Merle A. Evenson Department of Medicine, University of Wisconsin, Madison, Wis. 53706
for
The
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Clinical Chemistry Training Programs of the rising cost of health care is a factor focusing attention on the field of clinical chemistry. T h e use of computers and mechanization in niedical laboratories, justified by predicted decrease in unit cost of the tests, has interested the Federal government, industry, and some academic departments in the field. The kind and extent of the coiitributions froin each of these resources is not yet apparent. A significant effort by analytical chemists would certainly result in major contributioiis in the clinical laboratory field. While this report is written for chemists, it should be kept in niiiid t h a t a clinical chemist niust have training beyond that of analytical chemistry, Previously, a clinical chemist's duties called for him t o develop and supervise chemical testing of end products of metabolism. Only recently have the measureinents on the rate of enzymatic transformation of intermediates been undertaken. As mechanized equipment becomes more available. a clinical chemist's duty will invohe the study of biochemical parameters in man. These studies vi11 be directed toward diagnosis and a,,qqessnieiit of abnormalities. The clinical cheniistry laboratory of the future will most likely serve a inore diagnostic function. The clinical chemist on one hand will be expected to draw more on the biochemistry of disease and on the other hand to introduce new physical chemistry measurements previously used only in research. T h e critical shortage of clinical BTIOSAL AWARESESS
chemists adequately trained in analytical chemistry soon will result in a manpower crisis. Federal Health Insurance for the Aged (Medicare) will enforce niinimum qualifications for the chemists under Title 20 of the Medicare Bill. effective in fiscal year 1972. The classification and requirements for each personnel category in the Medicare Bill are given in the Purdy and LIelville report ( 1 ) . Several training prograins have been initiated t o meet the challenge, but recent tightening of Federal funds for training grants has dampened much of the enthusiasm for additional new programs. What role analytical chemistry plays in the training of personnel a t all levels depends upon their willingness to recognize clinical chemistry as a worthy field and to work with human biological specimens. The magnitude of health care costs a t the national lesrel is interesting. Cost for health care increased from 26 to 60 billion dollars between 1962 and 1969 owing principally t o increased salaries for health care personnel. The gross national product IG.N.P.\ went from 4 to 8% in that seyen-year period. B y comparison, in Sweden, 2.5% of the G.X.P. was spent in 1955 for health care and 5.8% of the G.Y.P. was spent in 1968. 111 contrast to the increasing percentage 01' the G.X.P. spent for health care, the percentage spent for science in the U.S. decreased froni 2.5% in 1965 to 2% in 1969, according to TF'einberg ( 2 ) . These statistics lead to the conclusion that the priorities of increased support
for health care and decreased science support are not a recent trend. I n 1969 it v a s estimated that there were more than 8000 operating hospitals in the United States and more than 50% of these operated their olvn clinical chemistry laboratories. Today in the U.S., only 1600 people have more than a bachelor's degree in chemistry, and are members of the hnierican Association of Clinical Chemists IASCC) . There is a national need for qualified clinical chemists today. It was estimated that more than one billion laboratory test-3 mere performed in clinical laboratories in 1967 and more than 300 million chemistry procedures were peTformed in hospital laboratories in 1968. The 20 most coniinon clinical chemistry tests are glucose. blood urea nitrogen, sodium, potassium, chloride, bicarbonate, total bilirubin, uric acid. calcium, albumin, pH. Pco2and Poz serum, glutaniicoxalacetic transaminase. total protein, lactic dehydrogenase, alkaline phosphatase, creatinine, choiesterol, phosphorous, creatine phosphokinase, and protein-bound iodine. These tests usually provide 907. of the work volunie in the chemistry laboratory. I n addition, conimercia1 clinical laboratories perform a substantial percentage of the test volume done in the United States. T h e clinical laboratory business is yery large and growing rapidly. Currently each clinical cheniistry laboratory doubles its own size every f h e years. Can analytical chemistry make contributions to this field nosT and in the future?
