Friday, November 5, 2010

Karl Link and Warfarin

Karl Paul Gerhard Link (31 January 1901 - 21 November 1978) was an American biochemist best known for his discovery of the anticoagulant warfarin.



In the subsequent years, most of his research focused on plant carbohydrates. However, the most fruitful period began when Ed Carson, a Wisconsin farmer, attracted Link's attention to sweet clover disease, described in 1924 by veterinarian Frank Schofield. In this condition, cows bled to death after consuming hay made from spoilt sweet clover. Carson's stock had been affected, and he brought a dead cow, blood that would not clot, and 100 pounds of sweet clover hay. Under the direction of Link, PhD students Harold Campbell, Ralph Overman, Charles Huebner, and Mark Stahmann crystallised the putative poison - a coumarin - and synthetised and tested it; it turned out to be dicumarol (3,3'-methylenebis-(4 hydroxycoumarin)).



Dicumarol was subjected to clinical trials in Wisconsin General Hospital and the Mayo Clinic. It was for several years the most popular oral anticoagulant.


Warfarin, one of the several compounds synthesised as part of the coumarin research, was patented in 1945 with the Wisconsin Alumni Research Foundation, Link and researchers Stahlmann and Ikawa jointly owning the patent. Initially marketed as rat poison, warfarin would later, in the 1950s, become the second most important anticoagulant for clinical use (after heparin).

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