Historical data regarding the experiences with coumarin anticoagulants at the University of Wisconsin Medical School.

IT'WAS 1938, 20 years ago, when, in conversation with Professor R. A. Brink of the Department of Genetics at the University of Wisconsin, that I first heard of the work beingfr done in the Department of Agriculture to identify the substance in spoiled sweet clover accountable for hemorrhagic disease in cattle. This had been initially undertaken in 1934 at the Wisconsin Agricultural Experiment Station by Professor Karl Paul Link and his associates. This group of workers, including Campbell,' Stahmann and Huebner,2 finally isolated the anticoagulant, a coumarin derivative, and established its chemical characteristics. The yield was about 1 Gm. per ton of clover, an amount which was not practical for clinical usage. However, by April 1940, these investigators had synthesized a 3-substituted4-hydroxycoumarin which was chemically, physically, and biologically identical to the naturally occurring substance. This could be prepared cheaply and in abundant quantities. The potential significance in the treatment of thromboembolic disease was then obvious, and hence we were happy when a supply was made available to us for basic studies in September 1940. The anticoagulant for clinical purposes was given the name Dicumarol. My early associates in the field included James B. Bingham, now in Seattle, Dr. Frederick J. Pohle, deceased, Dr. John McCarter, now of Boise, Idaho, Dr. Charles T. Thill of Chicago, and Dr. Maryloo Spooner Schallek of Nutley, N. J. It was promptly established that this anticoagulant was a potent hypopro-