar to Skinner's. He ridicules the basic American values: Love of the individual. love of liberty. personal responsibility. and the spiritual nature of men. These men. Skinner and Delgado. the psychosurgeons here today. represent the greatest future threat that we are going to face for our traditional American values. as promoted in the Declaration of Inde- pendence and the Bill of Rights. This totalitarianism asks for social control. including social control of the individual, at the expense of life. liberty, and the pursuit of happiness. It undermines Jefferson's self-evident truths. These men. T believe, are doing nothing more than giving us a new form of totalitarianism “in medical and ethical language.” The reliance on professional ethies and medical control over these issues leaves the physicians in charge of the situation. Tt creates for themselves an elitist power over human mind and spirit. Tf America ever falls to totalitarianism. the dictator will be a behavioral scientist and the secret police will be armed with lobotomy and psychosurgery. And. by the way. lobotomy is still with us; NIMIT was wrong about that. And T just want to make one spiritual comment. Senator. You have been told a lot about heart sureery today, kidney surgery. But what goes on in your mind is a very different thing from what 200s on in your kidney or your heart. Blood passes through vour heart and circulates in a rather limited fashion. T believe vour eternal spirit passes through vour brain and lives there for a while and then oes on. Tampering here in the brain is considerably different than tam- pering with the heart or the Tungs. Tt must impair the expression of vour spiritual self. Tt is my own belief—and T hope to give vou enough evidence to point vou in this direction——that it is time to take away the power over mind and spirit from professionals. Lobotomy and psvchosurgery is an ethical, political and spiritual crime. It should be made illegal. 359 Senator Kexyepy. Do you think all psychosurgery ought to be made illegal? Dr. Bregein. Yes. It is not, in my opinion, a medical procedure any more than the mutilation of an arm as punishment of a crime is a medical procedure. The mere fact that a physician performs the mutilation does not make it a medical procedure. That was established at Nuremberg. Senator Kex~epy. Well, what about a person who has terminal cancer, pain, suffering ? Dr. Brecarn. Very, very little psychosurgery is done in the United States today for that purpose. Senator Kexnepy. Should we permit it ? Dr. Breen. I would say no, for this reason: it opens up a Pan- dora’s Box of possible approaches; men like Dr. Andy invent diseases to operate on. You may wish to make an exception in that case, but I wouldn’t. I think it involves the issue of euthenasia, a partial de- struction of a living person, of his mind, before he dies. I feel that giving the power of euthenasia to physicians is too dan- gerous, too big a power; but I would be willing to compromise on that particular issue. It is a miniscule problem. Of all the cases I covered in the Congressional Record—1,000—none of them involve the question, although they are doing psychosurgery at the National In- stitutes of Health on terminal cancer patients. Senator Kex~epy. Epilepsy? Dr. Brecery. That would not be psychosurgery. The definition of psychosurgery is to destroy normal brain tissue to control the emo- tions or behavior or, a diseased tissue when the disease has nothing to do with behavior of the man is trying to control. For example, some of Dr. Andy’s patients may be brain damaged, but that is not what makes them violent. It is just a good excuse to mutilate further: damage, damage, damage, until you get the calming effect. So if you are operating on epilepsy, you are not talking about psyvchosurgery. Senator KexnEpY. It is your position that the Government ought to prohibit psychotherapy? Dr. Breceix. Yes. Very definitely. I think it falls into the class of atrocities, as defined in Nuremberg. Let me get to the specifics on what is going on at the present time, in regard to lobotomy and psychosurgery, or psychiatric surgery— which I describe extensively, by the way, in my research papers in the Congressional Records of February 24th and March 30, 1972. William Scoville, president of the Association of Psychosurgery is a lobotomist. Do not believe what you have been told today, Senator, about the demise of lobotomy. There is a great deal of lobotomy going on in this country right now. Scoville and most of the knowledgeable psychosurgeons admit that all of the newer procedures do the same thing: they are partial lobotomies. Let me review one quote, from 1972, by a very well-known psychosurgeon: After the operation, there develops a sense of fear. In cases that are still mildly troublesome. the threat of punishment quiets them. They are shy with strangers. In case 73 the psychologist was able to notice the difference in the immediate post-operative period. The patient became more cooperative and obeyed commands. 360 Dr. Brown is not telling you the facts when he tells you that this procedure is not closely related to lobotomy. Ruth Anderson, in Psy- chosurgery in 1972 says that the newest operations have the same effect as lobotomy : emotional blunting, passivity, reduced capacity to learn. Senator Kex~zepy. Doctor, do you have the same feeling about the use of drugs or drug treatments? } Dr. Breceix. No. This is a permanently mutilating operation; it 1s a permanently destructive operation, reducing spiritual and emo- tional responsiveness-—and this is the only way it can work. Senator Kexzepy. Well, aren't the results rather dramatic? Dr. Brecein. 1 think that we get into a real question of where psychiatry is taking us when they are drugging our population or when they hold hospital patients chronically under tranquilizers; 1 think there are better solutions than that. But what we are facing here is a different issue in terms of the permanency of what is done and also the atrocious manner. you know, in which it is handled. We have 50,000 people, by Walter Freeman's estimate, lobotomized in the State hospitals the first time around through 19535. We are now fighting, as you probably know, to stop them from operating like that again in our prisons and hospitals. We have a renewed threat of a mass of atrocities. Bert. Brown was not telling the truth, by the way, about the best way to go about psychosurgery. There was three controlled studies, noted in my February 24th Con- gressional Record. and they found uniformly no improvement. No psy- chiatric improvement in the patients, but severe damage resulting from the surgery. I might say that one physician can do massive numbers: Walter Freeman did 4,000 operations. Senator Kexzepy. How many psychosurgical operations do you think are being performed ? Dr. Brecain. Well, the best thing I can do is name you some of the places it is going on from some of the data T have. My answer would be a thousand and maybe more; but an unknown figure. But we know a lot more data than were given to you by Dr. Brown. For example. in Boston alone, we have three hospitals at least—the Boston City. Mass. General and Leahy Clinic. The Hartford Hospital has a big project. In New York, there are four or more big projects: Bellevue: Columbia P&S: New York Medical College and St. Vincents, In every city that we have been able to examine. we have found psychosurgery projects. Even the VA is doing psychosurgery, doing lobotomy. but they wouldn't like to tell you that. One of the accomplishments, by the way. of all this campaigning is that the VA has tightened up what it is doing. Bert completely misled vou Senator, in his written testimony, not his oral testimony when he said that most current operations are for violence. Read my Congressional Record : 1.000 eases in that. not one for violence. Most operations are being done on women. and most of them are being done on people who suffer from neuroses : depression, anxiety, obsessions—not violence. And that is all in this data that T am giving you for inclusion in the Record, 361 Senator Ken~epy. Doctor, did you ever think that they might be right and you might be wrong ? Dr. BregeiN. Senator, all I can do—— Senator Kex~Nepy. I am sure you are familiar with other examples from medical history: Dr. Satterwhile saw childbirth defects caused by bacteria transmitted by surgeons; and he was ostracized, and he turned out to be right. Dr. Morton was ostracized because of his beliefs about ether. He was right. Copernicus thought the earth was not the center of the universe. And he was given a very hard time. Now, why do you think you're right and they are wrong? Dr. Breeein. First of all, the men you have mentioned are much better identified with the anti-psychosurgery movement. The anti- psychosurgeons are the ones likely to be burned at the stake, not the psychosurgeons. The anti-psychosurgeons are the ones fighting the medical establishment. The pressure is on us because we present a view that is extremel unpopular and is rejected by the establishment and the mental health profession as well. Whether I am right or wrong, you have to make up your mind about that. I can only present you with the truth. Senator Kexnepy. That is why we are hearing from you and Dr. Andy, too. Dr. Brecein. Let me tell you a little bit about Dr. Andy. Dr. Andy is professor and department director of neurosurgery who operates on little children as young as six years of age with little or no psychia- tric supervision over whom he selects for multiple mutilating opera- tions. His youngest cases are not seven, but are six and five. In writing to me, before he knew who I was, he spoke of “30 or 40” cases, and he said the majority were children who were hyperactive, aggressive, and emotionally unstable. I can provide you these letters if you want. Now he says he has operated on fewer. He does not know exactly what he is doing. Concerning peer review, I called down to the Chairman of the Department of Psychiatry, who is on the same hallway with Dr. Andy, and I said, “Do you know Dr. Andy is doing surgery on chil- dren?” He said, “Oh, my God, no.” That is the Chairman of the Department of Psychiatry at the University of Mississippi. I have already told you that I think he is simply inventing a disease. These children either have no disease, or if there is disease, there is not the slightest relation between the brain disease and their behavior. Let me say that in a letter to me he said he often cannot find any disease in their brains. Dr. Andy’s most publically touted case, a boy named J.M., is de- scribed by Andy in the press as an individual who is mentally retarded. In his professional writing Andy told his colleagues that J.M. was of average intelligence. In his testimony Dr. Andy also did not know the age at which he had operated on J.M. He was nine years old in the literature. I must say it is very difficult to trust anything you hear. For exam- ple, in Andy’s latest book J.M. has had three operations. But in an earlier work, Andy says there were six operations on J.M. He gives the time, the kind of operation, the place. The IQ issue is a gross distortion. Any neurologist would tell you that you can have a lesion the size of an apple in the front of your 362 brain without a change in IQ. Tt is a red herring. Let me talk to you about Mark Ervin and Sweet. Senator Kexyepy. Would you please summarize that part of the testimony, if you will. Dr. Brecon. First of all, the National Institutes say Mark, Ervin and Sweet did not operate on any patients under NIMIT money. Let me tell you Dr. Sweet has testified to the contrary before Senator Magnuson’s committee. He has said they operated on two. Second, these men were awarded a $£108.000 grant from the Justice Department and another £500,000 imposed directly as a line item from Congress to the National Institute of Mental Tlealth. I believe vou have not been informed about the collaboration between the Justice Department and NIMIL Justice, contrary to a popular belief, was funding the Boston group for treatment techniques. Justice turned them down this year, and have gone so far as to allege in an in-house memo that they attempted to sell to themselves noncompetitively from Ervin's privately owned profitmaking cor- poration. The racial issues involved here are also enormous. To quote Dr. Sweet: “we are talking about senseless behavior—individuals who bring discredit on their movement by excesses of one sort or another.” NIMH in its report to you touts the surgery on a woman known as Julia. But we have a signed document from a highly responsible professional on the ward that at the very moment they were touting her in Life magazine, the nurses and staff on the ward were so dis- turbed over her disastrous outcome that they were literally erving about her. She had lost her ability to play music, to carry on her formerly lively interchanges with the nurses and staff, and she was intellectually deteriorating. She was suicidal. I told NIMI about this. I showed them the report. and then they wrote a report with Julia in it as a good example of psvchosurgical benefits. She happens to be in a custodial State hospital. They did not tell vou that, either. Senator Kex~eoy. T thought NTH took a very strong position on psychosurgery. Dr. Brecon. 1 do not think anywhere near hard enough. Senator Kexxeny. They indicated rather eloquently today that they had some very serious concern. They feel that control research should continue in a very carefully supervised fashion. They even indicated that there are questions within their department as to the proper way to proceed. It did not seem to me they were advocating psyvchosurgery. Dr. Brecon. This is a repeat of a sad old song and dance. In 1949 the National Institutes of Mental Health empowered The Group for the Advancement of Psychiatry to do a report on lobotomy which Dr. Brown did not tell you about. The Group for Advancement of Psychiatry reported back that lobotomy was an atrocity: it was destructive of the self. and so on. And they suggested more study. I believe it is tine to give up study. I do not think it is a medical issue. 1 think it is nonmedical surgery on people who do not have disease in their brain, and it should be stopped. Senator Kexxeny. T would like vou to make just a final comment. We will include all of your testimony in the record. 363 Dr. Brecein. There are very serious questions about Mark, Ervin and Sweet, which need investigating. There is the Justice Department memo I want to draw your attention to that alleges that they may have attempted to feather their own nests by selling themselves as a corporation largely owned by Dr. Ervin. hen there are things in their book, “Violence and the Brain,” which make you wonder about what they do not print. Their own book sug- gests that despite all the talk at NIMH about research standards there is no protection for the mentally ill. Senator Kexnepy. Please proceed. Dr. Brecon. I would like to read a quote about how a patient gave “consent” to Mark and Ervin. This is described in their book “Vio- lence and the Brain”: He agreed to the suggestion while he was relaxed from lateral stimulation of amygdala. However, 12 hours later, when this effect had worn off, Thomas turned wild and unmanageable. The idea of anyone's making a destructive lesion in his brain enraged him. He absolutely refused any further therapy, and it took many weeks of patient explanation before he accepted the idea of bilateral lesions being made in his medial amygdala. 1 think this should be stopped. Senator Kex~Nepy. Thank you very much, Dr. Breggin. I know you have spent a great deal of time and have reviewed this in great detail, and we are going to have all your testimony printed in the record. Dr. Andy, would you like to make any comments? You may do so, or you may submit a memo to us, whatever is your choice. Dr. Axpy. The patient J.M. has come up several times. I would just state he did have several operations, and after the first two or three he returned to school, and after about a year or so he regressed to the same type of psychotic behavior. We then did another thalamot- omy, and subsequent to that another operation. He had seizures. The patient has done well ever since the last surgery, 9 years ago. Senator Kex~epy. Where is J.M. today ? Dr. Axpy. He is in Jackson, and working six days a week, eight hours a day, and sometimes over eight hours a day, with a trucking firm. He is very happy living with his family and doing very nicely. Senator KExxepy. If there is anything else you want to add to the record, feel free to do so. Our next witness is Dr. Robert Heath, professor and chairman of the department of psychiatry and neurology at Tulane University. Dr. Heath, welcome to the subcommittee. STATEMENT OF ROBERT G. HEATH, M.D., PROFESSOR AND CHAIR- MAN, DEPARTMENT OF PSYCHIATRY/NEUROLOGY, TULANE UNIVERSITY, SCHOOL OF MEDICINE, NEW ORLEANS, LA. Dr. Hearn. Thank you, Senator Kennedy. It is a pleasure to be here to appear before this committee. Our psychosurgery research efforts in the department of psychiatry and neurology at Tulane University are centered around techniques involving implantation of small electrodes and cannulas into precise, predetermined brain regions. These techniques, developed in our lab- oratories, were first applied to patients in 1950—our series of human subjects now totals 65. Both the techniques and the rationale for thesa 364 procedures were derived from extensive animal experimentation, which provided the direction for our therapeutic efforts with patients. New procedures are never used in patients until they have been intensively tested in animal preparations—and then, only with application of every conceivable safeguard. Our aim has been the development of less injurious—and more effective and specifie—treatments for severe mental and nervous system diseases, which have been untreatable. The primary requisite in patient selection is failure of all existing treatments and a prognosis, without this intervention, of long-term, virtually complete disability, usually requiring permanent institutionalization. Further, we must be con- vinced that our procedures will be beneficial. While applied for thera- peutic reasons, the procedures have the added advantage of providing heretofore unavailable information concerning brain function—as it relates to behavior and to disorders of the nervous systen. Since the implanted electrodes and cannulas remain securely in the brain sites for many months, we are able to correlate mental activity and behavior with physiologic changes in the brain and alterations in body chemistry. These studies have permitted us to build a mean- mgful bridge between mental activity and physical activity of the brain, the organ of behavior. They have also elucidated precise altera- tions in brain activity, which occur with some neurologic diseases, such as epilepsy and narcolepsy, and with physical pain. During the period of treatment and study the patient is comfortable and. depend- ing on the presenting pathology for which the treatment was under- taken. he is usually ambulatory and able to leave the hospital for frequent visits with family members and friends. The behavioral phenomena of feeling and of emotion are basic in the development of normal—healthy—behavior and they are the kev to understanding maladaptive behavior—in the form of neuroses—as well as to understanding the grossly disrupted behavior of the psy- chotic patient. Our brain physiology studies in animals and patients have enabled us to localize pathways for emotion and feeling. With our techniques, we have demonstrated brain sites and pathways which are involved with pleasurable emotional states and those involved with painful emotional states—such as rage and fear, which are basic to violence and aggression. Brain recordings obtained from precise sites deep in the brain during these emotional states. whether spon- tancous or induced. show predictable altered activity. I have samples of brain recordings of patients, if anvone wishes to look at them. showing brain activity in association with these emo- tional states. For example. the pleasure-inducing. commonly abused drugs have been shown to activate the pleasure “circuitry.” So do spontaneous pleasant thoughts and feelings. Contrariwise. outbursts of violence suppress activity of pleasure sites and activate other focal sites, Elee- trical or chemical stimulation of brain pleasure sites induces feelings of well-being, whereas stimulation to adversive sites induces violence. rage, and related adversive emotional states. Therapy evolves from the consistent demonstration of an inverse relationship between the “eirenitry™ for these two basic affective states, pleasure and adversive emotion—for example, when pleasure is induced. violence. rage. and ageression are obliterated. Should stimulation fail to produce the 365 anticipated beneficial result, our brain recording data may indicate that interruption of one circuit can indeed be therapeutic. Then, on the basis of the recording data, our chances of making a discrete brain lesion in the right spot, in order to alleviate symptoms with- out undue damage, are notably enhanced. We are aware of—and have long debated—the ethical factors of these treatment procedures and the “safeguards that are essential for the protection of the patient. The medical school human research committee is composed of medical scientists, attorneys, and clergy- men. All of our procedures are subject to the review and approval of this group. We insist that all patients, as well as responsible family members, are thoroughly informed of the nature of the procedures and of every possible undesirable complication before forms are signed and the procedures are undertaken. Senator Kexxepy. Do you think that is terribly important? Dr. Hearn. Terribly important. The patients, as well as their fam- ilies, are interviewed by doctors on the faculty of our medical school department at regular intervals during the entire period of study. Senator Ken~epy. They are presented not to one doctor, but to a group of doctors? Dr. Hearn. Correct. Senator KenNepY. So it is not only the ones who are going to be actually participating in a particular procedure but it includes the other doctors? Dr. Heat. Yes, that is correct—doctors who are not actively involved. There are also ethical questions from another viewpoint. Is a doc- tor justified in withholding treatment with a procedure that might carry some risk if the alternative is the certainty that the patient will spend the rest of his life in the back ward of a mental institution ? For example, one of our patients previously had years of psychia- tric treatment without effect before we initiated the depth electrode implantation procedure that IT have described. Both she and her fam- ily offered to testify because she is now so much better. Dr. Nolan Tewis, a former professor of psychiatry at Columbia University, repeatedly stated that any procedure which offers even minimal hope of preventing chronic hospitalization—even if it is risky—is worthy of trial since life in the back ward of a chronic mental hospital is worse than death. It was Dr. T.eo Alexander, a psychiatrist, who proposed the basic points which constitute what is now known as the Nurenberg Code. 1. Enlightened voluntary consent, in the absence of duress, coer- cion or deceit, and with full disclosure of hazards and inconveniences. In the case of a mentally sick subject, such valid consent may have to be obtained from the next of kin, as well as the patient whenever possible. 2. Humanitarian purpose, unachievable by other means. 3. Sound basis on all other sources of knowledge, including ani- mal experimentation. 4. Avoidance of all unnecessary physical and mental suffering and/ or injury. 5. Absence of a priori reason to believe that death or disabling in- jury will occur. 93-999 (Pt. II) 0-173 -3 366 6. Risk proportionate to humanitarian importance of problem. 7. Proper preparation for adequate protection against even remote possibilities of injury, disability or ot 8. Experimenter scientifically qualified, possessing highest degree of skill, and exercising highest degree of care. 9. Option for discontinuance always available to subject on request. 10. Discontinuance mandatory whenever experimenter discerns dan- ger of injury, disability, or death of subject. In my opinion these 10 conditions continue to form a sound basis for the physician when he weighs the options of potential therapeutic gain against possible injury. Our therapeutic results at Tulane up until now have been gratify- ing, by and large. Perhaps more important, they have led to the establishment of a necessary foundation for the development of more precise and specific therapies than now exist for the treatment of behavioral disorders and some neurological diseases. Cries of concern are frequently heard about “mind control.” Cer- tainly. the possibilities of brain research are broad and awesome. But this is no reason for introducing a dark age. Exciting and potentially beneficial basic new information is available and more is forthcom- ing. It seems to me that it is the physician's responsibility to ascertain that new technics are used constructively to alleviate, whenever pos- sible, personal handicaps and discomforts and to increase man's ability to live with his fellow man. Senator Kenney. Very good. Dr. Hearn. If there is time, I might make one other point. There is always a tremendous amount of emotion and sometimes confusion and concern about procedures, particularly new procedures which involve the nervous system. Horsley was practically ostracized when he did the first spinal sur- gery. An editorial in a 1972 British medical journal described this : “A cry of outrage from the medical establishment-——Horsley had gone too far, encroaching on the canal that carries the spinal cord and soon.” Iiverytime a new procedure involving the nervous system is intro- duced. there is an outery. Ignorance breeds fear. Senator Kexzepy. Of course, on the other hand, there are some very legitimate and real concerns. Dr. Hear. Correct. Senator KexNepy. Maybe we could have the films. Dr. Heart Thad better give you some background for them. Senator KENNEDY. You can monitor as we move through. Dr. Hearn. I just want to introduce the first sequence film as it is not adequately labeled. (Motion pictures were shown.) Dr. Hearn. This sequence shows a patient in whom we turned on the adversive brain circuitry to induce violent impulses. In the second film. pleasure sites of the brain are stimulated to relieve physical pain. 367 And in the third film, pleasure sites are stimulated to remove the emo- tional pain of episodic rage and paranoia. Before psychosurgery this first patient was in a mental hospital; his prognosis was for lifelong hospitalization. Since our studies—I be- lieve they were in 1953—he has remained outside of the hospital. This is the start of the stimulation. The patient begins to cry out with rage. He tells the doctor who is nearest to him, a neurosurgeon, that he 1s going to kill him ; that he wants to murder him. As soon as the stimulus goes off, this emotional state disappears. We ask him why he wanted to kill the doctor, and he answers that he had no awareness of wanting to do this; that he likes him. Then he begins to associate, i.e., to recall similar violent episodes, that he had had spontaneously in the past that were a part of his illness. What we were able to do was to induce this violent reaction that may occur spontaneously in association with some types of behavioral pathology. Senator Kexnepy. As I understand, you were trying to replicate his feeling of violence; is that right ? Dr. Hearr. That is correct. Senator Kex~epy. To identify it, with the idea of treating it fur- ther? Dr. Hear. Yes, identifying it and how it works, we can then treat it. Emotion is basic to all types of behavior, normal and pathological. This second patient is telling about receiving morphine. (Sound track of film was turned on.) Senator KexNEDY. Is that an electrode implant ? Dr. Hearn. Yes, there are multiple electrodes in hei: brain. This third patient is in restraint because he had a violent attack of paranoid rage—psychotic behavior. When a patient 1s psychotic, even as a result of schizophrenia, there is a localized brain pathology—nothing you can see under the micro- scope. Senator Kex~epy. Doctor, what are the real implications of this technic, looking down the road maybe 5 or 10 years? Dr. Hearn. Regardless of how we intervene in a patient with be- havioral disorder; we have to be cognizant of the role of emotion, pain- ful emotion as well as pleasurable. This is important in the whole learning process in normal human subjects. The neurotic is neurotic because of maladaptive behavior. He dis- plays in appropriate fear and rage. The psychotic, who has hallucinations and illusions, is unable to feel pleasure. Thus it is important if we are to understand and treat be- havioral disorders that we establish the brain mechanisms underlying the basic behavioral phenomena of feeling and emotion. To develop more effective specific treatments for behavioral disorders, we need the kind of tools I have described. Senator Kex~epy. What you are really talking about is controlling behavior. Dr. Hearn. I am a physician and T practice the healing art. T am interested in treating sick behavior—not in controlling behavior. The tools can be misused, whether misuse of treatment by drugs or any other medical procedure. 368 Senator KENNEDY. You have shown and testified about how you can replicate pain and pleasure by the implantation of these electrodes in different parts of the brain. Dr. Heartu. Yes. Senator KeN~epy. This is behavioral control. As I understand it, you are trying to use this technique to treat people. Dr. Hearin That is correct. Senator Kexzepy. Would it not be adaptable to treat other people as well, normal people ¢ Dr. Hearn. I think it would be, but I think normal adaptive people are already being treated. I am sure Dr. Skinner is going to talk on that. Our learning experiences, our attitudes are modified every day. Senator KenNepy. Could it be used as say, alcohol or drugs have been in the future ? Dr. Hearn. We have had very good results. The data forthcoming from these technics have made it possible to establish correlations be- tween brain activity and basic emotional states. We can simultaneously interview a patient and observe his brain activity. We can also administer drugs to produce intense pleasure or pain and concomitantly observe brain activity. We have similarly made these observations while a patient is smoking marijuana. I should point out that marijuana would only be given to a patient if he is al- ready a chronic user. That is true of other deleterious substances as well. Two of our patients have been chronic marijuana users (this is a side issue) but they were being treated for other disorders. Since this treatment program was carried out—since they were stimulated, par- ticularly in the pleasure circuitry, neither one of them has wanted to touch marijuana. The pleasure achieved with marijuana did not begin to approach the pleasure that was induced with stimulation of the pleasure sites. Senator KENNEDY. As you pointed out, this has great implications in terms of behavioral concepts, but how are we to know they are always going to be used constructively, positively / Dr. Hearin. For one thing, about a million dollars worth of equip- ment is required for our studies, as well as a large number of highly skilled personnel. Senator Keepy. What about in five years or so? Is it that complex from an engineering view point ? Dr. Hearn. I think it is probably too complex. I do not think you will have to worry about too many being done. By these technics, we can work with one of two patients a year at the most. I cannot con- ceive of it being done off the cuff simply and quickly. t I' hope we can come up with less complex procedures in the future. Senator KeNyepy. Should we not be concerned about mass application? Dr. Hearn. 1 do not see any cause for concern of mass application of such technics. I think drugs do have marked effects and they are readily available. I think they will continue to be a problem unless their use can be effectively controlled. Senator Ken~eny. Thank you very much. Our next witness needs very little introduction. Dr. Skinner, you may proceed with your statement, sir. 369 STATEMENT OF PROF. B. F. SKINNER, HARVARD UNIVERSITY, CAMBRIDGE, MASS. Dr. Skinner. The control of human behavior through drugs, psy- chosurgery, or electrical stimulation naturally attracts attention, but far more powerful methods have been in existence as long as the hu- man species itself and have been used throughout recorded history. To a very great extent what a person does is determined by the physical and social environment in which he lives—by his past exposure to that environment and by the immediate situation. Behavior is selected and strengthened by its consequences—by what the layman calls rewards and punishments, and this fact has long been exploited for purposes of control. Recent research has told us a great deal about the basic proc- esses, and the results permit us to interpret many familiar aspects of daily life and to make important changes in our practices. The commonest kind of control is punitive. A government controls its citizens by fining them, putting them in jail, or even killing them when they disobey its laws. One government controls another by mak- ing way. Many religions control their communicants with the threat of hell-fire. Corporal punishment is still common in our schools, and where it has been abandoned, other punitive consequences are often used. Companies keep their employees at work by threatening to dis- charge them if they stay home, come late, or work carelessly or slowly. Parents control their children by spanking them, and people control each other with criticism, complaint, ridicule, or even physical assault. As a result a good deal of what we do each day is done to avoid the con- sequences of not doing it. The result is not satisfactory. Under punitive control a person does not feel free. He is not doing what he wants to do or what he likes to do; he is doing what he has to do. The system fails when people avoid punitive consequences in unexpected ways. They may escape from the punisher—as by defecting to another government, giving up their religion, or playing hookey from school—or they may act to weaken or destroy the punisher—as by overthrowing a government, attacking religion, or vandalizing schools and assaulting teachers. An alternative form of control—the use of rewarding rather than punishing consequences or, in technical terms, the use of positive rather than negative reinforcement—lacks many of these disadvantages. It is scarcely to our credit that we so often punish rather than reward, but there are reasons why we do so in the very nature of human be- havior itself. Punishments have quick and powerful effects. Rewards are better in the long run, but the long run does not often make itself elt. Senator Kennepy. Is that not really basically manipulative, Doctor ? Dr. Skinner. Yes, it is. Both of them are basically manipulative. Extensive laboratory research has been needed to reveal the power of positive reinforcement and to suggest more effective ways in which it can be used. With the aid of that research, some important changes are being made, as in what is called behavior modification. 370 It has been possible to redesign the environment of the retardate or psychotic in such a way that he leads a more productive life. Senator KENNEDY. Let me ask you who is really going to redesign it. Dr. Skin~NEr. That is the question I am taking up later in this paper, if I may reserve my reply. Senator Kex~Nepy. Yes. Dr. Skix~er. The same principles are being applied in face-to-face psychotherapy. It has been possible to redesign life in a training school for juvenile delinquents—to reduce disciplinary problems and to en- courage boys to acquire the skills and knowledge needed if they are to live acceptable lives when they leave the school. It has been possible to design new classroom practices, from kindergarten through gradu- ate school, often with the help of special kinds of programed materials which make it more likely that the pupil or student will be reinforced rather than punished. It has been possible to design better incentive systems under which the employee not only works more -arefully and industriously but enjoys what he is doing. Relations between parents and children can be made pleasanter and more effective, and the prin- ciples have suggested improved technics of self-control or self-man- agement. It is just possible that governmental practices are within reach, and that domestic and international problems can be solved without resorting to increasingly violent measures. Under positive reinforcement a person feels free. He is said to be doing what he wants to do, what he enjoys doing. But these gains are viewed with alarm by many people. Danger lurks in the very fact that positive control may not be resisted. Punishment has at least the merit that it generates countercontrol. The punitive controller even- tually runs into trouble, but the positive controller may achieve a new and frightening kind of despotism. These are no doubt issues to be taken seriously. Almost any kind of scientific knowledge can be mis- used, and knowledge which bears on the control of human behavior is particularly threatening. Control itself needs to be controlled. But by whom and according to what principles? A useful pattern has already been worked out with respect to pun- ishment. Tt is true that punitive practices breed counter measures, but it is by no means the case that they are fully contained. We still live In a highly punitive society. Many people cannot countercontrol ef- fectively, and some longstanding examples of mistreatment illustrate the result. Old people, homeless children, prisoners. retardates, and psychotics have all from time to time been shamelessly mistreated, and simply because they cannot effectively protest. The citizen who can- not walk safely in the street at night shows our failure to control the punitive practices of the mugger. The most tyrannical or corrupt gov- ernment can be overthrown only if revolutionists gain control of puni- tive agencies, such as the police or military. Nevertheless, societies have long tried to establish the principle that the use of force is wrong and—characteristically—they have tried to suppress it by punishing those who use it. Punitive measures have been to some extent contained by setting up superior controlling forces. Something of the same sort must be worked out for technics of positive reinforcement the power of which we are just beginning to see. 371 But it is a mistake to suppose that this means that control itself is wrong. Whether it is wrong depends upon the consequences. When we escape from punitive control, we feel free, but we may still be con- trolled by nonpunitive conditions, and that is the danger. We are all controlled all the time—by what has happened to us in the past and our social environment. The prisoner of war who resists efforts to de- mean him or to change his views is not demonstrating his own auton- omy: he is showing the effect of earlier environments—possibly his religious or ethical education, or training in technics of resistence in the armed services. Those who must bitterly attack practical appli- cations of a science of behavior are themselves trying hard to control behavior and would do so more effectively if they knew more about the basic processes. We can solve these problems sensibly only by recognizing all the forms in which control may be exerted. Those who are now using recent discoveries to improve the care of the retardate or psychotic or to design better classroom practices or incentive systems are not in- creasing the extent of the control under which people live; they are simply correcting kinds of control which are ineffective or troublesome. A careful examination of thé behavioral processes involved in the prac- tices of a culture can lead to the redesign of that culture, so that it will more successfully solve its problems. Senator KXex~Nepy. Thank you very much, Dr. Skinner. In a very few comments you have covered a large spectrum of matters of great interest. How do we as a society determine what is positive and what is nega- tive? What is positive for one segment of our society might not be positive for another. For example, minority groups might have very different beliefs about what is required for them to feel free and to enjoy what they are doing. How do we handle that dilemma ? Dr. Skin~er. In the long run I think this is an experimental ques- tion. I myself take a survival view of ethics. I think cultures evolve in different ways, and as a result some are more effective in solving prob- lems than others. We have proved to be very effective up to a point, but no one is very happy about the state of our own culture today. Mainland China is evolving in a very different way, and there are many promising reports of what is going on there. Nations are in a sense organisms which are going to be competing with each other in a kind of natural selection, and IT think the only ultimate question is whether one practice is more likely to develop the genetic material in a culture to its fullest advantage. I would like to look at educational practices. I know many people disagree on what children should be taught, how long they should be taught, and so on, and how they should be taught, but I think in the long run we could design kinds of education which would make this society as successful as possible in solving its problems. Senator Kenney. Of course 1 suppose it raises the question of the criteria in terms of a desire to be free. How do you really handle the diversity of minorities, the Indians, the Chicanos? 372 How do you make sure when you are trying to determine positive forces for the majority that you are also going to be sensitive in pre- serving the rights of the minorities? Who is really going to say what is best for minority groups? } Obviously they have a different view of what are positive factors. Dr. Skin~er. T quite agree that diversity is extremely important, and there is a parallel in biological evolution. People who work on various kinds of wheat, for example, have dis- covered that when they have selected only a few and have allowed a great many natural deviations to disappear, they have less material to work with to find a new strain that will be more resistant. It would be a great mistake to design a culture in such a way that everyone in it was like everyone else. It would be a fatal mistake, and it is the survival of the culture that will tell us how much a mistake it really is. Senator Kex~epy. I suppose the key question is if we are able to have this kind of impact in controlling behavior in a sophisticated way, how we can be sure that it is going to be used in a constructive way and not used in a way that is counterproductive. Dr. SxixNEer. It is a problem. T believe it is possible to change class- room practices in the schools so that evervone will learn how to read and write at a reasonable level. But then someone will say. “Yes, but who are you to decide this is the right thing?" I am willing to make that decision and say that reading is a good thing for Americans to know. The techniques T would use would not he the techniques which induce a student to play truant or to attack teachers or sit around in an apathetic wav. They would give the teacher more power than he or she now has. but T am not worried about that because the teacher is there to do something, and new techniques make it possible to do it. Senator Kexxeny. You talk in your testimony about the potential of the reduction of violence even within a nation. There is no way of being able to detect whether those forces whieh may be effective in reducing violence may not also be forees which may escalate violence. Dr. Sxin~er. T think the mistake is to attack violence itself as if it had to be restrained. as in a straitjacket. That mav be necessary with some kinds of violence, but the violence exhibited by students in high schools today, for example. is not going to be contained by more severe punishment. It is going to be contained by changing the situations that generate violence. Our schools are creating the very problems which they find it so difficult to solve. If T were to take on the project of making students less violent toward each other and toward the teacher and school property. T would not begin by imposing punitive sanctions. I' would look into why they have been violent. Perhaps they are not enjoving what they are doing: it is more fun to be violent than to sit down and study. But you can redesign materials in such a wav that even students who have been called unteachable apply themselves, en- joy themselves, and learn. This is being demonstrated today in Ameri- can schools, but unfortunately on a very small scale, because the eduea- tional establishment is a very difficult thing to change. 373 Senator KEnxNepY. Do you think all behavior is predetermined? Dr. SKINNER. Yes; I think it is—by a great variety of circumstances. I think everything a person does is, first, a result of his genetic history. He is a member of the human species, and be behaves like one. Secondly, it is the result of the extraordinary environment to which he has been exposed—his family, his religion, his schooling, his gov- ernment, and so on. All of these put together, as far as I am concerned, determine what a person will now do, and if you want to change his behavior, then change some of these things. Senator Kennepy. Dr. Skinner, thank you very much. You have been very helpful. Our final witness this morning is Dr. Willard Gaylin, president of the Hastings Institute. Dr. Gaylin, welcome to the Health Subcommittee. We very much appreciate your taking the time to be with us, and we welcome your testimony with great interest. STATEMENT OF WILLARD GAYLIN, M.D., PRESIDENT, HASTINGS INSTITUTE, HASTINGS-ON-HUDSON, N.Y. Dr. Gavin. Thank you, Senator Kennedy. One of the advantages of being last is I can summarize my position in terms of some of the positions that have already been presented. I think behavior control is an enormously serious problem that has not been attended to adequately; that it needs a kind of regulation that is not at present available, that some of these are legislative, and some of these are not legislative ; some of them are already indicated and designed and some have still to be researched. About three years ago the Hastings Institute began to be concerned about the prospects of behavioral control technology. It was seen as roughly analogous to the situation of ecology before that term was invented. In those days technologists were concerned about urban crowding, marine biologists were concerned about the rivers and water- ways, etc. yet there was not an awareness that these isolated people were dealing with similar problems. Behavior control is seen by many of us in the field as a problem arising in a similarly disparate way. Psychosurgeons are beginning to do more meticulous and detailed operations for purposes of behavior modification. There are new drugs becoming much more refined than the old ups and downs we used to have, and there is the increasing impact of television (with an estimate of 4 year olds watching 40 to 60 hours per week). Total institutions are shaping people; the nature of the response to Dr. Skinner’s book with its “recommendation for mass social engineering” indicated the seriousness of the problem. So we undertook a kind of research, beginning with what we thought was the simplest and narrowest form of behavior control—psycho- surgery. I still feel psychosurgery is probably attended to much more than is warranted in terms of its real threat tc manipulation of the population as compared with some of the other things. Senator KenNepy. What other things? Dr. Gayruin. For example, it is getting a little ahead, but since I have an informal presentation 374 Senator Kexxepy. Just continue along with your presentation. Dr. Gayoin. It seems unlikely, if there were some plot to take over the country by a totalitarian, to use some of the ideas suggested today that psychosurgery would be the method of choice. T doubt that they would find the most eflicient technique for mass control would be plant- ing electrodes on a population of 200 million, or psychosurgery. when they have access to a limited national television, and to schools with compulsory education, to psychological inputs and to drugs, all of which afford a more convenient, cheaper, economic mass method of manipulation. One of the ways which has not been mentioned at all came up in- cidentally in the dialog between vou. Senator Kennedy, and Dr. Heath, and that is one of the real threats I as a psychiatrist have been concerned about; that is. the coercive aspect of the definitions of *normal.” By defining something as normal in the medical sense vou take it out of the moral field. and vou put it into the medical field. Medicine has traditionally had a coercive right—we allow doctors to coerce. Senator Kexxeny. Would you explain that? What do you mean by “we allow doctors to coerce #7 Dr. Gayrix. We allow doctors to coerce both directly and indirectly in a way we do not allow other professionals. Tf a minister tells us it is immoral, we are as likely to change—if it is a cherished belief—our minister, or our religion, rather than our behavior. This is evidenced in such problems within the Catholic Church in terms of birth control, abortion, etc. When a doctor tells us, you are going to die or live because of this, we generally tend to follow his orders. When you asked Dr. Heath, Does he want to “modify behavior?,” he said, No. of course I do not want todo that: T want to “treat illness.” But you see by defining something as “il” we then place it under the medical prerogative where, if necessary. as for example we have done with fluoridation of water, we can make it a legal mandate. We do not usually legalize morality. but when we get into psyeho- logical behavior rather than physical we are getting into a borderline category. It is interesting to hear Dr. Bregein refer to “normal con- cepts” with such assurance. What is “normal™ has been debated for 2,000 years. I think it should continue to be debated. For by utilizing definitions of normalcy we then become entitled to drug people. to operate on them, to deprive them of civil liberties. It has been demonstrated in the case of mental illness. We take these people away from the punitive aspect of the law, but we also take them away from the protective decency of the law. too. To go on. when the Hastings Center first became concerned with this problem we held our first conference on psvehosurgery, and we invited many of the men doing work in this field to find out how sensitive they are to potential abuses and what they really were doing in any way to understand the political implications of their work. Again, while T think the problem of psychosurgery is less pressing than other aspects of behavior control. I go along with Dr. Brown - it /s a lightning rod issue and it does deserve great attention because it focuses on some problems that transcend itself. 375 For example, the problem of defining experimental versus the therapeutic in surgery in general. One intriguing thing that came out of the first conference was the awareness that in contrast with all the legislation for control of drugs, we have absolutely no control over surgery. I suspect this is an historic phenomenon. At one time surgery was so monstrous that in order to undertake it you literally had to be in a position of extremis. Before sepsis was controlled you would die of infection—and before anesthesia the pain was excruciating. Be- cause of that we never visualized mass, easy surgery. We think of surgery as a terribly difficult procedure, but the lobotomies that were done by Dr. Freedman with an ice pick in his office show this is no longer true. You do not even have to have the special technical equipment. There is a total absence of control of surgical procedures. Let me give you an example of the importance of “this outside the field of psychosur gery. There is an operation, a revascularization operation for heart attacks. The operation had terrible mortality rates—60 to 80 percent. . As a result, only patients at death’s door were sent for this surgery. A very fine surgical team in New York developed the operation to a point where, miraculously, mortality rates were only 10 percent. They received a flood of patients. It should be noted that this is an operation to relieve the excruciating pain which debilitates the patient; that is, angina, but there is no evidence that it prevents future heart attacks. This is a procedure that is now being heralded. I ask you, however, to suppose it were a drug. If I told you I had a drug that relieves the pain of angina, has no guarantee, or there is no evidence that it particularly cures or prevents coronaries, that causes 100 percent morbidity, which surgery certainly does, and only causes 10 percent mortality, how would you respond if T proposed that as a drug for marketing? T would be thrown in jail or commitment procedures would be ‘instigated. There is a gr reat need for greater regulation of surgical procedures. We should demand distinctions between ther apeutic and experimental. Distinctions and clearly stated definitions. We should know the kind of operations done, by whom, and for what purposes. The confusion demonstrated today about the number of cases of psychosurgery does not, I think, represent duplicity, but simple ignorance. It is time for a registry of surgical procedures performed. Senator Kex~yepy. What would you do after you have collected that information ? Dr. Gayrin. I think there are a certain number of proposals that should be made, but Senator Kenxepy. Why not just continue? Dr. Gavyrix. There are other problems. I will skip some of this. Senator Kexxepy. No; you are doing fine. Dr. Gayrax. The problems of behavior control are not new. Obviously, as Dr. Skinner has said, people manipulate people all along, life’s courses, and I suspect that has happened from the time there were the first two men or, more accurately, one man and one woman. 376 The distinction is that in those days, in the early days, the sources of manipulation were available to everybody. and who could be manip- ulated was pretty much limited to those who were in earshot. The problem that is arising today is that the manipulation becomes much more complex, much more subtle, the techniques more difficult to understand, while more powerful and they are being focused in the hands of fewer and fewer people, and therefore, more capable of abuse by government, which represents the ultimate potential threat in terms of deprivation of liberty and autonomy. I am therefore dis- tressed to see so much attention directed to psychosurgery, when the real threat of manipulation will most likely arise in other areas. In addition. there may be in the future some great potential for relief of suffering. For example, Dr. Breggin is terribly concerned about blunting nor- mal behavior. but 1 am not sure how he is defining normal. We are not talking of you or me. For example, he goes to the extreme of saying that a person who is in the agonies of terminal cancer should not be allowed recourse to a pain relieving procedure because it is “partial euthanasia,” since pain is a component of self or identity in the living human being, and this should not be blunted. I do not know what “partial destruction of self” means, I am not sure what “identity” is. and T know I do not know how he defines “human” in a human being, but Dr. Breggin may be able to answer that. But we need not argue about what intractable pain does. Any of us who have experienced even mild pain know what that does to our sense of dignity. We are unalterably opposed to torture because it humiliates and demeans a person. It is a way of reducing him to less than human. Senator Kex~epy. In fairness to Dr. Breggin, T think he was not as strong on intractable pain as he was on some of the other forms. Dr. Gayrin. But intractable pain as defined by him is physical. As a practicing psychiatrist, he as well as I, know that there is mental anguish equally unbearable. T have seen patients who have literally rubbed the skin off their fingers from agitation, eventually leading to self-amputation of whole fingers. That is intractable pain. This does not mean that T am supporting psychosurgery at this time for even these conditions. But T am saving that some of those arguments about “reduction of the self” must be understood in terms of the conditions for which they might be prescribed. The sane reason- ing might be used to demand that we should not use drugs. They too reduce the individual and it does not really matter how vou destroy a brain function: whether vou drug it, whether vou destroy it with a toxin, with heat, or with a scalpel. These are not the important distinctions. Obviously there are certain problems which make psvchosurgery particularly needful of control. Tt deals with behavior that is quite different from the liver and the kidney. When vou talk about how the kidney affects human behavior, it will deal with such things as blood pressure, B.U.N., ete. but with the brain vou are dealing with social and political behavior and here you have to be particularly cautious. 377 Also, when you run into the problem of social deviance, a still fur- ther caution must be exercised. We are never sure whether what we do is in the service of the individual himself or the society around him. I think that is crucial. There are certain things a patient has a right to do to himself to serve his needs. This is a different category from those things we may do to an individual to serve someone else’s needs, or society’s. We must vigilantly make sure that “medical treat- ment” does not become a euphemism for social control. Also the consent problem is an enormous one in psychosurgery. The damaged organ of the sick person, is the consenting organ. If your foot is damaged, it does not affect your consenting ability except pe- ripherally, but if your brain is damaged, it does indeed. Here, there- fore, we will be dealing with a lot of people who are required to have proxy consent. All of these indices therefore would demand particular stringency and controls over psychosurgery, beyond that of other forms of surgery. The evidence is, as Dr. Breggin has very well documented, that the opposite is true. The kinds of controls in psychosurgery from our investigation, at the Hastings Center, have in some cases been casual to a point of irresponsibility. Follow-up has been very poor, controls have been poor or non- existent, peer review has been absent. Senator KExnepy. Let me just mention at this point we have had hearings that have lasted for two days on the use of drugs; and con- trol is just as completely inadequate and poor in that area as it is in the area of psychosurgery. These are two broad areas and the con- clusions you have drawn here today are the same that we have drawn over the period of the last two days, particularly with respect to Depo-Provera and DES which are being widely used among the large part of the population. Dr. Gayrin. I would say, Senator, that you can extend the ob- jections, even beyond these two areas, to the large field of medical care. Senator Kex~epy. What does that mean ? Dr. Gavin. A kind of paternalistic or authoritarian role has been adopted by medicine and allowed to them by the populace. A sick person relates generally to his physician the way a child does to a benevolent parent. Senator Ken~epy. What does that mean for the consumer, the patient? Dr. Gayrin. It means he has been deprived of many of his rights and is often unaware of the deprivation. Interestingly enough, the Ameri- can Hospital Association has just issued a statement on this. I found the statement somewhat misleading. The hospital's are “granting” rights which are not theirs to grant ; rights belonging to the patient but violated by the hospital. It is like a hold-up man telling his victim, Poy shouldn’t allow me to do this; be careful where you put your wallet. Senator Ken~epy. What is the medical profession doing to remedy this situation ? Dr. Gavin. Very little. Most of the researchers who violate basic rights, for example, are not doing it except for philanthropic and 378 humanistic reasons. If they were doing it for money. we would control them more readily. Recently the Tastings Center examined what seemed a case of clear violation of ethical medical procedures in a psychosurgery research. We then wrote the significant organizations: the Dean of this medical school, the professor of psychiatry. the professor of neurology, the Veterans Administration who had referred some patients: the president of the American Psychiatrie Association, the president of the American Neurological Association. the American Medical As- sociation, ct cetera, some 20 letters, asking them specifically what they considered their responsibility as an institution in controlling and overseeing this sort of experimental procedure. You may know that the American Medical Association Judicial Council works by an apellate reviewing hoard. Nothing concerns them unless it is brought to them: they do not feel that they have a moral institutional obligation to question the methods of certain doctors, In an active supervisory capacity. These groups are servants of the professional, and servants do not dictate to their masters. 1 think that the public will have to demand its rights through the legislatures and the courts which are in that sense their servants. I might say that IT do not particularly believe that psychosurgery should be outlawed. For one think T do not think you can outlaw some- thing you have not defined. and the definitions given have been grossly inadequate. I will say this. however, that 1f you took all of the precautions that were normally indicated and that i decent set of cuidelines would re- mand, you probably would prohibit some 90 percent of the surgery now going on, and rightfully. IT say. Senator Kexxeny. What do vou mean by that? Are you talking about psychosurgery or just general surgery Dr. Gavin. Psychosurgery I am talking about specifically. With general surgery I would have to lower the percentage. but otherwise I think it would still be true that guidelines and controls are impera- tive and long overdue. The percentage of other types of surgery that would be prohibited might he down to 10 or 20 percent. Recent atten- tion has been directed to radical mastectomy which has been done for years and years with no proof that it offers any greater success than simple removal of the tumor. To return to psychosurgery. I think the problem can probably be stated thusly. T do not want ab: Fr gp of psychosurgery because I think it may have some potential. T am sure it has not been give adequate safeguards, and supervision—and this is the current wrgent need. Senator Kex~eny. Tow do we develop those safeguards? Dr. Gavrix. T think we can begin to put the heat on the institutions like the American Medical Association, Neurosurgical societies, ete, and point out that there is a concept called institutional responsibility. Senator Kenxeny. What do vou mean by “heat™? Who is supposed to put what heat on whom ? Dr. Gavin. Well, I think a hearing like this is a good beginning. Senator Kexxepy. Do you mean regulations by the administration / 379 Dr. Gavin. These institutions were originally designed as protec- tive guilds, and they still function primarily in that sense. By writing letters to all of the heads of these organizations we hoped to stimulate them to reevaluate this sense of their function. But I suspect that they will always be more concerned with the protection of the rights of their constituents than with the public per se. That is their function, in the same way that I suppose a labor union is primarily concerned with the wages of its members, rather than the welfare of the total population. Patient-consumers must no longer trust exclusively the benevolence of the professional. But basic decisions must be returned to the hands of the patient population whose health and future will be affected. Too many things are passed off as professional issues because they have fancy language and involve difficult technology. Most are not professional at all, but ethical value issues in disguise. Here we should all share in the decisionmaking. Senator Kexxepy. What kind of conditions would you put in effect before an individual doctor could move ahead with a psychosurgery procedure ? Dr. Gayriv. I think the minimum he could do is to give us a proto- col, a written protocol. I think the protocol should be forced to subscribe to certain standard conditions that the National Institutes of Health and various other organizations should draw up. They have not as yet, or they are in the process, but T am hopeful that they will shortly. I think if a man cannot give you a set of written guidelines, you have a right to say: “Until such time as you prepare those guidelines, we would appreciate your not doing this surgery—no, we demand that you not do it.” I think they ought to define the conditions for which they operate with greater specificity. What is aggressive behavior? Who the hell knows? In the loosest sense we are all behavior problems, and we all re- quire protections from our aggression in one situation or another. 1 think that they ought to specify their diagnostic terms, define them clearly. They must define operative expectations, tell us what they ex- pect—how they will measure success and failure. I want a standard of how they are going to follow up. When a man says he has a followup procedure, I want to know what he means. IT always keep in touch with my patients after treatment. But I do not call that a “followup procedure.” Also I think there should be the same careful distinctions between the experimental and the approved that we use with drugs, at least that much. And this goes, I think, well beyond psychosurgery into all areas of surgery. Senator Kexxepy. We have seen that does not work at all. We have seen in our testimony of the last few days that you can permit an ex- perimental drug for one purpose and it will be widely used by physi- cians all over the country for an unapproved use. There is absolutely no control on that. Dr. Gayriy. Then T would say we have defective models and what should be done is to rectify that deficiency in the Food and Drug Administration. . 380 Senator Kexxeny. Back to the peer review procedure. In psveho- surgery. would vou include others than the physicians themselves? Dr. Gayrin. T think so. particularly since you are going to go into Ul defined areas of emotional behavior, Certainly we should demand also that more conservative techniques he adequately tried, tested and documented before we turn to something as irreversible as psycho- surgery. Senator Kex~eoy. You talked earlier about the political implica- tions of this. Could you develop that a little bit? Are you a Democrat or Republican? | Laughter. | Dr. Gave. T could say that T refuse to answer on crounds of in- crimination after that last election. It is hard to find us Democrats around lately. I'am concerned about the capacity to control large populations. 1 became concerned from my own field. as I earlier suggested, from the concepts of normaley. By defining something as normal you have enormous power, that is. as a psychiatrist you have enormous power. While Dr. Breggin is relieved that they do not perform psycho- surgery in Russian (and I am not sure whether that is still correct), I do know by recent work that they are getting more interested. But they exploit by other means which disturb me even more. L am concerned the way that values creep into schools. communi- ‘ations, textbooks. unintentionally as well as by ealeulation. I think the whole black experience indicates that they have suffered from stereotyping and its consequent humiliation as well as some of the realistic deprivations economically endured—I do not know how much was calculated or coereive, but 1 do not really care. It had the effect nonetheless of depriving a large part of the population. Senator Kennzepy. You think then the blacks have a legitimate con- cern about the implications of this behavioral research as it applies to them ? Dr. Gavin. Yes. T think that as a minority group with limited access to power, they have a right to anxiety about potential exploita- tion and abuse. I think they have a legitimate concern, even though I do not know of any calculated plot against them in this area. Dr. Brecers. May I have the same right to reply as vou gave Dr. Andy? Senator Kexxepy. Briefly. You mentioned his name during your opening statement, so we want to hear whatever his response is to those particular parts of your testimony that relate to him, and then if he wants to we will provide him an opportunity to develop that in a fuller manner. Dr. Brecary. Thank you. T have about five quick points. First of all. concerning phychosurgery for intractable pain. it is simply that we do not want euthanasia to be left in the hands of the physicians. Secondly, one of the reasons why Dr. Gaylin is not coming out against psychosurgery is that the men he works with are not fully antipsychosurgery. He does not have anybody on his ethics group who is against it on principle. In addition, a man on his board has covertly helped Dr. Mark clean up and improve his most recent polit- ical comments to make him appear less totalitarian. 381 Another point is the reference to totalitarianism—and the threat of psychosurgery for political control. I cannot exaggerate. We do not have to put electrodes in the brains of everyone in the entire popula- tion; all we have to do is do this to a few key people. The rest will be intimidated. Concerning the issue of man’s self and identity, I do believe that we are more than our molecules. I will leave it at that. On the issue of drugs being as dangerous as the scalpel, I think that makes his position very, very dangerous. The scalpel provides a per- manent mutilation. In conclusion, I simply think the real political issue is this—is America going to go forward toward more freedom or toward more control ? Senator KexNEpy. If you want 30 seconds, you may have it. Dr. Gayruin. No. Thank you, Senator. Dr. BreceIN. Your assistant helped write Dr. Mark’s article but did not put his name on it. It was even published by your institute. And you are attempting to be objective in evaluating psychosurgery? You are promoting psychosurgeons. Senator Kex~epy. We want to thank you, Doctor, very much. At this point I order printed in the record your biography along with pertinent material submitted in conjunction with this hearing. [The following was subsequently supplied for the record :] 382 BIOGRAPHY OF PETER ROGER BREGGIN Peter Roger Breggin, M.D., was born inlg36 and grew up on Long Island, New York. He is married, has two children, and lives in sub urban Maryland. He graduated with honors from Harvard College in 1958 where he directed the first large scale volunteer program and co-authored a book, College Students in a Mental Hospital, describing how untraine students can rehabilitate chronic state mental hospltal patients. This program was clted as a model by the President's Commission on Mental Health and Mental Illness. His medical training was taken at Case-Western Reserve in Cleve land (1958-1962) where he did research and published papers on the psychophysiology of anxiety. He interned at the State University of New York, Upstate Medical Center, in Syracuse (1962-1963), and then took his first year of psychlatrlc resident at the Massachusetts Mental Health Center (1963-1964) where he was a Teaching Fellow at Harvard Medical School. He returned to Syracuse for his last two years of psychiatric training (1964-1966) and then became a fulltim consultant with the Natlonal Institute of Mental Health in Washingt D.C., for another two years (1966-1968), Since 1968 he has been 1n private practice and has been agsocir wlth the Washington School of Psychiatry, first as a faculty member and since April 1972 as Research Fsychiatrist and Director, the Project to Examine Psychiatric Technology. In addition to publish papers on the scientific, ethical, political and spiritual implicat of psychiatric techniques, he has published twe rovels dealing wit! psychlatry and the society, The Crazy from the Sane (1971) and Aft the Good War (1972). He 1s a leading figure in the ant l-psychosurg movement, working with federal Institutions, Congress and a variet: of organizatlons representing health consumers and other intereste citizens, He 1s a member of the American Fsychlatric Association, the Amerlcan Association for the Abolution of Involuntary Mental H pltallzation, and the Citizens Committee for Hunan Rights 383 The Project to Examine Psychiatric Technology Tne Washington School of Psychiatry 1610 New Hampshire Ave NW. Washington, D.C. 20009 PROJECT ACCOMPLISHMENTS When the Project began in April 1972 the lay public and the mec- ical profession were largely unaware of the return of lobotomy, psy- chosurgery, and electrical stimulation of the bral. There were no critical evaluations available from a scientific, ethical or politi- cal viewpoint, ) Since then the Project Director, Dr. Peter R. Breggin, M.D., has published and spoken widely on the subject, and many other profession- als, the media, the public and the Congress have shown considerable concern avcut the issues. Several institutional reforms have also been initiated. Here 1a an outline of the accomplishments: 1. EDUCATIONAL ACCOMPLISHMENTS : Articles have been published or are forthcoming by the Project Director in the Congressional Record, Medical Cpinion and Review, the Proceedings of the Houston Neurological Symposium, the Proceed- ings of the Fourth International Conference on Soclal Psychiatry, MH (Journal of the National Association fur Mental Health), the Washington Post, The Washington Evening Star, Human Events, and several other publications. Medically oriented articles or statements by others in rebuttal or in support have been publiched 1n Medical Opinion and Review, Med- ical World News, Psychiatric News, The New Scientist, Science News, the Journal of the American Psychlatric Association, Frontiers of Psychiatry, and others. Major news stories, columns or editorials in the lay press have included the Associated Press, Reuters, Time, Newsweek, National Ob- server, Ebony, The Washingtm Post, The Washington Evening Star, San Francisco Chrenicle, Los Angeles Times, Christian Sclence Monitor, Boston Globe, London Times, and dozens, perhaps hundreds of newspap- ers and magazines around the world, including France, England, Can- ada, Germany, South Africa and Aiistralia. Radio and television coverage has included an hour long BBC special, a half hour BBC tzlk ehow, an NBC one hour dramatic presen- tation, network news, several lengthy educational radio and TV shows, and dozens of radio and TV interviews. : In addition, the Director has accepted dozens of invitations to speak, including The National Institute of Health, The National Insti tute of Mental Health, Harvard Medical School, Harvard University, George Washington University Law School, and the annual convention of the American Psychiatric Association. A special symposium will be presented at APA in May 1973, in Hawaill. II._INSTITUTIONAL REFORMS 1. The National Institute of Mental Health has terminated its support of a $500.000 psychosurgery »roject through Boston's Neuro-Research Fcvndation (Wm, Sweet, Vernon Mark, and Frank Ervin) and has enjoined them from spending leftover funds on surgery without specific case by case supervision. Since the start of the Project to Examine Psychiatric Technology, the Neuro-Research Foundation greup has been unable to operate on a single patient or to find grant funds. 2. The Justice Department has dropped its $108,000 support for a Neuro-Research Foundation project for the identification and treatment of violent individuals .and has rejected a new $1,300,00 project. 384 3. The Senate Committee on Appropriations (Labor-HEW) under Sen. Warren Magnuson, has ordered The National Institute of Health to delay funding its allocated $1,000,000 for study of violence involving psychosurgical techniques, and has ordered NII to report back to them on the criticism generated by the Project to Examine Psychiatric Technology. This f'mnding was intended to support the Neuro-research Foundation's work, as well as to establish other simllar centers around the country. Sam Ervin's Committee on Conatitutliaal Rights has also urged that the funding be reconsidered, and his commlttee 1s 1nves- tigatlng the allocation. 4, Attention 1s being drawn to Governor Reagan's allocation of over $1,000,000 to UCLA's department of psychiatry for a center for the study and treatment of violence to be headed by psychlatrls Frank Ervin, whose work has been turned down at NIH, Justice znd delayed at NIH, Some of the money for the UCLA project will again come through Justice via the Cal- ifornia Council on Criminal Justice. 5. The California Bureau of Prisons and the University of Califcrnia Hospitals 1n San Francisco have stopped thelr vt planned program of psychosurgery on prisoners, and other states have given up their plans as well. The Federal Bureau of Fris- ons has publicly announced that it will not conduct psychosur- gery in its.planned wnsychiatrlc treatment facility at Butner, North Carclina. 6. The Veteran's Administration has tightened its guldellnes for lobotomy and psychosurgery. 7. Ralph Nader's organization will be publishing an extneslve investigation of the Neuro-Research Foundatlon; Sharland Trot- ter 1s the investigator. 8. The Center for Law and Social Pollnsy of Washington,D.C. is invectigatlng other psychosurgical projects, particularly 0.J., Andy, under the directimof Alex Sanders and Charles Hal- pern of the Center, 9. The Mississippi Psychiatric Assoclation has been 1nvestl-— gating the work of Orlando J. Andy, and the American Psychiac- tric Association. 1s awaltlng thelr report before taking action, 10. The American Orthopsychlatric Association, The National Health Federation, The Medlcal Committee for Human Rights, Tie National Organization for Women(NOW), and other organlzations have taken public positions warning against psychosurgical a- buses. 11. Gabe Kaimwitz of Michigan Legal Services at Wayne State University in Detroit has successfully enjoined a state funded project from performing psychosurgery on the first of a series of state mental hospital patients. The case will be heard by a speclal three Judge panel in mid-March. 12. In Lsuisville, Kentucky a woman brought sult against a lobetomist for damages which involved the issue of Informed consent. Followlng testimony by the project director, the case was settled out of court fer an undisclosed "substantial amount," the first settlement involving a psychosurgenn. 13. The Black Caucus and several conservative and liberal Ser ators and Representatives in the U.S, Congress are forming leg- islation to limit or outlaw psychosurgery. 385 LEAA MEMO This is a copy of an in-house Justice Department report from Ann Sadowsky of the National Institute £6rLaw Inforcement and Criminal Justice (research arm of Justice's LFAA) to Jerris Leonard, Director of the Law Enforcement Assistance Adminis- tration {%7AA) of Justice. It explains why they turned down this years request for over a million dollars from Boston's Neuro-research Foundation, headed by Vernon Mark, William Sweet, Frank Ervin and others, Note some of the serious al- legations concerning possible intended misure of federal funds for personal advantage, PROBLEMS 1. Removal of the Project Director frum Boston to Los Angeles withou: notifIcatIon of Laten 0 e Institute, Dr. Frank Ervin is the psy- chlatrist around whose earlier work in Lewisburg Penitentiary the pre sent project was formed. The present three-month grant was signed by the Neuro-research Foundation on January 27, 1972. On February 3, 19 Institute staff were informed by staff from NIMH that Dr. Ervin was leaving his position at Massachusetts General Hi spital and leaving th Boston area. When confronted with this information, Dr. Ervin admitt that his duties at Massachusetts General would conclude as of April 1! prior to the conclusion of the present grant, He plans to begin a ne position early in the summer with UCLA, Despite his assurances that h will continue his work on the present project, he is being replaced b, another psychiatrist and in his capacity as project director, A pro- Ject being conducted simultaniously from Boston and Los Angeles will undoubtedly include both extra time and money for coordination and a greater opportunity for failure; however, no other alternative was of fered by the Neuro-research Foundation. Their present choice as pro- Ject director 1s woefully inadequate from the standpoint of the Insti tute. He has no background in behavioral science and has never direc ted a project of this size or complexity before, 2, Despite our stipulation that the support of a companion project b N e continued in order for Ins ute funding to con Shy no gran e a cation for continuation o funds has been received by . presen contract wi the Neuro-research Foundation concern in- tensive care and analysis of a few violent individuals not necessaril: in the criminal Justice system, The work done under this contract pr vides support to the Institute work in the development of diagnostic techniques. In order for the NIMH work to be continued past the August 30 con clusion of the contract, the Neuro-research Foundation would have to submit a proposal for grant review by February 2, No such proposal has been submitted. If the NIMH work is not continued, all costs for equipment and some costs for extended care will have to be subsumed nnder the Institute grant. 3. Financial problems with the grantee have included an attempt to purchase non-competiiively equipment from a firm whose major stnckhol er wa « vin and the ayment of $20 per day £0 a consultant with out prior approval f.r suc izh 3nnsultatlon fees, In addition, tra el and subsistence finds have teen requested although there are no su funds stipulated for in the grant award, A budget revision was requer ed allowing the grariee to place 20% of the finds in a miscellaneous category to be "distributed where most urgentiy needed within the var: lous budget categories." While none of the financila manipulations me tioned above 1s necessarily dishonest, they appear to demonstrate an attempt to use Goyernment funds to the advantage of the grantee, rath than with any feeling for the advantage of the public. 4, The planned cost for this research is now $1.3 million. We have requested of the grantee that the research design be limited to a cos not exceeding $600,000. Although a new schedule of activities has bes submitted, 1t contains most of the activities previously mentioned at the $1.3 million cost. No new cost estimates have been submitted. -2- 5. Despite LEAA's stated researen intent that ldeutificatiou vl med fcally disfunctional offenders was not sufficient unless treatment procedures were developed consurrantly, the present proposal of the grantee contalns no attempt to develop treatment or follow-up proced- ures. In earlier conferences, the grantee made glowing references to effective therapudlc techniques for dealing with braln dysfunction and chromosomal abnormalities; however, the present draft proposal now states that ther« 1s little expectation fcr such and anticipates spending less than € months time cn follow-up treated offenders. Signed Ann Sadowsky Originally published as 387 LOBOTOMIES ARE STILL RAD MEDICINE by Peter R. Preggin, M.D, in Medical Opinion, March 1972 "It is generally believed that psychosurgery went out of fashion with the advent of psychotherapeutic "drugs. This is a mistake. By conservative count, at least 40 neurosurgeons and psychiatrists in the U. S. today perform more than 600 procedures per " year. A personally conducted survey indicates that psychosurgeons anticipate a second wave of psy- chosurgery, at least equal to the first surge, which involved a total of 50,000 patients inthe U.S. alone. “Hatchet men” In an effort to control “pathologic” behavior, every day neurosurgeons and psychiatrists are ex- cising, irradiating, - burning or’ exposing to ultra- “sound the human brain. Yet there is no evidence that psychosurgery can blunt or modify specific emotional impusles without destroying other im- portant functions of the brain. While these tech- niques may be much more precise than those used by carly lobotomists, who won a reputation as “hatchet men” by indiscriminately pushing probes through the nerve fibers of their patients’ fron lobes, the outcome is basically the same: ' At worst, they are irreversibly damaging the patient's “self, the very qualities of insight, crea- tivity, judgment, etc. that separate man from the lower species. “At the very least, they are blunting the patient ’s’emotional response. Psychosurgecy once was reserved for intractable mental patients who were too violent to be amena- ble to other types of treatment, or for elderly and indigent institutionalized patients (often abandoned by their families) i in order to make them managea- ble. These days, it generally is directed toward a dif- ferent target population: the neurotic who not only is ambulatory but lives at home and may even hold a job. The indications comprise an amazing array of conditions: anxicty neuroses, obsessive neuroses, personality disorders, and reactive Qspressions, to ‘name a few. : : Women are ai victims . Equally alarming is the fact that women, mid- dle-aged and older, are particular victims of this type of therapy. Extensive research indicates that females are subjected to psychosurgery far more often than males. Depressed, often abandoned, casi- ly subjected to the authority of husband or physi- gian, such women always have been a target for whatever therapy the doctors currently were prom- oting: drugs, electroshock, and now psychosurgery. “427 Dr! Petter. Lindstrom: of Children’s Hospital i in San Francisco, who uses -a-beam of sound to irra- :diate the | frontal lobes, reports that 80 per cent of “his neurotic paticnts undergoing psychosurgery are female: sorare 72 per cent of psychotic parients who get the same treatment. * Dr. Robert Hetherington, of Kingston (Ontario) Psychiatric Hospital, declares he was ref- used permission to do lobotomies on malé patients, because of the adverse publicity the technique has received in Canada. But he was aliowed to operate . on 17 women! The extent of the resurgence of interest inl psy- _ chosurgery is difficult to measure, Neurosurgeons J publish much more about the treatment of somatic ills of the brain — tumors, vascular problems, etc. — than about operations for the psychic ills. Nevertheless, careful search of the literature reveals a spate of articles on the subject in various medical journals during the past five years. They have even organized their own specialty group: The Interna- tional Association for Psychosurgery. The Second International Conference on Psychosurgery at Copenhagen in 1970 included participants from 16 countries. Here are a few examples of the type of psycho". surgery now being practiced in the U.S. At Hartford (Conn.) Hospital neurosurgeon William Scoville favors orbital undercutting in which fibers at the base of the frontal lobe are severed, blunting the patient's emotional response. The scalpel is inserted under the frontal lobe, and a median line incision is made. He calls the operation a “last resort.” Among his patients are people with anxiety states and depressions, particularly older people, as well as certain types of schizophrenia, obsessive compulsions, drug addictions, etc. He is reported to have performed over 1, 00 lobotomirs of this type. ~-r a! . “Implantation barmless” “ . At Tulane University Dr. Robert Heath; profes. - sor of neurology and psychiatry, has implanted electrodes in the brains of 60 patients with a variety of mental ills and pains. Using as many as 125 clrc-. trodes per patient, Dr. Heath leaves them in place . for a minimum of six months in order to ciiminate . “any ‘variation introduced by operative, trauma, edema, and anesthetic effects.” He says ha ime plantation i is harmless. A few patients have been walking rad ith electrodes for years. Some of them are equipped with’ transistorized self-stimulating devices to trig- ger pleasure, and in one case to keep a patient from narcolepsy; when he starts to fall gsleep, other pa. tients can arouse him by pressing a buttod.. = - In San Francisco, Dr. Lindstrom first used ul- trasound to perform prefrontal lobotomies on ter- minal cancer patients, then branched out to include . psychotics and psychoneurotics not responsive to other forms oftreatment. He has operated onat - least '47§ patients suffering from anxiety, ‘depres: sive, obsessive, compulsive and phobic reactions; hypochondriasis, pain and certain addictions. #: In other parts of the nation, psychosurgeons are 388 directly intervening tn the ¢ingutum, the amygdala; and various midbrain structures such as the hypoth+ alamus, thalamus,” and. fornix; they are utilizing various other techniques, such as radioisotopes, for the purpose of modifying mood, emotions and be- havior. Studying the work of some of these pagel geons and the techniques they use, it becomes clear that many of their patients have psychiatric illness that ordinarily are amenable to drugs, psycho- therapy, or a (smbination thereof. Even the admin- rieation of electroshock — which 1 believe is widely ed — 15 less tightening than psychosurgery. : Medical rationale 2 What is the medical rationale for revival of these operations? The plain fact is, no sound theo- retical basis exists for these procedures, except the generally accepted hypothesis that the limbic sys- tem {frontal lobes and midbrain) control certain higher functions such as insight, foresight, empathy, imagination, creativ iy, abstract reasoning, emo- tional responsiveness, etc. It has been shown that psychosurgery has a damaging ¢ffe ct on all these functions; but it has not been shown that it is aff. tive in relieving psvchiatric problems. ts practitioners admit that while psychosurgery © promotes decility and tameness, it also produces loss of affect, spontancity and fantasy life. Dr. - Scoville readily concedes that all psychosurgery has * a “blunting function.’ omy, Dr: Walter Frosman of fad Francisgo (now retired) has written: . Theoretically, on the "basis. of personality’ stu- dies creativeness should be abolished by loboto- - my: #2" Tew patientstare Tum ther own businesses ofr resume their professional status -— medicine, law. ctc...,Although they may not become leaders in their own professions, they serye adequately ‘and comfor- ably.” This is the best that lobotomy can offer. An : operation that permits some women to be reinstat- ed in ‘their families as incapacitated housewives, that enables some blue-collat.workers to return to their jobs, or that permits a few lucky professionals to continue with their’ careers (albeit with limited achievement), is not good enough when the price exacted is “'blunting' of human personality. Ey A # Involves cota) person '’ The standard frontal lobotomy and its various modifications disrupts. the function of the frontal lobes and midbrain “limbic system™ by severing pathways to the midbrain. Although functional loss depends in pant upen the degree of brain surgery, the results tend to be global in character. That's because the functions of the frontal lobes involve the “total” person — what makes man the social, creative, intellectual, and fading individual that he is. According to Dr. SeailE, “Different types of mental disease do not require different arcas cf ablation or tract interruptions. There appears no need to vary the location of operation in the neuros- es, depressions and schizophrenius.' He adds, how- .ever, thatthe lower the cut, the more emotional impairment; the higher the cut, the more intellec- Rt ingpaigpent, Ci) } » The dean of American lobot- [i's 0 wouder that psychosursery is being tout- od as a panacea for everything from homosexuality to pederasty and gambling — even for agoraphob- ia. An unsigned cditorial in The Lancet recently recommended ps ychosurgery Jor sex offenders be- cause “castration is open to criticism on ethical grounds.” Spe «In England, it would appear, ‘a man’s brain is less sacrosanct than his testicles + + “Distroy symptoms wey i ** The only symptoms that- psychosurgery pallens seem ta have in common. are tension, anxicty, and emotionality — hardly reasons for destroying picces of the brain. Add to the overwhelming weight of argument Freud's concept of anxicty as a symp- tom of difficulty. By mutiliating the brain, these physicians are destroying Symptons without treat- ing the prob!=m. - Although thousands of lobotomics have” been performed around the world in the past few years, not a single well-controlled study of the procedure has been attempted, to my knowledge. In fact, only three major retrospective studies have been pub- lished all with negative conclusions. In 1962, Dr. Robert L . Vosbure of Dartmouth School of Medicine reported on 229 lobotomy pa- tients matched with controls who had comparable psychiatric problems. Five years jater, only 19 per- cent of both groups had been discharged from the hospital. Evaluation revealed that many of the lo- botomy patients had brain damage. Their alleged “improvement,” Dr. Vosburg observed, often de- pended upon the niche available to them in the hos- “pital or at home. The patients appeared withdrawn. “and hostile. : “In short,” he stated, “they act as if they have been Byres v va No potler off. | : in 1964, another team of Canadian investigators — McKénze and Kaczanowski — conducted their own retrospective, controlled study, and concluded that postlobotomy patients were no better off than "the operative group. They recommended that the standard lobotomy be abandoned. "+ i ? in W Physicians who tamper with the Bodies Zoe tients in order to control their minds must be pre- pared for the consequences; and sometimes psycho- surgery backfires, with disastrous results. Dr ! Scoville warns that surgical lesions — particularly in the limbic lobes and its connections with the hypothalumus—may cause rather than cure schizo- phrenic-like psychoses. And he believes that memo- ry is adversely allected when bilateral lesions are made in the temporal hippocarmpys, vy Take the ¢ase of 3 woman who vas subiected to psychosurgery in Boston City Hospital, One of their “most gratifying’ cases, she underwent a thalamotomy via electrodes. After the operation, she became enraged at her physicians. Nevertheless a second procedure was performed, and a third scheduled. According to her case history (onc of the few available, by the way) she eventually reached a state of “high spirits’ and was allowed out of the’ hospital to shop.- Whereupon she went to a phone booth, called her mother ta say “goodbye,” took poison, and killed herself. 2 t te, . Tie wr ie ah wt Ede na I i . 3 - Or take the Canadian patient who was so “lib- erated” by lobotomy that he went on to rob a bank. The judge gave him an extra heavy sentence— pre- sumably to allow him additional time for rehabili- tation. A physician wrote a letter to the Canadian Medical Journal, arguing that the judge was wrong; the patent’s ‘moral code would remain unaltered even with “an infinite jail sentence.™ + ¢ Hels ¢ wl gu, . . Ss . But who, in fact, was morally responsible for the patient's criminal actions? % ir : : A dey Surgery on children it fi wy exception—usually draw. the line at operating on children. At the University of Mississippi, Dr. Or lando J. Andy and his colleague, Dr. Marion F. Jurko, admit to performing psychosurgery on 30to0 40 persons, the majority of them children. In letters to me, they report that these patients suffered from “some form of hyperacitvity, ‘aggression, or emo- * tional instability” — what Dr. Andy termed “hy- perkinesis.” And they insist that various forms of." psychosurgery '— thalamotomy;" hypothalamoto= my, fornicotomy, and cingulectomy — alone or in combination have proved “most effective in con- trolling aggression in these patients.” Consider the case of a nine-year-old boy de- scribed by Dr. Andy as hyperactive, combative, explosive, gestructive, and sadistic. Initially, a bi- lateral mutilation of the thalamus was performed on this patient. The procedure was repeated unilat- erally nine months later, and the patient’s behavior improved. After a year, however, “symptoms of hyperirritability, aggressiveness, negativism, and combativeness’ slowly reappeared. He was operat- cd on moreextensively, this time mutilating the fornix: Not surprisingly, the child began to show signs of memory loss. Nevertheless, his brain was mutilated a fourth time. , 93-999 (Pt. II) O- 73 -4 Amicrican_psychosurgeons—with one notable” “Deteriorating” ts He became casy to manage. TIntellectually, however,” the surgeon reports, “the patient is dte- riorating.” "In a {etter to me, Dr, Andy claims that his pa- tients” psychiatric problems. are neurologic in ori- gin. But in some instances his diagnostic evidence is nothing more serious than difficulty in wrist coordi- nation (alternating supination and pronation). of Tey Rr a 4 A ev) Ta 2 gh Instead of sitting back silently, tne medical pro- fession should take an active stand against all kinds of psychosurgery. Hospital review committees should investigate all instances, physicians and hospital administrators sg their influence to, pro- hibit its practice. ¢ .To my mind, it doesn't matter whether psycho- surgery is performed on intractable, violent patients who cannot besubdued by psychotherapy, elec- troshack, or drugs, or on so-called neurotics who are amenable to other forms of treatment. £sycno- - surgery is a crime against humanity, a crime that _ cannot be condoned on medical, ethical, orlegal grounds. : } In 1951 the Socict Union made lobotomy an il- legal operation. I would like to sce the same thing happen here. oN gen, J Datemboatye Hea Fad 390 [From the Mental Hygiene, March 1973) lk oEGOUD UIE oBoToMY and psychosurgery arc LC upon us again! In Philadelphia a black man dics of an overdose of heroin, and a re- porter notices peculiar scars on his head. A portion of his brain has been burned out in an experimental attempt to cure his addiction. The neurosurgeon is located by the re- porter and admits that his monkey experiments were inconclusive be- fore trying his operation on human addicts. In Louisville a woman is blinded by a prefrontal lobotomy. Testi- mony in a lawsuit against her sur- geon indicates that this 30-year-old woman was lobotomized for pain of psychological origin without being given an opportunity in psychother- apy. In Jackson, Miss.,, a neurosur- geon uses a mutilating operation on hyperactive children as young as age 5. He describes one child whose brain he coagulated with electrodes half-a-dozen times. The child is now easier to manage on the ward, but intellectually he is deteriorating. This neurosurgeon refuses to answer questions about the race of his young patients and declines to let reporters and legal investigators see them. But someone slips onto the wards and discovers three of the children are black. In California, the prison system denies plans to operate on “difficult” prisoners until letters are uncovered detailing extensive plans for a psy- chosurgical program in cooperation with the University Hospitals of California in San Francisco. When it is then discovered that three pris- oners have already been subjected to multilating operations, the prison officials decide to boast publicly about their best case. But a lawyer discloses a prisoner's whereabouts, and he is found to be physically crippled and emotionally worse off than before the operation. Dr. Breggin is Director of the Project to Examine Psychiatric Technology at the Washington School of Psychiatry, where he is also in private practice. He is also the author of a recent novel, After the Good War. 391 In Boston a depressed woman is operated on several times with chronically implanted clectrodes un- til she refuses further surgery, tells her surgeon she never wants to sce him again, and expresses rage at her psychiatrist as well. She kills herself the first chance she gets, but the case is reported as “gratifying” by her doctors who argue that the woman must have been recovering from her depression, otherwise she would not have had the energy to kill herself. Meanwhile, more subtle research is in progress. In Boston, patients are skewered through the brain with two large electrodes, each eontain- ing as many as 40 smaller electrodes for brain stimulation and brain- wave recording. These electrodes are left in place for up to a full year for remote control experiments be- fore the psychosurgery is performed by heating up one of the wires. At Tulane, homosexuals are stim- ulated in their “pleasurg centers” while watching stag films—to con- dition them to heterosexuality. The same psychosurgeon holds the un- official “record” of 120 electrodes implanted in the same person at one time. X-rays give the impression of a living pin cushion, but the doctor writes that his work is “therapeutic” rather than experimental and that his electrodes can do no harm. T the San Francisco Children’s A Hospital, ultrasonic radiation (the stuff that knocks the calcium off your teeth) is sprayed into the frontal lobes of patients, including one 13-year-old girl. Not surpris- ingly, this inventive neurosurgeon is an ex-dentist. Nor do psychosurgeons limit themselves to clinical aspirations. A group of Boston psychosurgeons writes in the Journal of the Ameri- can Medical Association that ghetto riots cannot be caused by political factors alone and that violent rioters may suffer from brain discase. The Justice Department rewards them with a grant to develop “screening methods” to find the violent prone among us and to develop psycho- surgical means for their control. Even Congress gets into the act and awards them $500,000 onc year and a million the next. All this is not the work of a few cranks, but of a large number of respected neurosurgeons and psy- chiatrists working in several dozen or more medical centers around the country, including Boston, Hart- ford, New York, Philadelphia, New Orleans, Louisville, San Francisco, Santa Monica, and the National In- stitutes of Health.* No one knows how many opera- tions are being done each year in ‘the United States—perhaps 600 to 1,000—but everyone agrees that we are witnessing a worldwide resur- gence of lobotomy and psycho- surgery. The surgeons have even formed what's now called the International Association for Psychiatric Surgery. They meet and speak frequently at conferences. Besides that, many new books and papers are coming out, and even standard psychiatric texts are again describing psychosurgery as a legitimate treatment. The new targets are not backward state hospital patients, but mostly neurotics—depressed, anxious, ob- sessive and elderly individuals, the majority women. Having disgraced themselves with the wholesale muti- lation of 50,000 state hospital pa- tients through the 1950s, the psy- chosurgeons, many of them the same men, now turn their weapons upon those patients they can catch on a neurosurgical service of a general hospital. The variety of operations is enor- mous. One neurosurgeon places a net of electrodes across the frontal lobes and gradually coagulates the patient over a period of months, depending upon how “good” his behavior is on the ward and at home. Others still use the old- fashioned knife on the frontal lobes. * Most have been documented in detail in my resource paper published in the Congressional Record of Feb. 24, 1972, pp. E1602-1612, while others have been disclosed in the press and in the courts, 11 The area of the brain attacked also varies widely, including deeper por- tions of it (such as the thalamus, hypothalamus, cingulum, and amyg- dala). But all the operations have two things in common: they muti- late non-discased tissue, and they blunt the overall emotional and intellectual responsiveness of the mind. They subduc or pacify the individual, regardless of the nature of his symptoms or the cause of his difficulties. CIENTIFICALLY, the work of Ss these men can be quickly dis- missed. In the four decades during which they have published hundreds of papers, they have not produced one controlled study comparing the effects of their therapy to the effects of other therapies, or no therapy at all. In the last decade, they have almost given up reporting detailed case histories and usually rely upon one- and two-word clinical descrip- tions, such as “depressed” or ‘‘ob- sessive,” followed by a number to indicate the degree of recovery. Sadly, the only controlled studies we have from the entire onslaught are retrospective. Looking back over the first wave of lobotomies, the results are uniformly dismal. The patients still have their psychi- atric symptoms, now compounded by lethargy, loss of interest in them- selves, and intellectual deterioration _ —the natural outcome of mutilating the higher centers of the brain. We can expect the same results, though less severe, perhaps, from the newer, more limited operations. Writing about more conservative forms of lobotomy in 1959, Walter Freeman, the Dean of Lobotomy, describes the patients “loss of self.” After a successful lobotomy, he says, “What the investigator misses the most in the more highly intelli- gent individuals is the ability to in- trospect, to speculate, to philoso- phize, especially in regard to the self. Maybe it was the abnormal development of these intellectual- emotional exercises that got the pa- tients into trouble.” 12 392 The lobotomics described by Freeman are still being done throughout the country and arc the object of at least one current law suit. But even the most conserva- tive lobotomies are known as *“‘blunt- ing” operations. Arthur Winter states that his patients become “more placid—sometimes passive.” William Scoville, who has replaced the deceased Walter Freeman as the nation’s spokesman for lobotomy and psychosurgery, has described even the most refined of the recent operations as a “partial” lobotomy, even though they destroy tissue be- low the frontal lobes. With the advent of the current public controversy, some of these men have tried to retract, or even deny, their previously published re- marks. But these reports are too consistent to be so easily censored. In the most recently published pro-psychosurgery book, Ruth An- derson gives the most detailed de- scription now available of the effects of one of the most refined opera- tions (amygdalotomy). Although this operation avoids damaging the higher centers of the frontal lobes, she still finds that the effects are similar to those of a lobotomy. She observes, “Typically the pa- tient tends to become more inert, shows less zest and intensity of emo- tions. His spontancous activity tends to be reduced, and he becomes less capable of creative productivity.” She also finds that his ability to learn is sharply reduced. N a recent panel with me, Sano, another of the world's most experienced psychosurgeons, described his operation (hypothala- motomy) as ‘sedative neurosur- gery.” This is his “best” case, a young child: Emotional and person- ality changes: the patient became markedly calm, passive and tract- able, showing decreased spontaneity. Similarly, Balasubramaniam speaks of his psychosurgery (amygdalot- omy) as “sedative neurosurgery . . . where a patient is made quict and manageable by an operation.” His most “remarkable” case, again a child, became quiet, bashful and was a model of good behavior. Psychosurgcons most often ra- tionalize their work as an effort to reduce the individual's “anxiety” or “tension,” without mentioning that this merely reflects an overall loss of vitality. Their second most popu- lar rationale, that so-called mental illness is biological, is unproven. But even if it were true, it makes no sense as a justification for brain mutilation. If minimal brain dys- function (so minimal it cannot yet be detected) can produce severe disabling symptoms, then why would increased brain dysfunction from surgery improve upon anything? The occasional contention that psychosurgery treats specific dis- eases with specific operations is not even supported by most experienced psychosurgeons. Scoville has re- cently written that cach of the oper- ations produces the same “blunting” function and that one operation will eventually be settled upon for all forms of psychiatric disorder. Mean- while, each psychosurgeon has his own favorite operation, and he uses it on every case that comes along. Had there been any doubt about the non-specific leveling effects of these operations, the animal re- search literature should have dis- pelled them. In nearly all animals, the operations produce the same re- sult, regardless of the presence or absence of disease. The animals be- come more tame, more tractable, more helpless, and less able to learn and to adapt to their natural sur- roundings. They become much easier to manage in cages but use- less for anything else. The most serious questions about psychosurgery are ethical and politi- cal rather than scientific. Do we dare treat man in so cynical a man- ner, reducing his humanity to solve his problems? Do we wish to make life more tolerable for a woman and for those around her by taking some of her life away? Do we wish to in- vade the provinces of “self,” treat- ing the person by reducing his capacity to be a person. Do we wish to produce living abortions—or more accurately, victims of partial euthanasia? Euthanasia, controver- sial enough in those dying of dread- ful discases, becomes a menace when performed on psychiatric pa- tients. Psychosurgeons and their sup- porters are fond of saying that the brain, like the lungs and kidneys, can function adequately with a large part removed. But when a man’s respiratory potential is reduced or when his excretory functions are limited by surgery, the man himself —the person whom we know and who knows himself—remains the same. When the capacity of the brain is reduced by a psychosurgeon, so too is the capacity of the mind. The man is changed, reduced, made into something less than he was. T is one thing for a man to have i “shallow breathing,” another to have a “shallow mind.” Thus, all destructive changes in the mind, un- like the body, become qualitative as well as quantitative. Even if the loss is only partial, we are still dealing with a change in the essence of the person. This loss of “humanity” in the mutilated individual can be looked at from many sides. Whole books, entire novels only manage to touch upon the subject. Another way to approach the issue is this: “Is man a machine, or is he a creature with a creative will?” If life is to have any moral mean- ing, man must be treated as if he has free will. The problems of life can then often be examined and understood as reflecting the anxiety generated by free will, the agony of choice, the despair of failure to choose and to act. What is man without this capacity? When we partially destroy the individual's brain, we bring him and those around him some measure of peace, but at the price of his irrevocable and inescapable enslavement to a permanently defective mind. It is time to rid oursclves of the notion that lobotomy and psycho- 393 surgery are “medical treatments.” That somcthing is done by a sur- geon in an operating room docs not make it “medical.” Like the ampu- tation of the clitoris or the testes in cases of sexual deviance, psycho- surgical operations are best com- pared to the still more ancient prac- tices of cutting off a limb or poking out the eyes of accused criminals. That doctors do the mutilating should not distract us from the func- tion it serves—impairment of the individual to control his behavior. Nor is voluntary consent a suffi- cient protection from such atrocities. Witches volunteered for burning; some slaves willingly accepted their masters. Miserable, suffering, humil- iated human beings will often sub- mit themselves to the most cruel treatment. They will seek it out, as some individuals will maim them- selves or commit suicide. We can recognize the individual's right to harm or kill himself, but we can never permit someone else to harm him or to help him toward his self-maiming or suicide. Thus, while suicide itself is considered a right by libertarians, murder is never sanctioned. Psychosurgery is a par- tial murder, and no one should con- fuse the issue with a “personal right to treatment.” From a practical standpoint, the issue of voluntary consent becomes particularly hypocritical when ap- plied to prisoners and mental pa- tients. Due to their circumstances, they are easily subjected to intimi- dation. . IMILARLY, the consent form in Ss the psychosurgical unit of the California prison explicitly stated that the prisoner would be released from solitary confinement in return for his “consent” to treatment. Given the powerlessness and the vulnerability of mental patients and prisoners, it is folly to see any pro- tection in voluntary consent. The physician who chooses to command the spiritual life and death of an individual takes a terrible moral responsibility upon himself. The result at best is the hardening of the physician to moral issues. Thus, the latest texts on lobotomy and psychosurgery make no mention of any moral issucs. They seem not to exist for the surgeons! The exercise of this power brings “Very practical consequénces, many of which are already apparent in the treatment of psychiatric patients. Because we can resort to involun- tary hospitalization, stupifying and paralyzing drugs and electroshock, we too often overlook the real hu- man necds for love, kindness, un- derstanding, and courage. We may also fail to grasp the real life prob- lems confronting the patient. The political issues are ultimately the most important, for what is now a threat to individuals may event- ually become a threat to the nation. As technology more and more be- comes “the cure” for personal and political problems, we will increas- ingly lose track of ourselves as individuals. Minorities will, of course, be the first to suffer. It is no surprise that poor people, the elderly, and women were the primary victims of the first wave of lobotomy in the state hos- pitals. It is no surprise, either, that ghetto rioters were the first concern of the Boston psychosurgeons, that black prisoners and children are among the first victims as psycho- surgeons move into prisons and children’s institutions, and that women and older people again dom- inate the statistics in the new wave of psychiatric surgery. The first wave of lobotomy ap- palled many professionals and much of the public, but it slipped by with- out encountering any significant re- sistance. While they grumbled to themselves, the professionals did nothing to stop their colleagues; and the public, while somewhat dis- mayed, lacked initiative and infor- mation. It is time to take action— through professional and public so- cieties, through the courts, through hospitals and government institu- tions, and through state and federal legislation—to abolish lobotomy and psychosurgery. ® 13 Am. J. Peychiat,, 121: 394 487-450, 1964 CLINICAL NOTES (The Clinical Notes report the findings of the authors and do not necessarily represent the opinions of the Journal. RORSCIIACH STUDY OF PERCEPTUAL CIiANGES FGLLOWING DIENCEPITALOTOMY MARION F. JURKO, Pu.D., aNp ORLANDO J. ANDY, M.D.! This communication is part of a psy- chological study dealing with the short- and long-term effects of basal ganglia sur- gery on behavior. In this report an attempt is made to evaluate complex perception using measures from Rorschach protocols. METHOD Patients. Twenty-five Parkinson patients (10 males and 15 females) were tested serially over a 2-year period. Mean age was 54.2 years (range 40-70 years) ; mean educational level 13.8 years; mean dwra- tion of illness 5.4 years (range 1-10 years). All scored average or better on the pre- operative Wechsler Adult Intelligent Scale (WAIS). The patients all showed some degree of generalized Parkinson involve ment. The chief complaints ranged {rom moderate and unilateral to quite severe bilateral tremor and rigidity. All padents were right handed, i.e., left brain domin- ant. Surgery. Unilateral brain lesions weie made under local anesthesia. A 20-gaugc barrel electrode with a 4 to 10 mm. non- insulated tip was inserted into the dien- cephalon through a frontal burr hole(1). The sites of coagulation were primarily in the posterior ventral thalamus-subthalamic region(2). The stereotaxic atlas of Schal- tenbrand and Bailey (10) was used {or de- termination of electrode placements. Test Procedure. The Rorschach was ad- ministered throughout the study by the same examiner. All protocols were scored according to the Klopfer and Kelley sys- tem(6). Evaluation of the data was in tems of the basic and most frequently I Respectively, Research Associate, Professor and Cheirman, Dept, of Neurosurgery, Univ. of Missis- sippi Medical Center, Jackson, Miss. used Rorschach determinants rather than all inclusive. The determinants evaluated were: R (total number of responses) ; W (whole blot response) ; D (blot detail re- sponse) ; IY (pure {orm); A (animal re- sponse); M (human movement); IM (animal movement); FC (form-dominat- cd color response) ; CF (color-dominated form response) ; and C (pure color). The Rorschach was given at the following in- tervals: 1 weck preoperative; 5 days postoperative; 2 months postoperative ; 6-8 months postoperative; and 14-2 ycars postoperative. RESULTS 1. In comparing the preoperative Ror- schach protocol of the Parkinson patient with the norms of Cass and McRey- nolds(3) for an essentially comparable population (age, occupation, and mixed sex), differences were seen in only thrice of the basic scoring categories. The Park- inson patient produced a very high form response (F% at the 90th percentile), a Ligh blot detail response (D%, 78th per- centile) and a corresponding low whele blot response (W%, 30th percentile). The other major scoring categories as human movement (M), animal movement (FM) and color responses (FC and CF) ranoed from the 40th to the 64th percentile, all within the percentile rank of the majerity of the normal population. Also, the two major Rorschach ratios, the extraversive- intraversive ratio, Surn C :M, and the color dynamics ratio, (CF + C) : CI, were sim- ilar to the non-patient population investi gated by Cass and McReynolds. 2. Postoperative changes in the Nor- schach were both immediate and delaved. In the acute postoperative period (5 days- 487 \ 395 488 2 months) there was increased response to color (CF + FC) and movement (I'M + M) and reduction in responses determined by form alone (I'). In the chronic period (6 months-2 years) though the number of color and movement responses returned to preoperative levels, there was a change in the character of perception of these stim- uli. This was scen in the proportionally greater incidence of human movement to animal movement (FM:M) and form- color to color-form combinations (CF + C:JFC). The change in the manner of response to color (form predominant and color secondary in contrast to the reverse ‘preoperatively) was not evident until the 6th postoperative month and became more pronounced at 2 years. These trends are summarized in Table 1. CLINICAL NOTES - [ November appeared shortly atter placing the lesion, reached a peak at 5-19 days, and receded at 2 months in all but 3 patients. No florid psychotic episodes were precipitated. One patient did exhibit auditory Rallucinations for a few days after surgery. COMMENT Our patients showed changes in complex perception after placement of a lesion in the diencephalon. Some changes occurred in the acute postoperative period and some were not apparent until the chronic stage. In the early postoperative period there was increased response to the more evident and sensorially more vivid aspects of the environment, as color and move- ment. This enhanced response to the more obvious stimuli has been described for i TABLE 1 y Comparison of Pre- and Postoperative Rorschach Determinants FIM:M +" PATIENTS R F% FM% + M% CF% + FC% (CF + C):FCt Preoperative 25 21.9 58.4 25 2.0:1 16 1.9:1 Postoperative 5 days 23 21.6 * 440 26 22:1 21 20:1 2 months 14 18.7 *43.1 31 *1.3:1 24 13:1 6-8 months 13 19.2 53.8 26 *1.0:1 16 * 14: We 2 years 8 19.7 50.0 27 1.3:1 17 *0.8:1 = significant .05 ji or better (t test). ** Ratio of animal movement to human movement response. t Ratio of color dominated to form dominated color response. There was no change in the percentage of whole blot (W%) and blot detail (D%) responses postoperatively and little de- crease in the total number of responses (R). There was no deterioration in the * form quality of the responses. The extra- versive-intraversive ratio (Sum C: M) showed an early shift to extraversive (2.5: 1) in the 5th day postoperative period but returned to its ambicqual preoperative ratio (1.2:1) 2 months postoperatively. This was consistent with our earlier short- term investigation on a smaller group of patients(5). There was no significant dif- ferences between right and left brain op- erates for cither the carly or long range changes. Gross changes in behavior were appar- ent after surgery. These were mdinly eu- phoria or irritability. The manifestations chronic lesions but there has been little mentioned of acute lesions. Weigl(12) presenting a color-form sorting task to pa- tients with chronic brain damage reported that his paticnts had a decided tendency to make sortings first or exclusively on the basis of color. In a recent study of patients with long standing missile wounds, Semmes, et al.(11), found that their sul» jects had difficulty solving a visual con ditional problem because of concentra tion on the evident major design rather than on the relatively unobtrusive back ground serving as the conditioning ou Our obscrvations are similar to those of the above investigators for the morc acute phases of our subcortical lesions. However, in the chronic (long- range) period there was subdued handling of color and move ment. This is in conwast to the enhancwi 396 1961] CLINICAL NOTES 489 response reported in chronic cortical le- sions. There was no deterioration in the qual- ity of the responses after diencephalic sur- gery. Our observations tend to agree with those of Orchinik, et al.(&), who found no change in the quality or in the number of responses in 7 of 9 psychiatric patients alter thalamic lesions. They alse reported a slight increase in the form-color (IFC) responses which is in agreement with our findings. Riklan, et al. (9), described re- duced number of responses, poor form, and increased color responsivity in their aroup of Parkinson patients followed 2% weeks and 10 months after basal ganglia surgery. Site of lesion and ablation tech- nique, chemosurgery, may account for the differences in their findings. It should he noted that their unoperated control group, followed for the same period of time as the operated group, showed no significant changes in the Rorschach. Perception of movement is a complex perception involving in part an illusory experience. Our patients showed an in- crease in movement responses carly poste operatively, and a change in the character of movement in the long rane situation, ie, movement imparted to human rather than to animal figures. The pereeption of illusions in brain lesion subjects has been shown to produce seemingly parodoxical effects. Cohen(4) reported that unilateral lesions of either the right or the left frontal lobe led to abnormally low reversal rates on reversible figures (Rubin vase, double Necker cube). Bilateral frontal lesions, in contrast, were followed by either normal reversal rates (Rubin vase) or by unusual- ly rapid ones (double Necker cube), It is of interest that our Parkinson sub- jects preoperatively had a Rorschach pro- tocol similar to a comparable non-patient group (norms of Cass and McReynolds). Except for a hich number of form and de- tail responses, perception of the other ma- jor determinants as color and movement was similar to the norm population. How- ever the mean duration of iilness in our Parkinsonians was short (5.1 years). Mach- over(7) studied the protocols of Parkin- i son patients at the extremes of the range with respect to duration of illness. There were significant differences between the short duration (mean 2.5 years) and long duration (mean 19.6 years) groups in the incidence of human movement (AM) and color-form (CIY) responses. The long du- ration croup had only one-half the number of human movement responses given by the short duration group, and less than one- third the number of responses in which color dominates the percept. These differ- ences in the perception of color and move- ment between the short and long du- ation groups are in the same direction as observed in our Parkinson patients pre- operatively and in the chronic period. It is of note that there were no differences in the number of responses (R) or in the quality of responses of the long and short duration groups in the subjects studied hy Machover. It appears that the natural dis- case process affects predominantly per- ceptual organization rather than prodne- tivity. This also appears to be the case after placing a surgical lesion in the di- encephalon. ‘ SumMMARy A long range evaluation of complex per- ception was made on 25 Parkinson patients undergoing basal ganalia snrgery using determinants from Rorschach protocols. The patients were tested preoperatively and postoperatively at 5 days, 2 months, 6-8 months, and 1%-2 years. Changes were confined mainly to color and movement variables. In the acute period there was enhanced response to color and movement and, conversely, in the chronic period there was subdued response. There was essentially no change in the total number of responses, or no deterioration in the form quality of the responses. Tt was con- cluded that the lesion affects predominate- ly perceptual organizations rather than productivity or perceptual accuracy. BIBLIOGRAPHY 1. Andy, O. J.: Surg. Forum, 9: 698, 1939. 2. Andy, O. J, Jurko, M. F., and Sias, F. R.: J. Neurosurg., 20: &60, 1963. 397 ! 490 3. Cass, W. A., and McReynolds, P. A.: . J. Consult. Psychol, 15: 178, 1951. 4. Cohen, L.: Arch. Neurol. Psychiat., 81: ; 765, 1959. © 5. Jurko, M. F., and Andy, O. J.: Surg. i Forum, 12: 404, 1961. 6. Klopfer, B., and Kelley, D. M.: The Rorschach Technique. Yonkers, N. Y.: World Book Co., 1946. 7. Machover, S.: 332, 1957. 8. Orchinik, C., et al.: In: Life Stress and Psychosom. Med., 19: CLINICAL NOTES i} [ November Bodily Disease. Baltimore: Williams & Wil kins, 1950. 9. Riklan, M., Diller, L., and Weiner, H.. Arch. Gen. Psychiat, 3: 267, 1560. 10. Schaltenbrand, G., and Bailey, P.: In. troduction to Stercotaxis With An Atlas of the Human Brain. New York: Grune & Strat. ton, 1959. 11. Semmes, J., et al.: Brain, 86: 747, 1963. 12. Weigl, E.: J. Abnorm. Soc. Psychol, 36: 3, 1941. : 398 4th Symp. Int. Soc. Res. Sterenencephalotomy, Thalamotomy Stercotaxic surgery New York 1969 Hyperactive Brain Confin. neurol. 32: 322-325 (1970) Aggressive Treatnient Behavior Behavior disorder ’ Thalamotomy in Hyperactive and Aggressive Behavior / } 0. J. ANDY Department of Neurosurgery University of Mississippi Medical Center, Jackson, Miss. | Th . Introduction Ha 1 In 5 patients thalamotomy was used for the treatment of abnormal be- havior which did not respond to psychotherapy and medication. The be- haviors are predominantly characterized by emotional instability, explo- siveness, aggression, hyperactivity and nervdusness. Symptoms become manifest in childhood. Mentation may or may not be normal. Fine treror or jerking of the muscles may be present in the extremiiics and trunk. A statc of hyperirritability and hyperexcitability is erratically present a which time, even an ordinary sensory stimulus will set off an explosive or emotionally unstable reaction. Procedure Lesions were 5-10 mm in length and 3-5 mm in diameter and were used in the region of the centre medianum nucleus of the thalamus. Sur gery was performed under local anesthesia in four patients and genera! ancsthesia in one. Lesions were placed stereotaxically by utilizing the an- terior and posterior commissures as reference poinis. The atlas of Schat- TENBRAND and BAILEY was used as a guide for the anatomical localization. ‘Before placement of lesions, electrical stimulation with varying parame: ters through a bipolar electrode was done. Electrode location for the lesion placements in each of the cases dis: cussed are given in table I. It should be noted that the coordinates given 399 Thalamotomy in Hyperactive and Aggressive Behavior 323 Table I. Stereotaxic planes according to SCHALTENBRAND and BAILEY Patient Date Lesion site . RFp L H LFp L H AQ. 516-61 SIs 9 41 IM. J) 262 . 1 9 +3 © 1-30-62 11 54 +1, 9-8-62 10.5 9, _ +55 2 2-16-65 9.9 78 + +27 9.5 9 +18 W.B. 2-13-64 { LL 7 8 -1.5 12-17-64 5.5 8 -1 W.R. 7-24-64 9 6.5 +1 9.7 55 +1 J.P. 6-10-65 ’ 6.3 8 -1.8 R = right L = left H = horizontal Fp = fronto-posterior L = lateral in table I represent the location of the tip of the electrode and that the electrode is oriented in a 45° angle in the sagittal plane. Point of entrance in the skull is 10 mm lateral to the midline in the frontal area just posterior to the hairline. Case Reports W. B., a boy of 12, a mental defective with seizures, repetitive movement (rhyth- mia) and behavior disorder: Rhythmia consisted of body rocking, self beating of the head and regurgitation. Behavior disorder consisted of negativism and destructive- ness. Patient was constantly restrained in a chair and wore a football helmet to prevent self-mutilation. Pncumoencephalogram revealed bilateral large ventricles. Patient was mentally retarded. EEG revealed diffuse slow activity. Thalamotomy was done on the left, February 13, 1964 and right, December 17, 1964. Since sur- gery the rocking, self-beating, regurgitation and destructiveness have ceased. He is up and around with other mentally retarded patients and no longer restrained. W. R,, a man of 34, had behavioral difficulties since childhood (alcoholism, drug addiction, altempted suicide, aggressive and destructive outbursts, nervousness, and emotional instability). Pneumoencephalogram revealed moderate dilation of ven- tricles. Patient had normal 1Q and EEG was borderline normal. Thalamotomy was done on the right (July 24, 1964) and left (December 10, 1964). Behavior improved, he developed a leather shop business, supports the family and is well adjusted so- cially. He has not returned to drug addiction and alcoholism. 400 324 ANDY Electrical Stimulation Effects 10-24-64; right thalamus. ‘Electric current going down my chest and leh arm, left face, left Teg. Started in my left hand and went to left arm and shoulder, | came in the side of my neck and jaw. A rich tickling feeling and sensation in the left hand and feft arm.” The patient became agitated and restless. ‘I have a funny feeling like I want to get away from under it. A hot spot like 2 silver dollars here in my left eyc going to my left ear.” 12-9-64; left thalamus. Right arm ticklish sensation, Left pupil became smaller. Ticklish sensation right arm, side of body and side of the head. ‘I feel good. 1 feel like I want to do something. It's a rich fecling. 1 felt 4 ticklish sensation in the right hand, right arm, right face, down the right side of the body and right Icg. A sensation fecling a little jumpy, going down my right side, to the side of the stomach, down my right leg, right foot.’ A.Q., a man of 24 had behavior disorder (nervousness, spells of shaking all over, attempted suicide). Pneumoencephalogram revealed slight dilation of left ven. tricle. EEG was borderline normal and 1Q was within normal range. Torticollis movement to the right was associated with extreme nervousness, tension and agita- tion. Left thalamotomy was done on May 16, 1961. The patient has become rehubil- itated, remains happily married with children and supports the family. Electrical Stimulation Effects ! Tingling sensation right side of the face and head, bilateral pupil dilatation, cx- trancous movements of the face, lips, mouth, eyelids, eyebrows and neck, jerking of the head to the right, vibration in the head, speech became indistinct, patient be- came agitated and said, ‘turn that thing off.’ J. M., a boy of 9, had scizures and behavioral disorder (hyperactive, aggressive, combative, explosive, destructive, sadistic). Pneumocncephalogram revealed bilateral marked dilatation of the ventricles. EEG was abnormally slow. Mentally the patient was in the average range. Bilateral thalamotomy was done, left (January 12, 1962), right (January 30, 1962). Right thalamotomy was repeated on September 18, 1962. The patient's behavior was markedly improved and enabled him to return to special education school. After one year, symptoms of hyperirritability, aggressiveness, nc- 7 gativism, and combativeness slowly reappeared. A fornicotomy was performed on January 15, 1965. Impaired memory for recent events developed and the patient be- came much more irritable, negativistic and combative. Consequently, a simultancoos bilateral thalamotomy was done onc month later, on February 16, 1965. The pa- tient has again become adjusted to his environment and has displayed marked im- provement in behavior and memory. Inteiocioally, however, the patient is deterior- ating. . a Electrical Stimulation Effects 1-30-62; Patient aroused from sleep, ‘oh it hurts.” ‘where?’ ‘all over. Oh my head." Objectively the left hand and the left foot became restless during stimulation. The patient complained of stomach pain, wanted to urinate. 1-42-62; ‘that’s hurting my arm.” The patient cried and had tears. Pain in the right wrist, ‘the whole arm hurts.” Tears consistently developed in the right eye but not in the left eye. The face became flushed when he started to cry. 401 . Thalamotomy in Hyperactive and Aggressive Behavior 325 J. P,, a man of 51, was alcoholic, and had addictive and behavior disorder (ner- viousness, anxiety, aggressiveness, and depression). A very marked diffuse tremor with speech impairment associated with emotional stress. Pneumoencephalogram re- vealed dilated ventricles. EEG was normal and mentally the patient functioned in the nlormal range, A left thalamotomy was done on June 10, 1965. The patient has re- turned to watch repairing. Behavior has improved and there has been no continua- tion of alcoholism and addiction. Emotionally he is much more stable. ectrical Stimulation Effects 6-10-65; ‘oh going through both hands, going through my arms, more on the right side, something choking me up, shock in my right side. : " References " / ANDY, O.J.: Neurosurgical treatment of abnormal behavior. Amer. J. med. Sci. Jo 132/232-138/238 (1966). SCHALTENBRAND, G. and BAILEY, P.: Introduction to sterotaxis with an atlas of the human brain, 3 vol. (Thieme, Stuttgart, 1959). Alors address: O. J. ANDY, M. D., University of Mississippi Medical Center, 2500 Nolrth State Street, Jackson, MI 39216 (USA). } . Discussion i i LC S~ CL. BERTRAND: It is interesting to find that lesions in the centremedian have had ber} cficial effects on the behavior of these patients. These lesions and those used by Professor Hassler suggest that the change of pain perception in cases of intractable pait from lesions of nucleus parafascicularis and the adjoining area may be at least parply related to a change in the patient's affect. This points out how difficult it is to detérmine what mechanism is involved in supra-nuclear lesions, For instance, in our cass we have used fronto-thalamic sections both for pain and for obsessive compul- sive] ncurosis with satisfactory results, although no obvious change in personality was! evident in cases of intractable pain. 93-999 (Pt. II) 0-173 - 5 1. Neurol, Neviosurg. Fsychiat., 1964, 27, 516 Psychological aspects of diencephalotomy M. F. JURKO AND 0. J. ANDY Wl From the Department of Neurosurgery, University of Mississippi Medical C. entre, Juckson, Mississippi, U.S.A. The short- and long-term effects of surgery of the basal ganglia on behaviour have received relatively little attention. In previous studies emphasis has been on the more immediate post-operative changes for evaluating the effects of surgica! lesions on intellec- tual and perceptual functions. With respect to intelli- gence only one aspect, intelligence quotient (i.Q.), was emphasized. The objectives in this study were to evaluate several aspects of intelligence and simple perception for relatively longer post-operative periods. METHOD PATIENTS This study was done on 2S patients (10 men and 15 women). Mcan ave was 54-2 years (range 40-70 years); mean educational level 13-8 years; mean duration of illness 54 years (ranze 1-10 years). The patients all showed some degree of generalized Parkinson involve- ment. The chief complaints ranged from moderate and unilateral to quite severe and bilateral tremor and rigidity. All patents were right-handed, i.e. left brain dominant. SURGFRY Unilateral brain lesions were made under local anaesthesia. A 20-pauge barrel electiode with a 4 to 10 mm. non-insulated tip was inserted into the dien- cephalon through a frontal burr hole (Andy, 1959). The sites of coagulation were primarily in the posterior ventral thalamus-subthalamic region (Andy, Jurko. and Sus, 1963). The stereotactic atlas of Schaltenbrand and Bailey (1959) was used to determine placing of the electrodes. PSYCHOLOGICAL TEST SCHEDULE The test used to evaluate intellectual functioning were the verbal portion of the Wechsler adult intelligence scale (Wechsler, 1955) and a visual-motor performance group consisting of the Bender-Gestalt (Bender, 1946); memory-for-designs (Graham and Kendall, 1960); and tranl-making (Rettan, 1956) tests. Simple perception was followed with a group consisting of the spiral afteretfect! (Freeman and Josey, 1919); depth perception? ; two-point discrimination? and the memory-for-designs test oriented to evaluate percep- tion. Testing was done during a two-day period at the ‘Spiral Afteretiect Apparatus, Psychological Research and Develop- ment Corp, Tampa, } lords FApparatus No. 702, Latayctte Instrument Cou, Latayette, Indian. *Two-point westhewomenter (Wemsten Two-Point Type), Shaw Laboratories, luc, Syosset Island, New York. \ tollowing intervals: one week pre-operatively; five da. post-operatively; two months post-operatively; sis + eight months post-operatively ; and one and a half to tw. years post-operatively. All patients were tested throug out the study by the same examiner. EVALUATION OF DATA Since the Wechsler adult ini gence scale 1s a test which gives well-defined numero scores continuously distributed, mean scores could ~ obtained and appropriately compared pre- and post operatively with the parametric t test. However, the ten in the visual-motor performance and ihe simple pein: tion groups present scoring difficulties. Tests hhe tc Bender-Gestalt are commonly evaluated by chs judgment and there is no widely accepted method « numerical evaluation. Observations like those made f linear deviation in the memory-for-designs test are a! diflicult to present in numerical scores. For tests tral making the standardized scoring 1s dependent the patient's ability casily to execute motor mosemer and do require modification when used on the Puiki patient. The spiral afteretlect has such a limited spread of scores that tas usually evaluated in terms of a cutee score (normal vs. abnormal). tn view of these dificult oo the most feasible presentation of the data for the vives motor performance and simple perception groupy a peared to be reduction to categorized form. Though ts type of evaluation does not permit the use of the moe exacting statistical methods possible with mean sores it avoids a deceptive aura of mathematical rigotr © inherent in these types of tests. Since pre-eperaine performance was near optimum and in only polite! mstances was there a better score post-operatively, UV: follow-up data was dichotomized into impairment & non-impairment categories. The impairment cates represented the extremes of poor performance hax! on criteria which pre-operatively were well within t's physical and mental capabilities of the patients. 1:¢ following section describes the method of evalua s impaired performance for each test in the visual-mais performance and simple perception groups. The num of patients in the impaired and the non-impaired cates wits compared with the ron-parametric binomial ev pansion test. BENDLR-GESTALT These are free-hand reproductions with the test cards placed before the subjects. lmpanes performance was scored if two of the following four wet present: (1) deterioration in the form of the figures. (=! 516 403 Psychological aspects of diencephalotomy asals of figures, (3) perseveration of design, and (4) ied crowding or expansion in placement of the figures. .ewample of expansion is demonstrated in Figure 1. came patient displayed perseveration. He continued law the three rows of open circles on the desk, be- -Jthe limits of the paper. Note that two months post- «atively both expansion and perseveration were not nt. WRY-FOR-DESIGNS The task consisted of drawing «ms from memory after a five-second exposure. The Ls scored on total number of errors. Errors were not « than four for the pre-operative group. Post- catively cight errors or more was considered an im- ed performance. .WLMAKING This test is a paper-pencil maze consisting wo parts. Part A has the less difficult all-number sway and part B the more difficult alternating number- -r pathway. Post-operative impairment was the in- iy to perform part B. aL AFTERLFEECT This is a test of apparent (illusory) sion. When rotation of the spiral ceases the normal wons¢ is one of apparent movement of the spiral in copposite direction. The maximum score in our usc of ¢ test, after Blau and Schafer (1960), was 8 points sesenting four clock-wise and four counterclockwise is. All patients pre-operatively had a score of 6 or ser. Because of the stability of the illusion in most sets over time, a score of § or less was treated as wairment in performance (failure of the test). This cut- : 517 off score is also in accord with the findings of Blau and Schaller (1960) in which a score of zero through § was shown to be a highly predictive abnormal. MEMORY-FOR-DESIGNS This test was used in our test battery to cvaluate intellectual function after dience- phalotomy with a minor alteration in instructions to indicate changes in perception. The subject was required to draw cach figure from memory after a five-sccond exposure. He was asked to place the figures in columns down the page rather than across the sheet as is usually done. The test was scored for the presence of obvious lincar deviation of the columns to the left or right. Note the marked deviation to the left five days post-operatively (Fig. 2). DEPTH PERCEPTION In the performance of the test the subject aligned two rods suspended in an illuminated box devoid of cues. Twenty randomized trials were given, 10 trials with a 3 cm. misalignment and 10 trials with a 7 cm. misalignment. Impaired depth perception was scored when there was a decrease of one-third or more in both of the distances compared with pre-operative skill. TWO-POINT DISCRIMINATION / The threshold was tested for two arcas of both hands, the thenar and hypothenar eminences. Four descending trials (starting with a separa- tion that was casily discriminated and gradually reduced) and four ascending trials (starting with a separation that was not discriminated and gradually increased) were randomly given and averaged. Pre-operative thresholds ranged from a 6 to 18 mm. scparation. Post-operative 1 MOOR GESTALY +L THALAMOTOMY SDAYS - g neo rosror o> : g O ~ 2m08 rosT-0p A PE Cpa emsmane te” TO Pre-operative and post-operative (five days and two months) Bender-Gestalt protocols. Vote the marked tremor in the pre-operative drawings and the absence of tremor after surgery. The small size of the operative figures relative to post-operative size can be accounted for, in part, by restrictions imposed by the motor order. Note that five days post-operatively, perseveration is evident in the drawing of the three rows of open circles. “patient continued to draw more open circles on the desk beyond the limits of the paper. Also, the samme three rows of xn circles are erroneously connected by vertical lines in the pre-operative and again in the post-operative drawings two vaths later. This visual defect was not present in the post-operative period of five days. 404 M. F. Junko and O. J. Andy. SI8 sel = R THALANOTOMY A 4 4 S$ DAY o G MEMORY FOR OE SIGNS TEST 0 2 = #OST-0P » o PRE OP rs nN { £ n in 3 , % @ 4. 