The Clinical-Chemical Interface of Medical Science: Its Development in This Century*

A n n a l s o f C linical and L a b o r a t o r y Science, Vol. 4, No. 4 Copyright © 1974, Institute for Clinical Science The Clinical-Chemical Interface of Medical Science: Its Development in this Century* A. BAIRD HASTINGS, P h .D ., D .S c . Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA 92073 When I seriously sat down to prepare high state of the medical sciences. But each my remarks to you this evening, I was became involved in applying chemistry to aghast to see the title that I had given clinical problems through a fortuitous state Dr. Sunderman. Who am I to presume to of circumstances. speak on the “Development of the Clinical- Let me briefly introduce them to you. Chemical Interface of Medical-Science in First is Donald Van Slyke, born in 1883 this Century?” It’s a damn good title, but of Dutch descent, who left us in 1971. He I’m certainly not qualified to live up to it. worked hard in the lab and played tennis What I’d like to hear is a panel of friends throughout his life. He was unbeatable at such as Donald Van Slyke, Otto Folin, Wil either. liam Mansfield Clark and John P. Peters Second is Otto Folin, born in Sweden in gathered here to discuss the subject. So I 1867, who was head of biochemistry at invited them—and they accepted—or at Harvard from 1907 until his death in 1934. least let’s imagine that they have. Each in He invented many quantitative methods his way made technological and conceptual useful in clinical practice and was a much developments that have led to the present loved teacher. * Presented at the Association of Clinical Scien Third is William Mansfield Clark who tists’ Banquet, March 9, 1974, La Jolla, CA. lived from 1884 to 1964 and spent most of 213 214 HASTINGS his life as head of physiological chemistry Here he had intimate contact with a small at Johns Ilopkins. His contributions were group of clinical investigators and the re in acid-base and oxidation-reduction bio sponsibility of applying chemistry to the chemistry. He was a perfectionist in his solution of selected clinical problems and research and was highly respected by his here he remained until he reached the re students. tirement age of 65—after which he had a Finally, there was John P. Peters, always second productive career at the Brook- called Jack, born in 1887, who was Pro haven National Laboratory, dying while fessor of Medicine at Yale from 1921 until still active at age 88. He never really aged. his death in 1955. A scholar in medicine, One can say Van Slyke saw clinical who was feared and revered by his res chemistry develop; he contributed person idents and never compromised on prin ally to much of it. (As his first assistant ciple, Jack teamed up with Van to write from 1921-1926, I had the privilege of ob the classic two volume work Quantitative serving what was happening at the Clin- Clinical Chemistry. ical-Chemical Interface and of participat We’ll try to get a word from each of ing, at times, to a minor extent). them. This was the period when the chemical description of the body fluids in terms of mass and composition in health and disease was under investigation. Methods had to be devised for quantitative determination of individual constituents. Since existing chemical methods usually required large Donald D. samples of blood, they had to be modified Van Slyke and adapted to accommodate what were 1 8 8 3 - then regarded as small samples—meaning 1 9 7 1 one cubic centimeter of blood or other fluid. Quantitative measurement of the end products of the chemical reactions involved were limited to gravimetric, titrimetric, colorimetric and gasometric procedures. In his time, Van Slyke made use of all four— D o n a l d V a n S l y k e although he is best known for his ingenious Van Slyke had taken a Ph.D. in 1907 in use of gasometric techniques. organic chemistry under Moses Gomberg Each of our guests was young at the who discovered organic free radicals. He start of this century. Three, at least—Van had expected to follow in his father’s foot Slyke, Folin and Clark—were well equipped steps and become an agricultural chemist. to advance the chemical knowledge of the However, through a chance conversation day. The fourth, Peters, the M.D. of the between his father and P. A. Levene at a four, had the foresight to visualize a prom meeting of the American Chemical Society, ising future for the use of sound quantita he became an assistant to Levene at the tive chemical knowledge in the solution of newly-formed Rockefeller Institute for clinical problems and the ability to make