I recently came across a new manuscript while catching up on research efforts on our national APS (The American Phytopathological Society) website. The article is titled ‘The inhibitory effects of the natural product Esculetin on Phytophthora capsici and its possible mechanism’. This research article caught my eye because P. capsici, the fungal oomycete which causes Phytophthora blight, is one of the most economically-important and one of the hardest diseases to control in New Jersey and other regions where vegetables are grown. Not knowing what Esculetin was, I started a google search. Yes, I jumped down the rabbit hole, or in this case the rat hole, more on that later. The story actually starts in 1933 during the height of the Great Depression when cows in the Midwest started dying of unnatural causes. A distraught Wisconsin farmer in the winter of 1933 loaded up a dead cow, some of its blood, and 100s of pounds of molded sweet clover in his truck and drove it 200 miles to the University of Wisconsin campus and accidently came across biochemist Dr. Karl Park Link, who happened to be working on a Saturday morning. The new cow disease became known as sweet clover disease but no one knew its exact causes. Other than telling the farmer to throw away all his sweet clover away and doing blood transfusions on his cows there wasn’t much Dr. Link could offer the poor farmer. Fortunately, with a little encouragement from a graduate student at the time, Eugene Wilhelm Schoeffel, Dr. Link decided to work on the mechanisms behind the fatal cow disease. Jump to 6 years later, Dr. Link and his research group discovered the role of coumarin and vitamin K (or lack thereof) in causing sweet clover disease because of the rotting sweet clover in storage. Coumarin, I’ve heard of that, it just didn’t register at the time. Coumarin, is an active ingredient in rat poison, as you might have already known. Coumarin works by preventing the coagulation of blood – basically it’s a blood thinner. The poor mouse or rat ingests the poison and then it slowly bleeds to death internally. Interestingly, here is where the story takes another turn. Knowing that coumarin caused the thinning of the blood and after many more years of research, Dr. Link patented the newly discovered chemical, dicumarol anticoagulant, with the help of the Wisconsin Alumni Research Foundation (WARF) in 1941 who still manages patents and funds research today at the University today. At that time, the newly discovered compound was named Warfarin in honor of both WARF and coumarin. Warfarin, is a commonly prescribed blood thinner still used today. So, what does all of this have to do with P. capsici control. Well, as with so many times in research, when one door opens or closes, so does another two or three. In very generic terms, esculetin, is one part of the biochemical pathway in coumarin production. Esculetin, is a well-known natural coumarin which can be isolated from plant species in families such as Heptaceae, Euphorbiaceae (the surge family), and Oleaceae (the olive family) or it can be artificially-synthesized in the lab. Researchers from around the world have been studying compounds such as esculelin, for their biochemical activity against different plant pathogens for many years which leads me back to the beginning of the story. Wang et al (2021) in their recent work with esculetin discovered that it strongly inhibited zoospore production and germination as well as offered protectant and curative activity against P. capsici when inoculated on tomato plants and, was capable of inhibiting early infection of P. capsici on Nicotiana benthamiana, a close relative of tobacco. Although this is both interesting from a historical standpoint and exciting for future opportunities, there is still a great amount of research that needs to be done in the lab as well as from an ecological and environmental standpoint. To prove my own point and as I wrapped up my journey, I googled mouse control in Australia, where we have all either heard or seen the videos of the great mice epidemics they have down under every so often. I immediately came across a current story in Australia’s efforts to use bait to curb the mice population where, unfortunately, the bait was having harmful impacts native wildlife. The compound, bromadiolone, you guessed it, an anti-coagulant – not registered for use in Australia – but because of the mouse population and its efficacy (which may kill a mouse in a single day after feeding on it) is currently being deployed to mitigate a biblical mouse population. Which, interestingly, as I learned, the Australians are still blaming the British for over 250 years ago when mice hitched rides on ships.
For more information please visit this terrific essay about the history of Warfarin by Jacqueline Houtman where much of the information in this article was collected.
The Clot Thickens | wisconsinacademy.org
