The amount of sweet clover used as a feed for cattle nationally has diminished in recent years but its unique role in human medicine is worth retelling. Farmers of a certain age can vividly remember being admonished by their elders not to feed moldy sweet clover hay or silage to the cows. The reason for this warning was pretty basic — it made them sick and they would bleed to death. Pretty heady stuff for a 12-year-old with a pitch fork in his hand and not a lesson to be taken lightly.
Naturally occurring products called coumarins are present in sweet clover which during the process of spoiling, usually attributed to wet weather during the curing process, are converted to a toxic compound called dicoumarol. Spoiled, moldy sweet clover containing this lethal compound combines with the proenzyme required for the synthesis of prothrombin, one of the compounds required for the clotting of blood. When the blood is unable to clot in the normal way the stage is set for internal bleeding.
All species are susceptible but cattle are the species most often affected. The treatment for this condition in cattle is blood transfusions and large doses of vitamin K. To say that blood transfusions are necessary is often easier said than done under farm conditions. If the herd has eaten the same roughage, where does the blood come from? Vitamin K is necessary in the synthesis of certain essential anti-coagulation factors in the blood.
As the story goes, as told on NPR, a farmer showed up in the winter of 1934 at the lab at the University of Wisconsin with a can of cow’s blood. The uncoagulated blood had come from a cow that had eaten moldy sweet clover hay and had died. Several cows on the same farm had become ill after eating the same hay and had died a few days later. All showed the same symptoms — uncoagulated blood in the abdominal cavity. The director of the lab was a chemist named Karl Paul Link who became fascinated by the farmer’s dilemma and directed his lab to focus on finding the cause of the problem.
Given the multiple factors involved arriving at the cause was not an easy one. After several years of investigation Karl came to the conclusion that when a fungus that causes the mold in the hay reacts with a naturally occurring substance in the hay called coumarin the resulting product is dicoumarol, which has blood-thinning properties. It was not long before the scientist’s mind began to speculate as to other possible ways in which this product be used. It was reasoned that it might be used in human medicine in correcting conditions where a blood thinner might be required. Collaborating with clinicians the product was tried in patients with life threatening disorders that resulted in blood clotting and it worked, dissolving the clots.
Researchers soon began to develop compounds closely related to the original, but modified to make them more satisfactory for use in humans. Over the ensuing years these and newer modifications continue to be used in humans who were at risk for developing blood clots.
Not content with finding an important use in human medicine for his discovered compound Link set about trying to see if this product had a potential use as a rat poison. Rats he reasoned were not all that much different than cows and if they ate enough of it when attractively flavored they should hemorrhage internally and die. His theory was correct but there was one factor he had not counted on. Apparently the normal diet of rats contains foods that are high in vitamin K and that factor counteracted the effects of the dicoumarol that he was baiting them with.
Link was not deterred. In the many trials that his group had conducted they had developed one that they labeled No. 42 which proved to be a particularly potent. No. 42 proved to be the answer to the search for the better rat trap and was given the name Warfarin. It became an extremely widely used rat poison, one with which many readers are familiar.
Further trials revealed that in very small amounts a version of Warfarin named Warfarin Sodium was considerably easier to use in human patients than was dicoumarol. It was used to treat President Eisenhower after he had his heart attack in 1955. This drug became a best seller under the trade name Coumadin.
And so over many years a life saving drug was developed for use in human medicine to help those patients with clotting disorders lead more nearly normal productive lives. This all evolved from the curiosity of a Wisconsin farmer whose cows were dying from a strange malady to which there seemed to be no reasonable answer.