ANALYTICAL CHEMISTRY, VOL. 42, NO. 14, DECEMBER 1970
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Before looking to the future, let’s look a t the history of clinical cheniistry. I n 1526, Paracelsus stated that .‘chemistry should not be concerned with transmutation of elements but should serve as the foundation for medicine” ( 3 ) . Voii Helmont, Pregl, Priestley, and Lavoisier all worked on biological and medically related problems during the 17th, 18th. and early 19th centuries. I n the early 1800’s organic chemistry included human chemistry, chemistry of other living systems, and carbon chemistry. Later, organic chemistry was redefined as the study of only carbon chemistry. Early in the 1900’s biocheniistry divided into human chemistry as taught in medical schools and what has now become knomn as classical biochemistry, often taught outside of and independent of medical schools. I n 1906, a group of chemists studying living organisms formed the Biochemical Society and began publishing Biochemical Joua? ~ a l . The Journal of Biological Chemistry was first published six years later and contained several clinical chemistry studies. S u t r i tional biochemistry departments began working with microorganisms such as yeasts, molds, and E coli in the 1930’s. In 1948 the Society for Clinicai Chemists was formed. It principally attracted people trained in medicine and ’or biochemistry. I n 1955 clinical chemists published their onm journal, and in the 1960’s clinical chemistry began to draw more classically trained chemists into the field. h few analytical chemists such as Folin, Peters, T a n Slyke, and Somogyi actively published some of their work in the previously mentioned journals in the 1920’s. Several clinical chemistry tests and some equipment are named in their honor. The Folin-Vu and Somogyi-Nelson glucose methods and the Van Slyke gasonieter illustrate their contributions. Johns Hopkins University was one of the first medical schools in the early 1900’s to use chemists in the training of physicians. Many other medical schools have now followed in this practice. With the departure of biochemists from the medical school, a phy54A
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sician-pathologist frequently was pressured into administratively becoming responsible for clinical chemistry. The chemistry procedures were usually manual (cockbook), fern in number, and not very accurate or precise. (Gravimetric sodium and potassium are examples of the laborious, nonspecific, and manual clinical chemistry procedures formerly used.) The pathologist had the unpleasant task of being responsible for a laboratory that as the justified target of niany complaints. K i t h the advent of conimercially available instrunientation (the photoelectric colorinieter and the flame photometer in the 1930’s),the quality of the performance improved and the workload of the hospital laboratory increased rapidly. W i e n mechanization of manual procedures occurred v i t h the introduction of the Technicon Autohnalpzer in 1967, a quantum jump occurred in the laboratory‘s work volume. I n 1965, still another quantum jump occurred when multichannel AutoAnalyzers were introduced into clinical cheniistry laboratories, Conditions within the hospital laboratory began to improve. The heavy work load and service comniitment were still present but instrumentation had eleyated the laboratory stature. Financially, in 1965, the laboratory was Trery attractive and iionphysicians were entering the field a t a n increasing rate. As a result. n e v analytical techniques were introduced to the routine laboratory by the nonphysiciaiis The problem of the lack of adequate training in analytical cheniistry again is evident when one observes holy some of the new tools frequently are misused. The diverqity of analytical techniques used in a routine clinical chemistry laboratory is vast. Sodiuni, potassium, and lithium tests are usually accomplished by flame emission methodc. Calcium, magnesium. copper, zinc, and lead are frequently done by atomic absorption. Glucose. blood urea nitrogen, and phosphorous are usually carried out by visible absorption spectrophotometry. Total barbiturates are done by uv absorption. Kidney and gall stone analyses utilize infrared spectrophotometry while blood cor-
ANALYTICAL CHEMISTRY, VOL. 42, NO. 14, DECEMBER 1970
