In the foothills of a canyon in Arizona, a predator patiently awaits her next meal. Despite its ominous name, the Gila monster resembles more of a sluggish dragon than a true monster. It moves slowly, is active primarily in the early morning, and is not much of a hunter. Its diet consists mainly of eggs, young lizards, and birds. The Gila monster remains largely dormant throughout the year, becoming slightly more active in spring when birds nest and rodents and lizards reproduce. Its slow metabolism allows it to consume 30-60% of its body weight in one meal, acquiring most of its annual calories in the spring.
Our friend is not entirely harmless. Her claws and legs are adapted for digging eggs from deep nests, and her jaws are as powerful as a vise grip. Once she bites, her prey is unlikely to break free. While she uses these abilities to capture small prey like baby birds or lizards, she possesses a hidden superpower: venom glands in her lower jaw. When she bites, venom flows along her grooved teeth into the wound. Though she produces only a small amount, her venom is as toxic as that of a Diamondback rattlesnake. Her prey struggles as she moves her jaws, but this motion is not chewing; it’s a method to inject more venom into the bloodstream.
Our friend isn’t completely harmless though. Her claws and legs are adapted for digging eggs from deep nests. Her jaws are powerful, like a vise grip. Once she bites, the prey will likely be unable to pry her jaws back open. While she uses these abilities to capture small prey like baby birds or lizards, she possesses a hidden superpower: venom glands in her lower jaw. When she bites, venom flows along her grooved teeth into the wound. She only produces a small amount, but her venom is as toxic as a Diamondback rattlesnake. Her prey struggles as she moves her jaws, but this motion is not chewing; this action puts a significant amount of venom into the bloodstream.
She doesn’t need venom to subdue prey, as her bite is usually lethal. She rarely misses. However, humans bitten by Gila monsters report significant pain, described as electric pulses or an intense bee sting. Her venom serves primarily as a defense mechanism. One bite is likely to send a predator packing. Gila monsters may hold onto a potential predator for more than 10 minutes, long enough for the predator to rethink the bad decision. The bite can cause discomfort that lasts for hours. The bite is usually enough to deter predators from attacking a Gila monster again.
Scientists were interested in her initially because it’s unusual for lizards to have venom. There aren’t many: the beaded lizard, the Komodo dragon, the Gila monster. Why do these animals still have venom when most lizards don’t? The evolutionary benefit of their venom remains unclear, as it is not essential for killing prey and requires significant biological effort to produce. Although their venom is potent, a gila monster bite is usually not as severe as a rattlesnake bite and usually doesn’t cause necrosis. A 2021 review based on 22 cases of Gila monster envenomation reported symptoms such as angioedema, fluid loss, and atrioventricular conduction disorders. We know a lot about snake venoms (see here), but lizard venoms are poorly understood.
As a young research fellow, a man named John, Eng worked in the laboratory of Dr. Rosalyn Yalow, a 1978 Nobel Prize winner for inventing a method to find novel hormones in different animal species. Encouraged by Yalow to work diligently and think ambitiously, Eng pursued hormone research in various animals. He studied the hormones of guinea pigs, and chinchillas, and developed a method for protein identification. Looking for proteins to validate his test, he came across some studies done in the early 1980s by gastroenterologists at the National Institutes of Health. They noted that the venom in certain snakes and lizards caused inflammation of the pancreas, where insulin is made. Of particular interest was the hormone in the venom of the Gila monster. He also found research from Belgium on an interesting hormone in the venom of the Gila monster. He ordered some dried venom out of a catalog from a serpentarium in Utah to determine whether his new method could detect that hormone.
Eng found the hormone that the Belgium scientists had found, and uncovered another, which he named exendin-4. It was similar to a human hormone called glucagon-like peptide-1, which was beginning to attract interest as a possible diabetes treatment. GLP-1 increases insulin production in the pancreas. The lack of naturally occurring GLP-1 in humans is one of the causes of type 2 diabetes. We still do not know why the Gila monster has the compound in its venom. Human-produced GLP-1 is degraded quickly by enzymes in the blood. Unmodified, it would have to be injected into the body almost hourly. The Gila monster’s hormone, exendin-4, doesn’t degrade for hours, making it a much better candidate for a drug.
