key: cord-353330-j00jj2og authors: Rej, Robert title: Clinical Chemistry through Clinical Chemistry: A Journal Timeline date: 2004-12-01 journal: Clin Chem DOI: 10.1373/clinchem.2004.042820 sha: doc_id: 353330 cord_uid: j00jj2og The establishment of the modern discipline of clinical chemistry was concurrent with the foundation of the journal Clinical Chemistry and that of the American Association for Clinical Chemistry in the late 1940s and early 1950s. To mark the 50th volume of this Journal, I chronicle and highlight scientific milestones, and those within the discipline, as documented in the pages of Clinical Chemistry. Amazing progress has been made in the field of laboratory diagnostics over these five decades, in many cases paralleling—as well as being bolstered by—the rapid pace in the development of computer technologies. Specific areas of laboratory medicine particularly well represented in Clinical Chemistry include lipids, endocrinology, protein markers, quality of laboratory measurements, molecular diagnostics, and general advances in methodology and instrumentation. In this overview, I have selected numerous highlights and representative articles illustrating advances in the practice of clinical chemistry as they appeared in the pages of this Journal, and I have placed them in historical perspective by juxtaposing them with contemporaneous events in the broader world. I was guided by both the citation frequency of papers that had significant impact and opportunities that a paper provided to exemplify developments in technology, instrumentation, and medicine of the day. This journal timeline is not intended to be a detailed history of the Journal, as many facets of our heritage have already been reported (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) . In reviewing nearly 100 000 pages of the journal, I was again struck by how much has changed, yet how much has remained the same (1 ) . Over the years, many papers were devoted to general topics still very much of interest to our readers today: lipids, endocrinology, protein markers, quality of results, and advances in methodology. Of course, much has also gone the way of high-button shoes and 5¢ coffee, such as thymol flocculation tests and measurement of protein-bound iodine. The development of the field of laboratory diagnostics can be seen in tracing the evolution of figures within papers, from the large number of photographs and hand-drawn diagrams of glassware that were characteristic of the first years of publication to displays of results from devices, rather than the devices themselves. I was occasionally amused by the now-quaint spellings of "technic" and "computor", as well as the liberal use of the plural "serums". The AACC annual meeting played a central role over the years, with names of speakers, awardees, and their abstracts and biographies printed as regular or supplemental pages. Review of those entries will help to further document the interesting topics of the day, as well as to uncover such-today politically incorrect-entries as "ladies programs". Those days, however, also boasted hotel rooms with daily rates of $7.50 in Santa Monica and $8.50 in Boston; "charming" pictures of meeting venues also graced our pages. Many of today's efforts at standardization and harmonization were more than foreshadowed in several seminal papers appearing in this Journal during the 1960s and 1970s; perhaps if more attention had been paid to these papers when they were published three or four decades ago, current standardization efforts might not be so necessary, or at least not so difficult and costly in their implementation. Another theme that often appeared was the role of the profession of medical laboratorians and relationships among professional societies; some of the rhetoric makes for more-thaninteresting reading that borders on voyeurism. The give and take in correspondence regarding various view points on the various issues of the day (13 ) also seemed to contain far more spleen than the tamer exchanges that are encountered today. Nonetheless, it betrays an enthusiasm that can be admired whichever side one might have supported. I was also struck by the specific "personality" of the journal under each of its three editors as it evolved and developed. Although they appeared on our mastheads under differing titles, their role clearly match that of "Editor-in-Chief" in other publishing circles. It may be happenstance that their tenures were contemporaneous with reasonably defined advances and achievements in the field: "Managing Editor" Appleton (1955) (1956) (1957) (1958) (1959) (1960) (1961) (1962) (1963) (1964) (1965) (1966) (1967) (1968) (1969) with the period establishing the discipline as we know it today and with the automation of classical chemistry procedures; "Executive Editor" King (1970 King ( -1990 coincided with advances in immunoassay, computer-assisted techniques, and new instrumentation; and our current adjectiveless "Editor" Bruns (1991-) has been coeval with applications of molecular biology and evidence-based medicine. The journal has benefited greatly from the occupancy of the Editor's chair by these three; a history of the Journal's