With COVID-19 vaccinations well underway, it can make one wonder how vaccines and other medicines came about and became part of people’s everyday lives. It turns out one common drug got its start quite close to home.
In June, it will be 82 years since a mystery that devastated farms in the Midwest, particularly Deer Park, WI., heralded a major medical breakthrough-the discovery of warfarin.
Warfarin is a type of medicine known as an anticoagulant or blood thinner. It makes your blood flow through your veins more easily, which means your blood will be less likely to make a dangerous blood clot.
During the 1920s, hundreds of cows had succumbed to major hemorrhaging for what seemed to be no good reason after undergoing a minor procedure, such as dehorning or castration. Farms from Alberta, Canada to Wisconsin felt the effect of herds of cattle that bled to death.
The mystery piqued the interest of Canadian veterinarian, Frank Schofield, who determined all of the affected cattle had eaten moldy silage made from a sweet clover plant.
This “sweet clover disease” as it became known was only found in cows that had eaten hay that had gone bad, a point proved in an experiment by Schofield who fed both good and damaged clover to rabbits, discovering the latter form faced the same hemorrhaging effects as the cows.
In February 1933, Ed Carlson of Deer Park, Wisconsin, loaded up some hay, a dead cow and a bucket of blood and made the long drive to Madison.
Carlson’s cows were dying from a bleeding disorder somehow caused by their feed.
Carlson drove to the University of Wisconsin, but researchers were dismayed to say they could offer no help, according to an account published years later by scientist Karl Paul Link.
The incident inspired Link and colleagues to follow a research path that culminated with the discovery of warfarin
The farmer’s cows were dying from the sweet clover disease that had first been documented in the 1920s.
Link learned as cattle ate the spoiled hay, the animals’ blood slowly lost its ability to clot, resulting in fatal internal hemorrhages in about 30 to 50 days.
But veterinarians in the 1920s also recognized the disease was reversible if farmers gave the animals new feed and blood transfusions. No one knew exactly why.
The visit from the Deer Park farmer gave researchers a sense of urgency to figure out what was wrong because the standard advice – changing the hay and transfusing the cows – wasn’t an option for the penniless farmer.
It took six years for researchers to pinpoint the chemical compound in the hay that prevented the blood clots. Based on this knowledge, they developed a drug called Dicumarol that was tested by doctors in St. Paul and elsewhere to see if it could prevent blood clots in patients.
The medicine didn’t work so well, but in time Link and colleagues opted to develop a different form of the compound that ultimately took the name warfarin.
At the time, Dr Link’s work was supported by the Wisconsin Alumni Research Foundation (WARF), hence the decision to name a more potent molecule, synthesised from the coumarin-based anticoagulant, warfarin.
Its first approved use wasn’t as a medicine, however, instead being approved as a rat poison.
Safety concerns were the main issue behind its lack of use in humans, although these were eased in 1951 following the attempted suicide of man who overdosed on warfarin rat poison, but was successfully saved with doses of vitamin K – an important aspect in the synthesis of blood-clotting factor prothrombin.
With the knowledge its effects could be reversed, it wasn’t long before Endo Laboratories produced the first version of warfarin intended for humans under the trade name Coumadin, with the drug gaining widespread fame when it was used to help treat US President Dwight Eisenhower following a heart attack.
Since then, warfarin has remained a staple part of a treatment for clotting conditions, helping in the treatment of countless people, while many generics have been introduced.
These may overtake their predecessor as the main weapon in the treatment of blood clots, but warfarin’s discovery still stands as both one of the greatest medical breakthroughs of the 20th century and one of its great detective stories, largely because of a farmer from Deer Park.