5 > 5 nn 4, y 2 YEARS aw: o 4 ros (On 4 & w wr W ¥ % 7 pane Ret w NH nN y ene o Ul . i G 1980 HG. 2. Memary-for-desians test todified ta evaluate linear deviation as a test of perception. Note the extreme devia to the left five days post-operatively which tends to persist two impainwat of sensitivity was scored if there was an in- crease nt point separation of 5 mm. or greater for both test areas. | vears lafer. due to poor performance | The similarities sniv verbal 1.Q. was mainl orfc subtest, sunmilaricics. .. cvalualcs abstract thinking by requiring the cuit “to discriminate between essential and super RESULTS INTELLECTUAL FUNCTIONS A dgerease in verbal AQ. was apparent in the testing interval of onc and a half to years (mcan decrement, This represents a loss of 8 to 14 pois of : 57 sight patients (759, of the subjects). In contrast, there ws ho Signilicant change in (he acute post- operative period (five days) nor in the testing inter- vals of two months and six to eight months. The verbal 1.Q. and the subtests comprising the Wechsler adult intelligence scale, which reveal signiticant or clatively consistentincreased or decreased trends, are iven in Table I. 1t is to be noted that the decrease in TABLE 1 PRE- AND POST-OPERATIVE WECHSLER VERBAL 1.Q. SCORES Time of Test No. of Subtests (scaled score)! Verbal Patients 1.0. Digit - Similari- Compre Span tics hersion Pre-opcratively | 10-0 196 246 i4 Post-operauvely S days 2 109 i856 232 1o 2 mid 14 IE 17 28-3 3 hal, 1d HV] lord JL : - “ia bg "The remaining subtai (infarmation, arithmetic, and vocabulary) showed no consistent trends. *Significant at 0-05 level (t test). likenesses. No statistically significant change present in the remaining subtests. The compr sion subtest, which depends on tiie possession certain amount of practical informationand a yore ability to evaluate past experience, showed i decline. On the other hand, performance ind span, a test of attention and retentivencess, w.s sistently higher post-operatively. This was they to reflect the effect of practice. The remainin: « tests—information, arithmetic, and vocabuiun showed no signiticant changes. Unlike the 1.Q., which showed Little change car post-operatively, maximal decrement in all of ©. visual-motor performance tests occurred in i acute (five days) post-operative period (Table li: Greatest impairment was in the Bender-Gesl TABLE I1 NUMBER OF PATIENTS WITH POST-OPERATIVE IMPAIRVIESS IN VISUAL-MOTOR PERFORMANCE TESTS OVER A TWU-Yi ub PERIOD - Test Timeof © _ Total Bender Memorv-fors Trad Moon Test No. Gestalt Desens Paso anv ae wv YaST. Tle ® 2 mi. 4- RET SAN » ~8 mit. 13 Ja 403070 She 12 yr. 8 30850 4 (50%) be ‘Significant at 0-001 level (binomial expansion test). 405 st. Evidence of coindndimdion ent, one 4 a Af to two years post-operatively T ESTEE PATRI and memory Tor signs-tesTs, Subjects with elt BEAM operations ap- red 10 be more frequently impaired than those ath right brain lesions (Table 111). Though this «nd did not reach the level (p = 0:05 or better) ually taken as significant for our small sample, it is eeestive of a laterality difference and should be sued in a larger sample. TABLE 111 PAIRED VISUAL-MOTOR PERFORMANCE RELATED TO UERALITY OF BRAIN LESIONS FIVE DAYS POST-OPERATIVELY, Right Operation (12 patients) ar Left Operation (12 patients) ~il-making 8 (67%)! 3Qs% temory-for-designs 7 (80%) 433%) wder-Gestalt 11.90%) 908% nificant at 0-10 level (Chi-square test). IMPLE PE RCEPTION Th ¢ was impairment in all sys) period (Table greatest declin€ eth perception and two-point discrimination tests, ith decrenient present in over 50% of the patients. TABLE IV WMBER OF PATIENTS WITH POST-OPERATIVE IMPAIRMENT \ SIMPLE PERCEPTION TESTS OVER A TWO-YEAR PERIOD Test “me of Towl Spiral Linear Depth Two-point | on No. After- Deviation Perception Discriming- eect (MFD) tion "ate | xratively ’ Sdays 24 10 (425) 10 (42°) Tmith, 4 20142) 40%) «8 mith, 1" 0 4 (30%) "2 yr, x 0 223%) 0 113%) fad on 20 patients, ‘nificant ut 0°02 level (binomial expansion test); vnificant at 0°06 level, Iwo-point discrimination remained impaired in a gnificant number of subjects two months post- weratively, and there was continuing deficit in one tient two years after surgery. Among the 12 “tients with decrement in two-point discrimination, X had contralateral decrement, three had ipsi- deral, and three had bilateral. Two of the three tients with ipsilateral deficits were operated on the dt brain. Linear deviation also gave evidence of ang-range impairment. Figure 2 illustrates extreme “wiation to the left five days post-operatively ad deviation still apparent two years later. There as a trend for a greater number of subjects oper- Psychological aspects of diencephalotomy TABLE V - IMPAIRED SIMPLE PERCEPTION RELATED TO LATERALITY OF BRAIN LESIgNS FIVE DAYS POST-OPERATIVELY Test Left Operation Right Operation (12 patients) (12 patients) Spiral after-effeyt 325%) 7(60%) Linear deviatign 6 (50%) 433%) (8 patients) (12 patients) Depth perception 338%) 10 (83%) Two-poind discrimination 38%) 9(70%) Significant at 0-10 level (Chi-square test). ated on the right brain to show impaired simple perception than those operated (Table V) on the left brain. COMMENT * Riklan, Diller, Weiner, and Cooper (1960) reported significant impairment in the Wechsler verbal 1.Q. in the ‘immediate’ (8 to 43 days) post-operative period. In the ‘long-range’ period (4 to 13 months) there was no significant difference compared with post- operative performance. Our patients, in contrast, showed no impairment in the Wechsler verbal 1.Q. immediately post-operatively. Deficit was only found one and a half to two years after operation. Further- more, the decrement was due to a decline in one specific subtest, similarities. It should be noted that in the series of Riklan er al. (1960) patients represent a mixture of chemothalamotomy and chemo- pallidotomy testable ‘usually between two and four weeks subsequent to surgery depending upon the clinical condition of the patient.” This implies that the post-operative morbidity was pronounced in some patients which may account for the carly impairment, especially in those who could not be tested within five days alter surgery. ‘The technique utilized in our study consisted of electrolysis of diencephalic structures and 21 out of 25 patients could be so tested within five days alter surgery, In addition, our long-range testing period was 181024 months in contrast to theirs which was four to 13 months. Our observations of delayed impairment in verbal 1.Q. are in accord with a recent case report by Watkins and Oppenheimer (1962). They described late decline in the Wechsler-Bellevue intelligence scale after an apparently good recovery from uni- lateral chemothalamotomy. The Wechsler verbal 1.Q. was 114 pre-operatively, 100 at one month post-operatively, 109 at five months, and 98 at 18 months. No information was given on their sub- test scores. It is of interest to note that studies in lobotomy patients also reveaied decrements which were specific for only some Wechsler subtests (de 406 520 Mille, 1962; Smith and Kinder, 1959). In addition, the changes were not present immediately after surgery, but became evident eight years later (Smith and Kinder, 1959). The question arises as to whether the delayed post- operative decrement in the (Wechsler) verbal 1.Q. can be attributed to deterioration associated with Parkinsonism. Riklan er al. (i960) reported no significant change in Wechsler 1.Q. scores in their unoperated Parkinson patients in a mcan test- retest of nine months. Machover (1957) used the Rorschach test to evaluate intellectual function in two groups of Parkinson patients, cach representing a relatively short and long period of illness. A com- parison of the short duration group (mean, 2-5 years) _with the long duration group (mean, 19:6 years) showed ‘no really significant difference in degree or kind of impairment in cognitive integrity or ctlici- ency’. hip view of these obser unlikely that the Tong-term imp. study is due UTR to the Joe ol Neer le TT eT occurred in the acute “period alicr 0 SKITS —obviousty—mpircate a dificrent intelicctual function than the Wechsler 1.Q. There are many reports of impairment in percep- tion following cortical lesions but only a few follow- ing subcortical lesions. In a recent study Proctor, Riklan, Cooper, and Teuber (1963) reported decre- ment in two-point discrimination and punctuate pressure thresholds immediately after chemothala- motomy. Significantly higher thresholds for punctu- ate pressure were sull evident five months post- operatively. These findings parallel our observations of maximal number of patients showing decrement in somesthesis in the acute (five days) period following dicncephalotomy. There was little long-range deticit; only one patient still had impairment one and a half years post-operatively. It should be noted that Teuber (1962) found decrement in two-point dis- crimination 10 years after penetrating missile wounds of the cortex. The above investigators also found that impairment was greatest contralateral to the lesion and ipsilateral impairment was more frequent in the group with lesions of the left brain. Our observations on diencephalic lesions are in accord with those findings. Two-point discrimination and aepth perception tests showed impairment in more patients after diencephalic lesions than did spiral aftereffect and linear deviation tests. It is of interest that the former tests are to a large degree tacule-spatial in contrast to the latter which are visual-spatial. This difference may be duc to the greater involvernent of the primary ons, nocontiast ampairment hn would appear Lt {i nour | whe natural course we of Parknsan’s for-des: M. F. Jurko and O. J. Andy - sensory relay nuclei of the thalamus conseguent 1, the diencephalic lesions. Tt must also be noted the impaired perception was not accompanied general intellectual deficit. Disturbed perception without involvement of general intellect has ai, been reported by Denny-Brown, Mever, and Hogen stein (1952), Gerstmann (1958), and others, The laterality of the lesion appears to aij, intetligence and simple perception ditferentially. Tr, 1s now quite well documented tor cortical represen. tation but has received hittie attention in relation (0 diencephalic function. Greater impairment of simp, perception appeared among our patients with rly subcortical operations. Recently Piercy, Hécaen and Ajuraguerra (1960) reported on 67 patients wi, had constructional apraxia associated with unilatey cerebral lesions. The deficit was measured by hayvios the patients draw a house and a cube. They conclude ‘that, in general, constructional apraxia associated with right hemisphere lesions involves greater im paiement of perceptual functions than as the ce wn the eft hemisphere syndronice’, perception, impairment of In contrast to sim mtethirence was moe “frequent among our patents with lett dienceplin lesions. This as in accord with laterality ciiecn noted on patients with cortical lesions. Reitan (1v8¢) in a carefully controlled study of 14 patients wit, surgical verification of pathology, found pair! verbal intelligence (Wechsler-Bellevue) more free quently in patients with left-side cortical lesions. SUMMARY Intellectual function and simple perception were evaluated before and during a two-year period atic placement of lesions in the diencephalon of 2% Parkinson patients. Psychological tests employed were verbal 10 (Wechsler) and visual-motor tests: Bender-Gestat memory-for-designs. and trail-making tests. Tests perception consisted of spiral afteretiect, memein ns, depth perception, and two-point dn crimination threshold. Immediate impairment was veritied in all the te comprising the motor performance battery, aii recovery was present within six months. Howes the verbal 1.Q. was not immediately impaired. Delayed impairment of verbal 1.Q. one and a hail to two years post-operative. Jf shiould be noted that the decrement was con to onc subtest only, similarities (a test of abstra. thinking). All perception tests revealed immediate pn operative impairment. Oniy one (lincar deviatio: showed decrement at two years. appeain. 407 Right diencephalic lesions produced greater spairment of simple perception and left dience- alic lesions produced greater impairment of wellectual function. REFERENCES dh, 0. J. (1989), Globus pallidus coagulation technique. Sury. Forum, 1958, 9, 695-700, = Jurho, MLE and Sis, FRC Je (1963), Subthalamatomy in treatment of Parkinsonian tremor, J, Newrosurg., 20, 560-870, wder, Lo (1940), Bemder Vbvual Motor Gestalt Plates, Amer, Orthos payehiatric Ass. Ine, New York, fe, To HL, and Schatter, REL (SALT) as a predictor of normal and encephatographic records in children, J. con. Ps Mille, RO (1902), Intellect alter lobotomy in fuctor-analy ue study, Psychol. Monogr, 76, [Whole No. $15), ‘eny-Brown, 1). cr, J. S., and Horenstein, S. (1952). The sig- nificance of perceptual rivalry resulting from parietal lesion, Brain, 7S, 433-471, cman, b., and Josey, memory impairment. (Chic.), 62, 794.797, attmann, J. (1958). Psychological and phenomenological aspects of disorders of the body image. J. nerv. ment, Dis., 126, 499.512, saham, EF. and Kendall, B. (1960). Memory for Designs Plates. Psychological Test Specialists, Missoula, Montana, abnormal electro- ol., 24, 35-42 wphrenia: A LO, pp. 1-18, W. E. (1949). Quantitative visual index to A preliminary report. Arch. Neurol. Psychological aspects of diencephalotomy (1960). The spiral afteretlect test 2 Machover. S. (1957). Rorschach study on the nature und origin of common factors in the personalities of Purkinsonians. Psy- chosom, Med., 19, 332-338. ot 1., Hécaen, H., and De Ajuriaguerra, J. (1960). Constructional apraxia associated with unilateral cerebral lesions—left and right sided cases compared, Brain, 83, 225-242, Proctor, F., Riklun, M., Cooper, I. S., and Teuber, H. (1963). Somato- sensory status of Parkinsonian patients before and afier chemothalumectomy. Neurology (Minncap.), 13, 906-912. Reitan, R. M. (1955). Certain differential elects of left and right cerebral lesions in human adults, J. comp, physiol. Psychol. 48, 474-477. Piercy, —— (1956). Trail Making. Mimeographed. Indiana University Medical Center, Indianapobis, Riklan, Mo, Diller, E., Wemer, H., and Cooper, |. S. (1960). Psycho- loical studies on elects of chemosurgery Mo the basa ganglia in Parkinsonism. Arch, gen. Pyychiat., 2, 22: Schaltenbrand, G., and Hailey, P. (1959), Foire tion to Stercatuxis, with an Atlas of the Human Brain, Grose and Stratton, New York. Smith, A. and Kinder, E. F. (1959). Changes in psychological test urmances of brain-operated schizophrenics alter 8 years, nee, 129, 149-150. Teuber. HL LL (1962). Effects of brain wounds implicating right or lett hemisphere in man: Hemisphere ditferences and hemisphere interaction in vision, audition, and somesthesis. In farernational Symposium on Cerebral Dominance, edited by Vernon B. Mountcastle, pp. 131-157. Johns Hopkins University Press, Baltimore. and Oppenheimer, D. R. (1962). Mental disturbances alumolysis. J. Neurol. Neurosurg. Psychiat. 25, 243-250. Wechsler, D. (1955). W.A4IS. Psychological Corporation, New York. 408 Psychosurgery, edited by Edward Hitchcock, Lauri Laitinen, and Kjeld Vaernet (Proceedings of the Second International Conference on Psychosurgery held in Copenhagen, Denmark); published by Charles C Thomas, Springfield, Illinois, 1972 Chapter 11 THALAMOTOMY FOR HYPERRESPONSIVE SYNDROME Lesions in the Centermedianum and Intralaminar Nuclei OrLANDO J. ANDY AND MarION F. JURKO INTRODUCTION The hyperresponsive syndrome, as previously described in this conference, consists of abnormal behavior which is primarily characterized by an abnormally increased response to various sensory stimuli. Three major groups of abnormal behavior were identified and evaluated under the headings: aggression, hvper- kinesia, and patho-affect. This is a report of the thalamotomy results in the treatment of the hyperresponsive syndrome. An at- tempt is made to evaluate the results by applying the response weighted-description technique as previously described, in order to determine which, if any, of the three major abnormal behavioral symptoms responds best to thalamotomy. METHOD Thirty patients, 6 to 49 years of age, received either a uni- lateral or bilateral thalamotomy for the treatment of abnormal behavior. The patients represented various types of abnormal behavior which were at one time or another treated by psvchi- atric techniques, although not primarily considered as psychiatric problems. These patients were referred predominantly as prob- lems of hyperactivity, 14 patients; aggression, 2 patients; malad- justment, 11 patients; and rhythmia, 3 patients. Laboratory studies preoperatively and postoperatively were done on all pa- tients. In some instances the severity of the behavioral problem precluded the use of extensive psychological and other testings. 197 409 128 Psychosurgery Lesions were aimed at the center medianum and intralaminar nuclei of the thalamus. The coordinates for lesion placement were based on identifying the anterior and posterior commissure by contrast ventriculography at the time of operation.* The clinical results from the thalamotomy were classified under good. fair, and poor. The aggression, hyperkinesia. and patho-affect groups of abnormal behavior were then related to the good, fair. and poor results. The postoperative period of evaluation was 8 months to 10 years. RESULTS Thalamotomy Result Categories Based on Clinical Judgment There were six patients with good results (75 to 1009; improve- ment), 14 patients with fair results (25 to 759, improvement), and 10 patients with poor results (0 to 25%, improvement). Good Result Group D. D., age 19, aggression and scizures, thalamotomy, left, 2/8/66. Aggression no longer present and patient is productive and recently married. W. R,, age 34, maladjustment, suicide attempts, and drug ad- diction. Bilateral thalamotomy 7/24/64 and 12/9/64. Patient is productive, owns and runs an upholstery shop, and has six em- ployees. A. Q., age 27, maladjustment. tremor and suicide. Thalamo- tomy, left, 5/16/61. Patient is productive and happily married with no recurrence of major behavioral symptoms. J. M., age 9, hyperactive and destructive. Bilateral thalamo- tomy in 1962 and fornicotomy 1965. A manual laborer. (Patient would have been institutionalized if not operated upon.) J. P., age 35, maladjustment and tremor. Thalamotomy, left, 6/10/65. Patient returned to watch repairing. W. B., age 11, rhythmia, hyperactive self-destruction. Bilat- eral thalamotomy 2/13/64. Patient markedly improved and in open ward. *The atlas of Schaltenbrand, G. and Bailey, P.: Introduction to stereotaxis with an atlas of the human brain. New York, Grune and Stratton, 1959, 2, p. 57 was uscd to establish the coordinates. 410 Thalamotomy for Hypervesponsive Syndrome 129 Fair Result Group DP. B., age 7, hyperactive and destructive. Thalamotomy, left. 4/16/70. Patient is no longer destructive. Hyperactivity approxi- mately 50 percent improved. G. P., age 16, maladjusunent, aggression, and questionable seizures. Thalamotomy, right. 3/21/67. No longer hyperactive and is emploved although he constantly changes jobs. J. W., age 12, maladjustment and hyperactivity. Thalamotomy. left, 3/28/69. Patient has been able to attend school and has be- come more manageable. H. B., age 7, hyperactivity and seizures. Bilateral thala- motomy, 6/19/68 and 1/2/69. Moderate amount of improvement of both hyperactivity and the seizures. G. C, age 12, hyperactivity and aggression. Bilateral thalamo- tomy, 2/2/65 and 2/11/65. Marked improvement in the hyper- activity and aggression, but not productive. H. H,, age 42, hyperactivity and seizures. Thalamotomy, right. 5/7/64. Hyperactivity improved. died 3 months after operation due to pneumonia. ; S. L.., age 38, hyperactivity and self-mutilation. Thalamotomy. right, 3/4/65. Hyperactivity was lessened and self-mutilation ceased. The patient died 3 months after the operation due to respiratory pathology which was also present before surgery. R. M., age 12, aggression. Thalamotomy, right, 11/16/68. Aggression improved although not well enough to have the pa- tient attend school. R. M,, age 7, hyperactivity. Thalamotomy, left. 7/31/69. At- tends school although his performance is fair. D. D., age 6, hyperactivity and seizures. Thalamotomy, right, 3/2/66. Approximately 60 percent improvement in both hyper- activity and the seizures. B. H,, age 47, maladjustment and tremor. Thalamotomy, left, 5/22/68. Tremor improved, although psychiatric disturbances prevailed and patient died 6 months postoperatively due to coron- ary occlusion. C. H,, age 42, maladjustment and tremor. Thalamotomy, left, 5/6/65. There was marked improvement in the tremor, but only slight improvement in the maladjustment. 411 130 Psychosurgery G. L., age 14, hyperactivity and aggressich. Bila motomy, left 8/29/69, right, 2/12/70, and lgft, N15/ tient has approximately 60-70 percent impibv to attend school Poor Result Group E. P., age 40, hyperactivity (institutionalized). Thalamotomy, left, 10/28/66. Essentially no change in patient's condition. M. B., age 49, maladjustment, tremor, and alcoholism. Thala- motomy, right, 3/27/64. Slight improvement although the pa- tient remained an’ alcoholic. D. B,, age 42, hyperactivity (institutionalized). Thalamotomy, right, 3/25/65. Hyperactivity did not decrease. J. C., age 22, maladjustment and seizures. Thalamotomy, left, 7/17/68. No Spon L.W.,, age 22, rhythmia (rocking). Thalamotomy, right. 6/2/64. No improvement. J. H. S., age 44, maladjustment. Thalamotomy, right, 5/8/68. Slight improvement although not enough to enable the patient to hold a job. I. W., age 25, hyperactivity and abnormal movements (ballis- tic). Bilateral thalamotomy, left, 6/10/66, right, 5/18/66, and left, 7/1/66. Hyperactivity and movements became worse and the patient’s deteriorating state could not be reversed. Expired 6 weeks postoperatively. E. T., age 10, hyperactivity and seizures. Thalamotomy, right, 5/8/61. The patient had improvement of both seizures and be- havior but still had to be institutionalized. C. E,, age 37, maladjustment and tremor. Thalamotomy, left, 10/20/66. Performance was satisfactory when the patient was not under stress. A. S., age 14, hyperactivity and seizures. Thalamotomy, left, 5/30/68. Patient died 3 weeks postoperatively due to brain ab- scess. Lesion Site The average of the stereotaxis of the coordinates for the six pa- tients in which results were classified as good were F; 9-1 mm, L 7-1 mm, and H 41.3 mm. The average of the stereotaxic coordinates 412 Thalamotomy for Hyperresponsive Syndrome 131 obtained for the 14 patients in which the results were classified as fair were F, 7.6 mm, L 7.3 mm, and H 40.7 mm. The average of the stereotaxic coordinates for the 10 patients in which the clinical results were classified as poor were F, 6.6 mm, L 8.1 mm, and H +0.6 mm. The lesion sites in relation to the clinical im- provement are presented in the sagittal plane (Fig. 11-1). The horizontal bars represent the anterior-posterior commissure line and the vertical bars represent 5 mm ditferences from one another. Bilateral Versus Unilateral Operation in Relation to Clinical Improvement Three of the six patients with good results had bilateral operations and three had unilateral operations. Four of the pa- tients with fair results had bilateral operations and ten had uni- lateral operations. In the poor result group, all the operations Lesion Sites in Sagittal Plane in Relation to Clinical Improvement Good 1 . "2 a“ 0 Fp 5[° * Fp 10 Fair . | . Poor Co i : | ! Figure 11-1. 413 132 Psychosurgery were unilateral and there were no bilateral operations. It is of further interest to note and compare the effects of unilateral versus bilateral operation in two patients, D. D. and W. R. who presented a closely similar problem severity index 42 and 40 re- spectively (Fig. 10-4, previous chapter). The problem severity index which is presented in a graph form for patient R. W. (Fig. 11-3) reveals the preoperative aggression to be approximately 50 percent, hyperkinesia 38 percent, and patho-affect 58 percent with a 99 percent reduction in the postoperative aggression, a 97 per- cent reduction in hyperkinesia and a 76 percent reduction in patho-affect following the bilateral thalamotomyv. In contrast, the percentage reduction of almost a similar problem severity index in patient D. D. was not as marked (there was only a 45 percent improvement of aggression, 70 percent improvement in hyperkinesia, and 55 percent improvement in patho-affect (Fig. 10-3, previous chapter). Relative Severity of the Behavioral Problem in Relation to Clinical Improvement The three major groups of abnormal behavioral responses were expressed as percentage values in relation to the clinical result categories of good, fair, and poor (Fig. 11-2). Note that in the good result group aggression was the predominant component of the behavioral abnormality whereas in the fair group, hyper- kinesia was the predominant component of abnormal behavior, and in the poor group patho-affect was the predominant com- ponent of abnormal behavior. In relation to the differences in the relative degree of improvement for the problem severity index of the three categories of abnormal behavior, it is well demon- Relative Severity of the behavioral problem in relation to Clinical Improvement (expressed as percent) Aggression Hyperkinesia Patho-Affect Good 45 27.5 27.5 Fair 33 43 24 Poor 20.5 33.5 46 Figure 11-2. 414 Thalamotomy for Hyperresponsive Syndrome 133 strated in Figure 11-4 that patho-affect does not respond as well to thalamotomy as do aggression and hyperkinesia. Compare this graph for patient A. Q. (Fig. 11-4) with that of patient W. R. (Fig. 11-3). Note that the patient A. Q. had a unilateral thala- motomy whereas W. R. had a bilateral thalamotomy. However, in spite of the fact that the patient W.R. had a bilateral thal- motomy the results for patho-affect were not as beneficial as the results for aggression and hyperkinesia when considered in rela- tion to one another in the same patient. DISCUSSION By clinically categorizing thalamotomy treatment into good, fair, and poor results, and differentiating the hyperresponsive syn- drome according to aggression, hyperkinesia, and patho-affect, it was concluded that aggressive behavior was most improved and patho-affect least improved. This is an important differentiation R Ww, 105687 100 [ ° ° 80 [- Problem Severity Index 60 == Pre-ap E \\\\ post-op SH u ® % improvement — = es w a a. = “of = 20 pe = Hm 22 . AGGRESSION HYPERKINESIA PATHO-AFFECT Figure 11-3. 415 134 Psychosurgery since it suggests that those patients with relatively large amounts of patho-affect may benefit trom further trials on medical therapy or additional surgery at other sites. It should be noted that bilateral operations in contrast to uni- lateral were more effective in alleviating the abnormal behavior. This result, in addition to clinical impressions, suggests that the hyperresponsive syndrome in most instances represents a bilateral diffuse pathophysiologic condition. Since there is great variability in the size and location of struc- tures in relation to the established coordinates, it is hazardous to conclude which structures were implicated in the good result group. However, the results tend to indicate that the more poste- rior thalamic lesions at F, 9 mm, just above the horizontal zero line and approximately 7 mm lateral to the midline are most effective. Since the lesions are approximately 3 to 4+ mm in di- ameter and 5 to 7 mm in length oriented in a 45° angle in the sagittal planes it is felt that the center medianum and intralaminar nuclei are implicated, although not to the exclusion of other close- ly associated or bordering nuclei. : Provlen Severity Index 2 5 =» - Post-op =\ ® % improvement =\ =\ = N\ = = 2 AGGRESSION HYPERKINESIA PATHO-A Figure 114. = ECT 416 Thalamotomy for Hyperresponsive Syndrome 135 SUMMARY Thalamotomy results in the treatment of 30 patients with the hyperresponsive syndrome were evaluated. The hyperresponsive syndrome was separated into three major components: aggression, hyperkinesia, and patho-affect. Aggression benefited most and patho-affect least from the oper- ations. Bilateral operations were more beneficial than unilateral. The optimum lesion site for good results appeared to be in the area of the center medianum and intralaminar nuclei. 417 American Journal of the Medical Sciences, Vol. 252, No. 2, August 1966 PROGRESS r OF MEDICAL SCIENCE SURGERY UNDER THE CHARGE OF I. S. Ravoin, B.S, M.D. EMERITUS PROFESSOR OF SURGERY, UNIVERSITY OF PENNSYLVANIA PHILADELPHIA, PENNSYLVANIA AND Jaates D. Harpy, M.Sc., M.D. PROFESSOR AND CHAIRMAN, DEPARTMENT OF SURGERY UNIVERSITY OF MISSISSIPPI MEDICAL CENTER JACKSON, MISSISSIPPI NEUROSURGICAL TREATMENT OF ABNORMAL BEHAVIOR® By O. J. Axpy, M.D. DEPARTMENT OF NEUROSURGERY UNIVERSITY OF MISSISSIPPI MEDICAL CENTER JACKSON, MISSISSIPPI AN attempt is being made in this report to consider primarily the surgical treatment of those patients who have abnormal behavior which is not consid- ered a psychosis. The question arises as to what constitutes abnormal behavior. A definition for purposes of this pres- entation may be as follows?*S. Behavior is defined as “the manner of conducting oneself,” and the term abnormal, “devi- ating from the normal or average.” Norm is “a principle of right action binding upon the members of a group and serving to guide, control or regulate proper and acceptable behavior.” Thus, it is obvious that abnormal behavior ray include patients who suffer from a very mild emotional or neurotic dis- turbance to patients who suffer from a severe psychosis. However, it must again be stressed, this presentation does not include psychotic disorders. Symp- tems which characterize the abnormal behavior in this treatise are cmetional tension, anxiety, aggressiveness, de- structiveness, agitation, distractability, attack, suicidal tendencies, nervousness, mood oscillations, stealing. rage, neda- tivism, combativeness, and explosive emotions. These various symptoms or syndromes contribute to a social mal adjustment for which society demands correction or appropriate control. Con- sequently, the medical and surgicai therapeutic approach, in recent years. has received a great deal of attention both experimentally and clinically. The neurosurgical objective in the treatment of behavior disorders has been to em- ploy the smallest lesion and to attain This study was supported in part by the Clinical Research Center Grant GCRC FR-91 from the National Institutes of Health. (132/232) 93-999 (Pt. II) 0-73 - 6 418 Progress of Medical Science: the greatest beneficial result for the longest period of time with a minimum associated deficit. Consequently, many different operations aimed at different parts of the brain have developed. One of the main developments has been the introduction of stereotaxic surgery to clinical use by Spicgel et al 14-4 “Re reo- taxic technique s have provided a meth- od of approaching very small and spe- cific subcortical brain sites with minimal damage to surrounding brain structures. PREFRONTAL LOBOTOMY. In the carly development of psychosurgery, the frontal lobe was the first target site for the placement of lesions. The major incentive for development of various frontal lobe operations for the treat- ment of abnormal behavior came from the work and observations of I. Moniz®¢ who may be considered as having estab- lishe d the “standard prefrontal lobot- omy.” Freeman and Watts" introduced the operation in the United States. This classical operative procedure consists of a transverse section of the white mat- ter in the prefrontal Tobe. Anxiety states and neuroses appear to have responde d best. Patients with such illnesses can carry on with their job and daily activ- ities but with a great deal of associated tension and inability to enjoy life. Freeman and Watts! state that “long vacations, rest periods, and various psy- chotherapics, sometimes also shock ther- apy. fail to give these individuals a sufficient alteration in their character to enable them to carry on their activ- itics in a harmonious manner and to achieve satisfaction in their work and in everyday existence.” Those patients with tics, mannerisms and compulsions display no improvement in that particu- lar type of behavior following prefrontal surgery. Although the tld opera- Han of prefrontal lobotomy often re- licves or reduces the patient's mental Hines and improves some aspects of behavior, the improvements may be accompanicd by personality disturb- ances. Consequently, modifications of the frontal lobe operation developed SURGERY 133/233 in order to limit the lesion to more specific areas or sites (Fiamberti’, Grantham, Iofstatter, Smolik and Busch, Livingston'?, Lyerlyv®?, McKis- sock® Penficld®, Pool, Poppen®, Scoville®3, and Whitty ef ¢l.®), Crow, Cooper and Phillips” and White, Sweet and Hackett" described a technique of stereotavically placing chronic nultistrand electrodes in the frontal lobes to perform a selective leu- kotomy in accord with the progress of the patie nt’s illness. Anxiety and ar pres- sion have been relieved and in some patients the anviety will Rin com- pletely disappeared’ whereas the pain associated with malienaney or other pathology persisted (White, Sweet and Hackett), CINGULECTONY. This operative pro- cedure consists of excising arcu 24 of the anterior cingulate gyrus. Whitty et al. cingulectomized patients in whom aggressive outbursts or tension and obsessive features were pronounced. Results revealed no reduction of affect as one finds with prefrontal lobotomy and the personality was well preserved even following the bilateral operation. The ope vative procedure produced a marked improvement in the symptoms of obsession, tension and anxiety. Pu- tients who had behavioral manifesta- tions of spontancous and aggressive out- bursts had a temporary relict of the symptomatology but it was not perma- nent. Le Beau! performed cingulec- tomy in 44 patients for depressive and excited states, psychoses with violence, epilepsy, mental retardation and agita- tion. Beneficial results were obtained in reducing irritability and violence in both the epileptic and in the retarded group. Agitation was very markedly improved. In contrast to frontal topce- tomy, it was much more beneficial. Tt did not greatly alter seizures. There were no psychological deficits, A com- parison made between the frontal and cingulate lesion effects revealed the fol- lowing: frontal lesions produced iu- creased agitation and cingulate lesions 419 134/234 The American Journal of the Medical Sciences + August, 1966 did just the opposite. Cingulectomy pa- tients were characterized by clinical introversion and topectomy patients by extroversion. Sano®* reports that the calming effect following cingulectomy was most pronounced for several months to one year after the operation and gradually decreased thereafter. Sedation was obtained in long-term ob- servations in about one-half of the cases. He also found a relatively large inci- dence of recurrence of rage attacks. cincurotonmy. This operation consists of interrupting the rostral end of the cingulum (fiber tract presumably origi- nating from cells in the cingulate gyrus). Foltz and White* employed cingulotomy in patients with long- standing psychoneurosis and hyperac- tive autonomic mechanisms and in patients with neoplasms exhibiting agi- tation and pain. The hyperactive, labile and inappropriate emotional responses disappeared and the withdrawal reac- tions to drug addiction were insignifi- cant. The emotional tone was improved and stabilized with no associated ob- vious personality changes. HEMISPHERECTOMY. The entire cere- bral hemisphere, except for the thala- mus and parts of the basal ganglia, is removed. Hemispherectomy has been used in the surgical treatment of infan- tile hemiplegia with associated uncon- trollable epilepsy and behavioral dis- turbances. Krynauw!? states, “in most of these patients an outstanding feature has been episodic outbursts of violent temper tantrums which usually have no adequate cause, are short-lived and suggest the possibility of there being epileptic equivalents.” A marked im- provement in the personality and be- havior and mental state of the patients was observed following the hemispher- ectomy. Others also reported marked improvement in irritability and aggres- sive tendencies following hemispherec- tomy (Cairns and Davidson?, David- son, McFie®!, Obrador and Larra- mendi2®, Uecker, French and John- son? ). Hemispherectomy in one patient with “irritability and a tendency to fight and show violent temper toward her relatives” apparently showed a good response to hemispherectomy ( Orbador and Larramendi®®). Cairns and David- son® find that after hemispherectomy the patients stop having seizures and there is improvement in their mental state. In addition, these authors state “temper tantrums cease and the patients become happy and good tempered and begin at once to show intellectual and sometimes artistic development.” Im- provement in mental activities is greater following complete hemispherectomy than following partial hemispherectomy (McFie?!). This, in part, may be asso- ciated with a relative greater improve- ment in behavior after total rather than partial hemispherectomy. Hemispherec- tomy resulted in improved adjustment in at least 5 of 7 cases ( Uecker, French and Johnson”). Although the convul- sions and personality disorders re- sponded well to surgery, there was no significant improvement of intellectual function. TEMPORAL LOBECTOMY. This operative procedure consists of excising the ante- rior tip or 5 to 7 cm. of the temporal lobe, with or without inclusion of the amygdala and hippocampus. It origi- nally was devised for the treatment of psychomotor or temporal lobe seizures (Bailey and Gibbs® and Penfield and Baldwin®?). Following temporal lobec- tomy for psychomotor seizures, patients were observed to display improved behavior (Green et al.?). In order to modify aggressive behavior, Valladares and Corbalan*® removed the tip of the temporal lobe and the uncus. This was done in 16 patients with oligophrenia, 7 were psychopaths and 3 had psycho- pathic personalities. Following surgery, the patients displayed decreased aggres- siveness and a better adaptation. In addition, there was a personality change consisting of a change from introver- sion to extroversion. It should be noted 420 Progress of Medical Science: oat four of the patients had a previous .nculectomy and one of them a pre- «ontal lobotomy. Temporal lobe removals which in- ude the hippocampal gyrus and near- tw structures produce defects for recent memory (Milner). Bilateral temporal ".hectomy produces not only a loss of iar and rage reaction but also an asso- cated Kliver-Buey!'® syndrome which consists of loss of recognition of people, mercased sexual activity in the form of wlf-abuse and homosexual tendencies, hwpermetamorphosis, and bulemia (Ter- san?) and Terzian and Ore®?). TEMPORAL LOBOTOMY. Because of the associated undesired side effects from temporal lobectomy as mentioned shove, Turnert used bilateral temporal lobotomy for psychomotor epilepsy, a transsection of the temporal lobe white matter in the frontal plane. He per- formed bilateral temporal lobotomies in patients with bilateral temporal lobe clectroencephalographic abnormalities and psychiatric abnormalities such as psychosis, outburst of rage and suicidal tendencies. The associated mental change following operation was strik- ingly better. Early postoperatively there was euphoria and the patients were free from irritability, confusion, depres- don and mental tension. Relief from tension is like that from prefrontal lobotomy without the seriousness which follows the prefrontal leukotomy. AMYGDALOTOMY, Amvedalotomy was performed in 60 patients with behav- ioral disorders by stereotaxically inject- ing 1 ml. oil-wax into the amygdaloid veedeus either bilaterally or unilater ally t Narabayashi et al*7). The procedure was first directed at patients with seiz- ure problems who, in addition, had behavioral disorders. Eighty Jive per cent of the 60 patients had satisfactory improvement. Behavioral disturbances such as hyperexcitability, destructive- ness, and violent aggressiveness were markedly improved by the operative procedure. Bilateral lesions were placed SURGERY 135,235 in 21 cases and no Kliver-Bucy’® syn- drome developed. Postoperatively, in- oi deficiences could not be raluated because most of the patients were mentally retarded. Chapman placed electrodes in the amygdala and periamygdaloid area of patients with temporal lobe epilepsy in order to stim- ulate, record and electrolytically ablate. The major reason for selecting these patients for surgery was surgically to treat intractable assanltiveness, It is of interest to note that electrical stimula- tion, in no instance, evoked any subjec- tive or behavioral response which re- motely resembled aggressiveness. How- ever, other components of the temporal lobe seizure were elicited during elec- trical stimulation. According to Spiegel and Wycis® abnormal halavior in chil- dren, except for 2 cases, is essentially uninfluenced by amygdalotomy. HYPOTHALAMOTOMY ( Later al Hypo- thalamus). Lesions were placed in the hypothalamus in 25 instances because of inadequate improvement following lesions placed in either the dorsal medial nucleus or anterior thalamic nucleus (Spiegel and Wyeis®). Hypo- thalamic lesions were placed in only 2 patients who had no previous surgery. The one symptom complex which ap- peared to be most beneficially treated was the anxiety neurosis. The non- schizophrenic type of behavioral dis- orders appeared to benefit much more frequently than the schizophrenic type of disorders. HYPOTHALAMOTOMY ( Posterio-medial Hypothalamus). Six cases had stereo- taxic operations in this arca of the hypo- thalamus. Postoperative results revealed marked calmness, passivity, tractability and decreased spontaneity. Spontaneity recovers within one month and other changes are long lasting. Somnolence sometimes last 7 to 10 davs (Sano). FORNICOTOMY. In 21 cases the col- umns of the fornix were interrupted bilaterally at the level of the foramen cf Monroe. Improvement was obtained 421 136/236 The American Journal of the Medical Sciences + August, 1966 in patients with convulsions and rage attacks. The operation was followed by “sedation” (Sano®!). MESENCEPHALIC RETICULOTOMY. Elec- trolytic lesions were placed stereotaxi- cally at the rostral end of the mesen- cephalon ventral to the aqueduct. In “the 6 cases which were done, a tendency toward calmness was more or less noticed (Sano3!). THALAMOTOMY (Pulvinar Nucleus). A lesion placed in the pulvinar nucleus of one patient with agitation produced no beneficial effects (Sano?!). THALAMOTOMY (Anterior Thalamic Nuclei). Sano? placed a stereotaxic lesion in the anterior thalamic nucleus of one patient and a direct surgical ablation of the internal medullary lamina in another patient which resulted in long-lasting calming effects. Spiegel and Wycis®® placed lesions in the ante- rior thalamic nuclei in 21 patients who had lesions previously placed in the dor- sal medial nucleus or hypothalamus. THALAMOTOMY (Dorsomedial Nu- cleus). According to Spiegel and Wycis®, following thalamotomy in the medial dorsal nucleus of the thalamus, patients had a reduced emotional ten- sion. “The patients become less hostile and withdrawn and respond more easily to questions; their hyperactivity dimin- ishes; aggressive, assaultive, screaming patients become calm, better behaved, cooperative, and even obedient.” Le- sions in the dorsal medial nucleus did not significantly alter mental activity and appeared to improve the social adaptiveness of the patient and there was no disorganization of body image. If relapses occur, lesions may be added in the anterior nuclei and the hypothalamus. Lesions in the hypothal- amus appear to be more effective than those in the anterior thalamic nuclei. From the results, the authors state that dorsomedial thalamotomy is the method of choice in diencephalic operations. THALAMOTOMY ( Posteroventromedial Region). Oval lesions approximately 5 to 10 mm. in length and 3 to 5 mm. in diameter are aimed at the centre medi- anum nucleus in the area bordered by the posteroventrolateral portion of the mediodorsal nucleus, the nucleus para- fascicularis and the zona incerta. The following brief reports are from patients treated at the University of Mississippi Medical Center Hospital, Whitfield State Hospital and the Veterans Admin. istration Hospital in Jackson, Missis- sippi. Case Reports. W.B., a boy of 12 a mental defective with seizures, repetitive movement (rhythmia) and behavior disorder. Rhythmia consisted of body rocking, self beating of the head and regurgitation. Behavior disorder con- sisted of negativism and destructiveness. Pa- tient was constantly restrained in a chair and wore a football helmet to prevent self-mutila- tion. Thalamotomy was done on the left (Fcb- ruary 13, 1964) and right (December 17, 1964). Since surgery the rocking, self-beating, regurgitation and destructiveness have ceased. He is up and around with other mentally retarded patients and no longer restrained. W.B., a man of 34, had behavioral difficul- ties since childhood (alcoholism, drug addic- tion, attempted suicide, aggressive and destruc- tive outbursts, nervousness, and emotional in- stability). Thalamotomy was done on the right (July 24, 1964) and left (December 10, 1964). Behavior improved, he developed a leather shop business, supports the family and is well adjusted socially. He has not returned to drug addiction and alcoholism. A.Q., a man of 24 had behavior disorder (nervousness, spells of shaking all over, explo: sive anger and aggressiveness, attempted sui- cide). Torticollis movement to the right was associated with extreme nervousness, tension and agitation. Left thalamotomy was donc on May 16, 1961. The patient has become re- habilitated, remains happily married with children and supports the family. J.M., a boy of 9, had seizures and behaviora! disorder (hyperactive, aggressive, combative. explosive, destructive, sadistic). Bilateral thalamotomy was done, left (January 12, 1962), right (January 30, 1962). Right thali- motomy was repeated on September 18, 1962 The patient’s behavior was markedly improved and enabled him to return to special educa tion school. After one year, symptoms of hyper: irritability, aggressiveness, negativism, ant combativeness slowly reappeared. A fornicot- omy was performed on January 13, 1963 Impaired memory for recent events develope! and the patient became much more irritable. negativistic and combative. Consequently, * simultaneous bilateral thalamotomy was don 422 Progress of Medical Science: ore month later, on February 16, 1965. The patient has again become adjusted to his environment and has displayed marked im- provement in behavior and memory. J.P., a man of 51, was alcoholic, and has addictive and behavior disorder (nervousness, anxiety, aggressiveness, and depression). A very marked diffuse tremor with speech im- pairment associated with emotional stress. A left thalamotomy was done on June 10, 1965. The patient has returned to watch repairing. Behavior has improved and there has been no continuation of alcoholism and addiction. Faotionally he is much more stable. Conclusions. An attempt has been made to enumerate and discuss the various neurosurgical procedures util- ized in the treatment of abnormal be- havior. In comparing the results, it is difficult for this reviewer to reach any firm conclusions as to the best operation for a given bchavioral syndrome. spicgel and Wycis® concluded “thal- amotomy is able to afford long-lasting relief particularly in states of anxiety and depression refractory to psycho- therapy, drugs and shock treatment;” in other words, these two groups scem to iepresent the main indication for this procedure, particularly if one considers that its side effects are relatively slight. Furthermore, it has been shown that a combination of frontal leukotomy and thalamotomy may be effective in in- stances in which either of these two operations failed or produced only SURGERY 137/237 transient improvement. Sano con- cludes from his own experiences that the results obtained in cingulectomy, thalamotomy, fornicotomy and reticu- lotomy are far from satisfactory. A pref- erence for hypothalamic lesions is im- plied. Although not clearly stated, others appear to prefer amygdalotomy, cingulotomy, limited frontal lobotomy or other operations for treating be- havioral disorders. Thus, it is obvious that no definitive conclusions can be made at this time since the field, neurosurgical treatment of abnormal behavior, is still relatively very new. We need much more informa- tion concerning the functional interre- lation of varieus brain structures in terms of behavior. We also need a satisfactory classification of abnormal behavior in order more adequately and precisely to relate brain structure to brain function from a clinical approach. These are pertinent needs which must come from further animal experimenta- tion and empirical clinical observations before well established and significant conclusions can be made relative to the neurosurgical treatment of abnormal behavior. However, according to the present clinical observations and results the future of “behavioral neurosurgery” appears promising. 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Neurol, 2, 317, 1960. (50) Whitty, C. W. M., Duffield, J. E., Tow, P. M., and Cairns, H.: Lancet, 1, 475, 1952. (51) Wycis, H. T., and Spiegel, E. A.: Proc. Roy. Soc. Med., Suppl., 42, 12, 1949. a0 424 reatable Violence Tt is currently so fashionable to ascribe the roots of violence to so- cial ills that the role of brain dysfunction has been relatively ig- nored. The author doesn’t claim that we can end violence in our society by Dilantinizing our water supply. But he does believe that it is vital. for both patient and public. to cull out cases of episodic dyscontrol. Here's how he and his colleagues have proved that many such patients are treatable. R. J., a twenty-three-year old, unemployed mechanic, is brought into the emergency room by police in a drunken stupor. He has sus- tained minor lacerations after being hit on the head with a beer bottle. He is hand-cuffed but still assaultive, so you approach him cautious- Iv. You learn that he is an old friend of the police, actually quite an “incorrigible,” with a long history of truancy and arrests. He has been jailed several times already for assault and once for drunken driving. To top things off, he has been indicted once on a charge of manslaughter after shooting a friend in an ar- gument. Two weeks following that incident he had tossed his two year old daughter out the window of his moving car after she “talked back.” You remember it well, because you treated her for severe lacerations and sewed up R. J. later that same cvening after he cut his wrists in a suicide gesture, The ¢ know. But there was a difference this time. c isn't exaggerated, as most of you Dr. Maleizky is Chief, Department of Neuro psychiatry, US. Lyster Army Hospital, Fort Rucker, Alabama RESIDENT AND STAFF PHYSICIAN + FEBRUARY 1973 * Barry M. Maletzky, M.D. The psychiatry resident, routinely called on such matters, wisely elected to explore further just this once, much to the consternation of his medical colleagues, who believed this to be just onc more example of the deluded psychiatrist vainly doing battle against the sociopath. The resident learned that R. J. had been a hyperactive, clumsy child who. having quit school at thirteen, had learned neither to read nor write. He had experienced “spells” of vio- lence since adolescence—some unprovoked, some after excessive alcohol. One psychiatrist after another had plied his trade on R. Is psyche without any change in how R. J. be- haved. So, the resident did something even more unusual for a psychiatrist—a complete neurological examination. The examination re- vealed that R. J. was inordinately clumsy on various coordination tasks—he couldn't consis- tently tell left from right and he demonstrated some anomia and dysphasia. An EEG clinched the issue—anterior temporal lobe spiking. Al- though R. J. had never evidenced obvious psy- chomotor epilepsy, diphenylhydantoin (Di- lantin®) was begun. A year later, he is work- ing steadily, has learned to read and write and, 425 absence of hypercellularity. (C.) Post-Streptococcal Acute Glomerulonephritis (H&E Stain). Note diffuse hypercellularity; early crescent. membranous glomerular disease appear to re- (D.) Systemic Lupus Erythematosus (H&E stain). spond on occasion to steroid or immuno- Note focal hypercellularity and exudation. therapy. Amyloid renal disease will not re- spond to steroid or to other currently available immuno-suppressive therapy. Thus, renal biopsy appears indicated in the presence of the nephrotic syndrome to deter- mine the likelihood of success of treatment and how vigorously it should be pursued. If any patients with these diseases are subjected to such vigorous treatment, periodic evaluation of its effects on the renal lesions is indicated. 2. ABNORMAL URINE—When the disease re- sponsible for abnormal urine is not apparent on clinical grounds, renal biopsy may be the only procedure available that can establish a diagnosis. The considerations that go into the decision of whether or not to recommend a biopsy should not be applied rigidly. If a pa- tient with abnormal urine offers no clues as to the nature of the disease but has nor- mal renal function and blood pressure, the patient and the physician may elect a period of observation, especially if the urinary abnor- mality is isolated pro- Continued on page 74 FEBRUARY 1973 + RESIDENT AND STAFF PHYSICIAN 39 426 The brain is the organ that links man to his environment. a relation- ship crucial in understanding and changing behavior as complex as violence, vet a relationship too often ignored by social scientists. FEBRUARY 1973 « RESIDENT AND STAFF PHYSICIAN a 42 427 The resident did something even more unusual for a psychiatrist . . . a complete neurological examination. most significantly, has not committed a single act of violence—the first year of his life since the age of ten in which this has been true. Dramatic, But Not Unique The case is dramatic, but true and, sadly, not unique. Hundreds of such unfortunate pa- tients have now been recognized as suffering from “hidden” brain dysfunction and many, including R. J., fall into what has been called the Episodic Dyscontrol Syndrome. It is currently so fashionable to ascribe the roots of violence to social ills that the role of brain dysfunction has, until quite recently, been relatively ignored. No claims are made herein that all violence in our society stems from brain disease; nonetheless, of all those millions afflicted with poverty, social hatred, and urban stagnation, only a few behave vio- lently towards their fellow man. The brain is the organ that links man to his environment, a relationship crucial in understanding and chang- ing behavior as complex as violence, yet a rela- tionship too often ignored by social scientists. Perhaps this explains their relative impotence thus far in averting the unwanted consequences of human aggression. In our work at the University of Oregon Medical School, the Fort Rucker Mental Health Clinic, and various rural health clinics in southeastern Alabama, we have come to recognize that at least one kind of violent pa- tient may be suffering from hidden brain dis- case. The distinction is critical—because these patients can be successfully treated. We have come to classify them under the rubric of Ep- isodic Dyscontrol. When They Hit the 30s Such patients are usually referred to health authorities in their third decade of life. Their backgrounds are chronicles of disorder— RESIDENT AND STAFF PHYSICIAN « FEBRUARY 1973 broken homes with heavy family histories of alcoholism, crime, and epilepsy in the males and depression in the females. They usually carry a history of difficult birth, multiple head traumata, hyperactivity and poor school per- formances as children, plus aggression towards other children, cruelty to animals and fire- setting. Their histories from adolescence on read like a sccond-rate crime paperback. Tru- ancy and petty stealing launch them into grand larceny, assault and battery, and even murder. Particularly prominent in their dossiers are traffic violations, including drunken driving, recklessness, and hit-and-runs, Alcoholism has figured prominently in many of their crimes. Pathognomonic of dyscontrol, however, is the “storm of violence.” Upon minimal or even no provocation, these patients lose control, wrecking property and directing violence against anyone in their way. Most often, such storms arc directed against a close family member or friend, one in whom the patient has some cmotional investment; occasionally they direct violence against themselves in the form of suicide gestures or attempts. Storms may be preceded by an aura: a feeling of impending loss of control, a vaguc buzzing in the head, hyperactivity, or a nauseous feeling. They are often followed by a hcadachc and long-lasting torpor. Particularly prominent following such attacks arc extreme feelings of remorse. These patients all believe “something” came over them to make them lose control. They view such attacks as completely alien and many claim to have no memory of the contents of the attack, or at best, a vague recollection, “as if in a dream.” Most have been through the routine of making such claims to the obviously disbe- lieving cars of police and physicians—who somehow “know intuitively” that these unfor- tunates are only trying to camouflage their complicity. 428 Pathognomonic of dyscontrol is the “storm of violence.” Upon minimal or even no provocation, these patients lose control. . . . Yet, if thoroughly investigated, their stories do make sense. Relatives, who often live in constant dread of another attack, describe such episodes as foreign to the patient—happening fo him, not something under his control. They also describe other attacks of a non-violent nature, such as wandering or staring spells. To add to the neurological flavor of such patients, they often complain of severe headaches unre- lated to aggressive episodes. In addition, many of their storms of violence are exacerbated by alcohol in a fashion similar to epileptic attacks Of clinical significance is the fact that the di- azepoxide congeners, Librium™, Valium®, and Serax, also can precipitate violent epi- sodes, a fact sadly learned too late by physic cians who have tried to nonspecifically tran- quilize these patients, These Patients Are Armed and Dangerous Not surprisingly, almost all such patients complain of depression and anxiety. Most have a constant, slight hand tremor. Many have sex- ual problems which can range from impotence to a sadistic use of sex. All such patients we have treated have been male: some female patients have been described in other series, but we have been unable to ascertain whether they truly fit our definition of episodic dyscon- trol Almost all of these patients own weapons Many keep loaded guns or knives on their persons. A majority have used automobiles as weapons. They drive when angry to reduce tension and frequently try to get even with someone who has just cut them off or passed them It is not surprising that their records are filled with scrious and even fatal auto acci- dents. Most of these individuals pass a quick neu- rological exam casily. It is only a careful ex- amination that will reveal the half-hidden, “soft” signs so commonly found— left-right ambivalence, dysdiadokokinesis, mild ataxia, astercognosis, dysgraphesthesia, anomia, mini- mal dysphasia, perceptual reversals, and minor recent-memory impairments. Electroencephal- ographic abnormalities fail to reveal epilepsy Instead, reports frequently are noncommital; often, however, anterior temporal slowing or spiking is seen. In our series, which generally compared to that of others in the field, 60 of such patients demonstrated temporal lobe ab- normalities on the EEG. Other neurological examinations, including lumbar punctures, skull series, and sometimes brain scans, have not been fruitful. Just an Excus You may say, with justification, that many patients demonstrate vague EEG abnormali- ties: why excuse these patients’ behavior as the result of some neurological abnormality? Granted—but when you recall that the scalp EEG rarely demonstrates intracerebral events adequately. then as it not entirely reasonable to assume that such patients are suffering attacks of a form of epilepsy? Intracortical EEG re- cording and special drug activating procedures have now revealed focal epileptic activity in many patients, such as our own R. J. We are now convinced that should such procedures be- come feasible on a widespread basis, many cases of dyscontrol would be discovered and possibly treated by in-depth destruction of the offending cortical are Lacking such sophistication, we have elected to treat such patients with Dilantin and have been gratified and surprised by our results: when properly pre-selected, over 807 of such individuals have improved remarkably with our usual dose of 100 mgms. three times daily By improvement, we look for no more than an end to violent outbursts. However, many pa FEBRUARY 1973 + RESIDENT AND STAFF PHYSICIAN 43 a4 THIS MONTH'S COVER This month's highly-different cover illustrates the foregoing article, “Treatable Violence” by Barry M. Maletzky, M.D. The collage by artist Fred Otnes, while it is graphically represen- tative of the disordered, damaged life of the vio- lent personality, is, at the same time, a cohesive unit which evolved from many preliminary sketches and a great deal of advance planning and choosing of materials by the artist. This shabby framework of one man's violent life, held together only tentatively by bits and pieces of string, encompasses many symbolic ele- ments of his makeup and environment. Among them, we find a rusted lock which—if we had the key—might help in understanding man’s vio- lent nature; a clockwork with several essential parts gone awry; and an enigmatic wadded paper ball which, according to the artist, “adds a sense of mystery” to the work. The artist himself photographed his collage against a dark background, with lighting from above, in order to achieve a shadowy, somber effect. Fred Otnes is a native of Kansas, educated at the Chicago Art Institute and the American Academy. He has won over 60 awards at major shows throughout the country, and his work has appeared in many national magazines. His style ranges from highly-realistic illustrations to inter- pretive collages, such as this month's cover. RESIDENT AND STAFF PHYSICIAN + FEBRUARY 1973 | | | | | | | | | | | | | tients find their lives considerably changed for the better when thus able to control them- selves: Their families no longer dread aggres- sion, they no longer need to contend with the law constantly, and they no longer need to continually defend against their assaultive losses of control nor grieve over the results of their violent attacks. None of our patients claimed to no longer feel anger, only to be better able to prevent its escalation. But that's enough. We do not claim we can end violence in our society by Dilantinizing our water supply. Ep- isodic dyscontrol probably contributes but a small part to the violence and aggression of the modern day. But we do believe that it is vital to delineate and delimit examples of violent behavior attributable to brain dysfunction be- cause some of these patients are treatable. Our patients did not suffer from obvious temporal lobe epilepsy; neither were they schizophrenic, nor grossly brain damaged. In retrospect, it seems that most such patients may be afflicted with a form or variant of temporal lobe epilepsy. There is evidence to suggest that such patients actually have small, nonexpand- ing lesions of limbic structures, particularly of the amygdalar region—that area of the tem- poral lobe so exquisitely sensitive to emotional stimuli. Thus, it becomes just as criminal on our part to relegate all such patients to the waste-heap of “sociopathic personality” as it is criminal on their part to perpetrate senseless aggression. It is too easy and quick to judge such patients and believe they must be made to suffer for their crimes; it would be more diffi- cult, yet more profitable and humane to ask what we as physicians can do to discover which among them suffer from a treatable brain dysfunction. Hopefully, in the bargain, we may thus advance our understanding of human vio- lence. END 430 Medical Research Is Hurting by MICHAEL E. DeBAKEY and LOIS DeBAKEY hy so little public outcry against WW the recent disastrous slashes in medical research and educa- tion? Average Americans are quiescent, one suspects, because they have bought the notion that from now on we will be spending money on here-and-now pa tient care, as opposed to “irrelevant” medical research This widespread notion is, of course, dangerous nonsense, for like it or not, research, education, and medical care are completely bound up in one another. Any attempt to split them apart is specious, illusory, and the worst sort of false economizing. The d fact is that in slashing medical-re- search budgets by many millions of dollars the administration is creating tragic mischief, the effects of which will sooner or later touch every man, woman, and child in this countrv—as well as unborn generations of Ameri- cans. Is this an extravagant claim? Scare talk? Not really. Consider the unhappy recent memory called tuberculosis. In 1900 TB, “the white plague,” was as common a fact of life as mosquitoes, Hospital wards overflowed with TB's wasted victims, and emaciated “lung ers’ walked the streets wracked by contagion-spreading coughing spells, If TB as we knew it in 1900 were abroad today, full force, our already overburdened hospitals would have to cope with several million more pa- Miciiarl E. DEBAKEY is president of the Bavlor College of Medicine in Houston, Texas: he is also chairman of the Depart- ment of Surgery and director of the Cardi- ovascular Research and Training Center His sister, Lois DEBAKEY, is professor of scientific communications at Baylor and lecturer at Tulane University School of Medicine in New Orleans. tients. Fortunately, medical research. ers several decades ago developed isomazid and streptomycin; since the general introduction of these drugs after World War 11, the TB death rate in the United States has dropped by 95 per cent. Some foundation ought to do cost-benefit” study comparing the ex- pense of developing anti- TB drugs with the cost of maintaining, at today’s go- ing hospital several million “phthisical persons.” The ratio would be eye-opening The virtual elimination ot TB by medical research is only one instance among many of the central principle of medical advance: Research, teaching, and patient care go hand in hand. If you cut one, vou damage all three. That is why it is no exaggeration to say that the slashes in the funding of medical re scarch™over the past few _ycars Will most certainly cause a regression from which it will take American medi-= cine many years to recover—a regres sion, incidentally, that will also heavily aggravate many of the troublesome 56 cit problems now at a racing boil just” under the SaiTace of AMEE TTC “Sitice full, free, scientific Tnquiry is, then, indispensable to human welfare, it is appalhng that an enlightened peo- ple should rake retrogressive steps in this sphere of activity. Certainly, medi- cal science, the branch dedicated to the prevention of disease, the relief of suf- fering and disability, and the lengthen: ing of productive life, has obvious practical dividends to offer humanity. A people debilitated or incapacitated by infectious, nutritional, parasitic, cardiac, malignant, or other discase suffers a real handicap in developing the skills and acquiring the knowledge needed for the economic, educational, industrial, sociocultural, and scientific advancement of a nation. The attitude of society toward scien tific research and education directly rates, Saturday Review October 16, 1971 governs the expansion of medical knowledge and the direction of medi- cal research. It is difficult to imagine that an affluent society such as we have in this country, possessed of the facts about the productivity of the great re- search enterprise we have built in a relatively short period, would not give wholchearted support to the continued growth and development of that enter prise. Alexis de Tocqueville, in Democ- racy in America, gave this sage advi “You may be sure that the more a nation is democratic, enlightened, and free, the greater will be the number of interested promoters of scientific genius Possessing education and freedom, men living in democratic ages cannot fail to improve the industrial part of science; and... henceforward all the efforts of the constituted au- thorities ought to be directed tu sup port the highest branches of learning and to foster the nobler passions for science itself.” But perhaps the scien tific community has failed to communi- cate adequately the fruits of rescarch— or our present and future needs—1o the general public, partly because of its habit of modesty and partly because of the assumption that these benefits are self-evident. Yet, modesty and poor communications or no, it is still hard to believe that there are officials in high positions who actually think we can make America a healthier nation by al- tering the delivery of health services while deemphasizing research on the grounds that it is an esoteric activity of medical school faculties and unrelated to practical social needs. Without con- © most cxTravapamt tun carch, appTOPTIATIGRS Tor de “of heat careTam produce no be Qualls Yume (Re application of currenr scientific KOOWIEdge permits; without further re- search into new ways of treating, cur- ing, and preventing unconquered hu- man ailments, the system will remain SR/OCTOBER 16, 1971 at a plateau. Without education and training of future scientists, medical educators, and physicians, there will be no one to innovate and administer the health services when the current pool of health manpower dries up. Without exception, the major medi- cal discoveries since World War II, whether spectacular, like organ trans- plantation and the artificial heart, or less dramatic, like effective diabetic drugs, can be traced to the research laboratory. It was there that vaccines, antibiotics, and other “miracle” drugs were developed for the control of previ- ously fatal or disabling infectious dis- seases, including poliomyelitis, diph- theria, pneumonia, mumps, measles, and rubella. The nearly 100 per cent decline in the death rate from polio- myelitis since 1952 is due to poliomye- litis vaccine—the result of years of laboratory research. The tranquilizers and anti-depressants developed in the research laboratory have removed thousands of mentally and emotionally ill patients from mental health institu tions and returned them to gainful places in society. The anti-hypertensive drugs, such as reserpine, have drastic ally reduced the death rate from high blood pressure during the past two decades or so. Better methods for de- tection and treatment of rheumatic heart disease and stroke, particularly among persons below the age of sixty- five, have impressively lowered the fa- tality rates from these diseases. The spectacular feats of open-heart and vascular surgery, in which the heart and circulatory system are directly “By its attitude and actions, the administration is magnifying the present jeopardy to an important American enterprise that holds the key to the future health of the nation.” ~Monkmeyer 431 manipulated for repair and correction ol diseased or anomalous parts, are possible today only because dedicated saaentists spent years in the laboratory diligently the heart-lung machine, synthetic prostheses, and re lated concepts. The remarkable elec tronic medical devices, such as the cardiac pacemaker, and the wide range of monitoring equipment, which ¢n hances the reliability of diagnosis and the ethcacy of treatment, are all prod- ucts of medical rescarch and technol ogy. The news media notwithstanding, a new lifesaving operation, machine, or drug is not discovered overnight. Rather, these techniques and devices usually represent decades of zealous, unspectacular scientific inquiry. The achievements of medical scarch are too numerous—and too well known—to recount here, but they in- clude, in addition to the spectacular discoveries, a better understanding of sundry disease processes, which in turn has led to more efficient patient care. Provocative studies in genetics, molecular biology, virology, immunol- ogy, and biochemistry, and probings into the sull obscure mechanisms of the human mind and body are provid- ing vital information that will one dav be apphed to the treatment and, ulti- mately, the prevention of human de- fects and diseases. Because medical education, research, and patient care are intimately inter- hinked, robbing Peter to pay Paul will not do the job at hand. A few months ago the administration budgeted $100 million for a crash program in cancer research, over and above the budget for the National Cancer Institute for 1972 This special sum was actually less than the amount recommended by the working on tional Pancl of Consultants on the Con” QUEST BT CART for the first vear alone. Iremaking this altocation, the admints: tration failed to heed the panel's spe cific admonition: “It is of utmost im- portance that the Wmanetmg of this program mot result in cutbacks in other™ health programs.” During the past few Véars, the entire federal medical re scarch effort has been cut back disas- trously. To help regain lost ground and to allot to medical research an ade: quate percentage of the health dollar, we should indeed consider doubling the present budget of the National Insti tutes of Health, rather than reduce it Despite the sound recommendation of the cancer consultants, the adminis. tration sliced heavily into the budgets of other institutes, presumably to pay for the crash program in cancer. It did not provide new funds to fight cancer —it merely reshuffled existing medical research funds. The administration's overall budgetary reduction for medi- cal research and the Regional Medical Programs for heart discase. cancer, and 432 stroke for fiscal vear 1972 was about $75 million. If cost-of-living increases are added to this sum, the reduction would amount to about $100-million— the same amount by which the budget for cancer research is being increased At today’s prices, the administration's fiscal 1972 rescarch-support budget was $232-million less than that which sup ported the fiscal 1969 level of research activity, Fortunately, Cangress, recog nizing the serious threat of such a budget to the entire research and health enterprise, has insisted on m creasing it; for example, the budget for the Regional Medical Programs was increased to $103.million. However, that figure as still $8 million below the 1971 funding The of research activity has been substantially eroded by inflation. The cost of research increases by at least 6 per cent per year, without any expansion at all in activities; vet the proposed budget made no allowance leve for such inevitable increases. Grants requested for new research of known merit were cut by almost $10-million and those tor the general research sup port program by more than $11-million The budget for training grants and fellowships was slashed by $37-million below that of the fiscal vear 1971 Con gressional level. Programs of key in stitutes were also cut sharply below 1971 Congressional levels; as a result, laboratories in medical schools, hos- pitals. and research institutes all over the country have been faced with closure, and the brilliant voung grad- uates, who represent the hope for to MOITow's cures have been forced 10 abandon careers in research. The loss to society will reverberate many generations. Anyone with simple human feelings Knows how important it is that we find a cure for cancer. Yet, ironically, the current emphasis on cancer research at the expense of other needy health budg cts does little to advance the total re search cause. Going all-out on cancer is in many wavs counter-productive, since research is far from ideal when con ducted in isolation and is most pro lific when a broad spectrum of mutu- ally reinforcing scientific activities flourishes. Certainly it seems unwise to transfer funds to cancer research from research in stroke—one of the leading causes of death—and from the Regional Medical Programs, which are dedicated to the delivery of the latest products of research to the bedside of the patient. Yet the budget for Neuro logical Discases and Stroke was re- duced by the administration. Fortu- nately, Congress again insisted that this budget be increased. All Americans would rejoice if a cure for cancer, the second leading cause of death in America, were found or, better through vet, if a method of preventing the dis- case were discovered. Unquestionably, the recommended effort to search vig- orously the cause of this hideous disease is highly commendable. But we tor also need, now more than ever, to push forward in our studies of heart disease, which are beginning to show promising clues to underlying mechanisms. And ver the administration's budget of $1954 million for the National Heart and Lung Institute was at the same level as the appropriation for fiscal 1971. The budget therefore did not ac- commodate costolliving in crease; it would not even have allowed the maintenance of the present level of research activity. Moreover, $3-mil- hon ob it was earmarked for new research in sickle-cell anemia. Once apa, Congress wisely increased this item mn the budget to $232 million The curtailment of research in any health field is dificult to justify, but it puzzling in the field of heart disease, since this is the leading cause of death in America. Heart dis- case accounts for more than one mil- hon deaths annuallv—more than half ol all deaths—many during the most productive years of life. Every ninety tor a is especially seconds someone — a relative, co- worker, friend, or acquaintance—dics needlessly from heart disease. With adequate support for research in this field, it is entirely possible that we could extend the lives of filty million Americans who are currently doomed to die prematurely from heart disease About 1.4 milion Americans have al ready had one or more heart attacks, and cach vear more than 123,000 people below the age of sivtvednee die of heart attacks. Each vear, too, people below the ape of sixty five waste 141 million days because of cardiovascular and pul monary illness, and those sixty-five and above waste an additional 110 million dave, The resultant loss to the national CCONOMY is staggering These figures alone with a review of the during the decade in prevention and treatment of heart disease. make it difficult to under justify what amounts to an actual reduction in support of research advances made past stand or and training m cardiovascular disease Risk factors for premature heart at- tacks have been identified and docu mented, and this information is now ready to be disseminated to the popu- lation at large. Although we have not vet discovered cures for many of the Tving disorders, we are now able to correct surgically certain congenital malformations of the heart and to re heve some forms of acquired heart disease by coronary arterial surgery. We have also developed pacemakers, artificial heart valves, prosthetic vas- grafts, and assistors, which. along with such new drugs as cular cardiac the anti-hypertensive agents, and better methods of treatment for cardiogenic shock, have increased not only the length but also the quality of life for patients with heart disease. The thou- sands of patients alive and productive today—who would have been dead a number of years ago but for the products of cardiovascular research— testify to the practical dividends from this investment. Just as ill-advised as the curtailment of funds for research is any reduction in support of medical education and training, especially in light of our cur- rent serious deficit in health man- power. The education of more and bet- ter-trained doctors, nurses, and other allied health professionals will obvi- ously cost money. Yet, both fellowships and training grants for graduate level training are suffering serious cuts from 1970 to 1972. Some 440 fewer research- ers and physicians of advanced train- ing will be available at the end of 1972 than would have been available had the fellowship funding remained at the 1970 level. Nor is the decrease in fel lowship support offset by an increase in support available through training grants to specialty teachers; rather the reduction is substantial here too. All those involved in the operation of a medical school, both professional and lay persons, are acutely aware of the ever-escalating costs of training well-qualified medical practitioners, much of which can be attributed to general inflation. Almost every medical school in the country is dependent on alumni support, not only to build new facilities and equip them suitably but to establish what, in the best judgment available, is thought to be a balanced portfolio of stocks and bonds. As we all know, such portfolios have not pro- vided capital gains or reasonable divi- dends during the past several years. It will take some time, even if the ccon- omy recovers with miraculous speed. for these investments once again to help underwrite the costs of medical education. Until they do, and if our medical schools are not to go into bank- ruptcy, some emergency funds must be found. Furthermore, since the popula- tion as a whole profits from medical education and research, the allocation of federal money for such support is more than justified. Because research is an essential ac- tivity in maintaining and advancing the quality of teaching, some schools have been able to help pay the salaries of some of the teaching faculty from re- search funds, but now that these funds are in ever shorter supply, support of our teaching faculties becomes a criti- cal matter. Some members of Congress have tried to offer emergency aid to medical schools, but the $100-million that had been earmarked for this emer- 93-999 (Pt. II) 0-73 - 7 433 gency effort disappeared in the course of the Senate-House conference on the authorizing legislation, despite * con- certed efforts by various facets of the medical community to explain the plight of medical schools to Congress. By its attitude and actions, the ad- ministration is magnifying the present jeopardy to an important American en- terprise—medical research—the enter- prise that holds the key to the future health of the nation. Congress, aware that the administration's health budget was creating a crisis and, indeed, was courting disaster, has restored some of the cuts, but what is yet to be de- termined is whether the administration will apportion the money and allow its full expenditure. Even these Congres- sional increases, however, will only mitigate, not completely remove, the threat to the research enterprise caused by several years of retrench- ment. At the moment, most of the increases recommended by Congress are still be- ing withheld, and there are signs that the administration may frustrate the will and the efforts of Congress to re- suscitate the health budget. According to the September 15, 1971, issue of Drug Research Reports, “. . . the biomedical community will have to fight for every penny it gets” from the government. The report further notes that “fiscal "13 is now viewed by the White House as another good year in which to cut back research,” and suggests that the National Institutes of Health may be ordered to start these cutbacks “by nibbling away at ongoing projects.” The average citizen, who is both the potential victim of ill health and the potential beneficiary of medical re- search, can play a significant, positive role in maintaining the productivity of biomedical research and training. To do so, however, he needs to understand better some of our current health prob- lems—for example, that some of the high cost of health care today is due to the often cumbersome and complex equipment, the lengthy hospitalization, and the extensive health manpower needed in palliative treatment and in the prolonged care and rehabilitation of patients with obscurely understood diseases. To restrict additional funds to the delivery of this same kind of empirical treatment, invaluable though it is at our present level of knowledge, is penny-wise and pound-foolish when we could simultaneously be uncovering the underlying causes of these dis- orders and eventually their prevention. The annual savings accrued as a result of the virtual elimination of poliomy- elitis, for example, amounts to about one-third of a billion dollars, a sum that far exceeds the amount invested in the research that led to its elimina- tion. Added to the tangible dividends that accrue from the conversion of polio patients to useful citizens are the intangible benefits of a happier, and therefore a more creative, society. Prevention, whether by use of vac- cines, diet, or pharmacologic agents, is always more economical to the nation than disability and treatment. We are spending $70-billion annually for sick- ness, disability, and death. According to a national health survey made sev- eral years ago, more than half the people in the labor force (71.3 million) had one or more chronic conditions. As a result, during one year alone, 250 million work days were lost be- cause of acute illness of persons seven- teen years of age and older. The loss in wages and productivity is enor- mous. Yet, we continue to skimp on funds to support the search for the cause of these illnesses and methods of preventing them. From a purely economic standpoint, it is to the country’s advantage to transfer as much of our population as possible from the ranks of the disabled and handicapped, where they consti- tute a tax burden, to the ranks of the productive and employable, where they can contribute as taxpayers. A report of a study undertaken at the request of Mrs. Mary Lasker indicated that more than two-and-a-half-million wage earners whose lives had been saved in 1967 as a result of the declining death rate paid $1.69-billion in federal income and excise taxes. By contrast, the appropriation for that year for the National Institutes of Health (which at that time included the National Insti- tute of Mental Health) was only $1.4- billion. The figures for the period 1945- 1967 similarly show that the federal government gains more in taxes from persons whose lives have been saved as a result of better health knowledge than it appropriates for the National Institutes of Health. Most citizens would, if they knew the facts, consider as awry national priori- ties that expend about $400 per person for defense, $125 per person for the Vietnam War, $40 per person for high- ways, $30 per person for space explora- tion, but as little as $7 per person for all medical research. Our tax-dollar priorities seem ever more imprudent when we consider that it cost our na- tion §70-billion (7 per cent of our Gross National Product) last year to support all health activities, an amount ex- ceeded only by the cost of our defense activities. In other words, our lack of knowledge of health matters costs us about $315 per person, but we have been willing to spend only about $7 per person on medical research to help rid ourselves of this economic burden. Mental health services cost our nation $4-billion, or $20 per person, but we spend only 70 cents per person on mental health research. Hospital, nurs ing home, and physician care, along with drugs and other health services and supplies, cost more than $6 billion tor heart discase alone ($30 per per son); vet we allocate less than $1 per person tor heart research. We should regard medicine as a large dustry with an evolving research To remain viable, such a science dependent industry must expend sub- stantially more than 10 per cent of is total operational costs tor research and development, The pharmaceutical and electronic industries, in tact, spend about twice that much, whereas medi cal research spends less than 3 per cent of national health and development base Costs on research Press accounts of “hreakthroughs™ during the past few years have sug gested that a scientist, working in iso lation, suddenly Comes upon a miracu lous discovery. As dramatic and exant ng as this sugeestion may he, it oas simply antrue New scent knowl edge involves years of laborious effort 434 and the most disciplined perseverance; blind alleys, disappointments, and frus trations are numerous. The spectacu lar discoveries announced to the world at large are often a synthesis of ac cumulated bits and shreds of seem: ingly impractical information obtained from many previous vears of basic and applied research, Findings that may be considered trivial or impractical to day may provide just the fragment of knowledie that can be combined to morrow with another fragment to advance human understanding or unprove human hie. An extremely esoteric contribution may be the cru- cial hink in the synthesis of scientific data leading to a major discovery. Once the general populace grasps this, they will recognize the imprudence of demanding instant practical results from federally supported research projects and will support a policy of allowing scientists to pursue research freely and imaginatively, Society obviously has many other needs and desires besides those relat ing to health, but tulillment of the other needs and desires will be futile, if indeed itis at all possible, unless our population 1s healthy enough to enjoy our resources. We cannot atlord to let short-term goals eclipse long-range benetits Training and medical research are basically long-range projects, but unless something is done now to rectify the proposed drastic reductions in traming funds and the crippling cut backs in research money, we will have neither short-term gains nor long-term profits Louis Pasteur aptly expressed the humanitarian goal of research when he sad, “IE conquests useful to humanity touch vour heart, . take terest, beseech you, in those sacred mstitutions that we designate under the expressive name of laboratories Demand that they be multiplied and adorned; they are the temples of the future, There it is that humanity grows, becomes stronger and better” It indeed our hearts are touched by conquests usctul to humanity, we must turn trom inspiring rhetoric 10 post the action —and now. 435 A LAW To PROHIBIT NONMEDICAL BRAIN SURGERY (LoBoTOMY, PSYCHOSURGERY, PSYCHIATRIC AND BEHAVIORAL SURGERY) (By Peter Roger Breggin, M.D.) The purpose of this legislation is to prohibit all those operations currently referred to as lobotomy, psychosurgery, psychiatric surgery and behavioral surgery, and all other operations which fall within the category of nonmedical surgery as defined in this law. Non-medical surgery (lobotomy, psychosurgery, psychiatric surgery, behavioral surgery, etc.) is any surgery which falls into any one of the following three definitions : (1) Brain surgery whose aim is the modification or control of thought feelings, actions or behavior rather than the treatment of a known physical disease of the brain; or (2) Brain surgery which modifies normal brain function or normal brain tissue in order to control thoughts, feelings, action or behavior; or (3) Brain surgery which treats abnormal brain function or abnormal brain tissue to modify thoughts, feelings, actions or behavior when that brain abnor- mality is not an established cause for those thoughts, feelings, actions or behavior. ELABORATIONS AND EXPLANATIONS OF INTENTION (1) The term “brain surgery” is meant to include the application of any technology or any form of energy directly to brain tissue or directly within the circulatory system of the brain. This includes the use of scalpels, electrodes for electrical or heat coagulation of the brain, catheters for the injection of chemical agents, radiation and ultrasonic beams, and all other forms of technology and energy unless specifically excluded. Specifically excluded are electroshock and electrical stimulation of the brain. The definition is not intended to include the injection of drugs into the body, except when injected directly into the brain. (2) The terms “thoughts, feelings, actions and behavior” are to be taken in their most general sense to include all real or presumed psychiatric disorders (psychoses, neuroses, character and personality problems, violence, addictions, criminality, sexual deviations and others) and all behavioral disorders (hyper- activity, hyper-responsiveness, and others). The real or presumed biological origin of any of these disorders does not automatically exclude related surgical inter- ventions from the definition. Thus brain surgery to control thoughts, feelings, actions or behavior is not excluded on the grounds that the disorder is biological in origin unless the surgery improves the abnormal brain function or abnormal brain tissue known to be the cause of that disorder. (3) The presence of “physical disease” or “abnormal brain function” “abnormal brain tissue” is not to be determined by the opinion of individual physicians or by any one specificity of medicine or science. If this were permitted. then physi- cians or sub-specialties might invent diseases or stretch the definition of disease in order to justify brain surgery for the modification of thought, feelings, actions or behavior. Nor is the causal relationship between the “physical disease”, “abnormal brain function” or “abnormal brain tissue” and the thoughts, feelings, actions or behavior to be determined by the opinion of individual physicians or by any one specificity of medicine or science. Instead, these questions are to be determined upon the basis of prevailing opinion within the entire medical com- munity (including a spectrum of specialties, including neurology, neuro-surgery, general surgery, medicine, pediatrics, psychiatry and others) and within related non-medical sciences (including biology, anthropology, psychology and others). In determining the presence of disease or abnormality as well as its causal relationship to the disorder being treated, presumed or hypothesized diseases and causal relationships will not be sufficient. There must be demonstrated mal- functions or disease of brain tissue or a strong presumption for the presence of such a known disorder or disease. The “gray area” of surgery which may or may not fit into this category is extremely small, less than 19 of current non-medical surgery (lobotomy, psycho- surgery, psychiatric surgery, behavioral surgery). (4) Whether or not a surgical intervention is prohibited under this law should be determined through due process within the courts when and if injunctions are brought to prohibit any given surgical procedure under this law. No boards or 436 review panels should be set up. The purpose of this law is to bring non-medical surgery under the control of the public through the courts rather than under the control of boards or review panels of specialists or other vested interests. ILLUSTRATIONS A. Examples of Surgical Intervention which do not currently fall into the defi- nition of “non-medical” survery : 1. brain surgery which treats epilepsy 2. brain surgery which treats Parkinson's disease 3. brain surgery which treats tumor, stroke, or trauma of the brain B. Examples of Surgical Interventions which do currently fall into the defi- nition of “non-medical surgery.” 1. Brain surgery to treat hyperactivity, schizophrenia, neurosis depression, anxiety, obsessions, violent behavior, sexual deviations and addictions. 2. Brain surgery to control violence or other thoughts, feelings, actions or behavior in epileptic or brain damaged patients when the epilepsy ot brain damage is not itself improved by the surgery or when the epilepsy or brain damage is not the direct cause of the violence or other problems. Thus the mere presence of brain disease does not exclude the definition of non- medical surgery. In the future if any of these disorders or behaviors can be shown to be caused by disease or malfunction of the brain, and if the brain surgery can be shown to correct or improve upon these diseases or malfunctions, then these forms of sur- gery would not longer fit under the definitions of non-medical surgery. [From the Boston Sunday Globe, Sept. 24, 1972] SENATE URGED To KILL ‘BRAIN’ STUDY $1 MILLION EARMARKED FOR PSYCHOSURGERY (By Jean Dietz, Globe Staff) A nationwide campaign against revival of experimental brain surgery has forced members of the US Senate to reconsider approva’™ of a $1 million item in the giant Labor-Health, Education and Welfare approjriations bill due to be reported Tuesday. Until this week, the drive against so-called “psychosurgery” has been virtually a one-man effort conducted by Dr. Peter R. Breggin, a 33-year-old Washington psychiatrist and novelist, who has made several speeches accusing brain sur- geons of “multilating” over aggressive men, women and children. Jregein has charged that the $1 million proposal to continue the study of violent behavior related to brain disease supports the type of “brain surgery for criminals and other violent individuals” now being conducted at Boston City Hos- pital in aflilinton with Massachusetts General Hospital (MII). Massachusetts Sen. Edward Brooke Thursday said he vill “do all he can” to see that no further money goes to the project pending a complete review by the National Institute of Health. The project is being studied this weekend by mem- bers of Massachusetts Sen. Edward Kennedy's special health staff. Opponents charge that the project conducted by Dr. William Sweet, director of neurosurgery at MGI and Dr. Vernon Mark, chief of neurosurgery at Boston City Hospital, both Harvard Medical School professors, is a screening program to “pinpoint” individuals with a “low violence threshold” who may become subjects for “psychosurgery” which they call “a new form of lobotomy.” “1 thought we had them stopped. This item in the bill took me by surprise,” reggin said Friday. Breggin says that the Ralph Nader group investigating the mental health com- plex has promised to add a special chapter on psychosurgery to its report. According to Breggin, Sweet and Mark have advocated the use of amygdalot- omy, a neurosurgical operation in which small portions of the brain are destroyed by electrodes, for the cure of control of violence associated with psychomotor epilepsy. Breggin says the operation “has nothing to do with epilepsy. ” 437 He claims that the operation “blunts the emotions” in anyone, whether they suffer from epilepsy or not. He describes the procedure as a “partial deadening of the individual, a partial murder of the living person.” Dr. Sweet, who was the only witness to testify in support of the appropriation at a Senate committee hearing said the funds requested are subject to normal “peer review’ by the National Institute of Health. He also spoke on behalf of the Neurologic Unit of the University of Texas at Houston and the Neuropsychiatric Institute of the University of California at Los Angeles. No opposition witnesses were called. “We are really not trying to take over the world or influence people to do things they don’t want to do by installing electrodes in their brains,” said the noted neurosurgeon, who encountered Breggin for the first time last March in Houston at a symposium on violence sponsored by a neurological society. Sweet says that what was called “psychosurgery” in the 1940s consisted of mak- ing a destructive lesion in the brain of patients who suffered from obsessional neuroses or other psychiatric difficulties. He said these early lobotomies were “entirely different” from the current ef- fort to influence behavior symptoms related to physical disease. “There is no question but that there is organic brain damage in patients with chronic epilepsy,” said Sweet. “Many patients with temporal lobe epilepsy have behavior problems as well. Their behavior problems are often more incapacitat- ing than their other symptoms and seizures.” Sweet said “absolutely no evidence” of blunting of the emotions has been re- ported as a result of the operation on the amygdala of the brain, “unless you call blunting the removal of abnormal uncontrolable outbursts of rage.” “We have not done the procedure on any criminals in prisons because it would be unfair to guarantee they might not revert to breaking the law once they were out of jail,” the MGH surgeon said. Both Sweet and Mark noted that a number of self-confessed murderers un- known to the police came to MGH seeking help from the program, which was directed by Dr. Frank Ervin, a psychiatrist, who is now a professor at the Neur psychiatric Institute of California in Los Angeles. “My considered opinion is that the place of the physician is in the treatment of patients and that the protection of the public is the province of the police and the law,” said Mark. Ervin, for nearly 10 years, directed a special service at the MGH which treated most disturbed patients by medical or psychiatric methods. According to his former colleagues, the service was transferred to Boston City Hospital (BCH) because there was an apparent need for a special unit to insure that violent patients could be properly controlled. Also, some psychiatrists at MGH were opposed to the program. Surgery is now performed at BCH, while special X-ray procedures and animal experiments are still conducted at MGH. Marks says that of 13 epileptics who have undergone surgery after being asso- ciated with violent behavior, six have been studied for more than three years. Of the six, two are “strikingly better” and two are considerably improved, he said. Both surgeons claim there has been confusion in reports about the program due to studies of prison inmates at Walpole, Bridgewater and the women’s institu- tion in Framingham. These studies, which do not involve surgery, consist of fingerprint tests and chromosomal and blood analyses to determine if inmates possess unique characteristics. “With all this talk about human rights, I think one right is largely ignored in this controversy—the right of the patient to have treatment appropriate for his disorder,” Marks said. [From the Congressional Record—Extensions of Remarks, Mar. 30, 1972] NEW INFORMATION IN THE DEBATE OVER PSYCHOSURGERY [Copyright 1972 by Peter Breggin] PSYCHOSURGERY FOR THE CONTROL OF VIOLENCE—INCLUDING A CRITICAL EXAMINATION OF THE WORK OF VERNON MARK AND FRANK ERVIN (By Peter Roger Breggin, M.D.) (Nore.—Peter R. Breggin, M.D. is a practicing psychiatrist and faculty mem- ber of the Washington School of Psychiatry. He was trained at Harvard College, 438 Case Western Reserve Medical School, The New York Upstate Medical Center in Syracuse and the Massachusetts Mental Health Center, where Le was a Teach- ing Fellow at Harvard Medical School. Before going into private practice he was a fulltime consultant to the National Institute of Mental Health. He is the author of a variety of scientitic papers and two novels, as well as co-author of a book on the rehabilitation of state mental hospital patients.) Recent statements by lobotomists and psychosurgeons have appeared in the press and on television to the effect that lobotomy has been replaced by newer methods. Other reports say that psychosurgery is carried out under ‘arefully controlled conditions and that it is based upon careful scientific methodology. Several other psychosurgeons have tried to give the impression that the technique is limited to individuals with brain damage, epilepsy and violence. All these statements are false. In the Congressional Record of February 24th, I describe in detail the return of lobotomy and psychosurgery as a treatment for psychiatric disorders in which the patient suffers from neither brain disease nor epilepsy. In the entire study involving nearly 100 papers and 1,000 recent cases in America, none of the PSy- chosuregons were operating on individuals with brain disease and none were basing their work on the treatment of epilepsy. In facet, only one project in America is dealing with this combination of brain disease, epilepsy and violence, and 1 did not discuss it in the first review in the Record. But the zecent publicity necessitates an examination of this work by Mark and Ervin. Concerning the self-restraint and scientific orientation of lobotomists and psychosuregons, in the several hundred published articles by lobotomists and psy- chosurgeons, there are few if any that qualify as “scientific.” The matched con- trol group is the acme of the scientific method, and there are no such studies in the entire psychosurgical literature, except for three follow-up studies which showed that the surgery was no help and tended to produce severe side-effects, including lethargy. loss of interest in the world and intellectual deterioration (79, 94 and 121. See also 33, 81, 84 for descriptions of brain damage in follow-up studies.) Concerning the self-restraint of psychosurgeons, the situation has changed little since the Group for the Advancement of Psychiatry published a report condemn- ing psychosurgery as a method whose promoters exaggerated its good effects while denying its mutilating effects upon the personality. The Group for the Advance ment of Psychiatry advocated scientific research and careful controls and warned the psychosurgeons to limit their work and their claims. None of this has taken place. Mark and Ervin are the only group who have described a board whose duty it is to review pre-surgical candidates. But their board is concerned with certifying the presence of epilepsy, and can- not stop them from doing psychosurgery on their epileptics. In general, there are no controls on the activities of surgeons, and in several centers, disheartened psychiatrists have been unable to stop the activities of psychosurgeons against whom they have strong feelings, In one medical center I have contacted, the De- partment Chairman in Psychiatry did not know that the Department Chairman in Neurosurgeory was active in psychosurgery. So much for self-supervision and restraint. Because Mark and Ervin have received considerable publicity for their work on epileptics with violence, it is important to emphasize that this is the only psy- chosurgical group in the country specifically tying their work to a theory of epilepsy and violence. All the others are operating on patients without known brain disease and without any epileptic cause for their violence. In fact, as I describe in the Record, the majority of patients operated on in America are women with neurotic problems. (19). But the publicity given to Mark and Ervin in response to my disclosures in the Record necessitates a thorough examination of their work in this study. Limited as it is, it also offers unique political dangers which also require analysis. As I will try to show, they are simply performing a psychosurgical operation on vio- lent people who also happen to have epilepsy. Since the publication of the Record study, a new interest in psychosurgery for the control of violence has become apparent. Vernon Mark and Frank Ervin have drawn particular attention to brain surgery as a means of political control in their recent hook, Violence and the Brain, and in still more recent statements to the media. The President of the new International Association for Psychosurgery, William Scoville of Yale and Hartford, has also advocated the use of psychosur- gery for psychopaths in Arthur Winter's new book, The Surgical Control of Be- havior. 439 M. Hunter Brown has also advocated and described psychosurgery for psycho- paths in recent publications and at the March 9-11 Houston Conferences (89). O. J. Andy in Mississippi has operated on adolescents with criminal records and on little children as young as age five who demonstrate aggression and hostility. Aarons in the Washington Post has disclosed the use of brain surgery on violent inmates in the California prison system, as well as proposed plans to expand this program. In addition, Judy Randal of the Washington Star has reported that Frank Lorimer of the Illinois Prison system is advocating a similar program (131). Closely related to this “law and order” orientation, Fields has recently un- earthed the use of psychosurgery %n heroin addicts in Philadelphia. Experimental work on psychosurgery for addiction has also been carried out in Galveston with much publicity but with no scientific reports (92). The political dangers of psychosurgery for violence will be discussed in the conclusion of this study, but here it is necessary to point out that the psychosur- geons themselves have been advocating their approach for wide scale social con- trol. Mark and Ervin and Sweet in 1967 remarked that the Detroit riots could not have been caused by political conditions alone. Based on no evidence what- soever, they conclude that violent protesters may have had brain disease, and they advocate large scale screening and treatment. In their book in 1970 they elaborate upon their use of electrical methods of screening and control and even take it on themselves to describe what is “unacceptable violence” in both the per- sonal and political arena. They imply that 5-109 of Americans have brain dis- ease that may require treatment. Their work has obvious “law and order” appeal, and it is no surprise that they are supported in part by more than $100,000 from the Justice Department, Law Enforcement Assistance Administration (134). Sweet, Mark and Ervin are not alone in their interest in political applications of psychosurgery. In a recent popular paperback. Delgado of Yale has advocated “physical control of the mind,” including psychosurgery, for the control of dom- estic and international violence in the political sphere. He wants the United States to begin a billion dollar program for physical control of the mind, com- plete with mass education, public school projects and research into physcho- surgery. As we shall see in this review, psychosurgery has a long and awesome history as a means of social control, and it is being resurrected for this purpose within our institutions and within the society at large. It is no exaggeration to say that we are in danger of a massive use of psycho- surgery to intimidate and control our population. DEFINITION OF PSYCHOSURGERY Psychosurgery is any surgery which mutilates or destroys brain tissue to con- trol the emotions or behavior without treating a known brain disease. In 999, of the cases, the brain surgery will actually attack normal tissues. In a few cases, some brain disease will be present, but in these instances, the brain disease will have nothing in particular to do with the symptoms which the surgery is attack- ing. Thus, psychosurgery is a pacifying operation which blunts the emotions and subdues behavior regardless of the presence or absence of any brain disease or any particular psychiatric problem. It is simply a mutilating operation whose effect is to destroy the individual's ability to respond emotionally. Lobotomy, or destruction of a portion of the frontal lobes, is the original psycho- surgical operation. It is still in use, as recent books by Kalinowsky and Winter demonstrate. Lobotomy directly impairs the highest human centers for creativity, empathy, understanding, abstract reasoning and future planning. The original lobotomy operations left the patients in a state approaching vegetation. Newer operations attack the brain lower down in the “limbic system.” The lower down the operation, as Scoville says, the less intellectual damage and the more emotional blunting. The basic pacification is the same, and when the opera- tion is repeated several times, as in studies by Mark and by Andy, intellectual damage is also obvious. Since the parts of the brain attacked are all interrelated a generalized damage to the personality must always follow the surgery. 1. The first major studies in lobotomy The history of lobotomy is rooted in the problems within massive state custo- dial institutions. The very first recorded lobotomy/was done by Burckhardt in Switzerland for the specific purpose of taming some difficult patients under his 440 care. That was in the 1890's and the outery against these brain multilations was so great that it was not attempted again on a significant scale until Egas Moniz, John Fulton and Walter Freeman met at a conterence in 1936 and observed the effects of lobotomy on two monkeys and a man. All three subjects had become somewhat demented, passive and untroubled by any degree of frustration. With- in one year, Moniz had begun operating on mental hospital inmates in Portugal. His career was cut short, however, when the state hospital psychiatric director refused to let him operate any more and when a patient maimed him with five pistol shots. Moniz did live long enough to get the Nobel Prize for his efforts, but it was left to Walter Freeman to promote his work and to operate upon 4,000 Americans over two decades. Freeman, too, had his problems. While humanist William Allanson White was superintendent at St. Elizabeth's, Freeman was barred from operating at the largest institution in his home city, Washington, D.C. (41). Freeman also spoke openly about censure he met from his neurosurgical colleagues who believed that a psychiatrist should not be permitted to do major brain surgery (1950, 1971.) And he, too, met resistance from some of his patients, two of whom pulled guns during pre-lobotomy interviews (38). Freeman describes in Psychosurgery (1950) how his very first patient fought for her life prior to surgery. “Who is that man? What does he want here? What's he going to do to me? Tell him to go away. Oh, I don't want to see him.” Then she cried out, writhing about in bed so that the nurse was scarcely able to control her sufficiently to administer avertin by rectuin. After surgery the patient becomes docile, and the first question Freeman puts to her says a great deal about lobotomy : Q. Are you content to stay here? A. Yes. Q. Do you have any of your old fears? A. No. Q. What were you afraid of? A. I don’t know. I seem to forget p. xix. Freeman describes another patient who is operated upon under local anesthesia so that he can report on what is happening to him. The patient screams, “0 Gee whiz, I'm dying. O doctor. Please stop. O, God.” Freeman orders the patient to sing God Bless America, and then describes how the patient becomes more disoriented and passive with each “stab” into his brain. Freeman also describes “a negress of gigantic proportions who for years was confined to a strong room at St. Elizabeth's Hospital.” It takes five attendants to drag her to the operating room, but she immediately becomes passive after the surgery. The attendants are still afraid of her “300 Ibs of ferocious humanity,” so Freeman puts on demonstrations of her docility : “Yet from the day after operation (and we demonstrated this repeatedly to the timorous ward personnel) we could playfully grab Oretha by the throat, twist her arm, tickle her in the ribs and slap her behind without eliciting anything more than a wide grin or a hoarse chuckle, pp. 406-7 Freeman makes clear that the brain damage is responsible for this doecility. He advocates giving two or three electroshocks to knock difficult patients into unconsciousness, disrupting their brain patterns before the final surgical disrup- tion. He uses this electroshock technique on both the adults and the young chil- dren upon whom he performed single and multiple lobotomies. One six year old child is a difficult behavior problem for her mother, and so she is subjected to electroshock and two “radical” (large mutilations) lobotomies. After the first one, “she returned to her habit of smashing toys.” After the sec- ond extensive raking of her frontal lobes, she still has a great many problems. When seen at home, “she was quite withdrawn but less troublesome.” When she is seen several years later, “In spite of her increased speed and strength, she an be more easily managed at home, is beginning to put sentences together and the impulsive destructive behavior is subsiding.” p. 444. Writing in 1965, Freeman observes that there's no sense operating on a patient once the ward notes read “Gives no trouble on the ward.” And in one of his few direct observations on the problem of law and order, he notes in the American Handbook of Psychiatry, “lobotomized patients seldom come into confliet with the law precisely because they lack the imagination to think up new deviltries and the energy to perpetrate them.” 441 In 1971, Freeman is again advocting psychosurgery with pride in its useful- ness within large custodial institutions: “It proved to be the ideal operation for use in crowded state mental hospitals with a shortage of everything except patients.” The political pacification implications of Freeman's work has largely been ig- nored by Freeman and by critics, but they stand out in his summary of ideal surgical candidates in his textbook, Psychosurgery. He is obviously describing a leveling operation that controls oppressed and discarded elements of the society when he lists the following four top criteria for psychosurgical candidates: age: older; sex: female; race: black; and occupational role; the “simpler” ones. The Negro female—remember Oretha?—is described as his best patient, p. 515. Again publishing and lecturing, and new Honorary President. The Interna- tional Association for Psychosurgery, Walter Freeman is a significant figure in the revival of lobotomy and psychosurgery. Freeman's anecdotal style is complemented fully by the more scientific style of the second great classic of the lobotomy literature. Studies in Lobotomy, by Greenblatt, Arnot and Solomon, from the mecca of psychiatry at the old Boston Psychopathic Hospital, now the Massachusetts Mental Health Center, the main Harvard teaching facility. In a study of more than 200 of 500 lobotomized pa- tients, Solomon starts off by lauding the work as “adding to the total joy of liv- ing” of their patients. But the psychologist’s report, tucked away in a chapter no larger than the one on urinary problems, describes the patients as “slap-happy” from brain damage, many of them suffering from a downhill course of deteriora- tion brain damage. They cannot focus on their tasks and suffer from a cardinal sign of brain damage, “concrete thinking,” or the inability to think abstractly. But in the conclusion to the study, Greenblatt gainsays the psychologist’s report. He says outright that there’s nothing necessarily wrong with “concreteness,” and points out that “fewer variables concern the patient, less attention is given to the future, and the patient attends better to mundane realities.” p. 469. Brain damaged patients make good inmates! Furthermore, after lobotomy they can at last be made to work in the demean- ing jobs available within the hospital, so that “the hospital plan can be run more economically.” Also, “It is gratifying to know that they are apparently more com- fortable and less troublesome within the hospital.” pp. 136-137. Some patients even get out of the hospital, but almost invariably they are women who can function as brain damaged housekeepers, “because of the devo- tion of the spouse, or because they have shown some improvement mentally and were partially able to perform household duties.” p. 162. But the husbands don’t agree with this improvement, and they find that these brain damaged people “cripple the group activities and spoil the freedom and happiness of the entire family.” p. 173. Besides, it is openly admitted that more wives than husbands re- turn home because it doesn’t take much “for a wife to keep house.” p. 161. Wives apparently make good inmates, even at home. Five men in the entire study are able to return home, but a scanning of the book turns up some disastrous results even in these best cases. “Even though her husband was supporting her and her children.” the authors lament, one woman still declared, “I wouldn't sign permission for lobotomy on a dog.” p. 162. The authors seem to complain, “even if the dog was supporting you?” Another of these five men is lethargic around the house and terrorizes the wife with his surgically induced convulsions, while another is so bad to his children, his wife declares “It would be better off for all of us if he were dead.” p. 152-153. In only three instances did patients become less dependent on their families after lobotomy, p. 169. As a pacifying operation, lobotomy at best produced docile inmates in and out of the hospital. II. Current lobotomy and psychosurgery studies Pacification is equally apparent in the newer forms of lobotomy and psycho- surgery. In his recent text, Kalinowsky describes modern lobotomy patients as sometimes blunted and subdued, often with shallow feelings and impaired sense of self. In his articles and his recent contribution to Winter's book, Scoville speaks of lobotomy as a “blunting operation,” and he includes all the newer forms of psychosurgery as “partial” lobotomies which dull the personality. Arthur Winter, writing with Leo Shatin, says that psychosurgical patients become “more placid—sometimes passive.” 442 Operations aimed below the frontal lobes at the remainder of the limbic system produce the same effects, perhaps with less intellectual damage. Turner talks about the cingulotomy as the operation of choice for “intractable and uncontroll- able aggression,” independent of any brain disease. He recommends combining cingulotomy with frontal lobotomy and temporal lobotomy in people with rage, fear and depression—a kind of cranial clean out. Roeder describes the “cure” of a sexual deviant whose potency is weakened and who can no longer indulge in erotic fantasies after hypothalamotomy. Sano shows how the same operation will tame aggressive and hyperactive children as young as age four. His best case, recorded in the literature and read as his one illustration at a recent conference he and I both attended : “Emotional and personality changes: the patient became markedly calm, pas- sive and tractable, showing decreased spontaneity.” Sano calls it “sedative surgery.” Vernon Mark, Frank Ervin and their colleagues (1970) have also operated on the thalamus, in this instance upon a woman with “chronic intractable agi- tated depression.” This is frank, undisguised psychosurgery, for sure is no pre- operative indication that the woman has any brain disease whatsoever. This is the most detailed clinical case in the entire current psychosurgical literature, and it ix particularly interesting because the physicians consider it a “gratifying example of the efficacy of psychosurgery—even though the patient became en- raged at her doctors, refused further surgery, and finally killed herself the mo- ment she began to recover from the surgery 40 days after the operation. The au- thors state that the suicide was further evidence that she was getting better—well enough to act upon her underlying depression although the dynamies of her suicide seem grossly apparent and merit some description. The authors admit that the patient and her mother and “frankly antagonistic to each other,” and they describe her mother as “rigid, insensitive, and dominating.” But they do not comment on their observation that the mother, along with the patient, “insisted that something be done.” Nor do they comment on the fact that the patient brought the poison into the hospital with her prior to surgery, a poison her deceased father had told her about “in case she ever needed it.” She is operated on with heat coagulation of her anterior thalamus in an area in which when stimulated caused the patient to look “drawn” and to cry out “Don’t do that; don’t do that!” After this coagulation, she shows £ross brain damage : an acute brain syndrome marked by “confusion,” “severe” recent memory loss and moods swings “from near euphoria to severe depression.” Soon she responded to a confrontation with her neurosurgeon “with bristling hostility, and her anger spread to others including the psychiatrist. Her mood swings remain unpredictable and she is operated on a second time by means of her indwelling electrode. After surgery, she continues to be hostile and the authors tell us she is “definitely paranoid.” She refuses further surgery and even refuses to see her neurosurgeon ever again. She expressed “wishes that someone might ‘cut her throat.” ” She continues to suffer from obvious symptoms of severe post-operative brain damage. Her recent memory is “quite impaired,” as well as her remote memory ; she has periods of “confusion,” cannot find her away around, cannot recall names and suffers wide mood swings. When she is in a high period, clearly associated with a brain damage induced euphoria, the authors blithely quote the mother— this hostile, dominating mother—as saying “she is her old self again !”’ In December, forty days after surgery, she is finally recovering from the trauma sufficiently to become “concerned with reality problems.” Her “‘spirits are good” and she seems to be improving, and she is given a pass to go shopping on the forty-fourth day after surgery. She goes to a phone booth, calls her mother to say “goodbye,” and kills herself with the poison she had stashed away four months earlier. To me the clinical course speaks for itself: rage at her neurosuregon and her psychiatrist, rage at her mother who brought her in for surgery, persistent signs of brain damage, and suicide the first few days that her confusional state begins to clear Orlando J. Andy at the University of Mississippi has been pacifying so-called hyperactive children with a variety of operations, including thalamotomies. He writes fo me that he's operated on thirty to forty patients, the majority chil- dren. many of the others adolescents, some with criminal records. Tn operating on children, his avowed purpose is to control their aggressivity and to make them more manageable. In one case, he operates upon a nine year old boy of 443 normal intelligence, and after six operations and signs of gross brain damage, he becomes “adjusted.” “Intellectually, however, the patient is deteriorating,” Andy lets us know in 1970. Amygdalotomy is the pacification operation par excellance and we need to look at it more closely. The amygdala is an almond sized nerve center on the inner side of the temporal lobe. Envisioning the brain as a boxing glove with two thumbs, the fingers are the frontal lobe, and the thumbs are the temporal lobes, with the amygdala in the crease between the thumb and fingers, somewhat beneath the surface of the thumb. Anatomically it has connections to the basic structures of the limbic system, including the frontal lobes via the thalamus, and the hypothalamus as well. It is an important moderator and switchboard for the entire limbic system and hence for all emotions and drives, and even for all higher level activities through its connections to the frontal lobes. Destroying it to cure one “symptom” such as violence makes no more sense than bombing a railway center to stop one passenger on one train. The symptom may be knocked out, but many other tracks and greater numbers of humanity will be brought to a halt. Now let us examine the specific form of psychosurgery called amygdalotomy, the method which has received so much publicity in the hands of Mark and Ervin who claim they are treating violence associated with psychomotor epilepsy. This is the same surgery which has already been used on prisoners in California. There are dozens of animal studies which indicate that amygdalotomy pacifies the animal in the absence of any brain disease or mental illness. Now Kling has shown (89) while the chimp makes a good inmate after amygdalotomy (but a poor learner), once the chimp is let out into the monkey tribe, he cannot survive. He is isolated and sometimes withdraws and dies. Mark and Ervin them- selves describe in their book how amygdalotomy will pacify an aggressive or a frightened animal, making it tractable and easy to handle. They also acknowledge in passing that amygdalotomy has been used to pacify human beings in the same manner. Furthermore, of the four cases described in detail in their book, the first three are suffering from violence which clearly has no relation to their epilepsy. They are cured of their violence without curing their epilepsy, further evidence of the psychosurgical pacification which they are inducing in their patients. There is also a great deal of literature demonstrating that amygdalotomy pacifies human beings of every age regardless of the presence or absence of any brain disease or any particular mental illness. Balasubramaniam is probably the most experienced surgeon in the world when it comes to amygdalotomies. His basic theoretical paper is entitled “Sedative Neurosurgery,” and he states “Sedative neurosurgery is the term applied to that aspect of neurosurgery where a patient is made quiet and manageable by an operation.” He most frequently operates on ‘hyperactive children” whom he describes as “restless.” Writing in July 1970 in International Surgery, Balasubramaniam summarizes his results on 115 patients, 3 of them under age five and another 36 under age eleven. He produces this result with his amygdalotomies and occasional hypo- thalamotomies : “The improvement that occurs has been remarkable. In one case a patient had been assaulting his colleagues and the ward doctors ; after the operation he become a helpful addition to the ward staff and looked after other patients. In one case the patient became quiet, bashful, and was a model of good behavior.” He sums up his own work : “This operation has proved to be useful in the man- agement of patients who previously could not be managed by any other means.” In Japan, Narabayashi and Uno report on a follow-up of 27 children ages five to thirteen who have had amygdalotomies. Again the non-specific pacifying effect is apparent. They operate on children characterized by unsteadiness, hyperactive behavior disorders and poor concentration rather than violent behavior; it was difficult to keep them interested in one object or a certain situation. In five of their many cases, this is the best result they achieved: (they) have reached the degree of satisfactory obedience and constant steady mood, which enabled the children to stay in their social environment, such as kinder- garten or school for the feebleminded. Chitanondh has also performed amygdalotomies on a wide variety of patients, but his scientific justification is somewhat more specific. He operates on individ- uals who have a problem involving their sense of smell on the grounds that the amygdala is particularly involved in the olefactory system. In one case, his 444 pacification is particularly apparent as he operates on a nine year old boy who is involved in a struggle with his parents. They lock him up in his room but he runs away to “smell engine oil” in parked cars. In a number of the studies we have reviewed, multiple and combined opera- tions have been used to achieve at least the proper degree of pacification. The amygdalotomy is growing in popularity now, particularly abroad, and so this operation is sometimes superimposed upon other psychosurgical operations when pacification has not been achieved. At times the amygdalotomy may simply be the last straw, but at other times it may indeed suggest a more potent effect to- ward pacification. But since psychosurgeons never perform controlled studies (never! not in the entire literature is there a matched control group study !) it is difficult to differentiate the pacification effect achieved by multiple operations versus amygdalotomy by itself. Two studies indicate this problem, as well as illustrate the generalized prin- ciple that we are dealing with pacification rather than treatment of any one syndrome. First, Vaernet reports on 12 schizophrenic patients in whom aggressive and destructive behavior was a prominent feature. Five of the patients had been unsuccessfully pacified with prior lobotomies and two with prior cingulotomies, but now eleven of twelve are finally pacified with amygdalotomies. In addition, two patients were given lobotomies in the modified method of Knight with radium seeds. The second study has not been published, and I have only been able to read the 200-word summary in the programme of the Second International Conference on Psychosurgery. It is called “Neurosurgical Treatment of Aggressivity: Stereo- taxic Amygdalotomy versus Leucotomy,” and it is presented by J. Siegfried and A. Ben-Shmuel of Zurich. They performed lobotomies and amygdalotomies on different patients in a non-controlled fashion, so their results are of little signifi- cance. What is interesting is that they don't even bother to mention the psy- chiatric diagnoses of these patients. They were all being treated for “aggres- sivity,” and that was enough to put into the summary. No better illustration could be given of the generalized pacification sought by psychosurgeons. III. Violence and the Brain: an analysis of the work of Mark and Ervin Mark and Ervin never clearly state their hypotheses and so neither they nor their critics can clearly analyze their research work. But as the title indicates, they do hypothesize a direct connection between brain disease and a wide variety of violence that occurs in both the personal and political arena, from alcoholic outbursts, bad driving, child murder and rape to ghetto uprisings and warfare between nations. They further hypothesize that the violence in their patients is causally related to their psychomotor epilepsy. They then claim that their sue- cessfully pacifying surgery somehow proves the link between the epileptic brain disease and the surgery—even though the brain disease is untouched by the surgery. The most gross flaws in this study can be described in seven major categories. First, in a book devoted to amygdalotomy, they never review the existing litera- ture on amygdalotomy, thus ignoring the body of material indicating that amyg- dalotomy is a pacifying operation. In one place they do mention its taming ef- fects in animals, without drawing the logical conclusion from this. In their very brief summary of the literature, they describe only studies done on epilepties, lending the misleading impression that amygdalotomy for violence is somehow related to epilepsy. Second, they never discuss psychosurgery in general, and do not mention that all forms of psychosurgery produce a reduction in violence, even the old fashioned lobotomy. Thus they lend the impression that their surgery is unique in kind when in fact it is at best unique only in the degree of pacification which it pro- duces with relatively small lesions. Third, in their clinical presentations they ignore the fact that their surgery pacifies the patient no matter what the cause of violence in the patient. In one instance the violence is a direct product of surgically induced brain damage, in another the produet of diffuse brain disease, in another a possible response to the emotional frustrations of enduring psychomotor epilepsy: and in most cases, throughout the book, the picture is of a multiple causation, social, economic, per- sonal and perhaps biological. 445 Fourth, in most cases the epilepsy itself is uncured by surgery, again sug- gesting a lack of association between the pacified aggression and the epileptic brain disease. Fifth, in the first four cases there is no indication that the violence described is associated clinically with seizure phenomena, such as a distinet aura, auto- matic movements, or forced actions. Nor do the authors mention in this regard that most neurologists and neurosurgeons believe that violence in association with psychomotor epilepsy is rather rare. Sixth, their study fails to fulfill most of the qualifications ordinarily required of scientific methodology. There are no control groups and there are no attempts to prove that a group of clinicians would reach a consensus about the asso- ciation of the violence with the epilepsy. There are no discussions of the diffi- culty of judging the importance of an electrical discharge from an area which has recently been traumatized with an electrode. There are no considerations given to the notoriously difficult task of reaching consensus on the reading of EEG’s. When they finally discuss the basic hypothesis of their research, that there is a frequent and strong association between psychomotor epilepsy and violence, they offer no scientific evidence. They fly in the face of strong dissent from their view in traditional textbooks and in the opinions of most neurologists and psy- chiatrists, and yet show no diffidence to the notorious unrealiability of clinical impressions. But their entire work and enormous research funding depends upon this unproven, generally unaccepted assumption. The first case they cite as an illustration strongly indicates, in fact, that the violence has a specific root other than the epilepsy. “Mary” has psychomotor epi- lepsy for ten or more years without any associated violence. Her seizures, how- ever, become worse and worse, and finally she becomes a menance to herself and to other people, because she starts fires when she is smoking during a seizure. Then her “violence” appears for the first time: “Worst of all she insisted on smoking continually, even after she had started a number of small fires during her periods of unconsciousness—fires in which she herself was repeatedly burned. When anyone in her family said anything to her about her constant smoking, she would hit at them with her fists. She also used a broom handle to beat her husband on a dozen different occasions, and once attempted to stab him with a bread knife. “Eventually Mary's violence and her refusal to be reasonable about the dangers inherent in her smoking, as well as her uncontrolled attacks of epilepsy, prompted her physicians to seek a surgical opinion.” P. 64. The tests are then described, including findings of a seizure pattern, especially in her left amygdala, and so her left amygdala is destroyed. Now the authors write : “The initial results of this temporal lobe surgery have been gratifying. She still has seizures but her rages have disappeared. She has set no more fires, and she has become able to function once more as a housewife and mother. “Temporal lobe epilepsy, then, is an important example of a known disease state that is related to violent behavior.” P. 64. No, nothing could be further from the truth. This, their one illustrative case in the chapter, proves if anything that temporal lobe epilepsy is no related to violence, at least in this case. First, the patient develops her ‘‘violence” long after her history seizures. Second, the violence is not associated in any way with her seizures either temporally or clinically, but it is associated very directly with a struggle over her smoking habits and her endangering herself and others. Third, she is brought to surgery in large part to control her violence, not her seizures. Fourth, when “cured” of her violence—pacified—her epilepsy remains unchanged. An- other person has been pacified by psychosurgery—nothing more and nothing less. The fact that she is returned to being a satisfactory housewife and mother is again typical of psychosurgery studies. Not only have the vast majority of patients been women, both in the past and in the current literature, but the two most in-depth prolobotomy studies have already told us that psychosurgery is much more effective on women than on men because women can more easily be returned home to function as partially crippled, brain damaged housewives, while there are no soical or occupational roles for partially crippled, brain damaged men. 446 The second case is also a women and her violence is again unrelated to psy- chomotor epilepsy but instead develops post-operatively as a result of brain damage from a temporal lobe lobectomy. She is operated upon because she attacks hospital attendants. Ier rage is also cured by amygdalotomy, but not her seizures. The third case is a young man who is frankly psychotic and who suffers from typical paranoid suspicions and delusions. When his wife would deny his allegations, he would physically assault her, after which he would feel remorse, sob uncontrollably and eventually fall asleep. le also appeared to have suffered brain damage from a severe blood loss earlier in life, and on occasion he was noted to have psychomotor epileptic seizures, though these are only briefly mentioned and apparently observed by only one or two people. As the authors say, “Thomas's chief problem was his violent rage.” During a period of ten weeks of probing and stimulating his brain, they dis- cover one area in which the patient feels pain and states “I am losing control.” both of which are said to precede his seizures. Thomas is taken for surgery, but becomes violently opposed to it. Eventually he is talked into it. Since the op- eration bilateral, amygdalotomy — Thomas has not had a single episode of rage. He continues, however, to have an occasional epileptic seizure with periods of confusion and disordered thinking.” I. 97. The fourth case, Julia, is more complicated. She has a long history of brain disease with seizures beginning with encephalitis at age two. Sometime around or after the age of ten, she begins to have “temper tantrums,” but these are not associated with her seizures, At the age of 18, she begins to have periods of terror after which she assaults the person near to her. That she was already carrying a knife at the time of her first assault indicates a more planned process than a seizure, but there is no doubt she suffers from repeated outbreaks of panic and hostility. Nor is there any clinical evidence that her violence is a prod- uct of her seizures rather than a product of her life situation as a brain dam- aged person. Still the authors conclude : “Julia's case clearly illustrates the point that violent behavior caused by brain dysfunction cannot be moditied except by treating the dysfunction itself.” I. 98. Of some interest, in this one case, the authors were able to observe a seizure associated with amygdola activity and followed by an outburst of violence. After bilateral amygdalotomy, her violent episodes are reduced, but her seiz- ures and her psychotic behavior continue. In their four cases, the authors have demonstrated nothing more than the well established fact that amygdolotomy, like all psychosurgery, has a pacifying effect. In addition, they have conducted many experiments on a severely brain damaged youngster who frequently becomes violent and who sometimes shows spiking and a seizure after which she becomes typically violent. The subsequent violence does not even mimic her clinical pattern in which her outbreaks follow panic states, not seizure states. So what caused her violence? Panic in the experimental situa- tion? A disturbing sensation in her head produced by the experimental elec- trodes? A mimicry of something expected of her in the way of violence? Even that alternative is not out of the question, for Charcot had the entire medical pro- fession convinced that not only violence but all psychiatric disorders sprang from epilepsy. And Charcot was unconsciously able to train all his patients to throw fits for him! (103). But the authors consider no alternative but the one they have been searching for to justify their surgery— that violence is a product of psychomotor epilepsy and can be treated incidentally, by an operation which doesn’t event treat the epilepsy. The importance of their much heralded finding in this girl cannot be guessed. But it can easily be over-estimated in importance. These are the authors’ best cases. After the first four, they go on to discuss asses of “hidden brain disease” and hidden relationships between seizures and violence ! Based upon absolutely no evidence—since they have developed none—the authors assume that the violence they have observed was related to the brain dis- case of their patients, in particular the epileptic feature. They then describe common features of their brain diseased patients and a prison population, and come up with the absolutely meaningless observation that these violence people have four common characteristics—1, a history of physical assault, especially wife beating; 2. violence responses to a little drinking; 3. impulsive sexual as- saults; and 4. a history of traffic violations and accidents. 447 They then go on to repeat the obvious observation that a great deal of crime is produced by criminal repeaters, as if this somehow indicates a syndrome of bio- logic origin. Then they describe a case, Tony, who has had a number of these violent and irresponsible traits, plus a history of hallucinations. We are told he once suffered a head injury while driving, but we don’t know if this was before or after the start of his chronic violence. Nor would it make much difference in proving a con- nection between brain disease and violence, let alone limbic system disease and violence. Besides, his neurological studies are normal. “He is started on Dilantin and then we are told it produced a marked im- provement in his behavior. We were not able to see if the improvement kept up because he refused to return for a follow-up examination and there was no way for us to compel him to continue with treatment.” P. 128. So why do they mention this case at all? And why make it the first illustration of the correlation between a supposed ‘“‘dyscontrol syndrome,” brain disease and the necessity of somatic therapy? This book is nothing more than a collection of largely irrelevant anecdotes interspersed with a great many exhortations concerning the extent of violence all around us. It proves nothing, but does tend to illustrate the well-established fact that amygdalotomy, like all psychosurgery, has a pacifying effect upon emo- tions and behavior without otherwise changing psychiatric and seizure disorders. The inexplicable fact is that Mark and Ervin must have known this before they began their research. Decades of experimentation prove that removal of the amygdala in animals usually produces a de-fused creature who cannot get ex- cited about anything. Fierce animals become tame and fearful animals cease to act afraid. Placid animals lose interest in everything. An animal without its amygdala loses instinctual drive, sociability, and the motivation to learn. He is leveled off, deadened or blunted. He is, in short, less alive, but a good inmate. So it is with humans as well. Mark and Ervin clearly recognize all this early in their book when they note that killer rats no longer attack and that fearful mallards no longer take flight, but that both become manageable after amydalotomy, even after ‘normal pro- vocation.” Then they go on to say about humans : “Indeed, neurosurgeons have surgically removed areas of amygdala to treat assaultive behavior in patients for whom this symptom was a feature of some other brain disease.” P. 28, They do not footnote these references, ignoring them as they do when they later review the literature on humans, for this psychosurgical evidence under- mines their basic hypothesis about treating psychomotor epilepsy and instead lumps them along with lobotomists and psychosurgeons who practice the are of deadening their fellow men until they can no longer respond to “normal provocation.” Mark and Ervin also fail to point out that neurosurgeons have been using amygdalotomy to pacify patients whose assaultive behavior has no relationship at all to any brain disease (8, 9, 85, 86. 