COLUMBIA LIBRARIES OFFSITE HX64088863 QP915.A3C21 Tentative plan for a np ?/*-•/)? £ZL Columbia (BniV)ersftp intijfCttpirftogork College of •pijpstrians ano burgeons! llibrarp Digitized by the Internet Archive in 2010 with funding from Columbia University Libraries http://www.archive.org/details/tentativeplanforOOcarn t ft *t r. Gr. Frederic S, Le$ Qolnrnbia IMroraity Tentative Plan for a Proposed Investigation into the Physiological Action of Ethyl Alcohol in Man Proposed Correlative Study of the Psychological Effects of Alcohol on Man NUTRITION LABORATORY CARNEGIE INSTITUTION OF WASHINGTON Vila Street, Boston, Mass., U. S. A. January I, 1913 s Ol PROPOSED TENTATIVE PROGRAM EOR AN INVESTIGATION OF THE PHYSIOLOGICAL EFFECTS OF ALCOHOL TO BE CARRIED OUT IN THE NUTRITION LABORATORY OF THE CARNEGIE INSTITUTION OF WASHINGTON, BOSTON, MASSACHUSETTS. It is a well established fact that ethyl alcohol, when taken in small doses, the total amount per day not exceeding 7? grains, is completely oxidized in the body and thereby replaces nutrients as a source of energy. This fact suggests a large number of experimental problems in the domains of physiology and physi- ological chemistry which, when studied by the newer methods, should give re- sults of fundamental importance. The calorimetric researches of Professor Atwater and his associates in Middletown. Connecticut, were extended over long periods, usually of 24 hours. The evidence regarding the rapidity of the combustion of alcohol is very uncertain and it therefore seems desirable to again study this source of energy and to determine if possible its relation to severe muscular work. a^ _, /\. The Nutrition Laboratory is especially well fitted for studying problems U /GRAM. I. Subjects (numerous in each class). 1. Non-users of alcohol. 2. Moderate occasional users. 3. Habitual drinkers (exceeding 30 c.c. absolute alcohol per day.) 4. Excessive drinkers (with whom the effects of abstinence should he likewise studied). II. Alcohol Doses. Controls if possible under conditions in which the subject will nut know when alcohol is administered! 1. Ethyl alcohol in various forms. Pure alcohol, distilled spirits, wines, champagne, beers, ales and bard cider should he Used. The variation in effects of the different kinds of liquors, if any, to be de- termined on one or two simple physiological or metabolic processes. If the effects in the above arc not found directly proportional to the amount of abso- (3) lute alcohol present, this fact should be elaborated in a subsequent research, and this present investigation should adhere to pure ethyl alcohol + water. 2. Doses, amounts. a. one single dose, varying amounts. b. repeated doses at varying intervals. 3. How administered. a. by mouth (drinking). b. by mouth (stomach tube). c. rectal enema. d. inhalation of alcohol vapor (Leonard Hill). e. by the skin. Immerse hand or arm in vessel (arm plethysmograph) con- taining moderately dilute alcohol. Is there any cutaneous absorption ? Perhaps stimulate cutaneous circulation by massage or elec- tricity and note alcohol absorption. 4. When administered. a. empty stomach (cocktail) between meals drinking. b. with food. 1. with protein. 2. with fats. 3. with carbohydrates. 4. with condiments. 5. with glucose or nutritive enemata. (4) 6. after or with a very hearty meal, i. e., when stimulated by protein large amounts, and when large amount- of food with little protein or little stimulation. c. during fatigue. 1, mental fatigue. 2. physical fatigue. d. during sleep | wake up from sound sleep and take dose and sleep afterwards). III. Absorption of Alcohol. 1. Absorption rate. a. from stomach. After introduction into stomach, use stomach pump. ( Lavage. ) b. from colon. After enemata, irrigate, determining alcohol in re- sidue after varying lengths of time. c. by digestive tract vs. by respiratory tract. Which is quicker? Results to be noted by respiratory exchange. Leonard Hill. 2. Completeness of absorption to be ascertained. No alcohol in urine, feces, etc. ? 3. Absorption by skin to be tested. IV. Circulation. 1. Heart beat and pulse. ... , Radial artery a. graphic tracings by sphygmograph. Carotid artery Capillary plethysmography electrocardiograms. (5) Studying changes in the character and in rate of propagation of pulse waves. Effect of irritation of the stomach on the heart beat. b. Pulse rate. 1. resting subject, niichtern, lying quietly until pulse has reached minimum level before alcohol is administered. 