Warfarin has been used as a medication for more than 60 years. The discovery of Warfarin is interesting and sounds a bit like the plot of a movie; it includes a president, dead cattle, an attempted suicide and rat poison. Like many scientific discoveries of the last century it involved some serendipity, good fortune, the correct circumstances and the determination of a few individuals.
The story begins in the 1800s in North America in the state of Wisconsin, which is one of the northern states near the great lakes. European settlers moved into the state in the late 1700s mainly to trade fur and set up trading post with the local native Americans. However, it was not until the mid 1860s that the population started to grow and Wisconsin became a major wheat and corn growing region. This region became known as the “corn belt” and at one stage Wisconsin produced approximately one sixth of all the wheat in the US. However intensive wheat farming rapidly depleted nutrients in the soil, in particular nitrogen, and the plants became more vulnerable to pests. In 1860 the chinch bug arrived in the state and caused major damage to the crops, as a result, many farmers turned to dairy farming as an alternative and by 1899 over ninety percent of the farms in Wisconsin raised dairy cows and the region became a major producer of dairy products in particular cheese. It became known as American Dairyland and the locals were called Cheeseheads.
One problem with having large dairy herds is that they required additional forage particularly during the winter months when there was less grass available. In the late 17th century sweet clover was introduced into North America from Europe as cattle forage. It was seen as an ideal plant as it is not just useful as food but it improves soil quality by efficiently fixing nitrogen and it was rapidly introduced into Wisconsin. Sweet clover is a legume and gets its name from the sweet smell produced when it is cut. In fact, the smell is due to a chemical called Coumarin. Sweet clover can be stored for long periods as long as it is dried correctly, however if it gets wet it will spoil and become infected with various fungi including penicillium and aspergillus. As well as rotting the plants the fungi also convert the Coumarin to dicoumarol, an anticoagulant similar to warfarin.
In the winter of 1921 a number of cattle in Alberta and North Wisconsin were dying from a previously unrecognised disease. Autopsies showed that these animals had suffered from internal bleeding and extensive bruising. In some areas whole herds were affected with animals dying within a few days of the onset of symptoms. The disease could present in a number of different ways; in some cases, it was obvious bleeding from a minor procedure such as ear notching or dehorning, where as in other animals the bleeding was internal and the animals just became lethargic and died. Farmers also saw an increased number of miscarriages among the less severely affected cows.
Frank Schofield, a vet who had emigrated from England and was working at Ontario University, was the first to determine the cause. Initially he thought it was an infectious disease but the animals had no fever and he could not transmit the condition from one animal to another and soon realised it was related to the animal’s diet. The Winter of 1921 was particularly hard and a large number of farmers depended on stored sweet clover to provide fodder for their animals. Schofield recognised that the condition only occurred in animals fed on spoiled sweet clover. Unfortunately, Schofield’s University refused to continue funding his research and he was sent back to teaching. He was so disillusioned that he gave up research and became a missionary in Korea.
Another veterinary pathologist, Lee Roderick, working independently also concluded that the source of the problem was spoiled sweet clover and showed the condition could be controlled if clover was withdrawn from the diet or if affected cattle were given blood from unaffected animals. In spite of finding the cause of the problem, the only advice the veterinarians could give to the farmers was to find an alternative source of hay.
The condition was named Haemorrhagic Sweet Clover disease
Unfortunately, the problem didn’t go away and when the great depression hit in 1929 the problem got worse as many farmers were unable to afford addition cattle feed. One farmer, Ed Carlson, in North Wisconsin was particularly badly hit. I will tell you his story in the next part of the Warfarin Story.