leadership appears elsewhere (12 ) . Another theme that emerged in my review was the rapidity with which clinically useful procedures put major scientific discoveries to use. There are many methods and clinical applications described in our pages that swiftly followed the publication of major biomedical findings (many of which led to Nobel Prizes). The first research papers describing the structure of hemoglobins, immunoassays, HPLC, GC/MS, monoclonal antibodies, PCR, MS/ MS, etc. were followed in very short order by a multitude of applications of the knowledge in our pages. Predicting the future is tricky business. In 1967, a US Senate Subcommittee reportedly heard testimony forecasting that, by 1985, Americans would work 22 hours each week, 27 weeks a year, or that they would retire at age 38 (14 ) . If only that had come to pass! On the other hand, some true visionaries got it just about right. "I have not been reading science fiction," wrote David Seligson in 1962, on the future of clinical chemistry in these pages (15 ) . He continues: The time will come when blood is sent from a hospital to a large receiving center-that is, a laboratory which does large numbers of special analyses automatically and continually, day and night, weekends and holidays . . . special instruments can sort, analyze, punch out answers, and return reports. Even the latter, the report, will probably disappear in our new way of life because we shall have instruments which identify samples, analyze them, and electronically enter the result into a computer. The latter could be as much as 100 miles away. . . . Our laboratory instruments will feed the data into the computer and the computer will convert it to a final report and store the information. A physician who wishes to know the electrolyte values for his patient will not call the laboratory, he will tell the computer what he wants and the computer will direct a typewriter which will give him the information at the rate of 1000 lines per minute. The same information can be requested 10 times in one hour without irritating the laboratory secretaries or anyone else. Furthermore, the laboratory will also have a computer outlet so that serial data on any patient can be observed for fluctuations. The clinical chemist will be able to get any information he needs in seconds without going to his own files or to the record room. There will be no useless files or the wasted effort of unnecessary searches. The computer will not lose data; the intern will not carry the precious report in his pocket where no one can find it. The computer will serve the laboratory in other ways too. It will provide automatic programs and will turn on and off the machines of the laboratory. It will digitalize data and provide direct readout of final answers. It will provide a new dimension for the clinical chemist. Pretty remarkable insight, considering not all that much in the way of automation existed in medical laboratories four decades ago and that there were only 15 computers in the entire US in 1955, just 7 years before his commentary was written. Admittedly, these prescient comments are rather atypical for our pages; the Journal has generally been filled with factual and useful information that advances our knowledge and profession in an incremental fashion. I was both rather surprised and more than slightly disappointed that there was precious little in the way of extravagant or, even better, dystopic, predictions of "clinical chemistry of the future" to regale the readers of this overview. As predicted by Seligson over 40 years ago (15 ) , computers have had a powerful role in clinical chemistry, as in most other disciplines. As we look back on 50 years of articles, the advances in laboratory medicine in many ways parallel the spectacular achievements in the semiconductor and computer fields: ever faster/better/cheaper. In the last decade, computers and the Internet have played a dominant role in the dissemination of scientific information. Our Journal was one of the first to embrace these technologies, and it went "online" in 1998 with full content available back to 1997. Abstracts of articles also were accessible for the period 1975-1996, and authors and titles of articles were listed for the period 1965-1974. This too will change. In the very near future, the full content of Clinical Chemistry, from Volume 1, page 1 up to the current issue will be made available online. With this occurrence of a totally electronic version, I take a fair degree of gratification in imagining that I may well be the last person to have browsed through all 50 years of Clinical Chemistry in its 200-kg paper incarnation (Fig. 1 ). Although librarians, and atavists of all ages, may bemoan the eventual demise of the medium of choice for the past few hundred years, I shall not be among them. This project has more than reinforced my leanings toward the obsolescence of a very inefficient vehicle for communicating data, ideas, and information. The hundreds of decaying, amber-colored pages that I reviewed also challenge the idea that electronic is ephemeral and that paper is permanent. Although large parts of the world remain technologically unconnected, I