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tisol uses fluorescence. Drug and steroid fractionations are often done by gas-liquid chromatography. The enzyme tests CPK, SQOT, and LDH are completed by kinetic methods. Serum protein fractionation is dolie by electrophoresis and lipid fractionation by thin layer chromatography. Chloride analysis may utilize couloinetry and pH, potentiometry. Spinal Auid protein analysis frequently is accomplished by ultrafiltration dialysis and/or gel permeation. This is but a sanipling of the techniques used every day in the production line of the routine clinical chemistry laboratory. Can anyone say that this is not analytical chemistry? Let’s look next a t the adininistrative and academic arrangements usually encountered by clinical chemists. I n an organizational structure. the clinical chemist is usually responsible to a physiciandirector of clinical laboratories. The physician will most often be a pathologist. The pathologist-director may not have financial freedom from the hospital administrator. so the clinical chemist niay not have direct access to the financial coiitrol of the laboratory. I n general, the clinical chemist may ha\-e significant responsibility without adequate authority. A clinical chemist map have an academic appointment in pathology or some other medical department. Alternatively, he may have a total or joint appointment in another science-related department such as biochemistry or physiology. Generally, hoTTever, the clinical chemist does not have the same type of formal training as the majority of the members of his department. This situation may not be very desirable for professional growth. I n addition, one occasionally hears from the chemist, “I don’t want some physician telling me how t o do a chemical analysis,” and the physician may in turn reply, “I won’t tolerate some chemist telling me about medicine.” It can be an unfortunate encounter for all concerned. A very large portion of a clinical chemist’s job responsibility is spent with service. A real danger exists when the clinical chemist becomes a supertechnician a t the expense of research and teaching. For the well
A Compact FID is ailable From GOWmMAC
Special Report
being of the individual this should not occur. Still another problem exists between the clinical chemist and the academic analytical cheniist. T h e anaIytica1 chemist frequently criticizes the clinical chemist‘s work as “an old application of an analytical principle and lacking in originality and sophistication.’’ T h e work of the analytical chemist is frequently criticized by the clinical chemist as ’ t o o expensive or not relevant to today‘s problems. It is lacking in recovery experiments, in interference studies, and in coniparison of results to the existing method on fresh human specimens.” TVith skyrocketing health costs, it is logical to direct more attention t o the biochemistry of human disease. If more fundamental human biochemistry is elucidated ( 4 ) using solid analytical chemistry. then steps toward disease prevention and earlier detection should alleyiate sonie of the financial pressure now on health care. The blending of analytical chemistry and hunian biocheiiiistry can make a n increasingly important contribution to health care. Analytical chemistry must continue to distinguish itself by maintaining high quality. Excellent analytical chemistry needs to be practiced daily in clinical chemistry laboratories. Frequently, hoxyever, high analytical quality in the ineasurements are lacking throughout the laboratory. Solid analj-tical chemistry training for all clinical chemists can help improve the quality in the field of clinical chemistry. I n summary, one strongly agrees with -1Ieinke ( 5 ) t h a t ‘.analytical chemistry is not a fading discipline” and with Siggia ( 6 ) that “when we as analytical chemists take pride in the quality of our work, we as individuals or we as a field cannot b e demeaned.”
Heart of the GC, FID Detector 12-700
I n response t o demand. Called the 6 9 - 7 0 0 , it has many desirable features. For example, operation i n excess of 300 “ C . Three-step i n p u t attenuator. Ten step, binary output attenuator. Sensitivity of 1 x 10 l 2 g / s e c hydrocarbon. Pyrometer readout, coarse and fine suppression cohtrols and many other features which will provide rugged, cont i n u ou s perf or ma nce. The 6 9 - 7 0 0 , Standard FID is a companion t o GOW-MAC’S compact thermal conductivity instruments. These units are a l l tough, inexpensive, reliable and deliberately simple i n design. They don’t replace research gas chromatographs b u t they can perform equally with t h e m i n routine analysis. This makes t h e research units available for t h e m o r e sophisticated work f o r which they were designed. It is not economical t o do routine analysis on a research instrument. Send f o r o u r literature. The technical facts are worth having.
References I (1) R. C Purdy and R. S. Melville, I A N ~ LCHEM. . 42 (12), 3 2 8 (1970). (2) A. &I. Weinberg. Science 167, 141 (1970). (3) S. Natekon, C h . Chem. 16, 258 (i9:n) ~~...,.
( 4 ) T. D. Kinney and R. S. Melville, Lab. liivest. 20, 382 (1969). ( 5 ) A. F. Findeis, >I. K. Wilson, and W, W.Meinke3 ANAL.CHE~CL. 42 (7), 27A (1970). (6) Sidney Siggia, ANAL.CHEM.41 (13): 50A (1969).
GOW MAC INSTRUMENT CO.
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