1. Use minute pulse as unit. 2. Use pulse in two respirator)' rhythms as a unit (electro- cardiogram). 2. during sleep, if possible. 3. During muscular work. a. riding a bicycle ergometer at definite rate of revolution and degree of resistance. Ride till pulse constant, then take alcohol while riding. b. is maximum pulse level affected by alcohol taken just prior to muscular work? Time to reach same or actual level. c. is time of return to minimum pulse lying down after work altered? Is actual level after work altered? 4. During various forms of mental activity. (6; 2. Vasomotor reactions. a. Plethysmograph observations. b. Rlood pressure. 1 . resting. 2. severe muscular work. Quasi-continuous records. (Erlanger sphygmomanometer) after rectal administration. c. Note alteration in cutaneous circulation. Is parallelism noted in temperature curves from rectum, groin, axilla affected? (Also skin temperature curve if possible). (See body temperature). d. Effect of alcobol on splanchnic circulation. Rapidity of stomach and intestinal movements. (See digestion). 3. Rate of blood flow (Krogh). 4. Blood. a. Morphology. b. Blood gases. Note effect of alcohol on tissue respiration. Is dissociation curve of blood changed? V. Respiration. 1. Respiratory center. Does alcohol affect the sensitivity of the respiratory center (Lind- hard). (7) 2. Alveolar air. Does alcohol affect the alveolar air 1. by reason of respiratory center changes or 2. by affecting the alkalinity of the blood? 3. Volume of lungs. Does alcohol affect elasticity of bronchial passage or alveoli? Tidal air. Vital capacity, etc. Dead space in breathing. 4. Respiration rate, depth, rhythm. Spirometer tracings under all conditions (best done in connection with experiments on gaseous exchange). 5. Rich oxygen mixtures. Is respiratory quotient altered by breathing oxygen rich mixtures, when the (easily and rapidly?) oxidizable alcohol is present? (pulmon- ary combustion). 6. Holding the breath. Does alcohol alter "breaking point" a. after breathing high oxygen? b. after forced deep breathing? Paying special attention to inhaling oxygen containing alcohol vapor. (Leonard Hill.) W VI. Digestion and Sf.cretion. 1. Motibility of stomach. X-Ray studies. Effect of alcohol on rapidity of movements and continuance of move- ments. Hunger (Cannon, Carlson). 2. Diuresis. VII. Nutrition (Metabolism). 1. Alcohol and general and total metabolism. Effect on character of katabolism. a. Respiratory quotient as index. If man at rest on high carbohydrate diet on preceding days has respiratory quotient niichtern of .90, how will alcohol ingestion affect the respiratory quotient? Is there a selective combustion for alcohol? If so, respiratory quotient should approach .666. b. If a niichtern quotient of .78 is obtained by regulation of diet on preceding days and alcohol -f- sugar is given will quo- tient 1. rise indicating prevailing carbonhydrate combustion? 2. or fall indicating prevailing combustion of alcohol? c. Relative combustion rates of alcohol and various sugars as de- termined by above method. What amount of various sugars will offset the ingestion of alcohol to prevent low- ering the quotient ? (9) Effect on amount of katabolism and energy output. a. Series of niichtern experiments with respiration apparatus, subject very quiet, pulse minimum, etc. then alcohol and note effect on total katabolism on 1. Carbon dioxide production. 2. oxygen absorption. This experiment can be advantageously made simultaneous with observations on pulse, temperature and respiration. Is intensity of effect proportional to dose? Is duration of effect proportional to dose? For example, will a 50-gram dose double the effect on the kata- bolism noted by a 25-gram dose, or will it simply prolong it twice as long? b. If any effect on metabolism, is there a compensatory effect later? i. e., Is there an after-effect ? What it its nature ? c. Protein ingestion results in a greatly stimulated katabolism. What is effect of alcohol on this increase? Study effect on rapiditj of beginning of initial increase, intensity of rise, prolongation of effect and return to normal base line. d. Ingestion of cane sugar or laevulose likewise increased noticeably the total katabolism. Has alcohol any effect on this increase? (10) 2. Alcohol and carbohydrate and fat metabolism. Effect of alcohol on the tolerance of various sugars. Influence of alcohol upon the amount of reducing material in the urine I I 'eters' Method |. Study this frmn the standpoint of the influence of alcohol upon the oxidative powers of the body. If alcohol given simultaneously with sugars and alcohol burned first, then possible lowering of sugar tolerance. To what degree? Are various sugars affected differently? 