Air Vehicle Safety Prevention and Protection System (AVSAPPS)

 

Unit 4 Individual Project

 

"discovery" 

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Warfarin Discovery 

Warfarin is a medication used to treat and prevent blood clots in the body.  It was first used in the 1940s as a rat poison (The History of Warfarin, n.d.), and it entered human clinical trials in 1941 at the Wisconsin General Hospital and the Mayo Clinic (The Invention of Warfarin, n.d.). Warfarin was later approved for human consumption in 1954.  It soon became a widely used rat poison, the first and most widely used blood thinner prescribed in the world. 

The Discovery of Warfarin

In the 1920s, there was an outbreak of sweet clover disease that caused cattle to die after mild trauma or “safe” procedures. Two veterinarians, Frank W. Schofield in Canada and Lee M. Roderick in North Dakota discovered that eating molded hay resulting from wet, spoiled clover was the source of the problem (The Invention of Warfarin, n.d.).  Eating the hay caused the cows to hemorrhage and bleed to death, but it was unknown which specific substance was the culprit.  

Scientists at the University of Wisconsin continued to research the phenomena over the next 20 years.  Geneticists Royal Alexander Brink and William K. Smith researched a chemical called coumarin that makes the clover smell sweet although it has a bitter taste. The identification of Coumarin would be a key discovery that contributed to solving the mystery of sweet clover disease.

In parallel with University of Wisconsin studies, Karl Paul Link, a professor at the University of Wisconsin, and his student assistant, Eugen Schoeffel, isolated a substance in the clover that prevented blood from clotting, dicoumarol (The History of Warfarin, n.d.). They later discovered that the substance was produced by a chemical reaction between coumarin and molds that grow when clover hay gets wet and spoils. (The Invention of Warfarin, n.d.). The researchers were awarded a patent in 1941 (Lim, 2017).

Subsequently, University of Wisconsin colleagues Mark A. Stahmann and Charles F. Huebner produced an identical substance in the laboratory that verified the molecule structure. Link and the other researchers produced more than one hundred similar compounds by varying the chemical structure.  Each compound inhibited the coagulation of the blood. The compound labeled number 42 was later named warfarin – a name that combines the acronym “WARF”, associated with the research funding source, the Wisconsin Alumni Research Foundation, and “arin”, derived from coumarin (The History of Warfarin, n.d.). 

Warfarin was first registered in 1948 for use as a rat poison. The sweet odor of the substance attracted rodents while the anticoagulant property delay ensured that they were repelled from eating the bait (Lim, 2017).

The Accidental Discovery that Led to Warfarin Use in Humans

Although Warfarin use for humans had been considered, it was deemed too risky due to the possibility of hemorrhage.  The concern was overcome due to an accident.  A man who attempted suicide using the Warfarin-based rat poison was treated with vitamin K and he fully recovered! The fact that the effects of Warfarin could be reversed enabled human research that led to the approval of Warfarin for human medical use in 1954 (Lim, 2017).

Endo Laboratories manufactured Warfarin for use by humans under the brand name Coumadin.  United States President Dwight Eisenhower was an early benefactor of the Warfarin accidental discovery.  He was given the Coumadin after suffering a heart attack.  Warfarin continues to be used to treat people and save lives.  Experts estimate that around one hundred million prescriptions of warfarin are still issued globally each year (The Invention of Warfarin, n.d.). 

Forces that Support the Warfarin Discovery

There are multiple forces that support the Warfarin discovery.  Environmental, financial, and societal forces initiated the chain of events that led to the Warfarin discovery.   The molded clover hay was caused by the wet climate.  This environment was killing cows that the society depended on for dairy and meat products, and that farmers depended on for economic survival.  In 1933, a desperate farmer traveled two hundred miles in a blizzard to Madison, Wisconsin with “a milk jug full of blood, a dead cow, and a pile of moldy hay” searching for a veterinarian and the cause of the problem (The Invention of Warfarin, n.d.).  The veterinarian was not available when he arrived since it was the weekend, so he took the samples to a laboratory at the University of Wisconsin where the research started.

Although Warfarin was approved for use in rodents, societal and legislative forces impacted its use on humans.  Societal fears about using “rat poison” to treat humans in addition to the risk of causing hemorrhage delayed clinical trials until another “accident” occurred.   Vitamin K was used to reverse the Warfarin effects for a man who attempted suicide using Warfarin-based rodent poisons.   This “accident” provided knowledge that enabled Warfarin clinical trials on humans to proceed.

Technological forces were also a key contributor to the Warfarin discovery.  University of Wisconsin researchers produced more than one hundred compounds while researching the causes of the sweet clover disease.  One of the compounds became Warfarin.

Conclusion

There were several accidents that led to the Warfarin discovery. Searching for a solution for clover hay disease led to the discovery of Warfarin for use as rodent bait. Vitamin K treatment for a Warfarin suicide attempt resulted in clinical trials to use Warfarin to treat humans.  President Dwight Eisenhower's heart attack treatment using Warfarin provided confidence in the medicine as a treatment in humans.  The benefits of the Warfarin discovery benefits are still impacting lives around the world!

 

References

(n.d.). The History of Warfarin. Eat On Warfarin. https://www.history.com/news/accidental-inventions#dynamite

(n.d.). The Invention of Warfarin. ACS Chemistry for Life. https://www.acs.org/education/whatischemistry/landmarks/warfarin.html

Lim, G. B. (2017, December 14). Warfarin: From rat poison to clinical use. Nature Reviews Cardiology. https://www.nature.com/articles/nrcardio.2017.172