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• W1488679357 abstract "Uricolysis in Normal Man (Wyngaarden, J. B., and Stetten, D., Jr. (1953) J. Biol. Chem. 203, 9–21) Incorporation of 4-Amino-5-imidazolecarboxamide-4-C13 into Uric Acid in the Normal Human (Seegmiller, J. E., Laster, L., and Stetten, D., Jr. (1955) J. Biol. Chem. 216, 653–662) DeWitt Stetten, Jr. (1909–1990) was born in New York City. He received his A.B. degree from Harvard College in 1930. Although he knew that he wanted to be a biochemist, he was encouraged by his father and his mentor at Harvard, Frank Fremont-Smith, to attend medical school before embarking on a research career. Stetten thus attended the College of Physicians and Surgeons of Columbia University and received his M.D. in 1934. After doing an internship and residency at Bellevue Hospital in New York City, Stetten chose Journal of Biological Chemistry (JBC) Classic author Rudolf Schoenheimer (1Schoenheimer R. Rittenberg D. J. Biol. Chem. 1935; 111 (Classics JBC): 163-168Abstract Full Text PDF Google ScholarRittenberg D. Schoenheimer R. J. Biol. Chem. 1937; 121: 235-253(http://www.jbc.org/cgi/content/full/277/43/e3)Abstract Full Text PDF Google Scholar) as his Ph.D. mentor. Schoenheimer had recently joined the faculty at Columbia University and was known for his use of isotopes to study metabolism. For his dissertation, Stetten used the newly developed technique of isotopic labeling with deuterium to follow the biological conversion of labeled palmitic acid to stearic and palmitoleic acid and the conversion of aliphatic alcohols to fatty acids in intact rats. This research was published in two papers in the JBC (2Stetten D. Schoenheimer R. The conversion of palmitic acid into stearic and palmitoleic acids in rats.J. Biol. Chem. 1940; 133: 329-345Abstract Full Text PDF Google Scholar, 3Stetten D. Schoenheimer R. The biological relations of the higher aliphatic alcohols to fatty acids.J. Biol. Chem. 1940; 133: 347-357Abstract Full Text PDF Google Scholar). Stetten received his Ph.D. in 1940 and remained at Columbia University, studying the origins of the extra fat in various types of fatty liver using 15N labeling to show the dynamic relationships of choline, ethanolamine, and related compounds, as well as the role of lipotrophic methyl groups in the synthesis of choline in rats. In 1947 Stetten moved to Boston where he spent 2 years doing research and teaching at Harvard University's Peter Bent Brigham Hospital. He then moved back to New York to become chief of the Division of Nutrition and Physiology of the Public Health Research Institute of the City of New York. Among Stetten's achievements during his 6 years in New York was his discovery that patients with gout produced higher than normal levels of uric acid. In the two JBC Classics reprinted here, Stetten investigates the fate of uric acid in metabolism by having his coauthors either inject or ingest 15N-labeled compounds. In the first Classic, Stetten and his postdoctoral fellow James Wyngaarden investigated uricolysis in humans by intravenously injecting [1,3-15N]uric acid into Wyngaarden. Studies done prior to this one had shown that only about 70% of injected uric acid was recovered as uric acid in urine, suggesting the occurrence of uricolysis. By analyzing urine and stool samples from Wyngaarden after he had received the labeled uric acid injection, Stetten and Wyngaarden were able to show that 18% of the administered uric acid was degraded to other nitrogenous products such as urea and ammonia. In the second JBC Classic, Stetten, Leonard Laster, and Jarvis Edwin Seegmiller investigated the involvement of 4-amino-5-imidazolecarboxamide in the biosynthesis of uric acid. The compound was known to be incorporated into uric acid and purines in rats, pigeons, yeast, and bacteria, but its usage in humans had not yet been proven. Laster and Seegmiller both ingested [4-13C]4-amino-5-imidazolecarboxamide with their breakfast milk, and the uric acid collected from their urine was analyzed. The researchers found that approximately 20% of the 4-amino-5-imidazolecarboxamide was recovered unchanged, with its isotope undiluted, from the