3. Acidosis. a. Meat-fat diet or non-carbohydrate diet induces an acidosis in nor- mal man. 1. Will alcohol ingestion retard or hasten the onset of the acidosis ? 2. In such an acidosis what is effect of alcohol ingestion? 3. Alcohol -\- large amounts of protean in an acidosis. Is in- creased metabolism due to protein ingestion plus the in- creased metabolism of acidosis affected by the alcohol? Will the body burn alcohol and facilitate the storage of the deaminized portions of the protein molecule? b. Alveolar air and respiration volume. By llaldane's apparatus and by the spirometer <>n the universal respiration apparatus study the relationship between alcohol (ii) ingestion and the alveolar air in acidosis also the respiratory volume. 4. Protein metabolism. a. Nitrogen output. Probably affected by alcohol diuresis. If an increase, is it due to 1. Washing out. or 2. Increased cell katabolism? Controls should be made with distilled water diuresis. Nitrogen partition in blood may be studied by Folin's methods. b. Purine metabolism. 1. Uric acid in blood. By Folin's new colorimetric method ; study effect of alcohol on uric acid in blood. 2. Urine. On purine-free diet. With large volumes of urine by diuresis produced by alcohol and control by drinking large amounts of water. 3. Does alcohol ingestion alter exogenous or endogenous purine metabolism? (Beebe.) c. Effect of alcohol on the nitrogen partition and the total N balance on a. Starch-cream diet. b. Protein-rich mixed diet. c. Meat-fat diet (Kayser's work). (12) d. After-effect of severe muscular work mi X output. Is it affected by by alo ihol ingestii 'ii ? Is it exaggerated or not? Compare also X partition under these conditions. 5. Intermediary metabolism. a. Carbonaeccous material in urine. Any change in character <>f solids in urine. C : N ratio. Cal : X ratio. A possible index of a perturbed intermediary metabolism (Iliggins and Benedict). 6. Energy metabolism. a. Muscle tonus. Is it altered? Muscle hardness (Exner). b. As muscular work demands a rapid oxidation of material, increases the ventilation of the lungs, quickens the circulation, and there is in part at least a selective combustion of carbohydrate, a series of experiments to study the oxidation of alcohol by the body under the influence of intense muscular activity is of fundamental importance. 1. Is there a selective combusion for alcohol during severe muscular work ? With no alcohol the respiratory quotient always tends to rise during severe work. If alcohol is burned in preference to protein, fat or carbohydrates, the quotient would be markedly lowered. 03) 2. When alcohol and carbohydrates are ingested and muscular work follows, is the metabolism chiefly of carbohydrate, i. e., high quotient or alcohol low quotient? 3. In a body depleted of glycogen by severe muscular work a. is the carbohydrate first stored if fed with alcohol, i. e., does the respiratory quotient remain low? b. when alcohol is given is there any evidence of formation of glycogen from either protein or fat to replace the store, the maintenance-combustion being from alcohol ? 4. Does muscular work increase the capacity of the body to burn alcohol ? To what extent? Maximum amount burned? During muscular work are larger amounts tolerated before signs (incipient) of intoxication appear? 5. Is appearance of "second wind" quickened or retarded by alco- hol ingestion? 