Arizona’s Adorable Monster

The Gila monster uses its bladder as a canteen, inspires medical drugs, and has excruciatingly painful venom. What secrets will its genome reveal?

In a hallway at Arizona State University, I’m watching a sleeping lizard. It’s the size of my forearm, covered in a mosaic of bumpy black and yellow scales, and—rather endearingly—is curled up on its back. “It reminds me of a cat,” says Melissa Wilson Sayres. “It’s lazy. Once a week, we’ll get a call from students who think it’s dead.”

The creature is a Gila monster—a native of Arizona, and named after the Gila River that flows through the state. Their venomous saliva has already led to the development of a drug for managing type 2 diabetes, which is partly why scientists are so intrigued by them. Others are less enamored. Perhaps because of their name, their garish warning colors, or their infamously venomous bite, these lizards are often persecuted, even though it is against state law to harass, harm, or catch them. Those at the university are all rescued, and spend their days in the care of Dale DeNardo, a physiologist who studies how animals survive in deserts.

“Dale made me fall in love with the monsters, because they’re gentle,” says Wilson Sayres, one of his collaborators. “He has rattlesnakes too. When you see them, they’ll rattle, and your heart races because you realize you’re a primate and you’re terrified of snakes. But the Gila monsters will just sit and stare at you. They’re chill.”

That’s actually part of the danger, says DeNardo. Rattlers are fairly docile in the wild but easily agitated in captivity. Gila monsters are the opposite. “If you take that same lizard and put it in the sun for a few minutes, it’ll turn, hiss at you, and moonwalk away into a bush.”

DeNardo has long been fascinated by the lizards because they live life on the edge. They get all their food—rodent pups, bird chicks, and eggs—by raiding nests, which are few and far between, and only available between spring and late summer. They make the most of whatever they find, eating up to a third of their weight in one sitting and storing fat in their stumpy, bulbous tails, which they live off the rest of the year. But they have to find their meals first. “An egg doesn’t come rolling past, so they can’t be like a rattlesnake sitting in a shady spot and waiting for a rat to run by,” says DeNardo. “They have to be out searching.” And that means braving the scorching desert.

Partly, they cope by having a naturally low body temperature. DeNardo also discovered that they can use their bladders like a giant canteen. If they binge drink in spring, they can fill their bladders to around 20 percent of their body weight—the equivalent of an average human carrying a 30-pound jug of water inside them. With this reservoir, they can go for almost three months without dehydrating.

On their long foraging walks, the sluggish monsters are vulnerable to coyotes and birds of prey. That is probably why they’re venomous. They certainly don’t need toxins to help them to subdue helpless eggs, chicks, and pups. Instead, they use their venom for defense. No one has ever died from a Gila monster bite because the toxins aren’t great at destroying cells and tissues. They do, however, hurt like a sonofabitch.

“It felt like my finger was caught in the door of a car,” says DeNardo of his one and only bite, “and then like being hit by a hammer every ten seconds. For 45 minutes, I couldn’t concentrate.” That was a hatchling too, and one that lightly nipped him. Adults have a reputation for hanging on with bulldog tenacity, chewing as they bite to release more venom. If that happens, “find a tree, sit in the shade, and suffer,” DeNardo advises. “Don’t drive yourself to a hospital. You won’t die from the bite, but you’ll die from an accident.”

“In many ways, this animal is perfect for the desert,” he adds. “They’ve been in the Sonoran Desert since as long as there’s been a Sonoran.”

Studying the Gila monster isn’t just an exercise in academic curiosity. This stumpy lizard has already improved human health. In the 1990s, endocrinologist John Eng identified a protein in its saliva, known as exendin-4, which was similar to a human hormone that controls our blood-sugar levels. It seemed like a promising way of managing type 2 diabetes, especially since it lasted much longer than its human counterpart, and would only need to be injected daily rather than hourly.

After years of development, a synthetic version of exendin-4, known as exenatide and marketed as Byetta, was approved by the FDA in 2005. It is currently used to manage type 2 diabetes, and it might even help to protect against degenerative brain diseases like Alzheimer’s or Lou Gehrig’s disease.

“The pharma industry has studied exendin-4 extensively but nothing else about the Gila monster’s genome,” says Wilson Sayres. The creature’s other genes are largely a mystery; the closest living relative whose genome has been fully sequenced is the green anole—a slender, tree-dwelling lizard. “It’s like saying we want to study humans but all we have is a kangaroo genome,” she adds. “We don’t even know very much about how exendin-4 works in the monsters.”

She plans to change that by sequencing the lizard’s full genome, and looking at the genes that it activates in its salivary glands and its tail. To do that, she raised more than $10,000 in a crowdfunding campaign and did a lot of outreach, from appearances on local TV to a delightfully snarky Twitter account.

The monster’s genome might reveal more medically useful substances like exendin-4, as well as offering clues about the lizard’s many weird traits—their venom, their fatty tails, and more. For example, unlike other lizards, Gila monsters can’t break off and grow back their tails, presumably because they use store fat there. “If you drop your tail, that’s a lot of calories you just lost and fed to someone else,” says Wilson Sayres. One of her colleagues is looking for the genes responsible for the regenerative abilities of other lizards, and it might be easier to find those genes by looking for those that have changed significantly in the Gila monster.

The Gila monster genome might also tell us something about another group of reptiles—snakes. It’s clear that snakes evolved from lizards, but it’s unclear which group they originated from. Currently, snakes are positioned as the cousins to a large group of lizards that includes the Gila monster, monitor lizards, iguanas, chameleons, and anoles.

Here’s the twist: The green anole determines its sex using X and Y chromosomes, just like us. Males have a mismatched XY and females have a matching XX. But both Gila monsters and snakes have Z and W chromosomes, where the males have matching ZZ and the females have mismatched ZW. If they're genetically identical (or similar, at least) that tells you that both the snakes and Gilas inherited their ZW from a common ancestor (rather than evolving them independently), and thus are more closely related than they are to anoles.That would shift their position in the lizard family tree and provide new clues about how they evolved.

As is increasingly the case, research like this is a race against time. As the world warms, the Sonoran’s spring rains will become more inconsistent and the summer monsoons will arrive later. The Gila monster is well-adapted to persisting through that dry spell, but may not be able to cope with longer droughts. By the end of spring, “they’ve pretty much filled their abdomen with as much water as possible,” says DeNardo. “If there’s no room to get larger, they won’t be able to stretch out much longer.” By changing the climate, we may be inadvertently slaying the monster.

And that, Wilson Sayres thinks, would be an incredible shame. “It’s such a cool animal, and it’s so lovable.” We’re now sitting in her office, and she’s holding a 3D-printed model of a Gila monster skull. It looks rather nightmarish—distinctly reptilian, full of sharp curved teeth, and covered in knobby bone. This, I venture, does not look like the skull of a lovable animal.

“I mean, if you had no flesh on your face, you probably wouldn’t be adorable either,” she says.