urine excreted in the first 8 h. However, between 20 and 23% of the l3C was recovered in uric acid excreted in the 2–3 weeks following ingestion of the labeled compound, indicating the existence of a mechanism that converted 4-amino-5-imidazolecarboxamide to uric acid. Laster and Seegmiller then ingested unlabeled 4-amino-5-imidazolecarboxamide along with [15N]-glycine and showed that 4-amino-5-imidazolecarboxamide administration interferes with the synthesis of uric acid from glycine. In 1954 Stetten was appointed Associate Director in charge of the intramural program of research at the NIAMD, National Institutes of Health. During his time there, Stetten helped to establish the Foundation for Education in the Sciences, a nongovernmental teaching institution located adjacent to the NIH campus, and later served as its president. In 1962 Stetten left NIH to serve as the founding dean of the Rutgers University School of Medicine. He returned to the NIH in 1970 to head the NIGMS. From 1974 to 1979 he was NIH's Deputy Director for Science. During this time he also served as chairman of the recombinant DNA advisory committee, which drafted guidelines for scientists using the new techniques. In 1978 Stetten asked to be relieved of his duties as deputy director because of his deteriorating eyesight, caused by macular degeneration. Donald Fredrickson, then NIH Director, appointed him Senior Scientific Advisor to the Director. In his new position, Stetten founded the Museum of Medical Research at the NIH, which now bears his name. Stetten has received many awards and honors for his research, including membership in the American Academy of Arts and Sciences and the National Academy of Sciences. He served as chairman of the Roche Institute of Molecular Biology's Scientific Advisory Committee from 1966 to 1970, was president of the Foundation for Advanced Education in the Sciences in 1971, and from 1977 to 1979 headed the Society for Experimental Biology and Medicine. Stetten was also coauthor of the first two editions of Principles of Biochemistry with Abraham White, Phillip Handler, and Emil L. Smith. 1Biographical information on DeWitt Stetten was taken from Ref. 4Seegmiller J.E. DeWitt Jr., Stetten Biogr. Mem. Natl. Acad. Sci. 1997; 71: 333-346Google Scholar.1Biographical information on DeWitt Stetten was taken from Ref. 4Seegmiller J.E. DeWitt Jr., Stetten Biogr. Mem. Natl. Acad. Sci. 1997; 71: 333-346Google Scholar. Stetten's coauthors on these Classic papers have also gone on to successful careers themselves. After leaving Stetten's lab, James B. Wyngaarden became an associate professor of biochemistry at Duke University Medical School and eventually assumed the leadership of Duke's medical research training program. He left Duke to become the chair of the Department of Medicine at the University of Pennsylvania, but then returned to Duke to serve as chair of the Department of Medicine at Duke University. During that time, he was also Duke's vice chancellor of health affairs. Wyngaarden eventually became the 12th director of the National Institutes of Health. Jarvis Edwin Seegmiller (1920–2006) became Chief of Human Biochemical Genetics at NIH, then left the NIH to become a founding faculty member of the new Medical School of the University of California, San Diego (UCSD) and was named the first head of the Arthritis Division of the Department of Medicine. Later, he was appointed Founding Director of the Stein Institute for Research on Aging. He is best known for his role in discovering the biochemical basis of the Lesch-Nyhan syndrome. Leonard Laster has served as Distinguished Professor and Chancellor of the University of Massachusetts School of Medicine, President of the Oregon Health Science University, Vice-president of Downstate Medical Center at the State University of New York, Assistant Director of the President's Office of Science and Technology, and Assistant Surgeon General." @default.
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• W1488679357 title "Investigating Uric Acid Metabolism by Ingesting 15N-labeled Compounds: the Work of DeWitt Stetten" @default.
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