6. After effects of muscular work as influenced by alcohol? a. Rapidity of return to normal metabolism. Is rate of return altered, i. e., does alcohol help out on the rapidity of recuperation? (u) Is pulse base line lower or the same after work as with- out alcohol '' Do alcohol and glucose superimpose their effects on after- work peric id c,r is glucose stored and alcohol burned? Is a larger amount of alcohol burned per hour after work when glycogen supply is low? 7. Heart beat, character of wave, etc., after severe muscular work. Does alcohol alter it? Electi tcardii lagrams, etc. 8. Intensity of work. Capacity for work. Endurance. Is it affected? Can subject do more or less with alcohol? Maximum working capacity. Bicycle ergometer sprint!) Flow long and how high revolutions per minute? Is the efficiency of the body as a machine based upon the rale of speed with a constant load altered by taking alcohol? Any compensating-aftcr effects? In a prolonged fatigue experiment, i. e., riding strong pace and load. How test endurance? Ratio of external mus- cular work and total energy output? 7. Heat regulation. a. On resting subject. Secure normal diurnal variation, i. e., after lying down for some time to avoid temperature rise clue to muscular activity. (IS) 1. Does alcohol administration alter character of the curve taken from minute to minute. Rectal temperature by thermo element. Benedict and Slack apparatus. 2. Body temperature rise produced by muscular work. Is it affected in intensity or time by alcohol? 3. Body temperature fall after work. a. Rapidity of fall. b. Level after work. 4. Sensitivity to temperature. Local plotting of skin area to tem- perature reaction (Tigerstedt's lab. technique). Is physi- ological zero altered? (Aesthesiometer tests should be of interest.) 5. Reaction to exposure to cold air 15° C. Shivering keeps up temperature. Will shivering take place after alcohol is given? Get body temperature curve of subject and expose to cold air by disrobing. Is curve altered? Is alcohol given before it is altered? Same experiments on drunken man. What effect of dis- robing on temperature curve? (16) PSYCHOLOGICAL PRI K3RAM. Prepared by Raymond Dodge, Experimental Psychologist of the Nutrition Laboratory. It is assumed without discussion that any complete investigation of the effects of the ingestion of ethyl alcohol must include nol only its immediate and remote effects on the general metabolism of the body, but also, as far as possible, its effects on special tissues thai arc influenced ui any peculiar way l>v that par- ticular kind of alcohol. It seems obvious further that among those special tissues, nervous tissue and the end organs of sense and motion are of particular importance because of their intimate connection with intelligence, personality and conduct, and their bearing on social welfare and economic efficiency. Unfortunately, only the simpler and the more elementary neuro-muscular processes can be studied directly by present laboratory technique. Of the important higher mental and moral processes there is at present scant probability for securing experimental data of scientific relia- bility. Modifications of the moral controls, of business judgment, tact and relia- bility, of mental stability and balance, are not experimentally measurable in any direct way. They must be studied, if at all, by some indirect method. Thi> tech- nical defect is a serious limitation to all experimental investigations of the psy- chological effects of the ingestion of alcohol since it is in precisely these direc- tions that general experience indicates that the effects of alcohol are probably most serious. It is consequently all the more necessary to choose the lines of direct investigation with experimental tact for probable correlation-. The direct («7) investigations must not only be reliable in themselves, but they should indicate as much of the higher and more complex mental mechanism as possible. Con- sequently, of the indefinite number of experimental facts concerning elementary processes that might be collected, actual experimentation should be determined by the following principles : (1) The technique must be scientifically adequate to the precise purpose in view and reliable with respect to instrumental constants, latency, variability, etc. (2) Relatively elementary neuro-muscular processes should be investigated in their simplest forms so far as possible. Complex processes should be so chosen as to be definitely related to the elementary processes and directly or indirectly analyzable into their several factors. (3) All experiments should directly contribute to a systematic analysis of neuro-muscular processes and their variations. The real value of an adequate test consists in its correlations or possibility of correlation. (a) It is of the utmost importance that there should be the highest possible