Historic Chemical Landmark designation goes to warfarin, a blockbuster blood thinner

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UW-Madison professor Karl Paul Link, Ph.D. (right) and his student Mark A. Stahmann (left) were part of a team that created the blood thinner warfarin, pictured here in 1949.
Credit: Courtesy of the University of Wisconsin Collection
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WASHINGTON, Oct. 10, 2022 — 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 (UW) biochemists in 1939 isolated a chemical compound that prevents blood from clotting. With support from the university, the state and the Wisconsin Alumni Research Foundation (WARF), further research on this compound and its analogs led to the development of warfarin, a revolutionary blood thinner still widely used today. On Oct. 12, the American Chemical Society (ACS) will honor that achievement with the National Historic Chemical Landmark designation.

The Landmark dedication ceremony will take place at 4 p.m. CT (5 p.m. ET) at the University of Wisconsin-Madison (UW-Madison).

“Warfarin has helped millions of patients lessen the risk of stroke or heart attack,” says ACS President Angela K. Wilson, Ph.D. “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.”

Warfarin’s story begins in 1933, when a farmer 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 professor Karl Paul Link, Ph.D. Link and his student assistant recognized the signs of sweet clover disease, which develops when cattle eat wet, spoiled clover hay.

After that fateful meeting, Link reoriented the work of his laboratory toward understanding the biochemistry at work in spoiled clover and in the cows that ate it. His team eventually 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.

To explore these possibilities, Link and his coworkers synthesized more than 100 related compounds. Each of these analogs had a slight difference in chemical makeup, but all produced similar anticoagulant effects. The most effective analog was named 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 for humans. The researchers 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.

As newer blood thinners have become available, prescription rates for warfarin have declined, but it remains one of the most widely used treatments for blood clots to this day. Experts estimate that around 100 million prescriptions of warfarin are still issued globally each year.

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. For more information, visit www.acs.org/landmarks.

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.

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