105, 120). Amygdalotomy will even undo the hostility of a patient whose anger is directed at a psychosurgeon who seeks to mutilate him. Thus psychosurgical patients rarely complain afterward— no more than a mutilated rat will fight, no more than a multilated mallard will take flight. The most striking exception I can recall belongs again to Mark and Ervin— their patient who killed herself after refusing to have anything more to do with her neurosurgeon. Mark, Ervin and their colleagues had planned a third opera- tion for her. Had she accepted it, she too would have stopped complaining. DISCUSSION A number of years ago I described how adrenaline may function as a sedative in the normal human being by crossing the blood brain barrier to calm the brain through its effects upon the trophotropic centers of the hypothalamus. I developed evidence (15, 16) this adrenaline feedback mechanism led to the fatigue and exhaustion experienced during chronic anxiety and severe stress. It crossed my mind at the time that we might someday develop means of reducing these inhibitory effects, thus ameliorating the debilitating effects of chronic stress and anxiety. Little did I imagine that quite the reverse would happen and that psychosurgeons would actually disrupt the balance of the hypothalamus and the limbic system to produce these same debilitating effects in order to control the hyperactive or aggressive individual. Sano has developed this to a 448 true science in which he stimulates the hypothalamus to discover its arousal centers. Then he coagulates them, leaving the child at the mercy of an imbalance which makes him inhibited and docile. To some degree all psychosurgery disrupts the limbic system to create this sort of imbalance. But the situation is far more complex, for the entire limbic stem is integrated within itself and with the frontal lobes. Disruption within this system must do more than create an energy imbalance. It must eventually disrupt the inter-relationships between all man’s higher functions in the frontal lobes and the energy centers that lie beneath. Eventually the effects will be felt in both the higher symbolic systems and the lower energy systems. When the surgery is aimed more directly at the frontal lobes, the higher symbolic functions will be more grossly disturbed. When the lower brain centers are the target, the blunting or deenervating effect will dominate. I believe the pacification effect of phychosurgery is now so well documented and so well understood that it is unrealistic to say that we do not know what is going on. We may not understand the exact mechanics or the details of the symbolic disruptions, but we do know that all psychosurgery destroys the capacity of the brain as an emotionally responsive organ, ultimately pacifying the individual without regard for any brain disease or psychiatric disorder. The ethical and political implications of this pacifying operation can only be touched upon here (17, 21, 22). As I have deseribed in my first novel, The Crazy from the Sane, and in “Coercion of Voluntary Patients in an Open Hospital,” (18, 14) mental patients are so vulnerable and so easy to victimize that even the most voluntary patient in the most open hospital has little control over what happens to him. Psychosurgery will be a particular menace to these individuals. But the situation of the captive child in a state institution or the incarcerated adult in a state prison is even more disastrous. Both are entirely under the control of authorities whose major intention is to manage them in the most economical and most efficient manner. Most of the first 50,000 victims of psychosurgery were incarcerated adult mental patients, The next 50,000 may be incarcerated children and state penitentiary prisoners. But there is a still greater political menace in the psychosurgery movement— the danger that all of our citizens will become potential victims as the nation is turned into one large therapeutic state dominated by technological totalitari- anism. This is not so far-fetched as it may seem. Thomas Szasz has already described the dangers of the therapeutic state in some depth, and I described its potential reality in my new novel. After the Good War including the political use of psychosurgery, before I had any inkling of the actual return of psycho- surgery. But even more impressive. Sweet, Mark and Ervin have been talking in some depth about the possibilities for screening large segments of our popula- tion for possible physical control (74, 76). In both a letter to the editor of the Journal of the American Medical Associa- tion, and in their book, Mark and Ervin advocate a national screening program for the identification and treatment of potentially violent people. And in both instances they clearly intend this as a large scale political measure. In the letter, they argue that the violence in the Detroit riots cannot be explained by environmental conditions, such as poverty and racism, because not all of the ghetto dwellers rioted and because even fewer become violent. Instead, they suggest the possibility of brain damage as a cause for rebellion, and in partie- Lar for violence, and then they advocate their screening and treatment program. In the book, they widen their interests to an “early warning” alert system whereby “unacceptable violence.” including crimes against property. can be detected and sereened out for prophylactic treatment. Their definition of “un- acceptable violence™ applies “equally to police or public authorities as well as to politically activist groups (students, racial, ete), and all violent acts that do not tit into this category would be ‘unacceptable’. Mark, Ervin and other psychosurgeons do have an effective pacifying opera- tion in their hands. It has already been applied to a few prisoners in California, to aggressive epileptics in Boston, to hyperactive children and adolescents with criminals records in Mississippi, to drug addicts, alcoholics and a wide variety of neurotic and psychotic individuals around the nation. Mark, Ervin and Sweet say they want to focus their research and treatment on individuals with brain disease, but this is irrelevant. The Justice Department is (134) interested in their work and their operation will pacify anyone, with or without a brain disease or a psychiatric disorder. Jose Delgado has gone so far as to advocate a National 449 Space Agency styled crash program pumping millions of dollars into physical control of the mind. Even if the projects of men like Mark, Ervin and Delgado find only limited ap- plication, the presence of these projects will most certainly intimidate large por- tion of our population. The growth of psychosurgery brings us much closer to a future state of totalitarianism based on technological intimidation. In the Congressional Record of February 24 I have advocated the abolition of all forms of psychosurgery and I am currently framing a bill to this effect. BIBLIOGRAPHY 1. Aarons, Leroy F., “Brain Surgery Is Tested on Three California Convicts,” The Washington Post, February 25, 1972, p. 1. 2. Andy, O. J., “Neurosurgical Treatment of Abnormal Behavior,“ Amer. J. Med. Sci. (1966) 252 :232-238. 3. Andy, O. J.; D. F. Peeler; J. Mitchell; D. P. Foshii and K. Koshino, “The Inphocampal Contribution to ‘Learning and Memory,’” Con. Reflex. (1968) 3:217-233. 4. Andy, O. J., “Thalamotomy in Hyperactive and Aggressive Behavior, Confin. Neurol. (1970) 32:322-325. 5. Andy, O. J. and M. F. Jurko, “Hyperresponsive Syndrome,” 2nd Int. Conf. on Psychosurgery (1970). See Scoville. 6. Bailey, Harry; Dowling, John; Swanton, Cydric; Davies, Evan, “Studies in Depression ; Cingulo-tractotomy in the Treatment of Severe Affective Illness,” Med. J. Australia (1971) 1:8-12. 7. Baker, Earle; Young, M. D.; Gauld, D. M. ; Fleming, J. F. R., “A New Look at Bimedial Prefrontal Leucotomy,” Canadian Med. Assoc. J. (1970) 102 :37-41. 8. Balasubramaniam, V.; Kanaka, T. S.,; Ramanugam, P. V.; Ramanurthi, D., “Sedative Neurosurgery,” J. Indian Med. Assoc. (1969) 53 :377-381. 9. Balasubramaniam, V.; Kanaka, T. S.; Ramanugam, P. V.; Ramanurthi, D., “Surgical Treatment of Hyperkinetic and Behavior Disorders,” Int. Surg. (1970) 54 :18-23. 10. Ballantine, Jr., H. T.; Cassidy, Walter; Flanigan, Norris; Morino, Raul, “Stereotaxic Anterior Cingulotomy for Neuropsychiatric Illness and Intractable Pain,” J. Neurosurg. (1967) 26 :488-495. 11. Ballantine, Jr., H. T.; Cassidy, Walter; Broduer, John; Giriunan, Ida, “Bilateral Anterior Stereotaxic Cingulotomy for Incapacitating Mood Disturb- ance,” 2nd Int. Conf. Psychosurgery (1970). See Scoville. 12. Barhol, H. S., “1000 Prefrontal Lobotomies—A Five-to-ten-year Follow-up Study,” Psychiat. Quart. (1958) as 32:653-678. 13. Batchela, Ivor, Henderson and Gillespies Textbook of Psychiatry, Oxford Med. Publishers, 1969. 14. Breggin, Peter R., “Coercion of Voluntary Patients in an Open Hospital,” Arch. Gen. Psychiat. (1964) 10:173-181. 15. Breggin, Peter R., “Sedative-like Effect of Epinephrine.” Arch. Gen. Psy- chiat. (1965) 12 :255-259. 16. Breggin, Peter R., “The Psychophysiology of Anxiety,” J. Nerv. Ment. Dis. (1964) 139 :558-568. 17. Breggin, Peter R., “Psychotherapy as Applied Ethics,” Psychiatry (1971) 34 :59-74. 18. Breggin, Peter R., The Crazy from the Sane, Lyle Stuart, 1971. 19. Breggin, Peter R., “The Return of Lobotamy and Psychosurgery,” Con- gressional Record, February 24, 1972, pp. E1602-E1612. 20. Breggin, Peter R., “Lobotomies Are Still Bad Medicine,” Med. Opin., March 972. 21. Breggin, Peter R., After the Good War, Stein and Day Pub., 1972. 22. Breggin, Peter R., “Psychiatry as Utopian Politics,” jth Intern. Cong. Soc. Psychiat, (1972). To be delivered and placed in Proceedings. 23. Breggin, Peter R., “The Politics of Psychosurgery,” jth Intern. Cong. Soc. Psychiat. (1972). To be delivered and placed in Proceedings. 24. Breggin, Peter R., “Psychosurgery for Hyperactive Children,” submitted for publication. 25. Brown, M. Hunter, and Lighthill, Jack, “Selective Anterior Cingulotomy : A Psychosurgical Evaluation,” J. Neurosurg. (1968) 29 :513-519. 26. Brown, M. Hunter, “Double Lesions of the Limbic System in Schizophrenia and Psychopathy,” 2nd Intern. Conf. Psychosurgery (1970). See Scoville. 93-999 (Pt. I) O-173 - 8 450 27. Canad. Med. Assoc. J., “Standard Lobotomy. The End of an Era,” (1964) 91 :1228-1229. 28. Chitanondh, H., “Stercotaxic Amygdalotomy in Treatment of Olefactory Seizures and Psychiatry Disorders with Olefactory Hallucinations,” Confin. Neurol. (1969) 27 :181-196. 29. Crow, H. J.; Cooper, R.: Phillips, D. G., “Progressive Leucotomy,” in Mas- serman, Jules, Current Psychiatric Therapies, III, Grune and Stratton, 1963. 30. Crow, H. J., “Brain Surgery in the Treatment of Some Chronic Illnesses,” a paper given at the British Council for Rehabilitation of the Disabled, Tavistock House (South), Tavistock Square, London, 1965. Published Separately. 31. Crow, H. J., and Phillips, D. G., “Multifocal Frontal Leucocoagulation in Anxiety and Obsessional Illness,” 2nd Intern. Conf. Psychosurgery (1970). See Scoville, 32. Delgado, Jose M. R., Physical Control of the Mind—Toward a Psychocivil- ized Society, Harper Colphon, 1969. 33. Dynes, John B., “Lobotomy—Twenty Years After,” Virginia Med. Quart. (1968) 95 :306-308. 34. Evans, Philip, “Failed Leucotomy with Misplaced Cuts: A Clinico-anatomi- cal Study of Two Cases,” Brit. J. Psychiat. (1970) 118 :165-170. 30. Fedio, Paul, and Ommaha, Ayub, K. “Bilateral Cingulum Lesions and Stimulation in Man with Lateralized Impairment in Short-Term Verbal Memory,” Exper. Neurol. (1970) 29 :84-91. 36. Freeman, Walter, and Watts, James, Psychosurgery, Charles C. Thomas, 1950. 37. Freeman, Walter, “Psychosurgery” in Arieti, Silvano, American Handbook of Psychiatry, 11; Basic Books, 1959. 38. Freeman, Walter, The Psychiatrist ; Grune and Stratton, 1960. 39. Freeman, Walter, “Psychosurgery,” Am. J. Psychiat. (1964) 121-653-655. 40. Freeman, Walter, “Recent Advances in Psychosurgery,” Med. Ann, D.C. (1965) 34; 157-160. 41. Freeman, Walter, A Taped Interview for the American Psychiatric Asso- ciation Museum and Library, April 17, 1968. 42. Freeman, Walter, “Frontal Lobotomy in Early Schizophrenia : Long Fol- low-up of 415 Cases,” Brit. J. Psychiat. (1971) 119: 621-624. 43. Fulton, John, Frontal Lobes and Affective Behavior: Norton, 1951. 44. Gallagher, Cornelius E., “Federal Funds of $28,000 to Harvard Psy- chologist B. F. Skinner,” Congressional Record. Dec. 15, 1971, pp. H12623-12633 (A summary of his investigation in “mind control”). 45. Greenblatt, Milton; Arnot, R.; Solomon, H., Studies in Lobotomy; Grune and Stratton, 1950. 46. Greenblatt, Milton, and Solomon, Harry, Eds., Frontal Lobes and Schizo- phrenia; Springer Publishing Co, 1953. 47. Group for the Advancement of Psychiatry, “Lobotomy,” in Report #6, 1948. 48. Hassler, R. and Dieckmann, G.. “Stereotaxic Treatment of Compulsive and Obsessive Syndromes,” Confin. Neurol. (1967) 29: 153-158. 49. Heath, Robert G., “Electrical Self-stimulation of the Brain in Man,” Amer. J. Psychiat, (1963) 120: 571-577. 50. Heath, Robert G., “Developments Toward New Physiologic Treatments in Psychiatry,” J. Neuropsychiat. (1964) 5: 318-331. 51. Heath, Robert G.; Stanley, John B.:; Fontana, Charles J., “The Pleasure Response: Studies in Stereotaxic Technics in Patients,” Kline and Laska, eds. Computers and Electronic Devices in Psychiatry; Grune and Stratton, 1968. 52. Heath, Robert G. and Guerrero-Figuroa, R., “Stimulation of the Human Brain.” Acta Neurol. Latino Amer. (1968) 14: 116-124. 53. Heath, Robert G., “Perspectives for Biological Psychiatry,” Bio Psychiat. (1970) 2: 81-87. 54. Heimberger, R. R., “Stercotaxic Amygdalotomy,” JAMA (1966) 198: T41-745. So. Heatherington, R. Fu: Haden, P., and Craig, W., “Neurosurgery in Affec- tive Disorder. Criteria for Selection of Patients,” 2d Intern. Conf. Psychosurgery (1970). See Scoville. HG. Hirose, 8. “Orbito-ventromedial Undercutting, 1957-1963," Amer. J. Psy- chiat. (1964) 121: 1194-1202. 57. Hirose, 8. “The Case Selection of Mental Disorders for Orbito-ventromedial Undercutting,” 2nd Intern. Conf, Psychosurgery (1970). See Scotville. 451 58. Holden, J. M. C.; Itil. T. M.; Hofstatter, L., Prefrontal Lobotomy: Step- ping-Stone or Pitfall?” Amer. J. Psychiat. (1970) 127: 591-598. 59. Kalinowsky, Lothar, and Hippus, Hanns, “Psychosurgery,” in their text. Pharmacological, Convulsive and Other Somatic Treatments in Psychiatry Grune and Stratton, 1969. 60. Kalinowsky, Lothar, “Psychosurgery Panel,” Dis. Nerv. Sys. (1969) 30: suppl : 54-55. 61. Kalinowsky, Lothar, “Psychosurgery Said to Help in Certain Neuroses,” Psychiatric News (1971) April 7, p. 7. 62. Khachaturian, A. A., “A Criticism of the Theory of Leukotomy,” Nevro- patol. I. Psikhiatrya (1951 20: No. 1. Microfilmed English translation, Library of Congress. TT 60-13724. 63. Knight, Geoffrey C., “Stereotaxic Tractotomy in the Surgical Treatment of Mental Illiness,” J. Neurol. Neurosurg. and Psychiat. (1965) 28: 304. 64. Knight, Geoffrey C., “Intractable Psychoneuroses in Elderly and Infirm— aoa ment in Stereotactic Tractotomy,” Brit. J. Geriatric Practice (1966) 115: 257-266. 65. Knight, Geoffrey C., “Bi-frontal Stereotactic Tractotomy: An Atraumatic Operation of Value in the Treatment of Intractable Neuroses,” Brit. J. Psychiat. (1969) 115: 257-266. 66. Lancet (1962), “Leucotomy Today,” 2: 1037-8. 67. Lancet (1969), “Brain Surgery for Sexual Disorders,” 4:250-251. 68. Lewin, W., “Observations on Selective Leucotomy,” J. Neurol, Neurosurg. (1961) 24 :37-44. 69. Lindstrom, Petter A., “Prefrontal Ultrasonic Irradiation—Substitute for Lobotomy,” Arch. Neurol. and Psychiat. (1954) T72-399-425. 70. Lindstrom, Petter A.; Moench, L. G.; Roynanek, Agnes, “Prefrontal Sonic Treatment,” in Masserman, Jules, ed., Current Psychiatric Therapies, XV ; Grune and Stratton, 1964. 71. Lindstrom, Petter A., “Prefrontal Sonic Treatments (P.S.T.). 16 Years Experience,” 2nd Intern. Conf. Psychosurgery (1970). See Scoville. 72. Livingston, Kenneth, “The Frontal Lobes Revisited The Case for a Second Look,” Arch Neurol. (1969) 20 :90-95. 73. Manchester Guardian, April 2, 1968, p. 18. 74. Mark, Vernon: Sweet, W. H.,, and Ervin, F. R., Letter to the Editor, JAMA (1967) 201 :895. 75. Mark, Vernon. Testimony on H.R. 13111 before the House Appropriations Subcommittee. Part 6 p. 1002. Senate FY 70 Appropriations Hearing, Dec. 1969. 76. Mark, Vernon, and Ervin, Frank, Violence and the Brain. Harper and Row, 1970. 77. Mark, Vernon, Barry, Herbert ; Mc Lardy, Turner, and Ervin, Frank, “The Destruction of Both Anterior Thalamic Nuclel in a Patient with Intractable Depression,” J. Nerv. Ment. Dis. (1970) 150 :266-272. 78. Marks, I.M.; Birley, J.; Golden, M.G., “Modified Leucotomy in Severe Agoraphobia,” Brit. J. Psychiat. (1965) 112 :757-769. 79. McKenzie, K. G. and Kaczanowski, G. “Prefrontal Leucotomy : A Five Year Controlled Study,” Canad, Med. Asso. J. (1954) 91-1195-1198. 80. Medical World News, “The Lobotomists Are Coming Again,” January 15, 1971, pp. 34. 81. Miller, A., “The Lobotomy Patients—A Decade Later,” Canad. Med. Asso. J. (1967) 96: 1095-1103. 82. Moniz. Bgas, “Attempt at Surgical Treatment of Certain Psychoses,” in Wilkins, Robert, ed. Neurosurgical Classics; Johnson Reprint Corp: 1965. 83. Moore, D., “Prefrontal Leucotomy,” Canad. Med. Assoc. J. (1970) 102 :875. 84. Moser, M.H., “A Ten-Year Followup of Lobotomy Patients,” Hosp. Commu- nity Psychiat. (1969) 20 :881. 85. Narabayashi, H.; Hagao, T.; Salto, Y.; Yoshido, M.; and Nagahata, M., “Stereotaxic Amygdalotomy for Behavior Disorders,” Arch. Neurol. (1963) 9: 1-17. 86. Narabayashi, H.; and Uno, M., “Long Range Results of Stereotaxic Amyg- dalotomy for Behavior Disorders,” Confin. Neurol. (1966) 27 :168-171. 87. Narabayashi, H., “Functional Differentiation in and around the Vertical Nucleus of the Thalamus based on Experience in Human Stereoencephalotomy,” Johns Hopkins Med. J. (1968) 122 :295-360. 88. Newsweek, “Probing the Brain,” April 21, 1971. Covery Story. 452 89. “Neural Bases of Violence and Behavior,” a conference sponsored by the U. Texas Medical School, Houston, March 9-11, with a panel on the “Role of the Neurosurgeon,” including Vernon Mark, Keiji Sano, W. H. Sweet and Earl Walker. Frank Ervin delivered a separate paper enttiled “Studies of Aggressive Benavior in Penitentiary Inmates.” 90. Pippard, John, “Leucotomy in Britain Today,” J. Ment. Sci. (1962) 108: 249-255. 91. Post, F., “An Evaluation of Bimedial Lencotomy,” Brit. J. Psychiat. (1968) 114 :1223-1224, U2. Psychiatric Ncws, “Psychosurgery Hailed in Experimental Texas Study,” Dec. 16, 1970, p. 1. Also see, News Rerease, U, Texas Medical Branch at Galves- ton, Sept. 1, 1970, 7 pages. 93. Rinkel, Max, The Biological Treatinent of Mental Illness; Farrar, Straus and Giroux, 1966, p. 66 and p. 146. 94. Robin, A. A, “A Controlled Study of the Effects of Leucotomy,” J. Neurol. Neurosurg. Psychiat. (1958) 21 :262-269, 95. Roeder, EF. D., “Stereotaxic Lesion of the Tuber Cinerium in Sexual Deviation,” Confin. Neurol. (1966) 27 1162-168. 96. Sano, K., Yoshioka, M., Ogshiwa, M., Ishijma, B., Ohye, C., “Postero-medial Hypothalamotomy in Treatment of Aggressive Behavior,” Confin Neurol. (1969) 27:164-167. 97. Sano, K., Hiroski, S., and Yoshiaki, M., “Results of Stimulation and Des- truction of the Posterior Hypothalamus in Cases with Violent, Aggressive or Restless Behavior, 2nd Intern. Conf. Psychosurgery (1970). Nee Scoville. 98. Sargant, W., and Slater, SE., Physical Mcthods of Treatment in Psychiatry; William and Wilkins, 1964. 99. Scoville, William B., “Recent Thoughts on Psychosurgery,” Connect. Med. (1969) 33 453-456. 100. Scoville, William B., ed., Transactions of the Second International Con- ference on Psychosurgery; Charles C. Thomas, in press. Held at Copenhagen, Denmark, August 24-26, 1970, with approximately 100 participants and 41 papers, including 12 papers from America, representing approximately 20 American in- vestigators. William B. Scoville of Hartford and Yale was elected President, with Walter Freeman, San Francisco, as an Honorary President. My bibliog- raphy is based upon full pre-publication reprints from M. Hunter Brown, Wil- liam Scoville and Petter Lindstrom: newly published Vaernet and Madsen, and Freeman (1971) papers, and summaries. 102. Sem-Jacobsen, Carl W., Depth-Electrographic Stimulation of the Human Brain and Behavior; Charles C. Thomas, 1968. 103. Shipley. Thorn, ed., Classics in Psychology; Philosophical Library, 1961. 104. Shobe, Frank, and Gildea, Margaret, “Long-term Followup of Selected Lobotomized Patients,” JAMA (196%, 206 :327-332). 105. Siegfried, J., and Ben-Schmuel, A., Neurosurgical Treatment of Aggres- sivity. Sterotaxic Amydalotomy vs. Leucotomy,” 2nd Intern, Conf. Psychosurgery (1970). See Scoville. 106. Slater, B., and Roth, M., Clinical Psychiatry, 3rd Ed. ; Williams and Wil- kins, 1969. 107. Smith, Aaron, “Selective Prefrontal Leucotomy,” a letter, Lancet (1965) 1:76. 108. Solomon, P., and Patch, K., Handbook of Psychiatry, 2nd Ed., Lange, 1971. 109. Spiegel, E. A, and Wycis, H. T., Steroencephalotomy, I; “Thalamotomy and Related Procedures,” Grune and Stratton, 1962. 110. Spiegel, BE. A., Progress in Neurology and Psychiatry; Grune and Strat- ton, 1970. See pp. 67-69. 111. Steegmann, A. T., “Dr. Harlow’s Famous Case: the ‘impossible’ accident of Phineas I. Gage,” Surgery (1962) 52 :952-938. 112. Strom-Olson, R., and Carlisle, “Bimedical Stercotactic Tractotomy: A followup Study of its effects on 210 Patients,” Brit. J. Psychiat. (1971) 118:141- 154. 113. Sweet, William. Testimony before the Senate Appropriations Committee, Part 6, p. 1002, Senate FY 70 Appropriations Hearings. 1970. 114. Sykes, M. K. and Tredgold, R. F., “Restricted Orbital Undercutting: A study of Its Effects on 350 Patients over the years 1951-1960,” Brit. J. Psychiat. (1964) 110 :609-640. 115. Szasz, Thomas S., The Myth of Mental Illness ; Hoeber-Harper, 1961. 453 116. Szasz, Thomas S., Ideology and Insanity: Anchor Books, 1970. 117. Tan, E., Marks, I. M., Marset, P., “Bimedial Leucotomy in Obsessive- Compulsive Neuroses,” Brit J. Psychiat. (1971) 118 :155-164. 118. Tooth, G. C. and Newton, M. P., Leucotomy in England and Wales; H. M. Stationery Office, London, 1961. 119. Turner, Eric, “Operations for Aggression, Bilateral Temporal Lobotomy and Posterior Cingulectomy.” 2nd Intern. Conf. Psychosurgery (1970). See Scoville. 120. Vaernet, K., and Madsen, Anna. “Stereotaxic amygdalotomy and Baso- frontal 8ractotomy in Psychotics with Aggressive Behavior,” J. Neurol. Neuro- surg. Psychiat. (1970) 33 :858-863. 121. Vidor, R., “The Situation of the Lobotomized Patient,” Psychiat. Quart. (1963) 37:97-104. 122. Vosburg, R., "Lobotomy in Western Pennsylvania: Looking Backward over Ten Years,” Amer. J. Psychiat. (1962) 119 :503. 123. Williams, J. M. and Freeman, W., “Evaluation of Lobotomy with Special Attention to Children.” A. Res. Nerv. Ment. Dis. Proc. (1953) 31:311. 124. Winter, Arthur, Ed. (Contributors: Winter, A.; Brazier, M.; Heath, R.; Osmond, H.; Scoville, W. and Shatin, L.) The surgical Control of Behavior; Charles C. Thomas, 1971. 124a. Witter, Charles., “Drugging and Schooling.” Transaction, July/August 1971. 125. Wortis, S. B., ed., The Yearbook of Psychiatry and Applied Mental Health: Yearbook Medical Publishers, 1970. Reviews. Brown Lighthill favorably (1968). 126. Wycis, Henry T., “The Role of Stereotaxic Surgery in the Compulsive State,” 2nd Intern. Conf. Psychosurgery (1970). See Scoville. ADDITIONAL NOTES 127. Breggin, Peter R., and Greenberg Daniel, “Return of the Lobotomy,” The Washington Post, March 12, 1972, p. 1 Outlook Section. 128. Fields, Larry, “Addict Who Died Had Brain Surgery to Fight Habit,” Philadelphia Daily News, March 13, 1972, p. 3. This was the first in a series in which an unpublished psychosurgery project surfaced for the first time. The surgeon, Jewell Osterholm, Director of Neurosurgery at Hannemann Hospital, had operated on twelve people with cingulotomies for addiction, alcoholism, pain and “emotional problems.” 129. Hampton, Jim, “Erie Brain Surgery,” National Observer, March 25, 1972, p. 1. Contains considerable independently gathered opinions and reports. 130. von Hoffman, Nicholas, “Brain Maim,” The Washington Post, July 18, 1971. This was the first article in the media based on my research. 131. Randal, Judith, “Psychosurgery Trend Alarming,” The Washington Star, February 1972. This is the first of several by Randal on the return of psycho- surgery, some containing new material. Text reference refers to her second article, Wash. Star, “Psychosurgery is Denounced,” Mar. 12, 1972. 132. D. Arazien, Steve, “The New Lobotomists,” Boston After Dark, March 7-13, 1972. This is one of the more detailed analyses published. 133. Trotter, Robert, “Clockwork Orange in a Calif. Prison”, Science News, March 11, 1972. This is important reading, including new material uncovered by Trotter concerning grants from the Justice Department and the National Insti- tue of Mental Health to support the work of Vernon Mark and Frank Ervin, and including some of the difficulties these men have had gaining support for their work from the medical establishment. 134. The Justice Department, Law Enforcement Assistance Administration, has given to William Sweet, and to Mark and Ervin, a grant of $108,930, for the following purpose (summary from Justice Department) : “The role of neurobio- logical dysfunction in the violent offender. Specifically, the grantee will deter- mine the incidence of such disorders in a state penitentiary for men; establish their prevalence in a nonincarcerated population; and improve, develop and test the usefulness of electrophysiological and neurophysiological techniques for the detection of such disorders in routine examination.” In addition, Vernon Mark, Frank Ervin and William Sweet have two other grants from the National Institute of Mental Health totaling more than $500,000 and dealing with violence epilepsy and brain surgery. 454 135. Greenberg, Daniel, “Lobotomy : The Brain Cutters Return.” Science and Government Report, P.O. Box 21123, Washington, D.C., March 135, 1972. In addition, the Associated Press and Reuters and numerous newspapers, columnists and magazines have begun covering the return of lobotomy and psychosurgery. [From the Congressional Record, Feb. 24, 1972] THE RETURN oF LoBoroMy AND PSYCHOSURGERY (By Hon. Cornelius I. Gallagher, of New Jersey, in the House of Representatives) Mg. GALLAGIER. Mr. Speaker, 1 rise today to insert into the Congressional Record one of the most shocking documents I have ever seen. “The Return of Lobotomy and Psychosurgery,” by Dr. Peter R. Breggin has not been previously published and represents the first critical review of the current resurgence of this mutiliating operation on a wide scale. Dr. Breggin covers the world scene in the first section, concentrates on its use in the United States in the next two sec- ions and concludes with a sensible program for prompt action. His bibliogra- phy is extensive and indicates the depth of his research. Psychosurgery is now being used to control so-called “hyperactive” children and it is even used on children as young as 5 years old. Dr. Breggin describes the frightening use of this surgery on individuals who suffer from “anxiety” and “tension” and other forms of behavior which might be classified as neuroses, and he documents an increasing tendency to select women, older people and now children as targets. He cites dozens of on-going projects. While there was a strong negative response to the original wave of psycho- surgery which claimed up to 30.000 victims in the United States alone, this human revulsion was not widely expressed in the medical literature. I have been informed that the decline of lobotomy in America during the late 1950's was because of the increasing use of electroshock and drugs, not because of any public or professional outery. This current wave of lobotomy and psychosurgery of all forms should be met with a prompt public interest and. in no case, should it be allowed to spread without informed serutiny. Dr. Breggin performs a distinet public service by bringing forward an immense amount of information which has hitherto been buried in somewhat arcane journals. Jecause of the nature of this unpublished material which 1 will insert, a few words about Dr. Breggin are in order. He is in private practice here in Washing- ton and is on the faculty of the Washington School of Psychiatry. His training began at IHarvard where he majored in social relations and graduated with honors. There he led the first large scale student-run mental hospital volunteer program which became a model of patient rehabilitation in the final report of the President's Joint Commission on Mental Health and Ilness—1961. He took his medical training at Case Western Reserve in Cleveland and his psychiatrie train- ing at the New York Upstate Medical Center and the Massachusetts Mental Health Center, where he was a teaching fellow at Harvard Medical School. Dr. Breggin has already written a much briefer paper without a bibliography which will appear in Medical Opinion and Review in March. He will give a paper analyzing the history and polities of psychosurgery at the Fourth International Congress of Rociety Psychiatry in May, and T am proud that Dr. Breggin has asked me to disclose the full details in a narrative form. complete with names, places, and descriptions of current and planned activities in this area. Mr. Speaker, IT have used the words “shocking” and “frightening” to describe what Dr. Bregegin has disclosed. T am especially upset to discover that irrever- sible brain mutilation is being used on hyperactive children. When my privacy inquiry held a hearing on the use of behavior modification drugs on grammar schoolchildren in September 1970, we learned that there was nothing wrong with these children in the medical sense. It was behavior and behavior alone that created the diagnosis of minimal brain dysfunction and perhaps the only proper definition of that term was presented by Dr. Francis Crinella: “one of our most fashionable forms of consensual ignorance.” At least 230.000 children, in all parts of the country, are now receiving drugs to mask the effects of MBD, but the drug therapy can be stopped. Nothing can undo brain mutilation. accord- ing to Dr. Breggin, and T am convinced that public debate must take place over the use of such irrevocable destruction of the creative personality. 455 Mr. Speaker, “shocking” and “frightening” are too mild to describe my reaction to this material. The following article, ‘The Return of Lobotomy and Psychosurgery,” is copyright by Dr. Peter R. Breggin in 1972 and I think many Americans will be grateful to Dr. Breggin for allowing its publication in the REcorDp. As a man who has been concerned about the erosion of human values for some 7 years and who has taken effective steps in the past to guarantee our citizens the right to pursue happiness in their own way, let me say that I am personally grateful to Dr. Breggin for his courage, scholarship, and humanity. I am proud to insert his copyrighted article in the Recorp at this point: THE RETURN OF LOBOTOMY AND PSYCHOSURGERY (Copyright 1972 by Peter R. Breggin) INTRODUCTION The purpose of this report is to alert the American public to the details of a i resurgence of lobotomy and psychosurgery in America and around the world. In lobotomy and psychosurgery parts of the brain which show no demonstrable disease are nonetheless mutilated or cut out in order to affect the individual's emotions and personal conduct. In each of the studies presented here, the ex- pressed purpose will be the control of some form of behavior—most often aggres- sive behavior—or the blunting of an emotion, usually “tension” or “anxiety.” The surgical methods vary widely both here and around the world, including the old-fashioned “modified” pre-frontal lobotomy, essentially a mutilating opera- tion in which the surgeon cuts a narrow slice through the midline base of the frontal lobes, partially incapacitating the highest and most refined functions of the human brain and the human being. These frontal lobes, the highest evolu- tionary organ in the human being, are also being attacked with ultrasound, electrical coagulations and implanted radium seeds. Newer operations also attack the amygdala of the temporal lobe of the brain, the cingulum which lies beneath the frontal lobes between the hemisphere, the thalamus, hypothalamus and related structures. As you will see in this survey, the great body of evidence supports the notion that all these operations accom- plish the same thing—a “blunting” effect upon the human’s emotional responsive- ness. They are partial lobotomies. The first wave of lobotomy and psychosurgery, which claimed 50,000 persons in the United States alone, was primarily aimed at state hospital patients with chronic disabilities. The current wave is aimed at an entirely different group— individuals who are relatively well-functioning, the large majority of them with the diagnosis of “neurosis,” many of them individuals who are still living at home and performing on the job. Women constitute the majority of the patients, with old people and children as other large groups. In Japan, Thailand, and India, children have been large target populations for some time; but now in America, for the first time in many years, numbers of children are again being submitted to psychosurgery, particularly at the University of Mississippi, where O. J. Andy is operating on “hyperactive” children as young as age five. The current rate of psychosurgery in the United States is difficult to ascertain, but you will be able to make your own estimates from the mass of material presented here, including about 1,000 cases since 1965 which have come to my personal attention during my informal survey and review of the literature. Three American psychosurgeons have accounted for more than 500 among themselves in recent years, and I have counted at least 40 individuals currently involved in psychosurgical projects. In addition, several psychosurgeons who will be quoted have estimated a current rate of 400-600 cases per year, and most important, every psychosurgeon agrees that we are just beginning to witness a massive increase in psychosurgery to rival the wave of 50,000 two decades ago. There are a number of signals indicating the start of a major resurgence. A new International Association for Psychosurgery has been formed with an American, William Scoville, as its head. Many promotional statements are again appearing in print in widely circulated magazines such as Newsweek, Medical World News and Psychiatric News. Current textbooks in psychiatry and current year books of treatment will be found reviving psychosurgery, and major publications such as the Journal of the American Medical Association and the American Journal of Psychiatry have been offering pro-lobotomy articles based upon inadequate scien- tific studies. 456 Current scientific studies will be found as wanting as those which originally led the prestigious Group for the Advance of Psychiatry to condemn the entire body of lobotomy literature as promotional and marred by exaggerations of sue- cess and denials of grossly mutilating effects upon the personality. Those few follow-up studies with matched controls (56, 73, 93) will describe a disastrous first wave which leaves little optimism for the future. The material will be prescribed in three parts: I. Current Psychosurgery Around the World. 11. Current Psychosurgery in the United States, and III. Newest Advances in Mind Control. It is useful to start with the material around the world because it more clearly documents the menace of psychosurgery. The bibliography is oy far the most extensive published on psychosurgery since 1965. The great majority of articles describe current psychosurgery, while a few are retrospective evaluations, and most refer to the United States (1, 2, 10, 18, 22, 23, 206, 28, 29, 30, 37, 38, 39, 40, 42, 43, 44, 50, 51, H4, 58, 61, 65, 66, 71, 72, 77, 78, 79, 3D, 86, 87, 95, 96, 98), England (3, 12, 20, 21, 24, 42, 46, 47, 48, 53, 55, 57, 5S, 70, 5, TY, 820 83, 84, 88, 89, 90), and Canada (4, 5, 7, 18, 52, 56, 59, 60, 88, 89, 90, Finally, I am grateful to Congressman Cornelius Gallagher for the opportunity to present the body of my research to the general public. I. CURRENT PSYCIIOSURGERY AROUND THE WORLD Psychosurgery is currently being done in Canada, Australia, France, Spain, Italy, West Germany, Norway, Sweden, Denmark, Finland, Switzerland, Thailand, India, and the world's leaders. Japan, England and the United States, nearly all of whom were represented among the one hundred psychosurgeons gathered in Den- mark for the Second International Conference on Psychosurgery in the summer of 1970 (79-80). Russia outlawed iobotomy and psychosurgery in 1951, and Khachaturian published a lengthy polemic explaining why. My survey is based upon material which was presented at the International Conference, published in the literature or sent to me hy the psychosurgeons with whom I have been in contact here in the United States. It is bound to be selec- tive, since only the better work tends to get published or reported, while the less satisfactory work is discarded or kept out of sight. This will be particularly true in regard to a procedure like psychosurgery that has received considerable nega- tive publicity. Similarly, the published work and reported cases in any field of medicine are likely to reflect only a small portion of what is going on, and in the field of psycho- surgery, the effects of the current promotion may not show up for some time. Now for a review of psychosurgery around the world. Some of the most candid reports come from Madras, India, one of the leading medical centers in that part of the world, where several high ranking medical and psychiatric authorities are deeply involved in the psychosurgery of children. The chief investigator is Dr. Balasubramaniam, Honorary Neurosurgeon. Gov- ernment General Hospital and Government Mental Hospital, Madras. He is well- known among western psychosurgeons, delivered a paper at the Second Interna- tional and publishes in English language journals. He headlines his basic theoretical paper “Sedative Neurosurgery” and then opens with one of the most forthright and simplistic descriptions in the lobotomy literature: “Sedative neurosurgery is the term applied to that aspect of neuro- surgery where a patient is made quiet and manageable by an operation.” P. 377. (Classical prefrontal lobotomy, the operation done on so many tens of thousands, is one variant of sedative surgery, he says. His own up-to-date amygdalotomy and more occasional hypothalamtomy are newer variants. lis work heavily in- volves children who are hospitalized, and he tells us: “The patient who requires this operation may manifest with one of the various behavioral disorders listed below. The commonest is restlessness.” B. 377. You will see that this is not a practice limited to India, and that both Japan and the United States are doing psychosurgery on hyperactive children. Writing in July, 1970 in the American Journal, International Surgery. Balasu- bramaniam summarizes his results with 115 patients, three of them under age five and another 36 under age leven. Using diathermy or injections of foreign matter, such as olive oil, to destroy areas of these childrens’ brains, he produces this result: “The improvement that occurs has been remarkable. In one case a patient had been assaulting his colleagues and the ward doctors ; after the opera- tion he became a helpful addition to the ward staff and looked after other patients. 457 dn Sua case the patient became quiet, bashful and was a model of good behavior.” Balasubramaniams sums up in his concluding sentence: “This operation has proved to be useful in the management of patients who previously could not be managed by any other means.” P22. If this turns out to be true, as I believe it will, then cingulotomy surgery will be the ultimate “theapeutic weapon” for any state hospital superintendent or prison warden. A bizarre report comes out of Thailand, where Chitanondh is also performing amygdalotomies on brain damaged patients, psychotics, neurotics, epilepties and behavior problems under the psychiatrically absurd rubric of “olefactory seizures and psychiatric disorders with olefactory hallucinations.” In other words, if he finds a case where the sense of smell is involved in any fashion, then he chops out the amygdala on the grounds that it is involved in smell perception and elaboration. This is the same amygdala that Balasubramaniam mutilates on the grounds that it is involved in aggression. Again and again we will find this phe- nomenon—that the psychosurgeon picks out the symptom that he wants to focus upon, then destroys the brain’s overall capacity to respond emotionally, in order to “cure” the symptom which he focused upon, completely neglecting that he has simply subdued the entire human being. One of Chitanondh’s patients is a nine-year-old boy whom he thinks has an ole- factory hallucination but who is obviously involved in a behavioral struggle with his parents. This patient has a “habit” of running away from home, allegedly to smell engine oil in cars! “Chief complaint of an obsessive smelling habit. For two years before admis- sion he had a strong compulsion to smell engine oil . . . He would not give any reason why he had to do this. The parents punished the patient but he would not give up the peculiar habit” P. 192. But despite the boy’s denial that he was hallucinating, the neurosurgeon per- forms this “sedative neurosurgery” and of course the bqy no longer runs away to smell engine oil. In a rare show of public disagreement, the discussants quoted after this report seem piqued at their colleague’s assault upon this child. One, a neurosurgeon. says: “If the neurosurgeons move psychosurgery from the frontal lobe to the temporal lobe (amygdala), we need to know some elementary psychiatry.” P. 196. Does this mean, as it seems, that it is not necessary to know elementary psy- chiatry if the neurosurgeon sticks to the frontal lobes—Iliterally the heartland of man’s highest and most subtle functions? Another discussant of Chitanondh’s work, a Japanese, warns that he, unlike the Thai, only operates on the mentally retarded! In a sentence he thus condemns his own methods as too gross or too inhumane for children of normal intelligence, while at the same time condemning the mentally retarded to sub-human status. The Japanese have been doing both frontal lobotomies and the newer amygda- lotomies (temporal lobotomies) steadily without going underground during the late 1950's and 1960's. They publish their work in English language journals and influence the international and American movement. Narabayashi and Uno of Tokyo report in 1966 on a follow-up of 27 children ages five to thirteen who have had amygdalotomies. They operate on: “. . . chil- dren characterized by unsteadiness, hyperactive behavior disorders and poor con- centration, rather than violent behavior ; it was difficult to keep them interested in one object or a certain situation.” P. 168. Here is a description of the best results as achieved in five of their many cases : “(They) have reached the degree of satisfactory obedience and of constant, steady mood, which enabled the children to stay in their social environment, such as kindergarten or school for the feebleminded.” P. 167. Sano, also in Tokyo. reports on 22 cases beginning with the youngest age four. His best results? “Emotional and personality changes: the patient became markedly calm, passive and tractable, showing decreased spontaneity.” P 167. Remember these descriptions when we get to the same operation as it is being done to depressed people, obsessive neurotics and a raft of others in the United States. Again and again we will find a kind of “tunnel vision” that allows a psy- chosurgeon to obliterate the liveliness and spontaneity of the individual while acting as if he is merely attacking a symptom or specific “illness” such as depres- sion or obsessive neurosis. Professor Sano is not as incompetent whose hypothalotomy operations cannot be trusted for technical expertise. He is an Honorary President of the Interna- tional Association for Psychosurgery. Sano will be joining several American 458 psychiosurgeons (W. H. Sweet, Frank Ervin, Vernon Mark and others) at a large upcoming conference on violence and its treatment at the Texas University Medical School on March 9-11 in Houston (98). The Japanese have not given up the more traditional frontal lobotomy either. From the recent Second lnternational Conference, Kalinowsky comments “An impressive clinical report of 519 patients was given by the Japanese neuropsy- chiatrist 8. Hirose, who prefers the orbitoventromedial undercutting procedure.” This is a more limited, modified frontal lobotomy, involving cuts where they will do the most, in the brain pathways which lie toward the midline underside of the frontal lobes. I have a summary of IHirose's talk given at the Second International in the sumer of i970 and there he describes 119 cases that he has done since 1957. He says that he operates on neurotics and psychotics, individuals with “pro- tracted emotional tension states, over-sensitivity, excessive self-consciousness, and obsessive states.” Much as he did in his 1965 American Journal of Psychiatry report, he continues to recommend mutilating the brains of people who are: “delicate, warm-hearted, conscientious, enthusiastic, perfectionistic . ,."” This is important—that even the old-fashioned lobtomists are now advocating their gross forms of intervention for more normally functioning human beings. “A kind of plastic surgery of mental states,” Hirose calls it in 1965. Moving away from the Far East, we tind that the West Germans are very active. Hassler and Dieckmann have been operating on the thalamus of children—13 cases reported in this article—in order to reduce “aggressiveness, destructiveness and agitation.” They also believe they can “treat” specific psychiatric illnesses when they attack and destroy sections of the brain. Their psychiatric rationalizations are extremely crude; “Obsessive-compulsive neuroses are comprised as well of the perpetual repetition of non-sensical ideas as also of the psychomotor phenomenon of compulsion . .. (sic) Thus the irrational activation of thought may result from functional disturbance of the intralaminar nuclei.” The notion that specific neurotic disorders might be traceable to a disturbance in a nucleus within the brain is so crude that even the Russian, Khachasturian, with his own lack of sophistication, was able to dismiss it two decades ago. The gross destructiveness of this kind of surgery, despite all apologies to the contrary in the literature, is again indicated by Hassler and Dieckmann’s report that it can produce severe amnesia which lasts up to six weeks after surgery. And in their minds, this is not an untoward side-effect, but an important aspect of the treatment which helps the therapeutic result. This is in fact a common theme—increased damage leads to increased result— in the early lobotomy literature of Freeman and Watts (1950). Freeman (1959) suggests that it is good to damage the intellectual capacity of the neurotic be- cause the neurotic thinks too much (p. 1526) ; and similarly the West Germans boast of : “alleviation of impulsion and over-subtle reasoning in all cases.” One of their patients became dangerous and attacked two nurses after sur- gery. Still in West Germany, IF. D. Roeder experimented with lesions in the hypo- thalamic region in an effort to cure “sexual deviation.” The written report is only 25 lines long but the pathology slide takes up half a page, in typical psychosur- gical reverence for technology. This is what he accomplished : “Potency was weak- ened, but preserved... The aberrant sexuality of this patient was considerably suppressed, without serious side-effects. One important feature was the patient's incapacity of indulging in erotic fancies and stimulating visions . . .” Ile boasts in addition that there was a disappearance of homosexual impulses and that psychiatric commitment could therefore be avoided. Psychiatric com- mitment avoided by obliterating a man’s fantasy life. Now for the English-speaking world. In Sidney, Australia, a group including Ilarry Bailey and John Dowling has published a report of 50 cases of cingulotomy with a report of 50 more on the way. The patients include a wide variety of people with depressions, including psychoties and chsessive-compulsive neurotics, and the cases were purposely selected to limit them to individuals with “basically sound personality struc- ture” rather than to hopelessly deteriorated individuals. 459 The Australians report “excellent” results in the form of a statistical outline of psychological test results and impressions of post-surgical adjustment, including comments on the return of professional people to a successful professional life. But there is only one very short clinical description, and we must take their statistics on faith. Nor can we trust their assertion that many return to professional work, since Freeman (1959) and Sargant and Slater (1964) have already disclosed that modified lobotomies return individuals to professional work but that they function with less sensitivity toward others and even with ruthlessness. This Austrian study also displays the typical lobotomist preference for women : 649, according to a small print footnote to a chart. These psychosurgeons lament public resistance to their work which apparently limits their access to patients. pop some unexplained reason. They label this public resistance “the Ben Casey effect.” Nearer to home in the English speaking world, the Canadians are becoming active again. In recent years the old-fashioned modified prefrontal lobotomy has been used on a variety of non-schizophrenic patients by R. F. Hetherington, P. Haden and W. Craig, Departments of Surgery, Psychiatry and Psychology, Kingston Psychiatric Hospital and Queens University, Kingston, Ontario. Their report to the Second International Conference in 1970 admits that the hospital refused to allow them to operate on males because of the unfavorable publicity given to lobotomies in Canada after the negative follow-up studies of McKenzie. But they were allowed to operate on women, 17 in number. Still in Canada, we find Earle Baker, Assistant Professor of Psychiastry, University of Toronto, reporting in 1970 on “A New Look at the Bimedial Pre- frontal Leucotomy.” (Leucotomy, or ‘cutting of the white matter,” is used as a synonym for lobotomy.) He describes 44 cases with “hard core functional psychiatric illness,” including siz with personality disorders and twenty-five with neuroses, who have been lobotomized between 1958 and 1968! The article is fairly typical of the older literature with the exception of its more modern claim that lobotomy offers something for everyone: “. . . Safe and effective method of reducing the symptoms of excessive tension, anxiety, fear, or depression in patients with a wide variety of illnesses, including anxiety neurosis, phobic psychoneurosis, obsessional neurosis, neurotic or psychotic de- pressive reactions and schizophrenia. This operation should be considered in such neurotic, personality and psychotic illnesses when medical treatment has failed.” P. 37 Baker openly acknowledges that the operation produces an organic brain syndrome—a sign of generalized damage to the entire brain. In this instance, it is characterized by “some disorientation, apathy, silliness and denial,” lasting up to two or three weeks and sometimes longer. In addition, as in the old days, there are “occasional changes in moral code, anger, sexuality, or interpersonal relations,” which the authors admit are permanent. Women are their main targets, too, 27 females and 17 males, age 20-58, and as we continually see, the women “do better,” 12 of 25 women accounted for declared to have an “excellent” result, while only 4 of the 17 men accounted for have an “excellent” result. That's 489, against 23%, but the investigators involved do not even mention this enormous discrepancy. It must be taken out of a chart! Baker and his associates give us come fascinating vignettes to support their contemporary use of the frontal lobotomy. Case #1 is a suburban housewife who is promiscious, runs away from home and becomes suicidal on occasion. After her lobotomy she is no longer promiscuous and becomes a faithful partner in her marriage. These modern lobotomists describe considerable changes in the lives of their patients and make facile moral judgments about these changes. One man sold the family business that he never wanted, one middle aged man went out dating for the first time in his life, two couples came to blows for the first time, and three marriages broke up—all of which the authors put their approval upon as signs that the operations made the patients “more open” and “less dependent.” One of their patients became so liberated that he went on to rob a bank. The judge gave him an extra heavy sentence, presumably to compensate for the moral obtuseness produced by the surgery. Moore then wrote a response to the Canadian Medical Association Journal stating that the judge was wrong in giving the longer sentence because the 460 patient's moral code would be unaltered by an “indefinite jail sentence,” as a result of his surgery. But who is in fact morally responsible for that bank robber's actions? I believe that one single legal judgment holding a lobotomy a thing of the past. Unlike the Far Eastern and some European psychosurgeons, the English by- and-large have retained an unabated preference for mutilating the frontal lobes. The English total is now reaching or surpassing the 20,000 mark. Tooth and Newton took a national census of England and Wales and came up with an official count of 10,827 as of 1954—but even this figure excluded the several hundred done in general hospitals, as well as the unknown hundreds done before 1942. Extrapolating from Pippard’s official count of 400 plus in the year 1961, Sargant and Slater estimate a total of 15,000 by 1962. If that rate remained as constant as it had, we would now be reaching a grand total of 18-19.000 in 1972. But the rate seems to be accelerating! The British surgeon, Geoffrey Knight, for example presented statistics on 1,050 cases of his own at the 1970 Second International, and much of his work originates after 1960. I can only give a small sampling of the English literature, for England appears to have led the world since the relative decline of the lobotomy in America. Knight and his associates to be the most busy, at least in the published litera- ture. I add this qualification because Walter Freeman told me of one British surgeon who had done 4,00 without any follow-up studies, published or unpub- lished! But to return to Knight, his original method is described as a bimedial lobotomy with orbital area undercutting of the frontal lobes really the old- fashioned modified frontal lobotomy which so many psychiatrists think has been long dead. It is an extensive mutilation of the brain, involving a nar- row longitudinal 2 em. wide by 6 em. deep cut at the midline of the frontal lobes at about the level of the eyes, or orbits. His first series included 550 patients, many of them with depressions. It is impossible to judge the effects of his surgery, since he is a statistical lobotomist who offers practically no data whatsoever about the people involved. Even a surgeon reporting on a new technique for removing an appendix is likely to tell wus something about the general condition of his patients as well as the exact kind of appendix he is talking about, purulent, ruptured or whatever. But in taking out pieces of the brain, Knight tells us nothing or next to nothing about the nature of the individuals involved either before or after surgery. It is no surprise then that Kalinowsky, in a phone conversation with me, said that same psychosurgeons read Knight's own data completely differently than he does, in this instance favoring the results of his older methods to his new radi- ation implants. Knight new radioactive technique, again applied to hundreds of patients, is simply a more sophisticated method for destroying frontal lobe tissue. He plants radioactive seeds in the areas he might otherwise attack surgically (57, 58, 83). But the actual effects upon the personalities of his patients cannot even be guessed at—except on the basis of our general knowledge about the effects of lobotomy. All we can find in Knight's many journal articles are mean- ingless lists of one or two word diagnoses paired statistically with equally meaningless categories of improvement. Kuight tells us in a 1966 report that he was inspired to action after reading about the increased admission rate of old people to the state hospitals. What is his solution? Rehabilitiation centers? Better housing and more social oppor- tunities for the old? No. His answer is increased lobotomizing of older people, and he has done exactly that. An article by Sykes and Tredgold follows up another series of 350 patients, some of them apparently done by Knight. Again we have empty statisties, and the general impression that the lobotomy never had a bad side-effect on anyone, or hardly anyone. But one statistic tells us a great deal about the mentality of the lobotomist—only 59 of these 350 patients had a serious trial of psychotherapy before being subjected to surgery. What is Knight's theoretical justification? It is the same old “reduction of in- tensity of emotional reaction.” Knight tells us in 1969. And the elaboration of the theory behind this is crude and simplistic beyond belief: “Since primitive emotions are damaging emotions, it might be deduced empirically that the in- terruption of connection from primitive cortical areas would contribute to the results obtained.” P. 257. 461 This theory amounts to nothing more than a bias—that strong emotions are bad. He calls these emotions “primitive,” when in fact they may be the highest expres- sion of our human development. Indeed, the frontal lobes are integral to all of man’s most sensitive, subtle and human qualities—love, empathy, creativity, abstract thinking and such (25, 26, 34, 92). Severing the connections between these lobes and the lower brain does not bleach the lobes of their primitive influences, but in fact ruins the function of these lobes. The lower portions of the brain are no more “primitive” in functtion than the heart and lungs which phylogenetically pre-date much of the brain's development. But to return to Dr. Knight, he does give us a paragraph or two, more about the theoretical basis for his operation, drawn entirely now from animal expiri- ments—as if the whole body of lobotomy literature did not exist. But what he says is what the labotomist have been saying all along anyway. Animal psycho- surgery succeeds in producing “quiescence and tameness.” Post and his colleagues are again representative of the statistical lobotomist, reporting on 52 patients in middle and late life who are alledgedly helped (40% of them) by the old-fashioned bimedial frontal lobotomy. Marks and his colleagues somehow came up with twenty-two cases of “agora- phobia”—fear of open spaces—and lobotomized them, again with the bimedial frontal lobotomy. They present no case material, so we can’t judge what they mean by “agoraphobia” or why they would destroy a person's brain to cure such a symptom. In fact, agoraphobia as an isolated symptom is so rare that one must distrust their clinical judgment in its entirety. People crippled by such a symptom almost invariably demonstrate a complex of psychiatric symptoms, as do almost all individuals who are psychologically crippled. The absurd becomes obscene in an unsigned editorial comment in 1969 in the Brittish Medical Journal calling for brain surgery for sexual disorders (5). The editorial comment praises German investigators for destroying a portion of the brain (hypothalamus, in this instance) of three male homosexuals, resulting in a “a distinct and sustained reduction in the level of sexual drive,” and all other drives of course, though they are unmentioned. This editorial considers the “need to protect the public,” but also suggests that voluntary consent should be obtained. But voluntary consent is a myth when the individual involved is a social deviant subject to the alternative of prison or involuntary mental hospitalization (13). But why call this editorial obscene? Because the writer brings up the alter- native of castration for homosexuals and argues that castration is “open to question on ethical grounds,” while lobotomy is not. This Englishman would rather lose his brains than his testicles. The Manchester Guardian, April 2, 1968, reports that a gambler who has stolen money has been sent from court into psychiatric custody for “voluntary” brain surgery to cure his gambling. The psychiatrist involved was Harry Fleming, senior consulting psychiatrist, Winwick Hospital. Dr. Fleming did not go uncontested. Another psychiatrist, F. R. C. Casson wrote into the medical journal, Lancet, to complain: “I have not previously heard of leucotomy being suggested as a remedy for compulsive gambling. By its reduction of moral inhibitory factors, one would imagine that it might facilitate irresponsible gambling behavior.” P. 815. But Dr. Casson, as usual, is not protesting on ethical grounds, or even on any general principle against lobotomy. Instead he is merely taking care of his own, for he is the “Hon. Psychiatrist to Gamblers Anonymous.” Now for a look at the Americans in some greater detail and depth, and then one final look at the British again with one of their newer more frightening and futuristic techniques of mind control. II. CURRENT PSYCHOSURGERY IN THE UNITED STATES Peter Lindstrom, who has many hospital appointments around the country, including the Children’s Hospital and Adult Medical Center in San Francisco, estimates that 400-600 psychosurgical operations are performed each year in the United States, and he personally accounts for 250 in the past five years in a recent letter to me. H. T. Ballanttine, a psychosurgeon at the esteemed Massachusetts General Hospital, writes to me that he agrees with this estimate and that he has done 160 since 1965. Both Jack Lighthill and Mr. Hunter Brown in Santa Monica, California, also agree with the estimate and personally account for 110 cases in the past five years. 462 All the psychosurgeons who have written to me agree that the current rate is going up rapidly and that we are, in the words of one of them, approaching a “second wave” of psychosurgery. No one knows for sure how many persons were mutilated in the “first wave". Walter Freeman, America’s dean of lobotomy, has given me a personal and prob- ably reliable estimate of 50,000. Most chronic mental hospitals—and there are hundreds in the country—have a caseload of old lobotomy patients. The past literatunre contains hundreds of articles, and many lobotomists and hospitals accounted for several thousand at a time. Freeman, for example, says that he did about 4,000, Freeman, formerly Professor of Neurology, the George Washington Univer- sity School of Medicine in Washington, D.C., has come out of retirement with invitations to speak at national and international conferences, including his appointment as an Honorary President of the new International Association for Psychosurgery. In a very recent (late 1971) article in the British Journal of Psychiatry he advocates operating upon schizophrenic patients carly in their illness rather than as a last resort. This will open the way for another phase of massive Institutional lobotomization of young people. Speaking at the Washington, D.C. academy of Neurosurgery in 1965 Freeman accurately describes the effects of his surgery when he points out that lobotomy leads to some of the same results as the last stages of deteriorating schizophrenia. When such a patient is so demoralized and deteriorated by institutional life that he no longer gives the ward any trouble, then there's no purpose to giving him surgery. Says Freeman: *. . . a deteriorated schizophrenic looks and acts the same with or without his frontal lobes. When the progress notes such a patient read, “Gives no trouble on the ward,” it is generally too late to expect any substantial result from operation.” I’. 157. And Freeman agrees with many modern lobotomists and psychosurgeons that the true aim, the best results, is the blunting of emotions: “A sucesssful operation bleaches the affect [emotions or feelings] attached to the ego, without disturbing intelligence, memory, or personality funetions.” P. 158. Lothar Kalinowsky, Prefessor of Psychiatry, New York Medical College in New York City, has written numerous books on somatic therapy, and more recently has spent considerable time on promotional for psyehosurgery, including the Psychiatrist News article, plus a publisher panel, and at least one unpublished panel on the West Coast. In the published panel discussion Chairman Kalinowsky is again touting lobhot- omies for “intractable and disabling neuroses, chronic depression unresponsive to other treatments.” Panel member Henry Brill, a very well known state hospital psychiatrist from Pilgram State, Long Island. where several thousand lobotomies were once done, spoke with indignation when he defended this treat- ment as prematurely discarded and “cast aside too cavalierly.” Brill also let on that “informal communications with American psychiatrists indicate that the operation has not been abandoned as completely as one might imagine from a casual reading of the literature.” Fritz IFreyhand of St. Vincent's Hospital, New York City, James Cattell of the department of psychiatry of Columbia P and S, and Joseph Ransohoff, from Bellevue, both again in New York City, participated in the panel, Dr. Ransohoff mentioning that he'd done 35 lobotomies in the past five years. Kalinowsky himself refused to give me an estimate on the phone or by mail concerning the number of lobotomy referrals he had done in the past few years. Only a few, he kept protesting, but with further questioning he admitted to having seen three patients in the last week (May 3, 1971) as possible candidates for lobotomy, one or two of whom he said would probably end up under the sur- geon’s knife, I. A. Spiegel, Professor Emeritus at Philadelphia's Temple University, has been active as President of the International Society for Research in Stereo- encephalotomy and as editor for the annual review called Progress in Newrology and Psychiatry. For the first time in many years. in 1970 he allowed psycho- surgery to appear in his review book in the form of a three page survey. Spiegel and his Philadelphia colleague, Henry T. Wyeis, are pioneers in stereo- taxic brain surgery, but they have done only a few psychosurgery or psyvehiatrie cases in recent years, Wycis reporting at the Second International on four “com- pulsive neuroses” operated on during the previous four Years (79). 463 Spiegel’s Progress in Neurology and Psychiatry is not the only annual review to resurrect psychosurgery in America. The Yearbook of Psychiatry and Applied Mental Health, edited by Wortis, abstracts an article I will review in this section, and then the American psychiatrist Francis J. Braceland makes an editorial comment: “It is interesting that psychosurgery is once more being con- sidered . . . The followup study is encouraging . . . Nevertheless, three pro- odes should be used only as a last resort, and after all other methods have ailed.” Another major promotional figure in American psychosurgery, William B. Scoville of Hartford Hospital and Yale University, is President of the new International Society fogPsychosurgery. In Medical World News he reports doing about two a month, (57) and in a letter to me he notes the demand is going up now. This Associate Clinical Professor of Neurology at Yale uses orbital under- cutting, a frontal lobotomy not unlike that used by the dean himself, Walter Freeman, so many years ago, except that it is done under direct visu- alization, rather than through the eyesockets by Freeman's “ice pick method,” as some lobotomists have called it. Writing in 1969 Scoville recommends lobotomy for depressions and for anxiety states, especialy in the aged, much as Knight recommends. He also lists some cases of conversion neurosis, severe obsessive-compulsive neurosis, and certain forms of schizophrenia, even though he says the delusions may get worse. And going contrary to many other lobotomists, he suggests it for some drug addicts. Most important is his recommendation for depression, for depression is one of the most common problems in any psychiatric practice, especialy in the elderly for whom he strongly favors lobotomy. His comments are particularly dangerous because he favors lobotomy over repeated courses of electroshock, stating: “More than one or two courses of shock treatment probably causes more diffuse brain damage than the newer fractional lobotomies.” P. 153. He repeats this allegation about electroshock in his promotion of lobotomy in Medical World News in January 1971. It is important because electroshock is used so very widely, tens of thousands of patients every year, so that any trend to replace it with surgery would vastly increase the lobotomy population, a trend already apparent in England. Still in his 1969 article, Scoville argues that all forms of psychosurgery accomplish the same basic mutilation, partial destruction of the “limbic system” or emotional regulating connections between the midbrain and frontal lobes, with a resultant disruption of the emotional component of the mind. As he succinctly puts it: “All prefrontal surgery probably benefits by a blunting function.” P. 456. Consistent with this, he says: “It is apparent to this writer that different types of mental disease do not require different areas of abiation or tract interruptions. There appears no need to vary location of operation in the neuroses, cyclical depressions and schizophrenia.” P. 456. He adds that the lower down the cut, the more specific the suppression of emotion, while the higher the cut, the more intellectual impairment. I agree with Scoville that the mind functions as a whole and is disrupted as a whole, and that the basic goal and the basic consequence of psychosurgery are always one in the same—to blunt, tame, quiet, sedate, or otherwise submerge or partially destroy the individual's unique emotional responsiveness. In Medical World News, Scoville is said to have performed over a thousand lobotomies. J. M. C. Holden, Associate Professor of Psychiatry and Physician Superin- tendent of the St. Louis State Hospital Complex, offers one of the most extensive and candid reviews of frontal lobotomy in late 1970 in The American Journal of Psychiatry, reporting on over 400 cases done some time ago in the St. Louis area. 1 wrote and asked about the numbers currently being done, and his colleague, 1.. Hofstatter, replied that the state hospitals no longer do them and that those being done are carried out in private practice. Holden is very candid about the kind of damage done by the original lobotomy operations. “The frequent effect of such overoperation was irreversible change in mood, emotion, temperament, and all higher mental functions. The more extensive the section, the greater likihood that such symptoms would develop. Postoperative mortality and morbidity, incidence and duration of confusion, urinary incontience, unequal pupils, facial assymetry, convulsions, and other extensive the section, the greater likelihood that such symptons would develop. neurological sequelae were greater when the section had been more extensiv. 464 Excessive weight gain and temporary or permanent changes in performance on the rational learning test and conventional intelligence and personality tests after operation were also reported . . . Nome patients showed frank clinical deterioration that persisted after operation.” I. 595. He adds that not only did this prefrontal lobotomy destroy areas of the frontal lobe, but that the degeneration reached down into the thalamus. Holden candidly describes the operation that mutilated tens of thousands in the English-speaking world alone, and then goes on to praise it as a necessary phase, a stepping stone, toward the newer, better surgery, and toward a better scientific understanding of the brain. He recommends experimenting with more limited and localized surgery, but he himself admits that the areas attacked and dest royed—the hypothalamus, the nuclei of the thalamus, the amygdala—are all functionally inter-related “to mobilize the total body resources in stressful situations.” “Interference With any part [my italic] of these circuits is reflected in changes in the homeo- stasis in others, but the nature of this interdependence and its precise relation- ship to behavior remains speculative.” 12. 593. He acknowledges that some people have raised ethical objections, but he doesn't discuss it himself, and instead concludes that the modified frontal lobotomy should be continued in the United States as a “treatment” in neurotic and psychotic states characterized by a high degree of emotionality or tension. Dr. Arthur Winter of East Orange, New Jersey, will soon be coming out with a book on lobotomies in collaboration with Scoville and with Heath. Winter writes to me that he is doing “stereotaxic prefrontal lobotomies,” limited to one side of the frontal lobes, in some instances at least. Ie would not tell me how many cases he had done, but sent me a detailed report on one 33 year old man with a diagnosis of schizophrenia on whom he had operated in 1969. A photo- graph provided by him in Medical World News shows a good size “1 em.” oblit- eration looking as large as a walnut squarely in the middle of one frontal lobe. Winter bases his work in large part on Shobe and Gildeas article in the Journal of the American Medical Association, October 7, 1968. a report which describes “excellent” follow up results with a group of largely older private patients with agitated depressions, There are no control groups and insufficient clinical data. The use of prefrontal lobotomy on individuals with agitated depressions opens the way to massive lobotomization of large segments of the population. The individual with an agitated depression is typically an older woman (18 females to 9 males in Shobes study) who became depressed, hypochondriacal, obsessive and generally tense during her midlife and menopause, and this person has always been a target for whatever current “therapy™ someone wishes to push—— insulin shock, electroshock, anti-depressants, tranquillizers, and now, lobotomy. Peter Lindstrom of San Francisco has been reporting for many years on the use of destructive ultrasonic energy as a substitute for the surgeons knife in frontal lobotomy. He calls it PST for Prefrontal Sonic Treatment. In Medical World News he is reported to have done 475 patients over the past twelve years on a variety of people from children age eleven to elderly people age eighty suffering from just about everything—anxiety, depression, obsessive neuroses, phobias, hypochondriasis, addictions and pain. In a recent as yet unpublished paper presented at the Second International Conference on Psychosurgery (1970) and intended for {he forthcoming hook, Lindstrom presents this case: “A 13-year-old schizophrenic girl became disabled by progressive anxiety and psychosomatic symptoms in spite of drugs and psychotherapy, and was unable to go to school. Following the PST she was able to return to school and now has attended school regularly for four years, achieving passing grades. She has been helping with the work at home. Both the patient and the parents are pleased with the progress. Writing in 1964, and talking about a series of 60 psyehoties and 154 neuroties, he drops that typical statistic without remarking upon it-—72¢9, females among the psychotics, and S07 females among the neuroties, Lindstrom apparently balks at being called a lobotomist. He says that he has been able to titrate his doses of energy so that he can reach a point where the damage is not grossly perceptible and hence does not constitute a lobotomy. But if he's getting a behavioral effect, he's done a lobotomy, even if it’s merely a lobotomy hy disruption of the brain chemist ry. Otherwise its a placebo. Lindstrom, Winter, Scoville, and other lobotomists are making direct attacks on the frontal lobes, This is very likely still among the most popular approaches to the psychosurgery of American patients. 465 H. T. Ballantine, Jr., is performing cingulotomies at perhaps the most pres: tigious general hospital in the world, The Massachusetts General of Boston. Scoville says that this type of surgery represents a “fractional lobotomy” (77, 78), and we have seen its “sedative” taming effect on Asian children. Ballantine also notes that the operation, when done on monkeys, produces “tameness and placidity,” which certainly puts it in the class of the lobotomy in this regard. Scoville, in his introduction to the unpublished Transactions of the Second International, believes that cingulotomy surgery is only successful because it is inaccurate and inadvertently cuts directly into some of the fiber tracts of the frontal lobes. Ballantine makes references to other surgeons with series of 52 and 16 patients, and briefly describes his own series, mostly psychotics, ages fifteen to eighty-three with that typical distribution, 20 females, 14 males. He tells us virtually without explanation, that 22 wére usefully improved, 10 were failures and 8 became symptom free. Only dead people are symptom free. Ballantine writes me that he is still active and has operated on 160 patients since 1965. M. H. Brown and Jack Lighthill of Santa Monica, California, report in 1968 on another group of patients who have had their cingula obliterated. They have done 110 cases, 71% women. Two thirds of them had intractable neuroses, and 91.99, are considered good results, with little explanation of how this evaluation was arrived at. “Destructive emotional forces were removed,” they tell us, includ- ing a reduction in anxiety, phobias, depression, hostility and obsessive thinking. In recent personal correspondence with me. Dr. Lighthill sent copies from letters from other psychosurgeons applauding a “second wave" of psychosurgery around the world. He agreed with Lindstrom, as I mentioned, that 400-600 operations are being done a year in the United States, and said that his own group had operated on 110 patients before 1966, and an equal number, 110 since 1966. Lightbill writes to me and Brown mentions at the Second International, that they see a bright future for operating on criminals, especially those who are young and intelligent, a promise you will see being fulfilled in Mississippi. Neurosurgeon Glenn Meyer and psychiatrists at the University of Texas Med- ical Branch in Galveston have also been experimenting with cingulotomies for the past several years, with a total of 27 performed on “alcoholics” and “drug addicts”, as reported in an unsigned front page article in Psychiatric News, the official newspaper of the American Psychiatric Association, December 16th, 1970 (71). A psychiatrist, Winston Martin, reports on the data in this article entitled “Psychosurgery Hailed in Experimental Texas Study.” The report speaks of re- sults that are “nothing short of spectacular.” “The procedure either helps or com- pletely rids the patient of his emotional illness.” No side-effects are found whatso- ever, but it is noted that 15% of the patients have seizures post-operatively. Their press release announces that a “cure” is found to “diseases” which will go on being incurable for some time (71). Vernon Mark, Frank Ervin and his associates from Boston City Hospital re- port in 1970 the details of one case of depression in which the psychosurgical operation was a great success but the patient killed herself. Briefly here is the story. A woman with a long and difficult psychiatric history is brought in for psychosurgery, specifically a thalamotomy, mutilation of an emotion regulating portion of the brain. Her mother is heavily involved with her and with the psychiatrist and surgeon, and is probably a significant force in getting her to submit to surgery. The patient gets obviously worse after the first mutilation is performed, so she is done again with the convenience of her im- planted electrode. But after the second mutilation she becomes enraged at her psychiatrist and her neurosurgeon, and refuses to talk with or deal with her neurosurgeon any more. Nor will she ever submit to a suggested third operation. Her electrodes are therefore removed, but her rage is dismissed as “paranoid” by V. H. Mark and his associates. Her mood then improves, as we are told, until she reaches a state of “high spirits.” She is allowed out of the hospital to shop whereupon she goes directly to a phone booth, calls her mother to say “goodbye” and takes poison and kills herself. “Her suicide is not seen as the vengeful act of a mutilated soul against her mother and her physicians. Instead her suicide is interpreted as a sign that she was getting over her depression, a “gratifying” result of the operation—the word 93-999 (Pt. II) O-173 -9 466 gratifying cropping up several times. All this is based upon the simplistic notion, sometimes taught to beginning psychiatric residents, that the occasionally ob- served phenomenon of suicide in the midst of an apparent recovery can be ex- plained by a hydraulic conceptualization of increasing energy permitting the patient to suicide before the depression is fully over. This explanation overlooks the individual dynamics, which ery out in this case, This is the only detailed case report I have found in the entire current lobotomy literature, and I am grateful for this one instance in which enough material is provided for an independent judgment of the “gratifying” effects of psycho- surgery. But I have left something considerably more disturbing for my last detailed report—the mutilation of very young children for the admitted purpose of making them more manageable at home, at school or in the hospital. Led by Congressman Gallagher's committee hearings, there has been a public outcry against the drugging of hyperactive children. Now we have physicians performing mutilating surgery upon hyperactive children, sometimes with multi- ple operations that can lead to gross intellectual deterioration. Surgery, unlike medication, is always permanent! And while only one center in the United States is known to be pursuing this work at the present time, there is the current prec- edent of psychosurgery on hyperactive children around the world (8, 9, 19, 62, 64, 75) as well as a past precedent for multiple severely mutilating lobotomies on children have in the United States by IFFreeman, Watts and Williams (25,94). In addition, Ballantine has operated on children as young as fifteen and Lindstrom on children as young as eleven. I also have had personal communications with one well-known American professor of psychiatry who advocates lobotomy on children but feels that “irrational” public resistence would prevent it at the present time, and Brown and Lighthill want to operate on young psychopaths. 0. J. Andy, Professor and Department Director of Neurosurgery at the Uni- versity of Mississippi School of Medicine in Jackson is currently active in op- erating on hyperactive children. He is assisted by a psychologist, Marion Jurko, but lists no psychiatrists on his team. In 1966, he describes his surgery as “under the charge of I. 8. Ravdin. Professor Emeritus of Surgery at the University of Pennsylvania and James D. Hardy, Professor and Chairman, Department of Surgery at the University of Mississippi in Jackson. In a personal letter to me dated May 28, 1971, Andy writes that he has op- erated on 30-40 patients ages seven through fifty, the majority children. In another personal letter to me, his colleague. Jurko, writes that the age range beings at five. The goal is frankly stated by Jurko—to “reduce the hyperactivity to levels manageable by parents”! Andy and his colleague, Jurko, reported their work at the Second International Conference on Psychosurgery, as well as in American and international journals, but nonetheless Andy appears wary of the accusation that these children have “psychiatric problems.” These are not psychiatric cases but “behavioral prob- lems.” presumably with neurological causes, he writes to me, though even he admits that he can find nothing neurologically wrong in many of these children, except something as meaningless as difficulty in a specific form of wrist co- ordination (alternating pronation and supination) which any anxious child might fumble with. Whatever his protests about the non-psychiatric nature of these problem chil- dren, he goes on to describe them as suffering from “some form of hyperactivity, aggression and emotional instability.” He makes this quite specific: the triology of symptoms is hyperactivity, aggression and emotional instability. As we'll see, all of his patients suffer from very well-defined psychiatric problems, and his surgery, thalamotomies and a few cingulotomies, is aimed at nothing more nor less than controlling aggression in difficult children. Andy writes to me: “In relation to the operative results, the category under aggression appears to be alleviated to a much greater extent than the other two categories [hyper- activity and instability ].” But as Freeman and Watts discovered years earlier in Psychosurgery and as Williams and Freeman report in their study of lobotomized children, it can be very difficult to control a child surgically. But you can usually multilate him repeatedly until he stops bothering anyone. Quoting Andy's letter : “On the other hand, although a child who is somewhat retarded and non- productive can also undergo a very dramatic change from an extremely aggressive and hyperactive individual to one who is cooperative and easily managed, although still not productive.” (sic) 467 Just how hard it is to control a child is illustrated in a case which he reports on two occasions. In 1966 he describes J. M. as follows: “A boy of 9, had seizures and behavioral disorder (hyperactive, combative, explosive, destructives, sadis- tic).” [His parentheses.] In the tradition of Freeman's mutilation of children and aggressive adults, he simply operates and operates and operates until the child causes no more trouble. He begins with a bilateral mutilation of the thalamus, and repeats it on one side nine months later. The patient's behavior then “improves” and he can return to special education. After a-year, though, “symptoms of hyper- irritability, aggressiveness, negativism, and combativeness slowly reappeared,” so he brought back and operated on more extensively, this time mutilating the fornix. But now the patient gets worse and shows signs of brain damage from the surgery in the form of the loss of recent memory. So the child’s brain is muti- lated a fourth time. Now, Andy tells us, “the patient has again become adjusted to his environment and has displayed a marked improvement in behavior and memory.” Because Andy repeats the same four cases in a 1970 report, we find out that J. M., this little boy of 9, had about as bad an outcome as we might have imagined. He is of course still easy to manage. “Intellectually, however, the patient is deteriorating.” Andy operates in Jackson, Mississippi, but does not tell us the race of the children he has operated on. Andy does not limit his brain surgery to children. The adolescents upon whom he operates, according to Jurko's letter, often have criminal records, with “ex- plosive, impulsive and unpredictable behavior.” Thus they are fulfilling Brown and Lighthill’s hope for a great future for psychosurgery operating on people with criminal behavior. Jurko does not say, however, whether these adolescents are young and intelligent, as Brown and Lighthill would hope for their surgery candidates. In the absence of an outraged response from the medical and lay public, we will probably be in for a tide of psychosurgical mutilations of children, much as we already have in India, Thailand and Japan! Andy also operates on adults. Here is how his colleague, Jurko, pictures these adults in a letter to me: “The adults are average to above average in intelligence. Many have held jobs of responsibility prior to and even during their years of increasing discomfort (2-10 years). Most of them have a constant pain syn- drome, face, chest quadrant, ete. . . . Most of them will tell you that they are tense, nervous, anxious, depressed, and have strong suicidal thoughts. Many show high specific anxiety and some have evidence of “free-floating” anxiety. These people sound remarkably like very many psychotherapy patients prior to successful therapy. Andy’s case reports in the literature, so limited in number and simplistic in presentation, yield similar thumbnail sketches: in one case, “alconolism, drug addiction, attempted suicide, aggressive and destructive outbursts, nervousness, and emotional instability,” or in another case, “nervousness, spells of shaking all over, explosive anger, attempted suicide.” Earlier we found Brown and Lighthill advocating the use of psychosurgery for young criminals, and now we find Andy and Jurko are operating upon young individuals with criminal records. And at the time that I am making this re- port, a project has been uncovered in the California prison system aiming at one use of psychosurgery for the control of prison inmates (66)! A sharp con- demnatory response from the press, congressional interest, and the work of the Berkeley Medical Committee for Human Rights (Edward Opton, Jr.) has caused the project to be temporarily tabled. But just today I have learned about the planned conference on violence in Houston sponsored by the University of Texas School of Medicine. Scheduled for March 9-11, this conference will give Sano, Ervin, William Sweet, Mark and other psychosurgeons an opportunity to again impress the public and the profession with the possibilities of pacifying prisoners and criminals by means of psychosurgery (98). III: NEWEST ADVANCES IN MIND CONTROL The psychosurgical techniques in this chapter seem especially suited to totali- tarian application on a large scale for a wide variety of citizens, and so I have separated them out for special attention. Each of them has been developed for the specific purpose of controlling the individual without requiring prolonged hospitalization and without preventing him from returning to his family and his 468 work. In each case the blunting of the individual can be carefully tailored to the needs of his family and his job. The first study involves the direct use of “psychotherapy” by psychiatrists to monitor the gradual, progressive lobotomization of the individual. It first ap- peared in 1963 in Current Psychiatric Therapy, a widely read American year- book, and it is still continuing. The work, described as “progressive leucotomy,” is reported by three Britishers, H. J. Crow, R. Cooper and D. G. Phillips, Burden Neurological Institute and Frenchay Hospital, Bristol, England. The technique involves a carefully organized management of the individual patient as he undergoes progressive electrical frontal lobotomy over a period of half a vear or more under the direct supervision of a psychotherapist. The targets of the new technique are people with “anxiety-tension states” and “obsession syndromes,” particularly individuals “of good intelligence and per- sonality,” who “sometimes have heavy responsibilities.” The goal is a carefully titrated lobotomy which blunts the individual's emotional responsiveness without incapacitating him in the performance of these responsibilities. The technology utilizes 24-36 tiny electrodes which produce small coagulations of tissue when the current is turned on. After they are implanted within the frontal lobes through two holes in the skull, they can then be left in place within the brain for up to seven months, taped to the scalp in a hidden fashion which permits the patient to walk around and even to leave the hospital between his treatments. His physicians can then talk with his family and with the ward staff to evaluate how “good” his behavior has become, before subjecting him to further partial lobotomies. That these physicians are not talking about minor damage to the brain is indi- cated by the admission that they “overdid it” in one of their fourteen cases, though they do not tell us what happened to the victim of this error in medical judgment. As a psychiatrist, T am haunted by one aspect of this technique, the participa- tion of the “psychotherapist,” who literally sits beside his patient conducting an interview with him while the neurosurgeons gradually turn up the electrical cur- rent. In this manner the “therapist” monitors and titrates the amount of tissue destruction required to change the patient’s ongoing emotional reactions. The patient cannot tell when his brain is being coagulated, but the therapist can tell immediately, since destruction of frontal lobe tissue is immediately reflected in a progressive loss of all those human functions related to the frontal lobes— insight, empathy, sensitivity, self-awareness, judgment, emotional responsiveness, and so on. When Freeman and Watts' (1950) operated on their patients without general anesthesia, the patients sometimes cried out that they were dying from the sur- sory as they felt their vital mental functions being cut away. The surgeons would then tell them to pray or to sing patriotic songs or simply ignore them while coing on with the cutting. The newer methods of these Britishers are much more subtle, but basically the same. The patient is fussed over and given reassurance. And the process is so eradual and remote from him—controlled electrically with no obvious interven- tion taking place—that the patient never realizes what is happening to him. In fact. the patient gets so mueh attention from the ward team that other patients on the ward, who cannot discern the gradual extincition of his human qualities. ask if they can have the treatments, too. II. J. Crow reports again on his work in 1965. and his report is noteworthy as a typical lobotomist article, all technology, a few sparse statistics about his successes, many diagrams, and not one sentence that could be called a clinical or human description of a patient. He continues to use “up to 34 separate small electrodes widely spread like a net across each frontal lobe,” and has added electrodes in the anterior portion of the cingulum for patients with “obsessional” symptoms. thus performing both lobotomies and cingulotomies on some of his patients. This article not only leaves out any deseriptions of the patients beyond these one and two word diagnoses (“all anxiety syndromes, some having obsessional features”). it also seems to leave out that one disastrous case which they admit they “overdid™ in the first article. Thus Crow says, “Of the first 25 cases . . . all have returned to a social life which is more or less normal.” 469 We are told that individual and group psychotherapy goes on during the pro- gressive lobotomization and then that intensive forms of therapy continue after- ward for years. What we see described is a very directive influence, the sort we might expect would work with someone who has been brain damaged : “From my experience, patients at this stage are amenable to, and eagerly seek advice about their future. Common-sense planning of their work and leisure, and advice about more ordinary attitudes in personal relationships, allows them to get started in a workable pattern of new life which they soon stamp with their own new and individual characteristics. They often need reassurance that an ap- propriate anxiety about, say, health or money is not a sign of returning illness. After an intensive course of advisory therapy an interview, often short, every month or two for half a year with lengthening intervals thereafter, is usually sufficient to help the patient to make and keep his readjustments.” He then says that some of these patients “require support for a long time,” and goes on to describe social work, welfare, rehabilitation and psychological services, all of which may be brought to bear upon the patient. Their lobotomized patients are thus given extensive often long-term services probably made available to very few if any other patients in Great Britain, cer- tainly not to patients suffering from “anxiety syndromes,” and yet they never once mention the possibility that whatever useful effects they achieve may be due entirely to these massive efforts mobilizing psychiatry, social work, welfare, rehabilitation and psychological services. And of course they have no control groups with patients who are given these services without lobotomies ! If the patients are not brain damaged, why do they need such intense supportive help in the management of the details of their everyday life? Why would regular psychotherapy be contra-indicated as “unnecessary and unprofitable at this stage, and will at best delay intrapsychic and social adjustments”? Freeman and Watts also found that lobotomy patients needed daily guidance and were poor candidates for psychotherapy, but the reason was obvious in their case— the surgically dam- aged patients had lost the capacity for insight and judgment. Crow reassures us that there are no bad side-effects, specifically no ‘“‘insensi- tivity in social relationships.” But a few pages after this reassurance, he tells us that the surgery sometimes produces “an over-optimistic attitude to his own capacities and to others’ good will.” He also seems to imply that this may often be a “permanent euphoria” typical of brain damaged patients: “This can, of course, be a permanent euphoria, but I have seen cases where it has been a transient phenomenon and seemed to be a true joyfulness of release.” This kind of euphoria from brain damage is apparent in the two largest Ameri- can studies from the 1950's: Greenblatt, Arnot and Solomon, and Freeman and Watt. Freeman and Watts’ book is filled with case histories that read like classic studies of brain damaged individuals. In the other study, Harry Solomon in the introduction speaks of a “joyfulness” much as Crow does, but in a remote portion of the book the psychologist says the clinicians are too biased to be trusted and that the patients are actually brain damaged and “slap-happy.” Many followup studies have found severe brain damage and deteriorating states years after lo- botomy (23, 59, 61, 93). Crow has sent me a page summary of his report at the Second International Conference on Psychosurgery, August 1970, in which he reports that he has done 103 patients since 1958. He summarizes a very naive and crude psychophysiologi- cal theory to justify his surgery, one in which, for example a specific region, “the anterior para-cingulate” is “involved in retaining mental items in consciousness, and thus to obsessionalism.” Unlike some other lobotomists, he is unwilling to admit the inter-relatedness of human brain and mind functions, and the general blunting function of all psychosurgical interventions. Implanting electrodes into the brain is at the heart of all of what is called ESB, for Electrical Stimulation of the Brain. The “stimulation” can be mild and prob- ably reversible, or permanently destructive, depending upon the strength of the electrical current. One of the most active ESB psychosurgeons is Robert G. Heath, Chairman and Professor of the Department of Psychiatry and Neurology at Tulane in New Orleans. He will soon be publishing a new book as part of the revival of psychosurgery. According to Medical World News, which provides a disturbing photograph of one of his patients “wired up,” Heath holds this record of 125 electrode implan- 470 tations at one time, a brain turned into a human pincushion. These tiny electrodes are attached to wires or injection catheters which must also pass through the brain tissue. Heath claims that these implantations are “harmless,” but in an aside he lets on that they are in fact so traumatic that “studies were not initiated until a minimal period of six months following operation, assuring elimination of any variation introduced by operative trauma, e.g., edema, anesthetic effects.” 1963, p. 572. Six months is a long recovery time for a non-traumatic procedure. But since Heath will let a patient remain wired up for years, six months may not seem a long duration to him. The justification for all this is “therapy,” and Heath claims that it is never done for any reason except “therapeutic.” But if you read his articles, you will find almost nothing about therapy in them. Sometimes he doesn't even mention what disease the patient is supposed to have! And many of his “results” offer nothing more than a sentence or two about a curious response of some scientific interest elicited by an obviously non-therapeutic stimulation exercise. And in keeping with this, and typical of most modern psychosurgical literature, his em- phasis is almost entirely on developing a new technology. There are pages and pages about technique for every few lines about its effects upon the patient. In “Electrical Self-stimulation of the Brain,” Heath describes individuals who wear their own self-stimulation units on their belts, transisterized packets, which they can take with them as they walk around, even as they go to work outside the hospital. These experiments often involve research into “pleasure centers” within the brain, and sometimes patients will indulge themselves at the rate of more than one thousand stimulations an hour. In one case a man pressed one of his several buttons in a “frantic” fashion be- use it built him up toward a feeling of orgasm that he was never quite able to consumate. This particular man’s problem was “narcolepsy,” a tendency to fall asleep unexpectedy in inappropriate situations, and since he wore his pack on his belt, his friends or other patients could simply press his “wake up” button for him when he began to doze off. Electrodes can be implanted in pain centers as well as pleasure centers. The totalitarian potential is beyond belief-—a permanent set of buttons for pain and pleasure which other people can control. And as we'll see when we get to Delgado, these portable stimulators can be manipuated by remote control, even by com- puters at a distance! As we will also see in Delgado’s work, sexual responses seem particularly easy to elicit by ESB. Another of Heath's patients was so subject to this kind of con- trol that he would make a sexual reference whenever one particular electrode was activated. And though Heath gives us no clinical details about this or any other of his patients’ experiences, Medical World reports that Heath has used these techniques to treat homosexuals and frigid women. On rare occasions Heath elaborates a philosophical basis for his work. Writing in The Journal of Neuropsychiatry, for example, he takes a strong moral stand that Einstein's level of thought was better than Christine Keeler's, the woman who created a scandal around her sexual activities with British politicans in 1963. Heath explains that Einstein's thought was of a higher level because Ein- stein's thought was less pervaded with “emotion and wishes.” It is an exact equivalent of Knight's statement that “primitive emotions” are bad emotions. And these men present these observations as their justificaion for coagulating, radiating slicing up or stimulating the brains of their patients. In a more recent publication (1968A), again technological rather than clinical, he lists some of the sites of “pleasure responses” and they correspond to the same areas of the midbrain that the lobotomists are now destroying surgically to pro- vide us with more lobotomists may be simply obliterating the patient's capacity to respond pleasurably to life, so that the patient doesn’t feel frustrated in his empty life. Heath's concerns go far beyond the laboratory. He was elected President of the Society for Biological Psychiatry in May, 1969, at their Miami Beach annual meeting. In his presidential address, published as “Perspectives in Biological Psychiatry,” he takes the stand that all the significant advances in psychiatry have been biological, and he postulates that so-called mental patients suffer from “inappropriate anxiety.” Therefore the cure—“instantaneous replacement of irrelevant anxiety with positive pleasure feelings” by psychosurgical techniques. He becomes quite specific in his presidential address when he talks about drug addiction. Is the root of the problem poverty and racism, since drug addiction 471 around the world and in America is overwhelmingly a problem of the poor! No, it’s not that. Is the new phenomenon of drug addiction among middle class youth related to the disaffection of youth from the society? No. Does it relate to the tremendous profits made by criminal groups from promoting drugs among the poor? No. What then is the problem of drug addiction according to Dr. Heath? Drug addiction, he says, is an attempt at self-medication for pleasure in people who have a neurologic defect in their pleasure centers! His cure then is corrective surgery or a better, more efficient pleasure producing compound. Three or four years ago (1968B), Heath had already reported psychosurgical operations on 58 patients, at least 44 with psychiatric illnesses. By now he has most likely done many more. But the influence of his work goes far beyond the clinical through his positions of leadership within the psychiatric world, includ- ing his directorship of the Department of Psychiatry and Neurology at Tulane. Perhaps the first of the new batch of books on electrical psychosurgery is Depth-Electrical Stimulation of the Human Brain by Mayo Clinic trained C. W. Sem-Jacobsen, M.D., who has returned to Norway, where he is Medical Director, Gaustad Sykehus, Oslo. Sem-Jacobsen’s book is a classic of technology devoid of human considerations. The book can be read from cover to cover without ever gaining a clear idea what purpose all this psychosurgical gadgetry will serve. His discussion of ethics is limited entirely to medical considerations, such as not causing undue pain, avoiding unnecessary surgery, showing concern for the patient, and the like, all admirable, but hardly inclusive when dealing with physical control of the human mind. We learn more about Sem-Jacobsen’s work from his unpublished report to the Second International Conference on Psychosurgery, and from a description of it in Medical World News. He has operated on at least 132 patients for various psychiatric problems. Feeding half a dozen or more electrodes through a single hole in the skull, he can elicit, he says, almost every mood and emotion—depres- sion, wild euphoria, grave fright, irrational confusion. His methods for treating people involve stimulating the brain electrically until the unwanted behavior is located, and then coagulating the area with electricity. Though technologically exacting, this method must rank as one of the most anachronistic, considering the outmoded theory behind it—that mental illness can be reduced to foci of disordered brain tissue. That theory was outmoded and even an embarrassment to lobotomist Freeman (1950) when Moniz first proposed it in 1935 to justify the very first mutilations on a large scale. But since Sem-Jacobsen doesn’t report anything about his patients’ lives—not even the usual thumbnail sketches—in his book or in any sources available to me in the literature, we have no idea what his psychosurgery is actually doing to his clients. The political potential of lobotomy and electrical stimulation of the brain is promoted outright by Jose M. R. Delgado, M.D., Professor of Physiology at Yale University and author of the recent book Physical Control of the Mind, “Toward a Psychocivilized Society,” published in 1969 and available in paperback. Del- gado was brought to America from Spain by John Fulton, an American physi- ologist whose animal lobotomy experiments and whose enthusiasm for experi- menting on the human brain inspired Moniz and Freemand and whose book, Frontal Lobotomy and Affective Behavior, praises Moniz for his courage in de- fying the outrage of the medical community against his brain mutilations. Delgado’s goal is nothing less than physical exploration and physical control of the mind for the advancement of civilization : “The thesis of this book is that we now possess the necessary technology for the experimental investigation of mental activities, and that we have reached a critical turning point in the evolution of man at which the mind can be used to influence its own structure, functions and purpose, thereby ensuring both the preservation and advance of civilization. The following pages contain a dis- cussion of what the mind is, the technical problems involved in its possible con- trol by physical means, and the outlook for development of a future psychocivi- lized society.” P. 19-20. Note that he is specifically talking about tampering with the “structure, func- tions, and purpose” of the mind and “Its possible control by physical means.” After pages of documentation about what has already been done hy a few in- vestigators working with very little funds, he then proposes a giant billion dollar government investment in mind control : “National agencies should be created in order to coordinate plans, budgets. and actions just as NASA in the United States has directed public interest and 472 technology, launching the country into the adventures and accomplishments of outer space.” P. 259. He advocates a complete educational program, from infancy and nursery through adulthood and mass education for the indoctrination of the people into a respect for physical control of the mind : “The mass media must be mobilized for this purpose, and preparation of en- tertaining and informative programs should be encouraged and promoted by the neurobehavioral institutes.” P. 262. In his introductory remarks to the section on controlling “behaving subjects” he promotes the ideal of remote control of human beings by other human beings. He points out that he can open garage doors from a distance, adjust a television set without leaving our seat, and direct orbiting space craft from earth.. Then he makes his point: “These accomplishments should familiarize us with the idea that we may also control the biological functions of living organisms from a distance. Cats, mon- keys, or human beings can be induced to flex a limb, to reject food, or to feel emotional excitement under the influence of electrical impulses reaching the depths of their brains through radio waves purposefully sent by an investigator. P. 75. (My Italic.) But he is aware that this may disturb some of his readers, and so he denies time and again that the human being can be controlled in any “bad” ways, turn- ing them into robots, or the like. But he says outright that the problem fascinates him and preoccupies him : “.. .we have the possibility of investigating experimentally some of the classic problems of mind-brain correlations. In addition to new answers, implanting of electrodes has introduced new problems: Is it feasible to induce a robotlike performance in animals and men by pushing buttons of a cerebral radio stimu- lator? Could drives, desires and thoughts be placed under the artificial command of electronics? Can personality be influenced by ESB? Can the mind be phy- sically controlled.” P. 97. Delgado is working on the ultimate lobotomy-—direct long term physical con- trol of human beings. IHe has even gone so far as to work it out cosmetically : “Nome women have shown their feminine adaptability to circumstances by wearing attractive hats or wigs to conceal their electrical headgear, and many people have been able to enjoy a normal life as outpatients.” I’. 88. Again despite his denials that there is anything reminiscent of 1984 about all this, he has been working on remote control of humans by computers which can selectively inhibit various emotions as they are detected and recorded from brain waves: “A two-way radio communication system could be established between the brain of a subject and a computer . . . anxiety, depression, or rage could be recognized in order to trigger stimulation of specific inhibitory structures.” I’. 201. While this is “speculative,” it is by no means a remote possibility. If a few men can do what they have done working in isolated labs with little financial support. they might in a crash program develop complete computerized control of humans in a matter of years. They are well on the way already. Using the computerized remote control technique, they have been able to suppress the activity of a monkey's amygdala simply by putting an inhibitory or negative and painful stiumlus into the brain every time the amygdala sent out any signs of activity (p. 92). The amygdala is that portion of the brain which the psychosurgeons cut out in order to tame human beings. There is no doubt that they will soon be able to do this to humans with computers and electrodes by remote control! The experiments Degaldo describes with monkeys have gone further than any he tells us about with human beings, but the model can be easily transferred to human behavior. In groups of monkeys he has been able to activate the followers to depose the leaders, and to activate the leaders in more aggressive activities against the followers, But he and his colleagues have already done enough to show us what is in store for mankind in the “psychocivilized” society. Not only do we have the work of Heath and Sem-Jacobsen with chronically implanted electrodes and human beings working and living with self-stimulator packs on their belts, but we have the reports of Delgado himself. 473 In one case, a 36-year-old woman was stimulated electrically : ‘“ . .. the patient reported a pleasant tingling sensation in the left side of her body ‘from my face down to the bottom of my legs.’ She started giggling and making funny comments, stating that she enjoyed the sensation ‘very much.’ Repetition of these stimulations made the patient more communicative and flirtatious, and she ended by openly expressing her desire to marry the therapist.” P. 145. This was a woman who had no interest in her therapist and who showed no unusual behavior when not under ESB. Another woman who was ‘rather reserved and poised” became ‘more intimate” with the therapist when under ESB: “This patient openly expressed her fondness for the therapist (who was new to her), kissed his hands, and talked about her immense gratitude for what was being done for her.” P. 145. In a third case, an 11-year-old boy who was otherwise normal in his behavior became so sexually excited about his male therapist while being stimulated electronically that he defied his identity and decided that the would rather be a girl: “Following another excitation he remarked with evident pleasure: ‘You're doin’ it now,” and then he said, ‘I'd like to be a girl.’ ” P. 147. Delgado is also able to control both physical activity and the person's inter- pretation of that activity. In one case a patient is being stimulated and doesn’t realize it, so that when the stimulation makes him turn and look around in robot-like searching behavior, he makes up explanations to justify what he is doing, such as “I heard a noise,” or “I was looking under the bed” (p. 116). In another case where the client is being made to flex his hand, he is told to fight the impulse, but he cannot. He admits, “I guess, Doctor, that your electricity is stronger than my will.” In another example, Delgado shows that the subject's state of anxiety can sometimes be brought under the direct control of the psychosurgeon: “One could sit with one’s hand on the knob and control the level of her anxiety.” P. 135. The degree of overall brain control is then alluded to in experiments which we can only imagine : “Often the patients performed automatisms such as undressing or fumbling, without remembering the incidents afterward. Some of our patients said they felt as if their minds were blank or as if they had been drinking a lot of beer.” P. 174-175. And then he concludes his section on “Electrical Activation of the ‘Will,”” with this portentious pronouncement : “We may conclude that ESB can activate and influence some of the cerebral mechanisms involved in willful behavior. In this way we are able to investigate the neuronal functions related to the so-called will, and in the near future this experimental approach should permit clarification of such highly controversial subjects as “freedom,” “individuality,” and ‘spontaneity’ in factual terms rather than in elusive semantic discussions. The possibility of influencing willful activities by electrical means has obvious ethical implications, which will be discussed later.” P. 189. Delgado does discuss these ethical implications and invokes the model of in- voluntary psychiatric treatment and electroshock therapy (p. 216) as justifica- tions for going ahead with ESB control. The degree to which Delgado wants to control people comes out most clearly as he summarizes what's wrong with current therapy and how much more effec- tive ESB can be. “Psychoanalysis requires a long time, and a person can easily withdraw his cooperation and refuse to express intimate thoughts.” P. 216. Even electroshock is no good in part because he can’t use it on normal people: Electroshock is a crude method of doubtful efficacy in normal people.” P. 216. Now listen to what his methods have to offer compared to analysis or shock : “Although electrical stimulation of the brain is still in the initial stage of its development, it is in contrast far more selective and powerful; it may delay a heart beat, move a finger, bring a word to memory, or set a determined behavorial tone.” P. 216. He offers us a vision of generals and armies controlled by Electrical Stimula- tion of the Brain—in the interest of “preventing violence” of course (p. 176). And finally leads himself into sophistries about freedom and individually which under- mine the basic tenets of western political freedom : 474 “The individual may think that the most important fact of reality is his own existence, but this is only his personal point of view, a relative frame of reference which is not shared by the rest of the living world. This self-importance also lacks historical perspective, for the brief existence of one person should be con- sidered in the terms of the world population, mankind, and the whole universe.” Pr. 236. He then goes on to attack the notion that man has “the right to develop his own mind,” to develop his own unique potential “while remaining independent and self sufficient.” As he concludes: “This kind of liberal orientation has great appeal, but unfortunately its assump- tions are not supported by neurophysiological and psychological studies of intra- cerebral mechanisms.” PP. 239. Delgado is the theoretician of the lobotomists, the great apologist for Techno- logic Totalitarianism (17), complete with an outright attack on “liberal” politics, meaning not the liberalism of the left, but principles of personal autonomy, inde- pendence and freedom, man’s “inalienable rights™ as annunciated in the Declara- tion of Independence. IV. CONCLUSIONS AND RECOMMENDATIONS All forms of psychosurgery blunt the individual's emotions and make him more docile. Each technique attacks and mutilates brain tissue that has nothing demon- strably wrong with it, and each does this within the delicately balanced “limbic system” of the brain which harmonizes the most highly developed human capaci- ties, including emotional responsiveness. While the more advanced methods of brain stimulation have a greater variety of effects, to the extent that they destroy tissue within the brain, they will tend to reduce emotional responsiveness as “partial lobotomies.” And of course they subject the individual to the control of others. Scientifically, lobotomy and psychosurgery have no rational or empirical basis. Empirically, no study has ever been done involving matched control groups. That ix, no one has ever taken two similar groups and subjected one to surgery and left one alone for compariscn. This is the scientific method at its best and it is totally absent from the hundreds of pro-lobotomy articles in both the first and second waves of psychosurgery. Three controlled studies have been done retrospectively matching as nearly as possible the surgical groups and the regular hospital population upon which no surgery was done (Robin, Vosburg and McKenzie). In all three studies lobotomy was found to have no beneficial effect whatsoever. Vosburg, Moser and even pro- lobotomy followups such as Dynes and Miller found that the lobotomy surgery had left the patients with crippling brain damage. Vosburg found that the pa- tients had surgically-produced brain damage as well as their initial psychiatric difficulties and that “In sum, they act as if they have been hurt.” The current literature is as woefully inadequate scientifically as the earlier literature, and in fact bases itself on studies by Shobe, Tooth and Newton and others which fall by every standard of scientific research. The scientific rationale is no more solid than the empirical evidence. As we have seen, psychosurgery is a uniformly damaging operation—exactly what one would expect from mutilating normal brain tissue. There can be no rationale for “helping” an individual by blunting his highest adaptive mechanisms. This method simply hides the individual's failure to adapt by partially doing away with the individual's responsiveness. In every case we are dealing with the eradication of symptoms by partially eradicating the individual. To repeat the obvious, improvement in function cannot follow multilation of the functioning brain. In defense of psychosurgery, the alleged biological origin of “mental illness” is often raised. Elsewhere Thomas Szasz and T (14, 15, 17) have raised serious questions about the medical model for human problems. But this distinction is not even relevant here. If we grant that some problems may be biological, it makes even less sense to mutilate the biologic process. Since the brain is such a delicately balanced instrument with unimaginable inter-relations, sense- less mutilations of one part or another can only disrupt the harmony still further, resulting in a general subduing of the organism and a general malfunc- tion of his adaptational processes. 475 Vidor describes how an artist can no longer create after the lobotomy, and the dean of lobotomists, Walter Freeman (1959), tells us how in the newer modified lobotomies creativity is still reduced to zero : “What the investigator misses the most in the more highly intelligent individ- uals is the ability to introspect, to speculate, to philosophize, especially in regard to the self.” P. 1526. “Creativeness seems to be the highest form of human endeavor. It requries imagination, concentration, visualization, self-criticism, and persistence in the face of frustration, as well as trained manual dexterity. . . . Theoretically, on the basis of psychologic and personality studies, creativeness should be abolished by lobotomy. . . . On the whole, psychosurgery reduces creativity, sometimes to the vanishing point.” P. 1534-5. He then says that some businessmen can return to work, but that they too are impaired : “Although they may not become leaders in their professions, they serve ade- quately and comfortably.” P. 1535. This is not the writing of an anti-lobotomist, but the statements of the world’s most experienced psychosurgeon, an Honorary President of the new International Association for Psychosurgery. And the words are written as the definitive state- ment on psychosurgery in the prestigious source book, The American Handbook of Psychiatry (1959). Ethically, psychosurgery is equally unsound. At best it blunts the individual, and at worst, it destroys all his highest capacities. As Freeman has said on many occasions, this amounts to destroying the “self” of the individual (1950, 1959). The “self” is the ethical foundation of many modern psychological theories, where it often appears in terms of “identity” or ‘“self-insight,” and other related concepts. Similarly, psychosurgery blunts or destroys the individ- ual’s capacity for autonomy and independence (14). Crow, a very modern British psychosurgeon, describes how his clients need careful guidance and support for years after their surgery in the most simple life problems. Psycho- surgery offends the whole western ethical tradition of respect for the individual. Politically, the dangers from psychosurgery are so vast as to defy summary. In his definitive text in 1950 we can see the political function of psychosurgery in the state hospital system in terms of Freeman's first four categories of success over a fifteen year period (p. 515) : First, “older patients.” Second, women more than men. Third, Negroes especially, particularly Negro females, his most successful group. Fourth, “simpler” occupations. Thus he used the surgery to blunt those people whom the society found most vulnerable and most easily returnable to relatively non-functional or low level tasks within the society. Greenblatt, Arnot and Solomon blithely sum up that “Freeman and Watts offer the opinion that results of prefrontal lobotomy are slightly better with females, Jews and Negroes.” p. 21. Freeman and Watts did not say slightly. Both Freeman and Watts and Greenblatt, Arnot and Solomon in their classic studies say that a major function of state hospital lobotomy is to make it easier and economically cheaper to keep the patients institutionalized! No wonder, as Greenblatt, Arnot and Solomon again quote their colleagues, “Freeman and Watts reported that patients showing the best post operative results were those who were confused, dull, and retarded for several days after operation,” p. 23. We are again seeing an attempt to revive the use of psychosurgery to blunt and control inmates—Andy with institutionalized children, the California prison system with difficult prisoners (66) and the upcoming Houston conference on psychosurgery approaches to violence and penitentiary problems (98). We are on the verge of a new slaughter of inmates—men, women and children. But the total political threat of psychosurgery is considerably larger than the institutional threat. In my newest novel, The Hebrew Disease (15), 1 de- scribe a futurist use of psychosurgery for political control within the society. 476 But while I was writing this novel, I had no idea that Delgado had already formulated a political program for the control of the society under an enormous NASA-like project for physical control of the mind. Nor did 1 know that he and others like Heath were already far along in experimenting with implanted electrodes for the longterm (years!) control of individuals—even by remote control! Nor did I know that a number of social, economic and political prob- lems—drug addiction, alcoholism, homosexuality, depressions of old age— were being dealt with psychosurgically. We are in danger of creating a society in which everyone who deviates from the norm will be in danger of surgical mutilation. The increasing application of these methods to “neuroties” and to people who are already well enough to work and to live with their families raises the specter of wide applications, particularly of women, who continue to be the majority of victims. On a tape recording made for the archieves of the American Psychiatric Association Museum and Library, Walter Freeman discusses the original outery against lobotomy when it first began in Portugal (29). Dismissing this outery, Freeman laughs and quips “Oh, there's plenty of Portuguese.” This is an attitude which cannot be permitted to thrive again in America as it did in the 1940's and 1950's when 50,000 victims fell to psychosurgery. Russia outlawed lobotomy in 1950 (45). We are too far behind them in this regard. While accepting these scientific, ethical and political objections to psycho- surgery in general, some well-meaning physicians and laymen still see a use for psychosurgery in the relief of intractable pain and anxiety in terminal illness (96). But the use of psychosurgery for this purpose borders on euthanasia—a partial destruction of the responsive “self” or “identity” of the living human being—and therefore suffers from all the dangers inherent in euthanasia. But still more important, to allow its use for this one purpose opens up experimenta- tion on thousands of dying patients and further promotes its future use for other more dangerous purposes. Some individuals with a civil libertarian orientation also believe that while psychosurgery is personally repugnant to them it should nonetheless be left up to individual choice. According to this principle, involuntary psychosurgery would be abolished, but not voluntary psychosurgery. But the distinction between voluntary and involuntary becomes very blurred within psychiatry. We have already found examples of “voluntary” psychosurgery performed on a chronic gambler and upon sexual deviants who were under threat of criminal prosecu- tion. The psychosurgery to be performed upon the prisoners in California was also suppose to be “voluntary.” And as I have analyzed in some detail (13) and described at great length in my first novel (15), so-called voluntary treatment is often forced upon the psychiatric patient by threats and outright coercion even in the best of voluntary hospitals. There is still another reason to prohibit voluntary psychosurgery, and that has to do with its mutilating effect upon the individual's mind. To the extent that psychosurgery “blunts” the individual, I personally feel that it partially kills the individual. If we accept this concept, then we can allow the person the right to suicide or partial suicide but we cannot allow a second party to aid him in the suicide. Just as it is against the law to take a person’s life even with his consent, so it should be against the law to take part of a person’s life, even with his consent. I'or these reasons, I believe that all forms of psychosurgery should be out- lawed in America as they were in Russia (45). The outlawing of psychosurgery can be accomplished directly by federal and state legislation. It can also be accomplished indirectly by taking psycho- surgeons to court when this seems warranted. Suits might be based upon any tendency to make exaggerated claims, thus leading to “uninformed consent” on the patient's part. Other suits might be brought upon the grounds that the patient has been robbed of his civil rights by being deprived of his mental capacity to exercise them. In the meanwhile, the public must apply the sort of pressure that has brought a temporary stop to psychosurgery in the California prisons. Psychiatric hos- pitals, institutions for the mentaly retarded and general hospitals (where most are now being performed) must prohibit psychosurgery within their walls. 477 Hospital review committees must set up where necessary to determine if ques- tionable cases fall into the category of psychosurgery—brain surgery which multilates healthy tissue for the purpose of blunting emotions and controlling personal conduct. Well over 100,000 persons have already been subjected to psychosurgery around the world, including 20,000 in England, perhaps 50,000 in America, many more thousands in Canada. We are now in the midst of a resurgence, including multipule forms of psychosurgery upon hyperactive children. It is time to take action before this revival takes on the proportions of the first wave that peaked in the 1950's. BIBLIOGRAPHY 1. Andy, O. J., “Neurosurgical Treatment of Abnormal Behavior,” Amer. J. Med. Sci. (1966) 252 :232-238. See reference 99. 2. Andy, O. J., “Thalamotomy in Hyperactive and Aggressive Behavior,” Confin. Neurol. (1970) 32:322-325. 3. Anonymous, ‘“Leucotomy Today,” Lancet (1962) 2:1037-8. 4. Anonymous, “Standard Lobotomy. The End of an Era,” Canadian Med. Assoc. J. (1964) 91:1228-1229. 5. Anonymous, “Brain Surgery for Sexual Disorders,” Lancet (1969) 4 :250-251. 6. Bailey, Harry ; Dowling, John; Swanton, Cedric; Davies, Evan, “Studies in Depression: Cingulo-tractotomy in the Treatment of Severe Affective Illiness,” Med. J. of Australia (1971) 1:8-12. 7. Baker, Earle; Young, M.D. ; Gauld, D. M. ; Fleming, J. F. R., “A New Look at Bimedical Prefrontal Leucotomy,” Canadian Med. Assoc. J. (1970) 102 :37-41. 8. Balasubramaniam, V.; Kanaka, T. S.; Ramanugam, P. V.; Ramanurthi, B. “Sedative Neurosurgery,” J. Indian. Med. Assoc. (1969) 53 :377-381. 9. Balasubramaniam, V.; Kanaka, T. S.; Ramanugan, P. V.; Ramanurthi, B.; “Surgical Treatment of Hyperkinetic and Behavior Disorders,” Int. Surg. (1970) 54 :18-23. 10. Ballantine, Jr., H. T.; Cassidy, Walter; Flanagan, Norris; Morino, Raul, Stereotaxic Anterior Cingulotomy for Neuropsychiatric Illness and Intractable Pain,” J. Neurosurg. (1967) 26 :488-495. 11. Barhol, H. §., “1,000 Prefrontal Lobotomies—A Five-to-ten-year Follow-up Study.” Psychiat. Quart. (1958) 32 :653-678. 12. 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(1968) 29 :513-519. 19. Chitanondh, H., “Stereotaxic Amygalotomy in Treatment of Olefactory Seizures and Psychiatric Disorders with Olefactory Hallucinations,” Confin. Neurol. (1969) 27:181-1960. 20. Crow, H. J.: Cooper, R.; Phillips, D. G., “Progressive Leucotomy,” in Mas- serman, Jules, Current Psychiatric Therapies, I11, Grune and Stratton, 1963. 21. Crow, H. J., “Brain Surgery in the Treatment of Some Chronic Illnesses,” a paper given at the British Council for Rehabilitation of the Disabled, Tavistock House (South), Tavistock Square, London, 1965. Published separately. 22. Delgado, Jose M. R., Physical Control of the Mind—Toward a Psycho- civilized Society ; Harper Colophon, 1969. 478 23. Dynes, John B., “Lobotomy—Twenty Years After.” Virginia Med. Quart. (1968) 95 :306-308. 24. Evans, Philip, “Failed Leucotomy with Misplaced Cuts: a clinico-anatomi- cal study of two cases,” Brit. J. Psychiat. (1970) 118 :165-170. 25. Freeman, Walter and Watts, James, Psychosurgery; Charles CO. Thomas, 1950. 26. Freeman, Walter, “Psychosurgery,” in Arieti, S., American Handbook of Psychiatry, 11; Basic Books, 1959. 27. Freeman, Walter, “Psychosurgery.” Am. J. Psychiat. (1954) 121:653—-655. 28. Freeman, Walter, “Recent Advances in Psychosurgery,” Med. Ann, D.C. (1965) 34:157-160. 29. Freeman, Walter, A Taped Interview for the American Psychiatrie Associ- ation Museum Library, April 17, 1968. 30. I'reeman, Walter, “Frontal Lobotomy in Early Schizophrenia : Long follow- up of 415 cases,” Brit. J. Psychiat, (1971) 119 :621—4. 31. Gallagher, Cornelius E., “Federal Funds of : 3,000 to Harvard Psychologist B. ¥. Skinner,” Congressional Record, H12623-12633, Dec. 15, 1971. A summary of investigations into “mind control.” 32. Greenblatt, Milton; Arnot, R.; Solomon, H., Studics in Lobotomy, Grune and Stratton, 1950. 33. Greenblatt, Milton and Solomon H., eds., Frontal Lobes and Schizophrenia, Springer Publishing Co., 1953. 34. Group for the Advancement of Psychiatry, Lobotomy,” in Report #6, 1948. 35. Hassler, R. and Dieckmann, G., “Stereotaxic Treatment of Compulsive and Obsessive Syndromes,” Confin. Neurol. (1967) 29 :153-158. 36. Health, Robert G., “Electrical Self-stimulation of the Brain in Man.” Amer. J. Psychiat. (1963) 120 :571-577. 37. Heath. Robert G., “Development Toward New Physiologic Treatments in Psychiatry,” J. Neuropsychiat. (1964) 5:318-331. 3K. Heath, Robert G.: Stanley, John B.: Fontana. Charles J., “The Pleasure Response : Studies in Stereotaxic Technics in Patients,” Kline and Laska, ed., Computers and Electronic Devices in Psychiatry; Grune and Stratton, 1968. 39. Heath, Robert G., and Guerrero-Figuroa, R., “Stimulation of the Human Brain,” Acta Neurol" Latinoamer, (1968) 14 :116-124. 40. Heath, Robert G., “Perspectives for Biological Psychiatry,” Bio. Psychiat. (1970) 2:81-87. 41. Hirose, S., “Orbito-ventromedial Undercutting, 1957-1963," Amer. J. Psy- chiat. (1964) 121:1194-1202. 42. Holden, J. M. C'.; Ttil, T. M. Hofstatter, L.. “Prefrontal Lobotomy : Stepping- Stone or Pitfall?” Amer. J. Psychiat. (1970) 127 :591-598. 43. Kalinowsky, Lothar, “Psychosurgery Panel,” Dis. Nerv. Sys. (Feb. 1969) 30 suppl 54-55. +4. Kalinowsky, Lothar, “Psychosurgery Said to Help in Certain Neuroses,” Psychiatric News (1971) Vol. VI, No. 7, p. 7 (April 7). 45. Khachaturian, A. A., "A Criticism of the Theory of Leukotomy,” Newvro- patol. I. Psikhiatriya (1951) 20:41. Microfilmed English translation, Library of Congress, TT 60-13724. 46. Knight, Geoffrey ('., “Stereotoxic Tractotomy in the Surgical Treatment of Mental Illness,” J. Neurosurg. and Psychiat. (1965) 28 :304. 47. Knight, Geoffrey C.. “Intractable Psychoneuroses in Elderly and Infirm— Treatment in Stereotactic Tractotomy,” Brit. J. Geriatric Preceice (1966) 3:7-15, 1966. 48. Knight, Geoffrey C., “Bi-frontal Stereotactive Tractotomy : An Atraumatic Operation of Value in the Treatment of Intractable Neuroses,” Brit. J. Psyciat. (1969) 115 :257-266. 49. Lewin, W., “Observations on Selective Leukotomy,” JJ. Neurol. Neurosurg. (1961) 24:37-44. 50. Lindstrom, Petter A.. “Profrontal Ultrasonic Trradiation—A Substitute for Lobotomy,” AM. A. Arch. Neurol. and Psychiat. (1954) 72:399-425. a1. Lindstrom, Petter A., Moench, I. G.. Roynanek, Agnes, “Prefrontal Sonic Treatment,” in Masserman, J., ed., Current Psychiatric Therapies, IV, Grune and Stratton, 1964. 479 52. Livingston, Kenneth, “The Frontal Lobes Revisited. The Case for a Second Look,” Arch. Neurol. (1969) 20 :90-95. 53. Manchester Guardian, April 2, 1968, p. 18. 54. Mark, Vernon H.; Barry, Harbert; McLardy, Turner and Ervin, Frank, «he Destruction of Both Anterior Thalamic Nuclei in a Patient with Intractable Depression,” J. Nerv. Ment. Dis. (1970) 150 :266-272. 55. Marks, I. M.; Birley, J.; Gleden, M. G., “Modified Leucotomy in Severe Agoraphobia,” Brit. J. Psychiat. (1965) 112 :757-769. 56. McKenzie, K. G., and Kaczanowski, G., “Prefrontal Leukotomy : A Five- Year Controlled Study,” Canad. Med. Assoc. J. (1964) 91 :1193-1196. 57. Medical World News, “Neurosurgeons Take Route V-90 to Lobotomy,” Jan- uary 24, 1968, pp. H3-H4. 53. Medical World News, “The Lobotomists Are Coming Again,” January 15, 1971, pp. 34ff. 59. Miller, A., “The Lobotomy Patients—A Decade Later,” Canad. M ed. Assoc. J. (1967) 96:1095-1103. 60. Moore, D., “Prefrontal Leukotomy,” Canad. Med. Assoc. J. (1970) 102 :876. 61. Moser, H. M., “A Ten-Year Followup of Lobotomy Patients,” Hosp. Com- munity Psychiat. (1969) 20 :381. 62. Narabayashi, H.; Nagao, T.; Saito, Y.; Yoshido, M.; and Nagahata, M.; “Stereotaxic Amygdalotomy for Behavior Disorders,” Arch. Neurol. (1963) 9:1- 7. 63. Narabayashi, H. and Uno, M., “Long Range Results of Stereotaxic Amyg- dalotomy for Behavior Disorders,” Confin, Neurol. (1966) 27:168-171. 64. Narabayashi, H., “Functional Differentiation in and around the Vertical Nucleus of the Thalamus based on Experiences in Human Stereoencephalotomy,” Johns Hopkins Med. J. (1968) 122 :295-300. 65. Newsweek, “Probing the Brain,” (Cover Story), April 21, 1971, pp. 60-77. 66. Opton, Jr., Edward, mimeographed communications on behalf of the Medi- cal Committee for Human Rights, Berkeley, California, December 30, 1971. See also, “Doctor's Warning on Vacaville’s ‘Torture’ Cures.” The Berkeley Barb Dec. 2, 1971, and “Prison Reform, California Style,” d.c. gazette, Feb. 9, 1972. 67. Personal Communication by letter. 68. Personal Communication by telephone. 69. Pippard, John, “Leucotomy in Britain Today,” J. Ment. Sci. (1962) 108: 249-255. 70. Post, F. “An Evaluation of Bimedical Leucotomy,” Brit. J. Psychiat. (1968) 114 :1223-1224, 71. Psychiatric News, “Psychosurgery Hailed in Experimental Texas Study,” Dec. 16, 1970, p. 1. See also, News Release, U. Texas Medical Branch at Galveston, Sept. 9, 1970, 7 pages. 72. Rinkel, Max, Biological Treatment of Mental Illness; Farrar, Straus and Giroux, 1966. See p. 66 and p. 146. 73. Robin, A. A., “A Controlled Study of the Effects of Leucotomy,” J. Neurol. Neurosurg. Psychiat. (1958) 21 :262-269. 74. Roeder, F. D. “Stereotaxic Lesion of the Tuber Cinerium in Sexual Devia- tion,” Confin. Neurol. (1966) 27:162-3. 75. Sano, K., Yoshioka, M., Ogashiwa, M., Ishijma, B. Ohye, C., “Postero-medi- cal Hypothalamotomy in Treatment of Aggressive Behavior,” Confin. Neurol. (1969) 27 :164-167. 76. Sargant, W. and Slater, E., Physical Methods of Treatment in Psychiatry; William and Wilkins, 1964. 77. Scoville, William B., “Recent Thoughts on Psychosurgery,” Connect. Med. (1969) 33 :453-456. 78. Scoville, William B., ed., Transactions of the Second International Confer- ence on Psychosurgery ; Charles C. Thomas, in press. See reference 99. 79. Second International Conference on Psychosurgery, August 1970, Copen- hagen, Denmark. Summaries furnished by participants provide the material cited. See Scoville above for in press source and see Kalinowsky (1971) for summary in print. Psychosurgeons from more than a dozen ccuntries contributed. Now published as reference 99. 480 80. Sem-Jacobsen, Carl W., Depth-Electrographic Stimulation of the Human Brain and Behavior; Charles ('. Thomas, 1968. S1. Shobe, Frank and Gildea, Margaret, “Long-Term Followup of Selected Lobotomized Patients,” JAMA (1968) 206 :327-332. 82. Slater, E., and Roth, M., Clinical Psychiatry, 3rd ed. Williams and Wilkins, 1969. S3. Smith, Aaron, “Selective Prefrontal Leucotomy,” a letter, Vancet (1965) 1:765. 84. Solomon, P., and Patch, K., Handbook of Psychiatry, 2nd Ed., Lange, 1971. 85. Spiegel, E. A. and Wyecis, H. T., Stereoencephatotomy, I, *'Thalamotomy and Related Procedures,” Grune and Stratton, 1962. 86. Spiegel, E. A., Presidential Address, list Meeting Amer. Br. Int. Soc. Res. Stereoencephalotomy, Atlantic City, 1968, Confin. Neurol. (1969) 31 :5-10. 87. Spiegel, I. A., Progress in Neurology and Psychiatry, Grune and Stratton, 1970, see pp. 67-69. 88. Strom-Olson, R., and Carlisle, “Bifrontal Stereotactic Trackotomy: A Fol- lowup Study of its effects on 210 patients,” Brit. J. Psychiat. (1971) 118:141-154. 89. Sykes, H. K. and Tredgold, R. F. “Restricted Orbital Undercutting: A Study of Its Effects on 350 Patients over the years 1951-1960,” Brit. J. Psychiat. (1964) 110 :608-640. 90. Tan, E.; Marks, I. M.; Marset, P., “Bimedial Leucotomy in Obsessive-Com- pulsive Neuroses,” Brit. J. Psychiat. (1971) 118 :155-164. 91. Tooth, G. ("., and Newton, M. ., Leucotomy in England and Wales; H. M., Stationery Office, London, 1961. 92. Vidor, R., “The Situation of the Lobotomized Patient, “Psychiat. Quart. (1963) 37:97, 104. 93. Vosburg, R. “Lobotomy in Western Pennsylvania : Looking Backward over Ten Years,” Amer. J. Phychiat, (1962). O4. Williams, J. M. and Freeman, W. “Evaluation of Lobotomy with Special Attention to Children.” A. Res. Nerv. Ment. Dis. Proce. (1963) 31:311. 95. Wortis, ed. The Yearbook of Psychiatry and Applied Mental Health : Year- book Medical Publishers, 1970. Review of Brown and Lighthill Article. ADDITIONAL RECENT BIBLIOGRAPHY 90. Fedio, Paul and Ommaya, Ayoub. “Bilateral Cingulum Lesions and Stimula- tion in Man with Lateralized Impairment in Short Term Verbal Memory.” Fa- perimental Neurology (1970) 29:84-91. This psychosurgery is being carried on at the National Institute of Neurological Disease and Stroke in Bethesda, Mary- land, apparently for the relief of terminal cancer patients, and represents a more conservative approach to psychosurgery according to my initial inquiries. 97. Vaernet, K. and Madison, Anna, “Stereotactic Amygdalotomy and baso- frontal tractotomy in psychotics with Aggressive Behavior,” J. Neurol, Neurosurg. Psychiat. (1970). 98. Neural Bases of Violence and Aggression, a conference sponsored by the U7. of Texas Medical School, Graduate School of Biomedical Sciences, and The Houston Neurological Society, Houston Texas, March 9-11, 1972. This includes a panel on “Role of the Neurosurgeon’ involving W. R. Sweet, and Vernon Mark of Boston and Keiji Sano of Japan. Frank Erwin, another psychosurgeon from Bos- ton, will present a study of aggressive behavior in penitentiary inmates. 