comparability of data obtained from different individuals and from the same individuals under different conditions. All instrumental constants should be known and the technique should be reproducible. (b) Unless the personal peculiarities and idiosyncracies of voluntary at- tention and effort are directly the subject of investigation or are otherwise capa- ble of estimation, experiments should be as independent as possible of the caprice of the subject. This is particularly true of the elementary processes. Uncon- (iS) trolled complex tests, such as ergo tents, addition and multiplica- tion experiments, are particularl) questionable. < )ne must know whether de- crease of achievement is due to decrea ed specific capacitj or to fatigue of gen- eral psychological controls, such as interest and incentive. (c) All experiments should be as free as possible from practice effects. Thoroughly practiced processes that require no special training should be chosen wherever possible. This excludes most of the common reaction experiments except for a few trained subjects. Dnder all circumstances base lines should be complete enough to include a measure of any practice effects thai m iy develop. ( (/ ) In all psychological experiments it is desirable, and in the inv< tion of processes subject to the caprice of the individual it is essential, that the ingestion of alcohol of one subject or set <>i subjects should be rigidly controlled by other normal subjects and by the same subjects Under normal circumstances. (e) I believe that the ingestion of alcohol should be masked as completely as possible. I do not know the best technique. Suggestions on this matter are especially requested. (/) It seems desirable also to get quantitative data wherever possible of remote neuro-muscular effects; especiallj should this be studied with reference to the deterioration of memory residua, and associations established under alcoholic use, and conversely. (<7) I regard it as extremely importanl thai experiments be made on habit- ual moderate and excessive users of alcohol under abstinence. It seems to me highly important to study the psycho-physiology of the facts whose extreme form is represented in the mental complex by craving. SECTION I. Sensitivity of the End Organs of Sense and Motion. Since all stimuli must be given through the end organs of sense, and since muscular contraction is the most accessible indicator of nervous action, the in- fluence of alcohol on the organs of sense and motion is a primary, though prob- ably not a very important, consideration. (a) For most accurately reproducible threshold experiments I propose the use of Martin's electrical threshold apparatus and technique. Aesthesiometric and pain threshold tests depend on a large number of variables extremely diffi- cult to control. Sound, taste, smell, and muscular sense thresholds do not seem to be of sufficient probable significance to warrant special investigation. The pain threshold, on the contrary, is not unimportant. It may be that many changes in the higher complexes depend on modified sensitivity to pain. Sugges- tions for technique would be especially welcome. (b) Since vision will be the sense most used in the higher tests I recom- mend tests for changes in visual acuity, preferably the E test, after proper cor- rection of the subject for astigmatism. (c) The following muscle conditions should be determined: (1) muscle threshold for electrical stimulus (Faradic current) ; (2) fatigue and recupera- tion. The development and duration of relatively permanent muscle contraction as the result of work. I propose the use of reciprocal innervation of the autogonistics of the middle finger moving back and forth as rapidly as possible for 30", a rest of 5" and renewed innervation for 5". This is a modification of (20) the tapping test, eliminating the stop; (3) steadiness of mil cle contraction, either visual nystagmus in lateral fixation or dire'd measurement of involuntary movements of the hand ; i wel j of musi ction. [n order to elimi- nate voluntar) control I iuggesl photographic registration of eye movements, for reasons explained in "The Ocular Reactions of the [nsrine" 1 by Diefendorf and Dodge; (5) the corresponding metabolic demands should be measured directly or by their effeel on the pulse rate, h, fact, pulse rate should be taken with every test. I regard this