Current and Emerging Oral Anticoagulants:
Rational Drug Design or Just Luck?
The Warfarin Pioneers
The discovery of warfarin was the result of a sequence of coincidences, which were probably regarded as anything but fortuitous at the time. The story begins in the US during the Great Depression in 1920s, where previously healthy cattle began dying as a result of internal gastrointestinal bleeding. This was a time of great financial
hardship, and livestock was one of the US' major industries, so identifying the cause of the condition became a priority. The cause was later attributed to spoiled sweet clover (Melilotus alba and M. officinalis) and the condition was referred to as 'sweet clover disease'1. The financial pressures of the
time probably contributed to the problem, as cattle feed may well have been kept for longer than normal making spoilage more likely. Even the weather played a part - a series of wet summers giving rise to an epidemic of sweet clover disease during this period2.
Despite the general interest, the discovery of warfarin was due to the efforts of a single farmer. In desperation, he decided to transport his dead cow 190 miles to the nearest state veterinarian, but since the office was closed, he ended up at the doorstep of the Biochemistry Building at the University of Wisconsin and the laboratory of one Professor Paul Link, whose pioneering work resulted in the identification and isolation of dicoumarol, a precursor to the first anticoagulants - figure 1. ►