am confident that access to all of the information in our pages will be facilitated in those regions as a result of these initiatives. Obtaining the paper copy of this, and other, journals is still impossible in many laboratories around the globe. Although Internet access may not be universal, access to the electronic version will be far easier-and less expensive-than is access to the print copy. This Journal, and others, have shown their commitment to wide dissemination of the information in their pages by making content available without charge to institutions in developing countries (16, 17 ) . The sightings of cyber cafés in remote regions of the planet attest to the view that access to information will be increasingly electronic. In many respects, an even greater "digital divide" exists regarding access to the older literature; if information is not available electronically, it is often ignored. Review of the past 50 years of this journal has underscored for me the importance of the fact that every advance is based on the findings of previous work. Many today may think that use of mass spectrometry for newborn screening is a relatively new application, but this use was already described in 1972 (18 ) . With the electronic republication of the first four decades of Clinical Chemistry, access to many of the seminal articles in the field will be instantly available to all readers. I hope that the sampling from the Journal in this timeline will inform, and occasionally amuse, and that you will be persuaded to explore the vast archive that is scheduled to be available at your desktop early in 2005. Like as the waves make towards the pebbled shore, So do our min hasten to their end; Each changing place with that which goes before, In sequent toil all forwards do contend. Vol. 1, number 1. AACC establishes a bimonthly scientific journal-Clinical Chemistry-"to raise the level at which chemistry is practiced in the clinical laboratory; to stimulate the development of new methods for use in the clinical laboratory; to encourage those engaged in this field to pursue advanced studies so as more effectively to render service to the public; and to create and maintain a forum where clinical chemists may exchange ideas and information concerning their scientific, technical and professional problems." The first volume comprises some 430 pages. A multinational study of the effects of diet on serum lipid concentrations suggests the benefits of a Mediterranean diet. The authors understatedly-but correctly-infer that the mechanisms by which diet affects blood lipids "must be complex". Keys The role of serum lipoproteins in atherogenesis is at an early stage of development, and new analytical tools are described. The analytical variation of the newly described methods is said to be lower than "spontaneous intraindividual variability". QC for me. "[It] seems very likely that many more laboratories will organize their own systems of quality control within their own walls. There is also every indication that more countries are about to commence schemes of issuing certified samples". Wootton ID. Standardization in clinical chemistry. Clin Chem 1957; 3:401-5. Dry with a twist. The first routine application of reagents in a dry chemistry strip also introduces an enzyme catalyzed reaction: glucose oxidase replaces the widespread alkaline copper reduction test. Clinical Chemistry at a crossroads. The role of laboratory professionals and their accreditation and licensure are reviewed, and a position paper is issued; licensure is advocated as the "quality of laboratory service being Abstracts make their appearance in the Journal at the start of each article rather than as a final "Summary" as in earlier volumes. The roles of the laboratorian and the status of the profession of clinical chemistry were covered extensively in the first 10 volumes of the Journal. Volume 7 had more than its share of coverage, and readers interested in the topics of concern of the day are directed to Clin Chem 1961;7:75-91;303-7;421-2 for a comprehensive overview. Move over Dr. Karmen. The "International Unit" is born as the preferred manner for expressing catalytic activity of enzymes (Clin Chem 1961;7:199). Serum as a "standard"? Say it isn't so. The role of reference materials in the calibration and quality control of laboratory assays is examined. Calibration using serum-based materials is criticized as substituting "compensation" for reliability. Klugerman Not another enzyme method! Lipase measurement by turbidimetry decreases analysis time from 3 h to 20 min. Vogel WC, Zieve L. A rapid and sensitive turbidimetric method for serum lipase based upon differences between the lipases of normal and pancreatitis serum. Clin Chem 1963;9:168 -81. Tonks' formula. The quality of laboratory testing is examined by use of an approach based on biological variability. Tonks proposes the formula, which will eventually become eponymous, that analytical variability should be less that 25% of biological variability ("1/4 of the normal range"). According to this criterion, more than 40% of 4762 results obtained in an interlaboratory survey are considered unacceptable. Tonks DB. A study of