as of the utmo I importance a. indicated in mj paper on "Mental work" 2 ; (6) Most of these muscle and threshold experiments should he made before and after severe physical work and periods of rest. SECTION II. Latency, Sensitivity, Configuration, Refractors Phase vnb Recuperation or tiii: Simi'i.i- Rj flexes. Since the entire psychophysical mechanism must he studied as a complica tion of nervous ares, the nervous are should he studied in its simplest form. according to Principle (3), i. e., in the simple reflexes. The refractory phase may he of peculiar importance in connection with the problem of fatigability and recuperation. Because of the adequacy of the respective techniques £es1 particular study of the knee jerk and the protective wink reflexes. (1 ) The knee jerk should he measured by muscle thickening, with special reference to latent time, sensitivity, height and configuration of the curve, and (1) .In experimental study of the ocular reactions of the insane from pho- tographic records. Brain. Vol. XSSI. pp. 451— 489. Psychological Review, January. 1913. the duration of its return to the abscissa from which it starts. For reasons de- scribed in my "Systematic Exploration of the Knee Jerk" 1 I prefer a pendulum hammer stimulus and direct registration of the muscle curve; (2) the protec- tive wink reflex should be studied with special reference to latent time, sensi- tivity, height and configuration of the curve, and the duration and completeness of the subsequent refractory period. For reasons described in my paper on the "Refractory phase of the wink reflexes"- the stimulus should be a sound stimulus and the registration should be photographic. SECTION III. Complicated Reaction Arcs. Practiced reactions of more complex arcs which would be comparable in different individuals are relatively few. I suggest (1) eye reactions to suddenly appearing peripheral visual stimuli. These are in the nature of choice reactions and demand a definite space complication of the muscular response. They are thoroughly practiced for all normal adults and relatively independent of the caprice of the subject. (See "Ocular reactions of the insane"); (2) Since speech is the best practiced universal (for literates) reaction, I should combine these records of the eye movements with speech reactions, naming the letter presented (one of 2 or 4), as carried out in my "Experimental study of visular fixation"*; (3) I believe further that in specially trained individuals their regular (1) A systematic exploration of a normal knee jerk, its technique, the form of the muscle contraction, its amplitude, its latent time, and its theory. Verworris. Zcitschrift fur allg. Physiologie, Vol. XII, pp. 1 — 58. (2) The refractory phase of the protective wink reflex. Am. Jour, of Psychology, January, 1913. (3) An experimental study of visual fixation. Monograph supplements of the Psychological Review, Vol. VIII, No. 4, Esp. pp. 53 — 55. (22) business reactions should be studied as in the Kraepelin and Aschaffenberg experiments. SECTION [V. M I Mni;-, AND ASSOI tATION TESTS. Since distinctively mental functions chiefly involve memory and association' some approved form of memory and association tests should be used, i should not be too time consuming or too exacting in the subject, (a) For mem- ory I suggesl the speech reaction to a "normal" series of 12 gradually appearing words; three repetitions of the series should show a quantitative preservation valm- with,,,,! actualh, learning tin- series. This tesl has the tentative approval "' ''• K - M " ,llT (^ottingen); ,1:) Controlled association test should be made either '" the form "'" Kraepelin mathematical tests or some similar method. Pulse rate must be taken with these tests. 2 Free association tests for the possi- ble changes in tin- character of the associates should be made with special refer- ence to time of response and pulse rate; (c) I also recommend tests on the rapidity of reading aloud, including photographic registration of the fixation pauses of the eyes (Dodge and Dearborn) and a record of tin- pulse rate. SEi TI( i\ V. Correlated with the above experiments there should he some investigation of the perseverance of the subject, i. e., of tin- fatigability of the higher psychological controls involved in persistent effort and prolonged voluntary attention. (1) "A working hypothesis for inn.