99. Hitcheock, et. al, Psychosurgery, 1972, published by Charles C. Thomas, is the latest most complete pro-psychosurgery compendum with articles by Andy, Mark, Ervin and Sweet and others. An article by Ruth Anderson describes the destructive effects of the latest operations. The papers are from the Second Inter- national Congress on Psychosurgery in 1970. Senator Kenzepy. We will resume these hearings on March 6. [At 1:05 pan. the hearings were concluded. | QUALITY OF HEALTH CARE—HUMAN EXPERIMENTATION, 1973 TUESDAY, MARCH 6, 1973 U.S. SENATE, SuBcoMMITTEE oN HEALTH OF THE COMMITTEE oN LaBor AND PuBrLic WELFARE, Washington, D.C. The subcommittee met, pursuant to notice, at 11:30 a.m., Senator Jacob J. Javits presiding pro tempore. Present: Senators Kennedy, Cranston, Javits, and Dominick. Committee staff members present: LeRoy G. Goldman, professional staff member and Jay B. Cutler, minority counsel. Senator Javits. The subcommittee will come to order. Senator Kennedy, chairman of the subcommittee, has authorized me to start the hearing. His opening statement will be printed at this point. OpeNING STATEMENT oF Hon. Epwarp M. Kenney, A U.S. SENATOR FroM THE STATE OF MASSACHUSETTS AND CHAIRMAN OF THE SENATE HearTH SUBCOMMITTEE Today’s hearing focuses on the past accomplishments and future prospects of biomedical research. These are important subjects at any time, but have added significance today because of the threat posed to this Nation’s biomedical research effort by the President’s budget. All Americans have been touched by, and have profited from the fruits of biomedical research. And all Americans will suffer from the consequences of a drastically reduced research effort. We have already seen in these hearings that the new developments in biomedical research hold great promise for significantly improving the health of the American people. But we have also seen that this new technology of man raises profound ethical questions—questions which our society must address if we are to apply the new knowledge wisely and constructively. We will be confronted with this dilemma again today as we look into the future of genetic research with all of its Orwellian implications for the control and manipulation of our population, and the future of surgery, where the ethical dilemmas of the transplant era have yet to be resolved. We are indeed fortunate to have some of the most eminent scientists in our nation with us today to discuss these problems, and we look for- ward to receiving their testimony. Senator Javits. As our first witness this morning we wish to ac- commodate Dr. Callahan, as we understand he has some travel evi- (481) 93-999 (Pt. II) O - 73 - 10 482 gencies. We understand that is agreeable to Dr. Sherman. Is that correct? Dr. SHERMAN. Yes. Senator Javits. Will you proceed. STATEMENT OF DANIEL CALLAHAN, PH. D., INSTITUTE OF SOCIETY, ETHICS, AND THE LIFE SCIENCES, HASTINGS-ON-HUDSON, N.Y. Dr. Cavnamax. In the wide range of issues posed by the quality of medical care and human experimentation, genetic research and tech- nology take a special place. The subject of experimentation is not only the individual person or patient; the ultimate experimental subject is the human species itself. However, the old debate between genetics and environment, nature and nurture, comes out, it is not likely to alter one fundamental fact: we are to a considerable extent what our genetic makeup has created us to be. We are human beings in the first place because we are of the species homo sapiens; and we are as individuals the genetic product of the parents and families from whom we have descended. When we experi- ment with genetics, we are experimenting with the future of human life. It is theoretically possible, and in some cases already feasible, to make a significant difference in the genetic makeup of our children, our grandchildren and all of their descendants. One can hardly help being both excited and nervous at the prospect of this power. For generations, humans have speculated on the meaning of human heredity; only recently has it been possible to gain some solid scientific knowledge of the process and dynamic of the transmission of genetic information and characteristics. For generations, humans have also been troubled and burdened by genetic disease; only recently has it become possible to understand such disease and to do something about it. For generations. humans have speculated about the possibility of creating biologically “better” human beings; only recently has it become possible to give some scien- tific substance—however slight—to those speculations. The question is: how are we to respond to those possibilities? How are we to respond as individuals, and as a society ¢ The sense of thrill and excitement must eventually give way to a more mature sense of responsibility and prudence. All things may be possible, but not all things may be desirable. We need to know who will make the critical decisions to go forward with genetic research and technology. And we need to know what ethical, social and legal standards should be brought to bear in making the critical decisions. The most important point to be made is that ignorance reigns. What is not. known about heredity and genetics far exceeds what is known. We do not know the consequences for our children or for future gener- ations of attempts to intervene in genetic processes. Because of this ignorance, any direct interventions into the human genetic makeup must be considered a form of experimentation, with the results yet to be determined. It is easy to understand this point when the subject is genetic engi- neering, that is, research and applied technology directed at effecting some direct and significant alteration of genetic makeup. The process of cloning, for example—the production of genetically identical be- 483 ings—poses the most obvious kinds of problems concerning the social and ethical acceptability of one group of people manufacturing another group with pre-established genetic characteristics. What right does one group have to determine that another group should all share identical traits? What would happen to the cloned person’s sense of identity and integrity? What kind of society would result if there were a large number of genetically identical people? The answer to all of these questions is that no one has any real idea at all, thus, we are clearly talking about human experimentation. Very similar points can be made about the development of in vitro fertilization—test-tube babies; the creation of artificial placen- tas, making it possible for a fetus to mature outside of the female womb; the devising of genetic surgery, making possible the replace- ment of defective genetic information with healthy genetic informa- tion. In each of these instances, no one can have any solid notion of the societal or genetic consequences, either for the individuals first experimented upon or the consequences for future generations. Yet if we are ignorant of the possible results of genetic engineering, we are hardly less ignorant of the consequences of those less radical forms of genetic intervention already present in our midst. The field of genetic counseling grows apace, as a new most rapidly expanding part of medical practice. Genetic counselors are able to give increasingly sophisticated and Drosiss knowledge to individuals or couples JONAS their prospects or conceiving or bearing a genetically defective child, either before or during marriage. The technique of amniocentesis, allowing for the prenatal diagnosis of a growing list of genetic defects, can provide exact information on the prospect of a defective child in many instances. With that knowledge, women or couples can choose to bear the child or have an abortion. Yet for all this new knowledge no one yet knows what the impact upon families will be, how social attitudes toward defective children will be influenced, or the way in which individuals and couples will tend to make use of the information they are given. Mass genetic screening raises still other problems. Such screening will make it possible to test large populations either for the presence of genetic disease, or for the presence of a defective gene. With the latter information in hand, couples considering whether to have a child, or considering whether to get married, will be able to know in advance what the odds are that they will bear a defective child. Such mass screening programs are already underway for Tay- Sachs disease, a fatal genetic defect which occurs predominantly among Ashkenazi Jews, and for Sickle cell anemia, which primarily affects blacks. Yet even with these diseases we are ignorant. No one knows with any certainty how large-scale populations will react to the knowledge that they carry some possibly lethal genes. No one knows what a more exact genetic knowledge will do to the individual's sense of self-worth and dignity. No one knows what the social consequences will be of screen- ing programs carried out for a growing number of identifiable genetic defects. Nor do we know what the long term political effect will be. The course of wisdom in the face of great ignorance is care and caution. More than that, because the implications of genetic interven- 484 tion are social as well as individual there is a desperate need for public participation in those decisions which may radically and irreversibly affect genetic welfare. It is all too easy, especially when ignorance reigns, to let matters drift, to deal with the problems as they arise. But the important reality of genetic intervenion is that the most serious thinking may have to be done before the technology is actually developed. For once crucial developments take place, it may be too late to do anything at all{The great rush in some States to put man- datory laws on the books for the screening of children for Sickle disease was followed within a year by no less frantic attempts to get those laws removed. Fortunately it was possible to do so, but there is no guarantee that matters will be so comparatively simple in the future. The need for care and caution can, if not understood properly, be seen as a possible threat to scientific and medical advances. There is no reason to draw that conclusion. Genetic disease imposes burdens upon those affected, upon their families and upon the society. There is every reason in the world to engage in the most vigorous efforts to under- stand genetic disease, to work toward more effective means of testing for its presence, and to develop as rapidly as possible medical therapies for those diseases. The problem is not to make the case for genetic research and applied medical technology. As long as human beings suffer from genetic dis- ease, only the monstrously insensitive could be indifferent to the di- mensions of the human agony involved. More and better research should be a major scientific and medical priority. The real problem is to see that the scientific and medical research are matched by equally zealous, dedicated and vigorous social and ethical research. We simply cannot afford, as society or a species, to stumble around blindly in a thicket which may produce as many thorns as flowers. What, for example, will be the societal attitude toward de- fective and abnormal human beings once we begin to understand bet- ter the cause of their illness? Will we be all the more sympathetic and helpful, or will we become all the more condemnatory, particularly should we decide that their parents were irresponsible to have con- ceived them in the first place? Once we have declared all-out war against genetic disease, how can we keep that attitude from spilling over to become an all-out warfare against the afllicted and defective in our midst 7 Tt is not easy to draw a clear distinction between hating a disease and hating those who have the disease. One thing is certain. The progress to be made against genetic disease will be slow and halting: it will be centuries perhaps before genetic disease will be brought fully under control. In the meantime, we must learn to live with it, making every effort to provide the defectives and their families with necessary social and medical support. Moreover, it will be important to insure that, in our haste to detect the carriers of defective genes, or to expand the possibilities of prena- tal diagnosis of defects, that the search for effective treatments 20 forward with no less haste. It is tempting to search exclusively for ways of dealing with genetic problems before they arise, or to try to keep them from arising at all. But they will continue to arise and, 485 at the least, we owe it to those who will suffer to do everything we can to ease their burden. I have laid great emphasis here upon genetic disease, genetic counsel- ing and mass genetic screening. They are present realities, which should not be overlooked because of a bemusement with the more exotic possibilities of genetic engineering. In fact, the precedents we now establish concerning counseling and screening may be critical for the way in which the more troubling questions of genetic engineering are approached. Let me conclude by making a number of proposals. (1) A knowledge of genetics, and of genetic disease, should become part of the basic education of every citizen in our country. The place to begin is during primary school, when children are first provided with scientific information. More advanced knowledge should be provided at each stage of formal education. (2) Mechanisms for public understanding of the possibilities and implications of genetic research and applied genetic technology should be established as quickly as possible. This information should be sup- plied through the media, by public health organizations, in adult edu- cation courses, and in the churches and synagogues. (3) Since the impact of genetic intervention can bear so heavily on the welfare of present and future generations, with a wide social im- pact, public review, debate and participation are necessary at those points where major decisions are needed about the taking of future research or application steps. (4) Scientists and physicians working in the field of genetics bear a special burden to inform the public of important scientific advances, of benefits they perceive and of possible hazards they can envision. (5) A major research investment is needed to study the ethical, legal, social and political implications of genetic technology. This research must of necessity involve a wide variety of disciplines and skills, the scientific, the medical, the social scientific and the humanistic. (6) Public and legislative commissions should be established as quickly as possible to foster public understanding of the problems, pos- sible routes to their solution, and to promote the needed scientific and humanistic research. By far, I believe, the promise in greater genetic knowledge far out- weighs the hazards. But hazards there are. If we fail to confront them speedily and wisely, the progress of scientific research itself could well be impeded, and thus the needed confrontation with genetic disease hindered. Moreover, since our descendants even more than we will have to live with the fruits of our present genetic discoveries and ingenui- ties, we should bequeath to them a good inheritance of genetic knowl- edge and sensitivity. Human beings may some day want to clone other human beings. We cannot preclude their making that choice. At the same time, we do not want to preclude the possibility that they will not want cloned persons. What we do now will determine the choices they will have. That is a heavy responsibility. Senator Javits. Thank you, Dr. Callahan. Senator Kennedy has asked me to ask you three questions, and I will do that. T will not ask any myself in order to save time and to accom- modate others. 486 Many of the techniques that vou have described sound as if they come directly out of 1984, says Senator Kennedy. Is it possible that techniques such as cloning can be used to control the characteristics of a population? If we will be able to replace defective genes with good ones, why will we not be able to replace any gene with any other gene. thereby controlling the way a human being develops? What is your comment on that ? Dr. Canaan. I think there are two things to be said. First. the practical possibility of achieving those scientific results is still some- thing rather far oft in the future. Secondly, even if developed, it seems to me most unlikely that the scientific technics or medical technology could be effectively used on a very mass scale. Those are simply practical points about the 1984 possibility. In practice or rather in large theory one might imagine a situation where governments or societies try to make sure use of the genetic advances to control large populations of human people or to create certain types of people. That is why I think we need at this point to begin a medical and ethical discussion of the possibilities here to see if we really want to go in that direction or not. Senator Javits. The next question that Senator Kennedy wishes asked is the following: Are you saying that the physician of the future will Le able to correct or eliminate all diseases of genetic origin by therapeutic manipulation of the fetus? Dr. Carranax. I did not say that, and I think it would be very naive to predict that all genetic diseases could be so handled in the future. I think it will be perhaps many, many decades. if not centuries, be- fore most genetic diseases could be brought under control. Senator Javrrs. The last question is the following : Few areas of research seem to hold out more promise or to raise more problems than genetic research. As you have articnlately dem- onstrated, many of these dilemmas can be foreseen. What do we as a society need to do in order to resolve these prob- lems before the techniques become fully developed ? Senator Kennedy has not heard your recommendations. Do you stand by those as the answer to the question. or would you like to make any additional comment ? Dr. Carnanax. I think just two points. In the first place, a great deal of public education is necessary, and. secondly, far greater understanding than at present of the kinds of options open to us in the future. Unless we understand what those options are in the light of the different consequences or alternatives, we are not likely to make any significant progress at all. } } Senator Javirs. Thank you, Dr. Callahan. Senator Dominick. Senator Doaninies. T have just one question which may be a sociological one as opposed to a medical one. Who determines what is or is not a good gene?’ 487 Dr. Carranan. That is a very difficult question. I think within the medical community a bad gene at least would be defined as one which led to some seriously crippling disease or had some deleterious consequences for the functioning of the human body. } More broadly, I think there is a great deal of probing necessary to understand what we really think are good human characteristics and traits and which ones we think are not. } There is a real hazard here in deciding certain classes of people with certain kinds of genetic traits are somehow inferior or lesser human beings. I would hope that genetic research and thinking would not 2o in the kind of direction which would lead us to begin sorting out people according to their social or medical worthiness. Senator Dominick. The latter one is the problem that has been disturbing me all the way through on this. I can understand genetic research dealing with diseases, but it is only a short step from that point to someone making a determination as to what types of genes are good for people and what types are not, and T think at that point we get into this massive philosophical and moral argument that you are discussing. I am very interested in your paper, and appreciate it. Senator Javits. Thank you, Dr. Callahan. So that the witnesses may understand the legerdemain going on up here, Senator Kennedy designated me to open the hearings. We are very grateful to Senator Cranston whom Senator Kennedy has designated to succeed me in conducting the hearing. Senator CransToN (presiding pro tempore). I am pleased to be sand- wiched with Senator Kennedy and Senator Javits and also Senator Dominick in chairing these hearings. 1 thank you for your testimony. The second witness, representing the Administration, is Dr. John Sherman, who is presently Acting Director of the National Institutes of Health. ) Dr. Sherman has been Deputy Director of the National Institutes of Health since November of 1968. He has been associated with NTH for over 20 years, and I know that his testimony will be enormously useful to us. In addition IT am informed that Dr. Sherman has just been named recipient of the National Civil Service League Award of 1973. I congratulate you for that, and for your generosity in allowing Dr. Callahan to precede you because of his time problems. Senator Javits. Dr. Sherman, I suggest that you introduce your colleague at the table. STATEMENT OF JOHN SHERMAN, M.D, ACTING DIRECTOR, NA- TIONAL INSTITUTES OF HEALTH, ACCOMPANIED BY ROBERT W. BERLINER, M.D., DEPUTY DIRECTOR OF SCIENCE, DEPART- MENT OF HEALTH, EDUCATION, AND WELFARE Dr. Saerman. Thank you, sir. I am pleased to introduce on my left Dr. Robert W. Berliner, who is the deputy director of science, and an internationally recognized physiologist. 488 As has been indicated, both Dr. Berliner and I have been privileged to be associated with the institution about which 1 will speak for upwards of 20 years. I am pleased to be here this morning to set forth for this committee the role of the National Institutes of Health and to describe briefly what has been accomplished in improving the health of the American people. The mission of the NIH is clearly stated in the basic Public Health Service legislation. It is “to conduct in the Service, and encourage, cooperate with, and render assistance to other appropriate public authorities, scientific institutions, and scientists in the conduct of, and promote the coordination of, research, investigations, experiments, demonstrations, and studies relating to the causes, diagnosis, treat- ment, control, and prevention of physical and mental diseases and impairments of man.” The reorganization of the health activities of HIEW in 1968—which transferred to NIH the Bureau of Health Manpower Education and the National Library of Medicine—also gave NII responsibility for Federal programs for education in the health professions and for the improvement of biomedical communication. However, I shall confine my remarks this morning to the research activities carried out by the ten institutes and five research divisions of the NIH. It is axiomatic that people are a nation’s most important resource and that health is the people's most prized possession—even though its value is sometimes not fully appreciated until it is impaired. The availability, accessibility, and quality of health care are matters of very deep and very personal concern. Efforts to improve the scope, distribution, an effectiveness of health care are, therefore, also properly matters of national concern. This has long been the case and it. was unequivocally reaflirmed by the President in the message on National Health Strategy which he sent to the Congress exactly : year ago. There are, of course, differences of opinion on the precise extent of Federal responsibilities in this field and on the way in which these responsibilities can best and most appropriately be discharged. Public discussions and political debates on this question often lose sight of the fact that the best health care that can be made available is only as good as the current state of knowledge concerning the prevention, diagnosis, and treatment of disease. The state of knowledge is wholly determined, and limited, by the effectiveness of past research. The indispensable prerequisite for better health care—including more effective prevention. earlier and more accurate diagnosis, and more dependable treatment—is the acquisition of better knowledge which can only come from continued research. The mission of the NII, therefore, is to strengthen the foundations on which the whole health care edifice is built. I have just said that our goal must be better knowledge, rather than merely more knowledge. The dean of a medical school, addressing the graduating class a year or two ago, said: “You should be aware that half of what you learned here during the past four years is wrong— and it is unfortunate that the faculty does not know which half.” He was, of course, overstating the case but only to emphasize that the present state of medical knowledge is as much in need of revision as :Xpansion, 489 In judging the progress that has been made in research—and assess- ing future needs—it 1s well to bear in mind that medicine is a very young science. Concern for health may be as old as man, but the ability to prevent or treat disease systematically and effectively is a very re- cently acquired skill. For centuries, medicine depended entirely on careful observation and a few emperical experiments. By these means, it made some significant advances which, for lack of understanding, it was unable to exploit. A dramatic example of this was the observation by an English physician, Edward Jenner, that dairymaids who had had cowpox, a relatively mild disease, did not get smallpox, which was frequently fatal. In 1796 Jenner inoculated an eight-year-old boy with serum taken from a cowpox blister on the hands of a milkmaid and, several weeks later, inoculated him with smallpox—which the boy did not contract. Thus was discovered the preventive procedure which we call vac- cination—a derivative of the Latin word for “cow.” But a hundred years elapsed before vaccination became a tool for control of other in- fectious diseases for which there was no equivalent milder “cowpox” form. The science of bacteriology had first to be born. The virus that actually causes smallpox was not discovered until even later. The existence of cells, the basic building blocks of living things, was not discovered until 1839. The anesthetic effect of ether and chloro- form, which made the development of surgery possible, was first ob- served in the 1840’s. Modern medicine is less than 100 years old. It may be said to date from 1878 when the role of bacteria in causing disease was first recog- nized. Robert Koch, who, with Louis Pasteur, laid the foundations for bacteriology—one of the fundamental medical sciences—was a recent enough figure to have received a Nobel Prize in 1905. Paul Ehrlich who laid the foundations for chemotherapy—the treatment of disease by drugs prepared for that purpose—received his Nobel Prize in 1908. Karl Landsteiner received a Nobel Prize as recently as 1930 for his discovery that there are four main types of human blood. Modern medicine, as a science based on systematic re- search, is essentially a 20th century phenomenon. Progress during the past 80 or 90 years has been rapid and has been constantly accelerated. The NIH has played a part in this progress virtually from its beginning, and during the past 25 years has played a major role in the acceleration. The Hygienic Laboratory of the Public Health Service—which was transformed into the National Institute of Health by the Ransdell Act of 1930—was established in 1887 by Dr. Joseph Kinyoun after he had worked with Dr. Robert Koch in Germany. Tts research on cholera and other infectious diseases was part of the first wave of progress that brought such ancient and devastating scourges as typhus, typhoid, diphtheria, and scarlet fever under control. Tn 1912 the role of the laboratory was expanded to include health problems other than communicable diseases, and in 1914 Dr. Joseph Goldberger, a member of its staff, drew attention to diseases of nutritional origin by demonstrating that pellagra, a digestive and nervous disorder leading to mental deterioration, was due to a dietary deficiency. 490 From these modest beginnings—when the Hygienic Laboratory be- came the National Institutes of Health it had a staff of only 140-—the NTH has grown into a world-renowned research establishment. Since the opening, in 1953. of its 516-bed hospital. devoted wholly to re- search, the NTI has become a major national resource and an acknowl- edged leader in both clinical and laboratory research. One measure of its impact is that, for some years now, more papers have been accepted from the NTH staff for presentation at the pres- tigious annual meetings of the three 1 ading clinical professional soci- eties than from any other institution. A measure of its international repute is that, during the past 5 years, three members of the research staff at the Bethesda campus have won Nobel Prizes. I want to emphasize the scope and quality of the medical research done at the NTI because I believe that this lies at the heart of the success of the entire operation. In its dealing with academic and other research institutions, in the management of its grant programs, NIH can speak with authority, based on its own experience. and its views are, for this reason, respected. Quite apart from its obvious intrinsic value to the Nation as a first-class research facility staffed by capable and dedicated scientists, the intramural program assists in providing direction for the extramural program, which is approximately 80 percent of the NIH budget. The extramural programs were grafted onto the NTI in 1946 when it inherited the medical research-grant projects funded during World War II by the Office of Scientific Research and Development. The nine NTH grants then in existence, under authorizing legislation enacted in 1937, suddenly jumped to 79 and, with increased funds, to 335 In 1947 and to 1,042 in 1948. This marked the acceptance by the federal government of respon- sibility for the support of medical research on a national basis. Since then, the growth of the program has been rapid but steady—11.729 research grants were made in 1972. Funds for these rants had gone from $892,000 for 79 awards in 1946 to $805 million in 1972. Contrary to the fears expressed by some observers, the increase in federal funds did not dry up nonfederal support for medical research. While total federal expenditure on health research rose from $27 mil- lion in 1947 to $1.7 billion in 1970. nonfederal expenditure on health research also grew, though at a somewhat slower rate. from $60 million in 1947 to more than $1 billion in 1970. The combined effect, therefore, was to increase national expenditure on health research from a level of $87 million in 1947 to an impressive $2.7 billion in 1970. The result of this investment during the past 25 vears hag been to create a medical research capability—in terms both of physical plant and intellectual commitment—that is not equalled, or even ap- proached, in any other country. With the help of NTI funds, some 18 million square feet of space have been added to biomedical research facilities and about 50,000 scientists have received advanced training in the basic medical sciences and clinical specialties. Work on virtually every aspect of health prob- lems has been supported through the award of over 200.000 NTH research grants. Ch. kd 491 I cannot attempt to catalog the achievements of so vast a national effort. There are such obvious results as the new vaccines for measles and rubella; the application of hemodialysis technics to victims of chronic kidney failure; the refinement of kidney transplants to the point that their success is not longer newsworthy ; rapid strides toward the development of heart-assist devices; tremendous progress in the difficult task of tracking down the relationship of viruses to a broad spectrum of diseases ranging from the common cold to cancer; major developments in immunology that promise to clear the way for more uniformly successful tissue transplantation; an understanding of allergic diseases and the so-called auto-immune diseases. There have been innumerable advances in surgery ranging from delicate work on the eye to the transplantation of a heart. Perhaps the most dramatic progress, as has already been demonstrated, with the promise of sweeping and unpredictable consequences—is in the brilliant work being down on the complex chemistry of genetic inheri- tance which has brought us not only to the threshold of preventing or correcting hereditary defects but gives us an insight in the basic processes of life itself. The effect of all this research on the practice of medicine has been revolutionary. It has been said that much of what was taught in medical schools in the 1940’s is today no longer relevant. If we main- tain the momentum of the superb research establishment that has been created, it is predictable that much of what was taught in the 1960’s will no longer be relevant in the 1980s. The rapid advances that are being made and the sophistication of much of the work now being done should not, however, trap us into underestimating the immense and complex tasks that lie ahead. In comparison with the physical sciences, the biomedical sciences are still in a relatively primitive stage. The great underlying principles that brought order and predictability into physics and chemistry—such as Newton’s laws of motion and Mendeleev’s periodic table—are missing in the biological sciences. Einstein’s theory of relatively, that led to the unlocking of the energy of the atom, has no counterpart that will unlock the power of the gene. Most life processes continue to defy the kind of quantifica- tion that would make them accessible to the powerful tools of mathe- matics. Though some progress is being made in this direction, much of medical research must still rely on empirical approaches and on deductions from small groups of data. And it is still too often true that finding the answer to one question raises several more difficult ones. In short, we are nowhere near the end of the road, and it may well be that this particular road has no end. But it is, from every point of view, a road well worth traveling. In economic terms, the cost of medical research is small. Although there is no guarantee that con- tinued research advances will substantially lower health care costs, some successes of the past have had significant economic impact. The conquest of tuberculosis led to the closing or conversion of almost all the TB sanitoriums. More recently, the development of drugs for the management of several forms of mental illness has sharply reduced the number of hospitalized psychiatric patients. The new rubella vaccine is expected 492 to prevent the several thousand defective babies that would otherwise have resulted from the next epidemic of German measles and who would have required special care for the rest of their lives. Obviously, a successful vaccine for virus-caused cancers or even for dental caries would, in a relatively short time, purely on an economic basis, save much more money than the cost of their development. It has been facetiously said that the ultimate goal of medical re- search is immortality, but few scientists are even as distantly optimistic as the Apostle Paul who wrote to the Corinthians that “The last enemy that shall be destroyed is death.” They are more inclined to agree with Euripedes that “Death is a debt we all must pay.” They share, however, the belief of our founding fathers that life and the pursuit of happiness are two of man’s “unalienable rights.” The ultimate goal of their research is to prolong life to its allotted span and to factilitate the pursuit of happines by making it possible to pre- vent or cure disease and, when this is not possible, to ameliorate its effect. The most important contribution to man’s welfare that medical research can make is to improve the quality of life—to fend off “the heartache and the thousand natural shocks that flesh is heir to.” As Louis Lasagna wrote in the epilogue of 7he Doctors’ Dilemmas : “It would seem important to devote more of the energies of man to improving the quality of life . . . Otherwise, existence is nothing but the bored molecular unwinding of a dismal biological clock.” To speak only of the federal funds that have been made available for medical research through the NIH programs does not adequately reflect the role that the NTIT has played in its development. The impact on the quality of the institutions that have participated in his en- deavor has been equally important. The award of grant funds to these nonfederal institutions has been made on the basis of two criteria: scientific excellence and relevance to the mission of the NTH and its various categorical disease-oriented in- stitutes. The scientific merit of a research proposal is assessed hy an elaborate system of peer review which brings together, in a so-called study section, 10 to 15 competent and experienced scientists in the re- levant discipline. They base their recommendation of the priority to be accorded a particular application on the competence of the investigator, the sci- entific importance of his proposed project, the validity of his investiga- tive approach, and the adequacy of the research resources, that is. equipment, clinical facilities, et cetera, available to him. There is no doubt that the thoroughness of this review, which frequently includes a site visit, in a highly competitive situation has, over the years, served to raise the quality of the work done. The system of extramural support has evolved during the past 25 vears in response to changing needs, growing capabilities, and—ocea- stonally—congressional directives. What has emerged is a partnership batween the federal government, represented by the NII, and the nation’s biomedical research community. It is a productive partnership in which both partners now have a very considerable investment and which admirably serves the purpose of cach. The institutions are able to do more effectively the job they 493 were designed to do. The federal government has acquired a strong na- tional defense against its people’s most ancient enemy : disease. 1 do not know whether it is true, as the Wooldridge Committee sug- gested several years ago, that “there are few, if any, $1 billion segments of the federal budget that are buying more valuable services for the American people than that administered by NTH.” But I am certain that it is an arrangement by which the American taxpayer is well served. T will be pleased to answer questions. Senator Cranston. Thank you very much for a very fine statement of what I think is an excellent record of accomplishment at NTH. The point you make generally about how resolving one question will lead to some more difficult questions, and we are nowhere near the end of the road that may very well have no end, is I think of significance in our efforts to measure realistically our sights. Great accomplishments have obviously occurred at NIH. The ques- tion is where do we now go from here. Senator Kennedy had several questions for you, and I will now proceed with some of his questions. What would the proposed fiscal year 1974 budget do to NIH’s opportunity to move ahead effectively in all the fields where more work is needed ? Dr. Surman. The President’s 1974 budget contains an increase for research through the NTH of just under $50 million, so that there will be an increase in the capability to undertake these tasks. The President’s budget request highlights two areas which both the Congress and the administration have stressed as a result of recent hearings and legislation; those areas are an expanded effort in cancer research and similarly expanded effort in research related to cardiovascular disease, pulmonary disease, and blood disease. With the level of funding proposed in the President’s budget request for Fiscal Year 1974 of over $1.5 billion, it is our sense that we can undertake and continue a very productive and wide ranging research effort. I think I should add, however, Senator, that IT would be either a fool or a liar to say that we could not use additional funds effectively, but the overall consideration throughout the Executive Branch has to do, as President Nixon has stated, with fiscal constraints which must be placed in order to attack the primary problem which he sees facing the country, namely, the threat of inflation. Senator Cranston. Which of the institutes would actually receive less money in 1974 than they did in 19727 Dr. Suerman. There are reductions in most of the Institutes except for the Heart and Lung Institute and the Cancer Institute. Most of the reductions are accounted for by the elimination of programs for the training of research scientists. After considerable study it was felt that the federal role in this particular area should be re-examined and that greater emphasis should be placed on sources other than the federal government for the continuation of this type of activity. Senator Cranston. Do you feel that NIH does have more to con- tribute in those fields? Dr. Suerman. Very definitely. 494 Senator Cranston. If you had your way and could prepare what you would consider an ideal budget for NITI, where would you place the main emphasis in dollars? Dr. Surryan. With no fiscal restraints and no competing prior- ities in any other Federal areas of activity, and particularly looking at a program as diverse as that of the National Institutes of Iealth over a period of some time, that is multiple years, it is my considered judgment that we should look to the support of practically every field comprising what we refer to as the biomedical sciences. Our state of knowledge, as T and other witnesses have described before this and other committees, is altogether too meager in the area of most disease fields to permit us to relax in any given field; this is particularly true in the area of biomedical research where develop- ments in one field may contribute to advances in another field of re- search. Our overall consideration then. and particularly over a period of time, is to attempt to provide support in this instance to each of our categorical institutes, recognizing the inter-relatedness of the programs of those institutes. Senator Cranston. What have the schools of public health con- tributed? Dr. Suerman. The schools of public health have been institutions primarily involved in the elucidation of techniques related to ap- plied activities in the areas of sanitation and preventive medicine within a community or region. They train personnel to work within communities and regions in order to utilize existing knowledge in ef- forts to improve the general level of health. Senator Cranston. That is really important work, is it not? Dr. Streryax. I beg your pardon ? Senator Cranston. Do you consider that important work? Dr. Sireraran. Very definitely, and particularly as some schools of public health are attempting to re-examine their very purpose to see that their contributions are equal to new challenges. Senator Cranston. Where will the schools of public and allied health get support if the President’s budget is adopted and they are cut off from the aid they have been given up to now ? Dr. Sueraan. Most of the schools of public health are State sup- ported institutions, and on the basis of a broad re-examination of Fed- eral roles by the Administration, it is felt that these institutions should now be able to turn to State and local sources of funding more in concert with the nature of their activities and their populations. Senator Craxston. If the deans say they cannot depend upon that source, and many are now planning cutbacks in faculty, what do vou propose to do? Dr. Sueraan. I doubt whether any dean in this day and age would be listened to if he were to say he were not faced with some very serious decisions on the funding of his institution. However, within overall priorities which have been developed within the Administration on the basis of the twin considerations of Federal role and limited financial resources, the schools of public health have been assigned a somewhat lower priority than schools of medicine, osteopathy and dentisiry. 495 Senator CransTON. Suppose the States do not step in. Do you feel then that we should just accept the fact that some of these schools are cut back and others may have to close? Dr. SuermaN. It is not as though there is no money in our budget, Senator Cranston, for support of institutions of this sort. As a matter of fact, one of the proposals enacted in the Compre- hensive Health Manpower Training Act of 1971 gave a broad ranging authority for special projects in order to accommodate special situa- tions of which this could be one. Senator Cranston. The budget material we have received indicates there is no institutional assistance for schools in all these fields, just a total blankout. Dr. Suerymax. The approach has been to seek other sources of sup- port for these purposes. The special project authority under the gen- eral authority of the Comprehensive Health Manpower Training Act, the utilization of student loans and other support devices for student assistance are expected to make up for the changes reflected in the budget. Senator Cranston. What evidence do you have that actually there are these other sources ready, able and willing to become available as a substitute? Dr. Suerman. The evidence has to do with the enlargement of au- thority and of budget provisions for student assistance throughout the whole area of higher education. This expanded assistance will be administered in both the Office of Education and also in the NIH Bureau of Health Manpower Education. With respect to State and local sources, word indicates that in at least a number of instances there is a recognition on the part of State governments that support for schools of public health is not, in many respects, a Federal responsibility. It appears that in some instances at least, States will respond to this particular challenge and need. Senator Cranston. Turning to the medical schools, how have they generally reacted to the President’s announcement of the fiscal 1974 health budget? oo Dr. Sueraax. I think it is premature to speak of individual insti- tutions because these represent a considerable spectrum. One has to watch what happens in the State institutions versus the private institutions. But in a number of instances discussions have already been held with deans of these institutions. There is no question that they are concerned. oo On the other hand, it is also evident that they are beginning to ex- amine other sources of funds outside the NTH for these purposes. Senator Cranston. Thank you very much. Now that Senator Ken- nedy is here, having returned from the FBI hearings, if T understand it, he will preside as chairman. ] Senator Kex~Nepy (presiding). I want to express my apologies to Senator Cranston as well as to the witnesses, for not being here earlier. Dr. Sherman, I suppose you have gone over the impact of these various cuts. Dr. Surman. At considerable length, Senator. Senator KENNEDY. On the schools of public health? Have we talked about that? 496 Dr. SrErMAN. Yes. Senator KenNepy. Some of the advances in research, as I under- stand, have come from discoveries made as an incidental part of a particular research projedt, and that discovery leads the investigator to a new area. That. would argue that specifically targeted research is not always the best route to the major new advances. Would you agree with that? Dr. Sueraan. That depends on what one means by “targeted” this word seems to be caught in a thicket of semantics. But, no matter how one understands the meaning of the word, emphasis should con- tinue to be placed on what we describe as investigator-initiated or un- differentiated research, research in which it is difficult to specify the particular target to be accomplished, and where the outcome of that research may indeed make contributions to one or more fields or may make none at all. It is on the results of such fundamental research alone that so-called targeted research can be based. Senator KeNNepy. But the point, as I understand it, is there are many instances in which extremely worthwhile research is done as spinoffs from various research programs. The impact of some of these budget cuts reaches across the board. Targeted research can have rather broad impacts via this spinoff process. I think we heard some testimony to that effect earlier, and obviously the kind of cuts we are considering here are going to have a severe limiting effect on the potential progress in this area as well. I will look forward to reading your testimony. Dr. Sueraran. Thank you. Senator Kex~epy. T want to thank you very much for coming. Our next witness is Dr. Lewis Thomas, Dean and Professor of Pathology, Yale University School of Medicine. Dr. Thomas is also the President-elect of the Sloan-Kettering Cancer Center in New York. Ie was formerly Dean, Professor of Medicine and Pathology at the Bellevue Medical Center of New York University, and is a former professor of pediatrics and medicine at the University of Minnesota. Dr. Thomas 1s a member of the National Academy of Sciences, and trom 1967-1970, he served on the President's Science Advisory Com- mittee. ) Dr. Thomas, we look forward to receiving your testimony. which I know will be of great assistance to the subcommittee. STATEMENT OF LEWIS THOMAS, M.D., DEAN AND PROFESSOR OF PATHOLOGY, YALE UNIVERSITY SCHOOL OF MEDICINE Dr. Troaas. Mr. Chairman and members of the committee. T am grateful for the opportunity to appear before vou today to testify concerning the present and future prospects of biomedical research in this country. There is an argument these days about the value of biomedical sciences, and it looks as though science is, at least for the moment, on the defensive side. Something has gone wrong, either with the wav we have been doing science, or with society's interpretation of what we have been doing. The support for basic science has been weakened. and there is real danger that we will not be training the next genera- tion of scientists in the numbers needed. There is talk of dismantling 497 major parts of the NIH and devoting our energies wholly to the appli- cation of today’s knowledge to today’s problems. } I might as well acknowledge my own bias at the outset. I believe without reservation in the profound value of biomedical science to the health of human beings. I believe this has been proven beyond question in the past, and that it will be the only way for solving the major problems of human diseases in the future. Moreover, 1 believe that there are no disease problems that cannot be solved, provided we maintain the effort in science. I see nothing improbable in the idea of humanity relatively free of disease. Human disease does not strike me as being in any sense natural or inevitable. It is not part of the human condition for people to lose their wits when they age, or to develop leukemia in childhood, or to be born with mental deficiency, or to develop schizophrenia, or heart disease, or stroke, or rheumatoid arthritis, or cancer, or any of the rest of our present ills. I have no more difficulty imagining a healthy popu- lation of human beings than I do with the concept of freedom from disease in valuable stocks of animals, or disease-free plants. I do not suggest that this will come easily or quickly; it will require a great deal of effort and probably a longer time than most of us have patience for, but it is attainable. It is a very serious undertaking, with very high stakes. When people in biomedical science talk the way I have just been talking, we run the risk of seeming to overstate the case, promising too much. It sounds as though we are offering prospects of immortality, since disease and death have always seemed, in the public mind, in- extricably connected. I do not, of course, intend any such suggestion. I believe that death is and will always remain inevitable, the most natural of all natural events, but I also believe that it is, in its natural form, a process of running down and wearing out. Some of us live longer lives than others because this is the way our families are geneti- cally programed, and getting rid of disease will not change this very much. The great difference will be that we will not die pre- maturely, and our declining years will not be marred by the pain and humiliation of the diseases that now dominate the process of aging. We will still be mortal, but what we stand to gain from disease con- trol is an immense improvement in the quality of life. It is also said that we can never really rid ourselves of disease, that as soon as we abolish one set of major illnesses there will be new ones, waiting in the wings. This seems to me a myth, and I do not believe it. But even if it should turn out to be true, it must be said that if we can learn to control today’s finite list of diseases we will have gained so much knowledge and insight into disease mechanisms that we ought to be able to think our way around any new ones that come along. Nature is inventive, to be sure, but not so inventive as to contrive an endless series of brandnew, impenetrable mysteries be- vond our solving. If we get to be good enough at understanding those we have today, we will be far along toward understanding new ones. ~The criticism that troubles me the most is the one most often heard in policy-making circles, especially among economists, that we have had enough of basic research. that it is a luxury beyond our affording, and that we should now cut back on this activity and concentrate our energies on the application of today’s information. 93-999 (Pt. II) O- 73 - 11 498 You would think, to hear this argument, that there were two wholly different kinds of science, one “basic” and the other “applied.” ar- ranged as adversaries in competition for resources. In real life it does not. work this way. All of biomedical science is interconnected and interdependent, and you cannot do one kind without the other. There are important differences in the degree of predictability, and the terms “basic and “applied” have some limited usefulness here. In basic research, the outcome is relatively unpredictable: you do not know what the results will be or where they will lead you: you ean make guesses but you can have no certainty. You have to wait for answers before you can ask the next question. Therefore, in basic science what you are really looking out for is surprise, and the intensity of surprise is what you use to evaluate the quality of the science. The discovery that all genes are made of DNA ame as a total surprise, and the subsequent discovery that the DNA molecule is a double helix, constructed for the transmission of coded information, was flabbergasting. In applied science, you have to have a fairly clear idea what the outcome will be, and the results are therefore much more predictable. You can plan the work in great detail, over a long stretch of time, provided that you have confidence in the basic information available at the outset. The development of the polio vaccine was a spectacular example of this kind of research. Given the basic information that there were three different types of virus, that all three were antigenic, and could be grown abundantly in tissue culture, it was predictable that a safe aceine could be achieved by human intelligence, and this was done. There is a somewhat similar problem in the cancer field just ahead. It is now predictable that human cancer will turn out to be associated with virus infection, just as are the majority of animal tumors. It is not a certainty, but it carries a sufficiently high probability to justify the investment of a lot of time and resources. If it is proven conclu- sively, none of us will be especially surprised; indeed some of us will be astonished if it is not the case. This line of work is, by my definition, applied science. It is absolutely essential that it be done, since we must have certain key items of information about these viruses before we can go on to, research on prevention. But work of this kind is at the same time basic science, since it carries questions about the nature of cancer viruses, and the mechanisms underlying the transformation of normal cells to cancer cells, which are at the present time totally mysterious. No matter how this aspect of the research comes out, if is unpredictable right now, and we are all bound to be surprised. You cannot separate the two kinds of science, nor should you try lest they both grind to a standstill. You cannot decide to concentrate on applying information, unless the information is there, ready to be applied, and this is not the case today for the major disease problems. Important data is not to be found lying about, nor does it simply fall into our laps. It is dug out by fundamental research. We tend to forget that today’s technology for the control and cure of infectious disease—surely the undisputed triumph of modern med- icine—required a very long period of basic research, dating back to 499 the turn of the century. It did not appear full-blown with the dis- covery of antibiotics, as we sometimes assume. Senator KexNEepy. I suppose that is one of the key points, the long period of basic research in back to the turn of the century. As I understand it, part of the thrust of your testimony is that we are cutting that kind of effort now, as we look down the road toward the future. Dr. Taomas. That is my argument, sir. We have assumed that it has all happened in the last two decades, and, as a matter of fact, the major advances that we now are crediting with prolongation of life and cure of disease are based on science that was done decades ago. Long before the entire idea of an antibiotic drug could even have been imagined, it was necessary to work out the connection between bacterial infection and human disease, and this was a formidable achievement, requiring decades of hard science. We should not forget this; the fact that our hospital wards are no longer crowded to the corridors with cases of lobar pneumonia and typhoid fever could never have come about if it had not been discovered, by some extremely bright and imaginative scientists, that the pneumococcus and ty- phoid baccilus were the causative agents in these diseases. I believe that our situation today, for the major diseases that worry us the most—cancer, for example, or schizophrenia, or coronary dis- ease—is roughly equivalent to that which confronted students of pneumonia or typhoid fever decades ago, when the role of bacteria as pathogens was just being glimpsed as something altogether new. The mechanisms we are searching for today are quite different, and they may turn out to be even more puzzling and unpredictable. But they are there, and we must uncover them before we can develop the technology we need for the future. This does not mean that we are in for the same long stretch of time ahead. There are numerous threads connecting the mechanisms of different diseases, and as we study one kind of disease we inevitably uncover pieces of information that lead to advances in other fields. The early work on polio virus, carried out during the development of the vaccine, made its own connections with research on the viruses that in- fect bacteria, and the new field of molecular genetics opened up com- pletely new approaches to congenital disease in man. The early pneumonia research on the specific carbohydrates contained in the capsules of pneumococci led, more or less directly, to the discovery that the genes of these organisms are made of DNA, and this is now the central fact of molecular biology. These fields have become inter- connected, and we now know that viruses can behave like mobile genes: they can enter cells and become part of the permanent inheritance of these cells, and one of the important outcomes of this event is cancer. Senator Kexnepy. As I understand what you are saying through this part of your testimony, actually we are on the verge of some very significant potential breakthroughs which makes the effect of these cutbacks even more devastating. Do I gather from what you say it is even more devastating in terms of its impact now in perhaps delaying the kind of breakthroughs in a wide variety of different research areas that could otherwise be achieved ? 500 Dr. Triomas. Yes, sir. T must say although T am sure I am expected to say these kinds of things, because T am at the present time a dean, that as a clinician of somewhat long standing and an experimental pathologist of several decades, this seems to be the very worst of times to cut back on biomedical research. It is my view that all of us in the field who are obsessed with human disease have been waiting for just this decade. Behind us now stands the decade and a half—or is it two decades ?—of the biological revolu- tion, which is a very real thing. We had to wait this long for the kind of information we needed for exploring disease mechanisms, and here it is. T would look forward to the next two decades as being immensely productive in the study of human disease, as the last two decades have been in the study of fundamental life mechanisms. I think this is the wrong time to cut back. and particularly the wrong time to cut back on the training of young scientists who have to do this work. Senator Ken~Nepy. Does it make a great deal of sense to be cutting back in some of these research areas while increasing resources in. let us say, the war on cancer? Dr. Tromas. I do not think so, sir. IT am in favor of the President's initiative for the exploration of today’s needs into the cancer problem. I think that is a good idea and worth all the money that has been envisioned for investment in it. However, I do not think that that is likely to succeed if we cut back on the support of basic biological science. I would prefer to see, for example, increased support proportionately for the National In- stitutes of General Medical Science. I think that the kind of work that institute has been supporting in its recent history has been precisely the kind of basic biological science that the cancer problem is going to need most badly for the next decade, and I do not think this is the time to cut back. I think it is the time to expand. Senator Kexxepy. I of course could not agree with you more. It seems to me as one who has been very much interested in the develop- ment of legislation on cancer, that it was not meant to really side- track the other biomedical research that was taking place, but to add to and complement it. You are the expert in this area. The effort to conquer cancer is really going to have to build on a very sound biomedical research program, one that is amply supported and whose benefits are readily accessible to the biomedical research community. Dr. Tomas. I have just one other general point to make that I would like to make, Senator Kennedy, if T may. Another example of this sort of thing, starting out from an un- likely source and with total unpredictability. is the work that began during the Second World War on skin grafting, in an effort to improve the treatment of human burns. As it happened. some elegant biologi- cal scientists became interested in this problem, and. as always. one thing led to another. Today. in retrospect. we can trace a line of in- vestigation straight down through two decades, starting with the phenomenon of the rejection of skin grafts and culminating with the delineation of a powerful mechanism for immunologic defense which 501 is crucial for protection against cancer. The same line of research has uncovered mechanisms which seem involved in a major class of hu- man illnesses now termed auto-immune disease; these include, among others, rheumatic fever and rheumatoid arthritis. The recognition of the connectedness of the fundamental processes in living things is the most startling and exciting aspect of biomedical research today. It is in the very unpredictability of the new kind of science, the totally surprising linkages between items of information that used to seem unrelated, and especially the new observations that now lead us across from one field to another, that give us the greatest hope for the future. We are, at long last, beginning to get clear glimpses of how cells and tissues work, and it is precisely this insight that we need in order to learn how things go wrong. Meanwhile, however, we are still confronted by ule gaps in our knowledge about disease, and we are obliged to face up to this ignorance. Much of what we can do today, to prevent human disease or to turn it around, is still in the area of infection; it is here that we possess a really powerful technology. For most of the other major diseases—heart disease, cancer, strokes, insanity, arthritis, and the rest—we are beginning to glimpse important clues, and there will be more just down the road, but meanwhile we are stuck with technologies not designed to cope directly with underlying mechanisms. As it turns out, these are halfway, stopgap measures, sometimes effective in mak- ing up for the damage done by disease, but immensely costly, complex, and fundamentally inefficient. The transplantation of human organs is an example of this kind of halfway technology, where we must try to replace whole organs because of their destruction by disease proc- esses which we still do not understand. The expensive and complicated technology of the coronary care unit has become a necessity because we do not know enough about coronary disease to set about prevent- ing it. It is worth recalling that we went through a similar stage of half- way technology for the infectious diseases now under control, and it was an enormously expensive business. In the years before the devel- opment of the polio vaccine, we were already constructing whole institutions for the mechanical treatment of patients with paralyzed muscles. Just before the development of chemotherapy of tuberculosis in the early 1950s, we were planning new surgical facilities for all the TB sanitaria, in order to remove the infected parts of tuberculous lungs. We had evolved an extremely complex, laborious and largely ineffective technology for the management of typhoid fever in the years before the development of chloramphenicol, which now cures the disease within a few hours, and for a few cents. There is an important generalization here, which I believe to be true even though I cannot prove it. It is this: the cost of medical care is at its highest, and the technology at its most difficult, during the time when we must work with an incomplete understanding of disease. Whenever we have gained a genuine, penetrating insight, based on hard facts, and then developed a direct, decisive technology on the basis of this, it has always turned out to be relatively simple, and rela- tively cheap. It is simply not true that medical science becomes more expensive when it progresses to outright success. The greatest chal- lenge for the health care system of the future will be to replace today’s 502 ineffective or partially effective technologies with measures to solve our disease problems, one by one, once and for all. I do not see any choice in the matter, if health is to be given the priority in this country which it merits. We will need more and bet- ter research at all levels, and more bright, imaginative, and highly trained young scientists, coming into the enterprise for the future. There can be no shortcuts. Nothing is going to fall into our laps. The science lies behind us and ahead of us, we are in the middle of it, and we must not stop here. The stakes are indeed very high, and there is an element of gambling in the whole undertaking, in the sense that none of us can predict which disease will come down first, or when it will happen. The only certainty is that it can happen if only we will keep at it, and keep our minds open to the future. Senator Kexxepy. You are saying here it is much cheaper to give a child the polio vaccine than to spend a lifetime in treatment and care. Dr. Tuomas. In the early 1950’s we were about to invest vast sums of money in whole institutions for the mechanical treatment for peo- ple with paralyzed muscles. Now we are finished with that. In the early 1950's we were trying to build in new TB surgical fa- cilities because we wanted to remove the parts of the lungs that car- ried infection. This would have been a staggering investment. Senator Kex~epy. This could be true about the institutionalization of, say, people like retarded individuals and otherwise. You may have made some progress in these areas, but obviously in terms of expense to society for instituting these people, this could be greatly decreased. Dr. Troyas. I believe it to be true for most of medicine. It is when 'we are stuck with what I call half-way technology that the costs become unbearable, and I think we cannot afford to go on with that kind of technology for a much longer time, particularly with the increase in our population. Senator Kennepy. The impact of this on schizophrenia, for exam- ple, in mental institutions could be significant. Dr. Tromas. That is an example where I do not think we are more than half way along, and where I think if we can make decisive break- throughs in underlying disease mechanisms, we will see a demonstrable benefit to the country. Senator Kexnepy. Besides being a very distinguished researcher, you are a distinguished dean, could you tell us what the impact on the schools of public health would be in this country with the sug- gested budget ? Dr. Taomas. I know only that it is going to be bad. At Yale we do not have a school of public health, but we have what we call a de- partment of epidemiology and public health, which is the equivalent of a school. We do not know, nor do we think it is likely that we are going to soon discover, what these “other sources™ of money are to which we are now supposed to turn. I see it clearly as an unqualified disaster. The likely result of the reduction in funds for schools for public health will be an effect on both the students and the faculty, and on all the programs of inves- tigation and teaching. 503 At Yale we figure that something like 75 percent of the student body in the schools of public health will no longer have the resources on which they depended up until now, and we see little likelihood that they are going to find them. The tuition and other costs that they will encounter are going to be very high. We also expect to lose much of the money that now goes into the salaries of faculty in the public health school, and we do not know where new money will come from. Senator KENNEDY. It is not only Yale. Would you say that is typical of the other schools? Dr. Tuomas. I think it is typical of all of them, without any excep- tions. The State schools are in just the same kind of trouble. Senator KENNEDY. You think some schools are threatened with closing ? } Dr. Taomas. I do not know yet. It may not be that they are going to close, but they will have to cut back their programs so drastically that they are going to look closed. Senator KENNEDY. What is the impact of these cuts on the biomedi- cal research, in your medical school ? Dr. Tromas. The major effect, which at the present time worries most of us in the deaning business, is in the training area. We are ap- prehensive lest a whole generation of young graduate students sud- denly vanish, if we are without funds to train the medical school graduates themselves who should be undergoing training for research. I think one of the real catastrophies, although it is a relatively small scale problem, will be the loss of the M.D.-Ph. D. program, which involves six or eight men to a medical school class who have been es- pecially selected to go on for a simultaneous training in research and in medicine. This program will be, as I understand it, eliminated along with the other training programs, and the loss of this sector of the rising gen- eration of scientists is going to be a very serious matter indeed. Senator KenNepy. In the cutting back of the training program, who does that really affect? Does it catch one group in society more than any other? Dr. Tuomas. It catches the students, the young scientists. Of course portions of the faculty of medical schools that are now being funded through the training program will be affected, but I do not think that is as deadly serious a matter as the loss of the future scientists, on whom we are going to be totally dependent in the 1980’s. I do not think we can afford a four or five year gap in science train- 3% here. It will be very hard to put it back together again if it is ost. Senator Kennepy. Once you have dispersed, lost the teams, then it is going to be exceedingly difficult to bring them back? Dr. THomas. Yes. Senator KENNEDY. On your training scholarship programs, don’t they provide an opportunity for minority groups to enter these fields. or TroMmas. Yes. We have a better opportunity now than ever in the past. Senator KENNEDY. So that effectively would be curtailed ? Dr. Tomas. We expect it to be, yes. 504 Senator Kenx~epy. Thank you very much, Dean. You have heen very, very helpful. Our next witness this morning is Dr. Michael E. DeBakey, Dr. De- Bakey is President and Chairman of the Department of Surgery, Baylor College of Medicine, and Director of the Cardiovascular Re- search and T raining Center at the Methodist Hospital, both in Houston, Texas. Dr. DeBakey has had a long and illustrious surgical career, during which he has earned renown not only as a medical inventor and in- novator, but as a medical statesman as well. We have been privi- leged to have Dr. DeBakey before this subcommittee in times past, and wish to extend him a cordial welcome, and our thanks for trav- eling such a distance to be with us today. STATEMENT OF MICHAEL E. DeBAKEY, M.D., PRESIDENT, BAYLOR COLLEGE OF MEDICINE, HOUSTON, TEX. Dr. DeBary. Thank you, Senator Kennedy. First, I want to ex- press my appreciation for the opportunity and the pleasure of ap- pearing before your committee again. I have prepared a statement which I have submitted to the secre- tary, and, if I may, I should like to have your approval for it to be included in the record. Senator Ken~Nepy. It will be so. Dr. DeEBaxey. Therefore, I will not attempt to read that statement. I would like to supplement the statement by a few brief remarks and then show a film that will take about 5 minutes and which, T think, will help illustrate some of the points I want to make. First and foremost is the fact that as far as the biomedical sciences are concerned. I think it has been most responsible for bringing the health of the people of this country to the high level we now enjoy. That 1s not to say there is not a great deal that we can do to im- prove the health of the people of this country, but if biomedical re- search had not taken place over the past several decades, we would not be able to enjoy the quality of health care which we are able to give the American people. Now more than 70 percent of the research endeavor that has brought the knowledge of this improved quality of health in our country comes from the federal government. That is why the research funding that comes through NIH is so extremely important. It is all very well and good to say let us turn to other than federal sources for these purposes. but as one who has a responsibility at one of the medical schools of this country to help maintain the integrity of that institution, and to give leadership to the funding of the Tnstitu- tion, I can assure you that funds of this kind are extremely diflicult to come by. So far as I know, there is no way by which it will be possible to replace the funds that the federal government now provides for these various purposes. In the field of arteriosclerosis, vascular surgery, which is, of course, my own personal field of competence, more advances have been made to successfully treat various forms of cardiac emergencies in the past two decades than in all previous recorded history. 505 We have reached a state where we can effectively control a large variety of different kinds of heart disease. For example, we are able to completely correct 80 percent or more of the various forms of congen- tial heart diseases, and to restore these patients to a relatively normal life, and most of them can look forward to a normal lifespan. This is in direct contrast with the fact that before about 25 years ago none of this was possible, and all of these individuals were doomed to either early death or to disability, a life of various afflicted symp- toms over a period of time. In the field of acquired heart disease I would say here again we have made tremendous progress. Most forms of acquired heart disease are a result of conditions of the arteries, and the film that I am going to show will illustrate some of the various factors that have been un- covered through biomedical research during the past two decades in relation to disease which affects the coronary arteries and causes more deaths than any other disease in the country. Primarily the focus has been a better understanding of this form of heart disease as it affects different parts of the body. We now have a fairly good understanding of the patterns of this disease, which has as its underlying cause arteriosclerosis. Secondly, research has resulted in a means of treatment which, through the understanding of the patterns of the disease, provides a very effective way of overcoming the effects of the disease, so that one can restore circulation, which the disease affects and, depending upon the organ that the arteries supply, such as the heart or ey brain, kid- ney, and so on, the individual may suffer either death or certainly long- term disability. Now, this film which you will see in just a moment will show two patients who before 6 or 7 years ago would have continued either to be extremely restricted, to suffer severe chest pains, and probably to die within a period of several years, if not less; yet both of these patients are living today and leading perfectly normal lives. One is a relatively young man of about 37 years of age; the other a man of about 52. So these diseases do not affect just older people ; they do affect a large number of individuals in the prime of life. The methods of treatment that you will see have been developed, as 1 say, through research. The basic and important consideration here is the fact that the method of treatment used combines the scientific developments and the knowledge obtained from biomedical research; it combines all of the knowledge that is put together to finally make it possible to treat these patients effectively—in other words, it brings to 5 pl ymieal problem knowledge derived from research over a long period of time. If you want to call that a breakthrough, ultimately, that is one thing, but I think in most instances it should be recognized that there has been a long period of research in various areas, and the bits of knowledge thus acquired are finally put together in a form which can be applied to correct a clinical problem. If we may, Senator, I would like to have the film shown. Senator Kennepy. Certainly. [Motion picture film was shown. ] Dr. DeBaxey. What you are seeing is arteriography. This in itself took long years of research, but probably was the key to application 506 of cardiovascular surgery. It precisely delineates the location and ex- tent of the disease. What you are now seeing is the right coronary artery being opened by an incision, and then extended by the scissors, and you can see the opening there quite well. This is just distal to where the artery is blocked. One of the characteristic patterns of arteriosclerosis and athero- sclerosis demonstrates that these lesions have a localizing character, and very often the artery beyond the block is perfectly normal. If you could overcome that block either by removing it or by by- passing it, then you could restore circulation. That is what is being done here. A vein removed from the leg is to be attached to that opening in the artery. That vein will then be attached to the aorta above which is where the normal coronary artery arises. It is just being sewed by a simple continuous suture which attaches the vein to the opening in the artery. Now, you will see the other end of the vein being anastomosed to the aorta. An incision is made in the aorta and the vein is sutured to this opening in the same fashion that was done to the coronary artery. It is cut and tailored, to fit the opening, and then sutured te the aortic incision. Once that is completed the clamp is removed, and blood will go from the aorta into that vein, and then down into the distal segment of that coronary artery to supply an adequate amount to the muscles of the heart. Now you see it is working fine. That patient will now have an ade- quate amount of blood going to his heart. Tis heart muscle now is no longer suffering from a lack of arterial blood flow. There you see the arteriogram showing the vein functioning. That was made about three years after the operation. This patient is an active truck driver, leads a perfectly normal life, and has no difficulty of any kind. About 85 to 90 per cent of the patients respond that effectively. In this next procedure we will perform an endarterestomy. This is the arteriogram and you see that the right coronary artery is com- pletely blocked throughout its full course. All you see are little fili- ments, that we call collaterals. What we are doing is to inject into the blocked right coronary artery carbon dioxide under pressure in order to separate the other anatour plaque from the outer wall of the artery. An incision and separated is then made in the arterial wall to expose the atheramatous plaque. The carbon dioxide under pressure is then injected by means of a long needle to separate the plaque from the wall of the artery. You can actually see what the atheramatous plaque looks like as it is being freed from the arterial wall. This patient is being operated upon using the heart and lung ma- chine to keep him alive while this is being done. You will observe that the heart slows down and almost stops but because the patient is completely supported by the heart and lung machine he can be kept alive during the procedure. One can stop and start the heart at will now. You see some blood coming back into the arterial opening, that is blood coming retrograde, 507 as we say, through the small branches of the artery, as the atherma- tous plaque which has been blocking these branches is removed. You will see a gush of blood come out, as the atheramatous plaque is removed proximally and that means, of course, that we have re- moved the block completely and blood is now flowing normally in that coronary artery. We use a little dilator just to be sure it is open all the way. Then we repair that with a patch, so, of vein to keep from narrowing it when we sew it together, and that is all there is to the operation, but it does restore normal circulation to the heart. The patient’s heart is now functioning normally and off the heart and lung machine. Now you see the arteriogram, and you can see for all intents and putpases that is a perfectly normal coronary artery. This photograph was made about three years ago. Again, as 1 say, this patient has remained perfectly well. If one takes the various elements that have made this operation possible—and we are now doing this operation routinely; in our own clinic we do an average of eight or ten of these a day, and it is being done all over the country—it is being applied very effectively; 85 to 90 per cent of these patients now respond very well, with a very acceptable mortality rate of perhaps less than five per cent. Most of these patients are patients with disease that nothing could have been done for effectively before the development of this type of surgery. But the important point to make here is not so much that we have developed this type of surgery, but the fact that this type of surgery has become possible because of the long period of medical research in the laboratories that took place over the past several decades, particu- larly during the past two decades. This is why I think that research is so important to the future qual- ity of health care in this country. If you cut back on the research, you are simply going to reduce the future quality of health care in this country. This is one of the reasons that I believe that today cutting back not only on research but on research training, which is an integral part of research, is a disaster to the future of the quality of health care in the country. We can do all we want and say all we want about the ways and means of delivering health care. The quality of health care of the peo- ple of this country is dependent upon new knowledge, and no amount of money using current knowledge is going to improve that quality very much. The only way you are going to do it is with research and research training. Thank you, Senator. Senator Kenney. That was very powerful and moving testimony, Dr. DeBakey. You never cease to amaze us. We want to especially thank you for expressing so eloquently the impact these cuts will have in the area of which you are so well informed, and the work that you do in helping the sick. Could I ask you just a little bit about where we are in the artificial heart phase. What kind of progress is being made in that? 508 Dr. DeBakey. I think I can say very simply the progress that has taken place in the artificial heart program has been relatively good considering the restrictions in funding that have been placed upon this program. There has been a limited amount of money available for this pro- gram over the past decade. It never has been increased significantly each year, so that it has remained at a fairly comparable level each year. The progress that has been made has largely been made in a better understanding of the problems that need to be solved, and, secondly, in some of the by-products. I brought with me, in the event there was time to mention it, just two by-products of the research on the artificial heart program to sim- ply illustrate that in addition to the objective of the artificial heart re- search program, there are other by-products of research that sometimes have important clinical application. One of them is concerned with the development of new artificial arteries. We just released this type of new artificial artery on the market based upon 5 years of research, which really stems from the artificial heart program, supported largely by the artificial heart pro- gram, because one of the important problems concerned with the arti- ficial heart program was the development of a lining for the artificial heart, a lining that we call the blood interface, that would allow blood to flow across this lining in the pump, and in connections without dam- age to the blood. Out of this research came this type of artificial artery which, as I say, has proved to be the most successful artificial artery we have developed, and since we have been in the business of trying to develop and work with artificial arteries for 20 years, we have had some experience with it. We have just recently released this for manufacture to make it available to everyone else. A second by-product, of course, is valves. An artificial heart has to have valves because you have to have unidirectional flow. This is a valve which we have also released for manufacture and availability to the public. It is a valve which we developed in the artificial heart program, and which has proved to be the most successful valve we have yet used clinically. and again it is based upon more than 5 years of research. It is made of a special material which has proved to have very good response to blood. Those are two of the problems that we have had solved in the artificial heart program. A third is related to controlling mechanism and synchronization ; and a fourth one is related to the energy support. In contrast to our experience, say, 3 or 4 years ago, we can keep animals alive today for a week or so on an artificial heart, but that is about as long as we can go. A second and important byproduct is concerned with what we call the assistive devices. These, of course, support the heart temporarily, have proved to be very effective clinically, and are being used fairly widely, so that the program has, 1 think, been very productive, although it has not yet reached the stage where we can look forward within the immediate future to the complete replacement of a heart with an artificial heart. 509 Senator KennepY. During the course of our hearings we have been very much concerned about the distribution of various drugs, and we have seen that the Food and Drug Administration OK’s certain drugs for certain usages, and have found those drugs are being used for other purposes. Now, there really is no kind of review other than peer review of procedures which are practiced by individual doctors. Is there within your group the same sort of problems for medical devices as there is for drugs? Should there be more regulation of devices or should there not be ? Dr. DEBAkEY. You mean in the device area ? Senator KENNEDY. Yes. Dr. DeBakey. Yes. I have said that there should be, and it is my understanding—and I have worked from time to time with the agency and the FDA on this with those who are interested in develop- ing legislation on devices. I certainly do believe that there is a need for some standards in this regard, and some methods of control for standardization. I think that most workers in this field would agree with this. I think it is a ques- tion of how best it should be done, but there is a committee which has been working on this, and I have testified regarding this before on several occasions. So I would agree with the general principle that there is a need for this. Senator KexNepy. Do you think that when you use the first artificial heart you would consult with the family, and would you feel it neces- sary to consult with other doctors, as well as have a peer review ? Dr. DeBaxkey. I would say that before this should come to clinical application, there should be a very thorough review of the experi- mental results to clearly demonstrate it is feasible to apply to human beings. At the moment it is not. If one uses the guidelines of the National Institutes of Health, which all institutions who accept funds from the National Institutes of Health have been willing to accept, and willing to sign, then I think that it is possible to implement an adequate review before applying, let us say, a device of this kind to a human being. We certainly have two sets of committees in our own institution which would review anything of this kind. As a matter of fact, these committees function in the field of kidney transplantation as well as in the field of assistive devices. Senator Kennepy. After you have developed the artificial heart how are you going to decide who is going to get it ? Dr. DEBakey. I think, Senator, that I do not regard this as a serious problem, or as serious as it might seem to be at present, largely be- cause I believe that there are a number of practical considerations that would take care of it. First, I think it is important that there be established some rules and regulations which the institutions themselves would have to abide “i think that in the general framework of the National Institutes of Health these rules and regulations are at the moment anyway quite adequate. Secondly, I think that there would be a need to insure beforehand that the results of the experimental work justify consideration of its clinical application. 510 Now, I think we will just have to wait and see if it is going to be that expensive. My own feeling is once we have solved the problems I'am talking about, it will not be that expensive. Senator Kexnepy. Why are there so few heart transplants being performed? Dr. DeBaxey. I think there are several reasons. One is the general clinical assessment of the experience we have had would clearly indi- cate that the yield is not quite enough to justify the effort in the creat majority of cases. In our own experience, for example, out of 12 patients, only two survived more than a year. These two did survive four years, and one of those actually is still living and is going in his fifth year. This is rather unusual. A very small percentage of patients has survived that long. Secondly, I think that most people do not fully appreciate the donor problem and the logistics involved. We have seen patients who needed a heart transplant and there was nothing else that could be done for them, but the need was so desperate that they could not wait until a donor became available. The donor availability, as far as the heart is concerned, is very restrictive. For one thing, the donor has to be a rather young, healthy individual. Te has to have had a rather special type of accident, in which the brain is destroyed but the rest of the body. particularly the heart, is not, and the heart is still beating at the time he can be brought to the hospital or at the time he can be considered as a donor. For kidney transplants, one can reap cadavers’ kidneys. But one can- not do that with the heart transplant. One cannot bank them. Then, of course. there are these other developments, particularly in coronary artery disease, that have made it possible to repair the heart in a good many of the patients who were considered as potential recipients at that time. Senator Kexzeoy. Finally, Doctor, you are very much involved in the whole public area of discussion about reforming the health care system. Why do you think there has not been more a sense of concern expressed by the American people about the cutbacks in biomedical research ? Dr. DeEBaxey. I think there are several reasons. First and foremost, they constitute a very small constituency. The majority of people do not know where their medical advances come from or how they are made possible. I am amazed at how few doctors know anything about the NTH and its importance. I think that if there has been any single factor that has contributed significantly to the advance of the health of the American people, it has been the NTH, and the funding that Congress has provided to support medical research through the National Institutes of Health. Yet it remains an agency that has not really received the public notice it deserves. Therefore, T do not think the American people generally know enough about the importance of the National Institutes of Health, nor do they know that 70 percent of the research of this country and the training, even education and science, is dependent upon these kinds of funds. 511 The tragedy of all this lies in the fact that these funds constitute a relatively small proportion of our total budget, and to cut back on this small proportion of our total budget would not, I think, have that much of an impact as a constructive approach to our economy, as its destructive effect upon our health for the future. When you think that we are investing something less than 3 per- cent of the cost of health in this country on research, and you realize that in any science-based industry more than 10 to 20 percent of the sales of that industry is invested in research—and certainly health must be regarded as a science-based industry—we realize what a low priority we give to health in this country. Senator KennNepy. Thank you very much, Doctor. It has been very, very helpful. I know you have come all the way from Texas for these hearings, and we appreciate this very much. Our last witness this morning is Dr. James Watson, of Cold Spring Harbor Laboratory in Cold Spring Harbor, N.Y. Dr. Watson is also a professor at Harvard University and, most importantly, has won renown as a Nobel Prize laureate, a prize which he won for his dis- covering, in conjunction with others, the structure of DNA. Dr. Watson, welcome to the Health Subcommittee. I know we will find your testimony fascinating and immensely useful to us. STATEMENT OF JAMES D. WATSON, PROFESSOR OF MOLECULAR BIOLOGY, HARVARD UNIVERSITY Dr. Watson. Senator Kennedy, 1 greatly appreciate being given time to say something about gross genetics and the general state of biomedical research in this country. I have a prepared statement which people can read, but it is getting late. Senator KexnNepy. We will include it in its entirety at the conclu- sion of your testimony. Dr. Watson. I will limit myself to some remarks at the end because 1 think these are the ones which are most pressing. If you put it in the background of the last two decades, we have witnessed what we people call the biological revolution which has brought forth many new fundamental discoveries, most of which were worked out using bacteria. It is the feeling of the scientific community that the next two decades will witness the extension to higher cells, particularly human cells. We believe that in the next two decades you will witness a marked expansion of our fundamental knowledge of the human cell. That will go parallel with what we hope will be many more medical advances. 1, until recently, together with most of my colleagues, have thought this course of affairs so obvious as not to be doubted—the objective of the preservation of our health, both in the immediate and in future generations, should be clearly at the top of our national priorities. The events of the past several years, however, leave me with much less confidence. For the message increasingly coming out of the executive branch is that science is fine as long as the payoff is fast and our Nation’s scientists are skillfully channeled into work on major national problems. With the dollar weak and American products not always wanted by other nations, the word is out that we are not rich enough to do science 512 for science’s sake, but only if it generates a quick return for the buck. Unfortunately, this way of proceeding. which could at first sight sound like commonsense, represents a puerile understanding of both how good science is done and how its discoveries have been directed toward human application. We must never forget that for the most. part we have little insight about the truly unknown. The world we live in is immensely compli- cated and on the whole its natural phenomena are remarkably un- predictable. All too often, only after a chemical reaction within a cell has been observed do we find a reason for its existence. Thus it is almost impossible to plan ahead what the future will bring. About the best we can do is to try to bring our most intelligent and sensible minds to bear on a given problem, then let them go at their own speed and direction. This should be the way the hoped for “Conquest of Cancer” should be administered. This objective all too clearly depends upon the emer- gence of unexpected new discoveries and so demands the talents of the very best brains this Nation possesses. They will do the best job if essentially left to their own intuition, not to those of the National Cancer Institute's scientific bureaucracy who, despite the best of in- tentions, have no special calling for the undevined. Yet the forthcoming governmental prescription for cancer research, if not for most other forms of medical research, ominously points in the direction of more contract money, in which the Government calls the shots, and less free grant money in which the individual scientist decides where the future may lie. All too large a proportion of this contract money will go to senior established people as opposed to younger scientists who have yet to prove themselves. Yet almost every important new discovery comes from someone under 35 and who at the moment of his breakthrough is essentially unknown to the outside world and so unlikely to be given a contract by a government that looks with distaste on the unpredictable. Iiven more disturbing for the long run will be the effects of the current edict to shut down all NTH sponsored predoctoral and post- doctoral training and fellowship programs, as well as the career de- velopment awards which now support most of the better younger scientists in medically oriented research. If this threat is carried out, not only will all the money be tightly held by middle-aged entre- peneurs, but the science itself will have for the most part to be done by an age group not noted for working into the night, which in the past has only rarely been innovative and so cannot now be expected to have a better track record. I can, thus, only describe as lunacy a governmental policy that openly states the wisdom of choking off the supply of younger people into medically oriented research. One gets the horrid impression that somehow our Nation is mounting monmouth crash programs to de- velop new “pampers”—not to conquer a collection of well dug in diseases against whom conventional approaches bounce off as if they were ping pong balls thrown at concrete walls. Must. the new American tradition be to lose our wars and call them victory? Is it possible that some day we will have our Government say that the real problem is not cancer or strokes or coronaries, but 513 the scandalous behavior of the research scientists who lack the in- tegrity to carry out its Government’s wish for instant victory? For the sake of my children and their children, I hope not. Senator KENNEDY. Fine, Dr. Watson. You have said on other occasions that perhaps the most important period in a researcher’s life is in the earlier years. You have indicated the work done before age 30 is very significant if research efforts are to be developed. What is your impression of the impact of these cuts on those young people who are in the prime of their research lives? Dr. Watson. First, I think it will cut back the effective number going into medical research, probably to at best a third that could now go on. Second, they will be much less well trained. Now, by the age of say 26, graduate students are doing serious and important science. Thus they follow the current rule, will have to work their way through best creative years for experimental biology. As it is, the students, if they follow the current rules, will have to work their way through science, which means hold part-time jobs—drive a taxicab, wait on tables—and then try to do difficult experiments. You cannot do good science just 8 hours a day, being on another job for another eight. This is not the way medically oriented research can be done. Now the administration gives two arguments for their decimation of the fellowship and training program. One is, it is unfair to pay someone’s way through graduate school; the second is, we have too many scientists. They give you one or the other argument depending on their mood. The argument that we do not want to pay your way through because we are not paying anyone else’s way through does not answer the ques- tion: Who 1s going to pay it? I think young people just will not go into tough experimental biol- ogy in the necessary roan The general reaction is, “If I am going to have to borrow large sums of money, I am not going to do it for a career that is very uncertain at best.” One would like to say most young people who go into science make large piles of money, but they do not. A discovery in science is a very hard thing to make, and often takes real luck as well as much intense work. So for someone to borrow $20- or $25,000 to put themselves through for a career which may not go right, borders on the irrespon- sible, particularly if they have a family. The second argument is we have too many scientists. Well, that depends on where the Government decides on where it wants to spend 1ts money. I suspect the whole national cancer program will soon be a giant fraud if we do not have new people going into it. Senator KEx~Nepy. The cancer program ? Dr. Watson. The cancer program will be a fraud, because up until now most cancer research has been very ad hoc, being done by doctors who were not trained for the subject. But now we think that the next steps have to be done by highly trained people who now do not exist. For example, take something like Fort Detrick, where the NCI will soon put $20 million per year into 93-999 (Pt. II) O - 73 - 12 514 it. Now they are placing ads in the paper for people to go there. Un- fortunately they are unlikely to get the right people, since there are not enough being trained in the field of animal cell culture and animal virology. Senator KennNepy. Does it make any sense to have a war on cancer and not have adequately trained people to carry it on ? Dr. Watson. I said it is lunacy. I suspect the administrative people think in terms of careers like banking in which people make it to the top of their pack at something like the age of 55. However, good science just is not done that way. What would happen if the President decided there would be no new funds to train baseball players? Just use our existing ones. It would get pretty boring after a while. This is what they are proposing for science. There is a fraud in saying the money is going up. They have done it by taking it away from the Institute of General Medical Sciences where the money is for the unpredicted, throwing it toward more predictable branches of science. As a member of the National Cancer Advisory Board. I see most of our money going out for stuff that looks so sound you know it is not going to work. This is most depressing, since the money goes out with no sparkle or enthusiasm. I must confess, I find it a little depressing prospect going to the ad- visory meetings, because I never expect to hear the government com- ing forward with anything that sounds to me like it is going to do anything better than what is not working now. Senator KEnNepy. What do you suggest that we do ? Dr. Watson. T suggest that we have to bring some new people into the field, and in cutting off all training you just might as well cut off the program. Each of the graduate schools I know that is hoping to admit the people next year, still does not know where the money is coming from. Senator Ken~epy. So there is really a heavy burden on the Congress in this area. Dr. Watson. There is a heavy burden on the Congress to insure that people continue to have the opportunity to go into science. Mr. Caspar Weinberger’s approach, “Let them borrow the money for graduate school—after they have already borrowed the money to go through college,” is not just going to work. So, as at Harvard, our reaction will be just to cut down drastically the number of entering students. The Administration also flippantly says that we should use grant money, but the grant money going toward basic science is going down. Senator KenNepy. I do not know the researchers or the scientists that Mr. Weinberger has talked to in order to draw these conclusions. Do you? Dr. Warso~x. No. He certainly has not consulted anyone IT know, and T have no idea where the executive branch gets this advice. Senator Kexxepy. In your conversations with any of your friends or colleagues or other scientists, have you found any of them who think this is the proper path? Dr. Watson. Not one. What has happened is the entire biomedical community isin deep despair. 515 Senator Ken~epy. Who is advising the President on these matters? Dr. Watson. The National Cancer Advisory Board urged that the training program be continued, but that advice was certainly not listened to. I, of course, can only speak for the body of which IT am a member. Unfortunately, the academic community now seems not to have much fight in itself. They have seen themselves so impotent against the war that when something horrid happens, their back is already half broken. I think there is also somewhat a fear that if you oppose it, they will just cut you even more. Senator KennNepy. What is that? Dr. Watson. They will cut you even more. Senator KenxNepy. Who? Dr. Watson. The scientific community. Senstor KenNEepY. Do you mean: Be quite or you will be cut some more? Dr. Watson. Yes. This is not the time to speak out; just be thankful for the crumbs. Senator KexNEpy. Some medical educators have stated that the fiscal crisis is the greatest they have ever known. Dr. Watson. Certainly there has been nothing like it since I have been in science, that is over the past 25 years. There has been sort of an immediate cut to most medical schools at 25 percent, with a grow- ing fear that subsequent years will bring even more bad news. As a child I grew up being optimistic. Now one wonders: Is this still part of our tradition, or is it just another lie? Senator KexnNepy. Doctor, we are going to make every effort here in the Congress to restore those funds. I think you have made a very compelling and convincing argument for this, as have the other witnesses this morning. We are going to make those efforts in the Congress, and are hopeful of prevailing. We have every intention to do so. I want to thank you very much for your presence here and for your appearance. I now order printed in the record your prepared state- ment followed by all other pertinent material submitted in conjunction with this hearing. [The prepared statement of Dr. Watson, accompanied by additional material supplied for the record, follows:] 516 Testimony of J. D. Watson* before the Senate Health Subcommittee on the Quality of Medical Care March 6, 1973 Professor of Molecular Biology, Harvard University and Director of the Cold Spring Harbor Laboratory 517 Mr. Chairman and esteemed members of the committee, I am James D. Watson, Professor of Molecular Biology at Harvard University and Director of the Cold Spring Harbor Laboratory sited on the north shore of Long Island between the towns of Oyster Bay and Huntington. I have been a member of the Na- tional Academy of Sciences since 1962 and at present am a member of the National Cancer Board. For the past 25 years I have been an active scientist, with my primary research interest always being the nature and functioning of genetic molecules. Over the past five years I have been particularly interested in the relationship between viruses and cancer with the hope of pinpointing how the presence of one or more speci- fic viral genes convert normal cells into their cancerous equivalents. I am here this morning with two major objectives; one, to give you a broad overview of where the field of genetics now stands in relationship to medical research and clinical appli- cation, and two, to voice my strong apprehensions about proposed basic changes being proposed by the executive branches for the organization and support of biological and medical research within the United States. You must, of course, realize I am a biased advocate for the central importance of genetics to the well being of the American nation. I could not have kept the subject of heredity my primary concern for almost three decades if I did not find it of key importance to both basic biological thought, as well as to many key facets of our human lives. Ever since my student days at Indiana University when I listened to lectures from the great American biologist, Herman Joseph Muller, I have been very con- cious of the fact that the specific information carried by our genes is what makes us different from all other forms of life, giving to us our unique attributes which we call human. It is thus our most valuable human commodity and must be treated as a very precious and fragile gem carefully guarded from uninten- tional harm. I am, naturally, not saying that our genes completely determine all our vital attributes - the many ways our environ- ment governs what we become or don't become are too well known to bear repetition here. But no matter how optimal the environ- ment, a child born with the Tay Sachs Syndrome will never have a chance to become an adult. Because he received from both kis father and mother bad copies of a vital gene necessary for normal brain development, he will never be able to become an adult. The existence of this disease and many other equally dehabilitating affections, all caused by faulty genetic material, provides much of the interest that we now have in the furthering of our know- ledge of how heredity operates. We want to know the difference between good and bad genes, hoping somehow to prevent more of them coming into existence and to find ways to nullify their destruc- tive consequences. Very fortunately we have come a very long way over the past several decades in elucidating the chemical nature of genes and chromosomes. Now to remarkable detail, we understand how the chemical organization of genes allow them to play such a dominant role in the life of cells. We have found that genes are deoxy- ribonucleic acid molecules (often abbreviated as DNA). A DNA molecule is built up from the linear arrangement of a very large number (often many thousands) of four different building blocks (the nucleotides). The uniqueness of each gene lies in the speci- fic linear order with which these nucleotides are arranged. Each gene has a different nucleotide order, analogous to the way each word in the English language is characterized by a unique arrange- ment of some of the twenty-six letters of our alphabet. Such nucleotide arrangements control the precise order of amino acids in specific proteins like hemoglobin. This fact is often simplified by the phrase one gene - one protein - that is, a one to one correspondence exists between the number of genes and the number of different proteins which an organism may possess. Thus, if a gene is changed, so will be its protein product. Given this viewpoint, we can understand how a disease like sickle cell anemia arises. In this disease, normal hemoglobin molecules are not present. Instead the red blood cells of persons with this condition have slightly altered hemoglobin molecules with one specific amino acid being replaced by another. Because of this change, these mutant hemoglobin molecules are unable to bind oxygen well, giving rise to the resulting anemia. Correspondingly, the genes which carry the information to make the abnormal hemoglobin products differ from their normal counterparts by one very specific change in their nucleotide order with one of the "letters" of its nucleic acid alphabet being replaced by another. As far as we can tell, most chemical changes of genes, which we call mutations, have detrimental consequences. Thus we must minimize our exposure to any agent which we think may chemically modify our genes. Here we are greatly indebted to the geneticists of the past fifty years who have probed to greater and greater detail how mutations occur. While some seem to occur without external causes, the origin of many others are now seen due to exposure to various forms of EAA Ean specific chemicals. Equally important, we are just beginning to understand at the molecular level how these agents act. For the first time we can predict whether compounds have a good probability of harming our genes. For example, we now understand so well how nitrates can be converted at high temperatures to the very highly mutagenic nitrosoamines that as a geneticist I must become apprehensive every time I have a nitrate loaded pastrami or bacon sandwich. We can also begin now to look to the question whether it may be possible to nullify the consequences of specific bad genes, con- deivably replacingithem with externally added new genetic material. Here, however, we are on much shakier ground, since many past claims of genetically altering higher animal cells by addition of purified nucleic acid molecules have been justly regarded with great skepticism. Over the past year, however, several very clean experiments have shown that externally added DNA molecules can, in fact, enter animal cells 521 and become inserted into their chromosomes. The efficiencies of such insertions, however, are very low with at best maybe one cell in a million acquiring a desired gene. Greater efficiency in repairing genetically defective cells might come someday from the use of human viruses which have been so manipulated that their chromosomes now carry small parts of human chromosomes carrying a desired gene, say, for — one which specified normal hemoglobin molecules. Infection of the individuals affected with sickle cell anemia with such modified virus might conceivably expose most of their blood forming cells to the good genes leading to massive replacement of the bad sickle cell genes with good ones. Unfortunately while this method works well with bacteria, I suspect it will be horrendously difficult to apply to humans. One might draw the analogy of sending a man to explore Pluto under circumstances where he has a chance of returning to the earth. But you should remember that when scientists are asked to predict the future they tend to magnify difficulties. They cannot assume the emergence of chance observation that can suddenly make a difficult task much easier. None the less, it probably makes sound sense to assume that genetic therapy is not around the corner, and that we have no rational choice but to see that our human genetic material does not gradually decline in quality because of massive unforeseen mutagenesis caused by widescale dispersion of the all too many poisonous industrial products of our increasingly artificial world. 522 the origins of most cancers are changes in genetic material. Some of these changes occur "spontaneously' while others are due to chemical agents in our environment which chemically modify pre- existing genes. Still other cancers seem to be due to the entry of viral genes into host chromosomes. Very, very, likely, a sat- isfactory understanding of the cancer problem will also depend on further deep advances in our knowledge about the organization and functioning of the chromosomes of human cells. Here I must emphasize that despite our striking successes of the past twenty-five years in working out many fundamental genetic principles, we still have deep and fundamental gaps in our know- ledge of the fundamental biochemistry and genetics of human cells. For example, several years ago the general suspicion was that most of the DNA in a human chromosome carried information for ordering amino acid sequences. Each complete group of human chromosomes would contain some six million genes, a number much too large for us to effectively study in a comprehensible time period. Now, however, the suspicion exists that most of our DNA does not contain genes, and that the real number of human genes may be as low as 25,000 - 50,000 or only some 5 - 10X more than the average bacteria possesses. If this new hunch pans out, which work over the next few years should tell us, then the problem of someday describing all the human genes can be seen to be an accomplishable task - though it may require some 50 - 100 years more of dedicated research. Most likely, however, we will not require anything like this 523 interval before we understand the essential organizational principles which dictate how and when our genes are to work. The next 10 - 20 years will Eel give us this information, that is if this country, together with the other major nations, continue to place a high priority on fundamental biomedical research. I, until recently, together with most of my colleagues, have thought this course of affairs so obvious as not to be doubted - the objective of the preservation of our health, both in the immediate and in future generations, should be clearly at the top of our national priorities. The events of the past several years, however, leave me with much less con- fidence. For the message increasingly coming out of the executive branch is that science ts Tire as long as the payoff is fast and our nation's scientists are skillfully ¢hannelled into work on major national problems. With the dollar weak and American products not always wanted by other nations, the word is out that we are not rich enough to do science for science's sake, but only if it generates a quick return for the buck. Unfor- tunately, this way of proceeding, which could at first sight sound like common sense, represents ‘a puerile understanding of both how good science is done and how its discoveries have been directed toward human application. We must never forget that for the most part we have little insight about the truly unknown - the world we live in is immensely complicated and on the whole its natural phenomena are remarkably unpredictable. All too often, only after a chemical reaction within a cell has been observed do we find a reason for its existence. Thus it is almost impossible to plan ahead what the future will bring. About the best we can do is to try to bring our most intelligent and sensible minds to bear on a given problem. Then let them go at their own speed and direction.This should be the way the hoped for "Conquest of Cancer" should be administered. This objective all too clearly depends upon the emergence of un- expected new discoveries and so demands the talents of the very best brains this nation possesses. They will do the best job if essentially left to their own intuition, not to those of the NCI scientific bureaucracy who, despite the best of intentions, have no special calling for the undvined. Yet .the forthcoming governmental prescription for cancer research, if not for most other forms of medical research, ominously points in the direction of more contract money, in which the government calls the shots, and less free grant money in which the individual scientist decides where the future may lie. All too large a proportion of this contract money will go to senior established people as opposed to younger scientists who have yet to prove themselves. Yet almost every important new discovery comes from someone under 35 and who at the moment of his breakthrough is essentially unknown to the outside world and so unlikely to be given a contract by a government that looks with distaste on the unpredictable. 525 Even more disturbing for the long run will be the effects of the current edict to shut down all NIH sponsored predoctoral and postdoctoral training and fellowship programs, as well as the career development awards which now support most of the better younger scientists in medically oriented research. If this threat is carried out, not only will all the money be tightly held by middle aged entrepeneurs, but the science itself will have for the most part to be done by an age group not noted for working into the night, which in the past has only rarely been innovative and so cannot now be expected to have a better track ‘record. I can, thus, only describe as lunacy a governmental policy that openly states the wisdom of choking off the supply of younger people into medically oriented research. One gets the horrid impression that somehow our nation is mounting monmouth Mapa crash programs to develop new "panpflers" - not to conquer a collection of well dug in diseases against whom conventional approaches bounce off as if they were ping pong balls thrown at concrete walls. Must the new American tradition be to lose our wars and call them victory? Is it possible that someday we will have our ova raat say that the real prdblem is not cancer or strokes or coronaries, but the soandions behaviour of the research scientists who lack the integrity to carry out its government wish for instant victory? For the sake of my ‘children and their children, I hope not. (516) 602.6660 CoLb SrriNG HARBOR LABORATORY COLD SPRING HARBOR, N. Y. 11724 BIOGRAPHICAL SKETCH - DR. JAMES DEWEY WATSON Dr. Watson, a prominent biochemist and educator, is a 1947 graduate of the lhiversity of Chicago, receiving his Ph.D. from Indiana University in 1950. He was a Senior Research Fellow in Biology at the California Institute of Technology from 1953 until 1955, becom- ing affiliated with Harvard University as an Assistant Professor of Biology in 1955, advancing to Full Profes- sor in 1961. He is a recipient (with H.F.C. Crick and M.H.F. Wilkins) of the Albert Lasker Award in 1960 and the Nobel Prize in Medicine and Physiology in 1962. He is a member of the National Academy of Science and the American Academy of Arts and Sciences. He is presently Director of the Cold Spring Harbor Labora- tory, as well as Professor of Molecular Biology at Harvard University. 6/1/70 dds P.0. BOX 100 527 TA i ah RA U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Public Health Service "National Institutes of Health FOREWORD The Department's basic policy, quoted in the first few paragraphs of this Guide, is simple in concept. However, simplicity in conception is not always easily translated into simplicity in application. Many of the basic terms of the policy, such as subject, risk, and informed consent, are differently understood in the several professions that participate in the varied grant and contract programs supported by the Department. This Guide provides working definitions of the policy's more critical terms, and outlines flexible operating procedures which can be adapted to a variety of grant and contract mechanisms. A flexible policy is essential. Research, development, and the re- duction to practice of new ideas are not carried out in a practical, ethical, or legal vacuum. The public interest obviously would not be served by an inflexible approach to what can or should be done. Ultimately, the decisions required by this policy must depend upon the common sense and sound professional judgment of reasonable men. The Department's policy and the Guide are intended to provide room for the exercise of this judgment. In its present form, the Guide reflects several years’ experience with an earlier Public Health Service policy. It incorporates many comments and suggestions by representatives of grantee and con- tractor institutions, and by consultants and staff of the operating agencies of the Department. Future experience in the application of the policy in the fields of health, education, and welfare will simulta- neously raise questions and suggest changes. Correspondence should be addressed to the Chief, Institutional Relations Branch, Division of Research Grants, National Institutes of Health, Bethesda, Md. 20014. D.T. Chalkley, Ph. D. Chief, Institutional Relations Branch Division of Research Grants, NIH, DHEW 529 CONTENTS FOREWORD _________ POLICY: Grants and Contracts _ __ ___ __ __ _____ _____________ APPLICABILITY oc iiss im sion i i mmon®)» General _________________ Subject—Definition ______________________________ At Risk—Definition ______________________________ Types of Risks and Applicability of the Policy _________ Established and Accepted Methods _________________ Necessity to Meet Needs _________________________ INSTITUTIONAL REVIEW ________ ___ A. Initial Review of Projects _________________________ 1. Committee, Composition and Functions ___________ 2. Statement of Principles ________________________ B.. ROVIGW PrOCOSE. ce i ois oo ois ni 50 i ote ant a. Rights and Welfare of Subjects: Identity of Sub- jects, Confidentiality and Privacy, Legal Rights __ b. Risk/Benefit Considerations: Benefits to Subjects— Substantial or Negligible, Volunteers, Motivation_ c. Informed Consent: Basic Elements; Institutional Liability for Negligence, Debriefing ___________ B. Continuing Review ______________________________ C. Communication of the Committee's Action, Advice, and Counsel ___ ___ __ __ D. Maintenance of an Active and Effective Committee ____ ASSURANCES ______ __ __ _ __ o_o A. Negotiation of Assurances ________________________ B. Types of Assurances _____________________________ 1. General Assurance ___________________________ 2. Special Assurance ____________________________ C. Minimum Requirements for General Assurances _______ 1. Statement of Compliance ______________________ 2. Implementing Guidelines ______________________ a. Statement of Principles _____________________ b. Committee Membership ____________________ c. Specific Procedures, Review of Proposals _______ d. Specific Procedures, Advice to and Reports from Project DISCION ...omenonsmimmmmmesms seis e. Specific Procedures, Institutional Follow-up on COMMIMEE ACHON vv si ii smi i imei D. Minimum Requirements for Special Assurance ________ 93-999 (Pt. II) O - 73 - 13 530 vi TIMING AND CERTIFICATION OF INSTITUTIONAL REVIEW ______ A. General Assurances _____________________________ Timely Review _______________________________ Pending Review _____________________________ Completion of Pending Review _________________ Proposals Lacking Definite Plans_________________ Proposals Submitted With No Intent of Involving Human Subjects ______________________________ B. Special Assurances COOPERATIVE ACTIVITIES A. Institutions With General Assurances 1. Institutional Review Relationships _______________ a. Cooperating Institutions With Accepted General Assurances ______________________________ b. Cooperating Institutions With No Accepted Gen- eral Assurance ___________________________ c. Interinstitutional Joint Reviews ______________ B. Institutions With Special Assurances ________________ INSTITUTIONAL ADMINISTRATION OF ASSURANCES . Institutional Responsibility Executive Functions ______________________________ Assurance Implementation ________________________ Documentation 1. General _____________ __________ 2. Informed Consent ____________________________ a. Written Consent ___________________________ b. Oral Consent “Short” Form __________________ c. Modification of Written or Oral Consent Forms __ 3. Reporting to DHEW ______ ___________________ ENFORCEMENT nh wn Onw>» ATTACHMENT A EXAMPLE OF A STATEMENT OF COMPLIANCE (PART ONE OF A GENERAL INSTITUTIONAL ASSURANCE) _________ B SPECIAL INSTITUTIONAL ASSURANCE IN CONNECTION WITH SINGLE PROJECTS INVOLVING HUMAN SUBJECTS _ INSTRUCTIONS FOR PREPARING SPECIAL ASSURANCE __ C LIST OF CODES OR STATEMENTS OF PRINCIPLES 531 vii NOTE Bold face indicates policy as stated in DHEW Grant Administra- tion Manual Chapter 1-40. Light face indicates interpretation of DHEW policy. 532 POLICY Safeguarding the rights and welfare of human subjects involved in activities supported by grants or contracts from the Department of Health, Education, and Welfare is the responsibility of the institu- tion which receives or is accountable to the DHEW for the funds awarded for the support of the activity. In order to provide for the adequate discharge of this institutional responsibility, it is the policy of the Department that no grant or contract for an activity involving human subjects shall be made unless the application for such support has been reviewed and approved by an appropriate institutional committee. This review shall determine that the rights and welfare of the subjects involved are adequately protected, that the risks to an indi- vidual are outweighed by the potential benefits to him or by the importance of the knowledge to be gained, and that informed con- sent is to be obtained by methods that are adequate and appropriate. In addition the committee must establish a basis for continuing review of the activity in keeping with these determinations. The institution must submit to the DHEW, for its review, approval, and official acceptance, an assurance of its compliance with this policy. The institution must also provide with each proposal involving human subjects a certification that it has been or will be reviewed in accordance with the institution's assurance. No grant or contract involving human subjects at risk will be made to an individual unless he is affiliated with or sponsored by an insti- tution which can and does assume responsibility for the protection of the subjects involved. Since the welfare of subjects is a matter of concern to the Depart- ment of Health, Education, and Welfare as well as to the institution, no grant or contract involving human subjects shall be made unless the proposal for such support has been reviewed and approved by an appropriate professional committee within the responsible com- ponent of the Department. As a result of this review, the committee may recommend to the operating agency, and the operating agency may require, the imposition of specific grant or contract terms pro- viding for the protection of human subjects, including requirements for informed consent. APPLICABILITY A. General This policy applies to all grants and contracts which support ac- tivities in which subjects may be at risk. B. Subject This term describes any individual who may be at risk as a conse- 533 2 quence of participation as a subject in research, development, demon- stration, or other activities supported by DHEW funds. This may include patients; outpatients; donors of organs, tissues, and services; informants; and normal volunteers, including students who are placed at risk during training in medical, psychological, sociological, educa- tional, and other types of activities supported by DHEW. Of particular concern are those subjects in groups with limited civil free- dom. These include prisoners, residents or clients of institutions for the mentally ill and mentally retarded, and persons subject to military discipline. The unborn and the dead should be considered subjects to the extent that they have rights which can be exercised by their next of kin or legally authorized representatives. C. At Risk An individual is considered to be “at risk” if he may be exposed to the possibility of harm—physical, psychological, sociological, or other—as a consequence of any activity which goes beyond the application of those established and accepted methods necessary to meet his needs. The determination of when an individual is at risk is a matter of the application of common sense and sound profes- sional judgment to the circumstances of the activity in question. Responsibility for this determination resides at all levels of institu- tional and departmental review. Definitive determination will be made by the operating agency. D. Types of Risks and Applicability of the Policy I. Certain risks are inherent in life itself, at the time and in the places where life runs its course. This policy is not concerned with the ordinary risks of public or private living, or those risks associated with admission to a school or hospital. It is not concerned with the risks inherent in pro- fessional practice as long as these do not exceed the bounds of established and accepted procedures, including innovative practices applied in the interest ot the individual patient, student or client. Risk and the applicability of this policy are most obvious in medical and behavioral science research projects involving procedures that may induce a potentially harmful altered physical state or condition. Surgical and biopsy procedures; the removal of organs or tissues for study, reference, transplantation, or banking; the administration of drugs or radiation; the use of indwelling catheters or electrodes; the requirement of strenuous physical exertion; subjection to deceit, public embarrassment, and humilia- tion are all examples of procedures which require thorough scrutiny by both the Department of Health, Education, and Welfare and institutional com- mittees. In general those projects which involve risk of physical or psy- chological injury require prior written consent. 2. There is a wide range of medical, social, and behavioral projects and activities in which no immediate physical risk to the subject is in- volved; e.g., those utilizing personality inventories, interviews, questionnaires, or the use of observation, photographs, taped records, or stored data. However, some of these procedures may involve varying degrees of dis- comfort, harassment, invasion of privacy, or may constitute a threat to the 534 3 subject's dignity through the imposition of demeaning or dehumanizing conditions. 3. There are also medical and biomedical projects concerned solely with organs, tissues, body fluids, and other materials obtained in the course of the routine performance of medical services such as diagnosis, treatment and care, or at autopsy. The use of these materials obviously involves no element of physical risk to the subject. However, their use for many research, training, and service purposes may present psychological, sociological, or legal risks to the subject or his authorized representatives. In these instances, application of the policy requires review to determine that the cir- cumstances under which the materials were procured were appropriate and that adequate and appropriate consent was, or can be, obtained for the use of these materials for project purposes. 4. Similarly, some studies depend upon stored data or information which was often obtained for quite different purposes. Here, the reviews should also determine whether the use of these materials is within the scope of the original consent, or whether consent can be obtained. E. Established and Accepted Methods Some methods become established through rigorous standardization procedures prescribed, as in the case of drugs or biologicals, by law or, as in the case of many educational tests, through the aegis of professional societies or nonprofit agencies. Acceptance is a matter of professional response, and determination as to when a method passes from the experi- mental stage and becomes "established and accepted’ is a matter of judgment. In determining what constitutes an established and accepted method, consideration should be given to both national and local standards of practice. A management procedure may become temporarily established in the routine of a local institution but still fail to win acceptance at the national level. A psychological inventory may be accepted nationally, but still contain questions which are disturbing or offensive to a local population. Surgical procedures which are established and accepted in one part of the country may be considered experimental in another, not due to inherent deficiencies, but because of the lack of proper facilities and trained personnel. Diagnostic procedures which are routine in the United States may pose serious hazards to an undernourished, heavily in- fected, overseas population. If doubt exists as to whether the procedures to be employed are estab- lished and accepted, the activity should be subject to review and ap- proval by the institutional committee. F. Necessity to Meet Needs Even if considered established and accepted, the method may place the subject at risk if it is being employed for purposes other than to meet the needs of the subject. Determination by an attending professional that a particular treatment, test, regimen, or curriculum is appropriate for a particular subject to meet his needs limits the attendant risks to those inherent in the delivery of services, or in training. On the other hand, arbitrary, random, or other assignment of subjects 535 4 to differing treatment or study groups in the interests of a DHEW sup- ported activity, rather than in the strict interests of the subject, introduces the possibility of exposing him to additional risk. Even comparisons of two or more established and accepted methods may potentially involve exposure of at least some of the subjects to additional risks. Any alteration of the choice, scope, or timing of an otherwise established and accepted method, primarily in the interests of a DHEW activity, also raises the issue of additional risk. If doubt exists as to whether the procedures are intended solely to meet the needs of the subject, the activity should be subject to review and approval by the institutional committee. INSTITUTIONAL REVIEW A. Initial Review of Projects I. Review must be carried out by an appropriate institutional com- mittee. The committee may be an existing one, such as a board of trustees, medical staff committee, utilization committee, or research committee, or it may be specially constituted for the purpose of this review. Institutions may utilize subcommittees to represent major administrative or subordinate components in those instances where establishment of a single committee is impracticable or inadvisable. The institution may utilize staff, consultants, or both. The committee must be composed of sufficient members with varying backgrounds to assure complete and adequate review of projects and activities commonly conducted by the institution. The committee's mem- bership, maturity, experience, and expertise should be such as to justify respect for its advice and counsel. No member of an institutional committee shall be involved in either the initial or continuing review of an activity in which he has a professional responsibility, except to provide informa- tion requested by the committee. In addition to possessing the professional competence to review specific activities, the committee should be able to determine acceptability of the proposal in terms of institutional commit- ments and regulations, applicable law, standards of professional conduct and practice, and community attitudes.! The committee may therefore need to include persons whose primary concerns lie in these areas rather than in the conduct of research, development, and service programs of the types supported by the DHEW. If an institution is so small that it cannot appoint a suitable committee from its own staff, it should appoint members from outside the institution. Committee members shall be identified by name, occupation or position, and by other pertinent indications of experience and com- petence in areas pertinent to the areas of review such as earned degrees, board certifications, licensures, memberships, etc. Temporary replacement of a committee member by an alternate of comparable experience and competence is permitted in the event a mem- 1 in the United States, the regulations of the Food and Drug Administration (21 CFR 130) provide that the committee must possess competencies to determine acceptability of the project in these terms in order to review proposals for investigational new drug (IND) studies. 536 5 ber is momentarily unable to fulfill committee responsibility. The DHEW should be notified of any permanent replacement or additions. 2. The institution should adopt a statement of principles that will assist it in the discharge of its responsibilities for protecting the rights and welfare of subjects. This may be an appropriate existing code or declaration or one formulated by the institution itself.2 It is to be understood that no such principles supersede DHEW policy or appli- cable law. 3. Review begins with the identification of those projects or activities which involve subjects who may be at risk. In institutions with large grant and contract programs, administrative staff may be delegated the responsi- bility of separating those projects which do not involve human cubjects in any degree: i.e., animal and nonhuman materials studies. However, deter- minations as to whether any project or activity involves human subjects at risk is a professional responsibility tp be discharged through review by the committee, or by subcommittees. If review determines that the procedures to be applied are to be limited to those considered by the committee to be established, accepted, and necessary to the needs of the subject, review need go no further: and the application should be certified as approved by the committee. Such proj- ects involve human subjects, but these subjects are not considered to be at risk. If review determines that the procedures to be applied will place the subject at risk, review should be expanded to include the issues of the protection of the subject's rights and welfare, of the relative weight of risks and benefits, and of the provision of adequate and appropriate con- sent procedures. Where required by workload considerations or by geographic separa- tion of operating units, subcommittees or mail review may be utilized to provide preliminary review of applications. Final review of projects involving subjects at risk should be carried out by a quorum of the committee.? Such review should determine, through review of reports by subcommittees, or through its own examination of applications or of protocols, or through interviews with those individuals who will have professional responsibility for the proposed project or activity, or through other acceptable procedures that the requirements of the ition assurance and of DHEW policy have been met, specifically that: a. The rights and welfare of the subjects are adequately protected. Institutional committees should carefully examine applications, protocols, or descriptions of work to arrive at an independent deter- mination of possible risks. The committee must be alert to the possi- bility that investigators, program directors, or contractors may, quite unintentionally, introduce unnecessary or unacceptable hazards, or fail to provide adequate safeguards. This possibility is particularly true if the project crosses disciplinary lines, involves new and untried procedures, or involves established and accepted procedures which are new to the personnel applying them. Committees must also assure 2 Some of the existing codes or statements of principles concerned with the protection of human subjects in research, investigation, and care are listed in attachment C. 3 In the United States, the quorum reviewing investigational new drug studies must satisfy requirements of the Food and Drug Administration (21 CFR 130). 537 6 themselves that proper precautions will be taken to deal with emer- gencies that may develop even in the course of seemingly routine activities. When appropriate, provision should be made for safeguarding informa- tion that could be traced to, or identified with, subjects. The committee may require the project or activity director to take steps to insure the confidentiality and security of data, particularly if it may not always remain under his direct control. Safeguards include, initially, the careful design of questionnaires, in- ventories, interview schedules, and other data gathering instruments and procedures to limit the personal information to be acquired to that absolutely essential to the project or activity. Additional safeguards include the encoding or enciphering of names, addresses, serial numbers, and of data transferred to tapes, discs, and printouts. Secure, locked spaces and cabinets may be necessary for handling and storing documents and files. Codes and ciphers should always be kept in secure places, distinctly separate from encoded and enciphered data. The shipment, delivery, and transfer of all data, printouts, and files between offices and institutions may require careful controls. Computer to computer transmission of data may be restricted or forbidden. Provision should also be made for the destruction of all edited, obsolete or depleted data on punched cards, tapes, discs, and other records. The committee may also determine a future date for destruction of all stored primary data pertaining to a project or activity. Particularly relevant to the decision of the committees are those rights of the subject that are defined by law. The committee should familiarize itself through consultation with legal counsel with these statutes and com- mon law precedents which may bear on its decisions. The provisions of this policy may not be construed in any manner or sense that would abrogate, supersede, or moderate more restrictive applicable law or pre- cedential legal decisions. Laws may define what constitutes consent and who may give consent, prescribe or proscribe the performance of certain medical and surgical procedures, protect confidential communications, define negligence, define invasion of privacy, require disclosure of records pursuant to legal process, and limit charitable and governmental immunity (see, e.g., the University of Pittsburgh Law Manual). b. The risks to an individual are outweighed by the potential benefits to him or by the importance of the knowledge to be gained. The committee should carefully weigh the known or foreseeable risks to be encountered by subjects, the probable benefits that may accrue to them, and the probable benefits to humanity that may result from the subject's participation in the project or activity. If it seems probable that participation will confer substantial benefits on the subjects, the com- mittee may be justified in permitting them to accept commensurate or lesser risks. If the potential benefits are insubstantial, or are outweighed by risks, the committee may be justified in permitting the subjects to accept these risks in the interests of fy The committee should consider the posthlity that subjects, or those authorized to represent subjects, ay e motivated to accept risks for unsuitable or inadequate reasons. In suc instances the consent procedures adopted should incorporate adequate safeguards. 