the accuracy and precision of clinical chemistry determinations in 170 Canadian laboratories. Clin Chem 1963;9:217-33. More on urea. Diacetyl monoxime is used to quantify urea. Coulombe JJ, Favreau L. A new simple semimicro method for colorimetric determination of urea. Clin Chem 1963;9:102-8. PBI was a high-volume test. Protein-bound iodine assays are automated. Stevens CO, Levandoski NG. Automation of protein-bound iodine determination. Clin Chem 1963;9:400 -7. Benotti J, Benotti N. Protein-bound io-dine, total iodine, and butanol-extractable iodine by partial automation. Clin Chem 1963;9:406 -16. Clinical Chemistry to appear monthly. The price of subscriptions to the Journal will be increased by $2.00 per year to $8.00 per year to cover anticipated increases in expenses with proposed monthly publication. Julius Sendroy is elected to chair of the Board of Editors as Harold Appleton was named to the new position of Managing Editor (Clin Chem 1963;9:640 -2). Washington-to-Moscow "hot line" communications link opens, designed to reduce risk of accidental war. US President Kennedy is shot and killed by a sniper in Dallas; Lyndon B. Johnson becomes President the same day. There are 15 000 US military advisers in South Vietnam. The first "push-button" telephones are introduced. Simultaneous automation. The first multichannel analyzer to perform eight determinations simultaneously is described. The analyzer records directly on calibrated paper, providing an "immediately usable form". One operator can perform 960 individual tests per day, equal to the output expected per person in a month with manual techniques. Skeggs LT, Hochstrasser H. Multiple automatic sequential analysis. Clin Chem 1964;10:918 -36. Calcium and phosphorus: a completely automated flow system. Kessler G, Wolfman G. An automated procedure for the simultaneous determination of calcium and phosphorous. Clin Chem 1964;10:686 -703. Tyrosine and phenylalanine method helps to identify newborns with phenylketonuria Wong P, et al. Micromethods for measuring phenylalanine and tyrosine in serum. Clin Chem 1964;10:1098 -104. Let the cards fall where they may. A notched card system organizes reprints. Over 800 key words can be used. Weissman N. A punched-card reference system for biochemists. Clin Chem 1964;10:214 -23. Calcium. Atomic absorption spectroscopy is applied to determination of serum calcium. The method is claimed to be the "method of choice". Zettner A, Seligson D. Application of atomic absorption spectrophotometry in the determination of calcium in serum. A practical method is developed, suitable for screening of patients before anesthesia or after exposure to organophosphates or nerve gas. Garry PJ, Routh JI. A micro method for serum cholinesterase. Clin Chem 1965;11:91-6. A punch card system for the storage and retrieval of laboratory data is described. A day's results required 2000 cards, which were processed in batches at the end of the day. Nonetheless, introduction of the system Profiles in serum. The biochemical profile is born. Multichannel analyzers allow 10 simultaneous determinations on Ͻ1 mL of serum at a rate of 60 specimens per hour. Results appear on five two-pen recorders. "A very high level of preventive maintenance is required continuously." Acceptance by physicians is "enthusiastic". Johnson. The citation recognized his work as a pioneer in "the exact science of clinical chemistry, a specialized branch of biochemistry, represented by a profession whose members render most important support to clinicians in the diagnostic and prognostic aspects of their work in treating patients." Clin Chem 1966;12:453. A slippery slope? The trend to purchased reagents accelerates; a policy for "Reagent Sets and Kits" is published (Clin Chem 1966;12:43-4). The semiautomated pipette is devised. "People with little or no background in laboratory work can make accurate pipettings after a short practice period." Harrison NB. Semiautomatic pipetting device (the Governor Pipet) for clinical chemistry procedures. Clin Chem 1966;12:890 -3 The Great Proletarian Cultural Revolution begins in China. Metropolitan Opera House opens in Lincoln Center, New York City. The first episode of the science fiction television series "Star Trek" airs. What is a standard? A seminal report discussing standards, standardization, reference materials and methods, and definitive methods is published. The report has its origins in the AACC "Committee on Standards and Controls"; many issues are relevant LIMS arrives. The benefits of a newly implemented laboratory information system include the ability to use punch cards for requisitions and the issuing of patientsummary reports for 12 consecutive days or sets of results. The system was implemented on an IBM 1440 with "a core memory of 8K". Cillo AA. A simplified, economic, working "computerassisted laboratory information system" (CALIS Oak Ridge Conference. The Journal publishes the proceedings of the "Second Annual Conference on Automated, High-Resolution Analyses", a meeting that evolved into the AACC Oak Ridge Conference. Topics include such forward-looking topics as miniature photometers for liquid chromatography, resolution of overlapping