Here, we take another turn: no one was interested in Dr. Eng’s research. He worked for the Veterans Affairs Department and they didn’t want to patent it, as they couldn’t profit from it. Dr. Eng patented it himself and called multiple drug companies that weren’t interested. He patented this hormone in 1995. He marketed it to several drug companies but Amylin (then Lily) ended up with the patent. The first commercial product, Byetta, wasn’t approved until 2005. Drug creation takes a while.
In the foothills of a canyon in Arizona, a predator patiently awaits her next meal. Despite its ominous name, the Gila monster resembles more of a sluggish dragon than a true monster. It moves slowly, is active primarily in the early morning, and is not much of a hunter. Its diet consists mainly of eggs, young lizards, and birds. The Gila monster remains largely dormant throughout the year, becoming slightly more active in spring when birds nest and rodents and lizards reproduce. Its slow metabolism allows it to consume 30-60% of its body weight in one meal, acquiring most of its annual calories in the spring.
Our friend is not entirely harmless. Her claws and legs are adapted for digging eggs from deep nests, and her jaws are as powerful as a vise grip. Once she bites, her prey is unlikely to break free. While she uses these abilities to capture small prey like baby birds or lizards, she possesses a hidden superpower: venom glands in her lower jaw. When she bites, venom flows along her grooved teeth into the wound. Though she produces only a small amount, her venom is as toxic as that of a Diamondback rattlesnake. Her prey struggles as she moves her jaws, but this motion is not chewing; it’s a method to inject more venom into the bloodstream.
Being slow and deliberate, she doesn’t need venom to subdue prey, as her bite is usually lethal. However, humans bitten by Gila monsters report significant pain, described as electric pulses or an intense bee sting. Her venom serves primarily as a defense mechanism, deterring predators with a painful bite that can last for hours. Gila monsters may cling to a predator for over ten minutes, providing ample time for the predator to reconsider its attack.
Scientists were initially intrigued by her because venomous lizards are uncommon. Unlike their snake counterparts, lizards like the beaded lizard, the Komodo dragon, and the Gila monster retain venom. The evolutionary purpose of their venom remains unclear, as it is not essential for killing prey and requires significant biological effort to produce. Although potent, a Gila monster’s bite is generally less severe than a rattlesnake’s and typically does not cause necrosis. A 2021 review of 22 Gila monster envenomation cases reported symptoms such as angioedema, fluid loss, and atrioventricular conduction disorders. While snake venoms are well-studied, lizard venoms are less understood.
As a young research fellow, John Eng worked in Dr. Rosalyn Yalow’s laboratory, a 1978 Nobel Prize laureate for discovering a method to identify novel hormones. Encouraged by Yalow to work diligently and think ambitiously, Eng pursued hormone research in various animals. Seeking proteins to test his identification method, he encountered studies from the early 1980s by NIH gastroenterologists noting that certain snake and lizard venoms inflamed the pancreas, where insulin is produced. He was particularly interested in a hormone from Gila monster venom. Eng ordered dried venom from a Utah serpentarium to test his method.
Eng discovered the hormone identified by Belgian scientists and uncovered another, which he named exendin-4. He found it similar to glucagon-like peptide-1 (GLP-1), a human hormone of interest for diabetes treatment. Exendin-4 enhances insulin production in the pancreas, compensating for the lack of natural GLP-1 in type 2 diabetes. Although the reason for the Gila monster’s venom containing this compound is unclear, exendin-4’s resistance to rapid degradation makes it a promising drug candidate.
Despite the breakthrough, Eng struggled to gain interest in his research. The Veterans Affairs Department, where he worked, declined to patent it. Eng patented it himself in 1995 and approached several drug companies, but only Amylin (then Lilly) pursued it. The first commercial product, Byetta, was not approved until 2005, highlighting the lengthy process of drug development.
https://scholars.mssm.edu/en/persons/john-eng/publications/
https://scholars.mssm.edu/en/publications/purification-and-structure-of-exendin-3-a-new-pancreatic-secretag
https://pubmed.ncbi.nlm.nih.gov/6207171
https://www.sciencedirect.com/science/article/pii/0014579384806079