Medical Research. Seven years later, he it stick. was selected by Dr. Simon Flexner, the What can they be said to have left us? director, to head the chemistry division of First and foremost their students. I’ll wager the Hospital of the Rockefeller Institute. that every one of you medical scientists in CLINICAL-CHEMICAL INTERFACE OF MEDICAL SCIENCE 2 1 5 this audience has come under the influence been exposed to Emil Fischer’s pioneer of one of these students—or if not directly work on amino-acids and proteins: we —then one of their student’s students. would try to study the fate of proteins in What is taken for granted today was a the body. Folin adapted the Nessler re completely blank wall in the early 1900’s. action for the determination of ammonia Let me enumerate some of the things, following Kjeldahl digestion of proteins to which today you would regard as old hat the Dubosq colorimeter. Van Slyke took but for which they had to break ground: advantage of the reaction of nitrous acid with aliphatic amino acids with the evolu 1. The inorganic composition of the ex tion of gaseous nitrogen and devised a glass tra and intracellular fluids of the body. apparatus for its measurement. Both Folin 2. The transport of oxygen and C 02 and and Van Slyke used their respective meth the control of salt, water and acid-base bal ods to study the digestion of proteins, the ance. absorption of amino-acids and their metab 3. The metabolism of fats, carbohydrates olism in the tissues. Both greatly advanced and proteins by the several tissues. our knowledge. Folin was led to believe Subjects unknown to them in their early that all tissues were equally able to de- days were: aminate amino acids, whereas Van Slyke showed that the liver is the primary site of 1. The role played by vitamins and hor amino acid metabolism and urea formation. mones in metabolic control. When Van Slyke left Levene’s laboratory 2. That proteins were chemical indi for the Hospital of the Rockefeller Insti viduals. tute, he took his responsibility for aiding in 3. The composition and mode of action the study of disease through chemistry very of enzymes. seriously. Since F. M. Allen was then ap 4. Bioenergetics and biochemgenetics— plying the so-called starvation diet to the two subjects still under active investigation. treatment of diabetes, Van Slyke, with 5. Organelles of cells—their structure Glen Cullen, undertook to devise a method composition and functions. for the early detection of acidosis,-—an in 6. Membranes of all kinds and how evitable lethal concomitant of diabetes in transport is effected through them. the preinsulin days. This led to his sim 7. Immunochemistry. ple and adequately accurate gasometric 8. How the nervous system acts to method for plasma bicarbonate concen achieve a coordinated desirable metabolic trations. result. The method proved clinically useful in Included in this abbreviated list are all sorts of disease states involving acid- some topics that are essentially settled and base abnormalities and led Van Slyke, in others that are still under investigation and 1921, to his classic characterization of acid- obscure. base abnormalities which has stood the test For a moment, let us transport ourselves of time. back to the early 1900’s. What kind of H. “Tell us about your early lab days, Van.” questions would we first attempt to an swer? Remember, we’d have no isotopes, Van Slyke speaks: “First of all, I never set no chromatography, no sophisticated spec- out to be a clinical chemist. I was fasci tro-photometers—not even any glass elec nated by amino acid and protein chemistry trodes. and their metabolism in the body. During I expect we would do about what Van my seven years in Levene’s laboratory, I Slyke and Folin did, particularly if we had had the good fortune to literally dream up 2 1 6 HASTINGS a gasometric method for measuring amino gaseous state such as oxygen, C 02, CO and acid nitrogen. It was quite accurate and nitrogen. With the able help of Folch, with it Gus Meyer and I were able to show Sendroy and other fellows, gasometric that the liver is the primary organ for methods were developed for amino-nitro- amino acid metabolism and urea formation. gen, urea, lipids, sugar, lactic acid, chloride “After I transferred to the Hospital of the potassium and calcium. These proved use Rockefeller Institute to head its depart ful until they were supplanted by modem ment of chemistry, I was responsible for technology. chemical studies on the diseases under in “After I went to Brookhaven, I was able vestigation at the Hospital.

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