peaks by use of an on-line computer, multicolumn chromatography with computerized readout, two-dimensional thin-layer chromatography, separation of nucleic acids by high-resolution liquid chromatography, and analyses by electron spectroscopy (Clin Chem 1970;16:623-725). A new spin on analyses. The centrifugal analyzer is introduced to medical laboratory applications. Immediate reading and following of reaction kinetics make practical the use of rate measurements for analyses that were formerly carried out only as reactions that reached near end-point or equilibrium. Interferences that required deproteinization or other pretreatments were obviated. Fabiny DL, et al. Hard to believe that they didn't before. The FDA is given regulatory responsibility for in vitro diagnostic products (Clin Chem 1973;19:1425-6). Clinical chemistry as an "industry". Dr. King muses: For better or worse, like it or not, the "compassionate science" is becoming more and more indistinguishable from General Motors in its approach to the "customers," primarily of course as a result of quantum leaps in automation technology. The two major current trends foreseen for clinical chemistry in the United States are (a) a greater demand for "stat" instruments and (b) a demand for high-volume profiling machines. As an example of the latter, Metpath, a commercial laboratory whose revenues reportedly increased by 45% (to $16.15 million) from 1976 to 1977, found it necessary to purchase four AutoChemist analyzers, and has ordered five more ($500 000 each, 5000 samples/day capacity each). This example, not typical, illustrates that clinical chemistry increasingly is filing the popular image of Big Business, complete with mergers, acquisitions, diversifications and all its other accoutrements. The major commercial laboratories are growing at what one official called an "absurd" rate, with pretax earnings approaching 12% and steadily rising: not surprisingly, this gives the proprietors reason to expect even closer scrutiny by the federal government (Clin Chem 1977;23:1956 -7). The world's last known case of smallpox appears in Somalia. The number of hosts on ARPANET exceeds 100. British Airways inaugurates regular supersonic service on the Concorde. Now on film! An automated, drychemistry system is described and applied to several clinically useful analytes in serum. Curme HG, et al. 1980) . Other IFCC recommendations include renaming some common analytes: "carbamide" is preferred to "urea", "creatininium" to "creatinine", and "adrenalinium" to "epinephrine". Editor King doubts that US clinical chemists will soon adopt these recommendations (Clin Chem 1979; 25:1989 From the editor's desk: "One of the greatest technological advances since sliced bread, in our view, is the word-processor, by which we mean a typewriter with a "memory," in which pages and pages of material can be stored and called forth. If the typist has a word processor, making corrections involves minutes as opposed to hours, and no brand-new errors introduced . . . [I]f you have access to such a wondrous machine, by all means lose no opportunity to utilize it. All of our lives will be happier" (Clin Chem 1982; 28:2005) . When was the last time you've seen these words? IFCC neologisms promulgated: entic, areic, massic, baric, and ergatic (Clin Chem 1982;28:1438). Clinical Chemistry's circulation is 13 682. Harold Appleton, the first Editor of the Journal, dies. Argentina invades the Falkland Islands, and Britain steps in to protect its territory TCP/IP communication is defined. The first computer virus, Elk Cloner, is written by 9th grader Rich Skrenta. Another spin on the immunoassay ball. The latex immunoassay, a nonisotopic method based on agglutination by protein of calibrated latex particles coated with a specific antibody, is described. Bernard AM, Lauwerys RR. Continuous-flow system for automation of latex immunoassay by particle counting. Clin Chem 1983;29: 1007-11. CA 19-9. A carbohydrate antigenic determinant that is increased in sera from patients with adenocarcinomas is discovered and measured by a radioimmunometric sandwich assay. Del Villano BC, et al. Radioimmunometric assay for a monoclonal antibody-defined tumor marker, CA 19-9. Clin Chem 1983;29:549 -52. Get the phenols out. Because phenolic free radicals can cause anomalous results, a method is proposed that uses proteinase K and ethanol and obviates the use of phenol. Buffone GJ, Darlington GJ. Isolation of DNA from biological specimens without extraction with phenol. Clin Chem 1985;31:164 -5. Put the phenols back in! Certain phenol derivatives are found to enhance light emission from luminol by Ͼ1000-fold. The enhanced system enables a rapid, sensitive assay; it is applied to immunoassays for hCG, digoxin, and factor VIII-related antigen. Thorpe GH, et al. Phenols as enhancers of the chemiluminescent horseradish peroxidase-luminol-hydrogen peroxide reaction: application in luminescence-monitored enzyme immunoassays. Clin Chem 1985;31:1335-41. Clinical Chemistry publishes guidelines that outline the requirements for hardware, software, and program design to be used in the immunoassay laboratory. NMR is used to detect, identify, and study the