Warfarin designated National Historic Chemical Landmark

ACS dedication event collage

The American Chemical Society (ACS) honored the development of the blood thinner warfarin with the National Historic Chemical Landmark designation in a ceremony at UW–Madison on Oct. 12, 2022.

“Warfarin has helped millions of patients lessen the risk of stroke or heart attack,” says ACS President Angela K. Wilson. “It has also been used as a rat poison that has reduced the spread of rodent-borne diseases. In addition, proceeds from the associated patents are important contributors to other research funded by WARF at UW–Madison.”

ACS established the National Historic Chemical Landmarks program in 1992 to recognize seminal events in the history of chemistry and to increase awareness of the contributions of chemistry to society. Past Landmarks include the invention of Polaroid instant photography, the discovery and production of penicillin, the invention of synthetic plastics and the works of such notable scientific figures as educator George Washington Carver and environmentalist Rachel Carson.

Warfarin’s story began in February 1933 when a farmer from northwest Wisconsin drove to Madison to look for the state veterinarian to diagnose a condition that was causing his cows to hemorrhage and die. Finding most offices closed that Saturday, the farmer instead walked into the laboratory of UW–Madison biochemistry professor Karl Paul Link.

Link and his student assistant recognized the signs of sweet clover disease, which develops when cattle eat wet, spoiled clover hay, and Link reoriented the work of his laboratory toward understanding the biochemistry at work in spoiled clover and the cows that ate it. In 1939, his team isolated a compound in the hay that prevented cow blood from clotting. The researchers realized that such an anticoagulant might also be able to kill rodents and prevent dangerous blood clots in humans.

With support from the university, the state and the Wisconsin Alumni Research Foundation (WARF), further research on the compound Link’s team isolated in 1939 and its analogs led to the development of warfarin. Warfarin first went on the market in 1948 — but only as a rat poison. Fortunately, while it could kill mice and rats, it wasn’t toxic to humans. Link’s team developed a water-soluble version, known as warfarin sodium, which could be taken by mouth. It was approved for human use in 1954 and was sold under the brand name Coumadin®. Warfarin soon became both the most widely used rat poison and the most widely prescribed blood thinner in the world. Experts estimate that around 100 million prescriptions of warfarin are still issued globally each year.

“The discovery of warfarin and its continued use around the globe is the ultimate story of what drives our college, the College of Agricultural and Life Sciences,” says UW–Madison College of Agricultural and Life Sciences Dean Glenda Gillaspy. “This is what universities were created to do, and it’s what the truly great ones do every day.”

The National Historic Chemical Landmark commemorative plaque reads:

In the early 20th century, a devastating bleeding disorder swept through North American cattle herds. Focusing on the suspected spoiled hay in the animals’ food supply, University of Wisconsin biochemists in 1939 isolated a chemical compound that prevents blood from clotting. With support from the university, state and Wisconsin Alumni Research Foundation (WARF), further research on this compound and its analogs led to the development of a revolutionary new rat poison (warfarin) and blood thinner (warfarin sodium) still widely used today. These anticoagulant compounds have reduced rodent-borne diseases and helped millions of patients lessen the risk of stroke or heart attack. Proceeds from the associated patents are important contributors to the over $4 billion in research funded by WARF at the University of Wisconsin–Madison.

Photo caption: Clockwise, from top left: ACS Board of Directors Representative Lisa Balbes delivers remarks about the landmark designation; CALS Dean Glenda Gillaspy shares what the designation means to the college; WARF CEO Erik Iverson shares the importance of the designation and the patent process; Karl P. Link’s son, Tom Link (green jacket, center), listens to local author Doug Moe give a seminar about Link and his legacy at UW–Madison; Doug Moe (left) and WARF historian Kevin Walters (right) discuss Link’s legacy during a Q&A period; Biochemistry Chair Brian Fox (left) joins Balbes, Gillaspy, and Link for the groundbreaking. Photos: Andy Manis.

This article was adapted from an ACS press release. The groundbreaking was followed by a presentation from local author Doug Moe. Watch a recording of Moe’s presentation on the Wednesday Nite @ the Lab YouTube channel (start at 1:16:00).