What’s the link between South Georgia Island and the drug, warfarin?

If you were a Norwegian brown rat, then the island of South Georgia is probably a place you might want to avoid right now.  

South Georgiasits in the sub-Antarctic Atlantic Ocean about 2 thousand kilometres East of the southern tip of South America. It might appear a little bleak to us but it is a haven for wildlife. The Island has several webcams where you can see the terrain for yourself from the comfort of your own home.

One species of wildlife that is not welcome on the Island however, is the Norwegian brown rat. It is an invading species with no natural predators, lots to eat and it’s running amok.  Attempts are about to be made to cull the rat population by dropping nearly 100 tons of rat poison on the Island. As you might imagine there is some debate as to whether this approach is warranted or not, but I am not an ecologist, nor an environmental politician and so I’m staying clear of that argument. Instead, I want to take a look at rat poison, how it works and how it came about. A subject not so boring as you might think.

Under pressure rats will eat just about anything that’s available, which is one reason they are such asuccessful species. Of course, eating anything means that they often dine on the unfamiliar and so there are risks that the chosen meal of the day may well be toxic. Rats have a trick up their metaphorical sleeves however, in that they will just nibble at a food source initially and then only return to eat more if they don’t suffer ill effects. A successful rat poison has to take this behaviour into account.  It has to be slow acting to lure the rat back to the bait and it has to be as specific to rats as possible and not other species. Poisons such as arsenic were used to kill rats in Victorian times, but arsenic hardly fulfils either criteria of having a delayed action or having any specificity to rats.  

The first poison that made any attempt at making the grade was discovered, not because of dead rats but dead cattle. Farms in Alberta and Wisconsin in the United States of the 1920s suffered from a mystery illness where cattle died from internal haemorrhaging. The cause was eventually traced to cattle that ate mouldy silage made from sweet clover. The silage contained a naturally occurring chemical called coumarin that prevented blood from clotting.  Coumarin was in effect the chemical equivalent of the genetic disease haemophilia (a famous haemophiliac was Queen Victoria’s son, Leopold).

The problem with the cattle was solved by removing sweet clover silage but researchers at the University of Wisconsin realised that a coumarin-based anticoagulant would make a good rat poison (known in the trade as a rodenticide).  Dr Carl Link at the Wisconsin Alumni Research Foundation (WARF) chemically modified coumarin to make the first bespoke rodenticide, that was named after the research laboratory where it was synthesised: Warfarin.

Rats taking small amounts of bait laced with warfarin felt no immediate ill effects and so happily went back for more. (In the language of rodenticides, the rats did not become bait-shy). A fatal rodent mistake as the returning rat then received a higher dose and like the cattle before it, died of internal haemorrhaging.  By the 1950s the mechanism of how warfarin acted as an anticoagulant was understood.  Blood clotting relies on a biochemical cascade that involves vitamin-K. The vitamin is a substrate for an enzyme called vitamin-K epoxide reductase, which is a vital step in the clotting process. Warfarin inhibits this enzyme, essentially throwing a chemical spanner into the works. The discovery had a very important consequence as it led to the use of vitamin-K as an effective antidote to warfarin poisoning, if it occurred in people. 

By 1948 warfarin had been developed as a “blood thinning” drug, for use in patients were there was a risk from blood clots, such is deep vein thrombosis and pulmonary embolism.  One of the more famous patients treated with warfarin was President Dwight Eisenhower following a heart attack in 1955. Warfarin remains a somewhat tricky drug to administer as the dose has to be tightly controlled. Other anticoagulant drugs have therefore been developed such asapixaban, dabigatran and rivaroxaban but warfarin is still widely prescribed.

Warfarin is not being used as a rodenticide in South Georgia but another coumarin based rodenticide called Brodifacoum which is more potent that warfarin and somewhat more specific.  The biggest concern surrounding the use of rodenticides is the effects on other species.  Rats are particularly susceptible to Brodifacoum but other species, including birds are also affected. Effective use of rat poisons is partly down to the choice of bait, where the rat prefers the bait to other food sources but it is less appetising to other susceptible species. There are also concerns if scavengers eat rat carcasses containing high levels of rodenticide. It seems that “collateral casualties” (to use a military euphemism) are inevitable but it’s a matter of risk assessment at the end of the day, and the Norwegian brown rat is very likely to do far more damage to the ecosystem than Brodifacoum. I’ll leave that argument there.