e martë, shkurt 22, 2005

Hemorrhagic Sweet Clover Disease, Dicumarol, and Warfarin: the Work of Karl

Karl Paul Link (1901–1978) received his Ph.D. in 1925 from the University of Wisconsin, working with plant biochemist William E. Tottingham. He spent the next 2 years in Europe studying carbohydrate chemistry with Sir James Irvine in Scotland, microchemistry with Fritz Pregl in Austria, and organic chemistry with Paul Karrer in Switzerland. He returned to the University of Wisconsin as an assistant professor in agricultural chemistry (now biochemistry) in 1927 and was promoted to associate professor in 1928.

Initially when he set up his laboratory, Link concentrated on plant carbohydrates and soon established himself as one of the outstanding carbohydrate chemists of his day. Using the microchemical techniques he learned with Pregl, he and his students were able to characterize carbohydrate derivatives that they had isolated and synthesized.

However, the direction of Link's research changed drastically when he became involved in the isolation and characterization of the hemorrhagic factor produced in spoiled sweet clover hay. These experiments are the subject of the three Journal of Biological Chemistry (JBC) Classics reprinted here. Sweet clover was widely used as hay in the 1920s when a series of wet summers had led to an epidemic of "bleeding disease" in cattle. The cause of the disease was traced to sweet clover hay that had been improperly cured and infected with molds. There was also evidence that the defective coagulation in the cows was due to a deficiency in prothrombin.