edited bv ROGER R. FESTA School of Educat8on. Box U-33 of Connect,cut The Un~vers~ty Storrs. CT 06268
Otto Folin (1867-1934) Albert 8. Coda Duquesne University Pinsburgh, PA 15282 Around 1900. some scientists in Eurooe and America beean to call thenlselves biochemisrs. The profession itieli became formallvoraanized in the Unitedstates with thefoundineof the ~ o u k a l o~iological f Chemistry in 1905 and the ~ m e r E a n Societv of Biological Chemists in 1906. Among the first-eeneration biochem2sts was Otto Folin, a chartermemher ofthe American Society of Biological Chemists and its third president (1909). Most of his work appeared in the Journal of Biolo~icalChemistry, and for mans sears he was chairman of the journal's editorial committee. What made Folin distinctive among the first generation of American biochemist^ was his devotion to the develooment of microchemical analyses of the basic fluids in the iuman bodv. Until the twentieth centuw. neither blood nor urine test; were much used in medicin"e'. Such tests lacked both soecificitv and accuracv. and in the case of blood required too large a sample from'patients. Folin developed^accurate chemical techniques that used only small quantities of fluid; a needle prick often sufficed for a single hlood test. His work made possible the daily estimation of a person's hlood sugar, a technique that physicians quickly applied t o the study of diabetes. Otto Folin was born in Sweden, where his father was a tanner and his mother an official midwife. As a teenager he ioined the wave of Swedish immierants to the American id west, settling in Minnesota at age15 with an older brother. After graduating from the University of Minnesota in 1892, he enrolled in the newly opened University of Chicago, obtainine a doctorate in chemistrv in 1896. After two vears of advanced study in Europe, he returned to the unitedstates, hoping to obtain a position in physiological chemistry. There were few opportunities in this area at the end of the nineteenth century; the field was not represented in most chemistry departments in American universities. For two years he worked as an industrial chemist and as a teacher of analytical chemistry, waiting for a chance to study the chemistry of biological processes. In 1900, the McLean Hospital for the Insane in Massachusetts established a laboratory for the study of the chemical basis of mental illness. In so doing, it became the first hospital in the United States to have a biochemical research laboratory. Through the influence of his Chicago professors, Folin accepted an appointment a t McLean as a research biochemist. Folin made onlv one autobioeraohical statement in his lifetime (dated A& 9, 1924)."n'k he described how his task at the hosoital was to studv the chrmical hnsis of mental illness. He wondered whethkr there was a way to determine differences in metabolism between normal and osvchotic persons. He thought that perhaps the chemistr; o i urine would provide a clue, since urine is an end product of metab-
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' Kohler, R. E., Isis, 64, 181 (1973).
Shaffer,P. A., Biog. Mem. Nat. Acad. Sci.,27,47 (1952). JAMA. 69, 1209 (1917). Folin, 0.. 4Folin,0. and Wu, H., J. Biol. Chem., 38, 81 (1919).
olism, and its constituents should be an index and measure of the chemical reactions in the body. By quantitatively measuring these constituents, Folin hoped to learn about the abnormal variations that might turn up in mentally disturbed . ., ma1vmuaIs. A chemical study of urine required accurate methods of analysis, hut in 1900 they did not exist. Most urinaw constituents were known only qualitatively; the quantitative tests that did exist were complicated and of insufficient specificity. Indeed. no comolete analvsis of a urine soecimen-had ever been accomplished. Thus, Folin had to invent new, simple quantitative methods for the fluids of the body. This challenge became his life work. The psychiatric value of the results were of little importance, and he lost interest in the chemistry of mental disease. Instead, Folin became more and more interested in the development of analytical methods for biochemical research; from his endeavors grew almost the whole range of microchemical analyses of the urine, blood, and other body fluids that subsequently came to be used in hosoital and diaanostic laboratories in the United States. Folin's firit new microchemical methods were for the analysis of total nitrogen, uric acid, sugar, creatine, creatinine, ammonia, chloride, phosphate, and sulfate in urine. These were new colorimetric methods which employed color comparisons as a basis for the analysis of small amounts of samples. While colorimetric techniques had been used in a limited way to estimate biological materials, contemporaries regarded Folin's work as the introduction of colorimetry into modern hiochemical orocedures. Folin rema'ined a t McLean Hospital for seven years. In 1906 the Harvard Medical School ooened newbuildines with biochemical lahoratories, and Folin accepted a position in the Medical Schml. In 1909 he hecnme thr first orntessor of biochemistry a t Harvard. He took charge of the Department of Biochemistry in the Medical School, engaging in research and teaching medical students, including two future Nobel Laureates (Edward Doisy and James Sumner) and several other leaders in American biochemistry. At Harvard, Folin extended his studies to the chemistry of blood. A maior difficultv in hlood analvsis was how to identifv small amounts of nitrogen-containing substances present in the blood along with the abundant protein. In 1912, he developed a method to precipitate proteins and colloidal material without heat, which he followed hv filtrate treatment. That development led to the colorime&ic determination of the nonprotein constituents of the blood. Over the years Folin continually modified his blood tests, seeking greater accuracy and specificity. Accepting an invitation to deliver the 1917 Mellon Lecture a t the Universitv of Pittsburgh, he used the occasion to summarize his researcb.3 He noted that ohvsicians had seldom used chemical blood and . . urine tests hecause the methodi had been slow, had required lilrye snmples, and had been difficult to apply. For example,
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"Profilesin Chemistry" is a biographical feature, highlighting the contributions of distinguished chemists in the context of their lives. The column is designed for curriculum enrichment,allowing the secondary school teacher to enhance the vitality of chemistry with the sense of scholarship and adventure shared by chemists throughout history.
Volume 59
Number 8
August 1982
645
a urine ammonia test alone had taken four days. Folin's tests enabled one to obtain a complete urinalysis in two hours or less and with a 10-ml sample. Tests for individual constituents could often be done in 15 to 30 min. Blood analysis had been more backward. There had been no such thing as a quantitative hlood test and no systematic methods, only scattered analyses of constituents. His quick microchemical methods had led to the establishment of clinical laboratories accessible to physicians. In 1919, Folin published his best-known system of blood a n a l y ~ i sHis . ~ method provided accurate determinations of sugar, uric acid, urea nitrogen, creatinine, amino acid nitrogen, nonprotein nitrogen, and chloride. This achievement made his contribution to medicine especially important. The 1919 procedure consolidated his previous methods into a compact system. The starting point was a protein-free hlood filtrate
646
Journal of Chemical Education
from which all of the above constituents of hlood could be determined on a microchemical scale. The Folin hlood sugar method became the most widely used in clinical laboratories and has since provided the means to the accurate diagnosis of diabetes in a multitude of patients. Otto Folin was an important figure in the development of American biochemistry. His biochemical analyses greatly influenced the medical profession during the 1920s. As the use of systematic urine and blood tests spread throughout the medical profession, physicians gradually learned when to request them, what specific analyses were needed, and how to interpret the results. Folin's work meant that the Paracelsian dream of a chemically based medicine had a t last been realized: chemical tests to ascertain the health of an individual had become an essential tool in medical diagnosis and treatment.
