Want to get rid of a snake? Use painkillers!

Paracetamol is extremely toxic to snakes. A Leiden PhD student found out why

By Bart Braun

At a certain point, back in the fifties, a small group of brown tree snakes, or perhaps just one pregnant female, arrived on the Micronesian island of Guam. Most people have heard of the island because, legally, it’s part of the United States – the part that could be hit by a nuclear missile from North Korea. Biologists know about it because of all the snakes.

Usually, if a new species of animal or plant arrives somewhere, it just dies. However, sometimes that species manages to adapt to its new home and becomes part of the local wild life. For instance, typically Dutch animals like rabbits and pheasant were brought here by the Romans. And sometimes the introduction of newcomers goes entirely, completely wrong. Prime example: Guam’s tree snakes.
Without a natural enemy, the snakes could multiply almost without limit, so they did. The island was literally crawling with snakes; it had the densest population in the world: ten snakes for every island dweller. If a snake climbed an electricity pylon and electrocuted itself, large parts of the island lost power, an event that occurred with depressing regularity. The island’s unique bird population was not accustomed to predators and stood absolutely no chance. Once the birds had been eaten, the snakes turned to lizards, rodents and other small mammals, including kittens. They managed to worm themselves into houses and are just about poisonous enough to pose a risk to young children. Something needed to be done.
But how do you fight millions of snakes at once? You need a poison, preferably something that’s fatal to snakes but can’t harm humans. Researchers tried all sorts: there were, after all, plenty of snakes to experiment on. And finally, they found a suitable substance: paracetamol. A 500-mg pill contains enough active ingredients to kill off six adult snakes. Dead mice were filled with the painkiller and spread around the island.
Guam still has an astounding number of tree snakes, but at least there are fewer than there once were.
And that brings us to PhD student Harald Kerkkamp at the Institute of Biology Leiden. He wondered why paracetamol was so toxic to snakes but not to other animals. Kerkkamp and toxicologist Peter van den Hurk of Clemson University in America wrote an article on it in Comparative Biochemistry and Physiology.
People who take an overdose of paracetamol die of acute liver failure, but snakes suffocate, which means something else happens to those creatures.
When people take a paracetamol, the liver absorbs a large part of it, and that’s where the chemicals are broken down in various stages and prepared for excretion. Each stage requires a different protein, which the liver needs to make first.
Kerkkamp and Van den Hurk collected livers from nine species of snakes and from alligators, cats and a few other animals. They mashed up the livers and then tested the activity of the different proteins. The main difference is a protein that goes by the prosaic name of uridine 5’-diphospho-glucuronosyltransferase, or UGT for short.
Without that protein, one of the breaking-down stages cannot occur and a toxic, intermediate substance builds up. Humans produce UGT, and so do rats, cows and alligators, but not snakes. Cats can’t make it either – so please don’t feed your poorly puss a paracetamol!
However, the traces of the gene for UGT can still be found in cat DNA. It looks as if they once had the gene for that protein but lost it. It’s not clear whether snakes ever had a similar gene.
Perhaps the reason both species can do without UGT is that they are both exclusive carnivores who never eat plants and therefore never consume the poisons plants produce.

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