On a Mission to Heal Gila Monsters

Emily Anthes

By any measure, the diabetes drug Ozempic has been a blockbuster, racking up billions of dollars in annual sales. In the United States alone, pharmacies fill millions of prescriptions for Ozempic and related drugs, which have become popular for their weight-loss effects, every month. But in the beginning, before the celebrity endorsements and the think pieces and the global supply crunch, there was just a strange, venomous lizard with a flair for intermittent fasting. The Gila monster, which is native to the deserts of North America, can survive on just a few meals a year, thanks to a digestion-slowing hormone in its venom.

The discovery of this hormone paved the way for Ozempic, making the Gila monster an enormously profitable gift to modern medicine. And last summer, one particular Gila monster, a former pet named Pebbles, needed medicine in return. Pebbles, a resident at the Creature Conservancy, a wildlife education organization in Ann Arbor, Michigan, had been infected with a parasite called Cryptosporidium. Hard to kill, the parasite colonizes the digestive tract and is typically a death sentence for reptiles.

A veterinarian had recommended that Pebbles be humanely euthanized. But the Creature Conservancy wasn’t ready to accept that fate for Pebbles, who had at least another decade of life potentially ahead of her. “If we can fix her,” Steve Marsh, founder of the Creature Conservancy, said in July. He corrected himself: “If he can fix her,” he said. He nodded toward a sharply dressed man who was cradling Pebbles in his gloved hands: Tim Cernak, a pharmaceutical chemist at the University of Michigan.

A few minutes later, a veterinarian inserted a tube into the lizard’s throat, collecting liquid from her stomach. Later, Cernak would study this sample in his lab, hoping to isolate the parasite and find a drug that could vanquish it.

Pebbles was not the patient Cernak had in mind when he began his career. Until 2018, he had worked at pharmaceutical giant Merck, developing drugs for people with cancer, HIV, diabetes and other conditions. Along the way, he had helped develop cutting-edge approaches, involving robots and artificial intelligence, to speed up the invention of new human drugs.

A few years ago, however, Cernak decided that he wanted to use those tools to make medicines for ailing plants and animals, forging a new field he called “conservation chemistry.”

Gila monsters weren’t the only species that had inspired human drugs. There were antibiotics derived from fungi, anti-cancer drugs from plants and painkillers from animal venom. Cernak thought it was time for pharmaceutical chemists to give back. “To me, it’s this full-circle thing,” he said. “We’re attempting to solve the ultimate health inequity.”

Cernak, a native Canadian, had grown up catching leopard frogs and crayfish at his grandparents’ lakeside cottage in Quebec. When he left his job at Merck, he wanted to use his chemical expertise for a greater environmental good.

“Pharma’s rad,” said Cernak, who has a youthful face and the upbeat energy to match. “But I wanted to apply my talents to a love of nature.”

Initially, he thought he might do research on methane, a greenhouse gas contributing to climate change. But after COVID-19 hit, he began to think more about the existential, population-level risks posed by disease.

A fungal disease called chytridiomycosis, or chytrid, was driving frogs to extinction. Bald eagles and elephant seals were succumbing to bird flu. And sea turtles were washing ashore with a contagious form of cancer.

Treatment options left much to be desired. There were human medicines that could help some sick frogs and sea turtles, but they could cause severe side effects and were suitable for only certain animal patients.

Cernak had experience developing targeted anti-cancer drugs, which were designed to destroy cancer cells while minimizing damage to healthy ones. Would it really be such a stretch to do the same thing for a tumor-riddled sea turtle? “Precision oncology for a sea turtle — that could totally be done,” he thought.

The same idea could be extended to ecosystems. In some ways, the invasive, sap-sucking insects that were spreading through America’s hemlock groves could be considered a cancer of the forest. Perhaps the tools of pharmaceutical chemistry could help him design a precision pesticide that would wipe out the invasive insects while sparing native ones.

Cernak had a knack for seeing opportunities everywhere and a reluctance to do anything halfway. He began traipsing around hemlock groves at the university’s arboretum and asking sea turtle hospitals for samples of tumor tissue. He puzzled over how to get antimalarial drugs to rare birds in Hawaii and wondered, as “just kind of a fun thought experiment,” whether he could design monoclonal antibodies that selectively ferried poison to different species of invasive fish.

And on a trip to the Creature Conservancy in December 2023, he learned about the plight of Pebbles.

Drug development is a famously failure-prone pursuit. Cernak has ratcheted up the degree of difficulty by focusing on pathogens and patients that are poorly understood. “People haven’t chosen to look inside of the Gila monster too much,” he said.

But that’s exactly what his team was doing one day in July, in a chemistry lab on the University of Michigan’s leafy campus.

There are many species of Cryptosporidium, which can infect a wide range of mammals, birds and reptiles. All of them are understudied, Cernak said, but the reptile pathogens are a particular mystery.

And when the scientists put a sample from Pebbles under the microscope, they were startled by what they saw: a single-celled parasite wrapped in a thick, jellylike coating, an unexpected extra layer of cellular protection. “It’s like this citadel,” Cernak said.

Soon, they would begin looking for a drug to breach this line of defense. On another lab bench, however, the hunt for a better cure for chytrid, the amphibian fungal disease, was already underway. A modular robot in a transparent box glided back and forth, preparing to dispense minute doses of antifungal drugs into a grid of shallow wells.

The short-term goal was to identify an existing drug that would be more effective and less toxic than one common chytrid treatment. The robots — the largest of which could run more than 1,500 chemical reactions at once — could quickly test a pharmacy’s worth of possibilities on lab-grown chytrid cells.

Over the months that followed, the team identified a compound, which Cernak declined to disclose, that proved promising in both the cells and in the African dwarf frogs that were paddling around in a nearby biology lab. The next step is to test it in additional species.