The Missing Link: The Story of Karl Paul Link

Extract

If you ever wondered why the well-known rat poison is called Warfarin, it is from the initials WARF for Wisconsin Alumni Research Foundation. WARF funded the initial studies on coumarins in Karl Paul Link's laboratory, which gave rise to this compound and to its close relative, dicoumarol. Professor Link was a pioneer in what would now be called basic research in toxicology. Perhaps because his research was so oriented to biochemistry and so interdisciplinary, his name seems to be lost when pioneers in toxicology are discussed. His seminal work began with a problem among dairy cattle, the major industry in Wisconsin, which needed a solution.

Sweet clover (Melilotus alba and M. officinalis) is grown as a green manure and hay crop in the northern U.S. and in Canada. Its coumarin content gives it a distinctive sweet odor similar to vanilla. Its use as hay was widespread in the 1920s, when a series of wet summers led to an epidemic of “bleeding disease” in cattle. Epidemiological detective work by veterinarians traced the cause to sweet clover hay that had been improperly cured and had become infected with molds. When sweet clover is put up as hay, it is easy for it to be contaminated with molds. This is particularly likely when conditions are wet at cutting or curing, or when foliage is lush. Molds such as Penicillium nigricans, P. jensi, and the Aspergilli metabolize the coumarin into dicoumarol. Cattle or sheep consuming the spoiled hay showed less clotting power in their blood, a condition leading to fatal internal hemorrhage.