major normal and abnormal organic acid metabolites in urine from patients. The technique requires Ͻ1 mL, requires no extraction or derivatization, and takes Ͻ10 min. The authors "believe that it is particularly suitable for the rapid and acute diagnosis of inborn errors of metabolism, especially the organic acidurias, and for acute pediatric clinical care." Iles RA, et al. Use of proton nuclear magnetic resonance spectroscopy in detection and study of organic acidurias. Clin Chem 1985;31: 1795-801. TPA. Specific determination of tissue plasminogen activator, and its inhibitor, in plasma allows multiple samples to be assayed simultaneously within a few hours. A procedure for improving the specificity of ELISA methods also was devised. Chmielewska J, Wiman B. Determination of tissue plasminogen activator and its "fast" inhibitor in plasma. Clin Chem 1986; 32:482-5. Ranby M, et al. Age dependence of tissue plasminogen activator concentrations in plasma, as studied by an improved enzyme-linked immunosorbent assay. Clin Chem 1986;32:2160 -5. Heterophile antibody interference. Circulating human antibodies reactive with animal proteins are demonstrated and shown to be a previously unsuspected source of interference in immunoassays. Boscato LM, Stuart MC. Incidence and specificity of interference in two-site immunoassays. Clin Chem 1986;32:1491-5. Clinical Chemistry publishes the proceedings of the 9th Annual A.O. Beckman Conference for the first time; previously they were issued in book form (Clin Chem 1986;32:B1-106). The January issue inaugurates the appearance of Technical Briefs as a new format to "summarize findings that are of interest to a relatively limited audience". Readers are directed to contact the authors for fuller details. Briefs originally were of abstract length, with no references (Clin Chem 1986;32:2234). Following the Santa Fe conference in May, King editorializes on the "National Laboratory Human Gene Library Project" and other "Big Science" projects. King JS. Time to think big in human biology? Clin Chem 1986;32:1600 -1. One of the reactors at the Chernobyl nuclear plant explodes. The first laptop computer is introduced by IBM. There are now ϳ5000 hosts on ARPANET. Oliver North, Jr., tells a congressional inquiry that higher officials approved his secret Iran-Contra operations. AZT wins FDA approval for use in the treatment of AIDS. Digging commences for the Channel Tunnel. A rapid and precise assay is developed for a marker of fibrotic disease. Cocaine and pregnancy. Analysis of urine from neonates born to cocaine-using women shows that benzoylecgonine persists in urine for up to 5 days after delivery. Cocaine-exposed infants are shown to have neurobe- ECL. Electrochemiluminescence is used as a signal system for immunoassay. The new technology uses no radioisotopes, has stable signaling compounds, has a large dynamic range, and has limits of detection that are in the femtomole per liter range. Blackburn GF, et al. Electrochemiluminescence detection for development of immunoassays and DNA probe assays for clinical diagnostics. Clin Chem 1991;37:1534 -9. DNA enzyme immunoassay. A method to specifically detect products of PCR is described. Mantero G, et al. DNA enzyme immunoassay: general method for detecting products of polymerase chain reaction. Clin Chem 1991;37:422-9. More on accuracy. Laboratory data must constitute "timely and trustworthy information". CLIA'88 is said to place a high priority on test accuracy. Bowers GN Jr. Clinical chemistry analyte reference systems based on true value. Clin Chem 1991;37:1665-6. Clinical Chemistry publishes a detailed summary of classified documents from the former German Democratic Republic (East Germany) dealing with government promotion of the use of drugs in highperformance sports. The report details the use of anabolic steroids by athletes in a variety of sports, but their use with adolescent girls, particularly swimmers beginning at 14 years of age, is frightening: "The treatment of young girls with androgenic hormones was especially rewarding in the medal-rich swimming events, where it secured consistent international success." The authors caution parents around the world: "Even the androgenization of young girls has been, and remains, a documented practice in the sport system of countries outside the GDR and the socialist system." Franke WW, Berendonk B. Hormonal doping and androgenization of athletes: a secret program of the German Democratic Republic government. Clin Chem 1997;43:1262-79. The AACC Subcommittee on cTnI Standardization concludes that commercially available assays are useful for detection of cardiac injury; however, differences in cTnI results are attributable to a lack of standardization and heterogeneity in the cross-reactivities of antibodies to various troponin forms (Wu AHB, et al. Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I. Clin Chem 1998;44:1198 -208). Cardiac troponins T and I collected shortly after ischemic symptoms are used for predicting clinical outcomes (Christenson RH, et al. Cardiac troponin T and cardiac troponin I: relative values in short-term risk stratification of patients with acute coronary syndromes. Clin Chem 1998;44:494 -501). An approach for screening for deficiency of steroid 21-hydroxylase and congenital adrenal hyperplasia is published. Krone N, et al. Comprehensive analytical strategy for mutation screening in 21-hydroxylase deficiency. Clin Chem 1998;44:2075-82. Lab-on-a-chip. A glass microchip is described in which reagents and serum samples for competitive immunoassay can be mixed, reacted, separated, and analyzed. Chiem NH, Harrison DJ. Microchip systems for immunoassay: an integrated immunoreactor with electrophoretic separation for serum theophylline determination. Clin Chem 1998;44:591-8. www.clinchem.org:Clinical Chemistry goes online! The full text of the Journal is available to all subscribers; content from the previous year is also available. Abstracts and titles are available, starting with issues appearing after 1964. Eleven European Union countries agree on a single currency, the Euro. The US Department of Justice and 20 US states file an antitrust case against Microsoft. Hyperglycosylated hCG is shown to be a new marker for Down syndrome screening; its measurement is claimed to improve the performance of screening protocols [Cole LA, et al. Chechen rebels take 763 hostages in a Moscow theater. Terrorists detonate massive bombs in two nightclubs in Kuta, Bali. Quaoar is discovered in our solar system. It is estimated that 11% of the world population is on line; for the English-speaking world, the proportion is 43%. Start with STARD. A protocol for evaluating the completeness and accuracy of biomedical research is published. A checklist and flow diagram will aid researchers in improving the quality of reporting of studies of diagnostic accuracy; this will benefit clinicians, researchers, reviewers, journals, and the public. Paperless Clinical Chemistry. The Journal embarks on a program to have all of its content-from Volume 1, page 1 to the present (nearly 100 000 printed pages)available on line. Previously, full content availability was limited to articles published in 1997 (Volume 43) and later. Vladimir Putin wins a second term as President of Russia. The European Union expands to include Poland, Lithuania, Latvia, Estonia, the Czech Republic, Slovakia, Slovenia, Hungary, Malta, and Cyprus. George W. Bush elected to a second term as President of the United States. Abbott TDx monoclonal antibody assay evaluated for measuring cyclosporine in whole blood Bruns assumes the Editorship. Although King was not known for his indiscriminate endorsement of the latest technologies in publishing, he notes that "the days of the conventional printed scientific journal . . . may be numbered Iraqi troops invade Kuwait, setting off the Persian Gulf War. The Hubble Space Telescope is launched. ARPANET ceases to exist PSA is shown to exist in serum largely as a complex that blocks epitopes for certain antibodies directed against the PSA molecule. Lilja H, et al. Prostate-specific antigen in serum occurs rapid detection of group B streptococci Fifty years of Clinical Chemistry Clinical Chemistry: the history of a journal Recollections of the AACC and related activities, continued Some historical perspectives on AACC Clinical Chemistry: a fragmentary history (1969 -1977) Citation Classics in Clinical Chemistry highlight the cumulative impact of useful methods-a tribute to Editor John [sic] Stanton King. Essays of an information scientist: science reviews, journalism inventiveness and other essays They use enzymes for everything! Citation classics in intermediary metabolism The evolution of immunoassay as seen through the journal Clinical Chemistry Citation classics in lipid measurement and applications The clinical chemist Fifty years of Clinical Chemistry, three pioneering editors Correspondence: reference standards and substrates for alkaline phosphatase From carbons to computers: the changing American office Men and machines The clinical chemist Combined use of gas chromatography, mass spectrometry, and computer in diagnosis and studies of metabolic disorders I am grateful to past and present members of the Editorial Board of Clinical Chemistry who offered helpful suggestions in the preparation of this review. Particular thanks go to the Executive Committee of the Editorial Board and to our Publisher, Mac Fancher, and our Editor, Dave Bruns, for their helpful suggestions and encouragement. I would also like to thank BonoTom Studio, Inc., for rendering the collages of historic events and Christina McIntyre, Barbara Paternoster, and Valarie Watersun for their invaluable assistance in collecting and preparing items for inclusion. Clinical Chemistry adopts a new cover with an abstract design suggesting molecules, globes, or possibly, the harmony of the spheres. New typography is adopted, and Measurement of expression of hTERT, which codes for the catalytic subunit of telomerase, is shown to have the potential to discriminate between healthy and tumor cells. High-c. cRP is shown to have prognostic utility in patients with acute coronary syndromes and to be a strong independent predictor of future coronary events in healthy subjects. Rifai N, Ridker PM. High-sensitivity C-reactive protein: a novel and promising marker of coronary heart disease.