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J. Biol. Chem., Vol. 277, Issue 28, 17, July 12, 2002
The Preparation of the Crystalline Follicular Ovarian Hormone:
Theelin
(Veler, C. D., Thayer, S., and Doisy, E. A. (1930) J. Biol.
Chem. 87,
357371)
Characterization of Theelol
(Thayer, S. A., Levin, L., and Doisy, E.
A. (1931) J. Biol. Chem. 91,
655665)
The Constitution and Synthesis of Vitamin
K1
(MacCorquodale, D. W., Cheney, L. C., Binkley, S. B.,
Holcomb, W. F., McKee, R. W., Thayer, S. A., and Doisy, E. A. (1939) J.
Biol. Chem. 131,
357370)
Edward Adelbert Doisy (18931986) was born in Hume, Illinois. He received a Bachelors degree (1914) and Masters degree (1916) in Chemistry from the University of Illinois. He then continued his graduate studies at Harvard Medical School with Otto Folin. Together they developed many analytical techniques used to measure important substances in urine and blood including creatine, creatinine, and uric acid. (Folin was the subject of an earlier Journal of Biological Chemistry (JBC) Classic (1).) Doisy was drafted into the army in 1917 for service during World War I, and from 1917 to 1919 he worked first with D. D. Van Slyke at the Rockefeller Institute for Medical Research and subsequently at the Walter Reed Research Institute in Washington D. C. (D. D. Van Slyke was also the subject of an earlier JBC Classic (2).) After completing his army service, Doisy received his Ph.D. in 1920 for the work done with Folin.
In 1919, Doisy became Instructor and later Associate Professor of Biochemistry at Washington University in St. Louis. In 1923, he moved across town to St. Louis University Medical School to become Professor and Chairman of a new biochemistry department, the positions he held until his retirement in 1965.
His work at St. Louis University began with the study of the estrous cycle in mice. He determined that ovarian follicles precede the appearance of cornified cells in the vagina. He showed that extracts from sow ovaries, when injected into ovarectomized mice, resulted in the production of cornified cells in the vagina. Using this as an assay, Doisy isolated the female sex hormones, estrone (Theelin) and estriol (Theelol), from hundreds of gallons of human pregnancy urine. The first two JBC Classics in this set represent this work. Doisy told the following story about collecting the urine.
One driver, while making collections of urine, committed a traffic violation, and the policeman who glanced in the back of the car and saw the bottles with amber fluid thought he had caught a bootlegger. He would not believe the driver so he was invited to get in to sample the amber fluid. After pulling the cork (summertime and the preservative had evaporated) and sniffing, the cop said, "My God it is urine! Your job is bad enough without getting pinched for itdrive on."
Doisy later isolated a third estrogen, estradiol from pig follicular fluid. This work opened fertility research to biochemical analysis and had lasting consequences for the development of reproductive biology and birth control.
In 1929, Hendrik Dam discovered vitamin K as a new fat-soluble vitamin that promoted blood coagulation in chicks and rats (3). In 1936, Doisy started to isolate this vitamin, and in 1939 he succeeded in crystallizing vitamin K1 from alfalfa. This work is represented by the third paper in this set of JBC Classics. For his work on vitamin K, Doisy, along with Hendrik Dam, received the Nobel Prize in Physiology or Medicine in 1943. Many felt that the Nobel Prize was also warranted for his work on estrogens.
Doisy received many honors for his pioneering research. According to Robert
Olson, Doisy's successor as Chairman of Biochemistry at St. Louis University,
Doisy did not receive any research support from the National Institutes of
Health or other government agency. He supported his work entirely from patent
income from his research discoveries
(4). Doisy served as President
of the American Society of Biological Chemists (ASBC) in
1945.1,2
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1 Much of the background material for this Classic Introduction was taken
from an autobiographical prefatory chapter in Ref.
5. ![]()
2 Special thanks to William S. Sly, Professor and Chairman of the Edward A.
Doisy Department of Biochemistry and Molecular Biology at St. Louis
University, for providing biographical material for this Introduction. ![]()
REFERENCES
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