Honey badger venom resistance: biologists discover the secret

Biology Finally Explains Why Honey Badger Don’t Care

Biology Finally Explains Why Honey Badger Don’t Care

Wild Things
Slate’s animal blog.
June 16 2015 12:04 PM

Biology Finally Explains Why Honey Badger Don’t Care

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A honey badger eats a mouse at Prague's Zoo.

Photo by Michal Cizek/AFP/Getty Images

It’s official: Honey badger don’t care. This “crazy nasty-ass” critter—the subject of a National Geographic documentary transformed into a viral meme through satirical overdubbing—“really don’t give a shit.” Not about snarky documentaries, not about stinging bees, and especially not about venomous snakes.

Venomous snakes kill up to 94,000 people every year, on top of the millions of other animals that make up their diet. And death by venomous snakebite isn’t pretty: The toxins in venom can paralyze muscles, break down tissue, and even make victims bleed uncontrollably.

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So why don’t honey badgers care about venoms that can kill almost any other animal?

Danielle Drabeck, a University of Minnesota grad student, wanted to study this question on a molecular level, but she ran into a problem: Honey badgers aren't found in Minnesota or even the Western Hemisphere, but only in Africa, the Middle East, and India.

“The hardest part, honest to God, was finding honey badger tissue” to study, says Drabeck—which likely explains why no other biologists ever investigated how honey badgers resist cobra venom. Working with biologist Sharon Jansa and biochemist Antony Dean, Drabeck obtained some precious honey badger blood from the zoos of San Diego and Fort Wayne, Indiana.

With this blood, the scientists figured out, for the first time, how the honey badger defends itself on the molecular level against its venomous prey. The blood also revealed clues of an evolutionary arms race. And it might help us design better antivenoms for humans bitten by venomous snakes.

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But why would a honey badger need venom resistance in the first place? Why doesn’t it avoid venomous snakes, like more sensible mammals?

“Snakes,” says Drabeck, “are an excellent source of meat.” Up to 25 percent of the honey badger’s omnivorous diet consists of venomous snakes. But the honey badger doesn’t eat snakes out of desperation. Evolving to withstand snake venom is like being the only person at a party who can eat the extra-hot salsa: You get it all to yourself. Plus, Drabeck says, this means the honey badger gets to hunt fairly slow-moving prey with only one pointy end, rather than fast prey with one pointy end plus four sets of claws.

But it’s one hell of a pointy end. Venom has more than 100 proteins and other molecules that could potentially poison a snake’s victim—meaning that honey badgers need multiple defenses. To narrow the field, Drabeck guessed that the honey badger had probably evolved a defense similar to that used by other venom-resistant critters like mongooses. She focused on a defense against a nasty class of molecules in cobra venom called alpha-neurotoxins that paralyze the muscles used for breathing. These neurotoxins essentially park in a muscle cell’s nicotinic acetylcholine receptor, preventing the cell from receiving the nervous system’s signals to keep working.

Drabeck figured that the receptor targeted by cobra neurotoxin had probably changed to prevent the neurotoxin from parking there. Once she had the blood from the zoos’ honey badgers, Drabeck extracted DNA and sequenced part of the gene that contains the blueprint for making the receptor. Drabeck discovered several mutations in that gene that tweak the receptor. Cobra neurotoxin fits as well in the tweaked receptor as an SUV in a compact’s parking spot—and therefore it can’t paralyze the honey badger’s breathing.

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Drabeck wasn’t surprised by these mutations, but she was surprised when she compared the honey badger’s tweaks to those found in other mammals. These tweaks had evolved independently in at least four species: honey badgers, mongooses, hedgehogs, and pigs. The hedgehog—which loves to eat venomous snakes—wasn’t a surprise. But the pig? “We were pretty excited by that,” says Drabeck. She hadn’t expected pigs to have molecular defenses against venom; biologists knew wild pigs could survive snakebites but assumed that was because their thick skin and fat acts like armor against fangs. But wild pigs, like honey badgers, have long shared the same parts of the world as venomous snakes—giving them an incentive to evolve venom resistance. And that in turn has given the snakes an incentive to evolve more toxic venom.

Venomous snakes and resistant honey badgers, it turns out, are locked in what Jansa describes as a “tit-for-tat arms race.” This co-evolution is an unending cycle of one-upmanship between predators and prey. When venomous snakes are attacked by venom-resistant honey badgers, the snakes need to evolve more toxic venom to protect themselves.

But what does this research mean for the 1.8 million unfortunate people bitten by venomous snakes every year? Drabeck suggests that figuring out these molecular tweaks in the honey badger’s resistant receptor could suggest new ways to create better antivenoms. “That’s one of the important questions” about this research into honey badgers, says biologist James Biardi, an expert on venom resistance at Fairfield University in Connecticut. “What does this mean for people?”

Right now, many antivenom infusions are made of antibodies—molecules produced by the immune systems of horses and sheep exposed to venom, which can neutralize the venom in bitten people. But whenever someone gets treated with these antivenoms, they run the risk of having an allergic reaction as dangerous as the venom itself. By understanding more about the targets of venom—targets like the honey badger’s neurotoxin receptor—scientists can hopefully design safer treatments. Because unlike the mongoose, hedgehog, pig, and honey badger, we humans with our puny neurotoxin receptors do care—especially about venomous snakes.