538 7 Compensation ta volunteers should never be such as to constitute an undue inducement. No subject can be expected to understand the issues of risks and benefits as fully as the committee. Its agreement that consent can reason- ably be sought for subject participation in a project or activity is of paramount practical importance. "The informed consent of the subject, while often a legal necessity is a goal toward which we must strive, but hardly ever achieve except in the simplest cases." (Henry K. Beecher, M.D.) c. The informed consent of subjects will be obtained by methods that are adequate and appropriate. Note.—In the United States, adherence to the regulations of the Food and Drug Adminis- tration (21 CFR 130) governing consent in projects involving investigational new drugs (IND) is required by law. Informed consent is the agreement obtained from a subject, or from his authorized representative, to the subject's participation in an activity. The basic elements of informed consent are: 1. A fair explanation of the procedures to be followed, includ- ing an identification of those which are experimental; A description of the attendant discomforts and risks; A description of the benefits to be expected; A disclosure of appropriate alternative procedures that would be advantageous for the subject; An offer to answer any inquiries concerning the procedures; An instruction that the subject is free to withdraw his consent and to discontinue participation in the project or activity at any time. an BWM In addition, the agreement, written or oral, entered into by the subject, should include no exculpatory language through which the subject is made to waive, or to appear to waive, any of his legal rights, or to release the institution or its agents from liability for negligence.4 Informed consent must be documented (see Documentation, p. 16). Consent should be obtained, whenever practicable, from the subjects themselves. When the subject group will include individuals who are not legally or physically he tae of giving informed consent, because of age, mental incapacity, or inability to communicate, the review committee should consider the validity of consent by next of kin, legal guardians, or by other qualified third parties representative of the subjects’ interests. In such instances, careful consideration should be given by the committee not only to whether these third parties can be presumed to have the necessary depth of interest and concern with the subjects’ rights and welfare, but also to whether these third parties will be legally authorized to expose the subjects to the risks involved. 4 Use of exculpatory cl in ¢ t doc ts is considered contrary to public policy. Tunkl vs. Regents of University of California, 60 Cal. 2d 92, 32 Cal. Rptr.33, 383 P. 2d 441 (1963), Annot., 6 A.L.R. 3d 693 (1966). 539 The review committee will determine if the consent required, whether to be secured before the fact, in writing or orally, or after the fact follow- ing debriefing, or whether implicit in voluntary participation in an ade- Gusts! advertised activity, is appropriate in the light of the risks to the subject, and the circumstances of the project. The review committee will also determine if the information to be given to the subject, or to qualified third parties, in writing or orally, is a fair explanation of the project or activity, of its possible benefits, and of its attendant hazards. Where an activity involves therapy, diagnosis, or management, and a professional/patient relationship exists, it is necessary to recognize that each patient's mental and emotional condition is important . . . and that in discussing the element of risk, a certain amount of discretion must be employed consistent with full disclosure of fact necessary to any informed consent." § Where an activity does not involve therapy, diagnosis, or management, and a professional/subject rather than a professional/patient relationship exists, "the subject is entitled to a full and frank disclosure of all the facts, probabilities, and opinions which a reasonable man might be expected to consider before giving his consent." 6 When debriefing procedures are considered as a necessary part of the plan, the committee should ascertain that these will be complete and prompt. ’ B. Continuing Review This is an essential part of the review process. While procedures for continuing review of ongoing projects and activities should be based in principle on the initial review criteria, they should also be adapted to the size and administrative structure of the institution. Institutions which are small and compact and in which the committee members are in day-to-day contact with professional staff may be able to function effectively with some informality. Institutions which have placed responsibility for review in boards of trustees, utilization committees, and similar groups that meet on frequent schedules may find it possible to have projects re-reviewed during these meetings. In larger institutions with more complex administrative structures and specially appointed committees, these committees may adopt a variety of continuing review mechanisms. They may involve systematic review of projects at fixed intervals, or at intervals set by the committee com- mensurate with the project's risk. Thus, a project involving an untried rocedure may initially require reconsideration as each subject completes Fis involvement. A highly routine project may need no more than annual review. Routine diagnostic service procedures, such as biopsy and autopsy, which contribute to research and demonstration activities generally require no more than annual review. Spot checks may be used to supplement bo uled reviews. Actual review may involve interviews with the responsible staff, or $ Salgo vs. Leland Stanford Jr. University Board of Trustees (154 C.A. 2nd 560; 317 P. 2d 1701). ¢ Halushka vs. University of Saskatchewan, (1965) 53 D.L.R. (2d). 540 9 review of written reports and supporting documents and forms. In any event, such review must be completed at least annually to permit certi- fications of review on noncompeting continuation applications. C. Communication of the Committee's Action, Advice, and Counsel If the committee's overall recommendation is favorable, it may simultane- ously prescribe restrictions or conditions under which the activity may be conducted, define substantial changes in the research plans which should be brought to its attention, and determine the nature wl sey of interim review procedures to insure continued acceptable conduct of the research. Favorable recommendations by an institutional committee are, of course, always subject to further appropriate review and rejection by institution officials. Unfavorable recommendations, restrictions, or conditions cannot be removed except by the committee or by the action of another appro- priate review group described in the assurance filled with the Depart- ment of Health, Education, and Welfare. Staff with supervisory responsibility for investigators and program direc- tors whose projects or activities have been disapproved or restricted, and institutional administrative and financial officers should be informed of the committee's recommendations. Responsible professional staff should be in- formed of the reasons for any adverse actions taken by the institutional committee. The committee should be prepared at all times to provide advice and counsel to staff developing new projects or activities or contemplating re- vision of ongoing projects or disapproved proposals. D. Maintenance of an Active and Effective Committee Institutions should establish policy determining overall committee com- position, including provisions for rotation of memberships and appointment of chairmen. Channels of responsibility should be established for im- plementation of committee recommendations as they may affect the actions of responsible professional staff, grants and contracts officers, business officers, and other responsible staff. Provisions should be made.for remedial. action in the event of disregard of committee recommendations. ASSURANCES A. Negotiation of Assurances An institution applying to the DHEW for a grant or contract involv- ing human subjects must provide written assurance that it will abide by DHEW policy. The assurance shall embody a statement of com- pliance with DHEW requirements for initial and continuing committee review of the supported activities; a set of implementing guidelines, including identification of the committee, and a description of its review procedures or, in the case of special assurances concerned with single projects or activities, a report of initial findings and pro- 541 10 posed continuing review procedures. Institutions that have not previ- oisly filed assurances should request instructions for the preparation ¢ an assurance from the Division of Research Grants, National Institutes of Health. Negotiation of assurances is the responsibility of the DRG, NIH. Negotiation will be initiated on receipt of a copy of a grant applica- tion, a coniract proposal, or other documentation identifying the project and the offeror or sponsoring institution. Assurances will not be accepted from institutions or institutional components which do not have control over the expenditure of DHEW grant or contract funds unless they are an active part of a cooperative project or activity. An assurance will be accepted only after review and approval by the DRG, NIH. B. Types of Assurance Assurances may be one of two types: 1. General assurance.—A general assurance describes the review and implementation procedures applicable to all DHEW-supported activities within an institution, regardless of the number, location, or types of its components (see attachment A). General assurances will be required from institutions having a significant number of concurrent DHEW projects or activities involving human subjects. 2. Special assurance.—A special assurance will, as a rule, describe those review and implementation procedures applicable to a single project or activity (see attachment B). Special assurances may also be approved in modified forms to meet unusual requirements either of the operating agency or of the institution receiving a grant or contract. Special assurances are not to be solicited from institutions which have accepted general assurances on file. C. Minimum Requirements for General Assurances 1. Statement of compliance.—A formal statement of compliance with DHEW policy must be executed by an appropriate institutional official. 2. Implementing guidelines.—The institution must include as part of its assurance implementing guidelines that specifically provide for: a. The statement of principles that will assist the institution in the discharge of its responsibilities for protecting the rights and welfare of subjects. This may be an uppropriate existing code or declaration or one formulated by the institution itself. b. A committee or committee structure which will conduct initial and continuing reviews. Committee members shall be identified by name, occupation or position, and by other pertinent indications of experience and competence in areas pertinent to the areas of review such as earned degrees, board certifications, licensures, memberships, etc. c. The procedures which the institution will follow in carrying out its initial and continuing review of proposals and activities to insure that: 1n (1) The rights and welfare of subjects are adequately protected; (2) The risks to subjects are outweighed by potential benefits; (3) The informed consent of subjects will be obtained by methods that are adequate and appropriate. d. The procedures which the committee will follow to provide ad- vice and counsel to project and program directors with regard to the committee's actions as well as the requirement for reporting to the committee any emergent problems or proposed procedural changes. e. The procedures which the institution will follow to maintain an active and effective committee and to implement its recommenda- tions. D. Minimum Requirements for Special Assurance An acceptable special assurance covering a single activity consists of a properly completed statement of compliance, similar to that illustrated by attachment B. This assurance shall identify the specific grant or contract involved by its number, if known; by its full title; and by the name of the project or program director, principal investi- gator, fellow, or other person immediately responsible for the con- duct of the activity. The assurance shall be signed by a committee of not fewer than three members and executed by an appropriate institutional official. The committee shall describe in general terms those risks to the subject that it recognizes as inherent in the activity. Consent procedures to be used are to be described. Any consent statement to be signed, heard, or read by the subject or responsible third parties should be attached. The assurance should outline the circumstances under which the director or investigator will be required to inform the committee of proposed changes in the activity, or of emergent problems involving human subjects. The assurance should also indicate whether the director or investigator will be required to submit written reports, appear for interview, or be visited by the committee or committees to provide for continuing review. It should also indicate the intervals at which such reviews will take place. TIMING AND CERTIFICATION OF INSTITUTIONAL REVIEW A. General Assurances 1. Timely review.—All proposals involving human subjects submit- ted by institutions with accepted general assurances should, whenever possible, be given institutional review and approval prior to submis- sion to the DHEW. The proposal or application should be appropriately marked in the spaces provided on forms, or the following statement should be typed on the lower or right hand margin of the page bearing the name of the institutional official authorized to sign or execute applications or proposals for the institution: “HUMAN SUBJECTS—REVIEWED AND APPROVED ON __ (date)__." (This date should be no more than 90 days prior to the submission date, and must not be more than 12 months prior to the proposed starting date.) 2. Pending review.—If it will be necessary to delay the review, the 543 proposal is to be appropriately marked in the spaces provided on forms, or the following statement is to be typed in the lower or right hand margin of the page bearing the name of the institutional official authorized to sign or execute applications or proposals for the insti- tution: “HUMAN SUBJECTS—REVIEW PENDING ON __ (date)____."” (This date should be at least one month earlier than the proposed starting date of the project to avoid possible conflict with the award date.) 3. Completion of pending review.—Review should be initiated as soon as possible after the submission of the proposal so that final action can be completed prior to the pending review date. If this final action is disapproval, or is approval contingent on substantive changes in the proposal, the operating agency is to be notified promptly by telegram; an immediate confirmatory letter; and, where appropriate, by withdrawal of the application from further considera- tion by the agency. 4. Institutional review of proposals lacking definite plans or spe- cifications for the involvement of human subjects.—Certain types of proposals are submitted with the knowledge that human subjects are to be involved within the project period, but definite plans for this involvement cannot properly be included in the proposal. These include (1) certain training grants where trainee projects remain to be selected, and (2) research, pilot, or developmental studies in which involvement depends upon such things as the completion of instru- ments, or of prior animal studies, or upon the purification of com- pounds. Such proposals should be reviewed and certified in the same man- ner as more complete proposals. The initial certification indicates institutional approval of the applications as submitted, and commits the institution to later review of the plans when completed. Such later review should be completed prior to the beginning of the budget period during which actual involvement of human subjects is to begin. 5. Institutional review of proposals not submitted with the intent of involving human subjects.—If a proposal, at the time it is sub- mitted to the DHEW, does not anticipate involving or intend to involve human subjects, no certification should be submitted. In those in- stances, however, where funds are awarded in response to the pro- posal and it later becomes appropriate to use all or parts of these funds for activities which will involve human subjects, such use must be reviewed and approved in accordance with the institutional assurance prior to the use of subjects: a. Where support is provided by project grants or contracts, review and approval of such changes must be certified to the awarding agency or contracting agency, together with a description of the proposed change in the project plan or contract workscope. Subjects should not be used prior to receipt of approval from agency staff or from the project officer concerned. b. Where support is provided by a mandatory grant or institutional grant, in which cases the institution determines within broad guide- lines the project or activities supported, including the use of human 544 13 subjects (i.e., general research support grants, clinical research center projects), review must be carried out in accordance with the institu- tional assurance. Certification for individual projects need not be forwarded to the awarding agency. Whenever the committee is uncertain as to whether a change should or should not be reported, the question should be referred to the operating agency concerned. All certifications are subject to verfication by DHEW representatives authorized to examine institutional and committee records. B. Special Assurances When a special assurance is submitted, it provides certification for the initial grant or contract period concerned. No additional docu- mentation is required. If the terms of the grant or contract provide for additional years of support, with annual obligation or funds, the noncompeting renewal application or proposal shall be certified in the manner described in the preceding section. COOPERATIVE ACTIVITIES Cooperative activities are those which involve other than the grantee or prime contractor (such as a contractor under a grantee or a subcontractor under a prime contractor). In such instances the grantee or prime contractor may obtain access to all or some of the human subjects involved through the cooperating institution. Regard- less of the distances involved and the nature of the cooperative arrangement, the basic DHEW policy applies and the grantee or prime contractor remains responsible for safeguarding the rights and wel- fare of the subjects. The manner in which this responsibility can be discharged depends on whether the grantee or contractor holds an institutional general assurance or an institutional special assurance. A. Institutions with General Assurances 1. Initial and continuing institutional review may be carried out by one or a combination of procedures: —By the grantee’s or contractor's committee; —By the committee reviews conducted at both institutions; or —Through cooperation of appropriate individuals or committees representing the cooperating institution. The procedures to be followed must be made a matter of record in the institutional files for the grant or contract before funds are re- leased by the grantee or contractor for the cooperative project. There are three relationships that may govern in reference to the cooperating institution: a. Cooperating institutions with accepted general assurances When the cooperating institution has on file with the DHEW an ac- cepted general assurance, the grantee or contractor may request the cooperator to conduct its own independent review and to report to the grantee’s or contractor's committee the cooperating committee's recommendations on those aspects of the activity that concern indi- 545 14 viduals for whom the cooperating institution has responsibility in accordance with its own assurance. The grantee or contractor may, at its discretion, concur with or further restrict the recommendations of the cooperating institution. It is the responsibility of the grantee or contractor to maintain communication with the cooperating institu- tional committees. The cooperating institution should promptly notify the grantee or contracting institution whenever the cooperating insti- tution finds the conduct of the project or activity within its purview . unsatisfactory. b. Cooperating institution with no accepted general assurance When the cooperating institution does not have an accepted assurance on file with the DHEW, the awarding agency concerned may request the DRG, NIH, to negotiate an assurance. c. Interinstitutional joint reviews.—The grantee or contracting insti- tution may wish to develop an agreement with cooperating institutions to provide for a review committee with representatives from coop- erating institutions. Representatives of cooperating institutions may be appointed as ad hoc members of the grantee or contracting insti- tution’s existing review committee or, if cooperation is on a frequent or continuing basis as between a medical school and a group of affiliated hospitals, appointments may be made permanent. Under some circumstances component subcommittees may be established within cooperating institutions. All such cooperative arrangements must be accepted by the Department as part of a general assurance, ar as an amendment to a general assurance, or in unusual situations as determined by the DRG, NIH, as a special assurance. B. Institutions with Special Assurances While responsibility for initial and continuing review necessarily lies with the contractor, the DHEW will also require acceptable assur- ances from those cooperating institutions having immediate responsi- bility for subjects. If the cooperating institution has on file with the DHEW an ac- cepted general assurance, the contractor shall request the cooperator to conduct its own independent review of those aspects of the project or activity which will involve human subjects for which it has immediate responsibility. Such a request shall be in writing and should provide for direct notification of the contractor's committee in the event that the cooperator’s committee finds the conduct of ‘the activity unsatisfactory. If the cooperating institution does not have an accepted general assurance on file with the DHEW, the operating agency concerned must request the DRG, NIH, to negotiate an assurance. INSTITUTIONAL ADMINISTRATION OF ASSURANCES A. Institutional Responsibility The grantee or contracting institution's administration is accountable to the Department for effectively carrying out the provisions of the institutional assurance for the protection of human subjects as ac- 93-999 (Pt. II) O - 73 - 14 15 cepted and recognized by the Department. Revisions in the institu- tional assurance, including the implementing procedures, are to be reported to the Department prior to the date such revisions become effective. Revision without prior notification may result in withdrawal of departmental recognition of the institution's assurance. B. Executive Functions Specific executive functions to be conducted by the institutional administration include institutional policy formulation, development, promulgation, and continuing indoctrination of personnel. Appropriate administrative assistance and support must be provided for the com- mittee’s functions. Implementation of the committee's recommenda- tions through appropriate administrative action and followup is a condition of acceptance of an assurance. Committee approvals and recommendations are, of course, subject to review and to disapproval or further restriction by institutional officials. Committee disapprovals, restrictions, or conditions cannot be rescinded or removed except by action of the committee or another appropriate review group as described and accepted in the assurance filed with the Department. C. Assurance Implementation Under no circumstances shall proposed activity plans, not approved by the committee, be implemented with Department funds. The prin- cipal investigator, program or project director, or other responsible staff must be notified as promptly as possible of committee actions, including any restrictive recommendations made by the institutional committee or the administration. They must also be informed and reminded of their continuing responsibility to bring to the attention of the committee any proposed significant changes in project or activity plans or any emergent problems that will affect human subjects. Where continuing review of projects involves the channels of administrative authority in the institution, notification of committee actions should be sent through these channels. Establishment of mechanisms for consultation and appeal by investigators and subjects may be an important condition of acceptance of an assurance by the Department. D. Documentation 1. General.—Development of appropriate documentation and re- porting procedures is an essential administrative function. The files must include copies of all documents presented or required for initial and continuing review by the institutional review committee and transmittals on actions, instructions, and conditions resulting from review committee deliberations addressed to the activity director are to be made part of the official institutional files for the supported activity. Committee meeting minutes including records of discussions of substantive issues and their resolution are to be retained by the institution and be made available upon request to representatives of the DHEW. 547 2. Informed consent.—An institution proposing to place any indi- vidual at risk is obligated to obtain and document his informed consent; the terms “‘at risk” and “informed consent” will apply as defined previously. The actual procedure in obtaining informed consent and the basis for committee determinations that the procedures are adequate and appropriate are to be fully documented. The documentation will fol- low one of the following three forms: a. Provision of a written consent document embodying all of the basic elements of informed consent. This form is to be signed by the subject or his authorized representative. A sample of the form as approved by the committee is to be retained in its records. Completed forms are to be handled in accordance with institutional practice. b. Provision of a “short” form written consent document indicating that the basic elements of informed consent have been presented orally to the subject. Written summaries of what is to be said to the patient are to be approved by the committee. The “short” form is to be signed by the subject or his authorized representative and an auditor-witness to the oral presentation and to the subject's or his authorized representative's signature. A copy of the approved sum- mary, annotated to show any additions, is to be signed by the persons obtaining the consent on behalf of the institution and by the auditor- witness. Sample copies of the consent form and of the summaries as approved by the committee are to be retained in its records. Completed forms are to be handled in accordance with institutional practice. ¢. Modification of either of the above two primary procedures. All such modifications must be approved by the committee in the minutes signed by the committee chairman. Granting of permission to use modified procedures imposes additional responsibility upon the review committee and the institution to establish that the risk to any subject is minimum, that use of either of the primary procedures for obtaining informed consent would surely invalidate objectives of considerable immediate importance, and that any reasonable alter- native means for attaining these objectives would be less advanta- geous to the subject. The committee's reasons for permitting modification or elimination of any of the six basic elements of informed consent, or for altering requirements for a subject's signature, or for signature of an auditor- witness, or for substitution (i.e., debriefing), or other modification of full, complete, written prior consent, must be individually and spe- cifically documented in thé minutes and in reports of committee actions to the institutional files. Approval of any such modifications should be regularly reconsidered as a function of continuing review and as required for annual review, with documentation of reaffirmation, re- vision, or discontinuation as appropriate. 3. Reporting to DHEW.—No routine reports to DHEW are required. Significant changes in policy, procedure, or committee structure shall, however, be promptly reported to the DRG, NIH, for review and ac- . ceptance. Review of these changes or of institutional and other records of performance under the terms and conditions of DHEW 17 policy, may require renegotiation of the assurance or such other action as may be appropriate. ENFORCEMENT The DRG, NIH, will follow up reports by reviewers, evaluators, con- sultants, and staff of the DHEW indicating concern for the welfare of subjects involved in approved and funded grants or contracts, and of subjects potentially involved in activities approved but not funded, and in disapproved proposals. On the basis of these reports and of other sources of information, the DRG, NIH, may, in collaboration with the operating agency concerned, correspond with or visit insti- tutions to discuss correction of any apparent deficiencies in its imple- mentation of the procedures described in its institutional assurance. If, in the judgment of the Secretary, an institution has failed in a material manner to comply with the terms of this policy with respect to a particular DHEW grant or contract, he may require that it be terminated in the manner provided for in applicable grant or procure- ment regulations. The institution shall be promptly notified of such finding and of the reason therefor. If, in the judgment of the Secretary, an institution fails to discharge its responsibilities for the protection of the rights and welfare of the individuals in its care, whether or not DHEW funds are involved, he may question whether the institution and the individuals con- cerned should remain eligible to receive future DHEW funds for activities involving human subjects. The institution and individuals concerned shall be promptly notified of this finding and of the reasons therefor. DEPARTMENTAL REVIEW OF ASSURANCES All assurances submitted for approval are to be forwarded to the DRG, NIH, for review and acceptance on behalf of the Department. Review will be principally concerned with the adequacy of the pro- posed committee in the light of the probable scope of the applicant institutions activities, and with the appropriateness of the proposed initial and continuing review in the light of the probable risks to be encountered, the types of subject populations involved, and the size and complexity of the institution’s administration. Institutions sub- mitting inadequate assurances will be informed of deficiencies. The appropriate operating agency will be kept informed, on request, of the status and acceptance of an assurance. 549 18 ATTACHMENT A EXAMPLE OF A STATEMENT OF COMPLIANCE PART ONE OF A GENERAL INSTITUTIONAL ASSURANCE The (name of institution) will comply with the policy for the pro- tection of human subjects participating in activities supported directly or indirectly by grants or contracts from the Department of Health, Education, and Welfare. In fulfillment of its assurance: This institution will establish and maintain a committee competent to review projects and activities that involve human subjects. The committee will be assigned responsibility to determine for each ac- tivity as planned and conducted that: The rights and welfare of subjects are adequately protected. The risks to subjects are outweighed by potential benefits. The informed consent of subjects will be obtained by methods that are adequate and appropriate. This institution will provide for committee reviews to be conducted with objectivity and in a manner to ensure the exercise of inde- pendent judgment of the members. Members will be excluded from reviews of projects or activities in which they have an active role or a conflict of interests. This institution will encourage continuing constructive communica- tion between the committee and the project directors as a means of safeguarding the rights and welfare of subjects. This institution will provide for the facilities and professional atten- tion required for subjects who may suffer physical, psychological, or other injury as a result of participation in an activity. This institution will maintain appropriate and informative records of committee reviews of applications and active projects, of docu- mentation of informed consent, and of other documentation that may pertain to the selection, participation, and protection of subjects and to reviews of circumstances that adversely affect the rights or welfare of individual subjects. This institution will periodically reassure itself through appropriate administrative overview that the practices and procedures designed for the protection of the rights and welfare of subjects are being effectively applied and are consistent with its assurance as accepted by the Department of Health, Education, and Welfare. Official signing for the Institution Signature Title Date Enclosure: Implementing Guidelines, Part Two of a General Insti- tutional Assurance. (0) (1) (2) (3) (4) (5) 19 ATTACHMENT B EXAMPLE OF A SPECIAL INSTITUTIONAL ASSURANCE AND CERTIFICATION OF REVIEW OF SINGLE PROJECTS INVOLVING HUMAN SUBJECTS The (name of institution) will comply with the provisions of the Department of Health, Education, and Welfare policy as outlined in the “Institutional Guide to DHEW Policy on Protection of Human Subjects.” This institution has established a committee competent to review the project or activity identified below. The committee's membership, maturity, and expertise assure respect for its advice and counsel. No member of the committee has a vested professional interest in the project or activity that will conflict with the need for independent review for the purpose of safeguarding the rights and welfare of subjects. The initial review of the proposal identified as (give proposed title, project director's or investigator's or fellow’s name, and grant or contract or RFP number as applicable) indicates that: In the opinion of this committee the risks to the rights and welfare of the subjects in this project or activity are: The committee agrees that the following safeguards against these risks are adequate: In the opinion of the committee the potential benefits of this activity to the subjects outweigh any probable risks. This opinion is justified. by the following reasons: In the opinion of the committee the following informed consent pro- cedures based upon the six elements of informed consent as noted will be adequate and appropriate. Documentation is attached: The committee agrees to arrange for a continuing exchange of in- formation and advice between itself and the investigator or director, particularly to the criteria cited above. This exchange will be imple- mented by the following procedures: The signatures, names, and occupations or titles of the members of the committee are listed below. None of these signatories have a vested or professional interest in this project or activity that con- flicts with the need for independent review. Signature Name Occupation or Title Signature ~~ Name Ocwpation or Tile © Signawre Name Occupation or Tile © Signatre Name Occupation or Tile (Continued page 20) 551 20 (Add as many signature spaces as necessary. Review of projects involving investigational new drugs (IND’s) requires a minimum of two persons licensed to administer drugs and one person not so licensed. Review for other purposes should utilize committees of equal or greater breadth.) Date of Committee Approval | certify that this review was carried out in accordance with the provisions of DHEW policy. (6) Official signing for institution Signature Name Title Institution Address Telephone Number Date 552 21 ATTACHMENT B INSTRUCTIONS An acceptable special institutional assurance consists of a properly com- pleted formal statement of compliance with Department of Health, Educa- tion, and Welfare policy (see attachment B), signed by a committee of not less than three members and by an official authorized to sign for the institution. The explanatory paragraphs which follow refer to the corre- sponding section of the attachment. (0) (1) 2 (3 =z (5) This should identify the application for a grant, contract, or award by its identifying number, where known, or by its full title. The name should be that of the investigator, program director, fellow, or other individual immediately responsible for the conduct of the work. The committee should identify in general terms those risks that it recog- nizes as probable occurrences; i.e. 'Aggravation of anxiety status through contact with interviewers," "Preservation of confidentiality of data,” "Renal injury subsequent to multiple biopsy," "Possibility of side reactions fo drugs,” "Possible local hematosis and nerve injury associated with venipuncture." The committee should identify the benefits to the subject or to mankind in general that will accrue through the subject's participation in the project. This should be followed by a brief discussion, weighing the risks against the benefits. Consent procedures should be described and the minimum statement to be used should be attached. "Students responding to the attached ad- vertisement will be interviewed." "The project outline will be submitted to the executive council of the PTA." "Individual teachers will be asked to allow an observer in the rooms chosen." "Superintendents of several State mental hospitals will be approached. The attached statement to the next of kin or guardian will be signed by the principal investigator and the superintendent.” "The following special consent form will be signed by each subject and his or her spouse or next of kin before acceptance of the subject.” "No prior consent will be sought. The fol- lowing debriefing schedule will be followed within 30 minutes after com- pletion of the test." This should indicate whether the investigator or director will be required to submit written reports, or to appear for interviews, or will be visited by the committee or committee representatives, and at approximately ist intervals these steps will be carried out. No further explanation is necessary. (The committee must be composed of sufficient members with varying backgrounds to assure complete and adequate review of the project. The committee may be an existing one, or one especially appointed for the purpose. The institution may utilize staff, consultants, or both. The membership should possess not only broad competence to comprehend the nature of the project, but also other competencies necessary in the judgments as to acceptability of the project or activity in terms of institutional regulations, relevant law, standards of professional practice, and community acceptance. The com- 553 mittee's maturity and experience should be such as to justify respect for its advice and counsel.) (No individual involved in the conduct of the project shall participate in its review, except to provide information to the committee.) (Committee members should be identified in the assurance by name, positions, earned degrees, board certifications, licensures, memberships, and other indications of experience, competence, and interest.) The completed assurance should be attached to the application, or returned directly to the office requesting its submission. 554 ATTACHMENT C 23 Codes or statements of principles which are concerned with the protection of human subjects in research, investigation, and care have been issued by: Organization World Medical Association 10 Columbus Circle New York, N.Y. 10019 (code available from AMA; see address listed herein) : Nuernberg Military Tri- bunals: U.S. v. Karl Brandt American Medical Associa- tion 535 North Dearborn Street Chicago, Ill. 60610 (British) Medical Research Council 20 Park Crescent London W.I, England (Canadian) Medical Re- search Council Montreal Road Ottawa 7, Ontario, Canada American Association on Mental Deficiency 5201 Connecticut Avenue, N.W. Washington, D. C. 20015 American Nurses’ Associa- tion 10 Columbus Circle New York, N.Y. 10019 American Personnel and Guidance Association 1607 New Hampshire Ave- nue, NW, Washington, D.C. 20009 American Psychological As- sociation, Inc. 1200 17th Street, N.W. Weshington, D.C. 20036 International League of Societies for the Men- tally Handicapped 12 Rue Forestiere Brussels 5, Belgium Code; adoption date The Declaration of Hel- sinki; Recommendations Guiding Doctors in Clini- cal Research; 1964 Text from which the "Nuernberg Code" is derived. AMA Ethical Guidelines for Clinical Investiga- tion; Nov. 30, 1966 Responsibility in Investiga- tions on Human Sub- jects; 1964 Medical Research Council; Extramural Programme; 1966 Statement on the Use of Human Subjects for Re- search: May 1969 The Nurse in Research; ANA Guidelines on Ethi- cal Values; January 1968 Personnel and Guidance Association; Code of Ethical Stand- ards; no date specified American Ethical Standards of Psy- chologists; Copyrighted January 1963 Declaration of General and Special Rights of the Mentally Retarded: Oct. 24, 1968 Reference JAMA. 197(11):32, Sept. 12, 1966 Trials of War Criminals Before the Nuernberg Military Tribunals, vol. Il, pp. 181-82; GPO 1949 =~ Report of the Medical Re- search Council for 1962- 1963, (Cmnd. 2382), pp. 21-25 a American Journal of Mental Deficiency, 74 (1):157, July 1969 American Psychologist, 18 (1):56-60, January 1963 24 Organization National Association of Social Workers 2 Park Avenue New York, N.Y. 10016 American Anthropological Association 1703 New Hampshire Avenue, NW. Washington, D.C. 20009 American Sociological Association 1722 N Street, NW. Washington, D.C. 20036 Catholic Hospital Association St. Louis, Missouri 63104 Commission on Synagogue Relations Federation of Jewish Philanthropies of New York 130 East 59th Street New York, N.Y. 10022 555 Code; adoption date NASW Code of Ethics; Oct. 13, 1968 Principles of Professional Responsibility; May, 1971 Code of Ethics September |, 1971 Ethical and Religious Directives for Catholic Health Facilities September, 1971 A Hospital Compendium 1969 Reference « 2956 Reprinted from MicHIGAN QUARTERLY REVIEW Vol. VII, No. The Truth That Makes Us Free 2 “ April, 1068 SCIENCE AND HUMANISM By MicHAEL E. DE BAKEY N their purest forms, science, the system- | atic search for factual knowledge and natural law, and humanism, the con- cern for human welfare, are interdependent. Recently they have been at odds, assigned to “two cultures,” though the debate actually began in the seventeenth century. But I pre- fer to think of science as disciplined thought and therefore to include the humanities with the sciences in one intellectual category. Ad- mittedly, their approaches to truth differ, the one by observation and experimental testing, the other by philosophic thought. But so do the approaches to physical and biologic sci- ences differ, in degree of objectivity and pre- cision, for example. These differences I do not consider incompatible. Historically, the scientist and the human- ist have common bonds. Medicine, art, and religion were closely allied in ancient times, when the medicine man was priest and artist. Western man brought home from the cru- sades a rich store of Arabic-Hellenic learn- ing bascd on reason. Christianity combined with Greek logic to give a new meaning to theology. Allred North Whitehead has traced “thc motive power of research,” which he defined as the “inexpugnable [medicval] belief that cvery detailed occur- Dr. De Bakey (M.D, Tulane, 32) is a professor and Chairman of the Cora and Webb Mading Department of Surgery, Baylor University College of Medicine, and Director of the Cardio-vascular Research Center, The Methodist Hospital, Hous- ton, Texas. He has been a consultant on thoracic surgery and heart diseases nationally and inter- nationally, he has served in distinguished profes- sional posts and received outstanding awards and honors. He edits The Yearbook of Surgery. This essay is slightly revised from his lecture during The University of Michigans Sesquicentennial Celebration, “The Voices of Civilization,” October 3, 1967. 85 rence can be correlated with its antecedents in a perfectly definite manner” to “the medi- eval insistence on the rationality of God. . . .” “In Asia,” he explained, “the conceptions of God were of a being who was either too arbitrary or too impersonal for such ideas to have much effect on instinctive habits of mind. Any definite occurrence might be due to the fiat of an irrational despot, or might issue from some impersonal, inscrutable ori- gin of things. There was not the same confi- dence as in the intelligible rationality of a personal being. . . . The faith in the possibil- ity of science, generated antecedently to the development of modern scientific theory, is an unconscious derivative from medieval theology.” The Renaissance brought parallel rebirths of art, literature, and medicine. The artists, in fact, were the 12aders of medicine. After a separation of medicine and art during the Middle Ages, they united in the Renais- sance, when artists first began representing the human body with mathematical preci- sion. Medicine shifted from an alliance with magic, which arose from its origin in fear of the unknown, to an alliance with art and a study of the anatomy and function of the human body. Disease was no longer viewed as the vengeance of a punitive, wrathful deity, but as a disturbance of Nature. The artist, Leonardo da Vinci, became an anat- omist, and the physician, Vesalius, an artist. The door was closing on the dogmatism of Galen and Avicenna and on intuition and analogy as a basis for knowledge, and was opening to direct scientific observation and exploration, as practiced by Copernicus, Vesalius, and Paracelsus, and thus eventu- ally to modern science. In addition to his studies of anatomy, Leonardo da Vinci de- duced principles in physiology, cardiology, 557 86 and ophthalmology that paved the way for Harvey and others, and he displayed an amazing knowledge of engineering and me- chanics. Michelangelo probed human dy- namics and the anatomic structure of bones and muscle, and medicine, through art and artistic techniques, was on its way to be- coming a science. The most powerful force in the develop- ment of civilization, science has had a tre- mendous impact on man’s phylogenetic sta- tus and on his view of himself in relation to the universe. In primitive times man’s chief concern was his relation to God; during the Renaissance, his relation to Nature; and today his relation to his fellow man. In the evolution of this shift in interest, man has discovered ways of removing or controlling elements in Nature that are evil, threatening, painful, or uncomfortable to him and his fel- low human beings. His interests have be- come more and more humanistic, largely through the impact of science. The humanistic aspects of science have been responsible for progressively elevating modern man above paleolithic man and ani- mals. In ancient times, self-preservation and self-protection held tribes together, their communality ruled by fear. Primitive man worshipped the sun because he feared the sun. Emancipated from this fear by science, man has sought more and more knowledge about his world, to make it less formidable and more hopeful for his progeny. Modern man has become intelligent enough and bold enough to explore the heavens—a feat prim- itive man would have considered not only impossible but imprudent. Nature, once feared as a chaotic force manipulated by witchcraft and complicity with evil spirits, is now viewed as an ordered phenomenon gov- erned by physical laws, some of which man can control. Scientific knowledge has con- tributed abundantly to the conversion of the wrathful gods of paganism to the loving God of Judeo-Christianity. In seeking order, rea- son, and meaning in Nature and life, the scientist has merely been trying, like Milton in Paradise Lost, to understand and explain the ways of God to man. The argument that science lacks human values and that this deficiency creates a THE MICHIGAN QUARTERLY REVIEW schism with humanism is fallacious. Those who see only the impersonality of science re- strict their views to the means, not the end. For the true scientist fuses knowledge with wisdom, and although objectivity and imper- sonality are essential to his achievement of knowledge and truth, human values and sound judgment are equally essential in the use to which he puts his new knowledge. This union of knowledge and wisdom is the goal of education. The conclusion that science is evil simply because some of its products may be con- verted to destructive ends by madmen, and the demand that it must therefore be stifled, are the quintessence of anti-intellectualism, which will surely lead to the very destruction that the opponents of science fear. Of course, scientists produced our atomic weap- ons, but we must remember that their re- search was prompted by an imperative need —to go beyond Germany’s advances in nu- clear research—and we must remember too that an international body of scientists in- fluenced the treaty to ban atomic tests. E. J. Boell, in an article entitled, “Science and Liberal Education,” has posed the telling question: But I should like to ask whether it can rea- sonably be contended that those who produced the means of atomic warfare have been respon- sible for creating the problems which now face the world? The answer is “no.” The scientists have not created a new problem. “They have,” in the words of Einstein, “merely made more urgent the problem of solving an existing one.” But even if we accepted the charge that scien- tists are responsible for the present dangers to mankind and to civilization, whom are we going to blame? Shall we pillory Seaborg, and Fermi, Rabi, Conant, and Bush? What shall we do with Nils Bohr who drew for us the picture of the atom? Or with Einstein whose genius per- ceived the mathematical relationship between matter and energy? And what of those who de- veloped the aircraft by means of which delivery of the bomb was possible? Shall we bring Dae- dalus and Icarus to scorn for making man dream of the glories of flight, or Leonardo for bringing it nearer reality, or the hundreds who failed before the success at Kitty Hawk? Norman Foerster, the well-known humanist, put it slightly differently when he addressed 358 SCIENCE AND HUMANISM 87 himself to the antagonists of science to ex- plain that the origin of earthly ills is “not in any material structure raised by the genius of man, but in the deepest depths of the human soul where selfishness and greed, hatred and fear have displaced beauty and goodness! . . . The evil from which we suffer lies in the realms of the humanities. It was not caused by scientists and engineers and will never be destroyed by them.” Thomas Huxley has explained the fear some have of science on a historical basis. To our ancestors nature was the domain of the devil, and anyone who tried to interfere with it was his associate; the scientific inves- tigator, then, was a sorcerer. Remnants of the old beliefs and superstitions have filtered through the ages to modern times. The community of scientists is bound by the common goal of exploring the truth. In the pursuit of this goal, certain values inevi- tably emerge—aesthetic, intellectual, ethical, moral, social, and cultural. The aesthetic values are evident in the scientist's apprecia- tion of symmetry, correspondence, likenesses among differences, and of truth, which Keats perceptively equated with beauty. That sci- ence, like the humanitics, has an aesthetic aspect is surprising to some, but not to those who have experienced the delight of a care- fully conceived scientific theory or experi- ment, or a carefully established proof. Few things are as offensive and frustrating to a scientist as gaps in knowledge and few things as pleasant and exciting as fitting theory to fact. Science is not a catalogue of isolated facts, but an orderly, logical synthesis of re- lated facts to produce new knowledge. It is the continual questioning, testing, evaluating, and revision of ideas. The scientific process of inquiry, discovery, and invention, like the artistic process, is creative—creative of a new concept, a new relation, a new experi- ment, a new product. The scientist derives personal satisfaction in such creation, but service to mankind is the ultimate value of science. The primary ethical value that science has contributed is, in the words of Jacob Bro- nowski, “the habit of truth.” The scientist’s refusal to allow friendship, material wealth, or other considerations to interfere with his objective separation of the true from the false and the illusory nurtures self-discipline, honesty, and integrity. This practice tran- scends national, social, economic, cultural, religious, and political differences, removing these barriers to human understanding. Scientists from hostile nations have been able to meet on the most amicable terms to exchange ideas, information, and knowledge and to impart skills to their foreign col- leagues. This amicability can, and often does, extend beyond the intellectual level to dissolve personal, national, and international hostilitics born of ignorance, greed, or van- ity. The scientist’s intellectual values are illus- trated in his respect for reason, scepticism, and dissent; his social values in his reverence for human life and human dignity and his tolerance and compassion for others; and his cultural values in his dedication to human enlightenment and development and in his measurement of reality against a theoretic standard. His demand for independence of man is tempered by his regard for the wel- fare of men. The intellectual freedom that he prizes so highly fosters respect for the ideas of others, even when they differ from his own. Dialectic, a keystone of modern sci- ence, is practiced in a calm, rational, unemo- tional atmosphere. Modern science knows no persecution like that of Giordano Bruno and demands no recanting such as that exacted of Galileo. The values of the scientist— truth, honesty, tolerance, freedom of thought and speech, respect for human life and human dignity, justice and compassion—are the highest values of humanity. Human values are created only in com- munal living—when men living together dis- cover that their individual drives and needs conflict with the social needs. The scientist, guided by human values, preserves his inde- pendence without compromising communal welfare or universal, ideals. The insistence on verification of one researcher’s experi- mental evidence and observations by others presupposes honesty and integrity among scientists. Scientists live in a stable commu- nity of free, honest inquiry, speculation, and debate, untethered by prejudice or authority and marked by open communication, collab- 559 88 THE MICHIGAN QUARTERLY REVIEW oration, and mutual respect. Like the whole of society, the body of scientists has devised a code that merges the private with the public needs. There is no place in science for the dishonorable, the bigoted, the selfish, the mercenary, or the inhuman, and when these are bold enough or fatuous enough to try to enter the scientific community, they are quickly exposed and expelled. Both the humanist and the scientist are critics of the human condition, but the meth- ods and results of their criticism differ. The humanist expresses his observations and dis- satisfactions verbally—in direct, symbolic, or allegoric language. The scientist acts to improve or correct the imperfections, limita- tions, or deficiencies he observes. The poet provides emotional and aesthetic pleasure in his lyrical treatment of the conditions and tragedies of life and of the inevitability of death, whereas the scientist seeks ways of mitigating anguish, pain, or discomfort and of preventing premature or unnatural death. In the words of C. P. Snow, “. . . the great- est enrichment the scientific culture could give us is . . . a moral one. . .. The impulse behind the scientists drives them to limit the area of tragedy, to take nothing as tragic that can conceivably lie within men’s will.” Scientists are simple, humble, compassion- ate men who are aware of the limitations of the human mind, but who are dedicated to the expansion of human knowledge for the benefit of society. The scientist, therefore, subscribes to the doctrine of humanism, which focuses on human values and human welfare. A good scientist is, in fact, first a ‘humanist and second a scientist. He does not allow his thirst for knowledge or his efforts to control his environment to subvert his hu- manitarian purpose. Our world is full of wonderful—sometimes ~~ awesome—instru- ments, machines, vehicles, and other prod- ucts of scientific and technologic ingenuity, but these physical objects must always be subordinate to the welfare of the human race. Contemporary preoccupation with materialism and glorification of gadgetry do not entice the true scientist from his basic, "humane instincts. The humanistic effects of science are in- calculable. Science is ubiquitous; it pervades our lives and our civilization. It is a way of thinking and of solving problems, and its products are a way of life. Even those most resistant to new scientific concepts accept and enjoy—indeed would not relinquish— the technologic fruits of these concepts. Who among you would exchange places with the generation of our forebears who could not enjoy a book, make a telephone call, drive an automobile, take a plane trip, or hear a symphony at home? Who would surrender modern medicine, sanitation, lighting, trans- portation, refrigeration, air conditioning, heating, and automation? The material sta- bility established by science has created a wholesome environment for the intellectual, social, and spiritual development of man. With greater affluence, man has been able to express love, respect, compassion, and kind- ness for his fellow being in materialistic ways that have extended the security of health, comfort, and well-being to more of the pop- ulation than ever before. In addition to providing comforts, con- veniences, and measures for health and safety, science has in many other ways strengthened man’s understanding and con- trol of himself and of natural forces around him. The ancient evils of life—hunger, pov- erty, ignorance, disease—which breed un- happiness, social turbulence, and crime, are all susceptible to alleviation or mitigation through science. And through science new problems will be conquered: the population dilemma, the threat of inadequate food and water, air and water pollution, vehicular ac- cidents, and undeveloped human intellect and skills. Science knows few boundaries; it embraces not only physical and biologic dis- ciplines, but psychologic, social, and philo- sophic studies as well. All contribute to man’s understanding of order, his enjoyment of beauty, his recognition of meaning, and his comprehension of truth. Medical science probably illustrates most palpably the humane goals and products of research. Dedicated to the prevention of dis- ease, the relief of suffering and disability, and the prolongation of life, medical science provides for the comprehensive physical, emotional, and social morality of man. The World Health Organization has defined 560 SCIENCE AND HUMANISM 89 health as, “a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity.” This nonpolitical organization dedicated to the improvement of health care throughout the world vividly exemplifies the humanitar- ian interests of medical scientists. As Dis- racli said, “The health of the people is really the foundation upon which all their happi- ness and all their powers as a state depend.” In helping less progressive nations, improve- ment of health standards deserves priority, since health is the cornerstone upon which human achicvement depends. A people de- bilitated or incapacitated by infectious, nu- tritional, parasitic, or other disease can hardly acquire the knowledge or develop the skills required for the economic, educational, industrial, sociologic, cultural, or scientific advancement of a nation. The achievement of universal health pre- supposes scientific inquiry, which in turn re- quires support, opportunity, and freedom. The expansion of medical knowledge is gov- erned by the attitude of society. Today’s en- lightened people are curious about the activi- ties and advances of medical science; only by satisfying this curiosity can we hope to gain their recognition of the universal bene- fits of science to human health. Through ed- ucation, our society is becoming more and more aware that it is responsible for the health and welfare of all human beings, and that health is not a privilege or luxury for the few, but a right and a necessity for all. Since 1800, Medical rescarch has doubled the average life span, then only thirty-five years in this country, and has given us the highest standards of health and sanitation man has ever known. It has permitted cor- rection of previously fatal congenital and ac- quired heart diseases, eradication or control of certain forms of cancer, carly detection and prevention of strokes, conquest of po- liomyelitis, pneumonia, and many other fatal infections, and rehabilitation of the emotion- ally and mentally ill and the physically inca- pacitated. Diseased tissues can now be re- paired by synthetic products, and non-func- tioning limbs can be replaced by mechanical substitutes. The artificial heart-lung machine is used daily in operating rooms to help cir- culate the blood during repairs to hearts and circulatory systems, and the artificial kidney sustains the lives of certain patients with renal diseases. Medical scientists are now vi- gorously working to perfect transplantation of whole organs and to develop artificial or- gans. Many of these realities or ncar-realities were considered only a quarter of a century ago to be fanciful ideas of visionaries. Even now we are on the threshold of a biomedical revolution with the key of life and the ge- netic code of cellular biology close within our reach. Just as the practical value of science is often obscure, so its transcendent humanistic significance is often subtle. Science has not only provided physical and material com- forts but has cultivated reason, lifted the human spirit, and allowed man to achieve his highest role in life. The method of scien- tific inquiry disciplines the mind to conquer the inner temptations and outer pressures and to make rational, dispassionate deci- sions. Freed by reason from prejudices, ca- price, fears, superstitions, and dogmas, man can better approach his goal of making ours the best possible world—a world of unity of brotherhood, physical and mental comfort, and spiritual serenity—a world in which every human being has a fair chance of ful- fillment. The collaborative nature of modern science teaches rescarchers to work together harmoniously, not only within an institution, community, or nation but throughout the world—to understand and respect the views and opinions of their associates especially when divergent from their own. This mutual respect improves not only interpersonal but international relations. All men have essen- tially the same goal—an even better under- standing and control of life—and science can help them work together toward this goal and to resolve conflicting views ration- ally rather than destroy one another sense- lessly. Science is a highly organized, integrated, dynamic structure. Its branches are diverse, but widely disparate components can be combined in unusual ways to yield remark- able fruits. Apparently impractical or trivial findings may be potentially useful. Every new fragment of knowledge provides impe- 561 90 THE MICHIGAN QUARTERLY REVIEW tus for another discovery and holds promise for integration with other fragments to ad- vance our understanding of ourselves and our environment. However esoteric a contri- bution may seem, therefore, it may be the crucial link in a future synthesis of appar- ently unrelated facts. Isolated facts remain for the most part irrelevant, but their accre- tion and coalescence often invest them with previously unrecognized aesthetic, intellec- tual, or material value. The uncertainties, anxieties, disappoint- ments, frustrations, and the self-abnegation in the daily work of the scientist test his sin- cerity and dedication and readily exclude the seeker of instant affluence, easy success, ad- ulation, prestige, notoriety, or other ephem- eral gains. Those with intellectual and al- truistic motives and with the requisite imagi- nation, energy, industry, perseverance, cour- age, and stability to meet the challenge and the responsibility find the life of science highly rewarding and its gratifications more than compensatory for its liabilities. Partici- pation in the exciting world of inquiry and discovery is, in fact, its own reward. Fame, when it comes, may be accidental; always it is incidental—the by-product, rather than the goal, of research. A career in science carries serious respon- sibility. The scientist’s duty is not only to add to current knowledge, but to share his discoveries with his colleagues and the world. He has a further obligation to provide instruction, encouragement, and support to young scientists. Continued improvement of man’s state depends heavily on the transmis- sion and extension of knowledge from one generation to another. The scientist’s bequest of knowledge to the next generation of scien- tists and the free exchange of ideas among contemporaries illustrates the primacy of hu- manitarian interests over self-interest and self-glorification. All of us engaged in scien- tific endeavors begin where predecessors stopped; no researcher starts with a tabula rasa or works in an intellectual vacuum. Since the most inchoate stages of science, re- searchers have drawn on their predecessors. The work of René Descartes, Isaac Newton, and Louis Pasteur depended heavily on the totality of previous knowledge—the discov- 93-999 (Pt. I) O - 73 - 15 eries, both significant and minute, of their contemporaries and predecessors. The scientist’s moral responsibilities are grave. Man will undoubtedly be able one day to produce future generations of human beings with pre-selected biologic characteris- tics. He must somehow attain the wisdom and discretion to guide him in using this for- midable power. Above all, he must preserve a humane approach to science. Despite the characteristic scepticism of the scientist, few will deny that the order and beauty of life and the universe denote some deep meaning —however mysterious—perhaps never to be grasped by the human mind. Because he strives for the continual improvement of mankind, the scientist recognizes and seeks the guidance of the Omnipotent during di- lemmas, when equivocal consequences of ex- perimentation require critical decision. Science and humanism are, of course, two ingredients of education. Whereas the hu- manities have a traditional association with education, science does not, especially in America. The first doctorate in science in this country was awarded at Yale University in 1861, only a century ago, and until recently most American scientists went abroad for training. In this, the most scientific age in the world’s history, many college graduates have little knowledge or understanding of science. Yet scientific research directly af- fects all our lives. By discovering new knowledge, graduate scientists elevate our standard of living and stimulate industrial and technologic enterprises, which, in turn support our expanding and improving edu- cation. Since education produces scientists and since science is an integral part of our modern world, the growing cost of education and research makes their universal support imperative. Educators have an obligation, not only to recognize potential scientists early and to provide a wholesome environment for their development, but to help every student have a better understanding of science, which is now an integral part of American culture. Science is dependent on and governed by so- ciety, largely by the pressing needs of our daily lives; an enlightened society can make more intelligent judgments regarding the fu- 562 SCIENCE AND HUMANISM 91 ture status and direction of science. Even slight acquaintance with the spirit of science and indirect exposure to some of its excite- ment, breadth, and goals will enlist the sup- port of the average citizen for education and scientific research. Alexis de Toqueville, in Democracy in America, wrote, “You may be sure that the more a nation is democratic, enlightened, and free, the greater will be the number of interested promotors of scientific genius. . . . Possessing education and free- dom, men living in democratic ages cannot fail to improve the industrial part of science; and . . . henceforward all the efforts of the constituted authorities ought to be directed to support the highest branches of learning, and to foster the nobler passions for science itself.” Science may not be the final answer; it may never give us the final truth. And it re- quires the most judicious control; while freeing the mind from fear and ignorance and superstition, it must not be allowed to tyrannize or annihilate humanity. With all the knowledge, comfort, convenience, and well-being science provides, man must still exercise discretion—intellectual, ethical, and moral judgment, humility, faith, compassion, reverence, and constraint—using his scien- tific power for benevolent rather than male- volent ends. But the possible destructive uses of scientific products do not make me fear new knowledge, for my faith is firm in the scientist as humanist. I am confident that he will direct his energies toward solving our human problems and will exercise control to prevent the diversion of scientific discoveries into destructive channels. “We must expect . . . that the future will disclose dangers,” wrote Alfred North Whitehead. “It is the business of the future to be dangerous; and it is among the merits of science that it equips the future for the duties.” 563 Reprinted From The Journal of The American Medical Association February 19, 1968, Vol. 203, pp. 574-576 Copyright 1968, by American Medical Association Medical Research and the Golden Rule Michael E. De Bakey, MD ecent phenomenal innovations and discoveries in medical science have prompted reexamina- tion of ethical standards in experimentation. In the ensuing discussions and controversies, medical eth- ics has been defined in moral, legal, sociologic, theo- logic, and many other terms, and its limitations, flexibility, and function have been widely articu- lated and debated. But the essence of medical eth- ics, the golden rule, has been largely overlooked or undervalued: “Whatsoever ye would that men should do to you, do ye even so to them” (Matthew 7:12). If man lived alone, a code of ethics would be super- fluous; only in society does it become requisite and intelligible. Society, in fact, regulates human ethics. The canon of ethics of all communal living— regarding material possessions, etiquette, family or international relations, and other forms of social be- havior—emanated from the golden rule. In medi- cal science, the myriad considerations that affect the behavior of the physician toward his patient re- quire some elaboration of the golden rule. But the crux of the doctor-patient relation, about which so many words have issued forth recently, reposes in this precept. For centuries the Hippocratic oath served as the code of medical ethics, embraced voluntarily by physicians when they embarked on a medical career. Evolutionary changes in medical practice and research have necessitated certain revisions in medical ethics, in the form of the Ethical Guide- lines for Clinical Investigation established by the American Medical Association House of Delegates, the Nuremberg Code, the 1964 Declaration of Helsinki adopted by the World Medical Associa- tion, the formulation of the British Medical Re- search Council of 1964, the United States Public Health Service rules and regulations governing ex- perimentation and research, and others. These codes evolved because of the difficulty and the From the Department of Surgery, Baylor University College of Medicine, and the Cardiovascular Research Center, the Methodist Hospital, Houston. Reprint request to 1200 Moursund Ave, Houston 77025 (Dr. De Bakey). weighty responsibility of unprecedented medical decisions, but they all represent general guides, not categorical imperatives, and the physician-scien- tist’s self-discipline, judgment, and conscience must ultimately operate in individual decisions. Tyrannical restraints on experimentation would certainly have precluded the invaluable contribu- tions of Vesalius, Harvey, Jenner, Walter Reed, and countless other eminent scientists. Rigid pro- scriptions about human experimentation would also have prevented the remarkable discoveries during the past century regarding the cause, transmission, and prevention of infectious diseases." Imaginative experimentation is indispensable to the progress of medical science. Had research in transplantation never moved from the experimental laboratory to the operating room, problems peculiar to human subjects would have remained unknown and there- fore unsolved, and persons living today with trans- planted kidneys would surely have died. If all forms of treatment were, in fact, withheld until everything is known about them, physicians would not even be prescribing aspirin or performing ap- pendectomies today. Despite the right of man to make any discoveries he can about himself and his world, and despite uni- versal recognition of the essentiality of research to the medical sciences, the conduct of this re- search has always faced obstacles, as pointed out by Visscher”: Scientific inquiry has been the chief instrumentality in bringing men from barbarism to civilization, from darkness to light, while it has incurred, at every step, determined opposition from the powers of ignorance, misunderstanding and jealousy. As Maxwell Finland’ has suggested, the most vocif- erous critics or self-appointed custodians of medi- cal ethics are often poorly qualified to judge the ethi- cal or moral propriety of the experiments they condemn. When such criticism is based on emo- tionalism, rather than rational analysis, it violates the very principles that it professes to protect. Dowling’s' recent review of the evolution of human experimentation in infectious diseases during the JAMA, Feb 19, 1968 e Vol 203, No 8 564 GOLDEN RULE—DE BAKEY 575 past few centuries showed that successive genera- tions of medical scientists have been increasingly concerned with the rights and welfare of volunteers, have been more careful in planning and conduct- ing human experiments, and have avoided exploita- tion of the poor, the young, the imprisoned, and the mentally and physically infirm. Any form of treatment, even when proved effec- tive in a large series of experimental and clinical “trials, remains experimental when first applied to a given patient, since physiologic responses to the same treatment may vary widely among individual patients. Depending on the competence of the phy- sician, the status of the patient, and numerous other factors, some time-honored diagnostic and therapeutic techniques may, in fact, carry greater risk than new ones. The only way to eliminate risk completely, therefore, is to abandon all medical practice and research. The result would be unim- peded suffering, rampant illness, and premature death. The cost of continued suffering and prevent- able death from curable disease is an extravagance no code of morality can afford. In any application of a diagnostic or therapeutic technique, old or new, the physician must carefully weigh the potential gains against the calculated risks for the patient. Properly conducted research reduces risks and enhances potential benefits. The potential good must far exceed the potential ill. A century ago, Claude Bernard' defined the limits of human experimentation: Tt is our duty and our right to perform an experiment on man whenever it can save his life, cure him, or gain him some potential benefit. The principle of medical and surgical morality, therefore, consists in never performing on man an experiment which might be harmful to him to any extent, even though the result might be highly advantageous to science, i.e., to the health of others. But performing experi- ments and operations exclusively from the point of view of the patient's own advantage does not prevent their turning out profitably to science Realizing his lack of medical knowledge and his inability to take appropriate action to restore his health, the patient, in seeking professional advice, vests his trust in his physician and tacitly bestows upon him the prerogative of making a judgment. This trust is sacred in the doctor-patient relation, and the physician who violates it or takes undue advantage of it forfeits all privileges of medical licensure. As every physician knows, of course, fully informed consent is not always feasible. It is impos- sible to compress, in conversation with a patient, the highly technical and complex knowledge that the physician-scientist has spent almost a lifetime acquiring. Nor is it always advisable to explain every implication of a procedure, lack of thorough understanding of which may create undue anxiety. Moreover, the patient’s inability to evaluate such information dispassionately may distort his judg- ment. A personal physician who knows the patient intimately, therefore, may often be an objective intermediary in helping the patient to understand JAMA, Feb 19, 1968 e Vol 203, No 8 the proposed procedure and to make a rational deci- sion of acceptance or rejection. If a technique is highly experimental, the physi- cian-scientist must have produced adequate evi- dence of its safety and potential efficacy in human subjects, usually in the form of extensive controlled experiments and observations in lower animals; he must anticipate and safeguard against any addi- tional risks in human subjects; he must have the informed, and totally voluntary, consent of the pa- tient or his guardian after adequate explanation of the investigative nature and uncertainties in the procedure; and he must, ultimately and above all, assure himself that if he or a loved one were the patient, he would sanction the proposed procedure. When the considerations are excessively complex and the decision is overly onerous, he should seek the counsel of informed peers. Whenever he can an- ticipate the possible usefulness of a new technique or procedure in saving the life of the patient, he should obtain consent for its use in advance. If dur- ing an operation, however, a surgeon discovers unex- pected conditions that require instant decisions, he obviously cannot obtain the consent of the patient, but must proceed according to his best judgment. The investigator must never permit his zeal for research or his self-interest to blunt his reverence for human life and the right of self-determination. He must find the critical balance required to satis- fy society's demands for the advancement of knowl- edge while abiding by its strictures to protect the dignity, privacy, and freedom of its individual mem- bers. He must understand the dilemma of the prospective subject whose desire to contribute to human advancement is tempered by a natural re- luctance to subject himself to scientific inquiry and experimentation, and he must not use real or veiled threats or other forms of unfair suasion to resolve the dilemma. The betterment of society must be sought with the least possible risk to the people, singly and collectively. On the other hand, the whole must not be neglected for the part. These con- flicting social and personal values require continual reexamination, adjustment, and compromise. They cannot, however, be resolved by inflexible rules. Much has been said and written about the value of human life, the sanctity of the human body, the basis of human dignity, and the advisability of sus- taining the life of a patient who may remain bed- ridden or otherwise incapacitated. A physician’s duties are humanitarian: to cure disease, relieve suffering, and preserve life. Fulfillment of these duties requires reverence for human life, the human body, and human dignity. The decision of whether the life will be useful and productive is not his to make, and the physician who assumes this and other divine prerogatives regarding human life is guilty of the sin known to the ancient Greeks as hubris. The scientific community and the medical pro- fession can and should exercise certain controls against violations of medical ethics as a result of 565 576 GOLDEN RULE—DE BAKEY ignorance, negligence, or unscrupulousness. Control by association is almost inevitable today. Physician- scientists no longer work alone; they are members of research teams affiliated with an institution and usually sponsored by an agency, It is incumbent on every member of a research team and on the ad- ministrative personnel of related medical and scien- tific institutions, as well as related lay and govern- mental agencies, to maintain the highest standards of research and to prevent breaches of medical eth- ics by careful evaluation of proposed investigative procedures. Obedience to an ethical code is not properly ex- acted by rigid, formal laws or injunctions, but is prompted by integrity, humanitarianism, and benev- olence, qualities that every physician should pos- sess. When, however, individual members of any group violate basic social principles by failing to exercise restraint, prudence, and discretion, rules must be imposed from without. The danger lies in their formulation on an emotional or capricious basis, by persons with biased opinions and limited knowledge of the principles and complexities of scientific investigation. The clichés, illogicalities, rigidities, and ambiguities contained in such rules render them fallible or useless as guides; faulty re- search may be sanctioned and meritorious projects forbidden. When obedience to artificial precepts takes precedence over rational assessment of partic- ular circumstances, not only may the single pa- tient involved be denied benefit, but advancement of science for the common good may be seriously impeded. It is impossible to construct a formal ethical code that will embrace every circumstance, since each patient and each experiment presents a unique situa- tion. Because of their complexity, variability, and irreducibility to stereotypes, living systems, unlike inanimate nature, are not subject to formulas. Standards codified by laws are not only difficult to interpret in real life situations, but are virtually impossible to enforce. Ethical decisions in medical science must therefore depend finally on the wisdom, integrity, and self-imposed restraints of the sci- entist and his peers. A simple personal credo based on general ethical norms and on love and reverence for humanity has no equivalent for moral guidance. The medical researcher may find such a credo in Dogliotti’s® simple but prudent advice to young physicians: “Follow the way of wisdom, and do unto others as you would do unto yourselves, heed- ing the voice of conscience, love and compassion.” References 1. Dowling, H.F.: Human Experimentation in Infectious Dis- eases, JAMA 198:997-999 (Nov 28) 1966. 2. Visscher, M.B.: Medical Research and Ethics, read before the symposium entitled Science, Society, and the Public's Health —Ethical Issues, Baltimore, Oct. 5, 1966. 3. Finland, M.: Ethics, Consent and Controlled Clinical Trial, JAMA 198:637-638 (Nov 7, 1966.) 4. Bernard, C.: An Introduction to the Study of Experimental Medicine, New York: Macmillan Co., 1927, p 101. 5. Dogliotti, AM.: Moral Dramas and Dilemmas in the Prac- tice of Surgery, Bull NY Acad Med 41:1107-1116 (Nov) 1965. JAMA, Feb 19, 1968 e Vol 203, No 8 566 U.S. Coalition for Life Export, PA 16216 (412) 327-7379 March 7, 1973 Senator Ted Kennedy Senate Office Building Washington, D.C. 20510 Dear Senator Kennedy: Please find enclosed a testimony for the Senate subcommitte hearings on the human experiematation's, submitted by me from the U.S. Coalition for Life. We ask that this testimony and attachments be incorporated, and given serious consideration and discussion by the subcommitte. Thank you. Respectfully Yours, Mrs. Randy Engel Director U.S. Coalition for Life encl. RVE/plm 567 Testimony of Randy V. Engel Board Member of Woman (Concerned for the Unborn Child Excutive Director of U.S. Coalition for Life Prepared for The Senate Health Subcommittee on Human Experiematation March 6, 1973 Mr. Chairman, members of the Committe, I welcome this opportunity to to present the views of "Woman Concerned for the Unborn Child" and the "U.S. Coalition for Life" on human expermentation, specifically expermentation on unborn children carried out by bio-medical technicians and supported by pharmaceutical firms, family planning and population control groups, and Federal agencies including the Agency for International Development and the Dept. of Health Education and Welfare . What is an unborn child? A fetus? Dr. Samuel A. Nigro, a senior instructor in child pshychiatry at Case Western Reserve University School of Medicine, Cleveland says of the fetus, "A fetus is a living human creature with a genetic endowment from the moment of conception having a personal and natural history of developing into a freeborn citizen of the world". This statement is the full scientifically sound and correct definition of the fetus. (1) I agree. However, in the 20th century dictatorship of the labratory and the test tube biocracy, the unborn child, the fetus has become something else. He has become a coveted guinea pig, a labratory animal and therefore if for no other reason, his welfare should be of primary concern. to the Senate comittee on human experimentation. 568 (2) Never in all history has a simular labratory specimen held out such promise for the scientific-medical pharmaceutical! commun ty, in such areas as endocrinology, virology, immunology, mental and physical retardation, congenital deformaties and the behavorial sciences, and as a potential source of human material germ plasm, tissue, bone morrow, even organs. It is not surprising that in a nation which is currently braceing itself for an estimated 1.6 million anual "legal" abortions a year, large numbers of live aborted children will be packed on ice, and shipped to medical centers and labratories for experimentation - there to be used for research purposes and destroyed when they have outgrown their usefullness. Additionally, many unborn children, while still in their mother's womb, will become guinea pigs in utero until the abortion procedure is carried out. The clinical realities of experimentation conducted on the unborn for a half century are well documented. Consider the following: 1. Reports on the establishment of organ farms which specialize in growing organs from embryonic tissue in unlimited quanties. (1918,1968) 2. Reports of experiments involving the removal of brain cells and craniums and portions of the skull from LIVING, BREATHING, CRYING children-the by-product of hysterotomy abortions. (1922) 3. Reports of researchers cutting the spinal cord of a LIVE fetus to test his reflexes or stimulating the motor roots of spinal, cranial, or facial nerves to derive data on pre-matal neurological systems. (1922-1924) 4. Reports on the initiation of embryonic life in the laboratory and the subsequent destruction of these test tube "monstrooities" at various stages of development. (2) (1959-present) Since 1970 the rate of experimentation on the unborn has accelerated due to an increasing number of abortions, the main source of fetal research material, The following study will illustrate the need for a full Senate investigation or fatal experimentation since the unborn have not been given a voice during the current series of hearings. 569 The New England Journal of Medicine of May '8, '972 has an abstract on the findings of a research prcject funded by the [nited Cer¢nral Palsy Research and Educational Foundation, Inc., New York City, entitled "Isolation of Attenuated Rubella-Vaccine Virus From Human Products Of Conception ans Uterine Cervix". Researchers in this experiment were from U.S. and Finish institutions. The experiments were carried out in Helsinki on women recruited from applicants seeking abortions. Thirty-five pregnant women, scheduled for subsequent abortions were vaccinated with rubella-vaccine viruses to evaluate the dangers to the fetus from an accidental dose of the vaccine during pregnancy. In 30 of the cases, pregnancy was terminated by hysterotomy, which preduces a live child and in five cases by curettage. "AFTER REPEATED WASHINGS WITH BALANCED SALT SOLUTION THESE SURGICAL SPECIMENS WERE HOMOGINIZED IN A TEN BROECK TISSUE GRINDER......" (3) I leave this Committee to formulate its own conclusions in this matter. The use of "fetal tissue" obtained from the by-products of abortion, is already commonplace both in the U.S. and abroad. Dr. H. Biemann, Othersen of the Medical University of South Carolina has transplanted a thymus taken from an aborted child and implanted it into the abdominal wall of an unwanted infant. Dr. Leonard Hayflict of Stanford University has produced a polio vaccine from living tissue cells of surgically aborted fetusee, Likewise, abortion "lab specimens" in the State of Colorado are being provided to "responsible researchers" under the general catagory of "Surgical Tissue". At Standford Medical University, Dr. Robert Goodlin has been conducting experiments on live aborted children. Under questioning by Mark Swendsen, 570 (4) a law Student of California's Student Pro-Life Fed. ration on May 19, 1972 Df. Goodlin stated tht part of the experiments on the live :u.1d included slicing open the rib cage of a still-living human fetus ir Hrder to observe the heart action. The ages of these fetuses ranged upward tc 24 weeks gestation. In some cases, the women who had aborted the children were rct told that their babies would be used as human guinea pegs in Dr. Goodlin's labratory. (See attachment of sworn testimony by M. Swendsen) . An Englishman by the name of Mr. Philip Stanley, of the Langham (abortion) Clinio, when asked about his clinic's traffic in fetal tissue and live oabies to a local hospital for experimentation, told reporters that "The position is quite clear, A fetus has to be 28 weeks to become legally viable. Earlier than that it is so much garbage". 1 regret to say that Mr. Stanley would derive considerable support for his statement from members of this nation's medical-scientific community. At the beginning of my testimony, I mentioned the rea of the BIOCRACY where children will not be born, they will be manufactured. For a nation so deeply committed to the so called "PLANNED PARENTHOOD" ethic it is logical that babies be produced in a more rationale manner in which lovemaking will be totally separated from babymaking and man's control over his biological evolution tighteded. (5) Carl Djerassi, President of the Syntex Corp., producers of synthetic hormones for the Pill, in the Dec. 1972 issue of the BULLETIN OF ATOMIC SCIENTISTS, clearly sees the link between abortion and genetic engineering. "If one developed accurate diagnostic procedures ... it would provide us with information on a wide variety of potentially deleterious genetic diseases, and it could then be possible to inform the pregnant mother of that fact and leave the decision UP to her, whether or not 'she wants to termanate the pregnancy through an abortion. This incidently, is the reason why abortion is so intimately linked with genetic engineering". (6) 571 (5) But in fact will parents or the mother of an unborn child suspected of carrying a genetic "defect", of which there are 115 indentified genetic diseases today, be able to withstand the preasures to abort their offspring in order to improve the quality of human stock? According to Dr. Orlando Miller of Columbia University"s College of Physicians and Sureons, "I don"t know any doctor who would perform this procedure (amniocentesis) without at least, in general terms, having the parents agree to an abortion if necessary". Commenting on the questions posed by genetic engineering and the destruction of genetically inferior pre-natal life, Dr. Philip Handler, President of the National Academy of Sciences in a speech at the 57th annual Clinic Congress of the American College of Surgeons in 1971, stated that such intervention would require a change in medical ethics which would put the welfare of the species before the welfare of the indivual. According to Dr. Handler, abortion is one of the solutions to preventing contamination of the gene pool. "Many people think of the early fetus as a non-person". "As soon as you make that decision, the rest is rather easy." For those Committee members who perhaps share Dr. Handler's sentiments, it is perhaps necessary to remind this Committee that there are monetary motives involved in both genetic engineering and experimentation on the unborn-motivations which go beyond mere concern for mankind's well-teing. It is no coincidence that in addition to the bio-medical technician and the eugenic zealot drug manufactures and population controllers, financed mainly through the Agency for International Development and the Dept. of Health, Education and Welfare , should have a vested interest in unlocking the secrets of the womb, which experiments on humans at various stages of embryonic and fetal development will surely reveal as never before. 572 Today, with Federal financial support and ercouragment,irug companies are perfectiog a new science of Fetal Ktenology - the s~.ence of killing the unborn. No longer does "contraception" mean the proverting of conception. Rather it has taken on a more flexible meaning which can ve stretched to include the use of various chemicals and devices, such as tne IUD, which prevents early embryonic development and/or implantation. In deed, AID in its Population Report if Dec. 1971,confirms support fot the concept of pregnancy-centered family planning progress geared to the elimination of early "unwanted" pregnancies of women in the developing countries. Such women generally poor and ignorant, have become human guinea pigs like the unborn, in what promises to be the greatest experiment in recorded history-the EXPERIMENT OF POPULATION CONTROL. For a domestic version of AID's abortifacient program, I suggest the menbers of the Committee read HEW's Five Year Family Planning and Pop- ulation Plan of Oct. 1971. At this point in my testimony, I would like to return to the English experience in the matter of regulating experimentation on unborn children- an experience which came about as a result of the fact that England had develeped a black market for live aborted babies and this fact fell into the public domain and the domain of Parliament. Among the recommendations made by the Advisory Committee after a two year study on the use of fetuses and fetal material were: 1. That no money exchange hands 2. That experiments on the fetus be carried out in a place other than the operating theater or operating room. 3, That full and detailed records e kept of all experiments 4. That the use of the fetus or fetal material be determined by the medical attendents at birth and not the interested researcher. 5. That "IT IS UNETHICAL TO ADMINISTER DRUGS OR TO CARRY OUT ANY PROCEDURES 573 DURING PREGNANCY WITH THE DELIBERATE INTENT OF ASCERTA!NING THE HARM THAT THEY MIGHT DO TO THE FETUS, EVEN THOUGH ARRANGEMENTS HAVE ALREADY BEEN MADE TO TERMINATE THE PREGNANCY AND THE MOTHER CON3HNTS TO THE EXPERIMENT." 6. And finally, that the minimal limit of viability of human fetuses should be regarded as "20 weeks" gestational age. (8) In reviewing the full report of this Advisory Committee it is difficult to ascertain whether their primary concern is tor the researcher in cases of legal suit or for the unborn child and his welfare. The ethical inplications of experimentation on the unborn raises many profound questions. In most cases, the experimentation bestows no "compensatory profitable experience" on the unborn child. If the fetus is not dead at the beginning of the experiment, he will surely be at its conclusion. In most cases, also, the rationale given to permit the experimentors to use the unborn child as a labratory animal, is pragmatic one - SINCE THE FETUS IS TO BE KILLED OR DIE ANYWAY, IT IS ETHICAL TO USE HIM FOR EXP- ERIMENTAL PURPOSES, THE KNOWLEDGE FROM WHICH, MAY BENIFIT MANKIND. For this reason, I have enclosed as part of this written testimony Dr. Lee Alexander's Medical Science Under Dictatorship and Reverend Charles Carroll's Medicine Without An Ethic. In Conclusion —=- The refusal of those charged with organizing the nearing of this Committee to seat a Pro-Life attorney and physician from Women Concerned for the Unborn Child and the U.S. Coalition for Life is regretable. I understand there may be additional hearings held on human experimentation 574 (8) by this same Committee sometime in the future but that it is unlikely that the unborn will be given a hearing even then. Abortion is st:1l a palitical hot potato. No doubt public exposure of experiments of tre unborn in this country will stir the same sense of outrage exhibited in Sngland two years ago. In the mean time, the unborn of this country does not even possess the most elementary protection against undue pain and misuse which Government gives to ordinary labratory animals. He is cut open-alive and crying. His body is deposited into tissue pulverizers. He is attacked in his mother's womb and in the bio-technicians artificial womb. Perhaps somewhere in the world there is a greater injustice. But I simply can't imagine it. Can you? Thank you, Women Concerned for the Unborn Child P.0. Box 8071 Pittsburgh, PA 15216 (412) 531-9272 U.S. Coalition for Life Export, PA 15632 (412) 327-7379 1) 2) 3) 4) 5) 6) 8) 575 (9) FOOTNOTES "What Is A Fetus", Samuel A. Nigro, M.D. Marriage and Family Newsletter Vol.#2 - No. 11 = Nov. 1971 p.5 See attachments - "Experimentation With Prenatal and Neonatal Marriage and Family Newsletter, John Harrington, Editor Human Beings" Part 1 Vol.3 - No.1 - Jan 1972; Part 2, Vol.3 - No.2 - Feb.1972. Also, "The Use of Fetuses and Fetal Material for Medical Research", The Medical-Moral Newsletter,Editor, Frank J. Ayd Jr., M.D. Vol.IX = No. 1&2 - Sept.-Oct. 1972. "Isolation of Attenuated Rubella-Vaccine Virus From Human Products of Conception and Uterine Cervix", A.Vaheri, M.D. , T. Vesikari, M.D. N. Oker-Blom, M.D., M, Seppala, M.D., P. Parkman, M.D., J. Veronelli, PHD M.D., and F.C., Robbins, M.D. , The New England Journal of Medicine, Vol. 286 - No.20 - May 18, 1972 -.p.1071 - 1074. Minnesota Citizens Concerned for Life, Rochester Minn. reprint "THE LAST HOURS OF AN ABORTED BABY". Taken from The People, May 17, 1970 Cambridge, England. } "The Ethical Aspects of Genetic Controls", Rev. Joseph Fletcher, New England Journal of Medicine, 285:776 - 783, Sept. 30, 1971 "Can Man Contr9l His Biological Evolution?" Probabilities and Prac- ticalities, Carl Djerassi, Bulletin of the Atomic Scientists Vol. XXVIII - No.10 - Dec.1972 - pgs.20-27 "Diagnosed of Fetuses To Determine Defects Spur Growing Debate", Barry Kramer, Wall Street Journal Oct. 14, 1971. The Use of Fetuses and Fetal Materials for Research. Report of the Advisory group. H.M. Stationard Office. 1972, 184p. As reported in The Lancet, June 3, 1972, pgs.i222-1223 576 1 June 1072 SWORN STATEMENT OF MARK D, SWENDSEN: I, Mark Suendsen, of 4630 Fulton Street, San Francisco, California, 94121, hereby certify thet the following are true and correct to the best of my knowledge and belief: 1. That en Friday, 19 ¥ay 1972, the Student Pro-Life Federation, under my )eader- ship and direction, held a demonstration in front of Stanford Nedical Center; 2. That this demonstration was in protest of experiments on live, aborted human fetuses which Dr. Robert Goodlin has conducted at Stanford Medical Center; 3. That this demonstration sought a permanent ban en such experiments, which ben was refused by Dr, Goodlin; 4, That during the course of this demonstration I was invited to meet with Dr, Goedlin ir his laborctory, and that I did so, accoimpnnied by Jim Babcock ond Debbi Wiggins, both also of the Student Pro-Life Federation, and several members of the media; - 5. That during this meeting, in response to my questions, Dr, Coodlin adnitted that the precedures of these experiments had included slicing open the rib-cage of a ctill-ijving human fetus in order to chserve the heart action; that some of the women receiving abortions at Stanford Medical Center had not been told 1hat their babies would be removed from them alive for use in Dr. Goodlin's lah, and had net given their pernissicn for this te he done; thot some preaaturely born babies as old as 24 weeks of gestation were also used as subjects in these experiments; 6. That Dr. Geodlin stated during the meeting that he was not currentiy performing these experiments, due to financial difficulties, but hoped to restart his exparimeniation when funds became available; and that br. Goodlin alse stated that he thought it is not right to perform experiments on an inveluntary human subject, but that he is unable to resolve the question of when human life begins; 7. That wrile I was in Dr, Goodlin's lub he showed me a partially disassenb]ed hyperbaric oxygen chamber, used during his experiments to try to cevelon an artificial womb, and that he stoted that both human and anima) subjects had been used in his efforts toward that end; and 8. That a tape recording made during the mecting, with Dr, Goodlin's knowledge, is currently in my possession, I DECLARE UNDER PENALTY OF PERJURY THAT THE FOREGOING IS TRUE AND CORRECT TO THE BEST OF MY 'NOWLEDGE AND BELIEF, Signed this First day of June, 1972, A and Sworn to bfore me this Ulan 2 Sten ~ Go oy Swend sen & Director of External Affairs, no caunTy Student Pro-Life Federation QO Lia Ironnia Cmy Commiscina Expires Juou: L175 Cran pPuedt in BAN Piano JOHN MERTENS NOTARY FUELIC Ee Ctr ad Cow cy ot Bou Francisco, Eiate of Calic vp In oex? rata, abies dar. jung 577 V. Probabilities and Practicalities In my presentation I would like to give a fourth view of the question of genetic engineering and, in particular, of the possible involvement in- this area by the scientific industrial community. In order to do so, we first need to define genetic engineering, at least from the industrial viewpoint. One. convenient way of dividing the subject is to refer to it as con- structive genetic engineering, meaning the improve- ment of progeny, and preventive genetic engineer- ing, which would concentrate primarily on avoiding the birth of undesirable progeny. Professionally I am not a geneticist, but I have spent a great deal of time, both in my own research work and in terms of policy decisions, on a subject that is fairly close to today’s topic, namely the question of birth control. The moral, technical and policy questions are rather similar to those posed by genetic engineering, and I would like to point out some of these similarities. Preventive genetic engineering leads directly to the question of abortion, and this is an area of re- search in which a great deal of work is now going on in the pharmaceutical industry. I myself happen to be a strong believer in the importance of such research. 1 am firmly convinced of the great im- portance of abortion, and I consider it a human right (“Fertility Control Through Abortion: An Assessment of the Period 1950-1980,” Bulletin, Jan. 1972). I also recognize that this is a very controversial topic. Industry is involved in this field because of research on abortifacient agents, in other words, chemicals that will produce an abortion. If it is a very early one, then the question of abortion is almost a semantic one. Thus, do we consider expulsion of the fertilized egg after one or two days an abortion? If not, do we consider it after 10 days, or 20 or 30 or 80? In the Koran, for instance, life is supposed to start only around day 80, because it is then that the fetus is supposed to acquire a soul. Therefore, under the limitations of the Muslim religion, elimination of the fertilized ovum during most of the first trimester of preg- nancy (incidentally, by far the safest time from a clinical standpoint) would not be considered an improper abortion. Dr. Freund in his earlier talk raised the question of legal constraints and impositions in the field of genetic engineering and, 1 believe, that he con- sidered this especially in the context of potential human cloning. If we actually would reach that particular level of technical competence when hu- man cloning is actually feasible, then I have per- sonally great doubts about the efficacy and feasi- bility of effective legislative coercion in that field. 93-999 (Pt. II) O - 73 - 18 CARL DJERASSI Let me cite a fairly simple but not too well known example from the field of abortion to substantiate this view. Abortion is in many respects the most widely practiced practical form of birth control. It is, of course, not preventive medical practice, but rather might be considered a cure for a “disease,” if one actually considered an unwanted pregnancy to be a disease. In many countries, notably in eastern Europe since World War II, abortion is available free on demand. Furthermore, statistics from these countries are now fairly readily available and they indicate that in several instances the number of abortions greatly exceeds the number of births. This appears to be also true in a number of western European countries, notably the predominantly Catholic ones such as France, Belgium. Austria and Italy, where the number of illegal abortions ap- parently also exceeds or at least equals the number of births. Indeed, it is very likely that in the entire world somewhere on the order of 40 million abor- tions occur in any one year, which would mean that nearly 8 per cent of all women of reproductive age undergo an abortion in any one year. From these staggering statistics one can conclude that even very oppressive legislation is unsuccessful in stop- ping a practice in the field of birth control when the motivation exists to use it. Rumania happens to be the country in which. until fairly recently, the number of abortions per capita was higher than that in any other country and in the middle 1960s reached a level of approxi- mately four abortions per live birth. As a result, the birth rate in Rumania dropped to the second lowest level in Europe. The Rumanian government became concerned with the situation and, in the fall of 1967, suddenly passed a very drastic anti-abor- tion law according to which legal abortion in Ru- December 1972 Bulletin of the Atomic Scientists 25 578 mania became almost as difficult as that in any other European country. As a result, within one year, the birth rate in Rumania more than doubled, which is a spectacular increase and would tend to support Dr. Freund's fear that issues dealing with birth (quantitatively, that is, birth control, and qualitatively, that is, genetic engineering) can be legislated and manipulated. However, within two years of the initial passage of the strict anti-abortion law, the Rumanian birth - rate had again dropped very strikingly and started to approach its original level, because it apparently took the Rumanian population only about that long to adjust to the changed circumstances and to switch over predominantly to illegal abortions. The technical facilities for such abortions were, of course, available, and it was simply necessary to set up the original system in an illegal manner. While I am not aware whether precise data are actually available, T would suspect that the only conse- quence of the shift was probably an increase in the maternal death rate, an effect which the govern- ment hardly wanted to stimulate. The point that Tam trying to make, and which is equally applicable to abortion and genetic engineering, is that when we talk about such basic issues as procreation, we are dealing with individual decisions and there really are no legislative and legal mechanisms for changing them in a fundamental manner. Educa- tion, public relations, religion or appeals to chauv- inistic and nationalistic motives are much more effective means whereby quantitative and quali- tative issues of birth can be manipulated. Industrial Considerations Let me now indicate how industry would consider the question of whether it should get involved to any major extent in the field of genetic engineering. From a purely pragmatic viewpoint, the industrial manager would first carry out an ROI (return on investment) calculation. The factors that would be taken into consideration would be, for instance, the potential market (which, in this case, is essen- tially unknown), the development costs (which, in this instance, would be horrendous), the develop- ment time (which I think would be fantastically long), and, finally, the method of distribution (which probably would he highly restricted). Add- ing up all these factors, one would reach the almost inevitable conclusion that one cannot make a real case for any industrial organization to get involved in “constructive” genetic engineering unless that particular company is purely interested in doing basic research in genctics, However, to convert these research findings in the genetics laboratory into widely applicable agents for final human use would be prohibitively expensive and lengthy, and probably even unfeasible. It is for this reason that I believe that industry is very unlikely to get in- volved in this area. There is a second factor which industry would obviously take into consideration and that is the 26 question of the role that government regulatory agencies play in this field. I am rather surprised that Dr. Freund did not address himself to this topic because he would obviously be more compe- tent to do so than any of the other speakers at this symposium. I would say that this aspect raises another very significant barrier to research in this field, and here again there is a considerable amount of similarity to the present situation in the birth- control field, which I have actually covered in two articles which appeared fairly recently in Science (“Prognosis for the Development of New Clinical Birth Control Agents,” 166( 1969), 468; “Birth Con- trol after 1984,” 169(1970), 941). Thus, while there is more and more concern worldwide about the so-called human population explosion and about the desirability of carrying out more research in the area of reproductive biology and physiology, especially as it applies to birth control, in actual fact less work is being done currently insofar as practical applications are concerned. This is not something which one realizes if one reads ordinary newspapers or even most scientific journals. Ap- parently more and more money is being spent in this field, but actually less and less practical work is being done and fewer practical results achieved from such endeavors. Most of the interesting ad- vances are actually effected in the laboratory on experimental animals and less and less exciting new work is being carried out with humans because of the tremendously increased restrictions regarding human experimentation. I am not passing any value Judgment on these restrictions other than to point out that they exist and that it would be pointless to ignore them. FDA Regulations Let me offer a quotation from an article which came out recently in Science (1. Friedmann and R. Roblin, “Gene Therapy for Human Genetic Dis- ease,” 175(1972), 949). The authors were dealing with the way-out genetic engineering that everyone is afraid about, and notably about chemical treat- ment through modified DNAs. In the article the authors make what apparently seemed to them a new observation: “If synthetic DNA molecules are to be used, then we visualize the Food and Drug Administration or some similar organization en- forcing quality standards for DNA preparations used in gene therapy.” Note that the authors use the word “visualize.” This scoms to ignore the fact that it is not a question of “visualizing: enforcing quality standards for DNA preparations is already the current duty and function of the FDA. In this particular instance we are dealing with genetic treatment through chemical agents, and DNA is just another chemical. There is no question what- soever that any researcher in this field, if he wanted to work on human applications. would have to follow already existing FDA regulations which he would find very restrictive. The same authors indicate that in their opinion 579 Science and Public Affairs BULLETIN OF THE ATOMIC SCIENTISTS Founded in 1945 by H yman H. Goldsmith and Eu gene Rabinowitch ¢ DECEMBER 1972 « VOLUME XXVIII « NUMBER 10 Published by the Educational Foundati threat of nuclea for Nucl Qei r doomsd : Nati oomsday hovering over mankind, stands at ae 5 Clock, bol of the minutes to Midnight » ght. EDITORIAL STAFF Editor-in-Chief, Ei Richard Lowi Eft Manas Bor, | oo COMMUNICATIONS Production Editor Po emllin; Book Ea. Dighteenth Century Enlightenment, F' flor, Jane, Wilsons Reporter, Sally Ja Ed enry R. Korman; On Ecotheol nt, Frank T. Manheim; P y Elio] Atvisiony, Donna Seay. bit iri F. cology, Park J. White; Solar E ower Policy, fil, Bu Juss, Vat" Looce; ir : nergy, Marshal erriam; Space Exploits, Bruce Stewart; Mariners, Eugene A. Crai, 3 ; 8! h 8 CTRATTY B—— one should first carry out extensive studies on ani- of surgical interventions, because in the absence of mals to evaluate the potential therapeutic benefits. drugs regulatory agencies cannot, at this stage, These tests should include long-term studies of the enter. Thus, if one concerns oneself with questions possible induction of cancer and genetic disturb- of tissue transplantation, one does not really re- ances in experimen i i quire any government approval, or indeed any out- require the development of animal models for hu- side approval. The surgeon, if he so wishes, can man genetic diseases, etc. Apparently the authors decide essentially on his own within the confines of that article again overlooked the fact that this of the regulations that exist in his own hospital or is exactly what needs to be done already now in institution, to perform such experiments. This, of areas of medicine that are much simpler than gen- course, is what has happened in the case of heart etic engineering. In fact, according to the relatively transplants. However, since almost any form of new legislative mandates of the FDA, that agency genetic engineering that one could conceive of at has to approve for all practical purposes all proto- this stage will not be purely surgical but will in- cols for new clinical research upon humans. In volve, in one way or another. chemical manipula- other words, if the experimenter wishes to treat his tion; 1 believe that the tremendous barrier of ex- patient with any chemical, and DNA isa chemical, he first will have to get permission from the FDA to do so. In my opinion, it is exceedingly unlikely that any employee of that agency would in fact have the courage to permit any of these experiments to be carried out at this time. He would not neces- sarily have to forbid them, but he could procrasti- nate in a manner which would make such experi- mentation legally impossible. In my opinion, in- vestigators, whether they are academic or industrial ones, should not ignore this reality. Apparent Loophole There is an apparent loophole to this control of a government regulatory agency and of the impact of legal restraints on research. Specifically, it is an area where human experimentation is easily possible and where experiments are sometimes car- ried out without applying all of the ethical and moral considerations that might be exerted. 1 speak ternally imposed restraints by government regula- tory agencies should not be ignored and that this will probably be the most secure insurance that little, if any, of this research will actually be per- formed on humans. Prospects for Future Until now I have essentially covered only nega- tive factors and you might ack the question whe- ther there are any positive ones. Could industry conceivably get involved in the area of genetic en- gineering and, if so, could one really reach some goals in the foreseeable future? For the purposes of this talk “foreseeable future” might be con- sidered the time when the grandchildren of the class of 1972 are living. 1 am convinced that genetic engineering will be used relatively soon in the veterinary field, and Dr. Danielli has already addressed himself to this topic. Moral restraints do not enter here. and 580 neither do practical restraints. In this instance economic considerations are probably overriding and progress in the field is such that marked ad- vances can be anticipated. What about applications of “preventive” genetic engineering in humans? Surely there are some areas where a consensus on the part of scientists, lawyers and theologians can easily be reached; for instance, few of them will probably argue the point that the prevention of mongolism in babies is a desirable goal. In order to achieve it, advances in diagnosis at an early stage are crucially important. Techni- cally it is possible to aspirate amniotic fluid and to analyze it. If one developed accurate diagnostic procedures, preferably automated ones, it would provide us with information on a wide variety of potentially deleterious genetic diseases, and it would then be possible to inform the pregnant mother of that fact and leave the decision up to her, whether she wants to terminate pregnancy through an abortion. This, incidentally, is the rea- son why abortion is so intimately linked with genet- ic engineering. God-given Right? In fact, Dr. Ramsey in his book “Artificial Man” makes the explicit statement that people do not have the God-given right to have children and that he is prepared to give society and governments the decision-making power as to who should and should not have them under certain conditions. 1 would only go one slight step further and state that a woman who happens to be pregnant and is informed unambiguously that her child will be a mongoloid should have the option to decide by herself whether she wants to give birth to such a child. If you agree with that position, then you have already agreed with the principle that it is the prospective mother who should make the decision whether she wishes to have a child or not and, consequently, that the decision on abortion should be hers. This brings us finally to the spectre of human cloning, and I really feel that it is only a spectre. It 1S a topic that lends itself to sensational maga- zine articles, but the chance of this really happen- 28 ing in a human being is enormously far away. Dr. Ramsey alluded to my colleague Joshua Lederberg of the Stanford Genetics Department, who has written extensively on this subject. While Leder- berg certainly does not exclude the theoretical feasi- bility of this being demonstrated in higher animals, I believe that he is quite convinced that the lead times are much longer than most people are pre- pared to accept. I believe that no one working in + this particular aspect of human engineering, namely human cloning, has ever tried to construct a critical path map. This is something that academic scien- tists are not accustomed to do, whereas industrial scientists find this an important intellectual disci- pline. Let me again cite an example from the birth control field. Stark Realities Two years ago in a paper in Science, 1 considered what it would take to develop an ideal birth control agent such as a once-a-month pill for women which would be a menses inducer (“Birth Control After 1984”). A woman would take such a pill once a month, and this would induce menstruation, while if she had gotten pregnant during that past month, the pill would initiate what we might call a micro- abortion, because she would in fact have been pregnant for a couple of weeks. When I constructed a critical path map for such a hypothetical agent, I reached the conclusion that the lead times in- volved would be such that such an agent could not be developed until the mid-1980s at the earliest. This paper actually generated more attention than any of the hundreds of other scientific articles that I have written, and I believe that in part this was due to the fact that I called attention to the stark realities of time and money costs involved in de- veloping such complicated approaches for human application. It is a topic that academic and govern- ment scientists, as well as legislators and especially the press, like to ignore. If such a critical path map is prepared for developments in human cloning. then it will become perfectly obvious that we are talking about a development that, even if it got major scientific and governmental support. could not be developed until sometime in the next cen- tury. The statement is sometimes made that these are only technical problems in the sense that the fundamental scientific questions associated with cloning have already been solved, and that all that is required is a technological effort to apply these solutions to humans. Here again, mv colleague Joshua Lederberg presents a very good answer to this simplistic view. He stated in so many words that, while we technically know how to build bridges, it does not follow that we are able to build a bridge from San Francisco to Honolulu. I would extend Lederberg’s bridge building analogy to clon- ing by stating that this is not even equivalent to building a bridge from San Francisco to Honolulu, but rather from San Francisco to Sydney, or per- haps even across the Indian Ocean. 581 Vol. 286 No. 20 RUBELLA VACCINATION IN PREC Y-VAHERLETD AL nn ISOLATION OF ATTENUATED RUBELLA-VACCINE VIRUS FROM HUMAN PRODUCTS OF CONCEPTION AND UTERINE CERVIX ~ ANTTI VAHERL, M.D, “Fino VESIKARE, M.D. NiLs OKeR-BLoat, M.D, MARKKU SEPPALA, M.D, PauL D. PARKMAN, M.D, JORGE VERONELLI, Pi.D., M.D., AND Freperiek C. ROBBINS, M.D. Abstract To evaluate the fetal hazard of accidentat- administration of live rubella vaccine during preg- nancy, the varcine was given to 35 women certified for legal abortion. Twenty-four of these were rubel- la seronegative. Various specimens, including the products of conception, were tested for rubella virus independ- ently in three collaborating laboratories. Rubella virus was recovered from the placenta in six cases INCE their introduction in 1969, live, attenuated rubella-virus vaccines have been extensively used, both for mass vaccination of children and for the selective vaccination of post-puberal women. There has heen concern that infection of pregnant women with rubella-vaccine virus might result from exposure to a vaccinated contact. Thus far, however, only two presumable cases of transmission from a vaccinated person to a susceptible contact have been reported.’ Several studies specifically de- signed to test the contagiousness of rubella-vaccine virus ‘for susceptible pregnant women exposed to vaccinated children participating in field trials save no evidence of contact infection.”? The practice of vaccination of post-puberal wom- en, however, may lead to inadvertent vaccination during pregnancy. Indeed, a number of such occur- rences have been reported“ stressing the need for _ greater knowledge of the possibility of transplacen- tal transmission of vaccine virus. The collaborative project described below was designed to study the transplacental passage of live, attenuated rubella-vaccine virus (HPV-77 strain, de- rivatives DK-12 and DE-3) by examination of the products of conception obtained atter certified legal abortion in women who had volunteered for vacci- nation. A preliminary report on the first 10 cases studied has been published, and data from these cases are included in the present paper. MATERIALS AND METHODS Study Population and Clinical Observations The study population was recruited from wonien applying for abortion at the Department of Obstet- rics and Gynecology, University of Helsinki, or at the State Institute of Midwifery, Helsinki, Finland. The criteria for inclusion into the study were as fol- From the departments of Virology and Obstetrics and Gynecology. University of Helsinki. Helsinki. Finland. the Division of Biologics Standards, National Institutes of Health, U.S. Public Health Service. Bethesda. Md.. and the Department of Pediatrics, Case Western Re- serve University School of Medicine and Cleveland Metropolitan General Hospital (address eprint requests to Dr Robbins at Case Western Reserve University School of Medicine. 2119 Abington oad. Cleveland, O. 44106). Supported by research grant from the United Cerebri Re- search and Educational Foundation. Inc. New York Cry. and from the fetus in one case. Virus was also found in 13 of 22 uterine cervical swabs taken nine to 25 davs after vaccination of seronegative moth- ers. Virus was not isolated from comparable speci- mens obtained from women with pre-existing anti- body. The results indicate a hazard of placental and fetal invasion by the vaccine virus and emphasize the need to observe precautions when post-puberal female patients are vaccinated. . Jows: that they be certified for legal abortion by the National Board of Health: that they volunteer for the study after a full explanation of what was in- volved: that there be no contraindication to vaccina- tion; that the gestational period be less than 14 weeks; that adequate specimens be secured; and that the serum hemagglutinin-inhibition (HI) anti- body titer be low, preferably less than 1:10. The final study population consisted of 35 women between the ages of 15 and 43 vears, of whom 24 were seronegative and 11 had antibody titers rang- ing from 1:10 to 1:80. As in other studies. the sus- ceptible group was found to be vounger (average age of 28.3 years) than the immune group (average age of 34.1 years), althongh no selection for age was, applied: The vestational age at the time of vaccination (counted from the first day of the last menstrual pe- riod) ranged between 49 and 107 days. The interval between vaccination and abortion (VA interval) was between 11 and 30 days. All patients were interviewed six weeks after vac- cination concerning any reaction to the vaccine. Leukocyte and platelet counts were done on all pa- tients at the time of operation. Vaccines Employed Twenty-nine women received 1 ml of HPV-77 DK-12 vaccine prepared in dog-kidney cell cultures (Philips Roxane. Incorporated, St. Joseph, Missou- Ti), and six received HPV-7T7 DE-5 vaccine grown in duck-embryo cell cultures (Merck Sharp and Dohme, West Point, Pennsylvania). Collection Handling and Testing of Specimens Serum specimens were obtained from each sub- ject before vaccination, two to three weeks later and again siv to nine weeks after vaccination. Throat and nasopharyngeal swabs for virus isola- tion were collected from eight days after vaccination up to 36 days after vaccination. An average of four “ Lamples were obtained from each patient. Cotton- tipped applicators were used to obtain the throat swabs, and caleimm alginate swabs (Calaiswabs) tor the collection of nasopharyngeal secretions. Swabs were rinsed in 6 ml of Eagle's basal medium con- 582 1072 THE NEW ENGEAND JOURNAL OF MEDICINE taining 0.2 per cent bovine sermn album, too nu per milliliter of cent em sulbate and 30 neni tionad wines per milliliter of istatim A single blood sample was dawn at the tne of surgery. and either the whole heparinized Blood on the buthy coat was employed for viens studies Immediate uterine was swabbed with a cotton-tipped applicator. which was then handled as desenibed for the throat and before sureen the Cerin BasOp ia en] saad Pregnancy was terminated in 30 cases hy ha cterato- my and in five cases by curettase. Specimens from 15 prophylactic appendectonnes performed at the tinie of hysterotony were aso made avalable tor virolome studies. Alter repeated washings with balanced salt these suraical were homogenized in Ten Bioeck tissue aden The resulting suspension (20 per cent vio was cla ified by low-speed contrtneation Tissue suspensions were sinnlaly prepared placental and fetal specimens and from seanents of extra-embryonic Most of the samples, obtained by histerotoms were delivered to Hie Lib- oratory still sivounded by intact membranes. Re- peated washings with halinced salt solution were performed betore and after dissection, In one of the testing Laboratories (Helsinki of the specimens for virolowie studies were inmedi- ately inoculated into RK-13 cells caltires.' \W\ Len this was not possible. specimens were stored at =70°C before testing. Tuo additional aliquots of the same samples were frozen and shipped in dir ice to the Liboratories in Cleveland. Ohio, and Bethesda Marvland, where they tested in grivet-monkey-Kiduey cultures by the ECHO-11 in- terference technic? In addition. primary cell cultures lished trom the fetal specimens and were main- tained through two subcultures. Supernatant tuids from these cultures were collected and tested, as were the rest of the samples tor virolovic studies Occasionally, because of dels in transit samples were thawed when received in the United States laboratories. Virus isolates were adentified hy with robella-livpenmmnne rabbit antiseram Serologic tests consisted of the rubella hence lu- tination inhabition asso carried out in Helsinki ac- cording to the modification of Halonen ot J. ad in Cleveland and Bethesda by methods described. a1 solution speciiens from menihranes were primary were estab- neutralization previonsh RESULTS? Clinical Reactions to Vaccination The only complication of vaccination noted in- volved the joints. Two of IS susceptible women who received HPV-TT DR-12 vaccine reported pain or stiffness of joints approximately two weeks after thor more detailed information order NAPS Doane 01 K6 from National Mundin Publications Service. co CON Toon Corporation. 866 3d Ave Nea Yorke NOY T0022 canine NY a MICFOChC COPY reprsduction or SS fa cach photocopy lieoks or money orders shouhd be made pas able 10 CON Bator mation € orp ition Nationa Nui, Publications Sor ice May 18 1970 vacenndion: Sviptoms lasted for aboot two weeks and ne one case with swelling of WC jomt One of the ay were wiven HPV DISS vaceme complied ot mild wrthialgin two weeks after vaccination that last ed for only afew dans were associated ol wedtine snbpects who Serologic Response to Vaccination Seroconversion was observed in all the 24 initial- Iv susceptible vaccinated women. Amore the 11 patients with low prevaccination antibody titers. booster response, defined as a tourfold or wreater rise in HI antibody titer, was observed in hye Virologic Studies The results of virus isolations in the three labora- tories were, for the most part, an agreement, but some discrepancies were noted. Mam came detectable only after passage, suggesting tha such samples contained very low concentrations of virus, These presumably low titers, inactiv otion gure ing transit and the ditterent methods used in Hel sinkic as opposed to Cleveland and Bethesda, are ail factors that may have contributed to the discrepan- cres noted Respiratory secretions. Virus was throat or nasopharyngeal swabs (or both collected] trom 11 ot the 24 seronedative women 16 per cent! The intervals after vaccination when these isolations were recorded are shown mm Figure 1 nolates he- nolated trom A single positive specimen was obtained fron, each of two of the 11 participants with low initial antibody titers. No other virus isolations were made from any source from the seropositive women Cervical secretions. Of the 22 cervical swabs col- lected from patients without prevaccination immuni- ty. virus was isolated in 13 (39 per cent) over the terval of nine to 25 davs atter vaccination Blood and appendix. Viremia was documented in five of the 24 patients who underwent setocom er- sion (21 per cent). Appendives from 10 susceptible women and trom tive with pre-existing bmaunity were tested for virus, Two specimens. obtained 13 and 24 days after vaccination from susceptible pa- tients vielded virus. Placenta. amniotic fluid and membranes. Placental tissue trom each patient was studied, and six virus isolations were made. all from women without prevaccination immunity rate, 25 per cent). The time after vacemation that these positive specimens were obtained is shown in Figure 1. No virns was recovered from any of a wnmber of other extri-embryonic samples tested from suscepti- ble subjects even when the placenta was positive These specimens were 16 ammiotic Hinds, 11 decid- wa, four unmiotic membranes, two ambilical cords extra-embryonic disolation and five pooled membranes Foetal specimens A single vis made ham fetal tissue: This was obtaned from the Kidney hiomovenate of a fetus obtauned hom a year-old worn vaccinated on the 33th day of ess tation and aborted 214 Laer. Vitus wae covered motwo Laboratories and not ne the third. polation was Vy dans 583 Vol 286 No. 20 RUBELLA VACCINATION IN PREGNANCY = VAHERI ET AL [ ngsmmarons H TRACT r 8 rbd nn dH . 0 Hn Rr Hohe 1 0 jalxBEPe am 20 4 4 IN ENER NS! 1° oBdh of hein NUMBER OF SAMPLES » 8L000 A etn oH erm 4 APPENDIX CEN arn. nN PLACENTA A or FETUS = Al ini a6 8 10 12 14 6 18 20 22 24 26 28 30 32 34 3 38 [O & waarve souaron [3 a positive soLaT ON WA FETAL SOLATION DAYS AFTER VACCINATION Figure 1. Virus Isolations after Vaccination of Seronega- tive Mothers Specimens of eye, brain, lung, liver, intestine, skin- muscle and a mixed homogenate of tissues from the same fetus were negative as was a primary culture of fetal skin-muscle. Virus was isolated from the mother’s appendix and respiratory tract but not from the mother’s blood, cervix or placenta. DISCUSSION Although the primary purpose of this study was to determine whether or not rubella-vaccine viruses administered to the mother in routine fashion are capable of causing infection of the human fetus, there are a number of other aspects deserving comment. It was of interest to determine if pregnant women respond to vaccination in the same manner as non- gravid subjects. In the group of rubella-susceptible pregnant women joint symptoms occurred in approxi- mately 12 per cent, being mild in all. This figure is to be compared with results of various studies con- cerning the frequency of arthritis and arthralgia in young women who are not pregnant, with propor- tions as high as 56 per cent after administration of HPV-77 DK-12 vaccine and 14 to 44 per cent in those receiving HPV-77 DE-5.'%'" Our findings are from a small sample and must be interpreted cau- tiously but do suguest that pregnant women are less likely to experience post-vaccine arthritis and ar- thralgia than nonpregnant women, and when such cases do occur, they are less severe. The serologic response, the pattern of vaccine- virus excretion and the frequency of viremia are not appreciably different in the preunant subjects from those observed among nonpregnant vaccinated women, suggesting that pregnancy has no marked effect on the extent of viral multiplication within the host. An unusual observation is the finding of virus in the appendix. In one case virus was reco cred 24 days after vaccination at a time when circulating antibody * was present and uo virus conld be isolated from the blood, providing evidence that the vaccine virus persists in the tissues for a substantial period. The recovery of vaccine virus from 39 per cent of 1073 the cervical swabs obtained from the susceptible group was unevpected. Virus shedding secs to occur at this site. during the same interval after vaccination as it does in the respiratory tract. Al- thongh the virus content of the cer al samples was not quantitated, the frequent positivity of first- passage isolations and the reproducibility of cervical virts isolations in the three testing laboratories sug- gest that virus is present in considerable quantity. Similar observations havé been reported by Seppila et ul? in natural rubella infections. The pathogenet- ic importance of rubellasvirus excretion in the fe- male genital tract is not known at present but would be ‘compatible with the hypothesis that in- tranterine infection can occur in a retrograde manner. The finding of vaccine virus in 25 per cent of the placental samples from women undergoing serovon- version is similar to what occurs when natural rabel- la complicates pregnancy.® The absence of detecta- ble virus in extra-embryonic tissues and Huids other than the placenta indicates that this organ is prefer- entially infected. In amy attempt to assess the importance of the ngle virus isolation from fetal tissue it is first nec- essary to establish that the observation is not a labo- ratory error. The fact that the same results were achieved in two of the three testing laboratories, and that virus was recovered from the kidney and not from other organs of the same fetus, argues strongly against laboratory contamination or other errors such as improper labeling. The failure to recover virus more frequently trom the fetus cannot be taken to mean that the vaccine strains are less likely than unmodified ones to cause such infection. Alford et al? found that tetal inmolve- ment is infrequent when natural rubella infection occurs after the eighth week of gestation. Untortu- nately, none of the women i the study reported here received vaccine until the eighth week. and only five of the 24 susceptible subjects betore the ninth week. Furthermore, the intervals between vaccination and abortion were ot necessity relatively short. : Similar difficulties may explain the failure of Fu- rukawa et al?! to demonstrate intrauterine infection in 10 women vaccinated with Cendehill and RA 27/3 strains. Our data do not provide any evidence concerning the persistence of tetal or placental infection due to vaccine viruses. Virus has been recovered by Lar- son et al? from the placenta 69 days after inadver- tent vaccination, indicating that intrauterine infection with vaccine virus probably behaves similarly to natural infection. However, no. data are available concerning the teratogenic properties of any of the vaccine viruses. The failure to isolate virus (except to a minor degree from the respiratory tract) from any of the 11 vaccinated women who had low prevaccination anti- body titers stggests that even low levels of immunni- tv can adford protection. In conclusion, the evidence presented herve sup- ports the present recommendations of the United States Public Health Service that vaccination of post-puberal women should be undertaken with ex- 584 . 1074 FHE NFW ENCEAND JOURNAL OF MEDICINE Way 18 Ju7e treme canton These are as folloses, Tot acd nas NoChn EEE A Walon MCG etal vba ab als nen tion fo women in whoo ssc obibahiy bos been 2 an TREE WME Re Lean Sai nag gp proved yoo previons antibody determination oy clude pregame to the entent posable and asia that the recipient as cpoble of following a abl contraceptive prodran tor at least two months ols low me vacormation Stee divanostic Lihoraton assistance, me cisves of inadvertent vaccmation dine pregnancy is csual ls hampered Hy the unavailadnhte of prevaccination serinn samples. at seems advisable to obtan and store such samples hetore vaccination of an post- puberal female patient The practice of ribella vacenntion in the mumedi- ate post-partinn period” offers the possibilite of ex- tending the henehts of protective immnmization to a sizable proportion of susceptible women of cluld- bearing age. Recent reports, however, stress ti desirability of enforce a vehable contraceptive program when vaccine is administered dinine the carly puerperinm. REFERENCES Lo Wilkins 1 Leedom INL Pore Bet al Remntection with rubella virus despite hive vaceme nduced immnnny taals of HPN 77 and HPN 80 Dive robella virus saccines cid subsequent ariinonl and natural chalienze studies Amc Das Child TIN 275 203, tong 2 hefonits HB Raho RRO Tedanspe Cher al A contronded Family study of ves tenaated abel vivas vaca seroconver SON OF a suscepiible contact N Enel J Med 2832 etn 3 Werhel RE Stokes J he Bavoak TR dive ater oF rabel Lavirus vacomos prepared in duck cibreo cel culture HE Ciel tests an families sad moan ostoation FANMA 205 55408880 Tua 40 Veronelh JAC An open community tn of five tabella voocimes study of vaccine vars mamissitihiy and amtizenic ethoacy of three HPV-77 derivatives, JANA 213 I8N2Y- 1X36 (970 £0 Scott HDL Byine BB Exposure of susceplible pregnant women io rubella vaccinees servloeie hadines duninz the Rhode Islind rmmunization Campaten JANN 215 600 612 [97 6. Wall SA. Rubell ruminations. bent Annual Immusization € on- ference. Kansas Cty. Missour, March 240 1971 Atlanta. Geor- gia, Center tor Disease Control. 1971 pp 29-3] 7. Phillips CAL NMaeck INS. Rogers WA et al Intrauterine tubelli infection following immunization with rubella vaccine, JANA 213 624.625 1970 7 ra Lason HE Parkin PDC Davis WE coal Bnadvatent at ail SEs vacant dorm progam NO Lael DONGLE Oh STs wy Mabert AN esihan OKer Blom Neral Brasmission of atten tated belle vacames to the human fetus ape oamin ay report Nid Dis Child IR 233.2360 1969 MeCarhy Ko Landon Robinson CHL Pillinzer SE dso ton of pn bella viris from cases im Botan Lancet 2893 Sux, (uns Nunn PI. Fiopps HE, Mover HN 30 moll ies soko, characterization. and Lahdratony diagnosis. Amo J is Chiid IS 6X7 YT) Halonen PE Stewan JAD Hal AD Rubella hemaeelutimn pre pared an serum free suspension cultiie of BHR. cells Nan Med Fp Biol Fenn dv 8218S 1o6~ Stewart Gl Parknian PD. Hopps ME. of al Rubetla-vinas hemarglubnaton-intnbition test, No Engl 1 Aled 276 384.837 1967 Cooper 17. Zwing PR. Weis HE ot ab Transient anthini ater cubella vacation. Amo Dis Child THR 2IR225 pony Weibel REL Stokes J di Buynakh EBC et al Five rubella vaccines mn adults nd children HPS 77 and Merch Henao strains. Am Js Child 118226 229, Tuas Lerman SEONankervs GAL Hepeie AD en af Immunologic re SPORSE VITUS excretion. and Jot reachions with rubella accing a Study of adolescent anh and young women piven ve ateniated virus vacane (HPV 77 DE-ST Ann Intern Med “467 71 197] Monto AS, Cavallaa 1 Whale 1H Frequency of artheagia nm women recenine one of three rubella vaccines Arch Intern Med 126 635 639, [070 Seppala Mo Nahenn A Vesthan 1 Bsolation of abel cus tron atenne convin Scand FChn Faby Bnvest 25 Sapnl (18 Hon [970 Alford € A Ji Neva b A Weller TH Vinolowic and serofosic stud os on human products of conception after maternal rubeile NF nul J Med 2TH 1275 12K1 1964 Furukawa Fou Rondo Ket al Chimica triads of RA 273 ONS rubella vaccme im Japan Am 1 Dis Child ibs 262-2618 1969 Center tor Disease Control Recommendation of the Purl Health Service: Advisory Committee on Immunizaion Practices Rubella virus vaccine Morbidity and Mortals Weebly Report VOL 190 NO 3 Atlanta, Georg, The Center. 1970 pp 338-334 Boue A. Papiermich-Berkhaner F, Levv-Thiernn SS Atenuated rubella virus vaccine in women © chimcal tals dang the postpar wim penod. Am J Dis Child 118 230-233, 19649 Sever JL: Rubella immunization nish postpartum. JAMA 217.697, 1971 Buldwin JA. Freestone DS: Risk of early post-partum pregnancy in content of post-partum vaccination against rubella. 1 ancet 2 366-367. 1971 Reprinted from The Journal of the Louisiana State Medical Socicty pp. 313-320, Vol. 124, No. 9, September, 1972 Medicine Without an Ethic’ I MEDICINE has not already. it will soon find itself defenseless—without an ethic. When the California Medical As- sociation pronounces the erosion of the old ethic; when it claims that medicine has changed the law. public opinion and the church rather than been changed by them; when it insists that the time has come to place a relative value on human life: and finally when it pretends that medicine alone has the knowledge of human nature and human behavior to devise the new ethic. I think it time that that sweeping claim be challenged and that we ask what is happening to us—all of us. Let us begin at the beginning and re- view what happened in the abortion de- bate. When I returned to California in 1966 after a year in Berlin, friends approached me and asked for my views. At the time, 1 had not yet read the proposals before the legislature in Sacramento. Before spresented at the 92nd Annual Meeting of the Louisiana State Medical Society. May 1, 1972, New Orleans. **Priest. Episcopal Diocese of California; Fellow, Institute for Ecumenical and Cultural Research at St. John's Abbey and University in Collegeville, Min- nesota. SEPTEMBER, 1972—-VoL. 124, No. 9. REVEREND CHARLES CARROLL** Collegeville, Minnesota expressing myself. 1 thought it best to study them. They called for abortion on five grounds: incest, rape. potential de- formity, threat to the mental health, and threat to the physical health of the mother. At first blush, they made eminent good sense. Then surely I would have appeared to be a man without compassion had I op- posed abortion in the case of incest. It was only as the months wore on that I asked myself when, if ever, two parties to an incestuous relationship would seek an abortion on this ground—at risk of the at- tendant publicity. And no less surely I would have ap- peared to be without any genuine concern for others had I opposed abortion in the event of rape. Still, I asked why there had been no distinction made between stat- utory and criminal rape; why a woman who had been the victim of criminal as- sault would not seek immediate medical care; why rape would be given as grounds for an abortion a week or a month after it had occurred. Nothing troubled me quite as much. however, as the proposal that the right to abortion be granted on ground of po- tential deformity of the fetus. In read- 313 586 MEDICINE WITHOUT AN ETHIC — CARROLL ing that, the memories of a lifetime re- turned. particularly those of the German doctors’ trial before the American Military Tribunal in Nuremberg in the late spring and summer of 1947. It was then that I realized that incest and rape had been introduced into the discussion more because of their emo- tional value in debate. It was then—again mindful of how slowly but inexorably a people can move from feticide to in- fanticide to homicide—that I asked my- self, “What. in speaking of the potentially deformed, are we saving to and about those who are deformed after birth? What are we saying to and about the totally disabled victims of automobile and in- dustrial accidents? What are we saying to and about the totally disabled veterans of our wars?" During a visit to the Neurosurgical Re- habilitation Center of the University of Wisconsin four years ago. I met a simply beautiful girl in her early 20s who was quadraplegic and pregnant. Because the director of the center was a friend. I asked if he would be good enough to tell me something about her. He said that she had been in an accident: that she had been paralyzed; that she had met a handsome young man some months later who asked her to marry him: that he had overcome her misgivings. she had agreed and thev had been married. He then told me of a question asked her by one of the interns on rounds that morning “Enjoy your sex life?" “No” she replied. "I lost all sensitivity in that area of my body as a result of the accident. But my husband enjoys sex. We want a family. I am pregnant. And so, I have come here to learn how I might care for our child.” You who are doctors know how often we have sent our loved ones off to war or off on a trip with good food and good wine: and you. more than most men. know how indifferent and calloused we can be- come in our attitudes in our brief and in- frequent visits to even the most commit- 314 ted and sensitive when thev are totaliy disabled. If we are to allow potential deformity of the fetus as ground for an abortion. what are we saying to and about the irrever- sibly mentally ill? One of the ugliest chap- ters in German medical history. one which pales only in comparison to the extermination of the 6,000,000 Jews in the gas ovens of the Third Reich was written by German psychiatrists who. in German mental hospitals. liquidated 240.000 of their 300.000 German patients in specially con- structed carbon monoxide chambers dur- ing the years of World War II. Deformity can mean many things. Early in the Nazi period. it meant ‘‘Jewish,” later it came to mean other things. But as Hermann Goering could say. “Who is a Jew is for me to decide’. \When he needed a Jewish intellectual. he would want. (and later, unwant) him—without need of law or def- initions. Where there is no ethic, there 1s only one law—that of power—naked. brutal. ruthless power. Threat to the mental health of the mother was advanced as a ground for abortion though mental health was not defined. As one of the psychiatrists at the University of California Medical Cen- ter in San Francisco said to me shortly before I left last vear. ‘Charles. where are we headed”. What are we doing” My profession had best look to its own rep- utation. There were times not long ago when I would have authorized an abor- tion. for example. in a case of manic de- pressive psychosis. We have moved far beyond that. \We are granting abortions upon request to the denigration of psy- chiatry and our own good name." Threat to the physical health of the mother was also advanced as a ground. And this. at a time, when medicine had scored as great and significant advances as any in its long history and when such threats were minimal. Moreover. no state would have denied the physician the right to perform an abortion if he were faced with the terrible choice of taking one life in order to save the other. J. Louisiana State MM. Soc. 587 MEDICINE WITHOUT AN ETHIC — CARROLL What has caused me the greatest con- cern, however, is not the almost com- plete acceptance of these proposals in Cal- ifornia. Then. the potential deformity pro- vision was deleted. It was rather the editorial which appeared in California Medicine in September, 1970, to which I have already alluded. The first of many ‘‘eye-openers.’” this appeared in the official journal of the California Medical Association. It not alone claimed the right to formulate the new ethic to which we would all be asked to submit. It claimed that right for the community of medicine alone. It insisted that that ethic should be based on the scientific method and that it should be devised by scientists and scientists alone. At that point, I began to see ever more clearly how much this claim was merely an echo of a far more profound and so- phisticated argument which even then was reverberating throughout the worldwide community of the life sciences. Konrad Lorenz. the Viennese zoologist. in his book On Aggression. had made pre- cisely the same demand, calling for a new and becoming humility from all dis- ciplines other than his own. And he, who spent the better part of his life in Central Europe, did this in writing on aggression (the book's original title being Das So- Gennante Boese: Zur Naturgeschicte der Aggression or So-Called Evil: Concerning the Natural History of Aggression. men- tioning Alexander and Caesar; yet never in 300 pages mentioning Lidice or Oradour, Auschwitz or Dachau, Himler or Hitler. More recently, Jacques Monod, a biol- ogist and Nobel Laureate from France made much the same claim. In his book. Chance and Necessity, he called Jew and Greek. Christian and Marxist, in short. all of those who stood in the millenia—old Western tradition-animists. Discounting all of the contributions made by the humanities in the past and coming as close as any man in the scientific com- munity to embracing a doctrine of ab- solute biological determinism, he, too. has SEPTEMBER, 1972—Vor. 124, No. 9 insisted that science and science alone has the right to determine man’s future. Amidst all of these calls for sweeping change. it is interesting to note that some Germans have not yet forgotten the recent past. They have learned the high price that is incvitably paid when. human life is denigrated and the individual's claim to membership in the humanum is sub- ject to periodic review by a whimsical authority. When the German Democratic Republic. early this year, legalized and offered to subsidize abortion, the Luth- eran and Catholic bishops stood as one in opposition. Now, in the Federal Re- public where a similar measure is be- fore the Bundestag, the Catholic and Lutheran bishops have again taken their stand together. Not all Germans need to be reminded, as William L. Shirer reminds the readers of The Rise and Fall of the Third Reich. of the wisdom of George Santayana: “Those who do not remember the past are condemned to relive it’’. To those who have remembered and do remember our debt is incalculable. In reading a series of essays published last year in Munich by some of the most eminent physical scientists, life scientists. lawvers, philosophers and theologians of Germany and Switzerland (a collection which I trust will soon be translated into English) I, for one, became still more keenly sensitized to the debate on human values, provoked by the abortion contro- versy. In this anthology entitled Men- schenzuechtung: Das Problem der gen- etischen Manipulierung des Menschen, (Human Breeding: The Problem of the Genetic Manipulation of Man), mention was made of Gordon Rattray Taylor's The Biological Time Bomb not once but many times. Sensitive to his words and their meanings. they captured the full im- pact of what he had written much of which had been lost upon me. A scientific journalist. he wrote of the prospects of genetic engineering. the possibility of test tube babies. and the likelihood of defective embryos appearing in the first stages of 315 588 MEDICINE WITHOUT AN ETHIC — CARROLL experimentation. Then he declared: ‘The necessity of destroying the defective embyro which constitutes abortion under present laws in many countries. will no doubt arouse resistance. Those countries who do not consider destruction of the embryo te be abortion until after the fifth month of pregnancy, or some other stated period. will, therefore, be at an ad- vantage’. (p. 183) It was not lost upon the Germans that these words precede Taylor's subchapter on “The Spectre of Gene Warfare —not nuclear, not chemical, not biological, but gene warfare. In a world in which man is made for science rather than science made for man. those who seek abortion on demand of the woman — indeed. all of us — had best ask ourselves if abortion on demand of the state and sterilization on demand of the state and euthanasia on demand of the state can be far away. In a world in which men and women are being ma- nipulated by fears of a population explo- sion and a genetic apocalypse, there has been much concern for Spaceship Earth, but little for the crew. Within the American scientific com- munity. these fears have no more ar- ticulate spokesman than Garrett Hardin. professor of biology at the University of California at Santa Barbara, and former president of the American Academy for the Advancement of Science. Let us examine what he has written and said over the last four years. In Science on December 13. 1968. he wrote on “The Tragedy of the Commons’. Comparing the loss of the public grazing lands in Eng- land (because of population increase) to the loss of the wide open spaces in the American West (because of its explora- tion. settlement and increased use), he sees the world suffering the same threai— overpopulation. Two years later, in the same magazine. on July 31, 1970. there appeared an edi- torial of whirh he was the author entitled “Parenthood: Right or Privilege?" In this, he made it unmistakably clear that 316 he considered parenthood a privilege granted by society rather than a right enjoyed by man. Eloquent testimony to the change which he himself had under- gone — from statement of the problem to proposal for its solution—he left little doubt that mandatery rather than vol untary controls would be needed. How ardently he espouses this cause is underscored by Richard Neuhaus, for- mer pastor of the Lutheran Church of St. John the Evangelist in Brooklyn, author of In Defense of People, recently published by MacMillan, Neuhaus writes of a sym- posium held in New York City in 1970. Hardin, one of the principal participants, poses the problem, as he sees it, in the form of a mathematical equation: “Pop- ulation X Prosperity = Pollution’. Then, according to Neuhaus. Hardin adds: *‘To reduce pollution, one must reduce either population or prosperity, and it is better to reduce population rather than prosper- ity.” (p. 186) All this happened in the summer of 1970 when the United States Bureau of the Census released a report which ad- mitted that its 1967 projection of the United States population in the year 2000 was an overestimate of 100,000,000 (San Francisco Chronicle, August 13, 1970, p. 1) and this — in the richest nation in the world which has some of the best, if not the best, computers and computer scien- tists in the world. On February 15 of this year, in Internal Medicine News, Hardin is reported to have gone even further. He not alone takes the view that voluntary population con- trol is self defeating. He contends that ‘the desire and/or ability to use contra- ception effectively as a trait . . . will be perpetuated in the offspring who do so’: and he sees “‘the lack of this desire and/or ability perpetuating (itself) in the off- spring of those who do not.” Surely, it would be difficult to find a more un- equivocal statement of absolute biologi- cal determinism and ‘or a doctrine of man which represents a more radical reduc- tion of man to a molecular system. Im- J. Louisiana State \M. Soc. 589 MEDICINE WITHOUT AN ETHIC — CARROLL plying that the individual is genetically programmed to contracept or not to con- tracept by his forebearers. he believes that it is “'poorer people. those who come from a long line of poor ancestors, and are apparently unable to better them- selves who are least motivated to use contraception”. One of the rationales for mandatory controls. apparently, would be the presence of genes within certain groups in the population that were adapted to the ‘‘culture of poverty’. If anyone can believe that the ‘new ethic’ will be without its political. eco- nomic and social implications. let him think on these things. There could be no more dramatic portrayal of the inter- relationship of each and every problem and issue now encountered by the life sciences and the community of medicine. Let us take two—abortion and steriliza- tion. Today, doctors are doing two things, only one of which they did before. Loyal to the Hippocratic Oath, the Nuremberg Code or the Helsinki Declaration, they, in times past, often agreed not to do what a patient asked not be done. Then, a doc- tor on occasion, tells a woman patient that the results of a biopsy are positive; that her breast tumor is malignant; that it may well have metastasized. It is not unusual for him to respect her deci- sign when she refuses a mastectomy. Now, however, the doctor is doing what he is asked to do. And, given the temper of the times, and pressured by a society in which the legal has become moral, some are doing so in violation of their own ethics and their own consciences. Ad- mittedly, we live in a period of change, in a revolutionary era. But what will happen to the doctor who bows to the mood of the moment when the state de- mands of him what his patient has de- manded—and received? What will there then be to defend him — without an ethic? There is good reason to fear for the future of medicine in this country. It is one thing to pronounce the demise of the Judaeo-Christian ethic, as the Cal- ifornia Medical Association has done. It SEPTEMBER, 1972—-Vou. 124, No. 9 is quite another to say that a new ethic is needed but not specify what that ethic should be. Order without freedom is tyranny. Freedom without order is chaos. If you have any doubts. read the hictory of Japan during the 20 years armistice (1919-1939), the history of Germany (1919- 1933), the history of the French Republic (1919-1940). In the ‘‘no-man’s land" be- tween the alleged death of the old ethic and the birth of the new. in a time with- out an ethic which is commonly held and commonly honored, who speaks for med- icine? The doctor? The patient? And by what ethic does doctor or patient defend himself? When we succumb to fear of a genetic apocalypse; when we decry the **pollu- tion of the gene pool’: when we claim that amniocentesis is an infallible diag- nostic tool: when we demand prenatal ex- amination of the unborn. what is there to prevent abortion of the woman whether she wishes to be aborted or not? Can we not admit, if only to ourselves, that when we talk of such things and contemplate the ways and means by which we might “improve the gene pool,” we are talking about denying some the right to parti- cipate in the reproductive process and, if only by implication, we are talking about the ‘‘drafting’’ of others? When the physician, for example, agrees to sterilize every patient at his or her in- sistence, what is there to protect the physician or patient when it is the state that insists? : Let us examine what has happened in our courts in the last 50 years. In 1927, in the case of Buck v. Bell (274 U.S. 200, 47 S. Ct. 584, 71 L. Ed. 1000), Mr. Justice Oliver Wendell Holmes read the majority opinion of the United States Supreme Court. The court. having been petitioned for the right to sterilize a re- tardate in the Commonwealth of Virginia. granted the petition on eugenic grounds. Holmes’ words on that occasion — “Three generations of imbeciles are enough’ — have not been forgotten. What has been forgotten, however, is that his interest 317 590 MEDICINE WITHOU | in eugenics was inspired by his father: and his father's knowledge of eugenics was gained in the last quarter of the last cen- tury. In 1962, in the case known as “In Re Nora Ann Simpson: Judge Holland M. Gary of the Probate Court of Zanesviiie County. Ohio, decided to grant a mother the right to have her daughter sterilized. The daughter. who was a young, attractive retardate, had been impregnated and de- livered and her child had been put up for adoption by a public welfare agency. The court, while citing Buck v. Bell. found still other — perhaps more important — grounds for sterilization. To permit Nora Ann to have further children,’ the judge declared. ‘would result in additional burdens upon the county and state wel- fare departments . . . . (180 North East- ern Reporter, 2d. Series 206). With that, cost benefit analysis by judicial authority entered the practice of medicine. Why do I fear this trend? Because I have heard men in California, men of high ideals and noble purpose, ask quite openly and with disarming honesty whether we have the right to maintain the thousands of retardates at Sonoma State Hospital — in view of the burden their care imposes upon the welfare budget of California. With this, the question before the house becomes something quite other than it had been in the days when the Hippocratic Oath was honored. The question now is: “Who Is Human?". hen we start to count mouths on one hand and food sup- plies on the other, we will ifievitably talk first of the quantity of life; then, of the quality of life. But who is to define “‘qual- ity?” Who is to have the power to declare the other “wanted” or “unwanted?” To what branch of government — executive, legislative or judicial — shall we entrust the power to define; to “want” and ‘‘un- want’? What branch shall develop policy? What branch shall implement that policy? What agencies shall enforce the laws? Are we moving inexorably toward that day when the individual's claim to member- 318 AN ETHIC — CARROLL, ship in the hiomanon is subject to periodic review and his ability to pass the test dependent upon his productive capacit, and his value to society”? By what sten- dards does society judge an individual to be productive? By what value system does society accord his Ite vaiue? When I contemplate the extremes to which some very sane men are willing to go to avoid a genetic apocalypse, I re- call my meeting with a retired professor of zoology in Berkeley last year. A man of gentle mien who had taught for many years at one of the state colleges in Cal- ifornia, he asked. “\Would you approve the liquidation of all diabetics?’. “Of course not.” I replied. “Neither would I,” he continued, ‘but would you approve the sterilization of all diabetics?’. “No,” I answered. “Then,” he declared, ‘‘prepare your- self for a world population that. within a hundred years, could well be 50 percent to 60 percent diabetic’. I make no claims to expertise. But I do have some friends who are expert. When I returned to the University of Cal- ifornia Medical Center, I called upon one of them, Dr. Peter Forsham, an endo- crinologist and head of the metabolic unit. “Peter,” 1 began, ‘‘you have had dia- betes since your early teens. As a young man, you were doubtlessly told that you had a life expectancy of 40 years. You, as I, are now 55. Is there any merit to the dire prediction made me by this zool- ogist?" “Charles,” he answered, “I will tell you this. Within five years, I will be able to take the islet of Langerhans from the pancreas and transplant it to the kidney. Then the diabetic will again produce the insulin he needs." “But,” I added, ‘‘you have not discussed the sperm count.” “For that,” he concluded with a wry smile, “'I would ask ten more years.” It is not my intent to interpret Dr. For- sham's words for others. They may be differently interpreted by different peo- J. Louisiana State M. Soc. 591 \MEDICINE WITHOUT AN ETHIC — CARROLL ple. Still, I do not find him living in an Aristotelian or Newtonian universe but rather an Einsteinian universe: his world, not one of Euclidean but rather Rie- mannian dimensions. Conscious of the finitude of man and conscious of finite man’s limitations within the space time continum, he has applied some of the in- sights of the physical sciences to his study of the life sciences. And appreciative of the hard-won insights of the humanities, he accepts the fallibility of all human pre- diction and concentrates upon the elimina- tion of disease rather than the steriliza- tion of the disease bearer. Unhappily, however, the contrary as- sumption, the assumption of inerrancy is rather widespread. In The Atlantic in May, 1971, Edward Grossman, a student of George Wald at Harvard wrote an article on “The Obsolescent Mother”. In read- ing it, I asked myself—without the sligh- test desire to be facetious — if the penis envy of the woman. so well described by Sigmund Freud, had not been succeeded by the womb envy of the man, for surely the geneticist’s attempt to effect an ab- solute divorce between sexual enjoyment and sexual reproduction through the pro- duction of life in vitro could minimize if not eliminate the role of woman from the re- productive process altogether. Grossman suggests and supports the de- velopment of an ‘‘efficient artificial womb” in the hope that, if it catches on culturally, “it will mean that the awe- fulness associated with pregnancy and childbirth will have nothing to feed on, and motherhood, if it continues to excite any awe at all, will not do so more than fatherhood.” Furthermore, he insists that the mother ‘“‘will find that society does not expect her to have a special relation to her offspring” and that a ‘‘society that can grow fetuses in a laboratory will be more disposed to have meaningful day— and night—care centers and communal nurseries on a large scale for the state, being a third parent. will wish to provide for the maintenance and upbringing of its children’. Then. natural pregnancy may SEPTEMBER, 1972—Vor. 124, No. 9 become an anachronism . . . The uterus will become appendixlike”. (pp. 48-49) Immediately following Grossman's ar- ticle in The Atlantic there was one by James D. Watson, professor of molecular biology at Harvard, a Nobel Laureate, and onc of - the co-discoverers of the. genetic code, the secret of DNA. His was quite a different spirit. In posing the question: “Moving Toward The Clonal Man: Is That What We Want?" he undertakes a measured review of the advantages and disadvantages of test tube conception. Then he makes this sober plea: “This is a matter far too important to be left solely in the hands of the scien- tific and medical communities. The be- lief that surrogate mothers and clonal babies are inevitable because science al- ways moves forward, and an attitude ex- pressed to me recently by a scientific colleague, represent: a form of laissez faire nonsense . . .” “I would thus hope’ he concludes. *‘thai over the next decade wide-reaching discus- sion would occur . . about the manifold problems which are bound to arise if test tube conception becomes a common oc- currence . . . Admittedly the vast effort . . . will turn off some people — those who believe the matter is of marginal im-.: portance now, and that it is a red herring designed to take our minds off our callous attitudes toward war, poverty and racial prejudice. But if we do not think about it now, the possibility of our having a free choice will one day suddenly be gone.” (p. 53) TO SUM UP: Medicine without an ethic; the law without a norm: and the religious community without a theology of life and death, man and nature; will leave peo- ple—without a defense. This is particular- ly true in a world in which so many are willing to sacrifice the other rather than sacrifice for the other. For those in the community of medicine, the holocaust should provide sufficient warning. When Hitler came to power. the only oath that had been required of a Ger- 319 MEDICINE WITHOUT man physician was one of lovalty to the Weimar Constitution. That was later sup- planted hy an oath of loyalty to Hitler alone. Without an ethic. German medicine was defenseless. For those mn the community of law, the picture. “Judgment of Nurem- berg" should provide a caveat all its cwn. When. in the last moments of that film, the German Judge Janning runs to his cell door and. grabbing the bars. shouts to his American colleague. Judge Hay- wood. 1 did not know 1t would come to motion that. You must believe it. You must be- lieve it.”” Haywood first stares at hmm and then, almost without thinking. he spoke to him as though he were speak- ing to a child. “Herr Janning. It came to that the first time you sentenced to death a man you knew to be innocent.” (Judgment at Nuremberg by Abby Mann. p 136). Without a norm. German law was defenseless. a mere tool of the tvrant's will. For those in the community of religion: the words of Elie Wiesel in Night should provide a present day reminder of what happens to the man who pronounces God 1s dead. In this an account of his days at Auschwitz. he recounts the hanging by the 320 592 AN ETHIC - CARROLL SS of two adults and a child. the ch.ld “with the face of a sad angel”. The adults. he writes.” died quickly. the weight of their bodies speeding their deaths. But the child? “For more than half an hour he staved there, struggling beiween life and death. dving in slow agony under our eves. And we had to look him full in the face He was still alive when I passed in front of him. His tongue was still red. his eyes not yet glazed. “Behind me. I heard . . . “Where is God now?" “And I heard a voice within me answer him: “Where 1s He: Here He is — He is hang- ing here on this gallows.” (p. 76) Wiesel’s words are strangely reminiscent of another Jew who was crucified between two thieves. (Matthew 25: 34-35) Without a theology that calls each man to see the Wholly Other in his neighbor. the German people — Jew and Christian. believer and unbeliever — were defenseless. This is the Truth that sets men free. It was then. It is now. J. Lotisiana Srate NM. Soc 593 CIENCE under dictatorship becomes subor- LJ dinated to the guiding philosophy of the dic- tatorship. Irrespective of other ideologic trap- pings, the guiding philosophic principle of recent dictatorships, including that af the Nazis, has been llegelian in that what has been considered “rational utility” and corresponding doctrine and planning has replacedi moral, ethical and religious values. Nazi propaganda was higly effective in perveriing pubiic opinion and public conscience, in a remarnadiy short time. In; the medical pro- fession this expressed itself in a rapid decline in standards of mnfessianal cthics! Medical science in Nazi Germany collaborated with this Hegelian rly inf the follawing enterprises: trend parti the mass extermination of the chronically sick in the interest saving “‘uscless’ expenses to the community as a whole; the miss extermination of those considered socially disturbing or racially and ideologically unwanted; the individual, in- . | . conspicuous those considered of extermination of disloyal within the ruijng group;| and the ruthless use of “human experimental material” for medico- military research. | This paper discusses the origins of these activities, as well as their consequences upon the body social, and the motivation of those participating in them, | Preparatory Propaganda Even before the Nazis took | open charge in Germany, a propaganda'barrage was directed against i the "traditional conipassionate njneteenth-century attitudes toward the chronically|ill, and for the adoption of a utilitarign, Fegelixn point of view. i Sterilization and cuthanasia of persons with chronic : mental ilinesses was discussed at a theeting of Bavar- + rohiologic Unit . formerly, consuitant to the Secretary of War, anjdut , the _Cnief of Counscl for War Cqimes, Nurembgrg, Adults were propaganglized by ian psychiatrists in 1931.) By 1936 extermination of the physically or socially unfit was so openly accepted that its practice was mentioned incidentally in an article published ih an official German medical journal? Lay opinion was not neglected in this campaign. notion pictures, elusirueror in paychiatey. Tufts College Medic 2d School; director, Neu- Division of Paychiatric Retcarch, Boston State Hospital: with the Othce nf nited States Zune of Germany, 1946-1947. | 93-999 (Pt. II) O - 73 - 17 MEDICAL SCIENCE UNDER DICTATORSHIP Leu ALexaNper, M.D.® ROSTON onc of which, entitled “I Accuse,” deals entirely with euthanasia. “This hl depicts the life history of a woman suffering from multiple sclerosis; in it her husband, a doctor, finally kills her to the ac- companiment of soft piano music rendered by a sympathetic colleague in an adjoining room. Ac- ceptance of this ideology was implanted even in the children. A widely used high-school mathe- matics text, “Mathematics in the'Service of National Political liducation,” includes problems stated in distorted terms of the cost of caring for and re- habilitating the chronically sick and crippled. One of the problems asked, for instance, how many new housing units could be built and how many marriage-allowance loans could be given to newly wedded couples for the amount of money it cost the state to care for “the crippled, the criminal and the insane.” Euthanasia The first direct order for euthanasia was issued by Hitler on September 1, 1939, and an organization was set up to exccute the program. Dr. Karl Brandt headed the medical section, and Phillip Bouhler the administrative section. All state institutions were required to report on patients who had been ill five years or more and who were unable to work, by filling out questionnaires giving name, race, marital status, nationality, next of kin, whether regularly visited and by whom, who bore financial responsibility and so forth. The decision regarding which patients should be killed was made entirely on the basis of this brief information by expert con- sultants, most of whom were professors of psychiatry in the key universities. ‘I'hese consultants never saw the patients themselves. ‘The thoroughness of their scrutiny can be appraised by the work of onc expert, who between November 14 and December 1, 1940, evaluated 2109 questionnaires. "I'hese questionnaires were collected by a “Realm’s Work Committee of Institutions for Cure and Care.” A parallel organization devoted exclusively to the killing of children was known by the simi- larly cuphemistic name of “Realm’s Committee for Scientific Approach to Severe llluess Due to lleredity and Constitution.” “The “Charitable Reprinted from the New Encland Journal of Medi rin snes Ensiend I ausast of Medicina 594 Transport Company! for the [Sick™ transported paticnts to the Killing centers, and the “Charitable dation for Institutional Chee™ was in charge of collecting the cost of the Killings from the rela- tives, out, however, forming them what the charg s were Jor; in the death certificates the cause of death was faisined | What these activities meantito the population at large was weli expressed byja few hardy souls who dared to protest. A member of the court of appeals at Frankfurt-am-Main wrote in December, 1939: | ? | | There is constant discussion off the question of the destruction of socially unui hic — ithe places where there are mental anstitutions, in rechboring towns, somctimces over a large arca, throuzhout the Rhineland, for example. The people have come to recognise the vehicles in which the patients arc taken from their loriginal institution to the intermediate instituiion and from there to the hquida- tion institution. I am told that whdn they sce these buses cven the children call! out: “Theyfre takinz some more peopic to be gassed.” rom Limburs it is reported that every day from onc to three buses with shades drawn pass tiirouzh on the way from Welmunster to Hadamar, de- livering inmates to the liquidation institution there. Ac- cording to the storics the arnvals are immediately stripped to the skin, dressed in paper shirtsi and forthwith taken to a gas chamber, where they arc Bguidated with hydro- cyanic acid gas and ani added anesthetic. The bodies are reported to pe moved to a combustion chamber by mcans of a conveyor belt, six bodies to a furnace. The resulting ashes are then distributed into six urns which are shipped to ihe families. The heavy smoke from the crematory building is said to be visible over! Hadamar every day. There is talk, furthermore, that in kome cases ncads and other portions of the body are removed for anatomical examination. "he po workinz at this liquidation job in tae insti tutions are said {0 ve assigned from other arcas and are shuancd compictely by tid populace. This per- sonnei is cesciibed as frequenting the bars at night and drinking ncavily. Quite apart from these overt incidents that cxcrcise the imagination of tid people, they are dis- Guicted by the question oi whether old folk who have worked hard all their Jives and may merely have come into their dotage are also being iiquidated. There is talk that tne homies ior the aged arc to bq cleaned out too. The people are said to be waiting for legislative regulation pro- viding some orderly method that (will insure especially that the aged feeble-minded are not included in the pro- gram. i Here one sees what heathansaiyl® means in actual practice. According to the records, 275,000 people veie pukto deta these killing centers. Ghastly as [this seems, it snould a ized that this pro- gram was merely the ey wedge for extermina- tions of far greater scope in the political program for genocide of conquéred nations and the racially unwanted. The methods used ang personnel trained in the killing centers | for the chronically sick be- came the nucleus of the much layger centers in the East, where the plan was to kill all Jews and Poles and to cut down the Russian population by 30,000,000. The original program developed by Nazi hot- heads included also the genocide of the English, with the provision the the English males were to be used as laborers! in the vacated territories in the East, there to be worked wo leath, whereas the English females ee be brought into Germany to improve the qualities of the German race. (This was indeed a peculiar adinission on the part of the German cugenists.) In Germany the exterminations included the mentally defective, psychotics (particularly schizo phrenics), cpileptics and patients suffering from infirmitics of old age and from various organic neuro- logic disorders such as infantile paralysis, Parkin- sonism, multiple sclerosis and brain tumors. The technical arrangements, methods and training of the Liller personne! were under the duedtion of a committee of physicians and other experts headed by Dr. Karl Brandt. The mass killings were first carried out with carbon monoxide gas, but later cyanide gas (“cyclon B") was found to be more cfective. The idea of camouflaging the gas chambers as shower baths was developed by Brack, who testi- fied before Judge Sebring that the patients walked in calmly, deposited their towels and stood with their little pieces of soap under the shower outlets, waiting for the water to start running. This state- ment was ample rebuttal of his claim that only the most severely regressed patients among the mentally sick and only the moribund ones among the physically sick were exterminated. In truth, all those unable to work and considered nonrehabili- table were killed. All but their squeal was utilized. However, the program grew so big that even scientists who hoped to benefit from the treasure of material supplied by this totalitarian method were disappointed. A neuropathologist, Dr. Hallervorden, who had ootained 3500 brains from the killing centers for the insane, gave me a vivid first-hand account.® The Charitable Transport Company for the Sick brought the brains in batches of 150 to 250 at a time. Hallervorden stated: material among those brains, beautiful mental defectives, malformations and early in- fantile discascs. I accepted those brains of course. Where they came from and how they came to mc was really none of my busincss. There was wonderful In addition to the material he wanted, all kinds of other cases were mixed in, such as patients suffer- ing from various types of Parkinsonism, simple depressions, involutional depressions and brain tumors, and all kinds of other illnesses, including psychopathy that had been difficult to handle: I'hese were selected from the various wards of the in. stitutions according to an excessively simple and quick method, Most institutions did not have enough physicians, and what physicians there were were either too busy or did not care, and they delegated the sclection to the nurses and attendants. Whoever looked sick or was otherwise a problem was put on a list and was transported to the killing center. Fhe worst thing about this business was that it produced a certain brutalization of the nursing per- sonncl. They got to simply picking out those whom they did not like, and the doctors had so many patients that they did not even know them, and put their names on the list. Of the patients thus killed, only the brains were sent to Dr. Hallervorden; they were killed in such 595 large numbers that sutopsics of the bodies were not feasible. Thay, in Dr. Hailbrvorden's opimion, greatiy reduced the scientific value of the material. The brains, however were alwivs well fixed and suspended in formalin, exact according to his instructions. 1lc thinks that the kausc of psychiatry Was permanently injured by these acuvities, and that psychiatrists have 2 the respect of the German peopic foreyer. Jiallervorden con- cluded: “Still, there Ro Jnteriring cases in this material.” In general only previously haspitalized patients were exterminated for reasons of illness. An ex- ception is a program carried outlin a northwestern district of Poland, the “Warthegau,” where a health survey of the entire population! was made by an “8.S. X-Ray Battalion” headed by Professor Hohl- felder, radiologist of the University of Frankfurt- am-Main. Persons found to be infected with tuber- culosis were carted off to special extermination centers. Je is rather sgrifichme that the German people were considered by their Nazi Ipaders more ready tolaccept the exterminations of the sick than those for political reasons. it was for that reason that the first exterminations of the jlatter group were carried out under thel guise of sickness. So-called “psychiatric siperts’ "| were dispatched to survey a inmates of camps with the specific order to pick out members of racial minorities dnd political offend- ers from occupied territories and to dispatch them to: killing centers with speci ally made diagnoses such as that of “invetcrate German hater” applied to a number of prisoners who had been active in the Czech underground. Certain classes of patients with mental diseases who were capable of performing labor, particularly members of the armed forces sufiering from psychop- athy or neurosis, were lsent to copcentration camps to {be worked to death, or to|be reassigned to punishment battalions and to b¢ exterminated in the process of removal|of mine fields.® A large number of those marked for death for poli tical or racial reasons were made available for “medical” experiments involving the use of in- voluntary human subjects. From 1942 on, such experiments carried qut in concentration camps wete openly presented at medical meetings. This program included * “terminal hunian experiments,” a term introduced byl Dr. Rascher to denote an experiment so designed] that its sutcessful conclusion depended upon the wi person's being put to death. The Science of Annihilation A large part of this research was devoted to the science of destroying apd preventing life, for which I have proposed the term “ktenology,” the science of killing.™® In the couse of this ktenologic research, methods of mass killing and mass sterilization were investigated and developed for {use against non- ! _\ German peoples or Germans who were considered uscless. Sterilization methods were widely investirated, but proved impractical in experiments conducted in concentration camps. A rapid method develnped for sterilization of females, which could be accom- plished in the course of a regular health examination, was the intra-uterine injection of various chemicals. Numerous mixtures were tried, some with iodopine and others containing barium; another was most likely silver nitrate with iodized oil, because the result could be ascertained by x-ray examination. The injections were extremely painful, and a number of women died in the course of the experiments. Professor Karl Clauberg reported that he had de- veloped a method at the Auschwitz concentration camp by which-he could sterilize 1000 women in one day. Another method of sterilization, or rather cas- tration, was proposed by Viktor Brack especially for conquered populations. His idea was that x-ray machinery could be built into desks at which the people would have to sit, ostensibly to fill out a questionnaire requiring five minutes; they would be sterilized without being aware of it. This method failed because experiments carried out on 100 male prisoners brought out the fact that severe x-ray burns were produced on all subjects. In the course of this research, which was carried out by Dr. Horst Schuman, the testicles of the victims were removed for histologic examination two weeks later. I myself examined 4 castrated survivors of this ghastly ex- periment. Three had extensive necrosis of the skin near the genitalia, and the other an extensive ne- crosis of the urethra. Other experiments in steriliza- tion used an extract of the plant Caladium seguinum, which had been shown in animal studies by Madaus and his co-workers!® 1! to cause selective necrosis of the germinal cells of the testicles as well as the ovary. The development of methods for rapid and in- conspicuous individual execution was the objective of another large part of the ktenologic research. These methods were to be applied to members of the ruling group, including the SS itself, who were suspected of disloyalty. This, of course, is an es- sential requirement in a dictatorship, in which “cut- throat competition” becomes a grim reality, and any hint of faintheartedness or lack of enthusiasm for the methods of totalitarian rule is considered a threat to the entire group. Poisons were the subject of many of these ex- periments. A research team at the Buchenwald concentration camp, consisting of Drs. Joachim Mrugowsky, Erwin Ding-Schuler and Waldemar Hoven, developed the most widely used means of individual execution under the guise of medical treatment — namely, the intravenous injection of phenol or gasoline. Several alkaloids were also in- vestigated, Among them aconitine, which was used 596 - Dr. oven to kili several umpiisoned former fcdow SS mien wio were potential witnesses against the camp commander, och, then under investiga- ion oy the 83. At the Dachau concentration camp Rascier developed the standard cyanide capsaies, Which could! be casilv! bitten through, citier deliberately or dcadentally, if mixed with certain {ouds, and which, ironically enough, later became the means with which Himmler and Goering i nitied themseives. In connection with these poison experiments there is an interesting incident of characteristic and, most recently the Natfonal Multiple ‘Sclerosis Society. All these socictips, which are fco-ordinated with medical | societies and whi receiv od inspiration and guidance from out- -standing physicians, are having an ex{remely whole- ssome effect in introducing fresh mofivating power “into the ivory towers of academic; medicine. It indeed interesting and an assertion; of democratic ality that these societies are activated by and for people suffering from illnesses who. under certain dictatorships, would have een slated for cuthanasia. It is thus that these new socictiés have taken Tover one of the ancient functions of medicine — “namely, to give hope to the patient land to relieve “his relatives. These socicti¢s need theiwhole-hearted support of the medical profession. Unfortunately, -this support is by no meals yet unanimous. A dis- -tinguished physician, invéstigator apd teacher at ~an outstanding university recently [told me that . he was opposed to these aedial socictics and clinics “because they had nothing to offer th the patient. ‘It would be better to wait until sothcone made a « discovery accidentally and then stirt clinics. It is my opinion, however, that one cgnnot wait for vthat The stimulus suppijed by these societies is necessary to give stimulus both to fublic demand "and to academic medi icine, which at times grows stale and unproductive evep in its most outstanding +. ceaters; and whose existence did nothing to prevent the executioner from having logic on his side in + Germany. [ "Another element of this free demacratic socicty rand enterprise that has been a stimulus to new de- velopments is the pharma¢eutical industry, which, mous’ specia ject or several subjects alone, but must inevitably spread and be directed against one's entire surround- ing world, including one’s own group and ultimately the self. “I'he ameliorative point of view maintained in relation td all others is the only real means of sclf-preservation. A most important need in this country is for the development of active and alert hospital centers for the treatment of chronic illnesses. “They must have active staffs similar to those of the hospitals for acute illnesses, and these hospitals must be fun- damentally different from the custodial repositories for derclicts, of which there are too many in exist- ence today. Only thus can one give the right answer to divine scrutiny: Yes, we are our brothers’ keepers. 433 Marlborough Street . REFERENCES 1. Bumke, O. Discussion of Falilhauser, K. Zur Frage der Steril sicrung River. oe arte, Fat brary or 2, 1932. od Dicrichs, R. Beitrag zur 73 Shischen Anstaltsbehandlung Tuberku- loser. Zischr, “uberk, 74:21-2 936. Dorner, A. Mathematik in pry - N Ein Handbuch fur Lehrer, heramsgegeben nalpolitischen Ersichung: uftrage des Reichsvers und Vereine. Sceond Pp. 1-118. hen edition, (revised). 3 Haeite Pievterwes, 1935. Third edition (revised), 1936. Pp. . Alexander, L. Public mental health practices in Germany, sterilization an ecution of patients sutfering from nervous or mental disease, Combined jolineace Objectives Subcommittee, Item No. 24. File No. XXV1HI-30. Pp. 1-173 (August), 19435. Idem. Neuropathology and ncurophysiolosy, including electro-enceph- alography in wartime Germany. Combined Intelligence Objectives $i hrommitiee ltem No. 24, File No. XXVII-1. Pp. 1-65 (July), - Idem. German military neuropsychiatry and neurosurgery. Com- bined Intelligence Qolsstjves Subcommittee, Item No. 24, File No. XXVIH-49. Pp. 1-138 (August), 1945. Idem. Sociopsychologic structure of 5S: psychiatric report of Nurne berg trials for war crimes. Arch. Newrel. & Prychiar. 59:622-634, N 8. ldem. War ines their social-psychological aspects. Am. J. Psychiat. 105:170:177, 1948. P » Pe 4 by with gteat vision, has inveeced considerable effort 9. en War crimes and their motivation: socio-piychological structure ‘in’ the {sponsorship of new research sss nd sriminalization of society, J. Crim. Law & Criminsl : ‘Dictitorships can be indeed defined as SYSIeMS 30. Mudaus, G., and Koch, F. E. Tierexperimentelle Studien zur Feage .in which there is a prev alengce of thinking in destruc- Te a Gite b Ctintivm ay ‘tive rather than in amecligrative terms in dealing 941. " hi, - oh G. Zauberph m Licht teller Forschung, : with social problems. The ‘case with which destruc St Ss suburplanien im ichite xp morte Toons tion of life is advocated for those coifsidered either 1941. ‘socially; uscless or socially disturbing instead of 1 Algrander, L. Misccllancous svission medics] maven. (Soi educational or amcliorative measures may be the 21. Pp. 1-163 (Arwen), 1995, - first danger sign of loss of crfative liberty in thinking, 3 Dagirisnt 1903 2 0%: J : ent which is the hallmark of democratic society. All Alexander, L. Treatment af shock from prolonged gpowure to cold, - ion; spe rer, telly hjectives destructiveness ultimately fcads to self destruction; Sumit Jarlisense | Objettives Subs _ the fate of the 8S and of Nazi Germany is an clo- Seisw-lnapart, Order of the Reich Commissar or the Occupied Nether: 1 {0 t ct 3 quent example. The destructive pinciple, once containing he strate. Jor the ‘Occopsen” Netherivede Ferouonen unleashed, i is bound to engllf the whale personality pp. 1004-1026, December, 1941. and to} occupy all its relationships{ Destructive ois er, ECR Y Sciaer. Bath editions 492 pp. urges and destructive concepts arising therefrom 1s. Tope ghd 4 Sindy of Miners Nordeman: ment of Val. VI By cannot remain limited or |focused upon one sub- Dp omrvell. 6179p. New Yor ¥Ostore. | : Ll | 1" ‘ i Copyri 1949, by the M: h M Society Printed in the U. 5. A. 602 The Medical Moral Newsletter Edited by Frank J. Ayd, Jr.,, M.D. SEPTEMBER & OCTOBER, 1972 Volume IX. Numbers 1 & 2. THE USE OF FETUSES AND FETAL MATERIAL FOR MEDICAL RESEARCH. In a prior issue of this Newsletter devoted to experimentation on prenatal human life, some of the research being done by biochemists, molecular biologists and physiolo- gists, geneticists, embryologists, placentologists, and fetologists was reviewed. (See Newsletter 6/69). It was pointed out that there is a compelling need to consider the ethics of the means these scientists are using to achieve their desired ends, because there is no absolutely imperative end that would justify any means. _Neither the Dec- laration of Helsinki on human experimentation nor any other code of ethics governing “human experimentation includes guidelines for experimentation on germ-plasm or prenatal human life. Since there was no doubt then that there would be an increase in the number and types of experiments on prenatal human life, the formulation of a code of ethics governing prenatal human experimentation was deemed imperative. In May 1970, Mr. Norman St. John-Stevas, a member of Parliament in England declared that in that country aborted live fetuses had been sold for medical experiments. (British Medical Journal 2:433, 1970). Thus, he raised the temperature of an already feverish subject for there was serious disquiet among the lay public and many members of the medical profession about the use of fetuses for research. Mr. St. John-Stevas' charge stimulated not only much discussion of this subject by the lay public but also by physicians and scientists. This culminated in the decision by the Secretary of State for Social Services and the Secretaries of State for Scotland and Wales to set up an Advisory Group "to consider the ethical, medical, social and legal implications of using fetuses and fetal material for research. The members of this Advisory Group were appointed on May 19, 1970. Its chairman was Sir John Peel, Past President of the Royal College of Obstetricians and Gynecologists and this year President of the British Medical Association. This committee met six times to hear the views of a large number of interested parties. After two years work, they have pub- lished their report. Because the definition of terms such as "life" and ""death'' have been changing with advances in medical knowledge (See Newsletters 10/68, 11/71, & 12/71), and be- cause of the contemporary difficulty in defining viability of a fetus, the Advisory Group decided to introduce their own definitions of some of the more important terms used in their report. They believe these definitions reflect more accurately the current state of medical knowledge. Their definitions are: Coovricht 1977 pv St. 2 athonv Mescaaner Proes 11815 Fienokli~ St Cincinnat Ohio £5210 A'l richts rserved 603 -2- The Fetus -- the human embryo from conception to delivery (and therefore including what is normally termed the embryonic state). A Viable Fetus -- one which has reached the stage of maintaining the co- ordinated operation of its component parts so that it is capable of functioning as a self-sustaining whole independently of any connection with the mother. A Pre-Viable Fetus -- one which, although it may show some but not all signs of life, has not yet reached the stage at which it is able, and is incapable of being made able, to function as a self- sustaining whole independently of any connection with the mother. Fetal Death -- the state in which the fetus shows none of the signs of life and is incapable of being made to function as a self-sustaining whole. Fetal Tissue -- a part or organ of the fetus, e.g., the lungs or liver. Fetal Material -- any or all of the contents of the uterus resulting from pregnancy excluding the fetus, i.e., placenta, fluids and mem- branes. These definitions are important because there is a clear distinction between using the tissues of a dead fetus and experimenting on a live fetus. Research involving the use of the dead fetus, fetal tissues, and fetal material has been considered necessary in re- cent years in: (1). Virology -- the study of viruses pathogenic to man, notably those affecting the respiratory system, is possible on a large scale only by using cultures obtained from fetal tissues since most of these organisms do not grow on cultures of non-human cells. Fetal tissue cultures provide excellent purity tests for vaccines and vaccines, e.g., poliomyelitis and rubella (german measles), are manufactured from fetal tissue. (2). Cancer Research -- fetal tissues provide the best source of human cells that can be kept growing in tissue culture for the study of in- duction of disordered growth (analogous to cancerous growth) and of the effect of various agents on that disordered growth. This may lead to improved methods of diagnosing and treat- ing cancer in children and adults. (3). Arterial Degenerative Disease -- the study of fetal tissue cultures may contribute to the knowledge of the origins of such vascular disorders as hardening of the arteries. (4). Immunology -- some fetal cells are used in research into the treatment of certain diseases of infants where the normal mechanism for resistance against infection is deficient; others are used 604 w= to investigate kidney and liver transplant rejection phen- omenon, and for tissue typing in transplant surgery. (5). Congenital Deformities -- research on the whole dead fetus is essen- tial for the advancement of knowledge of fetal development and to investigate factors that might interfere with this so as to produce congenital deformities. Aware of the need for this research, England's Medical Research Council since 1958 has provided a grant to support the collection, preservation and distribution of fetuses, fetal tissues and fetal material by the Royal Marsden Hospital, London. This hospital supplies about 40 different establishments and individuals with this material. The Advisory Group concluded that the contribution to the health and welfare of the entire population is of such importance that the development of research of this kind should continue subject to adequate and clearly defined safeguards. RESEARCH ON THE FETUS IN UTERO. Investigations and tests on the fetus during pregnancy may be carried out with the intention of benefiting the mother, her expected child or both. The Advisory Group did not think that ethical or legal objections arise in such instances. However, it rejected categorically the suggestion that it would be permissible to administer substances to the mother in order to see if these are harm- } ful to the fetus, when there is the intention to terminate the pregnancy with the idea of = preventing a live-birth. It said, "it is unethical for a medical practitioner to admin- ister drugs or carry out any procedures on the mother with the deliberate intent of as- certaining the harm that these might do to the fetus, notwithstanding that arrangements may have been made to terminate the pregnancy and even if the mother is willing to give her consent to such an experiment." It also warned that such experiments are under- taken at the risk of the investigator since, if the fetus is alive on termination of preg- nancy but is handicapped or subsequently dies as a result of experiments conducted dyr- ing pregnancy, the persons concerned would be liable to prosecution. Also, if the fetus is born alive but is handicapped as a result of such experiments it would be open to the parent to seek compensation through the courts." RESEARCH ON THE VIABLE FETUS. The Advisory Group stressed that ''there should be no ambiguity about the circumstances in which research can be carried out on a viable fetus. In our view when the fetus is viable after delivery the ethical obligation is to sus- tain its life so far as possible and it is both unethical and illegal to carry out any experi- ments on it which are inconsistent with treatment necessary to promote its life, although in many instances the techniques used to aid a distressed fetus are so new that they are in some degree experimental." In England and Wales evidence of pregnancy for a period of 28 weeks or more is accepted as prima facie proof that the mother is at that time pregnant of a child capable of being born alive. However, because of medical advances, the Advisory Group con- cluded that it is "no longer acceptable to take the 28th week of pregnancy as indicating the time at which a fetus becomes capable of survival as fetuses delivered before that date, may, by modern techniques, be enabled to live." Hence, "for ethical, medical and social reasons we recommend that for human fetuses evidence of a period of gesta- 605 lis tion of 20 weeks (140 days: this corresponds to a woight of appraxtmately 400 200 grams) should be regarded as prima facie proof of viability at the present time. This proposal is in line with a similar recommendation expected from the World Health Organization. Fur- thermore, since medical progress will continue, the Advisory Group recommended that the date of viability should be reviewed regularly to take account of the rapid changes taking place in medical knowledge. RESEARCH ON THE PRE-VIABLE FETUS. Since Parliament passed the Abortion Act in 1968, under certain circumstances it is legal in England, Scotland and Wales to pre- _ vent a pre-viable fetus from attaining life. Some of the methods used to achieve this, for example, hysterotomy (a minor caesarian section), mean that a whole fetus can be de- livered which may live for a few hours independent of the mother. Such fetuses can be used for research. The Advisory Group noted that, in certain countries, research involving the whole pre-viable fetus has been carried out after delivery. It acknowledged that, in view of the abortion law, it would seem ethically justifiable to undertake such research. They con- sidered whether through research on whole pre-viable fetuses new knowledge may be gained which would ultimately benefit viable infants. The testimony they heard indicated that: (1). The whole pre-viable fetus has offered an important opportunity that cannot be obtained in any other way for making observations of great value on the transfer of substances across the human placenta, the reaction of the immature fetus to drugs, and on the endocrinological development of the fetus and the development of the placenta. (2). There is a particular need to determine the ability or otherwise of the fetus to deal with substances including drugs given therapeu- tically to benefit the mother, which may cross the placenta. (3). Observations on the pre-viable fetus are necessarily limited to a period of two or three hours. They have, however, already contributed significantly to our understanding of vital physio- logical and biochemical processes before birth on which the development of a fetus into a normal child essentially depends. (4). As yet our knowledge is not sufficient to enable us either to control or compensate for any deviation from the normal in such processes. (5). Research on the pre-viable fetus promises, however, to be the most hopeful approach to understanding certain failures of the human brain to develop properly and the influence such factors as variants in sex- ual differentiation in utero may have on inherent behavioral patterns after birth. Since '"in the case of single births any fetus of less than 20 weeks gestational age (400 - 500 grams) is pre-viable and as such has not yet reached the stage at which it can exist as a living entity," and after "exhaustive consideration" the Advisory Group reached the "unanimous view that it would be wrong to exclude the use of the pre-viable fetus for Send all correspcndence to The Medical—Moral Newsletter - 1615 Republic St., Cincinnati, Ohio 45210 9, hliche? Month v excant 'ily in Apagss hy © Agrhe~y Messenoer Press - €7 650 a var in US. and e sewhere. 606 po research, provided the following conditions are observed: (1). Only fetuses weighing less than 300 grams should be used. (2). The responsibility for deciding that the fetus is in a category which may be used for this type of research must rest with the medical attendants at its birth and never with the intending research worker. (3). Such research should only be carried out in departments directly re- lated to a hospital and with the direct sanction of the hospital's ethical committee. (4). Before permitting such research the ethical committee should satisfy itself: (a) on the validity of the research; (b) that the required in- formation cannot be obtained in any other way; and (c) that the inves- . tigators have the necessary facilities and skill. RESEARCH ON THE DEAD FETUS. Whether a fetus dies after birth or is born dead, the Advisory Group believes that "the benefits to be derived from the use of the whole dead fetus in the prevention and treatment of disease and deformity are such that it would be a retrogressive step to prevent it." Hence, it felt that this research should be allowed to continue, provided stringent precautions are taken to insure that such experiments are ethical, necessary, and likely to be informative. RESEARCH ON FETAL TISSUES AND FETAL MATERIAL OTHER THAN THE FETUS. Because of the "essential contribution that is made by this research to preventive med- icine," the Advisory Group said, "there is no reason to object to the use of fetal tissues and fetal material for these purposes," provided also that such research is ethical, necessary, and likely to be informative. CONSENT TO RESEARCH. No research can be done ethically or legally without in- formed consent from the subject or a responsible relative or guardian. In discussing this subject, the Advisory Group stated: "Where a fetus is viable the overriding res- ponsibility of the doctor is to promote and preserve its life and the parent's consent can normally be inferred for procedures consistent with this aim. There are also areas of research which whilst not jeopardising the health and welfare of the fetus are not of direct benefit to that particular fetus. In such cases we consider that express consent should be obtained from the parent." When a fetus is born alive and later dies, the Advisory Group pointed out that the laws governing the disposition of a deceased person and the laws concerned with cer- tification of causes of death and investigation by coroners must be complied with. In addition, the scientist must make sure that there is no objection on the part of the parent before the body can be used for research. Although there is no statutory requirement in England to obtain the parent's con- sent for research when the separation of the fetus from the mother leads to the termina- tion of its life (abortion), the Advisory Group noted that there also is ''no statutory pow- er to ignore the parent's wishes." Hence, even though some contend that to seek consent 607 “Be could be an unnecessary source of distress to parents, the Advisory Group, although sharing this view, expressed the belief that the parent must be offered the opportunity to declare any special directions about the disposal of the fetus. It suggested that the opportunity for the parent to do this could be provided by adding an appropriate clause to the form giving the patient's consent to abortion. This, the Advisory Group felt , would minimize any possible distress. CONSCIENTIOUS OBJECTIONS. Since some research staff members may have con- scientious objections to the use of fetuses or fetal tissues for research, the Advisory Group recommended that "no member of staff should be under any duty to participate in research on the fetus, fetal tissue or fetal material if he or she has a conscientious objection." It also advised that "experiments on the fetus or dissections for fetal tissues should not be carried out within the operating theatre or place of delivery." THE BUYING AND SELLING OF FETUSES, FETAL TISSUES, AND FETAL MATERIAL. Aside from paying the necessary cost incurred in administering services such as those provided by the Royal Marsden Hospital noted earlier, the Advisory Group emphatically avered that there should not be monetary exchange for fetuses, fetal tissue or fetal material. Thus, it expressed the general opinion of the medical profession and the lay public in condemning the buying and selling of fetuses for research. FUTURE CONTROL OF RESEARCH. The Advisory Group rejected the suggestion that there should be legislation to provide for the licensing of those who wished to undertake research using fetuses, fetal tissue or fetal material similar to the licences issued to those undertaking research on animals. It also rejected the establishment of any central body to advise in cases where there is uncertainty about the ethics of particular investi- gations. It did this because it felt that there would be too few inquiries to justify a per- manent advisory body. Instead, the Advisory Group recommended that arrangements be made for a small informal advisory body with legal representation and including members from various scientific organizations. This informal advisory body would be convened when the need for central advice arises. In 1967 the Committee on the Supervision of the Ethics of Clinical Investigations in Institutions set up by the Royal College of Physicians of London recommended that: "The competent authority (e.g. Board of Governors, Medical Schools Council, Hospital Management Committee, or equivalent body in non-medical institutions) has a responsibility to ensure that all clinical investigations carried out within its hospital or institution are ethical and conducted with the optimum technical skill and precautions for safety. This responsibility would be discharged if, in medical institutions where clinical investigation is carried out, it were ensured that all projects were approved by a group of doctors including those experi- enced in clinical investigation. This group should satisfy itself of the ethics of all proposed investigations. In non-medical institutions or wherever clinical investigation (i.e. any form of experiment on man) is conducted by investigators with qualifications other than medical, the supervisory group should always in- clude at least one medically qualified person with experience in clinical investi- gation." 608 oo This recommendation is now in effect in England and Wales and the Advisory Group strongly advised that all research using the fetus, fotal tissue or fetal material should be approved by such a committee whatever the institution in which tho research is undertaken. It also held that "research involving the pre-viable fetus should only bo carried out in departments directly related to hospitals. Finally, it recommended that ''the committee should accept responsibility for ensuring that such investigations are ethical," and suggested that the committee should use as a guideline the principles set forth in the Advisory Group report. EDITOR'S COMMENT: This Advisory Group report has been presented in detail because it merits very careful perusal and critical analysis. It is important for what it says explicitly and implicitly and also for what it fails to say. Some of the argu- ments advanced to justify the ethics of the research they considered, could be used by others to substantiate that other forms of human experimentation, and that infanticide and euthansia would be ethical under certain circumstances. The Advisory Group stated that "it is unethical for a medical practitioner to ad- minister drugs or carry out any procedures on the mother with the deliberate intent of ascertaining the harm that these might do to the fetus, notwithstanding that arrangements may have been made to terminate the pregnancy and even if the mother is willing to give her consent to such an experiment.’ It gives no explicit basis for this judgment, aside [ from warning the investigator who would do such research that he would be at legal risk if the fetus is born alive but is handicapped or subsequently dies as a result of the exper-: iment. He could be sued! The Advisory Group conclusion that such research is un- ethical is correct but the reason set forth for this is wrong. It appears that the Advisory Group is concerned primarily with protecting the researcher and not the inherent rights of the fetus. It says nothing about the right of the fetus not to be harmed or right not to | be an experimental subject who may be harmed solely for the acquisition of knowledge | for the possible benefit of others. They fail to mention, and possibly did not give con- sideration to the fact, that some knowledge, however desirable and useful, cannot be ob- tained licitly. ? The Advisory Group does say that the mother cannot authorize such an experiment on her fetus in utero but it neglected to say why explicitly. Undoubtedly, this Group be- "lieved that this was not necessary because it felt that people know that no one can licitly consent to unethical research and that all ethical codes forbid a parent consenting to the performance on their progeny of very hazardous and possibly lethal experiments solely for the accumulation of scientific knowledge and not for the benefit of the subject. Yet, many would deny that the mother does not have the right to consent to such experimentation. They argue that, since the mother has the legal right to an abortion under certain cir- cumstances, she also has the right to authorize the use of her fetus as an experimental subject prior to its execution via legal abortion. Such proponents ignore the simple truth that making something legal does not necessarily make it morally or ethically right. It is very dangerous and erroneous to argue that, since a fetus or a person is going to die or be killed shortly, it is ethical to use him for research purposes. Similar arguments have been offered in the past to justify using condemned prisoners or dying patients as experimental subjects. Such arguments have been rejected as fallacious by the framers of all ethical codes governing human experimentation. 609 li The Advisory Group says that scientists can ethically experiment on a pre- viable fetus delivered alive, provided certain conditions are met but that, when a viable fetus is delivered alive, "it is both unethical and illegal to carry out any experiments on it which are inconsistent with treatment necessary to promote its life." In the latter case, the Advisory Group states "the ethical obligation is to sustain the life of the fetus so far as possible.’ It seems that the Advisory Group feels that, since the pre-viable “fetus, although alive, cannot be made to continue to live after delivery because of the immaturity of its biological development, it has no intrinsic value or rights that protect it from being an experimental subject for the benefit of others or the right to have efforts made to sustain its life, such as a viable fetus delivered alive has. Hence, the Advisory Group arbitrarily says that a fetus' right to life and right not to be an experimental sub- ject depends on its biologic development and not on its intrinsic value as a potential human being. If it is valid to say that, because of the immaturity of its biological development, a pre-viable fetus can be used as an experimental subject for the benefit of others, then in vitro fertilization and embryo transplantation also would be licit. The ethical argu- ments against this position were set forth in previous issues of this Newsletter on in vitro fertilization and embryo transplantation. (See Newsletters 1, 2, 3, 4, & 5/72). The proposal of the Advisory Group to reduce the age of fetal viability in England from 28 to 20 weeks is significant, particularly in view of its contention that when a viable fetus is delivered alivd "the overriding responsibility of the doctor is to promote and preserve its life" and that it is unethical and illegal to carry out any experiments on it that are not for its benefit.’ In short, the Advisory Group affirms that the viable fetus has a right to life after delivery and should be given protection like any other conscious human life. It is enigmatic that a viable fetus in utero does not have a right to life but can be aborted legally. In fact, in New York and Maryland, for example, the law per- ~ mits abortion up to 26 weeks. Thus, in these and other states and countries that permit abortion of a viable fetus, infanticide and not fetecide is being practiced, while at the same time it is being proclaimed that we should protect every "viable" human life, like any other, from destruction and from being the subject of unethical experimentation! Man can be and is very arbitrary when he desires to attain a specific goal and thus he ignores immutable truths. Happily, the Advisory Group Report, despite its shortcom- ings, expresses concern throughout for the observance of impeccable standards of ethics and consequently, it is a valuable reminder that the fetus is a potential human being --- not an experimental animal. Saar REFERENCE. Advisory Group (Chairman, Sir John Peel), The Use of Fetuses and Fetal Material for Research. London. Her Majesty's Stationery Office. 1972. JAMA CALLS FOR DELAY IN TEST-TUBE BABY IMPLANTS. An editorial in the May 1, 1972 issue of the Journal of the American Medical Association entitled "Genetic En- gineering in Man: Ethical Considerations' urged a moratorium on any further experiments to implant into a woman's womb an embryo resulting from in vitro fertilization until the ethics of this procedure are settled. (See Newsletter 5/72). FOOD FOR THOUGHT. "If the price of the 'common good' is the sacrifice of the individ- ual, the price is too high." Irvine H. Page, M.D. On Being a Physician: Some Reminders. Modern Medicine. March 6, 1972.7) 93-999 (Pt. II) 0-73 -18 610 Marriage and Family Newsletter "ee JOHN E. HARRINGTON, MSW, ACSW, Editor & Publisher Usp P. O. Box 6066 Collegeville, MN 56321 Bary o peare WY VOL. 3, NO. 1 TANUARY, 1972 EXPERIMENTATION WITH PRENATAL AND NEONATAL HUMAN BEINGS - Part 1 by John E. Harrington, MSW, ACSW In his book Human Guinea Pigs: Experimentation on Man, M. H. Pappworth, M.D, states: In medical circles it is often considered an adequate safeguard if both parents have viven consent after full explanation and avowal of methods and possible conse- quences. But in actual fact the law both here and in America appears to be very definite, namely, that parents, either singly or together, cannot give valid legal consent to any action that is not qr the immedi- ate benefit of the child concerned. . .. ". Traditionally in medicine the physician has considered that in treating a pregnant woman that he was not just treating one patient, the woman, but that he was also treating the unborn child. Today, in the light of the pioneering work done by Dr. William Liley and others in the medical care of the unborn child, today’s physician has even more reason to consider that when he has a pregnant woman for a patient he has two patients. With abortion becoming a rather common form of birth control and the feverish interest of some in the scientific community to unlock all of nature’s secrets within this century it is no wonder that some unborn and some born children end in the labora- tory as guinea pigs while they are still alive. Copyright «© 1972, John E. Harrington, MSW, ACSW, Editor & Publisher, Marriage and Family Newsletter, P. O. Box 6066, Collegeville, Minnesota TET _— ie el Printed in the U.S. 611 Marriage and Family Newsletter - p. 2 - Vol. 3 - No. 1 - January, 1972 Experimentation with prenatal and neonatal human beings is felt to be necessary by some in order to further the practice of transplantation. There is a need for more organs. Some advocate organ farms: While organ storage will probably be the main source of supply for ‘spare-part’ operations in the next fifty years or so, beyond that we can expect to see a far more radical alternative: the growing of organs from embryonic tissue, in whatever quantities required. The maintaining of cells oy and tissues in culture is now a well-developed technique, the first steps in which were taken more than half a cen~ tury ago by an American, Ross Harrison, who maintained nerve cells alive in isolation. Since the war, notably at the Strangeways Laboratory in England, a start was made on maintaining organs. First, small thigh bones, taken from an embryo, were grown to many times their initial size. More recently, in Paris, Etienne Wolf at the College de France has grown embryonic tissue destined to become not only bone but skin and testis; he has even been able to change the sex of the gonadal tissue by the application gf hormones. He is now working on the growing of eyes. In the area of test-tube baby experimentation some unborn children have been kept alive for several days after conception and then when the experimenter no longer had a use for these children they have been left to die or have been destroyed. The nondescript object under glass might have been a blob of blubber. Yet it commanded the rapt attention of the man in the close-cropped beard. The blob was in fact a tiny embryo. Unlike the pickled-and-preserved embryos on display in the halls of museums and medical schools, this one pulsated with life - with human life. At least, its origins were human. It now lived and grew inside an artificial "glass womb" which the bearded gentleman himself had devised. More than that, he had been responsible for the conception of the child - if it could be called a child, In a sense, he had fathered it. It might even be said that he had mothered it. According to his account, he had begun with a female ovum removed surgically at just the right, ripe moment. After im- mersing the ovum in amniotic fluid from a real womb he had then admitted male sperm, and one of the teeming millions of spermatazoa had proceeded to fertilize the egg, just as it might have done in the fallopian tube of a real mother. Under his careful laboratory maternity, the egg had grown into an em- bryo. The embryo was still alive and growing there in its transparent manmade uterus, the cells proliferating even as he watched. Until the past decade or so any scene like this would have been out of a bad science-fiction novel. But this is reality - the place, No. 3 Via de Ruini, Bologna, Italy. The time, 1959, The man, an Italian experimental scientist and surgeon, Daniele Petrucci. 612 Marriage and Family Newsletter - p, 3 - Vol, 3 = No. 1 - January, 1972 Marriage and Family Newsletter 3 The first press reports of Dr. Petrucci’s work created a furor in Italy, Vatican sources as well as laymen roundly denounced Petrucci. An outraged citizen of Naples even demanded that the doctor be prosecuted for murder because he "terminated the experiment" - i.e., let the embryo die - at the end of twenty- nine days. Dr. Petrucci has reported that one of his in vitro embryos survived for fifty-nine days. Many others are attempting to experiment with test-tube babies and when they are finished with the experiment the child is left to die. Other researchers, including at least two Americans - Dr. John Rock at Harvard and Dr. Landrum B. Shettles at Columbia Presbyterian Hospital in New York - had already grown em- bryos in vitro before him (Petrucci), though their embryos lasted for only a few days each. Their results, too, were met with some skepticism, but Dr. Cecil B. Jacobson - himself a skeptic of earlier claims - now seems to be indisputably growing early embryos in vitro in his laboratory at George Washington Univer- sity. For many years unborn children have been studied and experimented with by psychol- ogists. Below is described how parts of the brain of a living child are removed. In a fetus less than 8 weeks old, Minkowski (1922) reports that percussion of the patellar tendon resulted in contraction of the quadriceps muscle. After this contraction had taken place, irradiation followed to other muscles. In this fetus the heartbeat was relatively constant at 80 beats per minute, but covering the fetus with normal salt solution at 40° led to an increase in the beat of the heart from a basal beat of 80 to 100 beats per minute. Extirpation of the cerebral hemispheres in this fetus did not change the reflexes de - scribed. Sectioning the medulla just above the cord region, however, abolished the reflexes due to change in the position of the body. In another experimentation in which the brain of a living child was removed in order for the experimenters to see what would happen to the contractions. In a fetus about 2 months old, Bolaffio and Artom report... . After this same fetus was decerebrated they note a greater vividness (vivacita) of the local contractions referred to above and the reappearance of diffusion of movement at a distance from the stimuli which had ceased. They further suggest that even in a fetus of this age removal of the cerebral cortex does remove some inhibition from the lower reflexes. 6 (1924) 613 Marriage and Family Newsletter - p. 4 - Vol. 3 - No. 1 - January, 1972 Some experimenters have observed reactions of unborn living children by dropping them from a short height. Bolaffio and Artom studied a fetus of about this same age (9-10 weeks). They report that dropping the fetus from a height of a few centimeters to a table led to tive con- tractions of the flexor muscles of the limbs. (1924) In another experiment in which the brain was cut out of a living child and after the experimenters observed the reactions they then note that after 15 minutes every reaction had ceased. After superficial and deep stimulation of numerous points on the body of a decerebrate fetus of 90 mm (about 11-12 weeks approx.), Bolaffio and Artom at first recorded very vivid contractions of apparently all muscles. After about 3 minutes, however, the contractions were still bilateral, but limited now to segments and homologous regions of the body. As time passed, the contractions became more and more circumscribed, and after about 3 minutes they were limited to the muscles corresponding to the stimu- i Jotat- After 15 minutes every reaction had ceased. 1924 Other experimenters have cut the spinal cord to observe what reaction this would bring about. By 13 weeks the top and back of the head alone remain insensitive. Minkowski, studying a fetus in the early part of this period (110 mm), recorded the fact that touching the lower lip or tongue with a blunt probe led to a closing of the mouth, brought about through the lowering and lifting of the jaw. He also noticed in the same fetus that reflexes of the trunk and extremities were seen prominently, but after the transection of the cord in the dorsal region the lower reflexes were discontinued at once. This seemed to prove that conduction of activation in this case, at any rate, was through the cord. After this operation, moreover, he noticed that the short reflexes remained unchanged but were themselves abolished after total extirpation of the cord. 9 (1944 and 1922) Researchers have also cut into the child’s brain to see what reactions might occur. In a fetus of 135 mm (approx. 13-14 weeks) Minkowski notes that a touch on the skin, using a blunt stimulus, led to reactions of diverse parts of the body. Characteristic of such stimulation were the flexion of both arms, the repeated opening and closing of the mouth, and simul- taneous retraction of the head. He notes that at this stage of fetal developmefit every part of the skin can act as a reflexogenous zone for various reactions. These reactions, however, tend to spread more or less over the entire 614 Marriage and Family Newsletter - p, 5 - Vol. 3 - No. 1 - January, 1972 —_— yr fetal organism. Direct muscle excitability still remained at this stage 1 hour after the cord had been extirpated. Total removal of the cerebral cortex did not change the observable responses noted above. Transection at the midbrain, however, seemed to geaken the responses, although they still continued. 1 (1922) Researchers have stimulated the motor roots of the spinal nerve of children who have been aborted. Direct mechanical stimulation of the motor roots of the spinal nerve at this stage showed that intersegmental spinal conduction is well established. (1922) Others have stimulated cranial nerves and facial nerves as well as the cortex and the medulla. Mechanical stimulation of the cranial nerves at the level of the medulla led to the opening and closing of the mouth. It is presumed by Minkowski that this reaction resulted from the direct stimulation of the facial nerve. At this period direct stimulation of the cortex does not lead to response, but breathing changes do result from stimulation of the medulla. 12 (1924) In another study researchers in experimenting upon a living child mechanically stimulated the Rolandic zone of the brain both through the cranial cap and then after removing the cranial cap, removed the hemispheres of the brain, stimulated the medulla, and then made observations on the muscular contractions disappearing as the child expired. In a fetus of this same length (230mm- approx. 18-19 weeks) Bolaffio and Artom noted . . . . (1924) In regard to the development of cortical dominance at this time it is interesting to note that mechanical stimulation of the Rolandic zone of the brain, either through the cranial cap or after its removal, did not call forth any reaction, Nevertheless, removal of the hemispheres did lead to more vivid local responses than in preceding excitations when the brain was intact. Stroking the pectoral muscles called forth adduction of the contralateral limb. In this case also these investigators reported that, if the intensity of the stimuli was increased somewhat, they got contraction of the whole corresponding limb, By stimulating the medulla they were able to call forth violent respiratory movements with active participation of the cervical, thoracic, and abdominal muscles, and those of the diaphragm. These movements were so violent they also led to elevation of the shoulder and adduction of the arms. It is further significant to realize that these investigators found, after repeated successive experiments and as the vitality of the fetus became less, that the muscular contractions disappeared first in the lower limbs and then later in the upper limbs, 13 615 Marriage and Family Newsletter - p. 6 - Vol. 3 - No. 1 - January, 1972 It is difficult to imagine how researchers could have a child who had been aborted, was crying, not a full term baby, and while the baby was crying would remove the top of the skull before death. ~ In another fetus of exactly the same size (330 mm- approx. 24-25 weeks) these same investigators (Bolaffio and Artom) report that the fetus cried weakly and moved about spontaneously but with less strong movements than those characteristic of a fetus at term. When death seemed imminent in this fetus the top of the skull was removed and the cortex directly stimulated electrically. All the various zones of the cerebral cortex were stimulated with negative results. Stimulation of lower brain centers, however, led to specific results such as increased breathing rate, shoulder, arm and finger movements. 1 (1924) One of the reasons put forward as the reason why unborn children are being experiment- ed with is that artificial placentas must be developed which could help prematurely born infants, who are liable to die of ‘respiratory distress’, i.e. breathing difficulties. At King’s College Hospital, London, one such machine has kept a human foetus, born at 26 weeks, alive for five hours, apparently in good shape. In design it is based on the well-known heart-lung machines. The = umbilical cord from the foetus passes through a lightly coiled cellulose tube, which bathes it in fluid, and oxygen is bubbled through. If the foetal blood is abnormal in composition - for instance the level of sugar in it may be too low - this can be corrected. 15 (1968) * Scientists have conducted rather extensive neurological experiments on children who have been aborted and who are still alive. In the experiment reported below the cortex is electrically stimulated, the internal capsule and peduncles of the brain exposed, the medulla and cervical cord stimulated, and also the lumbar cord is stimulated. In a fetus of 260 mm (approx. 20-21 weeks) Bolaffio and Artom attempted certain specific neurological experiments. By means of appropriate electric stimuli they explored the cortex but did not obtain any reaction even with intense stimulation. By operation the internal capsule and peduncles of the brain were exposed, but still electric stimulation gave no response. When they reached the pons, however, they got ready and synchronous responses from the muscles innervated by the facial nerve. Finally, stimulation of the medulla gave energetic respiratory movements. Stimulation of the cervical cord led to energetic movements of elevation of the shoulder with flexion of the upper limbs, and stimulation of the Jumbar cord gave movements of the lower limbs. 1 (1924) 616 Marriage and Family Newsletter - p. 7 - Vol, 3 - No. 1 - January, 1972 Generally children who are born prior to the 24th week of gestation are not able to survive, however a few children do. Normally we should expect that when a child is born or is living when aborted that ordinary medical measures should be used to keep the child alive but this is not always the case. Consider what is reported below: the direct stimulation of the cornea and removal of the brain during the seventh month of gestation, Direct stimulation of the cornea of the eye leads from this time on to an increasingly strong response. Decerebration in this month was found to lead to increased vividness of most reflexes, but also to a tendency to reflex spread. (1922) People often are in favor of abortions performed prior to the third month of gestation and yel in the experiment reported below, these children have high excitability, the neuro- muscular apparatus is capable of active functioning. Fitzgerald and Windle studied human fetal material that was not anesthetized or narcotized. Some of their observations were made while the fetus continued to receive oxygenated blood from the intact placenta, Under these conditions, in three fetuses of approximately 8 weeks’ postinsemination age, excitability was high. Quick arm, leg, and trunk movements were called out by tapping or pressing on the amniotic sac, These reactions occurred individ- ually and in various combinations. They did not involve a total reaction of the organism unless the stimulus was very strong. These investigators hold that, by the eighth week of development, if the fetus has an adequate supply of oxygen, if it is unnarcotized, unanes- thetized, and in other ways undamaged, its neuromuscular apparatus is capable of active functioning. They also believe that some receptors or synapses are more casily rendered nonfunctional by anoxia than others. Arm and leg responses are abolished in asphyxiated specimens after the time when stimulation applied to the skin of the face still calls out trunk flexion. In this stage of asphyxiation, strong stimulation calls out mass movements involving trunk, arms, and legs. This observation suggests, along with other evidence, that much early mass movement of the fetus is a function of decrease in oxygen in the blood and concomitant overstrong stimulation. 18¢ 1942) 617 Marriage and Family Newsletter - p. 8 - Vol. 3 = No. 1 - January, 1972 Much research effort today is in the direction of finding more effective forms of contraceptive devices. In terms of experimentation the definition of contraception has been expanded to include forms of birth control which go beyond conception control and which will interfere at some point after conception. Given this definition of contraception one can easily see how birth control researchers would feel that they could experiment with unborn and aborted children in order to find more effective contraceptives. In a Ford Foundation Reprint from Family Planning Perspectives by Oscar Harkavy and John Maier entitled ‘Research in Reproductive Biology a ontraceptive Technology: Present Status and Needs for the Future’ reprinted from the Vol. 2, No. 3, June 1970 issue there is a picture on p. 11 showing researchers at Sweden’s Karolinska Institute perfusing a previable human fetus. Consider the following quotations and their implications for prenatal human life from this reprint: However, it has been found that wrapping a length of fine copper wire around the stem of the T (IUD) lowers the pregnancy rate considerably, probably because the metallic copper is slowly ionized by the uterine fluids, with the copper ions either acting as a spermicidal agent or interfering with implantation. p. 4 Post-Coital Anti-Zygotic Pill: Several classes of compounds, some of which are also used in cancer chemotherapy, destroy the fertilized ovum or early blastocyst. p. 6 Luteolytic Compounds: . . . Several compounds are claimed, on the basis of animal experimentation, to produce degeneration of the corpus luteum, thus inducing menses whether or not a pregnancy has begun. p. 6 *Diczfalusy offers the following preliminary list based on steps in the reproductive process most susceptible to regulation: 1) interference with sperm motility, 2) chemical sterilization of women, 3) methods to induce endocervical hostility, 4) agents interfering with corpus luteum function, 5) agents interfering with implantation and early embryonic development. p. 15, Footnote. Subscriptions: 12 issues per year. Rates: 1 yr.- $5.00, 2 yrs.- $9.00, 3 yrs.- $12.00. Bulk Subscriptions to the same address: 1st subscription- $5.00, each additional subscription to the same address- $3.00. Back copies: 50¢ each for single copies of each issue, including postage. 2-5 copies of each issue: a each plus postage. 6-10 copies of each issue: 30¢ each plus postage. 11-25 copies of each issue: 20¢ each plus postage. 26 or more copies of each issue: 10¢ each plus postage. Marriage and Family Newsletter may not be reproduced in any form or by any means without the Tae A of the publisher. Marriage and Family Newsletter is copyrighted under Class B, Form B with the Register of Copyrights, Library of Congress, Washington, D.C. 20540. The editor and publisher is John E. Harrington, MSW, ACSW, P. O. Box 6066, Collegeville, Minnesota 56321 618 Marriage and Family Newsletter Yl JOHN E. HARRINGTON, MSW, ACSW, Editor & Publisher WN P. O. Box 6066 Collegeville, MN 56321 /F, wt ®8Rry o peATHOWE VOL. 3, NO. 2 FEBRUARY, 1972 EXPERIMENTATION WITH PRENATAL AND NEONATAL HUMAN BEINGS- Part 2 by John E. Harrington, MSW, ACSW Children who have been aborted have been used for research experimentation at the University of Rochester Medical Center, Rochester, New York. It is not stated whether the children were alive or not when tissues were removed. We have taken some passages from the report which is in the August 217, 1971 issue of Science, Vol, 173, pp. 829-832. The writers are Lowell W. Lapham and William R. Markesbery. Using specimens removed surgically for the purpose of terminating pregnancy (1), we prepared explants from ten human fetuses, varying in gestational age from 10 to 19 weeks, Cerebellar cortex, with leptomeninges intact, was undercut and removed deep cerebellar nuclei and brainstem structures being avoided. p. 829 ’ The primary explants surviving longest to date (4 1/2 months and 5 months) were obtained from fetuses approximately 18 weeks old. p. 831 Data from studies on experimental animals concerning histogenesis of cells in the cerebellar cortex, their morphology, synaptic connections, circuitry and biochemical-pharmacologic Copyright © 1972, John E. Harrington, MSW, ACSW, Editor & Publisher, Marriage and Family Newsletter, P. O. Box 6066, Collegeville, Minnesota 56321 i — PRINTED IN US.A. 619 Marriage and Family Newsletter - p. 2 - Vol. 3 - No. 2 - February, 1972 characteristics add another dimension to the potential usefulness of cultures from human fetuses in the investigation of the control mechanisms essential for the expression of developmental phenomena in man. p. 832 This study was done subsequent to changes in state law effective July 1970 and has been approved by the Clinical Investigation Committee of the University of Rochester, as required by the National Institutes of Health. p. 832, Footnote #1, Although experiments should not be performed on children unless the procedure has __some immediate benefit for the child, some researchers, as stated below, experimentally administered ammonium chloride in large amounts to children. Five (cases 1-5) of the seven babies had pyloric stenosis and alkalosis and were aged 2-11 weeks. The two other infants (cases 6 and 7), who both had hydrocephalus and were aged 4 months, were in a good state of nutrition and hydration and showed no abnormality in acid-base balance, (1953) In another experiment in which phenylalanine was given to a mentally retarded child aged two years, the researchers noted that they had given phenylalanine to a normal infant. We have also given phenylalanine ( 14 g. in four days) to a normal infant, aged 5 months, without producing any change in behavior or any comparable rise in the plasma-phenylalanine level, which did not exceed 6.1 mg. per 100 ml. 20 (1953) In a subsequent issue of Lancet, R. E. W. Fisher in a letter to the editor voiced his regret that the two experiments reported above made use of normal children for controls. It is a matter for regret that the use of normal children (or children suffering from some irrele- vant disease) as controls in clinical research appears to be increasing. No medical procedure involving the slightest risk or accompanied by the slightest physical or mental pain may be inflicted on a child for exper- imental purposes unless there is a reasonable chance, or at least a hope, that the child may benefit thereby. If this is true - and I hope that there are few doctors in this country who would disagree - then it must surely be difficult to justify the use of two hydrocephalic infants reported in the paper by Dr. Doxiadis and his colleagues, and the use of a normal control by Dr. Bickel and his colleagues. 620 Marriage and Family Newsletter - p. 3 = VoL 3 - No. 2 - February, 1972 In another issue of Lancet, Duncan Leys, alluded to other experiments done with children which appeared in the medical press. I could quote many examples, published without comment or attempted justification in the medical press of English-speaking countries, of the failure to observe this rule (no child may be experimented upon). Here are three, all quite recent: (1) Potentially harmful doses of agene given to children in an orphanage, in order to see whether such doses were toxic. (2) The use of patients with incurable cerebral tumours as experimental subjects for finding out whether intrathecal aureomycin was injurious: the experiments involved multiple lumbar punctures. (3) Attempts to reproduce dangerous syncopal attacks in a child in order to obtain graphic records. It is clear that the assumption by doctors of scientific methods and techniques calls for critical examination of the uses to which these methods are put. The scientific material of the clinical research- worker is human life. Some discussion of the issues involved took place in a symposium at the Chicago Medical School in 1952 (ed.-see Science, 1953, Vol. 117, p. 205). 22 In a report by Rowe and James they describe how heart catheterizations were carried out on 15 mongoloid children aged 2 days to 9 months with 8 of the children aged 31 days or less. The aim of these experiments was to study the changes in pulmonary artery pressures during the first few months of life. As part of a study of the cardiovascular system in mongolism, a number of measurements were obtained in newborn and older infants with this disorder who were free of intracardiac defects, as shown by cardiac catheterization performed in each infant, Initially no sedative was admin- istered. Subsequently premedication with a Phenergan-chlorpromazine-Demerol mixture was used. A No. 5 Lehman catheter was introduced into the main pulmonary artery from the saphenous vein at the groin and a No. 20 needle inserted into the femoral artery at that site. 23 (1957) 621 Marriage and Family Newsletter - p. 4 - Vol. 3 - No. 2 - February, 1972 In one study the researchers performed cardiac catheterizations on 38 infants in the first 30 hours after birth. Nineteen of these children were considered to be normal. Hemodynamic measurements by means of cardiac catheterization were obtained in 38 infants in the first 30 hours after birth. Nineteen of these infants were considered to have normal circulatory and respiratory systems. Nine had mild respiratory distress, and 10 had severe respiratory distress. « (1961) The difference in these findings as compared to those of Adams and Lind and Rowe and James may be related to the fact that no premedication was employed in our studies. 25 (1961) Another study was performed on 29 healthy newborn infants, aged 2 to 26 hours, by a catheterization technique. Twenty nine healthy newborn infants, age 2 to 26 hours, were included in the study. Each infant was studied asleep with its head and chest placed under an "oxyhood' into which oxygen was delivered at a flow of 7 liters per minute. Infants who were restless or crying were not included in the study. 26 (1955) The pattern of dye dilution curves and the cardiac output was studied in 29 healthy newborn infants during the first 26 hours of life by the method of Wood and his associates. Thirty-six per cent of all infants studied had curves of normal contour which occurred mostly in infants older than 15 hours. Infants younger than 15 hours tended to have curves of abnormal shape. 27 (1955) In Australia an experiment involving catheterization technique was performed on 27 infants with a mean age of 10 hours. At no point is there any mention of parental consent, although this would not justify the experiment. The infants were age 2-28 hours (mean age 10 hr). They had just received a feed, and lay quietly with intervals of sleep. Restlessness was not a problem, except on occasion during the collection of expired air at the nose. However, the amount of motor 8 activity was somewhat different between babies. 2 (1966) A 5 French feeding tube with blunt tip and two side- holes was passed in one umbilical artery to the aorta, to record pressure and take a blood sample, and was withdrawn. The thermistor and catheter assembly just described was then passed to_the bifurcation of the aorta, judged from markers. 29 (1966) 622 Marriage and Family Newsletter - p. 5 - Vol. 3 - No. 2 - February, 1972 In one study experimenters attempted to study the blood pressure and vasomotor reflexes in 113 newborn infants by observing crying, exposure to cold, postural tilting and catheterization of the umbilical arteries. Catheterization of the umbilical arteries was attempted in 113 normal newborn infants and was successfully accomplished in 100. In each case the procedure was discussed in detail with one or both parents followed by a written consent. Of the infants studied, 74 were full-term and 26 were prematurely born, The age at the time of study ranged from 1 to 77 hours and the birth weight from 1.2 to 4.5 kg. All infants were considered to be in good condition at birth and at the time of study. None had re- ceived any prior medication, The procedure was carried out with rigid surgical asepsis. One of the umbilical arteries was isolated and a No. 5F nasogastric feeding tube was inserted and advanced into the aorta. This caused little discomfort and, with few exceptions, the infants appeared to he completely content. 30 (1963) Cold pressor tests were made in 46 infants (29 full-term and 17 premature). This procedure was conducted as follows: 1 foot was immersed to the ankle in ice water at 4°C to 5°C for a period of 1 minute. The aortic pressure was recorded continuously during the immersion and at 30-second intervals thereafter for 2 to 5 minutes. Since the infant invariably cried when exposed to cold, 1 to 3 pretest immersions at 1-minute intervals were made until all signs of discomfort disappeared. This eliminated the complicating effects of crying and straining. 31 (1963) In 1958, Saskatoon, Saskatchewan a 1 month old baby was treated with methylene blue for well water methemoglobinemia. This child recovered and then a child who was severely microcephalic but otherwise normal was injected with methylene blue experimentally, Case histories of 2 infants who received large doses of intravenous methylene blue have been reported. One infant received the large amount during treatment for well water methemoglobinemia. The other infant was given a similar dose experi- mentally. The skin of both infants turned a grayish blue and remained so for about 4 days following admin- istration of methylene blue. This phenomenon has not been previously described. Both children de- veloped an acute hemolytic anemia about a week later. 32 (1961) Unless the medical profession and society return to a position where human life is held in respect then experiments alluded to above will become commonplace at all levels of the development of human life. Much concern is expressed now for the problems of ecology and the quality of human life. We must not have our priorities out of order. Human beings are the most important resource that we have and we must not sacrifice human lives in attempting to clean up rivers and streams. To do otherwise would take our society back to the 30°s and 40’s where in Nazi Germany children were put to death while goraniums sitting by the window were well cared for! 623 Marriage and Family Newsletter - p. 6 - Vol. 3 - No. 2 - February, 1972 FOOTNOTES 1m, H Pappworth, M.D., Human Guinea Pigs: Experimentation on Man. Boston: Beacon, 1967, p. 31. 2 Gordon Rattray Taylor, The Biological Time Bomb, New York: Signet, 1968, p. 72. 3 Albert Rosenfeld, The Second Genesis: The Coming Control of Life. Englewood Cliffs, N.J.: Prentice-Hall, y Pe N 4 bid, p. 104. 5 paul H., Mussen, Ed., Carmichael’s Manual of Child Psychology (3rd. ed.). New York: Wiley, 1970, p. 507. 6 bid, p. 507. 7 Ibid, p. 507. 8 Ibid, p. 508. Ibid, p. 509. 10 id, p. 509. 11 mid, p. 510. 12 iq, p. 510. 13 1bid, pp. 510-511. 14 mid, p. 513. 5 Taylor, op. cit., pp. 41-42. 6 Mussen, op. cit., p. 512. 17 bid, p. 513. 18g, 5s, Stevens, Handbook of Dnepand Drala New York: Wiley, 1958, pp. 285-286. 19g, A, Doxiadis, M.D., Margaret K. Inch, KR. 9. Holt,'Alkalosis in Infants.’ Lancet, v. 2, 1953, p. 801. 20 Horst Bickel, M.D., Ph.D., John Gerrard, D. M., Evelyn M. Hickmans, Ph.D.," Influence of phenylalanine intake on phenylketonuria.' Lancet, v. 2, 1953, p. 813. 21 R, E. W. Fisher, Letter to the Editor. Lancet, v. 2, 1953, p. 993. 22 puncan Leys, Letter to the Editor, Lancet, v. 2, 1953, p. 1044. 23 Richard D. Rowe, M.B., L. S. James, M.B.,' The normal pulmonary arterial pressure during the first year of life)’ The Journal of Pediatrics, v. 51, no. 1, p. 2.,1957 24 A, M. Rudolph, M.D., J. E. Drorbaugh, M.D., P. A. M. Auld, M.D., A. J. Rudolph, M.D., A.S. Nadas, M.D., C. A, Smith, M.D., and J. P. Hubbell, M.D.,"Studies on the circulation in the neonatal period: the circulation in the Respiratory Distress Syndrome.’ Pediatrics, v. 27, 1961, p. 565. 25 bid, p. 562. 26 Klara J. Prec, M.D. and Donald E. Cassels, M.D.,'Dye dilution curves and cardiac output in newborn infants.' Circulation, v. 11, 1955, p. 789. 27 bid, p. 789. 28 E, D. Burnard, A. Grauaug and R. E, Gray,'Cardiac ouput in the newborn infant.’ Clinical Science, v. 31, 1966, p, 126. 29 hid, p. 122. 30 Arthur J. Moss, M.D., Edward R. Duffie, Jr., M.D., and George Emmanouilides, M.D., "Blood pressure and vasomotor reflexes in the newborn infant.’ Pediatrics, v.32, 1963, pp. 175-176. —— 31 1hid, p. 176. 32 Nathan Goluboff, M.D., and Ross Wheaton, M.D.,' Methylene blue induced cyanosis and acute hemolytic anemia complicating the treatment of methemoglobinemia!' Journal of Pediatrics, v. 58, no. 1, 1961, p. 89. 624 Marriage and Family Newsletter - p. 7 - Vol, 3 - No, 2 - February, 1972 —————— ee BIBLIOGRAPHY F. H. Adams, and J. Lind," Physiologic studies on the cardiovascular status of normal newborn infants (with special reference to the ductus arteriosus). Pediatrics, v.19, 1957,431, K. Adamsons, Jr., G, M. Gandy, & L. S. James, "The influence of thermal factors upon oxygen consumption of the newborn infant. Journal of Pediatrics, v. 66, 1965, 495-508. Rene A. Arcilla, M.D., Magnus H. Agustsson, M.D., Zwi Steiger, M.D., and Benjamin M. Gasul, M.D.,"An Angiocardiographic Sign of Aortic Regurgitation.’ Circulation, v. 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Proceedings of the Royal Society of Medicine, v. 44, 1951,189. John H. McGovern, Victor F. Marshall, and Albert J. Paquin, Jr., "Vesicoureteral regurgitation in children." Journal of Urology, v. 83, no. 2, 1960, 122. K. J. Prec, and D. E. Cassels, Dye dilution curves and cardiac output in newborn infants." Circulation, v. 11, 1955, 789, K. J. Prec, and D. E. Cassels,'Oximeter studies in newborn infants during." Pediatrics, v. 9, 1952, 756. R. N. Ray, J. B. Chatterjea, and R. N. Chaudhuri,"Observations on the resistance in Hb E Thalassaemia disease to induced infection with Plasmodium vivax." Bulletin of the World Health Organization, v. 30, 1964, 51. R. D. Rowe, and L. S. James, The pattern of response of pulmonary and systemic arterial pressures in newborn and old infants to short periods of hypoxia.' Paper read at the 26th Annual Meeting of the Society for Pediatric Research, Buck Hill Falls, Pa., May, 1956. A. M. Rudolph, and G. G. Cayler, Cardiac catheterization in infants and children." Pediat, Clin. N. Amer., v. 5, 1958, 907. A. M. Rudolph, et al.,'Studies on the circulation in the neonatal period." Pediatrics, v. 27, 1961, F. R. Sanchez,'A new approach to catheterization of the umbilical vein for exchange trans- fusions.'Pediatrics, v. 25, 1960, 485. Samuel O. Sapin, M.D., Leonard M. Linde, M.D., and George C. Emmanouilides, M.D., "Umbilical vessel angiocardiography in the newborn infant."Pediatrics,v. 31, 1963, 946. Joseph Schwartzman, M.D., and Leo Grossman, M.D.,'Vincent’s ulceromembranous gingivostomatitis." Archives of Pediatrics, v. 58, 1941, 515. George P. Smith, II]'Through a test tube darkly: artificial insemination and the law!' Michigan Law Review, v, 67, 1968, 127. G. I Solish, M.D., J. G. Masterson, M.D., L. M. Hellman, M.D.,' Pelvic arteriography in obstetrics." American Journal of Obstetrics and Syneealost. v. 81, no. 1, 1961, 57. Byron H. Waksman, M.D., ymus experimentation.” Correspondence- New England Journal of Medicine, v. 270, no, 19, 1964, 18. R. A. Woodbury, M. Robinow, and W. F. Hamilton)'Blood pressure studies on infants." American Journal of Physiology, v. 133, 1938, 472. Robert M. Zollinger, Jr., M.D., Martin C. Lindem, Jr., M.D., Robert M. Filler, M.D., Joseph M. Corson, M.D., and Richard E. Wilson, M.D.,' Effect of thymectomy on skin- homograft survival in children." New England Journal of Medicine, v. 270, 1964,707. Subscriptions: 12 issues per year. Rates: 1 yr.- $5.00, 2 yrs.- $9.00, 3 yrs.- $12.00. Bulk ERE us to the same address: 1st subscription- $5.00, each additional subscription to the same address- $3.00. Back copies: 50¢ each for single copies of each issue, including postage. 2-5 copies of each issue: 260 each plus postage. 6-10 copies of each issue: 30¢ each plus postage. 11-25 copies of each issue: 20¢ each plus postage. 26 or more copies of each issue: 10¢ each plus postage. Marriage and Family Newsletter may not be reproduced in any form or by any means without the written permission of the publisher. Marriage and Family Newsletter is copyrighted under Class B, Form B with the Register of Copyrights, Library of Congress, Washington, D.C. 20540. The editor and publisher is John E. Harrington, MSW, ACSW, P. O. Box 6066, Collegeville, Minnesota 56321. 93-999 (Pt. I) O- 73 - 19 626 HENRY K. BEECHER, M. D. HARVARD MEDICAL SCHOOL 10 SHATTUCK STREET BOSTON, MASSACHUSETTS 02115 March 9, 1973 Senator Walter F. Mondale United States Senate Committee on Labor and Public Welfare washington, D. C. 20510 Dear Senator Mondale: I had the feeling (visceral sensation) that I had not adequately made clear how important it was to point out what I (and others) believed to have been the effect of my June, 1966 paper, published in the New England Journal of Medicine on "Ethics and Clinical Research". As you can see from the following table, 6.6% of applications to the National Institutes of Health were unethical or had unethical aspects. By March, 1967, the incidence was one-third of what it had been. This varied from a third to a half at sub- sequent times. (These data were provided by the Division of Research Grants, National Institutes of Health, through the courtesy of Eugene A. Confrey, Ph.D.) Total Projects involving Problem projects,% applications human subjects, Percent of received, estimated those involving Month and Year ~ number number Numbex humans June 1966 4100 1230 81 6.6 March 1967 4001 1200 27 2.2 June 1967 3931 1180 38 3.2 November 1967 3677 1100 35 3.2 March 1968 3651 1095 37 3.4 June 1968 4078 1250 40 3.2 November 1968 3393 1118 26 2.3 This half to two-thirds decline in incidence is, I think, a notable ad- vance. These are the only objective data that I am aware of in this area. To me, these data support the view that merely calling attention to the possibil- 627 Senator Walter F. Mondale 2 March 9, 1973 ities for serious error here was enough to produce the effect mentioned. This is no small gain. We must hammer at the importance of overcoming carelessness or ignorance. It is essential, of course, to search for other methods of reducing the incidence of unethical activities, but it would be a great mistake, I believe, to underestimate the value of the above data. I enjoyed very much the Hearing arranged by Senator Kennedy and yourself. Respectfully, ( (Aarahin— HKB :mv Henry K. Beecher, M. D. P. S. I would be most grateful if your secretary would send me three copies of the Congressional Record where I suppose my material will be pub- lished. 628 Ethical Issues in Genctics Robert IM. Veatch, Ph. D. Associate for Medical Ethics Institute of Society, Ethics and the Life Sciences Hastings-on-Hudson, New York ot NH, snsociate nstitate P 6 Has 11. Iv, 629 Value Orientations In Genetics .esesissssnsrvnssse vwsspswsssew 2 A. ‘'fhe Place of Values in Gens 2 B. Some Fundamental Value Orientations eeceseeees 5 6 8 i. Man's Relationship to Motive cevevrvvevaee 2. Individual versus Social Good ..... 3. Normative Ethical Theory: Maximization of the Cood versus Inherent Moral Obligation .s.eseeesosevesnseeas Ll a. Non-utilitarian considerations .e.eeesescsecesasns 12 (1) Not Haring .essvsvssssssnsorncossssnesnnnsvns 32 (2) Social Duties to Cnes with Whom One is in Spzcial Relation. usa ssmaswmereie sewegweve some 53 (3) Justice in Distributing Go00dS sseevesecsvsvess 13 b. Problems in Calculating the GOOG cevacvssrorverees 14 4, Organic, Psychological, and Social Considerations..... 16 5. Present versus Future Orientation ....eeecevesaccevess 18 The Ethics of Genetic Counseling ...ueeetecenscrcsunsresravenes 22 A. Values and the Genetic Counselor ...... B. Telling Patients of. Diagnosis ...seessesvessvisvsnsvsssses 25 C. Confidentiality of Genetic Information ....eeeeceseceecss. 28 Fase n Buss mn Laren OF Ethics of Auniocentesis ..cessvsreervessvesnrvnsessnosesss snes Jk A, The Relation to ADOTEion .scicesessesescscssscanes « 31 B. Medical Diagnosis without Consent .eeeesceseevecescccacees 33 1. Amniocenteses as Experimentation without Consent ..... 34 2. Medical Diagnosis without Consent ....eeeeeeceessscsee 35 3. Difficulties with the Anti-Amniocentesis Position .... 37 C. Amniocentesis for Sex Determination e.eececcecececcsseesss 38 Ethics of Mass Genetic Screening ..veevesceccevesecrerceneenses 41 Screening's Impact on the Concept of Normalcy eeeeececsess Active Change in the Genetic Code sessssserssssssvesscevsvveee 30 A. The Hyperargininemia Case eceseeceecrsesersesecccsnsrees 51 B. Risks to Affected Individuals and to Offspring ....eece... 54 C. Correcting and Improving GENES ..eciescssccsaccesscescenees 55 630 ETHICAL ISSUES IN HUMAN GENETICS by Robert M. Veatch Probably no development in the scientific age has challenged our understanding of the nature of man more than the rapid emergence of the field of clinical genetics. While intellectuals have speculated over what would constitute optimum man and what characteristics of man might be essential to his nature, now more than ever before we must begin to face these questions in a much more practical and immediate way with the real possibility of implementing our conclusions. It is not often that man can talk about progress in ethics, yet the rapid evolution of the field of genetics has brought forth a genre of new literature probing the philosophical, social, and ethical implications of advances in genetics, and it is not too much to say that we now have substantially greater sophistication in analysis of the ethical aspects of the field than we did only a few years ago. This chapter will review discussion of the underlying value orientations which are necessarily incorporated inte decision-making in the realm of genetics. Then we shall examine how these value orientations are brought to bear on the ethical decisions which have to be made in the various phases of genetics. First, we shall examine developments of the literature on the ethics of clinical genetic counseling. Next, the ethical dimensions of amniocentesis and prenatal diagnosis as a technique in genetic counseling -e will be examined followed by the ethical issues of mass genetic screening programs. The final section will be devoted to the special ethical issues raised by the possibility of actual genetic intervention designed to produce actual changes in the genetic code. 631 -2- I. VALUE ORIENTATIONS IN GENETICS A. The Place of Values in Genetics. The positivist tradition which has dominated science in the modern period since the days of Descartes, Newton, and Locke has — that ethical and other value considerations must be kept independent of science and the scientific perspective. This effort to separate science and values has been particularly constructive in counteracting tendencies to bias scientific findings in the direction of the researcher's values and more specifically calling into question the tendency of those with scientific expertise to transmit values to the layman along with their scientific findings. Thus, one view of the role of the genetic counselor. is that he is obligated to ‘transmit the genetic facts of the patient's case without offering moral advice or recommendations about what the individual patient should do given those facts. More recently, however, the fundamental claim that values and science must be kept separate has been called into question (Dahrendorf, 1968; Gouldner, 1963). Thus, there is now a major debate evolving over the extent to which the scientific enterprise can function independent of values and value orientations. It is increasingly recognized that in the field of genetics as in other scientific disciplines, values impinge at many stages in ti work of the geneticist. It is first of all readily goneded LHaL some value framework is required for the geneticist to choose his area of research on sickle cell disease rather than sex determination or viral transmission of bacterial genetic material to another organism. This reflects a value choice on the part of the researcher as well as that of funders, research institutions and the general public. 632 It is also increasingly recognized that decisions made in the geneotic counseling coutext at tha clinical level also require a value framawvork. It is impossible to choose among the clinical alternatives, once one is given a genetic diagnosis and description of the condition, without drawing upon a set of values upon which to base that decision. The theoretical reason for this is that a decision requires the interaction of at least two major components which we might call the (non-evaluative) factual and evaluative premises. It is, of course, necessary to become informed about all of the relevant facts of a case. These include not only the genetic condition and its implications, but also the economic, social, political, and familial facts which will relevantly bear upon a decision. But, after one has in front of him all of these facts (the choice of which, in itself, requires values), it is still necessary to evaluate them according to some frame of value reference. There will be cases when that frame of value reference seems obvious and a matter of nothing more than common sense. When a baby is diagnosed at or near birth as having phenylketonuria, the advice is given that a special diet excluding phenylalanine is required. What is implicit in this advice is that the mental effects of phenylalanine in such a case are obviously disvalued and disvalued to the extent that they outride any disvalue in the bland diet required to exclude the harmful amino acid. Thus, rephrased as a hypothetical imperative, the full statement of advice should be "If you value pregention of mental retardation more than you value a pleasing diet, you should opt to exclude phenylalanine from your child's food intake." If, however, one rejects the hypothetical imperative, then vhat appears for most to be an obvious conclusion clearly does not follow. When one sees decision-making in this light, it is apparent at least at the clinical level that a set of ethical and other values is required for every decision made. 633 This review will not deal extensively with the ethics of research genetics, however, it should be apparent that thc same argument applies. It does make sense to distinguish between clinical decision-making in the genetic context and research, where the objective is primarily the increase of knowledge. Yet, even at the stage of pure research investigation, decisions must be made and they must be made with a frame of value reference. This is most apparent when research involves, as it often does in the field of medicine, experimentation on human subjects. There is a vast literature in this field which is outside the scope of this review (Katz, Capron and Glass, 1972; Beecher, 1970; Ladimer and Newman, 1963; Pappworth, 1967, Freund, 1970). Remmington (1971) has argued for the "very great scientific value of well-performed {human/animal} hybridization experiments," This has led him to claim that high priority "should be given to a thorough study of interspecific genetics of Homo with one or more of the three types of pongids (chimpanzee, gorilla, orang) most similar w Homo," That major value choices are at stake in the decision to proceed with such research is obvious but it also must be recognized that value frameworks are a necessary component of other decisions made in the realm of research in genetics. A theoretical framework must be selected, a research methodology must be chosen, relevant” observetions must be made from the infinitely enlarged date field, choices must be made in the recording and analysis of data, statistical levels of "significance" must be selected, and finally the choice must be made about that which is "significant" for publication. Even beyond these choices within the research stage, it must be recognized that research generating new scientific and technological developments generates feedback loops so that we can predict that major scientific advances will have an impact on the value system of a society. Thus, a fundamental sct of value orientations has direct bearing not only upon decisions made in clinical genetics but in the purely research phase as well. B. Some Fundamental Value Orientations. Kluckhohn and Strodtbeck (1961) have formulated a number of fundamental value orientations which they consider to be deeply underlying patterns in various cultures. These patterns are such broad orientations that they will frequently go unperceived as relevant factors in the culture. Never- theless, they have central significance for the life style choices made. Particularly when two cultures or sub-cultural groups which differ on these fundamental value orientations interact,we can anticipate that there will be conflict or tension. Because they are such _— value dimensions, often these conflicts never rise to the surface, leaving a diffuse dissatis- faction and discomfort among the actors. Such conflicts are not uncommon among those discussing genetic policy, whether they be patient or counselor or professionals attempting to agree on the direction of genetic evolution. We shall examine five of these fundamental questions. In part, we shall draw upon the categories of Kluckhohn and Strodtbeck, but, in addition, shall fncorporate some of the major conflicts in normative, philosophical, ethical theory as these have beea reflected in the recent literature on the social and ethical dimensions of genetics. 635 1. Man's Relationship to Nature. Perhaps the most significant value orientation to have an impact on the field of genetics is the orientation of man's relationship to nature. White (1967) has argued that the Western scientific and technological era has been introduced by the Judeo-Christian philosophical premise that man's role in the world is to dominate and subdue nature with his intellectual and technical skills. Muller (1965) has made the case for what might be called the ''genetic imperative" when he argues that "the means exist right now for achieving a much greater, speedier, and more significant genetic improvement of the population, by the use of selection....The obstacles to carrying out such an improvement by selection are psychological ones, based on antiquated traditions from which we can emancipate ourselves." Sinsheimer (1969),. advocating what he calls "designed genetic change" argues that "for the first time in all time a living creature understands his origins and can undertake to design his future....even in the ancient myths, man was constrained by his essence, He could not rise above his nature to chart his destiny. Today, we can....It is a new horizon in the history of man. Some may smile and feel that this is but a new version of the.old dream of the perfection of man. It is that, but it is something more. The old dreams of the cultural perfection of man were always sharply constrained by his inherited imperfections and limitations. Man is all too clearly an imperfect and flawad creature. Considering his evolution, it is hardly likely that he could be otherwise. To foster his better traits and to curb his worst by cultural means alone has always been, while clearly not impossible, in many instances most difficult. It has been an Archimedian attempt to move the world, but with the short arm of the lever. We now glimpse’ 636 another route--the chance to ease the internal strains and heal the internal flaws directly, to carry on and consciously perfect far boyond our present vision this remarkable product of two billioa years of cvolution." Variation on this theme that it is man's role to use his technological and intellectual skills to overcome and subdue the natural genetic endowment of man--vhat we have called the genetic imperative--has been the under- lying philosophical premise of a literature arguing for the intervention into man's genetic development (sce Glass, 1972; Lederberg, 1966; Joseph Fletcher, 1971; cf Lappé, 1972). The September 1972 issue of Theological Studies provides the latest installment in the increasingly complex debate about man's role in nature. In this significant collection of essays, Francoeur (1972, p. 429) is the most blunt spokesman for the "technological imperative." He argues that "man is by nature a creator, like his Creator. Or at least a co-creator in'a very real awesome manner, not mere collaborator, nor administrator, nor caretaker, by divine command we are creators." There is an imperative to use our technological resources to overcome the imperfections in nature. This view of technological man, however, has generated a response. Crotty (1972, pp. 443-444) rejects the glorification of the technical and artificial. Rejecting the image of man as technological controller, he argues that "where noniatervention is foreseen to be more promotive of human good then intervention, where allowi®s nature to take its course is judged to be more in the interest of human persons and humaa fellowship than technical control, where unpredictability seems more favorable to human welfare than predictability, it is surely the former and not the latter that is truly human iu this situation...." 637 Paul Ramsey (1970 and 1972¢), contemporary critic of this philosophical view of man as technological intervener and controller of sabure, argues that the word “reproduction,” itself. reflects ite nage of man in which his role is the "manufacture'" of life. . This 50 SOREERTER to "procreation," the natural generation of childuen. which is part of the wisdom of fe natural created order of which man is a part. He claims that the "proper objective of medicine is to serve and care for nis 2a natural — to help in all our natural 'courses of action’ to tend the garden of el creation” (1972¢, p. 1485). This view of man gs a minute part of an ongoing natural order is much more in tune with the S wos tepoteny questioning of va man as technological conquerer which is seen in : ghe A movement and . other critiques of the technological pHa: These two views of man as’ controller; of nature ad véspecter of nature will have radical. Agee for decisions made in radii: ; 2. Individual Versus Social Good. A second major value orientation which is Aenessavily ‘brought to bear on genetic decislon-naking is that of the classical conflict among competing sources for identification and loyalty. It is sigaificant in the field of genetics that different professional groups visieh are dtfantly and intimately involved = the field have tradi- tionally had primary loyalty orientation to very different sectors. Many. population GERELLAAEYS have, by the very nature of their role, had an orientation to the patie, of the gene pool of the population. In contrast, the gehen Who becomes tnvolved in genetics has, from the day of the’ Hippocratic ons, had an alii and strong primary moral So fgation to the individual patient or family ho is sevvicing. Lappe (1972), the staff director of the Rescarchi Croup on tha Social pacts of CGonties of the Institute of Society, Ethics aad the Lifa Sciances, bas recently ocut- liacd varying allegiances or "goal identification biases" whieh he argues are values incorporated iato the value systems of gencticists La arcas of training and specialization prior to the time thay moved into the field of genetics. He suggests six such allagiances: 1. To the primacy of cultural tvaditions. 2. To human diversity. 3. To the gene pool. 4. To the primacy of the individual. 5. To the maximization of human genetic potential. 6. To reducing —— evils. It LI i” seen that some of these value eommitmpnts or allegiaaces, such as that to the quality of the gene pool, av globally oriented, while at the other extreme some geneticists maintain a primary value cor to the individual. John Fietcher (1972a) explores in detail the "parent- child bond" as a critical moral factor in genetic Snoluton-nalitng. Callahan (1973) points to the ambiguities of the moral norm of "freedom of parental choice in the use of genetic information." We should recognize that the modern Westera philosophical tradition, sincz the enlightoumeont, has had a particular value commitmant®to voluntarism and individual freadom. is value commitment to individual choice and control of genetic decision- making still dominates che current discusaion, but we sheuld anticipate thac sume population geaeticists aad others who emphasize more societal orieatatioas wight argue for of individual interests for the good of society (Paviz, 1955; Muller, 19393; Vukovicl, 1971; Glasas, 1972; Gorney, 1958; Ingle, 1967; Osiaundson, 1973; 639 -ay- Laws mandating compulsory eugenic sterilization are not the only instances of societal concern in the areca of genetics. Current interest - in genectics has not produced a resurgence of interest in compulsory eugenic sterilization. In fact, the laws which exist have been on the books for some decaiion, The ethical and legal aspects of compulsory eugenic sterilization are well reviewad elsewhere in the literature (Meyers, 1970; O'Hara and Sanks, 1956; Paul, 1968). Callahan expresses concern that under the rubric of freedom of parental choice, pressures will be generated through informal social mechanisms to require parents to make 'responsible" choices. Considering the choice of parents not to abort a fetus prenatally diagnosed as having Down's syndrome, Callahan says "that it is not difficult to discern an undercurrent in counseling literature and discussion that would classify such a decision as irresponsible." It is not only conflict between the interests of the individual and the broader society which raise ethical dilemmas, but also conflicts of interest between child and parents, child and siblings, and between immediate family and relatives. What, for instance, is the moral obligation of a counselor who has identified a recessive gene for a serious genetic disease if a member of a family refuses to transmit that information to relatives? It is not only the professional genetic counselor who faces the ethical dilemma of competing moral obligations and loyalties in making responsible decisions in the genetic context. Twiss (1972) traces the same competing . loyalty conflict in the role of parent as genetic decision-maker. He identifies five parental roles which give rise to conceptions of genetic responsibility, emphasizing that the obligations generated by these five roles wll may not always be consistent. These foci of loyalty ave: parent simpliciter parent/ family member parent/citizen parent/ethnic population member parant/species member. While the ethical dilemma of conflicting moral obligations being generated by competing foci of loyalty is a classical one, it arises afresh in the ethics of genetic decision-making and is particularly confounded by the radically different foci of moral obligation which have traditionally been assigned to different role players who are normally involved in genetic decision-making. 3. Normative Ethical Theory: Maximization of the Good Versus Inherent Moral Obligation. A third fundamental conflict that arises in the value commitment of moral decision-making can be traced to the classical debate in philosophical normative ethical theory between what has been called utilitarianism and formalism. Briefly stated, utilitarianism in its classical form, as seen in Bentham and Mill, holds that the ethically appropriate action is that one which will produce the greatest good for the greatest number. In contrast, the formalist position, held by Kant, holds that there are certain ethical requirements independent of the consequences. Such inherent moral obligations as tim telling of the truth, keeping promises, caring for one's own offspring and not harming those with whom one is in immediate contact may be considered morally required independent of the consequences of actions (although they also may be defined for consequentialist reasons). Within the current debate about the ethics of genetic decision-making, this conflict has emerged afresh. Joseph Fletcher (1971) articulates the classical utilitarian position arguing that that which promotes the greatest good is morally required and that must be determined independently according to each specific situation. The same type of moral argument appears upon occasion in the clinical literature. Under the title "The Cost of Life" (1970), a utilitarian argument is offered for amniocentesis for mongolism based on the high societal cost for maintaining a mongoloid child. The use of the cost benefit analysis and modern cost accounting techniques to derive a genetic decision has been seriously questioned (Callahan, 1973). It is particularly suspect from the moral perspective when the economic is the only factor considered. Even the classical utilitarian would extend the relevant kinds of good and evil far beyond the economic. In contrast, some cost-benefit decision-making apparatuses include only societal financial liability and do not include such nebulous moral considerations as personal mental anguish, the erosion of societally legitimated values such as individual freedom and moral worth, or even the qualitative impact on the gene pool. a. Non-Utilitarian Considerations. The narrowness of the utilitarian calculus is not the only moral argument against it. Several non-utilitarian (or formalist) arguments are currently appearing in tire literature (see Gustafson, 1973). These include: . (1) Not Harming. One line of tradition within medical ethics has held that the physician has a special moral duty to "above all do no harm." This is in contrast with the possible production of good. The prime moral obligation to alleviate suffering or harm in contrast to the use of genetics to produce good has recently been debated by Lappe et al. (1971). These 93-999 (Pt. II) O - 73 - 20 642 #13 authors reflect the substantial conflict in the ethical tradition over whether an individual, in this case the genetic counselor, has a more stringent obligation to prevent harm, what Kant called a duty of per- fection, over and above the less rigorous obligation to produce general good for individuals. Lappé, defending the special obligation to relieve suffering, traces this position to an Eastern view of man while some of his commentators question this special obligation either rejecting the notion that there is such a special duty or questioning that it can be identified specifically with an Eastern philosophical tradition. (2) Special Duties to Ones With Whom One is in a Special Relation. Even if one in utilitarian fashion bases his moral judgment to the production of good, he may hold that he has special obligations to produce good for certain individuals either because he stands in a special relation- ship to them or because there are special moral obligations to distribute goods in a particular way. Of those who are actively involved in making genetic decisions, several role actors have traditionally held that they have special moral obligations to individuals with whom they are interacting. The physician-counselor has traditionally held that his moral obligation is specifically focused on the individual patient. The patient is assumed to have a special moral obligation for the care and nurture of his childrea. (3) Justice in Distributing Goods. Even if one is not in such a special relationship, there is a major ethical tradition that holds that the distribution of goods is morally significant as well as the total aggregate. They would claim that the question of the total aggregate of costs to society of caring for a mongoloid child is not an overriding consideration in contrast to the obligation to provide for the good of the 643 individual child even if such subtle calculation of goods could be made, which, of course, if: cannot. A major mew ethical work destined to become a classic in ethical theory by Rawls (1971) articulates this claim forcefully. We can expect that it will have an impact on genetic ethics. Any of these formalist claims may be defended even though they will not produce the greatest good in aggregate. b. ne. of the Good. In addition to the debate between those who want to maximize the good and those who introduce other ethical con- siderations, there is rapidly increasing debate about man's ability to identify and to quantify the different kinds of good which are related to man's genetic endowment. In the literature of a somewhat earlier period, there were optimistic if somewhat vague statements about the potential to cleanse the gene pool of "deleterious genes" improving its quality as well as that of individual lives without devoting attention to the problem of identifying what con- stitutes a good or bad gene, a good or bad chromosomal configuration, or a good or bad life style. Such non-reflective statements have often reflected the biases of the commentators in assuming that particular characteristics are to be valued by consensus. Such characteristics are cognitive intelligence traditionally defined, physical appearance of a dominant group, or simply the value commitment against physical suffering. Galton, for instance, (cited in Lappe, 1972, p. 416) stated that the purpose of eugenics was "to give the more suitable races or straios of blood a batter chance of prevailing speedily over the less suitable than they otherwise would have had." In one recently reported study, the valuation of whether or pot a genetic decision was "responsible was based upon the relation of that decision to w]e the recurreace risk (Carter et al., 1971). The authors compared the decision made when the recurrence risk was greater than ove in ten to those decisions made when the risk was less than oaa in ten. Their conclusion was that on the whole, people made responsible decisions oa the basis of their information. The implication of this claim is that a decision can be judged resporsible on the basis of statistical differentiation in recurrence risk. Even though the authors claim to be dealing only with "serious disorders," it would appear that they would receive substantial argument in terming the decision to have children when there is relatively high risk, but the significance of the condition is debated (such as possibly hare lip and cleft palate), an irresponsible decision. Moral evaluation of the responsibility of the decision will depend upon factors far more complex and subtle than simply recurrence risk. In a study which raises similar problems in defining the relative good and evil consequences of an action, Fort et al. (1971) claim for a carefully defined group of pregnant patients with HbSS and HbSC hemoglobinopathies, they found that maternal mortality rate was 10 to 14 percent and perinatal mortality rate was 51 to 55 percent. They then make the moral judgment that "pregnancy outcome does not justify the maternal risk!" While this is a policy judgment that many would share, it is clearly a judgment extending beyond the realm of medical expertise and one requiring a particular evaluation of goods and evils. Certainly the authors' recosmendation of "primary sterilization, abortion if cenception occurs, and sterilization for those who have completed pregnancies" would not be universally accepted as the way to maximize the total good either for the patient or society. Evea the valuation of the prima facie goodness or evil of sickle cell trait is now being called into question by the recognition of possible anti-malarial characteristics of the trait (Cavalli-Sforza and. Dodaner, pp. 148-154) and 645 -1D- more general arguments for the value of diversity in the gene pool. Evea outside of malarial areas the seriousness of the trait characteristic is debated heatedly. 4. Organic, Psychological, and Social Considerations. A fourth fundamental value orientation which has an impact on genetic decision-making is orientation to the primacy of organic, psychological or socio-cultural factors in human life. The field of genetics and genetic decision-making has frequently been interpreted in the medical model. Thus, in the study cited above what many would take to be high risk, i.e., high maternal and perinatal mortality rate, is considered an indication for primary sterilization and abortion. Placing the field of genetics within the medical model brings with it a number of policy implications. It frequently will mean that the organic dimension is considered the most significant for viking genetic - judgments. Discussions of indications for amniocentesis are often limited to organic factors and incidence rates (Nadler, 1971). Criticism in the liter- ature of the use of incidence rates has been discussed above. As with other anomalies interpreted in the medical model, no personal culpability for the anomaly is to be assigned to the parent. Thus, it is frequently suggested that one of the genetic counselor's primary functions is communication to the patient that he is not personally responsible for possession and transmission of the gene which he carries (John Fletcher, 1972b). Also incorporated in the medical model is the policy implication that medically trained individuals should be involvee in the genetic counseling process. Finally, the medical model also leads to the judgment that correction of a "defect" will bring an individual up to "normal" Has a far greater priority in legitimacy thaa the use of genetic knowledge for improving the biological processes. Thus, the usc of genetic prenatal diagnosis "for purposes of sex selection independent of an X-linked genetic disease is considered highly questionable. The use of genatic engineering to "improve" man's characteristics would certainly meet with even greater resistance than the use of such techniques to correct an enzymatic defect, such as hyperargininemia (Ramsey, 1972a and 1972b). The primacy of the organic medical factors in genetic decision-making is, however, being called into question by those who wish to place greater emphasis on other dimensions. Those with orientations to the psychological sphere have argued that abortion for genetic characteristics of the fetus should depend heavily upon the psychological impact that this would have upon the mother. Still others would emphasize social, cultural, political, and religious factors in decision-making. Certain representatives of black consciousness have argued that sickle cell screening and the potential development of prenatal diagnosis for sickle cell anemia are culturally or politically unacceptable. Their conclusion is relatively independent of the medical considerations, although they presumably base their arguments on the presumed medical fact that sickle cell trait, in and of itself, is not what they would consider to ba a particularly sericus medical condition. The interaction of organic and socio-cultural factors is heightened by the fact that many genetic fizeaws are specifically linked to particular ethnic groups. Tay-Sachs disease has its impact primarily on the Ashkenazi- Jewish population. Judgmant about the ethical acceptability of prenatal 647 18 diagnosis and possible abortions of fetuses with Tay-Sachs disease might be based TE on the organic horrors of the disease. On the other hand, it is quite plausible for an orthodox Jew to argue on religious- moral grounds that such an abortion is unacceptable, even though he is fully aware of the organic medical consequences. Whether or not one opts to place primary value upon organic factors of physical pain, suffering, and deformity or he chooses to value more significantly psychological, social, political, and cultural factors which may generate arguments with contrary policy implications, will hava a significant impact on judgments made. It is critical to recognize that there are fundamental differences of this type in a society and we can anticipate that professionals in the realm of genetics will bave commitments in one direction or another which will have substantial impact on judgments made. 5. Present Versus Future Orientation. There is a fifth and final funda- * mental value orientation which has an immediate impact on the decision-making in genetics and genetic counseling. Kluckhohn and Strodtbeck (1961) suggest that there are fundamental cultural differences reflected as orientation to the past, present, or future. They identify modern Western society as being peculiarly future-oriented, while other societies may look much more to historical past or the timelessness of the present. This fundamental value orientation has its impact in the field of genetics primarily in the discussion of our genetic obligation oe future generations. Such an obligation is frequently assumed by those writing in the field of genetics (Muller, 1985; Gorney, 1968). Orientation to the future may have two coatradictory 648 wlD= implications. First of all, those reflecting a more apocalyptic vision claim that the obligation to promote the survival of the species is paramount, even justifying coapromises with what arc seen as lesser moral obligations to human freedom and dignity. Beyond this, it is also assumed that there is a moral obligation to preserve the quality of life in future generations. Sir Julian Huxley has summarized this intuition well when he states: "If we don't do something about controlling our genetic inheritance, we are going to degenerate without selection, bad mutations inevitably tend to accumulate; in the long rum, perhaps 5,000 to 10,000 years from now, we shall certainly have to do something about it..,.most mutations are deleterious, but we now keep many of them going that would otherwise have died out. If this continues indefinitely.... then the whole genetic capacity of man will be much weakened." Golding (1968 and 1972) commenting upon Huxley's moral argument for protection of future generations shows in two significant essays that the notion of obligations to future generations is much more complex. Colding argues that for moral obligation to exist there must be a plausible case for the existence of a common moral community. He then argues that the community of the future is one with which we cannot expect to share a common life: "It appears to me that the more remote the members of this community are the more problematic our obligations to them become. That they are members of our moral community is highly doubtful, for we probably do not know what to desire for them," 649 «30 In response to Huxley's claim, Golding argues: "Given that we do not know the conditions of life of the very distant future generations, we do not know what we ought to desire for them even on such matters as genetic constitution. The chromosome is 'deleterious' or 'advantageous' only relative to given circumstances. And the same argument applies against those who would promote certain social traits by means of genetic engineering (assuming that such social traits are heritable). Even such a trait as intelligence does not escape immune. ...One might go so far as to say that if we have an obligation to future generations, it is an obligation not to plan for them. Not only do we not know their condition of life, we also do not know whether they will maintain the same (or a similar) conception of the good life for men that we do. The moral to be drawn from this rather extreme example is that the more distant the generation we focus upon, the less likely it is that we have an obligation to promote its good. We would be both ethically and practically well advised to set our sites on more immediate generations and, perhaps, solely upon our immediate posterity." “\ Callahan (1971) argues for a clearer moral obligation to future sunuraliogs: He claims that although Golding may b% correct in saying that we cannot determine) what future human beings will need and desire, "ye should act on the assumption that it will not be all that dissimilar from our own; we have no special reason to think otherwise." His claim is that we must assume that members of future generations are part of our moral community and will share our social ideal until we have good reason to think otherwise. He states 650 wg] (1971, p. 28) four ethical norms which he would apply as sumeavy rules con- ceraing our obligations to our future generations: 1. Do nothing which could jeopardize the very existence of future generations 2. Do nothing which could jeopardize the possibility of future generations exercising those fundamental rights necessary for a life of human dignity. 3: If it scems necessary, in the interests of the cxisting rights of the living, to behave in ways which could jeopardize the equivalent rights of those yet to be born, do so in that way which would as far as possible minimize the jeopardy. 4. When trying to determine whether present behavior will in fact jeopardize future life, calculate in as responsible and sensitive a manner as one would in trying to determine whether an act with I, would be harmful to one's own children. This completes our review of some of the fundamental value orientations viiich are currently under discussion in the literature on ethical aspects of genetics. The descriptive task of identification and analysis of the presence and functioning of these underlying value orientations in genetic decision- making is far from complete. There has been relatively little empirical documentation of the value orientations and differences in value orientation among genetics professionals and between those professionals and the laymen with whom they interact. It is clear that even the theoretical analysis of the normative and orientational frameworks for genetic decision-making is far from complete. The first stage, however, in the development of the study of the value dimensions of genetics seem to have advanced a great deal in the past few years. The ideatification of the issues discussed above and their application in the ficld of genetics must certainly continue for the years to come. The more difficult task of the development of sophistication in dealing with these value orvicatations among genctics professionals and laymen iho are 651 wT Dw placed in a position of making genetically-oriented decisions has hardly begun. This will perhaps be the greatest challenge to those working in the field in the future. It is apparent that these fundamental value orientations penetrate all phases of research in clinical genetics. It would be redundant to trace each of these themes in the various types of research and clinical activity. We shall, however, in the remainder of this review take up more specific ethical dilemmas which have arisen in the field of genetic counscling, prenatal diagnosis, genetic screening and finally, positive genetic engineering. II. ETHICS OF GENETIC COUNSELING Before taking up a series of specific ethical issues pertaining to genetic counseling, let us bracket three primary topics. First, the ethical issues specifically related to amniocentesis and prenatal diagnosis shall be taken up in the next section of this review. ‘Secondly, it is apparent that at this stage of the development of genetics, one of the primary techniques available is what is euphemistically called "prevention." The techniques for prevention are primarily sterilization and abortion, although they also include the avoidance of trait-trait marriages and the decision not to bear children within marriage. Abortion and sterilization for what is judged to be high risk pregnancy is now being routinely recommended in some places in the literature. The morality of abortion and sterilization, however, is such a vast topic: that it cannot be dealt with in this review. The literature on abortion (Callahan, 1978; Crisez, 1970; Hall, 1970) and sterilization (McFadden, 1968; Joseph Fletcher, 1954; Noonan, 1966; Wood, 1968). provides a vast and adequate discussion of these ethical issues which are fundamental to the practice of genetic counseling, We shall, however, limit outselves to consideration of a number of ethical issues which are central to the counseling process, itself: the place of values in the 652 #23 role of the counselor, the ethics of telling the patient of a diagnosis, and the problems of confidentiality of geactic information (see Harris, 1972 and Hilton, 1973 for proceedings of two major conferences investigating the cthical issues of genetic counseling). A. Values and the Ceretic Counselor. The conflict between the value free interpretation of the scicatific and clinical role and the understanding of that role which recognizes that values and directive counseling is and should be incorporated has specific implications for the newly developing field of genetic counseling. Sociological and normative research on the conflicting role models is just in the early stages. Sorenson (1971 and 1973) reviews this work pointing out that there are two models operating. The first is that of technical consultant- client model (Sorenson uses the term "counselor-client relationship," but that seems to us to imply a "counseling" or "advice giving" function) (see Reed, 1963). Here the idea is that the professional's role is that of transfer of information without telling the counselees what they should so. The second model is that of the traditional doctor-patient relationship which is, rightly or wrongly, often seen as one in which the "patient" yields discretionary power to the doctor (sce Lynch, 1959). Fraser (1971, pp. 53-54) indicates that his position "has evolved toward a more rather than less directive approach in giving genetic advice....If the parents ask me 'Vhat would you do?’ I am prepared to say that putting myself in their shoes as best T can, I would or would not, as the case may be, take the chance.” Fort et al. (1971) appear to follow the same wodel in advocating primary sterilization which they claim to "uahesitatingly counsel” to women with sickle cell discase. Lappé (in his comments in Lappd et al, 1971) argues that the role of the yeeeoltic counselor can be seen as 653 wh Bodhisattva--"one who is himself enlightoned...and who has an ethical and moral obligation to use this knowledge to reduce the suffering of others...." That the professional background of the genetic counselor (whether physician, human geneticist, or social worker, for instance) may be critical in defining the willingness of the counselor to incorporate direct and indirect value judgments into the counseling is suggested by the origins of these two different models. Recent studies (Sorenson, 1971a; Hall, 1973; John Fletcher, 1972a and 1972b) indicate that whether or not the physician adopts a role in which he attempts to communicate just genetic facts and options open to patients or moves more actively into the advice giving function, counselors do, in fact, have an impact on the decisions made by their counselees. This is not to say, of course, that there is no difference between the decisions made when the counselor, on the one hand, adopts the view that he should communicate the conditions and options avoiding conscious attempts to offer advice or influence patient decision-making, or, on the other hand, actively tries to give decision-making advice. It appears that there currently exists an impass, a dilemma in role delineation. The "value neutral role model is impossible both in practice and in theory. Functioning as if value neutrality were possible might create a situation where needed checks on the counseling process are ignored. Furthermore, to make the counselor into a data transmitting technician remove® from him the responsibility of TE a moral man. On the other hand the "advice giving" model necessarily tends to impose the professional's — upon the wuehent who is, thus, deprived of responsibility as autonomous moral agent. It seems clear that this dilemma will not be resolved until much further work is done on the models for the relationship betweca the genetic professional and the layman he serves as well as on techniques for miniawizing the value conflicts between professional and layman, B. Telling Patients of Diaonosis. There exists a vast literature on tae revealing of a diagnosis to patients when the findings are grave. Studies have shown that in the case of a cancer diagnosis, 88 percent of physicians will tend not to tell the patient (Oken, 1961), while between 82 and 98 percent of laymea in different groups claimed they wanted to be told (Kelly and Friesen, 1950). Of course, one cannot read normative moral judgments from survey data, but such discrepencies are revealing. MNeither can one transfer terminal diagnoses to genetic diagnoses. Now, however, some of this same ethical and sociological analysis is being applied to the field of revealing genetic information. Four separate studies have shown that mothers of handicapped children feel that early and complete disclosure is desirable (Drillen and Wilkinson, 1964; Berg, Gilderdale, and Way, 1969; and Carr, 1970). The Report of a Working-pParty set up by the National Association for Mental Health (1971) dealing with the issue of telling the parents of on birth of an abnormal child concludes; We recommend that parents should be told as soon as a definite diagnosis has been made. If the parents make the first approach and ask whether or not their child is normal, they should be told the truth, as far as it is known, cven if the diagnosis is still in doubt. 655 “2m The nature of chremosomal analysis in either pre- or post-natal disanosis is such that we can anticipate that there will be a growing number of cases of unexpected discovery of chromosomal abnormalities. The typical case will be a pre-natal diagnosis for trisomy 21 indicated by maternal age in which inspection of the chromosomal pattern reveals another irregularity. Such a case was reported recently (Veatch, 1972) in which there was an unexpected discovery of XYY chromosomal pattern. The counselor's dilemma was whether or not to disclose this finding to the counselee in the light of the ambiguous data some of which indicated that there may be a relationship between XYY and socially aggressive behavior. The first problem faced in this situation was what we have called a "condition of doubt" problem. What is the moral obligation to disclose Zeluenalion when the data themselves are unclear in their implications? Should, for instance, a couple, both of whom have sickle cell trait be counseled in a pre-marital session that both treatment and prenatal diagnosis for sickle cell disease are currently being researched, or is it morally indicated that such "uncertainties" be withheld until such time that the uncertainties are clarified? Action in the "condition of doubt" will depend upon the fundamental value orientations of the actor especially whether one is generally optimistic or pessimistic about human progress and the extent to which individual freedom or "voluntarism" should be determinative in genetic decision-making. Whether or not a condition of dqubt exists, the arguments for and against revealing diagnoses have been summarized (Veatch, 1972) as falling into the two types of normative ethical reasoning systems outlined above, utilitarian and formalist. In each case there are arguments for and against revealing the diagnosis. The utilitarian arguments against telling 656 hinge upon possible psychological and, at times, physical harm to the adult or offspring. Included here could conceivably be the argument that physical harm will result to the fetus if genetic abnormality is disclosed prenatally, but more often the psychological trauma to parent and child, such as in the XYY case, is the primary concern. Utilitarian arguments in favor of telling also hinge upon bad consequences, in this case from not telling. The psychological harm from anxiety from failure to transmit information is an example of immediate harm. Deprivation of freedom of choice--for abortion for instance--is another. Longer range negative consequences include the gradual building up of the knowledge that medical professionals will withhold information or even lie when they consider it useful, a reputation which breaks down patient trust over the long run so that benevolent with- holding is eventually self-defeating. More complex is the argument (known as rule "utilitarianism') that more good will be done in the long run if the general rule "tell the truth" is followed than if in each case the professional exercises his own judgment, because, for one reason or another, the situational, individualized decision-making approach in many cases gives rise to mistakes of judgment. Some have argued this is the case when a professional group is systemically skewed in their estimate of the harmful consequences of telling. The non-utilitarian (formalist) argument in supporting the withholding of information are rather remote. On® offered is that the genetic counselor exists in a contractual relationship with his client who has engaged him simply to perform a prenatal diagnosis for trisomy 21 and for him to "meddle" in another area would be a violation of the contract. While this argument shows a respect for the coatractual nature of the professional-client relationship, it seems rather remote. Formalist argumnzats in favor of disclosure include the moral duty to disclose tha truth when it can reasonably be expected to be of meaning or use to the client. A broader interpretation of the contractual understanding of the professional-clicat relationship also leads to a similar conclusion. If the implied contract is not for specific information, but for a report of the potentially useful information one could argue that the contractual model would call for disclosure. To fail to disclose violates the implied contractual relation. It can be seen that the choice of a normative ethical theory, usually done implicitly, as well as the "quantifying" of the relative weights of the factors involved such as harms from disclosing vs. harms from not disclosing will be significant in the choice made. That there may be significant differences between genetic counselor professionals and laymen on this moral issue suggests that further study in this area is needed. C. Confidentiality of Genetic Information Another serious medical ethical issue at stake in the development of the practice of clinical genetic counseling derived from the general value orientational conflict between the welfare of the individual and larger social groups discussed above. Because of the nature of genetic disease transmission, there is at times substantial interest on the part of society or smaller groups in identifying the presence of the genetic trait judged undesirable. The usefulness or even "right" to su walormgion has been claimed for society at large (for "protection" of the gene pool), for potential employers, for potential adoptive parents, for family members who share a common genetic heritage, and for actual and potential offspring. Yet also because of the nature of genetic disease many afflicted individuals and even carriers, 93-999 (Pt. I) O- 73 - 21 658 ww for social and psychological reasons, would prefer that such information about themselves not be disclosed and invoke the traditional medical right to confidentiality. The most explicit discussion of the question of confidentiality in genetic counseling has been offered by Lubs (1973) in a paper on "Privacy and Genetic Information." He identifies two general routes through which the individual's privacy may be invaded. The first is through the proband (the individual through whom a family comes to medical attention); the second, through screening programs. The ethical aspects of screening will be taken up in a later section of this review. Lubs cites a case of hemophilia diagnosed at three months with severe bleeding. The parents refused per- mission for the medical geneticist to contact relatives and "sh amount of persuasion would change their minds." Here there is conflict between the medical model of genetic counseling where the traditional ethical obligation is to serve the patient's welfare and other models such as that of public health where obligations are more societal. Even the medical model may produce conflict in obligation when the genetic counselor might happen to be a physician in a professional relationship with both the proband and another member of the family which has an apparent interest at stake. Some have drawn an anology with cases where physician disclosure is expected or even required by law for public health purposes in cases such as venereal disease and, gun shot wound (Hall, 1933), but little attention has yet been given to the moral and legal differences when the disease is "communicable only genetically and other "harms" to the public are much less direct, A second aspect of the ethical problems of confidentiality arises when genetic data is stored systematically. While no national genetic data bank now exists such computerized data storage systems are already being developed on the local level. One objective is statistical research where the primary ethical concern is probably the possible risk that the codification of the data might be broken. There are, however, many possible practical and clinical uses of such data beyond the research stage. Proposals, for instance, to have a genetic registry for sickle cell disease have been made. The wider the public access to the information stored by name, the greater the potential benefit in identifying relatives who are carriers, yet the same information would also be available to employers, lawyers, and government officials and others to whom the affected individual might not want the information transmitted. Some question has already been raised about the use of genetic information stored in computerized records of the insurance industry by employers and others. The development of spem banks for use as a source of sperm for artificial insemination also raises serious ethical issues about the storage and transmission of genetic data about the sperm donor. The traditional right of the patient to control the disclosure of his own medical record is jeopardized by such developments. It appears obvious that much more work is needed to develop clarification of conflicting role models and the problems of confidentiality generated by them. III. ETHICAL ISSUES IN AMNIOCENTESIS Amniocentesis has become a major tool for diagaosis in genctic counseling. Recently the literature has begun to reveal ethical issues linked directly with the amniocentesis procedure itself. This section will examine some of these developments. A. The Relation tc Abortion. Amniocentesis is so closely linked with abortion that many have limited the discussion of the ethics of prenatal diagnosis to this major social- ethical debate (Dorfman, 1972) or recognize it as the most obvious ethical issue (Neel, 1972). John Fletcher (1972b, p. 52) has reported in a study of parents involved in genetic counseling that "abortion was the prevailing moral problem faced...." Hilton (1973) observes that arrival of amniocentesis at the same time as a radical social change in attitudes toward abortion which, in certain cases, gives parents the opportunity to decide the genetic characteristics of their offspring has profound ethical implications not only for parents, but for the counselor and his role and for society at large. He suggests these developments change the parent's question from "Is my baby normal?" to the future tense "Will my baby be normal?" and then ask what ought to be done about it. As indicated above, abortion, in and of itself, is a major ethical issue which has generated a copious literature and will not be discussed in this review. There are, however, ethical issues in abortion which are specifically related to emniocentesis. One is whether or not prior commitment to abortioa should be made a prerequisite for amniocentesis. Reports indicate that in many centers this is the prevailing practice (Epstein, 1969; Motulsky, 1972; Littlefield, 1970). John Fletcher (1972h), however, reports that it was not the policy of the center where his study was conducted to elecit a firm commitment to abortion as a prior condition. While at first, prenatal diagnosis without abortion commitment would appear to be a useless waste of medical resources, commentators have cited several moral considerations to support an open policy on prior commitment. First, we must assume that centers would only maintain such a policy when no other medical uses other than abortion can be made of the information obtained from amniocentesis. A development of a prenatal diagnosis for phenylketonuria, for instance, might lead to some changes in maternal diet beneficial to the fetus. Even when no medical use (other than abortion) can be made of the prenatal diagnosis, it seems that some might opt for amniocentesis and make use of the intervening days to make what they might consider to be a weighty moral decision about abortion. At minimum, it would appear that the rule should be that there must be commitment to considering abortion. Even then, it appears that there may be utilitarian and other factors in opposition to the moral judgment that amniocentesis should be linked to an abortion commitment. While no organic medical use may be made of knowledge coning from the amniocentesis procedure, this does not rule out the possibility of psychological and social benefits to the candidates for amniocentesis. The relief of anxiety in anticipating a second diseased child may be seen by some as sufficient justification. Certainly, knowledge of the presence of a serious genetic disease such as Tay-Sachs might modify the cathectic in- volvement of the parents. Cases can be made either for withholding of emotional involvement or the escalating of that involvement on the grounds that the child will "only be with us for a short time." Orthodox Jews who are both at risk for Tay-Sachs and by conviction opposed to abortion might 662 -33- claim such motivation for the procedure. There is at least one published report (Gendel ot al., 1972) where positive prenatal diagnosis of E Trisomy with abortion being refused by the parents produced the result that "their unhappiness was mitigated somewhat because of the warning they had been PP 5 3 given." The moral decision to link amniocentesis to aborticn will reflect an organic value orientation if such psychological and social dimensions are not incorporated. If a knowledgeable patient requests amniocentesis while withholding commitment to abortion there seems to be at least prima facie evidence of some value perceived in the procedure. There is risk that those values will be overlooked by professionals who may have other value orientations. B. Medical Diagnosis Without Consent. Beyond the abortion question there still remains ethical issues in amniocentesis per se. One of the most significant, centers on the morality of the justification for medical diagnosis without consent. It is obvious that the fetus upon whom a diagnosis is being made cannot consent to the procedure. We are, of course, assuming that the woman will give meaningfully informed consent to the test. Reasonably, informed consent for medical diagnosis and treatment, when it can be obtained (in the archetypal case from the mentally competent adult) is a first and fundamental moval requirement in medical ethics. It is inconceivable that prenatal diagnosis by amniocentesis could be performed morally on such an individual without her consent (sec sample consent form in Maciatyre, 1971.) The more difficult question arises in the morality of the justification in terms of the fetus. These argumzats require, of course, the assumption that the fetus has some woral claim (Kuss, 1973). Wa shall present the 663 ~34- arguments in the iterators against arniocentesis based upon this assumption and then take up the possible difficulties with it. These arguments have been developed with great sophistication by Ramsey, upon vhose work the following summary is based. 1. Amniocentesis as Experimentation Without Consent. Ramsey (1973) begins his critique of amniocentesis by observing that one criterion of ethical experimentation as stated in the Nuremberg Code and elsevhere is that experimentation on human subjects "should be such as to yield fruitful results for the good of society...." He argues that this is potentially in conflict with the moral maxim which he, following a major tradition in medical ethics, summarizes as the minimal standard: that medical practice do no harm. Citing evilends from early drafts of the first principle of the Nuremberg Code, he suggests that the intention was that proxy consent could be morally valid only when the subject could at least remotely be expected to receive some benefit from the experiment. If benefits and harms must include calculation of the potential benefits and harms for the individual subject exclusively, then the experimental development of the procedure of amniocentesis is ethically problematic. In a related discussion of the first experimental attempt at human in vitro fertilization and possible damage to the future human being, Ramsey argues (1972c, pp. 1347-8): - Unless the possibility of such damage can be definitively excluded, in vitro fertilization is an immoral experiment on possible future human beings. And, it is to say that this condition cannot be mat, at least not by the first "successful" cases....My point as an ethicist is that 664 =~ Gy none of these researchers can exclude tha possibility that they will do irreparable damage to the child-to-be. And wy conclusion is that they cannot morally proceed to their first obstnsibly successful achievement of the results they seek, since they cannot assuredly preclude all damage. It is not the place of this chapter to review the literature oa the risks of amniocentesis. It is clear that in the first experimental tests on a human being, risks and risk rates cannot be predicted with certainty. The literature on the risks of amniocentesis seem to indicate that certain risks are real (ocular trauma, dye injection, fetomaternal hemorrhage, infection, and abortion) even if their incidence is small (Creasman et al., 1968; Epstein et. al., 1972; Friedmann, 1971; Gerbie et al., 1971; Cross et al., 1972; Fuchs, 1972). Epstein et al. (1972, p. 218) state in summary that "Although the large series so far reported have not demonstrated any significant increase in fetal mortality or morbidity, the numbers ex- amined are still too small to eliminate entirely these possibilities." This is certainly the case if one includes, as one must, risks of developmental change to the fetus which might require long-term developmental and intellectual evaluation of individuals who had experienced amniocentesis (Friedmann, 1971). 2. Medical Diagnosis Without Congent. The argument of Ramsey does not rest exclusively on the experimental nature of the procedure during the early stages of clinical application of amniocentesis. The mein thrust of his argument is against what he sees as tue necessity for introducing consideration of potential non-fetal benefits ince the moral decision-making process. This argument incorporates two of the fundamental value orientations discussed above: the opposition to utilitarian normative ethical theory and to the societal perspective. Ramsey claims that the justification of amaiocentesis requires a "statistical morality" of cost-benefit analysis and an ethics of the "greatest net benefit" including goods for those other than the primary patient (fetus) being screeaed. He offers two arguments against these moral assumptions. The first is that the benefits (and here he includes both natural or induced impairments) may not be comparable. If this is the case, then it is impossible to speak of the "greatest good altogether." Second, he argues that even if potential harm to the fetus can be in some way compared to other potential goods and harms the "benefitees" are not comparable. They are irreducibly different. He rejects the claim that good and harm for one can be interchanged in moral reasoning for goods and harms to another. On these grounds, he also finds the term "greatest good altogether" empty. Ramsey argues that radically different types of goods may not be comparable in any way and, therefore, no summing of goods is possible. Can material trauma of successive abortions be compared iu any rational way with the trauma of having a child with a genetic disorder? Can naturally occuring defects be compared to induced damages, especially when one realizes that subtle factors such as Juile must be tekan into the calculus? Ramsey is particularly critical of the tendency to substitute incidence rates as a readily quantifiable basis for comparisons avoiding the critical question of the significonce of the incidences being compared. 666 wT Bet be argues further that even if the relative 2oods could be compared, such a calealus cannot avoid the problem of interchanging non- interchangeable lives. llis argument is one of distributive justice. His conclusion is that amniocentesis is ethically problematic at best and possibly worthy of moral csnsure. 3. Difficulties with the Anti-Amniocentesis Position. There are several lines of argumentation taken in the current literature against the position of Ramsey. First, some argue that the fetus simply cannot be taken as "One," as a patient with full moral significance. Certainly, this is the implication of the recent changes in abortion legislation and the moral views underlying those changes. Whether the fetus is taken as "merely a piece of tissue," as some rhetorical arguments have claimed, or simply as an individual with moral claims of a nature different and less rigorous than post-natal human life, the implication of this line of reasoning is that the fetus's interests count less than those of others. Of course, the presence of those arguments do not demonstrate their moral legitimacy over and against Ramsey. A second line of STR essentially accepts Ramsey's premise that the dominating concern is for the welfare of the fetus, but they argue chat vhe fetus has a "right to be born normal" or that a genetically diseased fetus has a "right not to be born" (e.g., Glass, 1972, p. 252). The assumption here is that there arcesome conditions that are worse than not living or not being born. Sadler (1972), reviewing the legal status of cases for wrongful life, finds that claims have —_ denied in each case. In Gleitman v. Cosgrove, the court ruled that "This court cannot 667 -38- weigh the value of life with impairments against the nosexisteace of life itself," levertheless, such arguaeats clearly undercut the charge that amniocentesis is justified by the bonum corm un and wast be dealt with in their own terms. Still a third line of argumentation attempts to integrate the nt utilitarianism of the position of Ramsey with the classical utilitarian concern for the grestest good taken altogethetr. Holders of this type of normative ethical theory admit with the utilitarians that benefits, including benefits for other members of society, are morally relevant considerations, yet they insist that non-utilitarian factors (duties arising out of special relationships, duties of just distribution, etc.) are also morally relevant independent of utility (Ross, 1939; Frankena, 1963). This kind of moral history is beginning to be applied to issues related to human genetics (Callahan, 1971a; Veatch, 1972). In principle, it could be applied to the justification of amniocentesis where risks to the fetus are minimal (rather than demonstrated to be ghsenid and benefits (to the fetus or others) are particularly great. Such a line of research remains to be carried out. C. Amniocentesis for Sex Determination. Beyond the question of the connection of amniocentesis to abortion and the inherent morality of non-consentual, non-beneficial medical diagrosis, there remains another moral issue dir2ctly related to amniocentesis. This is the use of genetic diagnosis for reasons which are either considered to be "non-medical" or trivial by those who possess the technical capabilities to perform such diagnoses. Post-natal genetic deterwination of sex has been reported (day, 1972) for verification of the sex of women athletes 668 -39-~ in the Olympics. Perhaps the wost typical case will be the use of pronatal sex determination (Cedarquist and. Fuchs, 1970; Papp et al., 1970; Abbo and Zellweger, 1970; Valenti et al., 1972). With the availability of the technique, there is no technical reason why it cannot and will not bao used for social purposes as well as prenatal sex determination in cases of possible sex-linked genetic disease. We may anticipate ethical conflict over the use in prenatal sex selection for purposes of fulfilling wishes of a child of a certain sex. Stenchever (1972) reports what he considers to an "An Abuse of Prenatal Diagnosis." The patient, a 38-year-old mother with one boy and two girls, sought amniocentesis ostensibly to rule out Down's syndrome. When informed that Down's syndrome was not present, the parents were apparently also told that the fetus was female. With this information, they chose abortion anyway presumably because they wanted another son. Stenchever questions both the morality of abortion on these grounds and the economic and time problem resulting from the use of the laboratory for this purpose. He suggests the with- holding of the diagnosis of the sex of the fetus unless it is "crucial to the management of the case," that is apparently until there is organic rather than social reason for obtaining the information. It is clear that the use of amniocentesis for sex determination has moral implications, Its widespread vse would, in addition, raise social and ethical questions (Etzioni, 1968). In addition, the judgment that such use of prenatal diagnosis is unjustified implies weighting of benefits to be gained by genetic sex determination such that diagnesing organic conditions is considered more important. The moral issue of withholding knoim 669 —4u= genctic diagnosis which could reasonably be cxpected to be of meaning or use to the counseloes has bezn discussed above. To our knowledge, no further discussion from the cthical perspective of the use of prenatal diagnosis for non-medical purposes has appeaved aud wore systematic ethical analysis seems to be called for. IV. ETHICS OF MASS GENETIC SCREENING Mass screening for genetic conditions is already taking place for Tay-Sachs, sickle cell anemia, galactosemia, phenylketonuria, aad other autosomal, recessive, genetic diseases. Additional diseases arc beiag added to the list, Many of the ethical issues raised by mass screening programs have already been discussed: the question of linking screening to abortion, the problems of withholding information thousht possibly harmful to the person being screened or to others, and the problems of necessity of confidentiality in records. Nevertheless, there are unique issues in mass screening and these are beginning to be discussed in the literature. A major, year-long study on the ethics of genetic screening was conducted recently by the Research Group on Ethical, Social and Legal Issues in Genetic Counseling and Genetic Engineering of the Institute of Society, Ethics and the Life Sciences (1972, hereafter cited as Research Group) consisting of a 23 member inter-disciplinary committee of geneticists, biologists, lawyers, sociologists, philosophers, theologians and ethicists. They attempted to deal with the unique ethical features of mass genetic screening. Above we discussed the literaturs on the patient-physician and the consultant-client models of the lay-professional relationship in clinical genetics. It is clear that in mass genetic screening contact with the . professional is normally brief and zeaerally falls outside the usual patient-physician relatioaship. While the mass screzniag program is clearly more societal in orientation than ths mora individual counseling situation, it is not yet clear what the implicatioas of this are for such things as the 671 principle of confidentiality. It is more likely that many members of an extended family may be screcned at the same time. Thus, notions of confidentiality in relation to the "proband may not be precisely the same. Nevertheless, early commentary on this issue suggests that the emphasis on confidentiality is to be preserved (Research Group, 1972, p. 1131). A. Goals of Mass Screening Programs. The goals of a genetic screening program will reflect the fundamental value orientations we have previously outlined (Scriver, 1972). Unfor- tunately many reports of mass genetic screening fail to make explicit the objectives of the screening. The Report of the Research Group on Genetic Counseling and Engineering (1972) has summarized three types of goals: 1. The provision of benefits to individuals and families. 2. Acquisition of knowledge about genetic disease. 3. Reduction of the frequency of apparently deleterious genes. The Research Group places primary emphasis on the individual, screenee- oriented objectives. They do consider acquisition of knowledge about genetic disease to be a legitimate objective, but claim that the value of screening programs "is enhanced when they also contribute information that is useful for counseling individuals or for public-health purposes.’ They have stronger reservations about the %stablishments of screening programs for the purpose of reducing the frequancy of apparently deleterious genes. In part, their objectives are based upon the primacy of the commitment to individual welfare, but their objections arc practical as well. They 672 argue that since 'virteally everyone carries a small number of deleterious eenes or lethal recessive genes....to reduce the frequency of a particular recessive gene to near the level maiatained by recurrent mutation, most or all persons heterozygous for that gene would have either to refrain from procreation entirely or to monitor all their offspring in utero and abort not only affected homozygote fetuses but also the larger number of heterozygote carriers for the gene." There are others (Muller, 1959; Vukovich, 1971; Class, 1972; Gorney, 1968; Osmundsen, 1973; and Ingle, 1967) who are more societally oriented in their emphasis, some of whom might not have the same reservations about the use of screening for the purpose of reduction of the frequency of apparently deleterious genes. B. Guiding Principles for Screening Programs. The Research Group (1972) on the basis of its study, has outlined a series of eleven principles for the design and operation of screening programs. These are summarized as follows, basically in the words of the report. For a full exposition see the original report. 1. Attainable Purpose. Purposes should be articulated before program is undertaken. 2. Communi ty Participation. From the outset, program plannars should involve the communities affected by screening in formulating programsdesign aad objectives, in administering the actual operation of the programs, and reviewing results. 673 nll Eq Information facilities related to the program should be available to all, though priority should be given to well-defined populations where there is a definitely greater frequency of occurreuce. 4. Adequate Testing Procedures. Tor autosomal recessive conditions, this should include tests to distinguish those carrying the trait from those homozygous for the variaat gene. 5. Absence of Compulsion. The Research Group strongly urges that no screening program have policies that would impose constraints on childbearing or would stigmatize those who still desire to have their owa children. Screening A should be conducted on a voluntary basis. 6. Informed Consent. In addition to signed consent documents from those tested or the legal representative, it is the program director's obligation to assure knowledgeable consent, design and implement information procedures, and review consent procedures for effectiveness. The HEW guidelines for consent are suggested as guidelines. 7. Protection of Subjects. Screening ought to be considered a form of "human experimentation.” 8. Access to Information. A Pog should fully and clearly disclose to the community and all pereons being screened its policies for informing those screened of the results of the tests performed on them, 93-999 (Pt. I) O - 73 - 22 674 ly 9. Provision of Counseling. Vell trained geaetic counselors should be readily availabla. As a general rule, counsaling should be nondirective, with emphasis on informing the client and not making decisions for him. 10. Understandable Relation to Therapy. All persons being screcned should be informed, prior to the testing program, about the nature and cost of available therapies or maintenance pro- grams with a description of their benefits and risks, 11. Protection of Right of Privacy. The Research Group endorses policies of informing only the person to be screened or, with his permission, a designated physician or medical facility, and of having records kept in order. ) C. The Question of Compulsory Screening. The guidelines of the Research Croup's Report which has received the most discussion is that dealing with compulsory screening. Bowman (1972) criticized the Research Group's Report for failing to call specifically for repeal of existing mandatory screening laws. He cited such laws in the District of Columbia and the state of Virginia, as well as the Massachusetts law for compulsory screening for sickle cell trait or anenia as a prerequisite to schools attendance which was cited in the Research Group's Report. Lappé (1973b) claims there are now 29 such bills for mandatory screening pending in various state legislatures. In part, the growing concern over mandatory screening (Culliton, 1972; Powledga, 1973; and Schwartz, 1972) grows from the increasing recognition of potential harm from screening. These include potential p P 675 -4o- danger of social stigmatization; unnecessary fear (in those with sickle cell trait, for instance) when counseling has been inadequate or the individual retains fears in spite of couaseling; realization that medical anomalies, even those without clinical significance, such as position of trait for an autosomal recessive disease, may becoms known to insurance companies or employers and effect the individual's ability to obtain insurance or employment; the danger of false-positive identification (as in phenylketonuria screening); as well as the somally small, but real medical risks of infection and trauma from the test itself. In addition, compulsory medical diagnosis violates the principle of individual freedom in an area where that tradition is particularly strong. In contrast others have criticized the Research Group's Report for its condemnation of compulsory screening. The Subsection on Heterozygous Carriers of the Task Force on Genetics and Reproduction at Yale (Duncombe, 1972) claimed: We believe that the right of a newborn infant to intellectual development takes precedence over the parents' right to allow or to refuse PKU screening for their child. As we approach a period when in utero tharapy may prevent or minimize the ‘effects of a genetic dissase, we suggest that a diseased fetus has the right to optima therapy. This will often necessitate screening of the parents. Much stronger criticism of the Research Group's opposition to compulsory screening comes from Osmundsen (1973). In particular he 676 ~47- challenges the Report in claiming "there clearly is 'public heelth justification for mandatory screening for the prevention of gevctic disease'." le cites as a "partial list of justifications”, reduction of pain and suffering in the genetically afflicted, reduction in genetic disability, reduction in economic costs, reduction of indivect costs, such as the individual's productive input to society, the nead to determine the medical, so >» ¢nd economic burden of genetic disease, and finally "assurance of good guality" which "becomes a vital con- sideration to the maintenance of the species” and which "can be achieved only through kuowledge and the exavcise of informed choice." The difference between Osmundsen and the Research Group rests, at least in part, in the definition of "public health" and Osmundsen's understanding of the position of the Research Group. Pain and dis- ability are "public" only in the sense that the public might have concern for individual medical problems while economic factors and loss of individual productivity may not be considered "health" interests. Osmundsen does, however, argue that genetic discase is "vertically" contagious. Lappé (1973a), the Program Director of the Research Group, claims that "contagious" as used in public health policies is usually used to refer to communicable disease, the spread of which is caused by exogenous agent and which can be transmitted horizontally. He claims there are obvious differences bat®een these and genetic diseases both with regard to eificacy of treatments and the qualitative differences in the means required to control each. Lappé (1973b) in reply to Osmundsen claims "All but one of the potential benefits for mandatory 677 screening. ...were goals vhose attainment was limited and which could better be met by voluntary than by cowpulsory screening.” Tha one goal which might "og require mandatory screcenieg is the "assurance of good quality" in thz population. This was rejected by the Research Group as a major goal of screcuing. There is apparently also confusion over the Research Group's position. Twice Osmundsen labels the group as an "opponent of mass genetic screening." This clearly is not the case. The key sentences are: ....there is currently no public-health justification for mandatory screening for the prevention of genetic disease. The conditions being tested for in screening programs are neither "contagious" nor, for the most part, susceptible to treatment at present. The group is silent about the possible justification of mandatory screening were prevention or treatment to be developed. Apparently, the only clear disagreement with the Subsection on Heterozygous Carriers of the Task Force on Genetics and Reproduction at Yale is over whether the potential benefits of screening for PKU so outweigh the risks at the present time to justify a compulsory, rather than a voluntary, screening program. D. Screening's Impact on the Concept of Normalcy. One of the reasons given against compulsion in screening in the Research Group's Report (1972, p. 1131) is that "it is unjustifiable to promulgate standards for normalcy based on genetig constitution.” Elsewhere concern has been shown for the generation of informal social pressures for the participation in mass screening programs. Hilton 1973) warns that the freedom to choose can become the "responsibility" to be screened. These 678 -40- couid become particularly strong when broad based comaunity organizition suppori is obtained for scresaiag such as in Jewish communities and religious cion organizations in screening for Tay Sachs. 1t has been observed that co is mot limited simply to legal and physical force, but can also be social and psychological. Ramsey (1973) develops further the concern for changing the concept of normalcy as part of his argument against screcning programs in general even if not compulsory. He observes that the effect of screening will be to "upgrade' the concept of normalcy in society. The impact could be the generation of pressures for abortion, guilt on the part of parents refusing to participate in screcn-abortion regimens, and new attitudes toward the genetically abnormal. He observes that since there will always be abnormals (through mutation as well as screening refusal), care and concern for this group could be greatly affected. He suggests that screening will raise questions about existing individuals who have characteristics for which mass screening is conducted. These questions--whether genetic diseases arc contagious in the sams moral sense as other contagious diseases, whether benefits outweigh harms and other moral objections sufficiently to justify compulsory screening, viether protection and improvement of the gene pool is a legitimate concern for screening programs, and what the impact on our concept of moimalcy will be--are all so new that very little systematic reflection on them has yet been produced and found iis way into the literature. Certainly, much more will be needed Levore any clear answers ererge. 679 ~50- V. ACTIVE CHANGE IN THE GENETIC CODE There is a widely, if intuitively recognized, distinction in -the literature between attempts to counsel, screen, and diagnose preaatally for genetic characteristics thought to be detrimental and active cfforts to change the genetic endowment pre- or post-natally of an individual or a gamete. There is great language confusion over the proper terminology for this genetic intervention. Some references use the term "genetic engineering" (Abelson, 1971; Danielli, 1972) to refer to the class of actions which actively try to manipulate or change genetic composition of the cell. Others, however, use this term more broadly to refer to the entire field of human clinical genetics including counseling, screening, and diagnosis, as well as clonal propagation, and in vitro fertilization (Nagle, 1971; McCullough, 1972). Still others insist that linguistic as * well as moral distinction must be made between genetic Yengineering' or "manipulation which is designed to introduce new characteristics or "improve" the genetic endowment. They suggest that the terms engineering and manip- ulation have a negative connotation also (Lederberg, 1971 and 1972; Davis, 1970; Aposhian, 1970). Many with this view have adopted the term ''gene therapy" for the om of the genetic code for purposes of correction of a disease- producing component (Lederberg, 1971 and 1972; Friedmann and Roblin, 1972; Anderson, 1972; Fox and Littlefield, 1971). pavis (1970) uses the term "genetic intervention" for the more inclusive active modificaticn. While the term still may maintain manipulative overtones, it is used in clinical medicine as well and will be used here in this sense of active, molecular 680 ~51- and cellular genetic change for whatever purpose. Fieally, Ramsey (1972a aad 1973b) objects to the usz of the terms "genctic therapy" or "genetic surgery unless they refer to treatment of pru- or post-natal individuals rather than gametic cells. He suggests the latter be called "genetic engineering or "ganotic manipulation." These linguistic differences, which at first seem to merely add confusion to the discussion, in fact, reflect differences in ethical or value orientational position. These ethically important differences will be discussed below. A. The Hyperargininecmia Case: Recent symposia, including those sponsored by the Fogarty International Center, Worchester Polytechnic Institute, and Washington Cathedral, have explored the technical and ethical issues in active intervention with the purpose of changing the genetic code. The first attempt to actively change the genetic characteristics of a human being has been the focus of much of the ethical discussion in this area. According to reports of the case (Schmeck, 1970; Friedmann and Roblin, 1972; Terheggen, et. al., 1969) two German sisters, ages two and seven, were suffering from hyperargininemia as a result of a genetic defect blocking the synthesis of arginase. The result is severe, pregressive mental retardation, spastic paraplegia, and epileptic seizures with no known treatment. The attempted therapy in the case was at the genetic level: injection of Shepe pepilloma . - virus. This virus is known (as a result of accidental exposure of lab- oratory workers) to increase levels of arginine, possibly by viral trans- duction of the neoded genetic material. Friedmann and Roblin (1972) offic: the first line of criticisw of the ethical acceptability of the procedura. Toney say they bellieva chat this -n first attampt at gene therapy was premature, and that it might "seorva as an impetus for other attempts in the neat future." They conclude that they oppose further attempts at gene therapy in human patieats for the foreseeable future because we lack understanding 'of such basic processes as gene regulation and genetic combination," the relation between the molecular defect and the diseasc state, and the short-range and long- range side effects. Mere exists an example of what we have earlier called the "condition of doubt." What action should be taken, if any, when it is clear that we do not have adequate information to make an informed choice and yet the clinical situation will not permit time to conduct the necessary research to gain that information. We have suggested that one's response to this condition of doubt will depend upon fundamental value orientations: man's relation to nature and attitudes about intervention into natural processes, general orieatation toward the triumph of good or evil in the world, and orientation toward "doing" or "being." The latter are value orientation variables of Kluckhoha and Strodtbeck (1961) which we have not previously discussed in this review. Rogers (1972) apparently differs with Friedmann and Roblin (1972) on these value orientations. Replying to Friedmann and Roblin, he disagrees to some extent about the degree of human experience with Shope virus, but the primary argument at the value level is over when it is appropriate to use an experimental procedure. He argues that "When one has a patient with a progressively deteriorating disease that is known not to respond to dietary or other known measures, aud one has a possible means of stepping the progression of the disease with an ageat that has been extensively investigated for 40 years, there appears to be littie alternative other than to txy it." Ramsey (19722) wpporeatly accepts Rogers' argument over agaiost Frieduaoa and Roblin that treatment even though unproven, would be Si i 5 morally acceptable provided it weve undertaken for the child's benefit. In reply to Anderson (1972), howe , he questions whether this is, in fact, the case. He claims (1972a, p. 163) that it seems likely in the case of the older girl that there is not evea hope for arrest of further progress of the disease, and argues that: If--as scems likely in the older girl at least-- The dying of these children is being prolonged purely for experimental purposes, I know of no line of moral reasoning that can justify what is being done. We ought not to speak of gene 'therapy" in this connection. It is rather a case of genetic experimentation in which men have chosen retardates and taken from them something which they cannot give, namely free consent to prolong their dying for the sake of scrutinizing it scientifically. We should bracket the possible disagreement on the medical facts of the case (which is possibly the only disagreement betwecn Ramsey aad Anderson) and note that Ramsey has introduced the ethical principle of informed consent for experimentation. We have reviewad his moral argument against the use of noa-beneficial experimental treatment for those incapable of giving their own couseat, above. ®riedmana and Roblin (1972, p. 954) also introduce the question of informed consent, but in a slightly different argument. They, reflecting their reservations about any human gena therapy at this stage of our knowledge, argue that there can be no valid proxy consent at this point in time ap ently even for possibly beneficial 683 lym therapics. "Clearly, uatil we know much more about the side effects of gene therapy, it will not be possible to provide them those giving proxy consent with adequate information about risks to the treated individual and his offspring." B. Risks to Affected Individuals and to Offspring. Davis (1970) emphasizes the difference between intervention which alters somatic cells and that which alters germ cells. While some considers the moral implication of (unknown) risks in genetic intervention to be little different than potential dangers in any other experimental drug (Aposhian, 1970), others warn that the potential side effects might not be observable for many years and, in come cases, may affect the germ cells and be heritable (Friedmann and Roblin, 1972; Lederberg, 1972; and McCullough, 1972), suggesting that the moral implications are certainly complex and possibly unique. Davis (1970) sees the possibility of genetic alteration of germ cells as a distinct advantage. "It could allow an individual with a defective gene to generate his own progeny without condemning them to inherit that gene. Moreover, there would be a long-term evolutionary advantage, since not only the immediate product of the correction but also subsequent generations would be free of disease." This view, of course, assumes that it will be the benefits and not the harms which will be propagated. The possibility of transmission of harms to offspring, even if remote, must change the benefit-risk calculus. For those who accept the inclusion of potential benefits to a future conceptus or to society at large into the decision-making calculus, as Davis does, this will simply be aan additional Lactor to be considered. Tor those who reject this mode of ethical reasoning, however, as Ramscy docs, the catire moral situation changes with the possibility of heritable (or ganctic) genetic change. Ramsey (1972a, p. 169) argues that in cases of genetic therapy which include gametic manipulation “the unknown acd uaforeclosed risks to [uture generations may outweigh any benefit that might be secured for the individual patient. In a matter of such grave importance, 'no discernible risk' is not adequate protection. Likewise, he (1972b, p. 15) claims that germinal engineering (where attempt is made to change genetic endowment of the germ cells for purposes of propagation) "would be an immoral experiment on a child-to-be" because there is no consent and the child suffers no defect which could justify Proxy conseat. We have summarized above arguments based on the lack of moral claim, on patient- or future patient- oriented utility, and on the system of normative ethics which mixes "formalist" claims with broader considerations of utility which are brought to be against Ramsey's position. C. Correcting and Improving Genes. Ve have noted that, when considering types of genotic intervention, one sroup desires to use the term “genetic engineering" for efforts to improve upon genetic endowment while rescrving the term "gene therapy" for modification of the genetic code for purposes of correction of a disease-producing component. . Ramsey (1972a, p. 158) limits "therapy" even more to pre- or post-natal individuals excluding gametic “therapy" on the grounds that there is not yet any patient to be treated. Those who distinguish betwcon "therapy" and "eaginecering"” have both practical and moral reason for it. Lederberg (1971) 685 =26~ suggests that genctic eagineering designed to improve upon wan is not so worthy of attention as the possibility of "amelioration of genetic defect.” Others appear much more optimistic about both the possibility aad the moral implications of improvement of man's genetic endowwmeant (Fagle, 1971; and Danielli, 1972). Danielli considers genetic engineering as the great possibility for advancing society. It is not clear at this point in the development of the discussion at the moral and evaluative level wnat the significance is of the distinction between "correcting" and Yimproving." There is certainly a traditional and intuitive greater weight given in medicine to the moral maxim of not harming. This is being reflected in the literature on the social and ethical aspects of genetics (Davis, 1972, p. 1282). There are classical parallels in moral philosophy dating from the Epicurean debate over the comparability of pleasure and pain including the Benthamite willingaess to include benefits and harms in the same calculus, the legal distinction between commission and omission, and the intuitive medical distinction between "therapeutic" and "elective" procedures, "positive' and "negative" euthanasia and "positive" and "negative" eugenics. All involve the postulation of a normal state, a baseline from which actions can be compared. The ethical dilemma is whether a condition below this baseline or state of normalcy is morally more weighty than the possibility of extending above the baseline, above the normal. There is today even doubt over the possibility of the exigtence of a concept of normalcy. Certainly, if such a concept is possible, the state of normalcy is changing from society to society and from day to day. 686 -57- In the literaturc in genetics, we see those with a more utilitarian orientation following their Benthamite tradition in minimizing the dis- tinction between correcting and improving man's lot. Joseph Fletcher (1971), who stands in the utilitarian tradition, argues for a "pragmatic" ethics for genetic control consisteatly claiming that "if the greatest good of the greatest number (i.e., the social good) were served by it, it would be justifiable not only to specialize the capacities of people by cloning or by constructive genetic engineering, but also to bio-engineer or bio- design parahumans or 'modified men'." Fletcher intermixes what he calls "therapeutic" and "eugenic" examples and, as we might expect, uses the term "genetic engineering" for both. Thus, Fletcher (1972, p. 3), revealing value orientation to man's technological subduing of nature, claims that "a baby made artificially, and by deliberate and careful contrivance, would be more human than one resulting from sexual roulette--the reproductive mode of the subhuman species." Classical utilitarianism is, of course, not the only normative system vhich would minimize distinction between "treating to restore normalcy" and "improving beyoad normalcy." Other (formalist) systems could maintain that producing good beyond some arbitrary concept of normalcy can be compared with and, other things being equal (which they rarely are), would be the moral equivalent to a comparable amount of eliminating disease. The only condition would be that the Kantian distinction between the moral significance of producing good and doing hamm (a distinction central to one tradition in ‘medical ethics) not be retained as a moral principle. 687 “SG In contrast to this position is the more dominant view which refloecis one of the traditional summaries of medical ethics, 'do no harm." Tie willingness of Ramsey (1972a) aad others to draw such a sharp moral line between therapy and engineering or manipulation (which does not have res- toration of normal health as its objective) rests on their willingness to distinguish sharply the moral principle by which they justify "therapy" (do not harm or some related principle) from the moral maxim governing the improvement of an individual which, for them, is less weighty. Precisely what the moral arguments are guiding these two nderstantings of the relationship between therapy and improvement have not, at this point in the development of the literature, been addressed specifically enough to allow a clear understanding of the differences in the ethical position. Whichever interpretation of the relation of therapy and improvement one chooses, one serious consequence has arisen from the general willingness to make the distinction. Often the impact has been to so divorce the two that only treatment of abnormal genetic conditions evaluated negatively receives attention in the social and ethical policy debate. Aside from the popular literature cataloging the fascinating, but unlikely, possible futures (super-soldiers cloned by the batallion, super-athletes, super-iantellectuals), very little serious attention is being given to the critical ethical questicns about morality of genetic modifications which would be broadly attractive. These might include, for example, marginal improvements in intelligence, elevation of the intelligence of offspring who would "naturally" be expected to have minimal intellectual capabilities, marginal "improvements in personality, and eliminations of bodily systems and functions causing harm without useful prupose (the appendix) or most plausibly genetic 688 -59- elimination of cancer ov heart dises (Gory 1872, p. 218). Tr way wall be that the scientific possibilities of controlling these polygenic discases scem minimal, but we are beiag warned (Fox and Littlefield, 1971; Joseph Fletcher, 1972; and Aposhiaa, 1970) to undertake the philosophical-cthical task of understanding the nature of man in the age of genetics bofore such possibilities arise. An initial attempt to deal with this question has begua in tha literatuve surveyed here (Rolansky, 1965; Joseph Fletcher, 1972). One of the more pro- vocative contributions has come from ethicist James Gustafson (undated) who poses four possible formulations of the moral imperative in response to tha actual and potential capabilities of active intervention to change the genetic material of the human cell. One, that "A scientist has no right to intervenc in the natural processes of human life, because it is sacred," he claims is universally rejected by scientists, theologians, philosophers and other humanists. Another, that "A scientist has the moral right to do anything he has the technical capacity to do in research," he finds more cecntroversial, suggesting, however, that even those who hold that this might be true for "pure research would raise moral questions about the right to use genetic technical developments. Mis third and fourth formulations both raise the crucial question of the normatively human: "A scientist has no right to intervene in the natural processes in such a way that he might alter vhat maa belicves to be, and value as the ®ost distinctively human characteristics,” znd "A scientist has the right to iatervene in the course of himan development in such a way that the vses of his knowledge foster geouth of thos: g 8 689 -60- distinctive qualities of life thai humans value most hizhly, and renove those qualities that ave deleterious to what is valued," Tt is the question of the norwnzively hwran which is raised by our sed not new capabilities in the field of genetics. The question is ra only by active intervealtion, but by counseling, screening and diagnosis as well. Work on this fundameatal question directly in the context of modern developments in genetics has hardly begun. Acknowledgment The cooperation of Marc Lappé, Tabitha Powledge, Sharmon Sollitto and Rosalie Miller in the preparation and criticism of this manuscript is acknowledged with gratitude. 93-999 (Pt. II) O - 73 - 23 Abbo, C., aad H. Zo11lw suet. 1870. Pronatal determination of aud chromosomal com 1:2156-217. Abelson, P, H. 1971. Ande about genetic cng Anderson, W, ¥. 1972, Geno therapy. fo Hamileon, M. (B1.): Genetics and the Feture of Moa. Grand Rapids, Mich.: REordmains, Pp. 109-124. Aposhian, H, V. 1970, The use of DNA fer gene therapy-the nead, experimental approach and implications. Perspect, Blol. Mad. 14: Beecher, H. RK. 1970. Research and the Tadividual: ‘Tuman Ztudies. Boston, Mass.: Little, Brown and Co. Berg, J. M., S. Gilderdale, and J. Way. 1969. 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Pp. 105-137. 700 THE FOUR CELTERS OF U.S. FOREIGN POLICY, By Lorman Cousins Feige THE Cli ZSE-SOVIET GAP VAGENS, By Hugo Portisch “Coryell's Ferry, 1776." by Joseph Pickett (sec page 35) PoE. TATA AS pIrettReal we an caeagn PATE ty { “0 | Baidu nnn seid ey i od Nglant Lad dec ienaande Side Ruswiirvw un —d oy BRI Arline Scheyn L700r + fol Loar Wopy fogs BEY OPW FO Gp pn reel) Bemilins vr ae warily bitte * SiH STOVE, fall» Blovninad fopfe Zou 35 of Loos 701 SR / Research | Ca SCIENCE & HUMANITY Sg DEPARTMENTS: Research in America eo Letters to the Science Editor EXPERIMENTS ON PEOPLE—THE GROWING DEBATE eT O WE NEED new rules for 1} experiments on people?” The question was asked by indirection in SR’s issue of October 6, 1962—just after the late United States Senator Estes Kefauver's amendments to the U.S. Food, Drug, and Cosmetic Act had heen approved by the Congress— and was asked again explicitly in SR's issue of February 5 last. The occasion for the repetition was the confusing phraseology of a disciplinary order against two New York City phy ians found guilty of “fraud and deceit” connection with the injection of live can- cor cells into twenty-two helpless old patients in the Jewish Chronic Discase Hospital of Brooklyn. The order had been voted by the New York State Board of Regents, which first suspended the licenses of the two accused doctors for a vear and then held the suspensions in abeyance on condition of good behavior. The fact that one of the two acensed— Dr. Chester Milton Southam—not only occupied a position of great prestige as an individual medical researcher but belonged to the stall of a famous Ameri- can medical institution, the Sloan-Ket- tering Institute for Cancer Research, shook the complacency that had obscured experimental ethics. Conservative clin- icians here and there in the country began to wonder about their own pro- fessional respousibility for the deterio- rating state of affairs. In Cleveland. Ohio, the Academy of Medicine and the Cuyahoga County Medical Society polled their respective memberships to determine a collective attitude, Since the Brooklyn cancer experiment had been exposcd by three young physi- cians whotopposed it and carried their opposition to My, William A. Hyman, a lawyer on the board of directors of the hospital involved, one of the questions: SY July 2, 1966 included in the Cleveland poll was: Are hospital directors and trustees in tune with the ethics of practicing physicians? It was discovered that experimentalists have much more ready access to hospital trustees than clinical physicians do. As one doctor explained it privately to SR’s science editor: “The usual member of a hospital board is a lay individual who has very little knowledge of medical matters. The responsibility for administration of the hospital is delegated to the hospital ad- ministrator, who is the influential force in the hospital. One or two members of the hospital board may be well informed, but they are exceptional and are usually dominated by the hospital administrator. The hospital administrator has a personal interest in publicizing the efforts of the various departments; men engaged in research are productive from his stand- point, so these are the individuals on the medical hospital staff who have close communication with him and to whom he turns for advice. The medical staff member whose primary interest is pa- tient care has very little influence in the direction of hospital policy and no chuan- nel of communication to the board of Arter the problem had been delib- erated for four months, a memorandum (reproduced on page 42) was sent out to chiefs of T and presidents of hos- pital boards of trustees in Cuyuhoga County. A “statement of position” re- viewed and approved by the medical practice and services committee, the ethics committee. and the hoard of diree- tors of the Academy of Medicine, said in part: There was vnanimity of opinion that physicians in the private practice of “One of the pivot medicine should play an independent role in advising on projects involving human expe tation, lhe practicing physician must be given a vital role in setting policy re- garding experiments to be carried out in a given institution involving human beings. He must be able to speak for the patient, the community, and the practicing phy 1. The presence of physicians at stafl discussions at which research projects are presented cannot be considered as indicating consent to the experiment nor can the inclusion of practicing phy- sicians in a minor and subsidiary post in the investigations be considered as implying consent to the projects. Our purpose is not to present an ob- stacle to the pursuit of scientific truth. We do not intend an intrusion into re- search and experimentation. We wish to emphasize, however. our very basic concern that the patient has human rights which must not be compromised. Ten days before the Cleveland memo as issued, the newly appointed Surgeon General of the U.S. Public Health Serv- ice, Dr. William 11. Stewart, addressed the American Federation for Clinical Re- search in annual session at Atlantic City. clinical research problems of the day,” he said, arose from “the judgments related to the use of human beings as research subjects.” He continued: There is a tendency te wave ide the legal aspects of the pmblem on the grounds that the Law is vague and certain at best, This is now strictly tra Enisting law is firm and clear on one principle: The decision to become a subject for research must be made by the subject. This concept is rooted in the basic principle that an individual has the right to control any use of his person. We may like it or not, but the indi- vidual subject aud only he, with all Lis 41 personal whines and superstitions and fables, can nike the portant cha Bema as fully informed as possible, 1 can ihe the choice tor any reason, or for no reason at all, LL No one denies that the legal princi ples need refinement, and that there are certain areas of darkness. For example, issues related to research with children wl with the mentally mconipetent are generally unresolved.” But if we accept the fundamental premise and wide ourselves accordingly, we shall be working within the accepted ley philosophical principles of our time and place: And if we do not? In my judument we ultimately threaten the future of esearch snpport in this conntry. The assembled researchers had heard hat Kind of talk often before. But what ame next jolted them. Always in the wast the U.S. Public Health Service had ACADEMY OF AND CUYAHOGA Cou 1031s Cameo ave Re ren Ours ners m0 [wei rT CHICFS OF STAFF Ail T0: 0 PRESIDENTS OF HOSPITAL BCADS The questionnaire addressed to you Comittee has produced an excellent resncnse. 702 evaded responsibility for abuse of pas tients” privacy by passing the buck to the individual experimenter. Dr. Stewart, however, enunciated a new policy: Reduced to its simplest terms, this policy seeks to avoid the danger of d rect federal intervention, case by case, on the one hand. and the dangers in- herent in deenion by an individual scientist on the other, We are assaming, essentially, that the medical school, hospital, or other medical research in- stitution—by accepting the administra- tion of public funds—accepts also a share of the public responsibility for their use. We are asking that the insti- tution assure ns that research pro- posals related to the use of human subjects are being systematically sub- jeeted to independent review, and we are urging that qualified individaals from outside the scientific arca be in- volved in this review. MEDICINE OF CLEVELAND NIV MEDICAL Sonny QUVIAND, OO 44106 + Croat 13300 May 10, 1966 OF TRUSTZES IH CUYAHOGA COUATY from the iledical Practice and Services It is otvious that all of you are vitally concerned with safeguarding tne welfare of patients and are keenly interested in seeing that patierts' welfare is given the most strincent safejuerd. There vas unanfcity of opinion that physicians in the private practice of medicine should play an independent role in advising on projects fnvolv- ng human experinentation. The practicing physician must be given a vital role in setting policy re- garding exp hur:an beings. and the practicing physician. nts to be carried out in a given institution involving lle must be able to speak for the natient, the community The presence of physicians at staff discussions at which research projects are presented cannnt be considered as indicating consent to the experirent nor can the inclusion of practicinn physicians in a rinor and subsidiary post in the investigations be considered as implying ccnsent to the projects. The questionnaires ture adopted to revieu rescerch projects, pethods of review, These will be Our purpose is not to present an obst Ve do not intend an intrusicn into research and experirentation. hasize, ho.izsar, our very basic concern that the patient has ¢ corpronised. truth, le wish to cv; human richts which must not submitted to us varied sorewhat in the form and struc- Two hospitals submitted excellent available to you {f you so desire. acle to the pursuit of scientific This statement of position has been reviewed and approved by the Hedicat Prectice and Scrvicas Co iitt + the Ethics Committee, and the 3oard of Directors of the Acadory of lledicinc. < 7b we igs b., Chara © Sincerely yours, [Jp llear 2-13 pesealit hf) Wize 0. Loukadfk, M.0. ident 7 72 er) Nile pd ety, 1.0.7 [hafman dicai Practice 8 Sirvices Connfttee Although he considered it “quite |, sible that some important research w, be delayed or perhaps lost” becanse ui the new policy, Dr. Stewart asserted his “conviction as a public official that the problem must be faced.” He proposed “a continuing dialogue” to evolve “better solutions.” AST month the invited debate opened with what had been intended as a whisper but came out as a shout. The New England Journal of Medicine pub- lished a paper signed by the occupant of the oldest endowed chair of anaesthesia on earth: Dr. Henry Knowles Beecher. of Harvard, who for thirty years has directed that university's anacsthes labora- tory at Massachusetts General Hospital During the lust decade and a half, he has campaigned quietly for a sharp upgrading of ethical considerations in experimental medicine. A small book he wrote on the subject is now read as a . His attitude boils down to a “firm tion of the golden rule.” pri- mary precept: An experimenter “has no right to choose martyrs for science.” As a simple safeguard against abuse of any patient, he advocates “the practice of having at least two physicians involved in experimental situations: first . . . the physician concerned with the care of the patient” and therefore primarily inter- ested in the patient's welfare; “second. the physician-scientist whose interest is the sound conduct of the investigation [that is, the experiment].” A man of astringent speech and manner, he sone- times strikes less scrupulous colleagues as an “avenging angel,” and he seemed cast in that role in March 1965 when he rose to speak at a symposium in Michizan on “Problems and Complexities of Clin ical Researc The most troubling problem he could see on the medical horizon was th problem of patient consent. He said so with customary precision. He also svid why. The “why” consisted of specific cases in which the rights of patients had been abused. This list of particulars wis 30 long and so utterly damning that 150 other prominent medical men David Rutstein of [Harvard and 1% Thomas Chalmers of Tufts—openh ac- cused Dr. Beecher ofexaggeration Anacrimonious deBate on stich a sore subject obviously held no advantace for the sponsor of the symposiun: the tp- john diag company. So « i Beecher's indictment was ent off abropt ly. He had na opportunity to asa his eosers, Although I avard’s confidence in his integrity was restated by mph ba ot tion several weeks Later thron pointment as chairman of tie con on man studies at haved AL School. he vatarally souaht fell vind cation. To that end, be tun documentation of fifty diferent cous to SR/Y onan 2, 1906 Na ”. ) pr. Joseph Garland, editor of The New EXPERIMENTS ON HUMANS—THE GROWING DEBATE England Journal of Medicine, Since the Journal conldn’t allot cuough space to coverzthem all, it was agfeed that the fifty, examples, would be reduced to twenty-two: still a shoekinir total. Names of involved physic and their res search institutions and the medical jour- nals in which their experiments were reported were omitted, But there was no honest way to eliminate mention of the twenty-five young soldiers who acquired” rheumatic fever because of an experi- | ment they didn’t know they were part | of, or the twenty-three unwitting experi- mental subjects who died unnecessarily of typhoid fever, or the children whose thymus glands were removed by doctors who couldn't possibly have known the 'YW77E ARE entering upon a period consequences of the surgery, or the de- | %. %/ of transition in the relationship liberate and dangerous manipulation of {| Vy between government as an ad- brains and hearts and livers to satisfy | ministrator of public funds for health other experimenters’ curiosity, or the | purposes on the one hand and non- mother who died of metastasis of a can- | governmental ‘biomedical science as a cer implanted in her body from the | generator of health knowledge on the body of her dying daughter. ~ other [SR, Oct. 5, 1963, Nov. 6, 1965]. The Massachusetts Medical Society, Funds appropriated for medical re- publisher of The New England Journal search are still going up, but not at the of Medicine, was no more eager for con- geometric progressions of a few years troversy over ethics than the Upjohn ago. And the public and the Congress company had been. Reproduction of the are beginning to ask searching questions Beecher text by lay publications was about the results of research and even therefore restricted to half or less of about the research process itself. what the Journal itself printed (see During the bonanza days of federal pages 45 and 46 of this issue of SR). rescarch support, fears of federal inter- Muted as the Beecher message thus was, ference accompanying federal dollars it novetheless commanded a full third of were kept in the background. Now, how- the front page of the Boston Herald on ever, there is a growing chorus of un- the moming of the Journal's publication. happiness about things as they are and Although The New York Times dutifully uneasiness about the future. played the story down on an inside page, This period of transition is of the high- its account made a full column of type. est importance to the Public Health No one involved in this aspect of the Service and to the institutions ethical debate=Dr. Beecher included— scientists of the nation. More basic still, paid enough attention to the fact that it is critically important to the future the Beecher report concerned only those health of the American people. It is experiments which had no hope or inten=} imperative that we manage the transi- tion of helping the individual patients’ tion succes fully, To this end we must who were being experimented on. Iva” engage in a continuing dialogue about sions of privacy committed by doctors as federal support and federal control. part of the patients’ own treatment were Let me put the question directly. ed over entirely. The one great mis-~ Does federal support _inevitably imply re of justice in the Kefauver drug’ federal control? ts so escaped the noto- My answer, with no apology, is a it deserves, The law still permits a © qualified “Yes.” phys wy physician) to undertake There are many derivative questions any experiment he chooses, without even which establish the qualifications: Coun- By WILLIAM H. STEWART, M.D. tel the patient what is going cn, gs = trol of what? How much control? Jong as iis the physician's own personal | Control exercised by whom, in what form? But to the basic question there can be no equivocation. Federal support does in fact imply some measure of fed- eral control over the uses of that support. How could it be otherwise? Federal opinion that the experiment is in the best interest of the patient; no consultations are required: no vecord-keeping is noces- sary; the individual physician is dictator. “fortunately, the public debate that Dr. Stewart invited (his text begins on this page) cannot be cireomseribed with- ont the consent of the patients. So let the coment begin, —Joux Lran, Science Viditor, Pope bs he fo be bbe Be be Be Be be Be le BB Dr. William H. Stewart is Surecon Gener- al. Public Health Seevi of Health, Education, remarks above are excerpted from 30 talk to the American Federation lor Chnical Research at Athotic City. an SR July 2, 1966 AN INVITATION TO OPEN DIALOGUE Surgeon General Stewart Makes It Official money is public money. The Public Health Service is entrusted with the administration of more than two billion public dollars this year. We are the agents of (he President, the Congress, and the people they represent. \Ve are, therefore, accountable to them. R ESPONSIBLE stewardship requires controls—in terms of priority of need, public interest, standards of quality. No one would, or should, tolerate a govern- mental agency which simply handed out money with no questions asked. Responsibility for stewardship is ex- ercised by the Public Health Service in a variety of ways. Research grant appli- cations are reviewed by a non-federal jury of scientific peers. Hospital con- struction grants are reviewed a state agency for compliance with the state's owh planning and priorities, We are now developing sets of standards to be ap- plied by state agencies in determining the eligibility of a medical facility to receive Medicare payments; for this purpose we are, incidentally, adopting standards already accepted by the pro- fessions concerned where such standards exist. In addition, there.are certain over- all qualifications for federal support on which assurances are required. One of these is the assurance that our funds, that is, the publics funds, are used for the purposes for which they are author- ized and granted. Another long over- due assurance is that federal funds are used without discrimination as to race, color, or national origin. These are the broad parameters of control. It is difficult ta quarrel with them in principle. You will note that the: Public Health Service almost never acts as both judge and jury in determining disbursement of funds, We are deeply committed to shared responsibility — vith non-federal scientists, with state agencies, with pri- vate organizations—in assessing priorities and propriet ain, 1 think, the principle is unas: When things get quarrelsonie is when the principles are applied to particular cases. For just as a govermmental agency which asked no questions wonld be un- 43 704 Reprinted From The Journal of The American Medical Association August 5, 1968, Vol 205, pp. 337-340 Copyright 1968, by American Medical Association Special Communication A Definition of Irreversible Coma Report of the Ad Hoc Committee of the Harvard Medical School ur primary purpose is to define irreversible coma as a new criterion for death. There are two reasons why there is need for a definition: (1) Improvements in resuscitative and supportive mea- sures have led to increased efforts to save those who are desperately injured. Sometimes these ef- forts have only partial success so that the result is an individual whose heart continues to beat but whose brain is irreversibly damaged. The burden is great on patients who suffer permanent loss of in- tellect, on their families, on the hospitals, and on those in need of hospital beds already occupied by these comatose patients. (2) Obsolete criteria for the definition of death can lead to controversy in obtaining organs for transplantation. Irreversible coma has many causes, but we are concerned here only with those comatose individ- uals who have no discernible central nervous sys- tem activity. If the characteristics can be defined in satisfactory terms, translatable into action—and we believe this is possible—then several problems will either disappear or will become more readily soluble. More than medical problems are present. There are moral, ethical, religious, and legal issues. Ade- quate definition here will prepare the way for bet- ter insight into all of these matters as well as for better law than is currently applicable. The Ad Hoc Committee includes Henry K. Beecher, MD, chair- man; Raymond D. Adams, MD; A. Clifford Barger, MD; William J. Curran, LLM, SMHyg; Derek Denny-Brown, MD; Dana I. Farnsworth, MD; Jordi Folch-Pi, MD; Everett I Mendelsohn, PhD; John P. Merrill, MD; Joseph Murray, MD; Ralph Potter, ThD; Robert Schwab, MD; and William Sweet, MD. Reprint requests to Massachusetts General Hospital, Boston 02114 (Dr. Henry K. Beecher). JAMA, Aug 5, 1968 e Vol 205, No 6 to Examine the Definition of Brain Death Characteristics of Irreversible Coma An organ, brain or other, that no longer functions and has no possibility of functioning again is for all practical purposes dead. Our first problem is to determine the characteristics of a permanently nonfunctioning brain. A patient in this state appears to be in deep coma. The condition can be satisfactorily diagnosed by points 1, 2, and 3 to follow. The electroencepha- logram (point 4) provides confirmatory data, and when available it should be utilized. In situations where for one reason or another electroencephalo- graphic montioring is not available, the absence of cerebral function has to be determined by purely clinical signs, to be described, or by absence of circulation as judged by standstill of blood in the retinal vessels, or by absence of cardiac activity. 1. Unreceptivity and Unresponsitivity.—There is a total unawareness to externally applied stimuli and inner need and complete unresponsiveness— our definition of irreversible coma. Even the most intensely painful stimuli evoke no vocal or other response, not even a groan, withdrawal of a limb, or quickening of respiration. 2. No Movements or Breathing.—Observations covering a period of at least one hour by physicians is adequate to satisfy the criteria of no spontaneous muscular movements or spontaneous respiration or response to stimuli such as pain, touch, sound, or light. After the patient is on a mechanical respira- tor, the total absence of spontaneous breathing may be established by turning off the respirator for three minutes and observing whether there is any effort on the part of the subject to breathe 705 338 IRREVERSIBLE COMA spontaneously. (The respirator may be turned off for this time provided that at the start of the trial period the patient’s carbon dioxide tension is with- in the normal range, and provided also that the patient had been breathing room air for at least 10 minutes prior to the trial.) 3. No reflexes.—Irreversible coma with abolition of central nervous system activity is evidenced in part by the absence of elicitable reflexes. The pupil will be fixed and dilated and will not respond to a direct source of bright light. Since the establish- ment of a fixed, dilated pupil is clear-cut in clinical practice, there should be no uncertainty as to its presence. Ocular movement (to head turning and to irrigation of the ears with ice water) and blinking are absent. There is no evidence of postural activity (decerebrate or other). Swallowing, yawning, vo- calization are in abeyance. Corneal and pharyngeal reflexes are absent. As a rule the stretch of tendon reflexes cannot be elicited; ie, tapping the tendons of the biceps, tri- ceps, and pronator muscles, quadriceps and gas- trocnemius muscles with the reflex hammer elicits no contraction of the respective muscles. Plantar or noxious stimulation gives no response. 4. Flat Electroencephalogram.—Of great confir- matory value is the flat or isoelectric EEG. We must assume that the electrodes have been properly ap- plied, that the apparatus is functioning normally, and that the personnel in charge is competent. We consider it prudent to have one channel of the ap- paratus used for an electrocardiogram. This channel will monitor the ECG so that, if it appears in the electroencephalographic leads because of high re- sistance, it can be readily identified. It also estab- lishes the presence of the active heart in the ab- sence of the EEG. We recommend that another channel be used for a noncephalic lead. This will pick up space-borne or vibration-borne artifacts and identify them. The simplest form of such a monitoring noncephalic electrode has two leads over the dorsum of the hand, preferably the right hand, so the ECG will be minimal or absent. Since one of the requirements of this state is that there be no muscle activity, these two dorsal hand elec- trodes will not be bothered by muscle artifact. The apparatus should be run at standard gains 10uv/ mm, 50xv/5 mm. Also it should be isoelectric at double this standard gain which is 5uv/mm or 25uv/5 mm. At least ten full minutes of recording are desirable, but twice that would be better. It is also suggested that the gains at some point be opened to their full amplitude for a brief period (5 to 100 seconds) to see what is going on. Usually in an intensive care unit artifacts will dominate the picture, but these are readily identifiable. There shall be no electroencephalographic response to noise or to pinch. All of the above tests shall be repeated at least 24 hours later with no change. The validity of such data as indications of irre- versible cerebral damage depends on the exclusion 93-999 (Pt. IT) O - 73 - 24 of two conditions: hypothermia (temperature be- low 90 F [32.2 C] or central nervous system de- pressants, such as barbiturates. Other Procedures The patient’s condition can be determined only by a physician. When the patient is hopelessly damaged as defined above, the family and all col- leagues who have participated in major decisions concerning the patient, and all nurses involved, should be so informed. Death is to be declared and then the respirator turned off. The decision to do this and the responsibility for it are to be taken by the physician-in-charge, in consultation with one or more physicians who have been directly involved in the case. It is unsound and undesirable to force the family to make the decision. Legal Commentary The legal system of the United States is greatly in need of the kind of analysis and recommenda- tions for medical procedures in cases of irreversible brain damage as described. At present, the law of the United States, in all 50 states and in the fed- eral courts, treats the question of human death as a question of fact to be decided in every case. When any doubt exists, the courts seek medical expert testimony concerning the time of death of the par- ticular individual involved. However, the law makes the assumption that the medical criteria for de- termining death are settled and not in doubt among physicians. Furthermore, the law assumes that the traditional method among physicians for determina- tion of death is to ascertain the absence of all vital signs. To this extent, Black’s Law Dictionary (fourth edition, 1951) defines death as The cessation of life; the ceasing to exist; defined by physi- cians as a total stoppage of the circulation of the blood, and a cessation of the animal and vital functions consequent thereupon, such as respiration, pulsation, etc [italics added]. In the few modern court decisions involving a definition of death, the courts have used the con- cept of the total cessation of all vital signs. Two cases are worthy of examination. Both involved the issue of which one of two persons died first. In Thomas vs Anderson, (96 Cal App 2d 371, 211 P 2d 478) a California District Court of Appeal in 1950 said, “In the instant case the question as to which of the two men died first was a question of fact for the determination of the trial court . ..” The appellate court cited and quoted in full the definition of death from Black’s Law Dictionary and concluded, “. . . death occurs precisely when life ceases and does not occur until the heart stops beating and respiration ends. Death is not a con- tinuous event and is an event that takes place at a precise time.” The other case is Smith vs Smith (229 Ark, 579, 317 SW 2d 275) decided in 1958 by the Supreme Court of Arkansas. In this case the two people were husband and wife involved in an auto accident. JAMA, Aug 5, 1968 e Vol 205, No 6 706 IRREVERSIBLE COMA 339 The husband was found dead at the scene of the accident. The wife was taken to the hospital un- conscious. It is alleged that she “remained in coma due to brain injury” and died at the hospital 17 days later. The petitioner in court tried to argue that the two people died simultaneously. The judge writing the opinion said the petition contained a “quite unusual and unique allegation.” It was quot- ed as follows: That the said Hugh Smith and his wife, Lucy Coleman Smith, were in an automobile accident on the 19th day of April, 19! said accident being instantly fatal to each of them at the same time, although the doctors maintained a vain hope of survival and made every effort to revive and resuscitate said Lucy Coleman Smith until May 6th, 1957, when it was finally determined by the attending physicians that their hope of resuscitation and possible restoration of human life to the said Lucy Coleman Smith was entirely vain, and That as a matter of modern medical science, your petitioner allege ud states, and will offer the Court competent proof that the d Hugh Smith, deceased, and said Lucy Coleman Smith, deceased, lost their power to will at the same instant, and that their demise as earthly human beings occurred at the same time in said automobile accident, neither of them ever regaining any consciousness whatsoever The court dismissed the petition as a matter of law. The court quoted Black's definition of death and concluded, Admittedly, this condition did not exist, and as a matter of fact, it would be too much of a strain of credulity for us to believe any evidence offered to the effect that Mrs. Smith was dead, scientifically or otherwise, unless the conditions set out in the definition existed. Later in the opinion the court said, “Likewise, we take judicial notice that one breathing, though unconscious, is not dead.” “Judicial notice” of this definition of death means that the court did not consider that definition open to serious controversy; it considered the question as settled in responsible scientific and medical cir- cles. The judge thus makes proof of uncontroverted facts unnecessary so as to prevent prolonging the trial with unnecessary proof and also to prevent fraud being committed upon the court by quasi “scientists” being called into court to controvert settled scientific principles at a price. Here, the Arkansas Supreme Court considered the definition of death to be a settled, scientific, biological fact. It refused to consider the plaintiff's offer of evi- dence that “modern medical science” might say otherwise. In simplified form, the above is the state of the law in the United States concerning the definition of death. In this report, however, we suggest that responsi- ble medical opinion is ready to adopt new criteria for pronouncing death to have occurred in an indi- vidual sustaining irreversible coma as a result of permanent brain damage. If this position is adopted by the medical community, it can form the basis for change in the current legal concept of death. No statutory change in the law should be necessary since the law treats this question essentially as one JAMA, Aug 5, 1968 e Vol 205, No 6 of fact to be determined by physicians. The only circumstance in which it would be necessary that legislation be offered in the various states to define “death” by law would be in the event that great controversy were engendered surrounding the sub- ject and physicians were unable to agree on the new medical criteria. It is recommended as a part of these procedures that judgment of the existence of these criteria is solely a medical issue. It is suggested that the phy- sician in charge of the patient consult with one or more other physicians directly involved in the case before the patient is declared dead on the basis of these criteria. In this way, the responsibility is shared over a wider range of medical opinion, thus providing an important degree of protection against later questions which might be raised about the particular case. It is further suggested that the de- cision to declare the person dead, and then to turn off the respirator, be made by physicians not in- volved in any later effort to transplant organs or tissue from the deceased individual. This is ad- visable in order to avoid any appearance of self- interest by the physicians involved. It should be emphasized that we recommend the patient be declared dead before any effort is made to take him off a respirator, if he is then on a res- pirator. This declaration should not be delayed until he has been taken off the respirator and all artificial- ly stimulated signs have ceased. The reason for this recommendation is that in our judgment it will pro- vide a greater degree of legal protection to those involved. Otherwise, the physicians would be turn- ing off the respirator on a person who is, under the present strict, technical application of law, still alive. Comment Irreversible coma can have various causes: cardi- ac arrest; asphyxia with respiratory arrest; mas- sive brain damage; intracranial lesions, neoplastic or vascular. It can be produced by other encepha- lopathic states such as the metabolic derangements associated, for example, with uremia. Respiratory failure and impaired circulation underlie all of these conditions. They result in hypoxia and is- chemia of the brain. From ancient times down to the recent past it was clear that, when the respiration and heart stopped, the brain would die in a few minutes; so the obvious criterion of no heart beat as synony- mous with death was sufficiently accurate. In those times the heart was considered to be the central organ of the body; it is not surprising that its fail- ure marked the onset of death. This is no longer valid when modern resuscitative and supportive measures are used. These improved activities can now restore “life” as judged by the ancient stand- ards of persistent respiration and continuing heart beat. This can be the case even when there is not the remotest possibility of an individual recovering consciousness following massive brain damage. In 707 340 IRREVERSIBLE COMA other situations “life” can be maintained only by means of artificial respiration and electrical stimu- lation of the heart beat, or in temporarily by-pass- ing the heart, or, in conjunction with these things, reducing with cold the body’s oxygen requirement. In an address, “The Prolongation of Life,” (1957), Pope Pius XII raised many questions; some conclusions stand out: (1) In a deeply un- conscious individual vital functions may be main- tained over a prolonged period only by extraordi- nary means. Verification of the moment of death can be detérmined, if at all, only by a physician. Some have suggested that the moment of death is the moment when irreparable and overwhelming brain damage occurs. Pius XII acknowledged that it is not “within the competence of the Church” to determine this. (2) It is incumbent on the physi- cian to take all reasonable, ordinary means of re- storing the spontaneous vital functions and con- sciousness, and to employ such extraordinary means as are available to him to this end. It is not obliga- tory, however, to continue to use extraordinary means indefinitely in hopeless cases. “But normally one is held to use only ordinary means—according to circumstances of persons, places, times, and cul- tures—that is to say, means that do not involve any grave burden for oneself or another.” It is the church’s view that a time comes when resuscitative efforts should stop and death be unopposed. Summary The neurological impairment to which the terms “brain death syndrome” and “irreversible coma” have become attached indicates diffuse disease. Function is abolished at cerebral, brain-stem, and often spinal levels. This should be evident in all cases from clinical examination alone. Cerebral, cortical, and thalamic involvement are indicated by a complete absence of receptivity of all forms of sensory stimulation and a lack of response to stimuli and to inner need. The term “coma” is used to designate this state of unreceptivity and un- responsitivity. But there is always coincident pa- ralysis of brain-stem and basal ganglionic mechan- isms as manifested by an abolition of all postural reflexes, including induced decerebrate postures; a complete paralysis of respiration; widely dilated, fixed pupils; paralysis of ocular movements; swal- lowing; phonation; face and tongue muscles. In- volvement of spinal cord, which is less constant, is reflected usually in loss of tendon reflex and all flexor withdrawal or nocifensive reflexes. Of the brain-stem-spinal mechanisms which are conserved for a time, the vasomotor reflexes are the most per- sistent, and they are responsible in part for the paradoxical state of retained cardiovascular func- tion, which is to some extent independent of nerv- ous control, in the face of widespread disorder of cerebrum, brain stem, and spinal cord. Neurological assessment gains in reliability if the aforementioned neurological signs persist over a period of time, with the additional safeguards that there is no accompanying hypothermia or evidence of drug intoxication. If either of the latter two con- ditions exist, interpretation of the neurological state should await the return of body temperature to normal level and elimination of the intoxicating agent. Under any other circumstances, repeated examinations over a period of 24 hours or longer should be required in order to obtain evidence of the irreversibility of the condition. Reference 1. Pius XII: The Prolongation of Life, Pope Speaks 4:393-398 (No. 4) 1958. 708 Reprinted from The Journal of the American Medical Association Oct 6, 1969, Volume 210 Copyright 1969, American Medical Association Experimentation m Children A Reexamimation of Legal Ethical Principles William J. Curvan, JD, SMHyg, and Henry K. Beecher, MD Reexamination of legal and ethical principles in the United States and England yields suggestions concerning standards for the use of children in clinical investigation. Where the research is therapeutic, a minor may be in- cluded if informed consent is obtained from the parents or guardian. Where the research is not therapeutic, minors may be included if 14 years of age or older and if intelligent and mature enough to give informed con- sent. Parental consent is also required with discernible A deal of attention has been given recently to the subject of legal and ethical constraints on medical experimentation in man.’ During the current decade we have seen the first enactment of federal laws and agency regulations in this field. Action in law has been accompanied by greater ef- forts on the part of investigators and research insti- tutions to provide effective self-regulation of clinical investigation, particularly through the use of pro- fessional review committees. One of the areas of this subject where further legal and professional guid- ance is required, however, concerns the involvement of children as subjects in clinical research studies. There would seem to be no disagreement with the need and the value of involving children in clinical research where the matter being studied is unique to the early years of life, or to adolescence, or where the problem is particularly acute or significant in children.” The problems that arise relate to the par- ticular vulnerability of children, the danger of long- term of later-occurring harm over their life span, and the incapacity of children to understand and to give consent to taking part in an investigation. This From the Harvard Medical School and the Massachusetts General Hospital, Boston The views expressed ave those of the authors and do not nec- essarily represent the position of the AMA. Reprint requests to 55 Shattuck St, Boston 02115 (Prof. Cur- ran) risks or hazards. For tissue and organ donation, the donor should be 14 years old or older and intelligent and ma- ture enough to give informed consent and have parental or guardian consent also. Donations should be restricted to relatives or close friends. Also children under 14 may participate in clinical investigation which is not for their direct benefit where the studies are sound, promise im- portant new knowledge for mankind, and there is no discernible risk. communication is an effort to reexamine some ol the pronouncements, legal and ethical, in this field and to offer some new interpretations of the per- missible boundaries for such research. We will sug- gest legal and ethical standards which can protect the interests and welfare of the child and which can also allow important and well-designed clinical in- vestigation to be conducted. The Legal Consent of Minors The primary legal issue in the use of children as subjects concerns their presumed mental and emo- tional incapacity to understand the nature and pur- pose of the experimental procedure and protocol and to weigh the risks it may entail for them. Be- cause of this immaturity, the common law generally declares minors (persons under 21 years of age) to be incapable legally of giving consent to a medical procedure or treatment to be performed upon them." The intent behind the law is to protect the minor from harm which may result from his own ignorance or rashness, and from situations where he cannot be expected to resist undue coercion or persuasion to give his consent. As noted earlier, however, this general rule is based upon a presump- tion of immaturity which continues to the arbitrary age limit of 21 years. It is readily admitted that Experimentation —Curran & Beecher 77 709 many minors are intellectually and emotionally able to make judgments on many issues at ages substan- tially below 21. In actual cases, the ability of the minor to assess the situation, understand it, and to arrive at conclusions will depend first on his own level of intelligence and emotional maturity, and second on the complexity and technical content of the issues confronting him. In realization of this, some American legal jurisdictions have modified the common law rule and have allowed minors to con- sent to certain medical procedures under these cir- cumstances. The Court Decisions In Bishop vs Shurley,' the Michigan Supreme Court held that a 19-year-old boy was intelligent and mature enough to choose a local anesthetic over a general anesthetic in a tonsillectomy, even though his parents had selected the general anesthetic. In a Mississippi case® a 17-year-old boy employed by a railroad was found legally capable of consenting to a smallpox vaccination given to him in the course of his employment. In Bakker vs Welsh," an earlier Michigan decision, a 17-year-old boy was found capable of consenting to an operation to remove a tumor from his ear. In accordance with the reasoning in these cases, the highly respected American Law Institute has this to say in its Restatement of the Law of Torts: If a child . . . is capable of appreciating the nature, ex- tent and consequences of the invasion [ie, the medical pro- cedure or treatment], his assent prevents the invasion from creating liability, though the assent of the parent, guard- ian or other person is not obtained or is expressly refused.” It must be admitted that there are American decisions contrary to this position. In Lacey us Laird,” the Ohio Supreme Court in a severely split decision held that a technical battery was com- mitted upon an 18-year-old girl who consented to a plastic surgery operation to improve the appear- ance of her nose. Parental consent had not been ob- tained. The minority of the court was of the opin- jon that the 18-year-old plaintiff could be found legally capable of consenting to the procedure. In their opinion, the minority reviewed the decisions allowing such a consent and pointed out that many of these cases involved minors younger than in the case before them. They also pointed out that the decision of the majority could be said to be con- trary to the state legislature’s intentions, since by statute a girl of 16 could consent to sexual inter- course and thus remove any charge of rape against her companion. They also said that the majority ruling raised “some other interesting questions” They asked, For example, does any boy who kisses a girl under 21 with her consent but without the consent of her parents thereby expose himself to an action for assault and battery; and 78 JAMA, Oct 6, 1969 e Vol 210, No 1 does every high school football player run the risk of as- sault and battery actions by boys under 21 with or against whom he plays? The Significance of Parental Consent These statements are not intended to provide an argument for the removal of the requirement of parental consent to most medical procedures per- formed on their children, whether the procedures are therapeutc or experimental in nature. Parental consent would continue to be required for all chil- dren younger than in their later teens. Even for minors close to their majority, such as college stu- dents from 17 to 21, parental consent should be ob- tained in medical situations requiring surgery or hospitalization. The only circumstances where parental consent is abrogated entirely and the decision is solely in the hands of the minor is when the minor is released or freed (known in the law as “‘emancipated”) from parental control and support. This occurs when the minor marries or when he or she leaves the parental home and undertakes his or her own support with parental concurrence, or when the parent abandons the child and neglects to supervise and to support the child. In emergency situations, of course, medical treat- ment may be given to a child of any age without parental consent in order to save his life or to pre- vent serious or permanent injury or harm. Parental consent would be necessary for continued treatment after the emergency has been met. Most American jurisdictions also have statutory law which allows the courts to abrogate parental authority and to order medical treatment or sur- gery upon a minor to save his life or to prevent seri- ous or permanent injury when the parents have neglected the child or have refused unreasonably to consent to the procedure. The courts will examine carefully each case on its merits and will act in the best interests of the child. The Issue of ‘Benefit’ None of the decisions or statutes cited here in- volved experimental situations or cases where the child was offering help to others. In all of these cases there was no question that the child was ex- pected to benefit directly from the clinical treat- ment or surgery, or from the preventive inoculation. Only on very rare occasions have the courts been faced with legal cases in which such “benefit” could not be assumed. The leading decision in this field is Bonner vs Moran.” The case has been much dis- cussed and much misunderstood. A detailed exami- nation of the facts and the reasoning of the court is essential to an understanding of its holding. The child involved was 15 years of age. A cousin had been severely burned and skin grafts were ad- vised. A number of unsuccessful attempts were made to find a donor with matching blood type. The mother of the burned child went to the home Experimentation—Curran & Beecher 710 of the 15-year-old and persuaded him to go to the hospital for a blood test. The boy’s mother was ill and was not informed. The boy’s blood did match and the surgeons went ahead with the first of a se- ries of grafts. The boy returned home after the first graft and informed his mother of what had hap- pened. He returned again to the hospital for a total of more than two months while the grafting was done. The mother of the donor child brought an action of assault and battery against the surgeon who per- formed the operations. She alleged that she did not consent and that the consent of the child, which was admitted, was immaterial. In the trial court, the judge ruled (in his charge to the jury) that if the donor boy was found to be “capable of appreciating and did appreciate the na- ture and consequences of the operation and actually consented, or by his conduct impliedly consented,” then there was no assault and battery, even though his mother might not have consented. On appeal, the United States Court of Appeals for the District of Columbia, a highly respected court, reviewed this ruling. It found the ruling to be in accordance with the cases and with the Restate- ment of Torts cited earlier in this report. The court expressed no disagreement with these authorities. However, it distinguished them from the case in hand because of the fact that the donor child re- ceiver no direct or indirect benefit from the medi- cal procedure involved. It noted that the grafting involved pain and discomfort for the boy and a loss of schooling of about two months. On this basis, it returned the case to the trial court to make a find- ing on the consent of the mother which it held es- sential to the case. The court admitted that this was a difficult ruling from the physician’s stand- point. The court noted that the doctor acted totally “without compensation” and “impelled wholly by humane and charitable motives.” The court also noted that the jury, in a retrial, could well find that the mother at least impliedly consented to the later operations and ratified the first operation by her conduct. The court noted that there was evidence that the mother “was apprised of her son's hero- ism and gloried in the newspaper notoriety” over the case which also “resulted in public contribu- tions of money for the boy's future education.” (The year of the case was 1941 when such skin homografting was relatively novel.) This is the holding of the Bonner case. It is still the leading, if not the only, appellate court case di- rectly in point on this issue in an American juris- diction. Tt should be noted thatithe case does not hold that medical procedures cannot be performed on minors where there is no direct benefit to them. On the contrary, it holds that such procedures can be legally permitted as long as the parents (or oth- er guardians) consent to the procedure. [The case specifically sanctions “heroic” actions in contribu- tion to others. The only other cases generally cited on this JAMA, Oct 6, 1969 e Vol 210, No 1 “benefit” issue are the Massachusetts decisions au- thorizing the donation of a kidney by an identical twin to his sibling twin." These decisions are not binding precedent of the same character as the Bonner case. They were three opinions by single justices of the Supreme Judicial Court of Massa- chusetts in declaratory judgment proceedings. The decisions were not appealed to the full bench and do not appear in the official publications of decisions of that court. The decisions are summarized and dis- cussed by one of the authors elsewhere. The Massachusetts cases involved a 19-year-old prospective donor in the first case and 14-year-old donors in each of the two later cases. Three differ- ent justices heard the three requests for legal au- thorization and all ruled in the same way and on the same grounds. In each case, the justice found that the donor twins understood the situation and the risks involved for themselves. They also under- stood that their siblings were suffering from end- stage renal disease and the transplants were an ef- fort to prolong their lives. At the time, 1957, such transplants could only be expected to be successful in identical twins because of the antigen-antibody rejection. The justices were convinced that the don- ors wanted to make the gift of a kidney in an effort to save the brothers they loved. In addition, the parents gave their own full consent. In fact, the parents joined with the surgeons and the hospital in requesting the declaratory judgment. The issue of “benefit” was raised in these cases and Bonner vs Moran was cited. However, counsel for the parties offered evidence which made it un- necessary for the court to make a finding that there would be no benefit to the well donor-twin. The tes- timony of a psychiatrist was presented in which the expert witness who had interviewed the children gave it as his opinion that the donor-twin in each case would suffer a grave emotional disturbance if he were not allowed to make the donation and the sick twin were to die. On the basis of this testi- mony, the justices found that the “operation is necessary for the continued good health and future well-being” of the donor twins and would confer “a benefit” upon them as well as upon the sick twins. These opinions have sometimes been miscon- strued as supporting the proposition that medical procedures, including experimentation, cannot be performed upon minors, even with parental consent, unless there is direct benefit to them from the pro- cedures themselves. As can be seen, this is not what the cases involved. The well donor-twins did not derive direct physical benefit from the surgery per- formed upon them. Like the young skin donor in the Bonner case, they made a sacrifice, a gift, a heroic offering, to their relatives. The direct benefit was to the recipient, not to the donor. However, the Massachusetts court also found “benefit” in the prevention of an emotional loss, the early death of the sick identical twin. This explanation of the “benefit” theory is offered in the report by Cur- ran." The Massachusetts decisions can therefore be Experimentation—Curran & Beecher 79 711 said to authorize procedures upon minors even as young as 14 years old where there is an indirect benefit to the child. It remains for later cases to spell out just how indirect this benefit can be. American Codes As noted earlier, there has been a great deal of activity in recent years in the United States in pro- ducing legal and ethical codes governing human ex- perimentation. Only limited attention has been given to the issue of the use of children in clinical studies. The so-called Nuremberg Code does not mention children specifically. However, it does re- quire that “the person involved should have legal capacity to gve consent.” On a strict interpretation, this phrase could outlaw all experimentation on children, at least those under 14 or so who cannot be found mature enough and intelligent enough to give their own consent, and on mentally incom- petent adults. However, the phrase is generally tak- en to mean that in these cases the consent of a legally competent parent or guardian is required. In the Food and Drug Administration’s regulations, which follow the Nuremberg Code closely in the consent requirement, the consent of a “representa- tive” may be obtained for an incompetent sub- ject." The AMA Ethical Guidelines for Clinical Investi- gation (adopted Nov 30, 1966) permit clinical in- vestigation involving children in nontherapeutic situations (“primarily for the accumulation of sci- entific knowledge”) on the following basis: 4C. Minors or mentally incompeten® persons may be used as subjects only if . The nature of the investigation is such that mentally competent adults would not be suitable subjects. ii. Consent, in writing, is given by a legally authorized representative of the subject under circumstances in which an informed and prudent adult would reason- ably be expected to volunteer himself or his child as a subject. By definition, this type of investigation involves no direct benefit to the child. Also, the AMA Guide- lines do not require that there be no risk involved in the study. The Guidelines of the United States Public Health Service (PHS), first issued in February 1966 and revised in July 1966, did not make any special provisions concerning children. A clarifica- tion issued in December of the same year contains the first mention by the PHS of the use of children as subjects. It says, Whatever the nature of the investigation, the concern for the protection of the subject and for the assurance of voluntary participation becomes most critical when the subject is not of age or competence to make an adequate judgment on his own behalf.'* There is no further restriction regarding the na- ture of investigations where children may be used 80 JAMA, Oct 6, 1959 e Vol 210, No 1 and no requirement of direct benefit to the minor subject. In the latest clarification of the Guidelines issued on May 1, 1969, however, in discussing methods to be used in obtaining “adequate, appropriate, in- formed consent,” it is asse: , “A parent, for ex- ample, may have no authority to expose his child to risk, except for the child’s own benefit.”"* It would seem that the PHS is merely attempting to caution institutional review committees concern- ing the legal right of parents to consent to the in- volvement of their children in such studies. As noted earlier, this view has been expressed, usually by nonlegal commentators. We respectfully submit that it is too sweeping a statement and can be mis- construed. On the face of it, the statement has legal support only in regard to young children, not to all minors. Bonner vs Moran and the Massachusetts cases specifically allow parents to consent to pro- cedures involving clear risks where there is no direct benefit to the child. The Bonner case requires no benefit at all as long as both the child and the par- ent give valid consent. The English View American common law is derived from the En- glish common law. The basic principles concerning the rights of minors and the obligations of parents are the same in both countries. There seems to have been as much misconception of the law by English commentators as by American. For example, Papp- worth in his much quoted Human Guinea Pigs" asserts, The law both here and in America appears to be very definite, namely, that parents, either singly or together, cannot give valid legal consent to any action that is not for the immediate benefit of the child concerned. This position as taken by Pappworth is often stated at medical and scientific meetings, yet our own research into English law produces no author- ity to support such a flat statement. There have been no English precedents which have involved the “benefit” problems presented by the underage donor cases of Bonner vs Moran and the Massa- chusetts opinions discussed earlier. English law is thus essentially silent on these issues. The respected and authoritative British Medical Research Council has, however, published a statement concerning re- search involving children.'® The essential parts of the statement are as follows: The situation in respect of minors and mentally sub- normal or mentally disordered persons is of particular difficulty. In the strict view of the [English] law parents and guardians of minors cannot give consent on their be- half to any procedures which are of no particular benefit to them and which may carry some risk of harm. Whilst English law does not fix any arbitrary age in this context, it may safely be assumed that the Courts will not regard a child of 12 years or under (or 14 years or under for boys in Scotland) as having the capacity to consent to any Experimentation—Curran & Beecher 712 procedure which may involve him in an injury. Above this age the reality of any purported consent which may have been obtained is a question of fact and as with an adult the evidence would, if necessary, have to show that irre- spective of age the person concerned fully understood the implications to himself of the procedures to which he was consenting In the case of those who are mentally subnormal or mentally disordered the reality of the consent given will fall to be judged hy similar criteria to those which apply to the making of a will, contracting a marriage or other wise taking decisions which have legal force as well as moral and social mmpheations. When true consent in this sense cannot he obtained, procedures which are of no direct benefit and which might carry risk of harm to the subject should not be undertaken Even when true consent has been given by a minor or a mentally subnormal or mentally disordered person, con siderations of ethics and prudence still require that, if pos sible, the assent of parents or guardians or relatives, as the case may be. should be obtained. Investigations that + of no direct benefit to the in- dividual require, therefore, that his true consent to them shall be explicitly obtained. After adequate explanation. the consent of an adult of sound mind and understanding can be relied upon to be true consent. In the case of chil- dren and young persons the question whether purported consent was true consent would in each case depend upon facts such as the age. intelligence, situation and character of the subject and the nature of the investigation. When the subject is below the age of 12 years, information re- quiring the performance of any procedure involving his body would need to be obtained incidentally to and with- out altering the nature of a procedure intended for his individual benefit We would like to point out that this statement does not outlaw all clinical investigation on all children where there is no direct benefit to them, as Pappworth suggests. The statement applies a benefit requirement only to minors below the age of 12 years. In the teens and older, the statement specifically asserts that it is a question of fact (just as in the American cases cited earlier) whether or not the particular child involved is intelligent and mature enough to understand the implications of the procedures to himself; ie, the risks he runs by entering upon the experiment. The statement does suggest (paragraph 3) that in all cases even where “true consent” is given by the minor (over 12 years of age) that considera- tions of “ethics and prudence” still require that, if possible, parental or guardian consent be obtained. No quarrel can be made with this suggestion. It is not a legal requirement. It is “prudent” to obtain such consent where it can be done merely to avoid questions and issues later. Most lawyers would agree fully, since they will always counsel their clients to avoid legal questions where this can be done. Tt is important, however, to realize that this is not a legal requirement but a precautionary prac- tice to make doubly sure of the firmness of one’s grounds. The final paragraph of the quoted portions of the statement should also be studied carefully. The first sentence of the paragraph sanctions investiga- tions where there is no “direct benefit” as long as there is “true consent.” Such consent can be given JAMA, Oct 6, 1969 e Vol 210, No 1 by an adult or by a minor intelligent and mature enough to make the necessary judgment. It is thus clear that minors over 12 years of age can consent to participate in clinical investigations where there is no direct benefit. Only the last sentence of the paragraph returns to the restriction regarding the use of children under 12 years of age. It would seem that such children can be involved in investigations only where the studies are intended for their indi- viduai benefit. However, it should be noted that the first paragraph, when it calls attention to “the strict view” of the English law, speaks not only of lack of benefit but couples it with carrying “some risk of harm.” If this further qualification can be added to the last paragraph, then children under 12 or 14 may be involved legally and ethically in clinical studies which are not part of their own therapy as long as no discernible risk is involved. One of the authors (H.K.B.) has been in corres- pondence with the British Medical Research Coun- cil concerning this statement. He asked for further information regarding the legal precedent or au- thority upon which the “strict view” of English law was based, since no legal citations had been provided in the original statement. The inquiry was referred to Sir Harvey Druitt, KCB, who answered by letter dated Dec 16, 1968. Sir Harvey has al- lowed us to refer to and to quote from his letter. First, he writes that the legal position taken in the statement of the Research Council was based upon his advice. He then continues, “I am confident about the correctness of that statement, but I can- not cite any Statute or decided case which is exactly in point.” The letter concludes with the following summary paragraph: It follows from the foregoing that a parent's right fo assault his child is in law strictly limited. No doubt the parent has the right to consent to a doctor carrying out upon his child medical procedures which are thought to be for the child's benefit. But I am confident that the parent has no legal authority to consent to medical procedures being carried out on his child for the advancement of sci- entific knowledge or for the benefit of humanity, if those procedur: ‘are of no particular benefit to” the child an: “may carry some risk of harm.” Suggested Standards for Investigation Involving Children It is hoped that the foregoing legal review pro- vides enough background so that some basic sug- gestions can be made regarding legal and ethical standards for clinical investigation involving chil- dren. 1. Where the research is therapeutic in nature, ie, where the minor is a patient and the study is intended to benefit him in the relief of his present clinical condition, or where the study is intended to add to knowledge about his present condition, then a minor of any age may be included in the study as long as informed consent is obtained from the minor's parents or guardian. Studies which are therapeutic in nature are generally defined in the Experimentation—Curran & Beecher 81 713 regulations of the Federal Food and Drug Adminis- tration.'” The concept of “informed consent” is adequately discussed elsewhere''® and is now gen- erally accepted by reputable investigators as an ethical and legal standard of primary importance. It is admitted that the nature of informed consent (giving full information on the risks and benefits reasonably to be expected) and the complexities often surrounding its attainment are such that sometimes it becomes only a goal toward which we strive. In any case, it is clear that informed consent requires that the parents be apprised of the experi- mental nature of the procedure, distinguishing it from the assumed treatment being received by the patient-subject-child who is involved. 2. Where the research is not therapeutic in na- ture, subjects (either patients or volunteers) who are minors may be included in the investigation if the minor is 14 years of age or older and is found after interview by the research team to be intelli- gent enough and mature enough to understand the nature of the experiment and its purposes (in a general, nontechnical manner) and the hazards reasonably to be expected to him, and gives his consent thereto. In addition to the consent of the minor, the informed consent of parents is also required in such situations only where there are discernible risks or hazards beyond simple incon- venience. Particularly well-informed and intelligent minors who are close to 21 years of age, such as 19- and 20-year-old medical students or college students majoring in biomedical sciences, may be allowed to enter into clinical investigations which other less technically trained minors, or adults, would not be able to understand. However, even with such subjects, parental consent (as well as the consent of school authorities in many universities) is required where discernible risk or hazard is in- volved. Clinical investigations in this category should always be well designed and carried out by qualified researchers. Involvement of minors should always be justified as either necessary or highly desirable for various scientific reasons which need not be specified here. We would not limit such studies to those which can be conducted only on children. This is an unnecessarily restrictive stand- ard where the minor is old enough, intelligent enough, and mature enough to understand and to give his informed consent as indicated herein. Such studies may be quite general in nature without direct benefit to the minor and intended only to increase knowledge of a particular disease or physi- ological functioning. The risks or hazards should be measured independently of the hoped-for gains in knowledge from the study. Minors should be allowed to volunteer for the study on altruistic grounds where the hazards are not too great to allow it. Parents may give their own consent to permit their children (of proper age, etc) to volun- teer under such circumstances as a means of en- couraging attitudes of unselfish service in their children. No coercion should be exerted on either 82 JAMA, Oct 6, 1969 e Vol 210, No 1 the minors or their parents in this vein by the re- search team, however. No prospective minor sub- jects or their parents should be made to feel guilty for not volunteering in situations such as those de- scribed here. 3. Special circumstances should exist for the legal and ethical justification of using minors over the age of 14 as donors of organs or tissue in experi- mental procedures. In such cases, the donor is not involved as a “subject” in the sense used in either of the first two situations discussed here. In each of those mentioned, a particular form of clinical innovation is tried out on the subject “as if” he were a patient or control in treatment or surgery. In the case herein, however, the donor-minor is entirely healthy and is used, not as a subject but as a reservoir of human organs or tissue. He is a “sub- ject” only in the fact that he is part of a two-person clinical investigation where the only possible physi- cal benefit is to the donee. The investigators may, of course, learn something about the donor side of the two-person procedure from the procedures used to remove the tissue from the donor and in the necessary matching and rejection mechanisms. In this sense, the donor is likened to the subjects in the second situation cited where no direct benefit to the subject is derived but where there is a con- tribution to scientific knowledge from which the subject may derive indirect benefit to himself, his family, or to mankind at a later time. However, the situation for the underage donor of an organ or tissue is different in that the primary objective is of direct benefit to another person at that time and as the direct result of the surgery. The surgery itself always involves risk. Tissue donation may involve scarring. Organ donation from a living donor always involves anatomical loss which leaves the person more vulnerable than before. In all do- nation cases, the minor-donor must meet all of the qualifications cited in item 2, including age (14 and over), intelligence, and maturity. His informed con- sent must be assured as well as that of his parents or guardian. (For anatomical gifts to take effect after death, the Uniform Anatomical Gift Act, which has been enacted into law in a number of states, authorizes gifts by persons 18 years of age or older without parental consent.) In addition, the donee should be a relative or a close friend of the child to whom the child feels love or affection enough to make this sacrifice. Such donations should always be regarded as heroic acts of charity in a very true sense. This standard is in accordance with the leading American case on the subject, Bonner vs Moran, discussed earlier. A requirement of such close relationship as siblings or an avoidance of “emotional loss” to the donor as set forth in the Massachusetts cases is rejected as unnecessarily narrow in application. However, in cases of dona- tion of an organ to a member of the immediate family, we would suggest that the age for an eligible donor might be more flexible than the arbitrary level of 14 set out in item 2. Children 7 years of Experimentation - Curran & Beecher 714 age or older (the time-honored age of “discretion”) might be considered for such donations if they were found clearly to understand the nature of the pro- cedures and the loss and risks to themselves in- volved. 4. There should be strong reasons in professional judgment for the use of immature children (those under 14 years of age) in any clinical investigation where there is no direct benefit intended for the child. However, such involvement should not be ruled out as illegal and unethical in all circum- stances. Neither American nor English laws de- mands such a flat and sweeping condemnation. Such involvement should be allowed where the study has firm medical support and justification, promises important new knowledge of benefit to science and to mankind, and where there is no discernible risk involved for the child-subject. Not to allow such studies would greatly hamper im- portant nutritional, psychological, and educational studies in children as well as studies of inborn errors or metabolism and genetic defects. It should be noted also that studies in this category, involv- ing no discernible risk, can be potentially, and sometimes unexpectedly, of direct benefit to a given subject. References 1. Special Issue, Ithical Aspects of Ixperimentation With Human Subjects, Daedalus, 98:219-597 (No. 2) 1969. 2. Hill, AB: Medical Ethics and Controlled Trials, Brit Med J 1:1043-1049, 1963. 3. Prosser, W.L.: The Law of Torts, ed 3, St. Paul, Minn: West Publishing Co., 1964 4. Bishop vs Shurley, 237 Mich 76, 1926. 5. Gulf and Ship Island Railroad Co. vs Sullivan, 155 Miss 1, 1928. 6. Bakker vs Welsh, 144 Mich 632, 1906. 7. Restatement of Torts, Section 59a, Philadelphia: American Law Institute Publishing Co., 1959 8. Lacey vs Laird, 1966 Ohio St 12, 1956. 9. Bonner vs Moran, 126 F 2d 121 DC Cir, 1941. 10. Masden vs Harrison, No. 68651 Eq, June 12, 1957; Huskev vs Harrison, No. 68666 Eq, Aug 30, 1957; Foster vs Harrison, No. 68674 Eq, Nov 30, 1957. 11. Curran, W.J.: A Problem of Consent: Kidney Transplan- tation in Minors, New York Uni Law Rev 34:891-898, 1959. JAMA, Oct 6, 1969 e Vol 210, No 1 12. Consent for Use of Investigational New Drugs on Humans: Statement of Policy, Food and Drug Administration, Federal Register, No. 11415, Aug 24, 1966. 13. Requirements for Review to Insure the Rights and Welfare of Individuals: Clarification, Washington, DC: Public Health Service, Dec 12, 1966. 14. Protection of the Individual as a Research Subject, Wash- ington, DC: Public Health Service, May 1, 1969. 15. Pappworth, M.H., Human Guinea Pigs, London: Routledge & Kegan Paul, Ltd., 1967. 16. Responsibility in Investigations on Human Subjects, Medical Research Council, Great Britain, 1963. 17. Curran, W.J.: Governmental Regulation of the Use of Hu- man Subjects in Medical Research: The Approach of Two Fed- eral Agencies, Daedalus, 98:542-595, 1969 18. Beecher, HK.: Some Fallacies and Errors in the Applica- tion of the Principle of Consent in Human Experimentation, Clin Pharm Ther 3:141-145, 1962. 19. Ladimer, I: Ethical and Legal Aspects of Medical Re- search on Human Beings, J Public Law, 3:467-511, 1955 Experimentation—Curran & Beecher 83 Printed and Published in the United States of America C-6-A.3 SM 30M 4.71 LAURRICT To From 715 MOUNT SINAI SCHOOL OF MEDICINE NEW YORK All Members of the Faculty Date Dr. S. Kupfer Subject The Research Committee has asked that this memorandum be distributed by the Dean's Office to all members of the Faculty. In essence this represents a revision of a previous bulletin (dated 7/71) on this sub- ject. The Committee has asked me to emphasize the importance of the new information contained in this memorandum. SK/sw Encl/as above May 12, 1972 Clinical Research XK 716 MOUNT SINAI SCHOOL OF MEDICINE MOUNT SINAI HOSPITAL TO: ALL MEMBERS OF THE FACULTY AND PROFESSIONAL STAFF CLINICAL RESEARCH The Research Administrative Committee wishes to inform all Principal Investigators and members of the professional staff of the School of Medicine and Hospital that all research contemplated, including clinical investigations, must receive the prior approval of the Chairman of Department in which the work will be carried out and the Research Administrative Committee. The Declaration of Helsinki which out- lines recommendations to guide doctors in clinical research has been approved by the Research Administrative Committee, and will form the basis for the conduct of clinical investigation at this Institution. When research procedures -- regardless of their scope, extent or nature -- are to be carried out upon patients, it is incumbent upon the physician to explain care- fully each proposed procedure to the patient or a responsible relative and answer all questions fully, before requesting his signature on the Hospital's consent form. While the Board of Hospitals of the City of New York requires that research performed on public charge patients must be carried out with the informed consent of the patient, this institution requires that this principle apply to research procedures performed on any patient in the Hospital, regardless of the financial arrangements. The standard consent form should be used, with the insertion of the specific nature of the research to be done. The signature of the patient or a responsible relative, or guardian, should be witnessed, preferably by a second physician who has observed the explanation of the procedure; in addition, a state- ment indicating that the patient or responsible relative, or guardian, understands the procedure should be included as a part of the consent form. Special provisions have been made and special forms are available, which include these requirements, for all investigations carried out on the Clinical Research Center facility. Rigorous adherence to this principle of informed consent is essential wherever the study is to be carried out in the Hospital, and will serve to protect the best interests of the investigator, the Hospital and the School of Medicine. Furthermore, the chances that patients and their families will misunder- stand or misconstrue the research to be undertaken will be greatly reduced. Prior approval by the Research Administrative Committee, for any clinical study to be undertaken, will insure that the protocol as outlined meets acceptable moral and professional standards. A full description of the approved protocol to be followed in carrying out the particular studies to be performed must be recorded by the principal investigator and/or his co-investigators in the patient's hospital chart. The patient's continu- ing progress and all results of these investigational studies also must be recorded in the patient's hospital chart. Adherence to these guidelines will assure high standards of patient-care and retrieval of important data should this be required. If the investigator desires to change a protocol previously approved by the Research Administrative Committee, such change must be submitted on the proper form for re- view and approval by the Research Administrative Committee before the new pro- cedure may be undertaken. It is the responsibility of the Principal Investigator to abide by the Institutional policy. 7/71 6/1/72 717 DECLARATION OF HELSINKI RECOMMENDATIONS GUIDING DOCTORS IN CLINICAL RESEARCH Adopted by the 18th World Medical Assembly, Helsinki, Finland, 1964 Introduction It is the mission of the doctor to safeguard the health of the people. His knowledge and conscience are dedicated to the fulfillment of this mission. The Declaration of Geneva of The World Medical Asso- ciation binds the doctor with the words: «The health of my patient will be my first consideration» and the Inter- national Code of Medical Ethics which declares that «Any act. or advice which could weaken physical or mental resistance of a human being may be used only in his in- terest.» Because it is essential that the results of lsboratory expe- riments be applied to human beings to further scientific knowledge and to help suffering humanity, The World Medical Association has prepared the following recommen- dations as a guide to each doctor in clinical research. It must be stressed that the standards ss drafted are only a guide to physicians sll over the world. Doctors are not relieved from criminal, civil and ethical responsibilities un- der the laws of their own countries. In the field of clinical research a fundamental distinction must be recognized between clinical research in which the sim is essentially therapeutic for s patient, and the clinical research, the essential object of which is purely scientific and without therapeutic value to the person subjected to the research. 1. Basic Principles 1. Clinical research must conform to the moral and scien- tifrc principles that justify medical research sand should be based on laboratory and animal experiments or other scien- tifically established facts. 2. Clinical research should be conducted only by scien- tif cally qualified persons and under the supervision of a qualified medical man. 3. Clinical research cannot legitimately be carried out un- less the importance of the objective is in proportion to the inherent risk to the subject. 4. Every clinical research project should be preceded by careful assessment of inherent risks in comparison to fore- seeable benefits to the subject or to others. §. Special caution should be exercised by the doctor in performing clinical research in which the personality of the subject is liable to be altered by drugs or experimental pro- cedure. of World Medical A Reprint World Medical Journal — 11. Clinical Research Combined with Professional Care 1. In the treatment of the sick person, the doctor must be free to use a new therapeutic measure, if in his judgment it offers hope of saving life, reestablishing health, or alle- visting suffering. If at all possible, consistent with patient psychology, the doctor should obtain the patient's freely given consent after the patient has been given a full explanation. In case of legal incapacity, consent should also be procured {rom the legal guardian; in case of physical incapacity the permission of the legal guardian replaces that of the patient. 2. The doctor can combine clinical research with profes- sional care, the objective being the acquisition of new medi- cal knowledge, only to the extent that clinical research is justified by its therapeutic value for the patient. 111. Non-Therapewtic Clinical Research 1. In the purely scientific application of clinical rescarch carried out on a human being, it is the duty of the doctor to remain the protector of th: life and health of that per son on whom clinical research is being carried out. 2. The nature, the purpose and the risk of clinical re- search must be explained to the subject by the doctor. 3a. Clinical research on a human being cannot be under- taken without his free consent after he has been informed: if he is legally incompetent, the consent of the legal guar- disn should be procured. 3b. The subject of clinical research should be in such a mental, physical anu legal state as to be able to exercise fully his power of choice. 3c. Consent should, as a rule, be obtained in writing. However, the responsibility for clinical research always remains with the research worker; it never ialls on the subject even sfter consent is obtained. 4a. The investigator must respect the right of each indi- vidual to safeguard his personal integrity, especially if the subject is in a dependent relationship to the investigator. 4b. At any time during the course of clinical research the subject or his guardian should be free to withdraw permis- sion for research to be continued. The investigator or the investigating team should discon- tinue the research if in his or their judgment, it may, if continued, be harmful to the individual. ber 1964. Inc. 10 Columbus Circle, New York, N.Y. 10019 718 STATEMENT OF DR. WILLIAM H. LUGINBUHL, DEAN, DIVISION OF HEALTH SCIENCES, UNIVERSITY OF VERMONT This docuzent is an attempt to provide an overview of Federal health programs and upconing Federal health legislation from the perspective af a medi:z1 school. Since the medical school in question has char- acteristiczs of both a private medical school and a public medical school, it is hopsd that the viewpoint expressed is relatively broad. Furthermore, an attenpt has been nade to consult with colleagues and to base opinions on a consideration of national need rather than local requirements. In the following peragraphs an attempt is first made to state the over- all objectives of Federal health programs. Two possible strategies for pursuing this objective are described and discussed. Since for reasons outlined the second strategy seems more likely, it is then discussed in some detail including specific comments on individual existing programs. Also, as a part of this strategy, several new or expanded programs are suggested. Finally, there is an attempt to summarize the views expressed. It is assumed that the objective of our health care system is to provide the best possible health to all of the people within the constraints of available resources and knowledge. When measured against this objective, the present system is admittedly deficient with problems in organization, distribution and cost. Two possible strategies might be employed in an attempt to bring about major improvement in the health care system. The first would be the imposition of major change by one or more broad pieces of Federal legislation and the second would be the encouragement of the more gradual evolution of such a system with Federal support and stimula- tion. The best example of legislation that would follow the first strategy would be the passage of national health insurance such as occurred in Britain immediately after World War II. Possibly the very widespread creation and imposition of the HMO concept might be included under this heading also. However, it seens unlikely that such a strategy of rapid change through Federal legislation will be followed during the next two years and probably during the next four years. One obstacle is our lack of knowledge as to the best means of organizing and financing a health care delivery system for our society. For example, there is relatively little experience with HMO's, effective audit and the creation of health care teams. A second obstacle, probably better assessed by others, is the political feasibility of enacting at this time broad health legislation such as national health insurance. : The second strategy, that of fostering gradual evolution, therefore, seems more likely at least for the present. Such a strategy would in- clude the accuaulation of knowledge by fostering experiments in health care delivery, the fostering of programs, such as health manpower de- velopment, that can confidently be predicted as a necessary part of any health care system, and the strengthening of the political base for fur- ther change. Tactics that would encourage the strategy of gradual evolu- tion include a reshaping and regrouping of current Federal programs in 719 aw research, education and care and the initiation of, or expansion of, pro- grams in a few vital areas. Suggestions for reshaping and regrouping programs may be timely because a number of these programs expire on June thirtieth and the President has advocated the termination of ‘some of these. The programs that might be reshaped or regrouped are discussed in the following paragraphs under the categories of research, education, and care, although admittedly there is some overlap in program areas and these headings cut across organizational lines and programs lines within HEW. The research programs with which we have familiarity are those of the NIH, Health Services Research and Development, and the NIMH. The re- cent more limited availability of NIH research grants has not been catastrophic to biomedical research. Similarly, a reduction in training grants in biomedical research will not be catastrophic if it is part of an overall plan for health manpower development. The rapid growth of NIH funds in the past resulted in the funding of some marginal work and the entry of poorly suited individuals to biomedical research fields. Furthermore, the availability of these funds has resulted in the domina- tion of faculties by research-oriented individuals and a decreased em- phasis on primary care as opposed to specialty care in medical educa- ‘tion. However, further cuts in research funds would begin to jeopardize higher quality programs. ‘The effect of targeted research is difficult to assess at this point, but the approach seems reasonable especially if there is a continued base of support for fundamental biological re- search in all areas. From my vantage point, the various institutes of the NIH appear well run and my most serious criticism would be that at times in the past they received more money than could be wisely spent. Research in health care delivery supported by the Health Services and Mental Health Administration has been of much assistance to Dr. L. Weed of our faculty in the development of the problem-oriented approach to health care. However, it is my overall impression that HSMHA has not developed the orderly, objective, peer-based review process that has char- acterized research programs of the NIH. The same can be said for research programs under the NIMH. I believe that serious consideration should be given to placing the supervision of all research programs in the health field under the NIH including those in mental health and health care delivery. The educational programs that we have been involved with include those of the Bureau of Health Manpower and of the NIMH. Dr. Ken Endicott is held in high regard as a sensible, extremely capable administrator. The Compre- hensive Health Manpower Training Act of 1971 has given a sound base of Federal support to medical education and shows how Federal support can encourage schools to meet public needs. In the future I would hope that better support could be given to nursing and allied health education tied to incentives to encourage the development of the health care team about the problem-oriented system. Some support for medical school construction is of course desirable, but the enormous sums spent by some institutions seem incredible by our local standards. If one million dollars or more in 720 3s capital is required to create each space for an incoming freshman in a n= school, the more reasonable solution to the problem would appear to be :- expansion of existing schools. Ww e We have received support from the NIMH both for undergraduate education in psychiatry and for residency training. From both a local and a na- tional perspective, these programs do not appear to have met the public needs. In my view, this is in part because behavioral disorders are so closely linked to other societal ills and in part because we do not pos- sess the basic fund of scientific knowledge to understand much of mental illness. Because the current approach has not solved the problem does not mean that the problem can be ignored. I would suggest that the pri- mary emphasis should be on research rather than education at this time. The approach would be that of a targeted research effort under the NIH dealing with behavioral problems. Funds would be used to support basic research in such areas as neurophysiology, neuropharmacology, neurochemis- try, psychology, sociology, and anthropology, all fields that may in the future supply us with the basic biclogical understanding of mental illness that we now lack. - We do interface with many Federal programs in planning and actual de- livery of health care. Frankly, these present to us a bewildering array best characterized as fragmented and uncoordinated. Health programs in- cluded would be the Veterans Administration, OEO, RMP, CHP, Medicare, Medicaid, community mental health, migrant health, family planning, and probably others, Compounding the problem is the fact that a number of these progrz=s dealing with health care planning and demonstration proj- ects in health care delivery possess very limited authority and that limited authority is fragmented. I would like to comment specifically "on some of these programs. The mission of the Regional Medical Program has undergone transition from the original concept of centers for the actual treatment of cancer, heart disease and stroke, through that of a program to improve the treat- ment of cancer, heart disease and stroke, to that of a program with a broad concern with improving health care delivery in general. At the local level this shift has produced many problems, the greatest of which is the lack of a clear, uniform mission. This lack results in the crea- tion of uncoordinated fragments without any design for their incorporation into an integrated system. The lack of a coordinated program is compounded by the lack of any real quantifiable output measures for the program. Evaluation of output has been neglected at the local level and at the national level, probably not by oversight, but simply because of the complexity in defining outputs of health care in general and fragments of health care in particular. A final major problem of the Regional Medical Program is the limited and - divided authority that exists at the local level. There is a grantee, usually a medical school or university, that administers the financial 721 -4- aspects, a regional advisory group that sets policy and directs the Pro- gram, and a staff including a coordinator. The grantee does possess the power to confirm the appointment of the coordinator and remove him if necessary. Obviously this has not been exercised in many regions, and there is real inadequacy in the coordinator's role. The regional ad- visory groups have become larger and larger with resulting impotence that inevitably accompanies expansion over a critical size. Comprehensive Health Planning has been almost totally ineffectual in our State. Others have told me that a few effective CHP's exist in the country, but only a handful. Since CHP has no authority to implement plans, it is largely ignored by both providers and consumers. Further- more, it has not been very well funded. However, it is possible that CHP will get a new lease on-life if it is given in each state the au- thority for certificate of need as provided by H.R. 1. Hill-Burton has enabled this region to build adequate numbers of hospi- tal beds and in some communities excess beds. With shorter hospital stays, decreased emphasis on hospitalization and increased emphasis on ambulatory care, communities will not need further beds with few ex- ‘ceptions. Funds will be needed to upgrade existing facilities and especially to develop facilities for ambulatory care. In medical centers the development of ambulatory care facilities would also increase the teaching of acbulatory care to medical students and de-emphasize complex subspecialty in-hospital care. ‘Finally, brief comments on three programs, community mental health, family planning, and health statistics: Community mental health centers like all mentzl health programs suffer from a lack of basic scientific understanding of behavioral problems as noted above. Furthermore, one questions the logic in separating mental health from other forms of health care delivery. Family planning is an extremely important program with the potential for enormous if indirect impact on other health prob- lems. Termination of support would be a major tragedy. Health statistics are esscntial to health planning and management but are only valuable if coupled to these processes. The various health planning and delivery programs just described suffer from fragmentation and limited authority as noted above. Any move that results in program consolidation and increases and aggregates authority would be salutary. Medical schools, at least from their records as manag- ing RMP's, do not appear to be a strong base for consolidation, and in the absence of any other, state government may be the best choice. The creation of state health authorities that could assume responsibility for a number of existing programs would seem to be a step towards the eventual creation of an integrated health care system. In summary, I would suggest the following realignment of existing health programs. Research programs, including research in health care delivery and mental health, should be concentrated in the National Institutes of 93-999 (Pt. mM) O- 73 - 25 722 w 8s Health since that agency has the most successful record of managing re- search in the health field. All the educational programs in the health fields including those of the present NIMH should be placed in the Bureau of Health Manpower. Health care planning and delivery programs would be consolidated to the maximum feasible extent and would be based on local or regional authority such as state government. Serious consideration should also be given to certain new programs or expansion of present programs. These are advocated in the belief that they will be essential and compatible components of any future health care systen. Furthermore, some of the programs advocated will provide much needed information to bring about the creation of that better sys- tem. The new or expanded programs suggested include (1) graduate medi- cal education, (2) nursing and allied health education, (3) research in the problen-oriented system of health care, especially the computer- based system, and (4) research in the biological basis of mental health disease. Currently graduate medical education, that is, internships and residencies, is largely funded by hospitals who charge the costs to the hospitalized pa- tients. The number of house officers trained is not based on societal needs but rather on the needs of the hospitals for house staff in vari- ous areas. This has been a major contributing factor in the determination of career choices of young physicians and has resulted in the overpro- duction of sone specialties, notably surgical, and the underproduction in primary care areas including general practice, pediatrics, and gen- eral internal redical. In Canada graduate medical education is now funded at the provincial level with the decision as to numbers in each specialty and in primary care based more on overall societal needs rather than on the requirements of individual hospitals. This has also resulted in a broader dispersion of the burden of residency costs. I would suggest that serious consideration be given to a similar mecha- nism for this country. Residents would no longer be a reimbursable cost by third parties including intermediaries under Medicare and Medicaid. Funding for residencies would be through Federal sources with alloca- tion based on public need in various specialties and in primary care. If the above proposal is politically unrealistic at this point in time, then serious consideration should be given to greatly expanded funding for residency programs in primary care and family practice. At the present time family practice programs are difficult to fund because much of the train- ing must be based outside of the hospital and cannot be reimbursed by third parties. Although the Comprehensive Health Manpower Training Act of 1971 included authorization for training in family medicine, only very limited funds were eventually appropriated, and it is understood that the administration plans to continue to hold down this program. It is my view that the funds originally authorized should be appropriated and the progran should be expanded as rapidly as possible. Stipends for residents would at- tract physicians to the family medicine area and the stipends for faculty would enhance the stature for these programs in the eyes of faculty and stu- dents thus tending to direct future graduates into this needed area. It 723 wb is difficult to conceive that there could be administrative resistance to a specific program designed to increase the numbers of physicians in the areas of family practice and primary care. If the future health care system is to be based on the concept of the health care team, then there is a pressing need for fostering this concept in nursing and allied health education. . There is growing national accept- ance of the problem-oriented system of health care among medical educa- tors and this same acceptance is just beginning within nursing and al- lied health. The availability of funds for experimental programs in nursing and allied health education related to the team concept of care would accelerate this acceptance and development. Unfortunately it is currently extremely difficult to raise private funds for experimental pro- grams in these areas. Federal funds are likewise very limited at the present tiue. There is a. continued need for high quality research in health care de- livery. In my opinion further development of the problém-oriented system with particular emphasis on the application of the computer to medicine is urgently needed. Under the Comprehensive Health Manpower Training Act of 1971, funds were authorized for grants for computer tech- nology health care demonstration programs. It is my understanding that only limited funds were appropriated in the first year and that further appropriations have been deleted from the administration request. This seems extremely shortsighted since research of this nature will be the essential basis for the development of an improved health care system. Research on thz biological basis of mental health and illness was men- tioned earlier in connection with existing programs. Although large amounts have been expended in education and training of mental health personnel, especially ‘psychiatrists, this approach has not solved the . mental health problems of cur society. This failure is in part related to the lack of basic biological understanding of mental illness. A targeted research program within the NIH including investigations in the area of neurochemistry, neuroanatomy, neuropharmacology, neurophysi- ology, anthropology, sociology, and related fields should be instituted instead of continuing with many of the present nonproductive mental health programs. : In summary, this document assumes that our objective is to create a health care system that possesses the ability to provide the best possible health to all of the people. It suggests that we might move towards such a sys- tem by a few major steps or by more gradual evolution. For the immediate future, it seems more likely that the latter will occur and, therefore, this strategy is discussed in detail. The discussion includes the reshap- ing and regrouping of current programs and the advocacy of certain new programs. Although the positions taken cannot help but be influenced by local experience, at all times the intent has been to advocate programs and positions based on national need rather than on local advantage. 724 Arthur J. Dyck and Herbert W. Richardson The Moral Justification for Research Using Human Subjects Reprinted from USE OF HUMAN SUBJECTS IN SAFETY EVALUATION OF FOOD CHEMICALS PROCEEDINGS OF A CONFERENCE National Academy of Sciences National Research Council 1967 725 Arthur J. Dyck and Herbert W. Richardson The Moral Justification for Research Using Human Subjects INTRODUCTION The use of human subjects in research that is of some risk to them is not only morally justifiable but, in certain instances, morally required. Two kinds of considerations lead to this con- clusion: the limitations of research with animals and the stringent moral demand to alleviate or eradicate human suffering. With respect to the limits of research with animals, there is surely no need here to rehearse the abundant evidence for the species-specific nature of various chemical reactions (1). Until, therefore, much more about species differences and similarities is known, clinical research that establishes sound medical prac- tice will have to rely upon the knowledge gleaned from the reac- tions of human subjects. In addition, whenever the use of certain food additives and environmental toxins is considered to be mor- ally desirable, it will be necessary to establish safety levels for their use. In certain cases, these safety levels can only be estab- lished by using human subjects under carefully controlled test conditions. Medical research affords abundant evidence that we sometimes require, on moral grounds, that humans be subjected to risk. The development and use of vaccines is but one case in point. Vac- cines involve statistically minimal, though very real, risks to their recipients. Yet we have undertaken the necessary research with humans, once animals are tested, and now make compulsory the use of some of these vaccines despite our knowledge that per- sons can and do die from them. The very great benefits derived from vaccines, and the very small risks associated with their use, serve as the moral justification for what we do. 229 726 230 Arthur J. Dyck and Herbert W. Richardson The benefits obtained by the use of vaccines and a vast array of other medical products are not luxury items; they are designed to prevent existing, highly undesirable threats to our existence. The struggle against existing threats to human life has a much higher moral urgency for us than the possibility to create bene- fits that add to human pleasure. In instances where great harm is to be prevented, the use of human beings in experiments in- volving risk is much more easily justified and more apt to be viewed as morally required. However, even risk-experiments for the sake of ascertaining safety levels for the use of food addi- tives and pesticides, which are primarily for the sake of increas- ing human pleasure, can also be morally justified under certain circumstances. The question, then, is not whether we shall at all use human subjects in scientific research or whether such use can ever be justified. The real question, the question we wish to deal with in this paper, has to do rather with the conditions under which we would consider the use of human subjects to be justifiable in those instances where the research in which they are to be used may, in some way, harm them. We shall take the position that the use of humans in research involving risk to them can only be justified if the following two requirements are satisfied: such research must anticipate specific benefits accruing from its results, and these benefits must more than offset all the potential, associated risks, and such research must be in accord with certain inviol- able moral values that can only be secured by satisfying the re- quirement of informed consent. We shall distinguish three types of research, namely, medical research, research with food addi- tives, and research with environmental toxins, and examine what it takes in each of these cases to comply with our two moral re- quirements for justifying research involving risk to humans. It should be noted that nothing we have said thus far, and noth- ing we expect to say, should be construed as an attack upon the general value of sheer knowledge or of sheer research for the sake of research. No research project, however, is totally exempt from moral scrutiny. It is important that the evaluation of any contemplated research projet consider the possible harm such research might inflict upon human beings, for in doing research for the sake of research, we could, at some point, seriously undermine the quality of our lives in our very efforts to enhance it. In short, the value of research, including its value as a con- tribution to knowledge, can be offset, in a given instance, by some harm it may cause. 727 The Moral Justification 231 TWO TYPES OF VALUE Let us now characterize the two sets of moral criteria by which the use of humans in research involving risks to them is to be morally justified. These criteria are specified by two types of moral values: benefits and structural values. Benefits may be determined by the calculation of relative pleasures and pains (or benefits and harms); structural values are maintained by sat- isfying the requirement of informed consent. Benefits presuppose specific social systems. Benefits are for the sake of increasing happiness by sustaining and improving the quality of human life. What things are considered to be benefits and the means thereto are matters decided upon and adjudicated by the members and institutions of a given social system. Social systems, to the extent that they are congruent with the aspirations of their members, seek to maximize these benefits. Any social system not only values the benefits that secure the happiness of its members, but also values restraints upon actions that threaten harm to any of its members. Activities that carry with them a risk of harm to human welfare can, however, some- times be morally sanctioned when they promise to bring about very great benefits or to prevent very great suffering. There is, then, a contextually calculated ratio of benefits and harms by means of which potentially harmful actions can be morally eval- uated. ’ ~ Although there are harms that can be balanced against bene- fits to help us decide whether a certain risk is morally justifi- able, there is a certain type of harm that cannot be outweighed by any benefit, no matter how great that benefit may be. This "harm' to the second kind of moral value we have mentioned above, that is, violation of a structural value. The loss of bene- fits is tolerable within a pleasure - pain calculus, but "harm" to, or violation of, structural values is not tolerable since these values maintain the social systems that are the presupposition of all benefits. To violate a structural value, therefore, is to violate the very condition that makes benefits possible and mean- ingful. With regard to experiments involving human beings, the underlying network of structural values is protected by the re- quirement that no person be an experimental subject without first giving his informed consent. Among the inviolable structural values that the requirement of informed consent protects are veracity, freedom, and justice: 728 232 Arthur J. Dyck and Herbert W. Richardson veracity refers to relationships characterized by promise-keeping and truth-telling; freedom refers to a person's general right to pursue his own happiness and to decide what risks to his own body and his own welfare he will take; justice refers to the distri- bution of goods in accord with a standard of equity and to redress for undeserved harm. These are values people will die to pre- serve, values without which social systems and interpersonal re- lations break down and cannot function. Because they are essen- tial to the very existence of society itself, these structural values may be distinguished from all those other "benefits that society seeks to attain—benefits that are legitimately ascertained within a benefit - harm calculus. Structural values are not part of this benefit - harm calculus because the loss of such values is so harmful that benefits become meaningless. What meaning would "benefits" have for those who had no freedom, or for those who were victims of extreme injustice, or for those who lived in a society where no one could be trusted and where no contract was honored ? THREE TYPES OF RESEARCH Having clarified the two sets of moral criteria to be satisfied if investigations that involve risk to their human subjects are to be morally justified, it is now necessary to see how these criteria can be satisfied. The calculation of benefit - harm ratios and the provisions for informed consent vary considerably from one sit- uation to another. For this reason, it is impossible to assume that what is being said about these matters in medical ethics will apply to research with food additives and environmental toxins. Indeed, the discussion that now follows will distinguish between the situations created by medical research, research with food additives, and research with environmental toxins, and seek in turn to demonstrate the marked differences in what it takes, in each of these instances, to calculate benefit - harm ratios and to honor the principle of informed consent. It should be recalled that all the research that concerns us in this paper involves risk to humans. For this reason, such re- search must contemplate some specific benefit that can justify the risk inherent in the research itself. Moreover, if the specific kind of research being undertaken is for the sake of establishing safety levels for the use of particular drugs, food additives, or pesticides, then we must assume that the particular benefit being 729 The Moral Justification 233 contemplated by such research as its justification is the use of such drugs, food additives, or pesticides. For this reason, the decision to undertake research involving safety levels implies also a decision to use the materials under investigation should this investigation prove successful, and, of course, it is only undertaken on the supposition that it will prove successful. If, on the other hand, someone would wish to argue that the decision to undertake research involving safety levels for the use of drugs, food additives, or pesticides does not imply a decision to use such materials if that research is successful, then the obvious reply is "Why expose people to the risks of such investigation when no benefits accruing from the use of such materials are contemplated ?"' By noting that the decision to test for safety levels implies a decision to use a given material because of its contemplated bene- fits, we have made a distinction that helps us to discriminate among various kinds of research involving humans. In certain kinds of research, e.g., medical research, the "test conditions" and the "use conditions'' closely resemble each other; in these cases, the contemplated benefits from use are usually not beyond the capacity of the individual investigator to determine. However, in other kinds of research, e.g., research with environmental toxins, the "test conditions for safety levels and the "use condi- tions" may be very dissimilar. The contemplated benefit from use is not easily determined by the individual investigator since it involves not only possible harmful effects to the primary user, but also extended effects upon secondary users and even the entire ecological system (2). Moreover, because test and use conditions vary from one kind of experiment to another, we must be wary of all arguments that attempt to justify one kind of experimenta- tion involving humans from the accepted legitimacy of another kind of experimentation. We can better see why this is the case by considering the difference between test and use conditions in the three types of research under discussion in this paper. In medical research the test conditions, and the conditions in which the results of the tests will be used, are quite comparable to one another. In both instances, the conditions are usually well controlled. A given drug, for example, is investigated under carefully controlled circumstances, and once the drug has been found to be acceptable, and a safe dosage has been established, the use of the drug will often be confined to circumstances that are quite similar to those under which the drug was accepted for use. Furthermore, the effects of the drug, whatever they may be in use, will generally be restricted to those who are given the 730 234 Arthur J. Dyck and Herbert W. Richardson drug, to those, in other words, who stand to benefit directly from its use. In medical research, therefore, we have to deal with a comparatively simple investigator - subject relationship (3). When, however, we turn to research involving food additives and environmental toxins, we are confronted with a much more complex nexus of relationships. Investigations in both of these instances encompass much more than simply risk to the subject under the controlled conditions of the laboratory. In the case of food additives, there are sometimes risks to the people who eat the food, risks that it is the purpose of the investigator to minimize by establishing safety levels (4). However, it is not easy to determine the extent to which a given food will be eaten and the extent to which, therefore, the controlled conditions of the laboratory are or are not approximated in society. It is also difficult to know or to predict the long-term effects of ingesting food additives in dosages that are otherwise harmless. Research involving food additives differs from medical research in still another way. Whereas in medicine it is sometimes quite difficult or even impossible to develop alternatives to certain risky ther- apeutic procedures, in research with food additives it is usually easier to do so. We can think here, for example, of a certain flavoring that may be quite toxic, a flavoring, however, that may have a less toxic flavoring substituted for it, a flavoring that will be much less of a risk both to the subject of any investigation and hence to anyone who will eventually eat the food. If we turn to investigations with environmental toxins (e.g., pesticides), we note that these not only involve risks to the sub- jects of such investigations and risks to many other people, but even risks to a considerable portion of the environment in which people live. Environmental toxins may very well have unpredict- able or even irreversibly ill effects upon our environment, so that the use of these does not depend solely upon the establishment of safety levels for subjects under highly controlled situations. In such cases, this means that the individual investigator is not in a position to decide for himself whether a given study is to be undertaken. What food additives and environmental toxins will be used in research and subsequently in the environment is some- thing that demands considerable knowledge of the larger environ- ment within which these products of research will be employed. In connection with environmental toxins, as with food additives, we should bear in mind that alternatives exist and can be developed for achieving the same effects, alternatives that minimize risks and maximize benefits, alternatives that are subject to greater degrees of control in use. 731 The Moral Justification 235 To summarize briefly what we have been saying, let us note that as we move from medical research, to research with food additives, to research with environmental toxins, the uses of the products of such research are more widespread in their effects, more difficult to control, and more likely to involve unanticipated hazards. For these reasons, the benefits accruing from the use of food additives and pesticides cannot be calculated with the pre- cision usually characteristic of the products of medical research. Hence, the benefit - harm ratio that justifies risk-experiments involving food additives and pesticides is generally less exact than in medical experimentation; for this reason the preponder- ance of contemplated benefits over possible harms required to justify testing and using these materials must be concomitantly greater. There are, however, two steps that both can and should be taken in order to increase precision in calculating these benefit - harm ratios. We should increase our research into the complex and widespread environmental effects of possible food additives and pesticides in order to be better able to calculate their potential benefits and harms, and we should take steps to bring the use of such products under more exact control. Let us turn, therefore, to a consideration of these two matters. CONTROLLING BENEFIT - HARM RATIOS In this paper, we have stressed that the decision to test toxins on human subjects for the sake of establishing safety levels im- plies a decision to use these toxins if the tests are successful. Whenever there is a significant discrepancy between test and use conditions, the researcher is not in a position to determine whether the possible benefits arising from his tests are suffi- cient to justify the potential risks to the subjects of his proposed experiment. In these cases, there must be extensive gathering of information about the short- and long-range effects of various materials on all living beings and their environment; there must be a consideration of various alternatives to attain the same goal; and there must be follow-up studies of materials already in use in order to discover possible unanticipated effects. Because the gathering of such information is for the sake of making a disinterested judgment regarding the effect of any given product upon the human environment, we suggest the necessity for a public data-pooling agency that could coordinate and promote research concerning the effects of different substances. The 732 236 Arthur J. Dyck and Herbert W. Richardson weighing of possible benefits and harms belongs more properly to some such disinterested data - pooling agency than it does to the representatives of particular vested interests (5). Although this data-pooling agency should carry out and promote research in ecology, especially in those areas where our know- ledge of the effects of various toxins on our environment is still deficient, it should not replace agencies already contributing such research. One example of a public agency that has done valuable research on the effects of environmental toxins is the United States Fish and Wildlife Service. It is essential that agencies like this receive adequate funds for research. Industries that develop and distribute environmental toxins also need to concern themselves with studies of the environment, and they should either sponsor research in this direction themselves or take steps to see that research of this kind is abundantly supported. Extensive research into the effects of toxins and other mate- rials on various human and biological systems and the pooling of this information in one or more centralized agencies will help to provide a clearer specification of possible benefits to be attained from the use of particular chemicals. With respect to food addi- tives, prior to testing them on human beings, there should be extensive study of their potential benefits, possible long-range effects, and consumption patterns. On this basis, the final testing of all such products to determine safety levels for use can be more exactly calculated in terms of benefit - harm ratios. More- over, because the benefit - harm ratio is essential to morally justifying all experimentation involving human subjects, it should be clear that our emphasis on the necessity for data-pooling to determine possible effects before testing, and upon continuous follow-up to discover unanticipated effects after testing, bears directly upon the legitimacy of such experiments. Only as we are striving to increase our knowledge and control over the use of various chemicals can we adequately calculate benefit - harm ratios and discriminate among various experimental proposals. The heart of moral discrimination in these matters is knowledge and control, and progress here is essential if the increasing use of humans in experimental projects is to be at all justified. A second way to gain increased control over our calculation of benefit - harm ratios is through more careful study of, and control over, the actual handling of chemicals by the primary users themselves. We have already seen that there is generally less control over the primary users in instances involving food additives and pesticides than in instances involving drugs. Not only are the former available without the equivalent of prescrip- tions, even in unlimited quantities, but directions for their use 733 The Moral Justification 231 are often less exact and detailed and are followed with less preci- sion (6). To gain greater control over the actual use of these products, there must be greater stress on accurate, sufficiently complete labeling and education regarding the necessity for use as directed. Even with these efforts, however, there will remain a clear difference in degree with respect to both the possibility of misuse and the calculation of the effects of possible misuse as we move from drugs to food additives to pesticides. The restrictions gov- erning the use of many drugs make it possible, where such re- strictions obtain, to calculate with considerable accuracy the results that accrue from their misuse. Since food additives are much more readily available, the effects of their misuse are more difficult to ascertain. Nevertheless, the effects of their misuse, as in the case of drugs, are likely to be confined to pri- mary users, and the possible harm they may cause is calculable. But the possibility for the misuse of pesticides, and hence the calculation of benefit - harm ratios for such substances, is pres- ently so great as to be almost out of control (7). Not only are pesticides easily available in concentrated forms, but they may irreversibly affect both primary and secondary users and even entire ecological systems. As long as their use is relatively unrestricted, there is no precise way of calculating whether their purported benefits significantly outweigh their harm—or even outweigh their harm at all. For these reasons, both pesticide research and the use of pesticides require much more stringent control against their possible misuse—if such products are to be morally justified. For example, it would not seem inappropriate that farmers and other large users of pesticides in concentrated forms be licensed to obtain and use them on the basis of qualifying examinations testing requisite competence. Misuse, thereafter, would constitute grounds for a fine or for revocation of the license. And, on the other hand, the availability of these same pesticides to the gen- eral public might be curtailed or otherwise regulated. By bringing the use and possibilities for misuse of pesticides and other en- vironmental toxins under greater control, their potential benefits can be calculated more exactly. SATISFYING THE REQUIREMENT OF INFORMED CONSENT The central contention of our paper, as we noted at the outset, is that experiments involving risk to human subjects should be jus- 734 238 Arthur J. Dyck and Herbert W. Richardson tified by meeting the requirement of informed consent and by promising the attainment of certain benefits that considerably outweigh all possible harms. In discussing the latter criterion, we have tried to show that in all experiments involving risk to human subjects, where these subjects are not themselves the immediate beneficiaries of the knowledge gained, the difficulty of calculating benefit - harm ratios varies in direct proportion to the degree of dissimilarity between test and use conditions. We have argued, therefore, that such calculations of the benefits and harms associated with the use of a given product, calculations that are needed for morally justifying experiments using humans to determine the safety level of that product, depend upon a thor- ough knowledge of the effects of that product and a stringent con- trol over its use. Without such knowledge and control, unantici- pated harms may arise from the use and/or misuse of a given product which may outweigh contemplated benefits. As we have sought to demonstrate in the second section of our paper, however, a highly favorable balance of pleasure over pain (benefit over harm) will not by itself morally justify investi- gations that involve risks to humans. Such investigations must also satisfy the principle of informed consent. How, then, can the requirement of informed consent be met by the three types of research under discussion in this paper? Satisfying the requirement of informed consent for medical research, though problematic, is certainly easier on the whole than it is for research with food additives and environmental toxins. In the medical setting, it is essential that the physician - patient and investigator - subject relations be kept distinct (8). The physician as physician is pledged to the welfare of his patient and to the use of practices in accordance with the standards of his profession (9). Striving to keep the patient as informed as possible, the physician will be called upon, nevertheless, to make difficult but necessary judgments as to what information, if any, might jeopardize the recovery of his patient (10). Informed consent should also be the general guide for the in- vestigator in the clinical setting. It is not always technically possible, however, to obtain the direct consent of the subjects of a clinical investigation (11). When this is the case, only those persons should be sought as subjects whose physicians are not participants in the research under consideration. This stipulation permits the physician in charge of a given patient to serve as that patient's "advocate," representing his interests and with- holding him from serving as a subject whenever the risks to the patient seem excessive or unnecessary (12). Additional advocates 735 The Moral Justification 239 have been, and indeed should be, provided at various institutions engaged in medical research in the form of review boards set up to scrutinize proposals for research thought to be potentially harmful to the participants (13). In testing the safety level of food additives and environmental toxins, the informed consent of the persons serving as subjects should also be secured. It is already the case that many investi- gators enter into written agreements with their subjects, i.e., contracts describing a particular study and also indicating to the subjects the possibility of removing themselves from the inves- tigation should they, for any reason, deem it advisable or neces- sary to do so. In many cases, provisions are also made to care for persons in the event of injury to them. The basic rights, therefore, of individuals are by these means recognized and honored in practice. For this reason, these practices should be universalized. Moreover, those who find themselves in certain offices or professions also have rights and privileges and should get the same kind of legal protection being given to the subjects of these investigations. Both investigators and subjects should have some form of insurance to indemnify possible injuries as well as protection from liability suits. There would seem to be no insurmountable barriers to obtain- ing informed consent as long as we are dealing with the subjects of a controlled experiment, who have advocates to represent their interests, medical supervision during the course of the in- vestigation, the right to cease being subjects when they so choose, and the possibility of insurance or indemnification for injuries that are unanticipated, though possible. The more serious problems arise when we consider the right to informed consent of those persons who are affected by the use of drugs, food additives, and environmental toxins such as pesti- cides. For, as we have maintained, unless the principle of informed consent can be satisfied here, the very research for the sake of establishing safety levels of such products is morally question- able. Procuring the informed consent of the subjects of a care- fully controlled test to establish the safety level of a given pesti- cide is not enough to justify testing when it is known or even sus- pected that the pesticide will be widely and indiscriminately used. For example, techniques such as aerial spraying subject many people to the effects of such a pesticide without their explicit and informed consent and, in some instances, against their express wishes. Instances of this kind were reported by Rachel Carson in her book Silent Spring. If we are to understand the public pro- test evoked by the knowledge of such instances, and if we are to 736 240 Arthur J. Dyck and Herbert W. Richardson understand why the public was not dissuaded from these protests by assurances from pesticide manufacturers of the great benefits of their products, we need to recognize that such practices violate the principle of informed consent. If the principle of informed consent is to be satisfied, we must invoke the notion of society as an implicit social contract and understand various public agencies as advocates of the interests of all individuals against the risks and possible harms resulting from the use of various products. Hence, what we have said in our earlier discussion of benefit - harm ratios regarding institutions for ensuring and increasing our knowledge of and control over the use of potentially harmful chemicals applies here as well. Our previous discussion, however, of existing agencies and of agencies that will need to be established (e.g., a data-pooling center) requires some supplementation and extension at this point. If the interests of the public are to be fairly and sufficiently represented vis-a-vis the vested interests of all specialized in- vestigators, manufacturers, and primary users of food additives, pesticides, and other environmental toxins (including drugs), consumers and property owners should be protected and directly represented in specifically institutionalized ways. For one thing, the substances we are here concerned with should be licensed for use by some public agency, perhaps by the data-pooling agency we have proposed (14). Moreover, such approval should be re- newed periodically on the basis of a continuous assessment of effects. It is, perhaps, necessary to remind ourselves that there are no perfectly disinterested men and that the best way that such a public agency can function is by allowing all the special inter- ests to plead their cases before a judicial board. Such a device is not foolproof, but it is nevertheless needed to help to prevent use of environmental toxins in ways that would violate the principle of informed consent. Moreover, only as we protect this principle with respect to the use of such products can we justify the in- creasing need for experiments with human subjects for the sake of ascertaining safety levels related to their use. Those who call for an increased right to experiment with and to use various toxins cannot, at the same time, oppose the increased need to regulate experiments with and use of these toxins. Licensing boards designed to represent the "informed consent" of the public to the environmental use of various toxins are not enough. Just as we have argued that, even in more restricted experimental contexts, those injured by statistically possible though actually unexpected injuries should be compensated, so we suggest that justice requires compensation to persons injured 737 The Moral Justification 241 by food additives, pesticides, and other experimental toxins out- side the confines of the controlled conditions of the laboratory. Such compensation should also be institutionalized independently of the licensing boards. It should be stressed, however, that com- pensation for injuries occurring from licensed food additives, pesticides, and other environmental toxins should not come in the form of a liability suit against the investigators and manu- facturers or primary users of these products whenever they have been given permission to use these materials and whenever they have met the criteria established for such use. Rather, the com- pensation should come from public insurance or even from taxes upon the product itself—in recognition of the inevitable statisti- cally probable risks associated with its use. If agencies were required to provide compensation for injury resulting from prod- ucts licensed by these agencies, they would surely stimulate efforts to reduce the need for such compensation. The Food and Drug Administration already provides consider- able protection to consumers through its powers, among other things, to certify antibiotic drugs and insulin, review evidence of the safety of food additives, establish tolerances of safety for food and drug color additives, establish tolerances for pesticide residues, and administer the Federal Hazardous Substances La- beling Act. Its hand as an enforcement agency should be strength- ened. At the same time, it is vital that there be a data-pooling agency devoted to research so that the FDA's work as an enforce- ment agency does not discourage research that such a data-pooling agency could show to be necessary or clearly beneficial. The in- terests of consumers are represented in the federal government by the office of the Special Advisor to the President on Consumer Affairs. Though much remains to be done to increase the direct representation of consumers' interests at the federal level, this is a step in the right direction. A great public service on behalf of consumers is rendered by the Consumers Union, a voluntary organization, through their monthly publication Consumer Reports. This publication procures and furnishes essential information about the benefits and harms, strengths and weaknesses of various products, information that helps to provide the possibility for in- formed consent and for the rejection of harmful and hazardous products, as well as those of otherwise dubious merit (15). Our argument in this section parallels our argument regarding benefit - risk ratios, namely, that greater knowledge of and control over use helps to satisfy the principle of informed consent and of legitimate research with human subjects designed to test and establish safety levels for using various chemicals. 93-999 (Pt. II) O - 73 - 26 738 242 Arthur J. Dyck and Herbert W. Richardson A FURTHER MORAL CONSIDERATION All these considerations concerning legitimate experiments on human beings have, of course, a certain air of unreality about them. For, as we all know, some food additives and pesticides are already in widespread use without the prior controlled testing we are calling for. In these cases, the widespread use of these products without something equivalent to public licensing and control constitutes de facto experimentation on humans without their consent. The build-up of DDT in human bodies from their consumption of various foods, the ingestion of antibiotics from fish or fowl that have been treated with these "preservatives" (often without informative labeling regarding this fact), and cer- tain aerial spraying programs expose persons to various incal- culable risks to which they have not given their informed consent— either in person or through competent public agencies. This widespread use of potentially hazardous materials has evoked a concomitant demand from many scientific investigators for the immediate testing of these products on human beings in order to establish safety levles and to achieve some degree of control over their dispersal. The extremity of the situation we are describing does, in fact, constitute a justifiable reason for some immediate research on humans, as long as the principle of informed consent is not vio- lated, and as long as serious efforts to control the unregulated use of these materials are intensified and extended. In this sit- uation, of course, it is necessary to proceed with experimentation without all the pretesting ideally required to justify such experi- mentation. Rather, the research with humans to establish safety levels for products already in use must be done immediately. The moral justification for the curtailment of this extensive pre- testing arises from the fact that incalculable and uncontrollable potential and actual harms are already being inflicted upon per- sons and their environments by the relatively indiscriminate use of the products in question. The existence of these incalculable and uncontrollable harms and risks legitimates a procedure that is less than ideal. Given the situation, it is incumbent upon us to take the morally best action and, in this instance, that means conducting carefully controlled investigations of the chemicals now in use whose potential or actual harmfulness to humans has not been scientifically established. Materials that are thus proven to be hazardous can, with just cause, be withdrawn from the mar- ket, and for other materials, whose benefits outweigh their neg- 739 The Moral Justification 243 ligible risks, more accurate safety levels can be determined to guide usage. Of course, the situation we are here describing is not just the exception; rather, it is the rule. In actual life, we are always confronted with existing evils, and our ethical decisions never can accord perfectly with ideal norms. But this acknowledgment only makes clearer the status of our considerations in this paper, namely, that we have been concerned with moral norms as factors in determining particular procedures. By themselves, moral norms do not decide how we shall proceed. Rather, procedural decisions must take account of existing circumstances, moral norms, and technical capacities. All these limit the options open to us and the choice we can make. Now, the recognition of the inevitability of falling short of what is morally required (in the fullest sense of this term) some- times gives rise to despair or to cynicism regarding the possi- bility of any moral action in certain spheres, for example, in relation to war, or to the use of environmental toxins, or to the application of technology. Some of this despair is generated by the recognition that none of our decisions in these matters can perfectly accord with all moral requirements, since every choice involves a selection from among a number of competing claims. To this we reply that morally responsible action has always con- sisted in doing what is possible and what is best in the situation confronting us. All our arguments in this paper are direct ex- pressions of this point: that we must do all we can to determine the differences among values and situations and do all that we can to maximize our discrimination of and control over these differences in order to discern those options that appear to be the best possible in the light of all moral claims, existing circum- stances, and technical capacities. If we acknowledge that actual moral behavior is never perfect, taking its cue as to what is right from among competing claims and choosing among the options actually available at the time, then we shall also recognize the moral requirement of foresight and planning. For by the maximal anticipation of the consequences of particular actions and the interrelationships of particular ac- tions, we help to prevent certain harms from occurring that create a situation that is less than ideal and that close off the possibility of relatively more ideal actions. If, for example, there had pre- viously been greater anticipation of the pervasive ill effects of certain pollutants on the atmosphere, the kind of radical govern- ment control over the dissemination of these substances which now seems imminent might not have been required. It is the oc- 740 244 Arthur J. Dyck and Herbert W. Richardson currence of actual harms to society that justifies and calls forth regulatory legislation and enforcement agencies. The maximiza- tion of foresight and the anticipation of the harmful consequences of certain courses of action is, therefore, not only morally re- quired, but also is the best technique for maintaining optimum free- dom consistent with justice and for preserving a plurality of types of social control. For these reasons, advances in science and tech- nology, upgrading the training and skills of scientific personnel, and rendering more precise our methods of understanding society and larger ecological systems are indispensable aids to moral discrimination and ethical insight. SUMMARY The use of humans in research that is of some risk to them is required because of the limitations of research with animals and the moral demand to alleviate human suffering. Though research for the sake of overcoming pain has a greater moral urgency than research for the sake of conferring additional pleasures or benefits, even this second type of research may use human subjects so long as two conditions are met: the anticipated bene- fits arising from use of a given material must be sufficiently greater than all concomitant harms also associated with its use and all possible harms to experimental subjects, and no person must be exposed to any of these potential harms unless he has first given his informed consent. The observance of these two conditions in research to estab- lish safety levels for the use of drugs, food additives, and pesti- cides implies that all such research presupposes the use of the chemicals under consideration (if the research is successful). Since such use involves potential harms, these potential harms must be calculated before testing such products on human subjects in order to determine benefit - harm ratios required to justify such research. The difficulty of calculating these ratios increases with the degree of dissimilarity between "test" and "use" condi- tions of various products. In general, therefore, benefit - harm ratios are most easily calculated in medical research and least easily calculated in research involving pesticides and other en- vironmental toxins. To the extent that the incalculability of potential harms arising from the use of certain materials originates in our ignorance of their total effects within ecological systems and from our lack 741 The Moral Justification 245 of control over their use, we can remedy this situation by promot- ing systematic research into the effects of all materials on living systems and by controlling the use of all chemicals through, for example, clearer labeling, licensing, and packaging. It should be noted that whenever there is a significant difference between test and use conditions of a given product, the individual investigator is usually not in a position to calculate the complex benefit - harm ratios necessary to justify experiments using human subjects. Rather, such calculations must represent the interests of various groups and the employment of data-pooling mechanisms. Whenever test and use conditions are similar, informed con- sent should and can be secured directly from the subject or, where technically necessary, from his immediate advocate (e.g., his attending physician). However, to the extent that test and use con- ditions are not similar, procuring the direct consent of subjects, though necessary, is not sufficient to satisfy the principle of in- formed consent. In such instances, information must be obtained concerning the effects of using the product being tested, and con- trols over its use must be implemented. Indemnity for those in- jured by chemicals, whether as subjects of experiments or as users of the harmful chemicals in question, should be provided. Similarly, investigators who exercise professional care in exe- cuting approved research should be protected from liability suits. Procedures for such insurance and protection were suggested. Finally, since many products are now in use even though their actual harms on living systems have never been adequately cal- culated, immediate steps should be taken both to curtail their indiscriminate use and to ascertain their total effects by imme- diate research using human subjects. Although this procedure does not allow the pretesting ideally required to determine the benefit - harm ratios that justify risk-experiments using human subjects, it is here justified by the fact that incalculable and in- controllable harms are being done by products already in use. Our argument throughout this paper stresses the moral neces- sity of maximizing knowledge of and control over procedures and products and increasing both feedback and planning in order to anticipate the widest range of consequences. Such knowledge, control, and planning are necessary if experiments with human subjects are to be morally justified. Moreover, such control and planning are the best techniques for maintaining the optimum freedom consistent with justice within a pluralistic society. 742 246 Arthur J. Dyck and Herbert W. Richardson Notes 1. For a thorough discussion of the issues at stake here, see other papers in this volume: "Limitations of Animal Data for Predicting Safety for Man'' by Karl Beyer (page 43) and "Limitations in the Value of Studies in Human Subjects'' by Alastair Frazer (page 63). 2. The terms "primary" and secondary’ user need to be roughly clari- fied. Primary users are those who directly seek to benefit from the use or consumption of the chemical in question; secondary users are those who are inadvertently affected by the use or consumption of a given chemical. Thus the farmer who sprays his apple orchard is a primary user of a pesticide; those who eat apples from that orchard are secondary users of that pesticide. 3. Drugs are not, of course, always used under carefully controlled conditions. Antiobiotics have been used as a growth food and medi- cine for animals and also to preserve freshness in raw poultry, fish, and shellfish. It is noteworthy that the FDA has found it neces- sary to rescind hitherto permitted residues in the latter case as of August 23, 1966, and to investigate the former use of antibiotics as growth food and medicine. 4. One should not assume from this discussion that food additives gen- erally are toxic substances and that safety levels must always be established for their use. Some food additives, for example, are nutritionally beneficial and widely used foods and need not, therefore, be tested for their safety. 5. Such a data-pooling agency should perhaps be a public corporation that would be responsible to both industry and government. Consumer Reports of March 1963 carried an article suggesting just such an agency. It should be noted that the agency proposed there was more limited in scope, limited as it was to the evaluation of the safety of drugs. 6. In July 1965 Consumer Reports reprinted a letter warning gardeners to read and heed the labels on pesticides by a man who died, soon after he wrote the letter, of chlordane poisoning—he had been dusting his roses. His letter implied that, although the label did provide the necessary cautions for users, the dangers of misuse were not empha- sized; certainly he did not expect what happened to him. Consumer Reports draws the conclusion that the wording on labels is as un- alarming as the law allows. 7. We are not unaware of the existing power of the FDA to establish tolerances for pesticide residues in foods. Laudable and necessary as this is, it does not prevent residues in the Mississippi River lethal enough to kill numerous fish, residues now to be found in the drinking water of New Orleans. (See Consumer Reports of June 1964.) 8. The importance of this distinction has been recognized in the litera- ture. See, for example, Henry K. Beecher, "Experimentation in Man," 743 The Moral Justification 2417 10. 11. 12. 13. 14. 15. J. Am. Med. Assoc., 169, 461-478 (1959); O. E. Guttentag, "The Prob- lem of Experimentation in Human Beings: II. The Physician's Point of View," Science, 117, 207-210 (1953); and Irving Ladimer, "Human Experimentation: Medical Legal Aspects," New Engl. J. Med., 257, 18-24 (1957). . These standards do, of course, constantly change as new discoveries are made. This means that some person does have to be the first patient to initiate what can reasonably be expected to become stan- dard practice. Before a physician begins to initiate a new practice on his own patient, there must be some reasonable assurance, where the risk is great or relatively unknown, that nothing else will do or, in accord with what is known, that the new procedure has at least as good a chance of success as existing procedures. If the initiation of a procedure is part of an attempt to procure information, it must not be an experiment by a physician on his own patient. A physician should generally not withhold information from his pa- tients nor assume that it is desirable to "protect" them from what he knows. Each case has to be judged on its own merits. Technical reasons include, for example, the "double-blind" technique. In every case, however, the investigator should have necessary and sufficient reasons for using research techniques that require unin- formed subjects. It should be evident that highly competent scientific personnel are needed to design and carry out research that will min- imize the risk of harm to humans. The public is justifiably indignant when physicians use their own pa- tients to conduct research, especially when this is done without the patients’ knowledge that they are involved in research. Drugs not cleared for sale, thalidomide, for example, were made available to consumers by physicians conducting clinical tests for the William S. Merrell Company. (See Consumer Reports, March 1963.) Conduct- ing research in this manner is a violation of the patient's right to expect therapy and not research to be the basis on which his own physician dispenses medicine. This practice is not and should not be restricted to medical research. For the sake of impartiality, it is important that board members not all be employees of the same institution and not all come from the same discipline or department. The FDA already has the power to license drugs. Nevertheless, the power to license pesticides and other environmental toxins might better be given to a public agency of the sort we are suggesting, beholden as it would be both to the government and to private industry. Recently, the FDA announced the publication of a new monthly maga- zine, FDA Papers, that will provide a great deal of valuable informa- tion, not only about its regulations and activities, but also about current practices in the food and drug industries as they relate to the health and welfare of the public. The first issue was published early in 1967. 744 MEDICAL SCIENCE, THE CLINICAL TRIAL AND SOC(ETY* Robert Q. Marston, M.D. Director National Institutes of Health Bethesda, Maryland There are several reasons for me to be pleased to be with you at the dedication ceremonies for the McLeod Nursing Building and the Jordan Medical Education Building. From the national standpoint, we have here highly visible, tangible evidence of progress toward a national goal to increase our capability to meet the health needs of the people, through combined Federal, State and local efforts. There are also personal reasons I am pleased to be at Mr. Jefferson's University today. I have had long and close friendships with many at the University--to name just two, President Shannon and Vice President Crispell. In addition, the first medical dean I can remember is Dean Jordan. As did many of my vintage in medicine, I used the textbook on histology authored by Jordan and Kindred. Also, Dr. Jordan provided me with one of my first difficult career choices--that of the choice between the University of Virginia School of Medicine and the Medical College of Virginia. 1 might add that thirty years later my son is attending the University of Virginia. Another reason for being *To be presented at dedication ceremonies for the McLeod Nursing Building and the Jordan Medical Education Duiiding at the University of Virginia, Charlottesville, Virginia, November 10, 1972. 745 - 3 pleased was to learn that my old friend, Dr. Thomas Hunter, has been conducting a series of socio-medical conferences covering the subject which I am addressing today. This occasion provides an appropriate setting in which to speak seriously about some of the boundary conditions under which the students passing through these buildings will carry out their professional careers. I have only two basic themes. The first is to express my rededication and that of the National Institutes of Health to the principle of insuring that all individuals involved as subjects of medical research be as fully protected as humanly possible. The second theme is related--an emphasis on the need for experimentation with human subjects including an assertion that there is immorality in not carrying out necessary research involving human subjects. I believe we should look directly at the implications of the subject, its necessity and its hazards. Such a discussion inevitably raises a question of the welfare of the individual versus the welfare of society--a subject with which Mr. Jefferson struggled so effectively. Just as he continuously stressed the ultimate importance of the individual--so must we as we deal with the many facets of this issue. 746 - Bu The need for scientific knowledge is intensified today because doctors have never before been in a position to produce so much positive good on one hand, or harm on the other, through the double-edged potency of their therapeutic weapons. However, the issue is not altogether a modern one. According to Dr. William Rowe, the Emperor Napoleon Bonaparte once said "TI do not want two diseases, one nature-made, one doctor-made." (1) Napoleon's pointed comment was sharper than he could possibly have known. The march of medical knowledge in the intervening years has expanded immeasurably the possibility of 'doctor-made" disease. Rene Dubos spelled out some of the specifics of the potential dangers from the tools of medical science in these words "who could have dreamt a generation ago that hypervitaminosis would become a common form of nutritional disease in the Western world?....and the use of x-rays would be held responsible for the increase in certain types of cancer? That the introduction of detergents in various synthetics would increase the incidence of allergy...that advances in chemotherapy and other therapeutic procedures would create a new staphylococcus pathology?...that patients with all forms of iatrogenic diseases would occupy such a large number of beds in the modern hospital?" (2) 747 - 4 = This very progress is the compelling reason for a continuing and close examination of the relations between medical science and clinical trials--and other research involving human subjects. We are dealing with a dynamic, ever-changing base of substantive knowledge. Sometimes the progress of a research project itself moves the state of knowledge so rapidly that serious and involved ethical problems arise concerning the continuation of that same experiment. For example, in Sir Austin Bradford Hill's article, "Medical Ethics and Controlled Trials," he described the complex situation which arose in a trial of long-term therapy using anticoagulants in cerebrovascular disease. He relates, "In previous uncontrolled studies there was a distinct if inconclusive suggestion in favor of their /anticoagulants/ use, and sufficient indeed, to make a trial difficult. Yet when put to the test of a controlled trial, with the comparison of a fully treated group and a group given a dose insufficient to interfere with the clotting mechanism, it not only appeared that no protection was afforded against the recurrence of cerebrovascular accident, but there was a small but definite 748 - 5 - risk of cerebral hemorrhage in the fully treated cases. Here we have an instance--and by no means unique--of the wheel turning full circle. At the start of the trial was it ethical to withhold the treatment? At its end, was it ethical to give it? It is very easy to be wise (and critical) after the event; the problem is to be wise (and ethical) before the event." (3) Any discussion of the benefits of scientific investigation involving the use of human subjects brings to mind a graduate of this University's School of Medicine, Walter Reed, who received his M.D. degree at the age of seventeen. He became a national hero because of his contribution to the control of yellow fever. Every school child knows the story of how the construction of the Panama Canal was stopped because of devastation from yellow fever. In 1900, Walter Reed and his associates discovered that yellow fever is transmitted to a non-immune individual by means of a bite of a mosquito that had previously fed on the blood of someone sick with this disease. (4) What is not always remembered about this event is the serious ethical question that was raised by Dr. Reed's experiments. At that time, it was not known that experimental animals could be given the disease; therefore, human studies were necessary. 749 “6 Army volunteers were both exposed to infected mosquitoes and given subcutaneous injections of virulent material. The subjects were aware of the risk, indeed, Dr. Lazear, the group's entomologist and bacteriologist, died after an accidental bite. None of the individuals living normally in non-risk areas could have been expected to benefit themselves from these experiments. It is highly unlikely that the experi- ments would have been permitted under today's guidelines. And yet the social benefits were great, the experiments were well designed and the moral implications were seriously considered at the time, and the results are part of our national history. In shocking contrast is the example from American history of the result of treatment by unverified methods. The central figure is Dr. Benjamin Rush. His conduct in earlier epidemics of yellow fever was described by Dr. William Bean as 'especially tragic because Rush treated literally hundreds of victims of the disease. His purging and bleeding became almost a routine premortal ceremony--the heroic aspects of Benjamin Rush, his many ideas about mental health, his signing of the Declaration of Independence, have made us forget the harm he did. His willingness to follow the guttering candle of ignorance, his 750 - Pw dogmatic conviction that he was right, his consummate ability to fool himself consistently helped to kill an unmeasured plenty of his patients in Philadelphia. That his motives were pure and serene constitutes another example of the unlimited capacity of man to fool himself." (5) Let me turn from the past to focus on the essential need for research involving human beings. There are several obvious reasons why such research must be carried on. First, in many instances, there may not be a suitable animal model. Second, even if such an animal model exists, there always comes a time at which the test must be carried out in man. Even when the situation is as clearcut as it was when it became possible to prevent the death of experimentally infected mice by treatment with penicillin, it still was necessary to test the antibiotic in man. Medical history is full of examples in which the promise of animal experimentation failed to hold up in humans, or in which the results in man exceeded those that would have been predicted from animal experimentation. Finally, and most relevant to this discussion, is the need to test definitively in humans the procedures and therapies which are already part of the practice of 751 “B= medicine. The potency of modern procedures and therapies is such that the experimental method is often the only effective way to determine if their benefits are outweighed by undue hazard. The late Dr. George James, known as an advocate for reform in health services, stated the problem well in one of his last talks; "In the discussion of ethical considerations relating to clinical research," Dr. James said, "the rights of the unborn generations to benefit from the fruits of the research must also be weighed. It can be debated that no man today has the free and moral right to condemn his grandchildren to the same perils of disease to which he is exposed by virtue of the present lack of effective scientific information, and his failure to participate in a search for it. It would help greatly to educate the population about this principle if the defects in our present medical armamentarium are to be made evident." (6) Dr. Archibald L. Cochrane has pointed out in his recently published book titled "Efficiency and Effectiveness' that the United Kingdom's National Health Service has in the main achieved its goal to make health services available and accessible to the 752 entire population at a cost that individuals could afford. However, he said the impact of the program on the health of the people of Great Britain was limited by the scientific base. In Dr. Cochrane's words, "There is a strong suggestion that the increase in input since the start of the NHS has not been matched by any marked increase in output in the 'cure' section. In the illustrative examples there were strong suggestions of inefficient use of effective therapies, and considerable use of ineffective ones." (7) A major theme in his book under lines the necessity of undertaking appropriate randomized clinical trials as a primary means for building the scientific base. There are several key areas in which the equivalent of Benjamin Rush's well intended but disastrous actions occur or may occur today. 1 have already quoted from Bradford Hill concerning the use of anticoagulants in the prevention of stroke. We have recently concluded scientific studies in the use of oral hypo- glycemic agents to control diabetes from which it has been possible to identify an increased risk from the use of such drugs. Studies concerning the side effects of smallpox inoculation, balanced 753 - XO = against the need for such inoculations in this country, have led to a modification in recommendations concerning the use of smallpox vaccine. Each branch of medicine has similar examples demonstrating the role of ignorance as a dominant deterrent in the achievement of effective health programe. Objective data on the hazards of medical practice are scarce. Such studies as we have can be over-interpreted in either direction. But let me give one example. Gardner and Cluff have found in their review of prospective studies of adverse reaction in hospital patients that "with certain exceptions, the percentage of patients with untoward reactions to drugs in the hospital has ranged between 10 and 18 percent despite the wide variety of institutions and investi- gational methods." (8) Even when one accepts the fact that serious disease justifies measures that increase the risk of adverse reactions, these figures are sufficiently high for concern. We stand today at a point at which there is a need and opportunity to strengthen markedly the scientific basis of medicine to the advantage of all. However, the need and 93-999 (Pt. II) O - 73 - 27 754 - 11 - opportunity exist at a time when (1) there is a trend back to "trial and error medicine;'" (2) there is a failure to recognize even in the health professions, as well as the public at large, the need for and the value of randomized clinical trials, and (3) there is increasing concern about the welfare of individuals _ involved as subjects in research. When all is said and done, there are really three ways for determining what actions to take in disease prevention, treatment or rehabilitation. First, is the logical extension of fundamental knowledge to its application in man--the movement from scientific theory to scientific practice. Increasingly in the future actions on this basis must be coupled with the practical demonstration of their effectiveness. For many years we knew that tobacco smoke contained potential carcinogens but until the evidence was gained that smoking does cause carcinoma of the lung in man, there was an insufficient basis to start a campaign to decrease smoking. We know today, as a result of epidemiological studies the risk factors which may account for 50 percent of heart attacks under the age of 65, but we must carry out through intervention trials, the crucial studies that will tell us whether elimination of such risk factors will, in fact, prevent heart attacks. 755 w 12 = The second basis for making decisions is the empirical use of the results of experience, the experience of colleagues and teachers. Medicine has been particularly dependent on this type of wisdom and will be in the future. This accumulated wisdom may serve both patient and doctor well. However, it is a transient type of wisdom. It is the best that one can do under the circumstances, weighing all of the factors, but subject to modification when and if adequate information becomes available. The third mechanism for making decisions is exemplified by the controlled clinical trial. Because such research tends to be long-term, difficult and expensive, the clinical trial is less understood and appreciated than the dramatic results of penicillin or a new vaccine. Further, the large clinical trial tends often to be unrewarding in a professional sense to the individual investigators who make up the scientific team. Although it is incompletely understood and incompletely applied, the clinical trial is the type of research on which we will become increasingly dependent as time goes on. Let me turn now to my second major theme. How best can we be sure that we protect the rights of individuals involved in clinical research? Many of you in this audience are well aware 756 =» 13 = of the many articles and books on the ethical aspects of the use of human subjects for research. A number of bills relating to scientific experimentation with human subjects were introduced in the last Congress reflecting a growing interest in the subject. I am particularly anxious that at NIH we interpret and enforce reasonable policies derived from basic and universal moral tenets as well as from requirements for sound scientific work. It is important also that as we review our policies we take into account the changing social, technical and political trends and even economic developments. New dimensions in medicine itself are creating changes. For example, the basis for choosing recipients of kidney transplants was a nonquestion umtil such transplants became feasible. Now it is an ethical problem to be solved. For more than a quarter of a century, the NIH has been the principal source of national support for biomedical research. We also conduct a very sizeable research program in our laboratories at Bethesda. Thus, we have a special responsibility for the ethical conduct of research involving human beings. 757 - A = From the beginning of our grant programs in 1937) the NIH Councils have been sensitive to the risks involved in research project proposals, often denying such proposals when the risks were unacceptable. About 1965, NIH led the way in the development of special policies and procedures to protect individuals involved in the experiments we support. Subsequently, we made clear our interest in the ability of institutions to wm.aitor adequately processes they had set up to protect individuals regardless of the source of research support. Along this line I was particularly pleased recently to hear that the Association of American Medical Colleges had declared that the institutions making up its membership do carry a specific responsibility for the assurance of rights of individuals involved as research subjects, and even more recently the AMA-AAMC Liaison Committee on Medical Education has included such institutional competence as a matter to be considered in accreditation review of medical schools. The current policy statement of the Department of Health, Education, and Welfare which is based on the NIH-developed statement emphasizes the grantee's basic responsibilities for safeguarding the subjects' rights and welfare and requires: 758 ~~ 1B ~ . That no grant or contract for such activity be made unless the application has been reviewed and approved by an appropriate institutional committee. That the committee determine that the rights and welfare of the subjects involved are adequately protected, that the risks w an individual are outweighed by the potential benefits to him or by the importance of the knowledge to be gained, and that informed consent is to be obtained by methods that are adequate and appropriate. That the committee be responsible for continuing review of the activity in keeping with its determinations. To date more than 750 institutions have filed general assurances of compliance with DHEW policy. These assurances include a statement of principles or code which the institution will use to guide its reviewers. Further, the assurances describe the committee or committees that will carry out the review and their procedures. The statement of principles relied upon by the great majority of clinically oriented institutions is the Declaration of Helsinki of the World Medical Association. The ethical principles set forth in the Declaration have been formally endorsed 759 - 16 = by the American Medical Association and eight of its component research groups. It is probably the nearest thing to a universal ethical code. Some few institutions rely on the older Nuremberg Code, others on the British Medical Research Council's statement on Responsibility in Investigations on Human Subjects and, in a few instances, on a code which is peculiar to the particular hospital or school. DHEW policy places strong emphasis on the need for breadth of review. It emphasizes that the institutional committee should have the professional competence not only to review clinical projects, but also to determine acceptability of the project in terms of institutional regulations, applicable laws, local standards of professional practice and community attitudes. National NIH review groups can provide in-depth scientific review, but they cannot provide the breadth of review possible in a Medical Center, which can assemble a local committee representing the full spectrum of medical disciplines, as well as ''lay" representatives from medical administration, legal medicine, and from other segments of the surrounding community. 760 - IF = Recently the Food and Drug Administration issued its own peer review requirements paralleling the DHEW policy which governs NIH clinical research. The only significant difference is that it has made lay membership on institutional review committees a "must," rather than a "should." T would propose any future amendments to the DHEW policy include a similar change. Our guidelines provide a high degree of flexibility for the institution in establishing its review procedures, but we insist that a responsible committee be established and that the committee adhere strictly to the three basic criteria I have already mentioned. . Protection of the rights and welfare of the subjects. . Weighing of risks against benefits. . Determination that informed consent is to be obtained by methods that are adequate and appropriate. It seems obvious that the first two criteria are the most critical to the ultimate decisions of any review group. Whether or not consent is in fact informed, admittedly it is difficult to assess. We oftentimes are in an uncertain situation in which inadequate information, communication problems, and the inability of the subject to comprehend--or to read--or to listen--can be misleading. . 761 - 18 = In the chain of events stretching from the first biomedical research concept to ultimate delivery of improved medical services the most critical link often is the human research subject. If through lack of care or an excess of zeal of the investigator and his interests we allow abuse of the human subject we endanger the beneficial forward march of research and fail ourselves as professionals. Has the NIH policy been successful? We believe it has. It has demonstrated that good science and high standards of ethics are closely linked. Indeed, the presence of risk places a special demand on us that only the highest quality of research be tolerated. The NIH policy has introduced a new sensitivity to the protection of individuals at every step in the process from the preparation of research proposals through the development of local institutional policies, the review at the national level by our Study Sections and Councils, as well as in the development of national public policy concerning biomedical research. The applications involving questionable procedures--never many--have become noticeably fewer in the past six years. However, we still interpose our judgment by disapproving applications (about 1%%) because of hazards, and we know that as new methods are learned, 762 - 19 - and new insights are gained, we will face additional agonizingly difficult decisions. However, even as I assert “hat the NIH-DHEW policy has been effective, I believe that more discussion, more visibility and clarification of the guidelines in some areas is needed today. Our policy is essentially egalitarian. It makes no distinctions as to race, color or socio-economic status. For instance, it touches only lightly on the handling of subjects with what it calls "limited civil freedom," a classification which includes prisoners, and residents of institutions for the mentally retarded and mentally ill, and minors. The policy assumes that the medical scientist similarly makes no distinctions in the choice of research subjects, except as his research interests are in diseases of a particular race, common in a certain socio-economic group, or limited to a particular hospital or institutional population. Unfortunately, this is not always the way it appears. Even more unfortunately this is not always the way it is. Many of our major research institutions are located in the large cities and their patients are drawn primarily from the 763 20. disadvantaged groups crowded in the center city. Thus, their research tends to be concentrated in these groups. Medical research trials frequently require that a convenient stable subject population be followed over a period of weeks or months rather than days or hours. The medical scientist naturally turns to groups whose availability can be controlled--hospitalized patients, institutionalized patients, medical students, and prisoners. Much research, particularly that which involves appreciable risks and requires frequent monitoring, is concentrated in such groups. I believe that the time has come when we must recognize that the risk of involvement in research is not distributed as uniformly among the nation's citizens as is the possibility of benefit from the products of this research. However, I expect that the Assistant Secretary's commission reviewing the Tuskegee Study will ultimately address itself to certain aspects of the problem of research using the disadvantaged as subjects. At this time, as I speak more specifically about some plans and proposals, I want to make clear that I am primarily concerned with those situations whete some significant risk is involved in research with human subjects. My comments will concern three general proposals: 764 “ ZL = 1. To develop regulations to strengthen the protection of subjects having "limited civil freedom," and to convene a series of workshops broadly representative of all concerned groups to discuss and refine the regulations and implementing guidelines. The first such workshop is scheduled for early February. 2. To undertake an examination of possible methods of compensation for subjects who, in spite of all precautions, are harmed by research activites. 3. To realert the scientists and administrators concerned with the research process, and to generate greater visibility for existing regulations and procedures. One way will be by insuring that all applications involving significant risk be specifically flagged for the attention of Advisory Councils throughout NIH. Let me reemphasize that while the requirement of high quality has characterized all of NIH programs, there is a special need to insist that the quality of research design and a high probability of obtaining definitive answers must receive special consideration where potential hazards to humans are a part of the price of doing the research. 765 - 22 = The additional regulations which I propose will be developed in consultation with affected agencies of the Department of Health, Education, and Welfare, particularly the Health Services and Mental Health Administration. Such regulations would govern the conditions under which an NIH grant or contract may be awarded for research involving inmates of prisons and correctional institutions, as well as hospitals for the mentally ill and retarded. If research is being done in such an institution under an NIH grant or contract, assurances would be required from the grantee/contractee (e.g. medical school) as now required and in addition from the institution when the work is done (e.g. correc- tional institution). Similarly, the institution where the work is done would now be required to establish suitable broadly-based institutional committees with the responsibility and expertise for reviewing research proposals and for assuring compliance with DHEW policy. Any financial compensation to subjects would be reasonably related to the prices paid for other services and not be so high as to constitute undue inducement. We would require a clear statement 93-999 (Pt. II) O - 73 - 28 766 - 23 = that neither participation in the proposed research project nor withdrawal from it will materially affect the conditions or terms of any subject's institutional confinement. In the case of the hospitals for the mentally ill and retarded, the research supported would be restricted to that which (a) is directly concerned with the issues of mental illness, mental health or mental retardation, or (b) will potentially benefit primarily a class of persons commonly confined to a hospital for the mentally ill cr retarded, or (c) which will lead to such knowledge important to the prevention of mental illness or retardation that may reasonably be expected to reduce the need for such hospitalization. Special attention will be given to the requirement for informed consent embodying all of the basic elements in current DHEW policy with special provisions to make sure that the risk- benefit balance is understood by the subject and that no undue inducement be offered. I would not like to depart from the subject of research involving children without commenting on the peculiar conflict 767 w 24 = between the medical needs of children as a class and the requirements of our laws. It is a medical truism that children are not small adults. They have their own diseases, they react differently to what are thought of as adult diseases and they do not react in the same fashion to treatment. The Food and Drug laws require that drugs be tested in all age groups for which a drug is intended. Yet, under English common law, no parent, no next of kin, or legal guardian can consent to the involvement of any child in a research project not intended for the good of that particular child. Thus, the law is not entirely consistent with the needs of children as a class, and particularly with the needs of mentally retarded children. Guidelines to be derived from the regulations I plan to propose, as well as the practicality of setting similar guidelines for oiher subject groups, will be discussed in detail at a series of workshops planned for the coming months in Bethesda. We plan to bring together research scientists, research administrators, lawyers, clergymen and others conce.ned with ethical matters, and representatives of other specialties. We 768 = U5 = will discuss the varieties and limitations of informed consent, the impact of consent procedures on the design of research projects, and the possib-lity of providing compensation to subjects who incur injuries in the public service. I do not intend, however, to wait until these discussions are completed before initiating changes. As 1 have said, we plan to require special procedures where experimentation with human subjects is carried out under conditions in which meaningful informed consent is difficult to achieve. I am initiating three other actions. First, my staff is reviewing recommendations made by members of Congress and experts in the field many of which were embodied in recent legislative proposals. We will focus our immediate attention on those measures for the protection of research subjects which can be adopted by adminis- trative action. Secondly, we have initiated an examination of possible mechanisms for fair and equitable compensation for subjects who despite all of the precautions we can take are harmed as a resuit. Third, we will give especially careful consideration to any proposal for research in which participants are exposed to risk when they themselves do not have reasonable chance of benefitting from such experiments. Under such conditions we will require special justification in terms of significant benefit to humanity. 769 = 26 = As I said earlier, if, in a specific case, I were forced to choose between the individual and the general welfare of society, I would choose to protect the individual. But, 'n the real world we must have both individual and social welfare. And in the real world, the day by day decisions are not made in Washington, nor can they be guaranteed by assertions by the Director of NIH nor the Secretary of HEW. We believe that the responsibility ultimately must rest with the individual institutioms, such as the University of Virginia, as well as with the individual investigator and physician. Our job at NIH is to supply unequivocal guidelines to monitor clinical research and to do all within our power to prevent clear abuses. The guiding principle for physicians down through the ages has been the dictum "first of all do no harm." To the students who pass through this Nursing Education Building and this Medical Education Building this dictum will be far more demanding than in the past. While they maintain a sensitivity to the possible adverse effects of their therapies, they will also be required to have an increased appreciation of the need to replace ignorance with knowledge. And the new knowledge, which will benefit all of society, must not be gained at the expense of any individual or any segment of society. 770 REFERENCES Ouoted in "Iatrogenic Disease," William S. Rowe, The Medical Journal of Australia, September 13, 1969, Vol. 2, p. 560. Forepage - The Complications of Modern Medical Practices, David M. Spain, 1963. "Medical Fthics and Controlled Trials," Sir Austin Bradford Hill, The British Medical Journal, No. 5337, p. 1043, April 20, 1963. Reed, W.; Carroll, J., and Agramonte, A.: 'Etiology of Yellow Fever: An Additional Note. Journal of the American Medical Association. Vol. 36, 431-440, Feb. 16, 1901. William B. Bean, the Archives of Internal Medicine, Vol. 117, p. 1, 1966. "Clinical Research in Achieving the Right to Health," Dr. George James, the Annals of the New York Academy of Sciences, Vol. 169, p. 301 Cochrane, A.L.: "Efficiency and Effectiveness, 1971, p. 67. Pierce Gardner and Leighton E. Cluff: "The Epidemiology of Adverse Drug Reactions. A Review and Perspective." The Johns Hopkins Medical Journal, Vol. 126, p. 77. 771 SELECTIVE BIBLIOGRAPHY DAEDALUS, Spring 1969 Experimentation with Human Subjects, Paul A. Freund 1970. Clinical Investigation in Medicine, Legal, Ethical and Moral Aspects, edited by Irving Ladimer and Roger W. Newman, 1963 Report of the Round Table Conference on Biomedical Science and the Dilemma of Human Experimentation held at the 7th General Assembly of the Council for International Organizations of Medical Sciences, 1967. Philosophy and Ethics of Medicine, Michael Gelfand, 1968. Experimentation with Human Beings, J. Katz, 1972. "The New Dimensions In Legal and Ethical Concepts for Human Research.'" Annals of the New York Academy of of Sciences, Vol. 169, Jan. 1970. "Early Diagnosis of Human Genetic Defects--Scientific and Ethical Consideration" Fogarty International Center Proceedings. No. 6, 1972. Report of Joint Hearing on ''National Advisory Commission on Health Science and Society" (S.J.Res. 75) Committee on Labor and Public Welfare. U.S. Senate. U.S. Government Printing Office 1972. "Clinical Pharmacology in the Human Volunteer' Journal of Clinical Pharmacology and Therapeutics. Vol. 13, No. 5, Part 2, Sept.-Oct. 1972. 772 RECENT LEGISLATIVE PROPOSALS RELATED TO THE ETHICS OF RESEARCH ON HUMAN SUBJECTS S.J.Res. 75 -- National Advisory Commission on Health Science and Society. (3/24/71) Mondale (Bayh, Brooke, Case, Fong, Harris, Hart, Hughes, Humphrey, Javits, Kennedy, McGee, McGovern, Moss, Nelson, Pell, Randolph, Schweiker) S. 3935 -- To amend the PHS Act to provide for restrictions on funds for experimental use. -- Javits (8/17/72) S. 3894 -- To amend PHS Act to provide for reservation of funds (8/8/72) for research into the possible social consequences ' of biomedical technologies. -- Tunney S. 3951 -- To establish within the executive branch an independent (9/5/72) board to establish guidelines for experiments involving human beings. -- Humphrey H.R. 16593 -- Dept. of Defense Appropriations -- Senator Kennedy introduced an amendment on October 2, 1972 -- None of the funds appropriated by this Act shall be available for any research involving un-informed or non-voluntary human beings as experimental subjects. 773 ISSUES IN HUMAN EXPERIMENTATI on or David Howard Wew York vuiversruvy :.cdaical Center 550 First Avenue New York, New Yorit 10016 774 liedical research has involved experimentation with human sub- Jects for many centuries, end few will deny its vast contributions to the clinical practice of medicine. The past decade in particu- lar has seen an increasing awareness of some very substantial legal end cthical issues surrounding the human experimentation process. This paper will discuss these issues and summarize some recent attempts by researchers, clinicians, government agencies, and other goncerned parties to replace emotion-charged debate with a set of orderly guidelines. In 196l, the World Medical Association forrmlated its Decla- ration of Helsinki.! “hile this concise code of ethics still sets the tone for policy at many major research institutions, the very censral) wording of the document provides only a rough framework within which must be constructed complex research procedures. A review of the literature since 106} reveals a wide variety of arti- cles dealing vith some of these unresolved specifics, among them the work of Beecher® and Jpthors. 33 To cite an example of the sort of conivoverey which may arise in this area, Lancet readers probably recall last year's heated correspondence alternately praising, and condemning the work of Dr. Saul Krugman in hepatitis research at the “Willowbrook State School in Staten Islané, New You 5-10 Opponents of the project concen- trated their attacks around ne point that the research involved proccdures in excess of those necessary.for diagnosis and treatment of the disenso; these critics noted that the situation appeared 775 2 even worse because the subjects involved were children institution- alized for mental retardation. On the other hand, cupportors of the rcscarch project emphasized its probable benefits to the medi- "cal care of the children in the study, the entire Willowbrook pop- ulation, and society in general; these proponents further noted that the side-effects to the children in the study seemed minor. As in any debsie, both sides in the Willowbrook donnybrook might have admitted to certain elements of truth in their adver- sarsaries' arguments had they not feared this would weaken their own. It is the firm conviction of this author that such partisan debate can only serve to impede progress in assuring the individual human subject's welfare. Formal Organization In the mid-1960's, the United States Public Health Service began to consolidate formal policy for the protection of research subjects. The great bulk of medical research and behavioral Vesuench in this country is performed in major institutions and AAPOTSA through grants, awards, or contracts by the Public Health Soervicé. All ‘such institutions rust cooperate in implementation of the Ccderal policy in its present form. To fulfill its responsibility for protection of human research ‘subjects, each institution appoints a committee of individuals who } are independent of research activities. This cormittee reviews all proposals for research projects involving human subjects. spadvl of any given propocal by the cormittee depends on satisfaction of 776 threc seneral requirements: 1. that the welfare of the experimental subjects will be protected adequately, 2. that the methods used by the investigators to obtain informed consent from subjects is appropriate, and 3. that the risks of the experimentel procedure appear small in relation to potential benefits. Specific details of cach research proposal rust be weighed by the review cormittee in Judging fulfillment of the above criteria, and examples will be presented later on. As a general rule, the cormittee rust evaluate any procedure in a medical or behavioral study vhich is ecmidered excessive of accepted disgnostic and/or therancutic practice. In orier to qualify for Public Health Service funding, each institution rust submit to the federal agency a formal acceptance of federal policy and alsc a complete description of the institu- tion's own policy cn human experimentation, the latter being based on the federal guidelinesi First of all, the institutional policy must include a statement of principles regarding the trcatment of human subjects. This may be either en existing document (such as the Declaration of Helsinki) or an original statement. Secondly, the institution must describe the structure of its review cormittee. The Public Health Service policy calls for a committec composed of members with diverse backgrounds in order to favor a broad-bascd revicw of all research proposals. Members of the committee may be regular institution personnel or consultants, 777 L but in either case they are presumed competent in evaluating both the specific research plans and their relation to the more general principles of rescarch acceptability. It is impossible to escape a comparison of such a committee with the jury system intrinsic to current judicial practice. In both instances, wé cannot catalogue all possible ramifications and therefore must resort to evaluation of each individual case by a qualified panel. The third and final component of institutional policy is a descrirtion of procedures to be followed by the review cormittec. This can be long and complicated, and only the major points will now be swmarized. Cormittee Procedures Review of all research proposals rust be completed prior to eward of funds by the Public Health Service. Furthermore, review should be carried out, if possible, before guint salon of proposals to the Public Health Service for funding. If a’long period of time _elapses between initial review by the committee and initiation of the research project, or if a researelior plans any changes in tho “protocol originally accepted by the committee, the review process should be repeated. In fact, institutional policy must guarantee thet continuing review of all proposals will be undertaken where appropriate. In order to maximize proteckion of subjects! rights and wel- fare during experimentation, review committees should determine for themselves the risks of any given rescarch protocol. IT these scem 778 5 greater then those stated by the projcet dircctor, appropriate sug- gestions should be jade to minimize such hazards. Coumittees may also decide to rejeet provosals which appear too risky oven after alterations in protocol. Anong other considerations, revicw commiitbane should mcasure risks with respect to the age, development, and physical and mental status of the particular subjects involved; effects of froquency of proposed test procedures rmst be gauged; and committees must agree that ontimel preparaticen for emergency situations is provided. Committecs should also be aware of specific legal rights where the proposed rescarch subjects will include children, prisoners, mili- tary personncl, or members of other special proups. Whenever possible, consent to rescareh participation should be obtained from the subjects themselves. Review committees must agree that this consent follows a careful explanation to cach subject of all experimental procedures, possible benefits, and attendant dan- gers; this explanation may be written and/cr — In cases where subjects cannot give informed consent (e.g., children or certain institutionalized individuals), review cormitteccs may reject the rescarch provosal unconditionally or may consider the validity of i —" ziven by third parties (e.g.. next-of-kin or legal guardians) where such consent is both authorized and deemed in the subjects! interests. Just as they cvaluate experimental hazards, review committees should evaluate expected and pogsible benefits to both the subjects participating in rescarch studies and society al large. As already 779 mentioned, cornittees must decide that these benefits cxceced the attendant risks in extending permission to perform research. Initial deliberation of a rescarch proposal by an institu- tion's revicu committee leads to one of several actions: 1. The committee may approve the project. 2. The committee may approve the project pending agree- ment by the project director to follow specific addi- - tional conditions. 3. The committee may request further information about the project in order to complete its review... li. The cormittee may reject the proposed project. Revicw cormittees should retain complete written records of all rescarch oroposals, discussion of provosals, correspondence with rescarch directors and the Public Health Service, and other perti- nent documents. Some Examples " The New York University Medical Center represents the type of major institution having research among its main functions. This institution has its own policy governing human experimentation, and, this statement fulfills all requirements of the broader Public Health Service policy described above. The actively operating Committee of Research ssaoeiabes consists of one Pro gery (chairman), one Professor of Medicine, I~ Professor of Psy- chiatry, and onc Dcan of the School of Medicine possessing a broad background in social science disciplines. 780 7 In addition to these regular members, representatives of other discivlincs arc invited to sit wish the cormittes when advisable. This author had the o»portunity to sit in on one such meeting of the committee (largely as an observer) and was greatly impressed by the members! acuity in digesting all details of rescarch proposals, focusing in on questionable points, and demonstrating deep concern for their task. To mention just a few sample discrepancies which mast be ironed out by the committee before approval can be granted: 1. Researchers often fail to svibull to the committee all forms necessary to evaluate protection of subjects. Example: failure to include the exact consent form to be utilized. - 24 Descrivtions of procedures or hazards may be too vague.’ Exannle: kidney study which states that an "evaluation of kidney function" will be performed, rather than stating exact method to be employed (clearance studies, biopsy, etc.). 3. Proposals may not clearly define the subjcects or the method of sclection. Ixarmvle: failure to state whether subjects are vol- unteers or hospital Lnepjilonts, ly. Proposals may nit carefully differentiate routine diagnos- tic and theravcutic podbean from thosc added for purposes of the research study. Example: variation in antibiotic dosage from stan- dard amounts for purvoscs of a drug study. 5. Investigators sometimes do not clearly state which speci- ade v3 fic procedures involve nwian subjects, ample: hehavioral study examining stress rcactions in both man and dogs. 6. Emergency precautions may seem inadequate. Example: every 781 8 medical study rust have an M.D. in attendance at all times. (This may seem obvious, but a surprising number of proposals initially fail to identify the attending hybolan.) 7. Proposals somobines. 40 not mention where experiments are to be carried out. The Committee of Research Associates must be satisfied that any prozosael first has the approval of all other institutions involved, as well as the approval of all pertinent lower cormittecs. E © . 8. Some studies may be allowed only in the case of "terminal" patients, and the cormittee may wish to know the criteria which the researchers will use to define the "terminal" state. Example: an alitenpt to transplant liver tissue only in cases of terminal hecpa- tio coma after all standard medical procedures have failed. 9. Certain projects may depend on third-party consent where ~ such authority is questionable. Example: parental onyeny for an infectious disease study where benefits to the participating chil- dren ere dubious. 10. Consent methods sometimes involve real or implied coer- elon, _ Exarple: a situation where admission to en experimental ward takes two days vhile admission to a regular hospital ward will take three weeks; this has a profound effect on an individual anxious to “initiate medical care for a given condition. 11. Research provosals may appear to duplicate previously com- pleted worl: which has showm to be unsatisfactory with respect to the treatment of human subjects. 12. Formal consent is often necessary for proccdurcs considered { 93-999 (Pt. I) O - 73 - 29 782 9 obtaining consent from by investisators to be too nmiror to bot subjects. sples: drawing of peripheral blood, skin biopsy. (Note: closely related to this concept, formal consent is required for research use of all blood samples and routinely discarded tis- suc obiained even in standard diagnosis and treatment.) 13. Rescorchers nay inadvertantly or intentionally exclude or underplay possible hazards in their description of studies to be role: peyehiatric study involving stress rcactions which docs not mention possible deterioratvion 14. Similarly, investigators may overestimate the benefits of their research to subjects and to humanity. As in all other cases, the expertise of the review committee serves to counteract this Conclusions By the very nature and scope of the issues, present guidelines of for human exvorimentatich are far from perfect, but they go a long way toward clecaring the morass. Hopefully this information will provide a basic introduction to other concerned parties; continued exanination, discussion, and revision of policies are peramount. 10. 11. 783 References World Medical Association: Declaration of Helsinki. Brit Med J 2:177, 1964. Beecher HK: Medical research and the individual. In Life or Death: Ethics and Options, Labby DH (ed), Reed College, Portland, Oregon, 1968, pp 114-152. Martin DC, Arnold JD, Zimmerman TF, Richart RH: Human subjects in clinical research - a report of three studies. New Engl J Med 279:1426-1431, 1968. Curran WJ, Beecher HK: Experimentation in children. J Amer Med Assoc 210:77-83, 1969. Ramsey P: The Patient as Person, Yale Univ Press, New Haven/London, 1970. Goldby S: Experiments at the Millowbrook State School. Lancet 1:749, 1971. Krugman S: Experiments at the Willowbrook State School. Lancet 1:966-967, 1971. Pasamanick B: Experiments at Willowbrook. Lancet 1:1078-1079, 1971. Giles JP: Hepatitis research among retarded children. Lancet 1:1126, 1971. Edsall G: Experiments at Willowbrook. Lancet 2:95, 1971. us Dept of Health, Education, and Welfare: The Institutional Guide to DHEW .Policy on Protection of Human Subjects, US Govt Printing Office #1740-0326, Washington, 1971. 784 “@ ASSOCIATION OF AMERICAN MEDICAL COLLEGES 5 oR J SUITE 200, ONE DUPONT CIRCLE, N.W., WASHINGTON, D.C. 20036 JOHN A. D. COOPER, M.D., PH.D WASHINGTON: 202: 466-5175 PRESIDENT March 5, 1973 Honorable Edward M. Kennedy Chairman Subcommittee on Health Committee on Labor and Public Welfare United States Senate Washington, D. C. 20510 Dear Mr. Chairman: The Association of American Medical Colleges has followed with deep interest the series of hearings on Quality of Medical Care and Human Experimentation which the Health Subcommittee of the Senate Committee on Labor and Public Welfare has been conducting. The ethical, moral and legal questions surrounding the ines- capable need for scientific observations involving human beings in advancing medical knowledge and capability, as well as in the application of such new knowledge, presents some of the most fundamental issues confronting contemporary society. We fully support broad and deep exploration of these matters both for fullest protection of the individuals involved as well as assuring the fullest benefit to mankind from scientific advance. You and your committee are to be commended for your resolute and constructive inquiry into these issues. We are pleased that your committee also intends to examine the continuing need for the further support and advancement of biomedical research. We should like to set forth briefly the views of the AAMC on this continuing need for the consideration of the committee and to serve as part of the record on this matter. The primary objective of biomedical research is to increase the understanding of the nature of man and his disorders and to develop the means for the prevention and treatment of disease, disability and ill health and to extend well-being. The many advances made in the past 785 Page Two The Honorable Edward M. Kennedy March 5, 1973 twenty-five years in the capability of medicine to cure disease, alleviate suffering and to forestall death present substantial evidence of the progress made toward the basic objectives of this scientific endeavor. The contributions made by, and the further promise of, the biomedical sciences for the well-being of mankind have been described in exten- sive detail in many recent studies. Among the more notable of these which should engage the attention of the committee are the following: 1. The Advancement of Knowledge for the Nation's Health, K Report to the President on the Research Programs of the National Institutes of Health, U. S. Department of Health, Education and Welfare, Public Health Service, July, 1967. 2. A Policy for Biomedical Research, A Report of an Ad Hoc Committee of the Council of Academic Societies, Association of American Medical Colleges, August, 1971. 3. The Life Sciences, A Report of the Committee on Research in the Life Sciences of the Committee on Science and Public Policy, National Academy of Sciences, 1970. 4. Biology and the Future of Man, edited by Philip Handler, President, National Academy of Sciences, 1970. Despite the enormous progress that has been made in advan- cing the scientific knowledge that underlies the practice of medicine, vast areas of ignorance still remain. The mass of essentially unnecessary and potentially controllable disease, disability and death with which we must contend because of this ignorance is formidable in its dimensions: . Fifty percent of all deaths are below age 70--the Biblically alloted span of life for man. People under the age of 65 generate two-thirds of all short-term acute hospital patient days. Forty-four percent of the entire population of the U. S. suffer from some chronic condition that imposes some degree of disability. . On any given day, an average of 1.7 million people, over two percent of the nation's employed labor force are absent because of illness. 786 Page Three The Honorable Edward M. Kennedy March 5, 1973 Medical ability to prevent, cure or alleviate these conditions is either non-existent or gravely limited by the simple lack of any adequate understanding of their nature and cause and thus, the means to deal with them in any definitive manner. All our efforts to improve the availability, access- ibility and quality of health care services; to diminish the financial barriers that stand between so many of the people of the nation and adequate health care; to overcome the nation's shortages in health manpower and health facili- ties are in the final analysis critically limited by the knowledge and technology that can be brought by the physician to the care of his patients. The further advancement of medical science and technology has the capability, as has been so amply demonstrated in the past, to completely trans- form the capacity of the physician to prevent and control disease, to extend life and promote health. Thus, our chief hope for restraining the rising costs of medical care and for diminishing the personal, social and economic burden of ill health and premature death lies in the continued advance of medical knowledge and technology through vigorous and substantial scientific effort in the biomedical sciences. Only through the acquisition of new knowledge and its application in sophisticated technology can we hope to further our capability to deal effectively with all aspects-- prophylactic, diagnostic and therapeutic--of disease. Federal support for this scientific exploration of the nature of life and disease during the past two decades has brought us to the threshold of an era of great potential for advancing the health capability of the nation. As a con- sequence of this effort, the United States has assumed a position of undisputed leadership throughout the world in biomedical and health research and in the scientific quality of its medicine. To gain the maximum benefit from this extraordinary achievement and assure continued progress in the medical science, we must endeavor to preserve and strengthen the structure of institutions, programs and operating relationships which have proved to be so successful thus far. This progress requires a balance between the research and scientific endeavor needed (1) to assure a vigorous environment for health pro- fessional education; (2) to advance the frontiers of man's knowledge and understanding of life through basic scientific investigation, which in turn; (3) provides for the vigorous organized pursuit of emerging opportunities to solve major health and disease problems. 787 Page Four The Honorable Edward M. Kennedy March 5, 1973 The continuity and productivity of this research enter- prise is critically dependent upon the emergence of young scientists through the research training process. Adequate support of new directions and new ideas in science and the stable financing of the research functions of academic insti- tutions. National policies which impair or contravene these basic requirements are a false economy and will result in a tragic interruption of many promising immediate developments and lead to a progressive deterioration of our capability to cope with the problems of tomorrow. Before closing this letter, I should like to comment briefly on the concern of the committee with the appropriate ethical, moral and legal safeguards for scientific inquiry involving the human subject. The AAMC, as I noted earlier, has a deep concern with this matter. It has fully supported the efforts of the National Institutes of Health to develop comprehensive and effective institutional review processes which submit the experimental proposals of an investigator to broad review and judgment by, not only his scientific peers, but also by individuals having broad ethical and legal concerns. The Executive Council of the AAMC recently reaffirmed its position on this matter by the issuance of the following policy statement during its September 15, 1972 meeting: "For moral, ethical, and legal reasons, it is essential to protect the rights and welfare of human subjects involved in biomedical research. The Association of American Medical Colleges believes that the primary responsibility for safeguarding the rights and welfare of human subjects properly lies with the individuals and institutions conducting the research. Accordingly, the AAMC supports the view that a review procedure designed to carefully monitor the moral, ethical and legal aspects of human experimenta- tion is an integral part of all biomedical research, both Federally and non-Federally funded. This review should apply as a minimum standard the NIH Guidelines for the Protection of Human Subjects and would best be accomplished by a diversified 788 Page Five The Honorable Edward M. Kennedy March 5, 1973 group representing basic science and clinical faculty, students, and appropriate members of the community (including ministers and lawyers)." I am sure the committee is fully aware that despite the progress of medical science, much of the scientific effort in these sciences is still dependent upon empirical observa- tion. In the final process of developing effective therapeutics, the stage is reached when this process of evaluation must move from the laboratory and the experimental animal to the clinical setting and the human patient. There is no other course if sound knowledge is to be gained and medicine advanced. Thus, the advance of medicine inescapably involves a degree of risk-- the only alternative to which is to bear the incommensurable risks of ignorance and the continuing burden of the status quo. The most intelligent management of this risk is a setting that fully protects the individuals involved is a condition to which all of us in academic medicine are clearly committed. I hope this communication will be of help to the committee. incerely, Jdhn A. D. Cooper, M. D. 789 Appendix 4 Page 1 §lLitnl 10-31-¢7 i August 30, 1967 T0 : See list below FROM : Surgeon General SUBJECT: PHS policy for intramural programs and for contracts when investigations involving human subjects are included I. Introduction Advances in health depend on the creation of new knowledge. The Public Health Service conducts and supports research in medicine, in the health sciences and in the sciences related to health to obtain this knowledgo. Some of this research can be done in the test tube and laboratory animals, but man himself is the ultimate necessary subject of study in the clinical phases of medical research, in most social and behavioral research and in epidemiologic and other public health research. The use of human beings as subjects in research poses problems for the investigator and his institution. The principles which follow r«flact the present position of the Public Health Service and apply to intramural programs and to contracts (a statement of policy applicavie to extramuzs. programs was issued in PHS Policy and Procedure Order No. 129, revised July 1, 1746, supplemented December 12, 1966, and January 24, 1967). Addressees: Director, Office of Comprehensive Health Planning and Development, 0SG Director, Bureau of Disease Prevention and Environmental Control Director, Bureau of Health Manpower : Director, Bureau of Health Services Director, National Institute of Mental Health Director, National Institutes of Health Director, National Library of Medicine Assistant General Counsel (Public Health Division) 790 Appendix 4 Page 2 6110.1 10-31-67 Zach Bureau Directarshall file with the Surgeon General a description of — the poiicy and procedure that his Bureau will follow in adhering to these principles, The Burcau Director shall report to the Surgeon General ? & all subsequent changes in this policy and procedure, II. Intramural Programs A. The Subject. The welfare of the individual is paramount. 1. Health and Safety. a. The subject myst have available to him the facilities and professional attention necessary for the PEOLOLEHEn Of his health and safety. b.. The health and safety of persons. other than the subject, if endangered by the research procedures, must be protected. c. Concern for the subject's comfort is essential. . Rights. a. Respect for the subject's privacy, dignity and legal rights is essentials . b. The individual must be free to make his own choice whether to be a subject in research. His participation shall be accepted only after he has received an explanation, suited to his comprehension’: of the reasons for the study and its general objectives, procedures, benefits, hazards and discomforts. Ab explanation so detailed as to bias his response or otherwise to invalidate findings may not be necessary in those behavioral, social, epidemiologic and demographic procedures that.invoive no risk of harm to the subject. He must, however, be informed oi his right to withdraw from the study at any time. 791 [From the Journal of Reproductive Medicine, April 1972] DEPO-PROVERA® CONTRACEPTION : INTERNATIONAL EXPERIENCE IN OVER 20,000 CASES (By Thomas J. Vecchio, M.D., Medical Research, The Upjohn Co., Kalamazoo, Mich.) Depo-Provera ® is a sterile aqueous suspension of medroxyprogesterone acetate which has been in use as a long acting progestational agent since 1960. In 1963 pilot trials were begun using it as a contraceptive agent, which demonstrated its feasibility and resulted in the selection of a dose of 150 mg every three months. To date, published and unpublished reports have been received from 53 investigators or groups comprising 24,233 patients, with an additional 10 groups reporting on other regimens in 2,405 patients. These studies have come from 36 countries for the three-month regimen and eight countries for the other regimens. Efficacy was determined from 30 pooled studies comprising 16,902 women and 124,692 woman-months. Twenty-five pregnancies occurred, yielding a pregnancy rate by the Pearl formula of 0.24 per 100 woman-years. The major disadvantage of Depo-Provera ® contraception is the loss of the normal menstrual bleeding pattern and its replacement by an unpredictable type of bleeding ranging from intolerably frequent bleeding and spotting in some women to complete amenorrhea in others, with most women showing oligo- amenorrhea. The average number of days of bleeding and spotting in each injec- tion interval decreases progressively with time. A few cases have shown heavy bleeding; eight authors reported a total of 37 curettages for bleeding in this survey. Despite this drawback, various authors report acceptance of the method in from three to 33 per cent of women desiring contraception at their clinics. One author recommends the routine use of supplementation with an oral estrogen such as ethinyl estradiol, 0.05 to 0.10 mg for seven days out of the mouth. It has been shown that such therapy tends to regularize the menstrual bleeding pattern. However, this has been used in only a small proportion of the patients studied. Estrogens are used for the control of troublesome bleeding. Side effects other than bleeding include weight gain and decreased libido in a few women. Reports are also received of nausea, vomiting, headaches, and irritability, but it is questionable whether these are related to Depo-Provera ® use. Thrombotic episodes were recorded in six women in these reports. Continuation rates com- pared favorably with those in patients using the oral contraceptives or IUD’s in the same clinics. The effect of Depo-Provera ® carries on for variable num- ber of months after the recommended three months interval due to the slow and variable release from the site of injection. The curve of cumulative preg- nancies in women discontinuing Depo-Provera ® to become pregnant runs paral- led to that of women discontinuing the diaphragm, with an average delay in the return of fertility of five months compared with the diaphragm. Senator Ken~Nepy. Tomorrow we will examine the medical experi- mentation on prisoners, and will hear of some particularly out- rageous abuses in the field of human experimentation. The subcommittee is in recess. [Thereupon, at 1:30 the subcommittee recessed the hearing until tomorrow, March 7, 1973, at 9:30 a.m. Oo 028779544