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When Skip Maas first adopted Agrapina, a mottled ball python, she hadn't eaten in 14 months.
But as he soon observed, she was still a taut coil of spring-loaded muscle. Presented with a rat, she struck quickly, constricted it and then gorged on her meal.
And then her body performed another feat pythons are known for: It accelerated its metabolism dramatically to deal with the sudden influx of protein and fats, says Maas, "to help break down that meal and extract all of its nutrients."
Most people prefer to keep their distance from pythons — and for good reason. A quick strike followed by relentless constriction can be lethal. But Maas, a molecular biologist at the University of Colorado Boulder, and his colleagues argue that these snakes may hold secrets that could help people live longer and better.
In addition to being able to fast for weeks or months and still maintain muscle tone, they're able to grow and shrink their heart and other organs during feast and famine with seemingly no issue.
"It makes a lot of sense that pythons, because they live in such extreme environments, would have secrets that would apply to humans," says Leslie Leinwand, a geneticist who, two decades ago, first came up with this idea of translating the unique biology of pythons into medical treatments.
She's currently the executive science officer of CU Boulder's BioFrontiers Institute. And her lab runs an ongoing research project studying the reptiles, regularly publishing findings they hope could lead to medical breakthroughs.
Pythons "are so adapted to their lifestyle," says Maas, who recently completed his Ph.D. in Leinwand's lab. "I think it's a really great avenue to look at something that evolution has already figured out to take inspiration."
A python's dramatic internal renovation
One particularly extreme feature of the python is its metabolism — the rate at which it can transform food into usable energy.
"Pythons ramp up their metabolism from 10 to 40 times following a feeding, depending on the size of the meal," says Tommy Martin, an assistant professor at the University of Nebraska Medical Center and a former researcher in Leinwand's lab.
That's "the equivalent of a Kentucky Derby racehorse at rest, compared to when they're sprinting around the track," says Jack Gugel, a molecular biologist at CU Boulder and former student of Leinwand. But pythons, he notes, can maintain "that high metabolic state for days as they digest the meal."
To handle such super-high metabolism, the python's body undergoes a dramatic renovation. "Their organs will actually grow," says Gugel. That includes the snake's heart — to be able to pump more blood and oxygen to digest the meal.
Human hearts can increase in size too, over years. When that growth is due to high blood pressure or a heart attack, the heart stays enlarged and it stiffens — with potentially fatal consequences.
"Some people, no matter what they do, even if they have the perfect diet and they're exercising every day, they're still going to have heart disease," adds Gugel.
In pythons, however, a month or so after consuming a meal, their heart returns to its previous size.
"And we were really interested in figuring out — OK, what are the signals that tell this heart to get bigger?," says Gugel. "And then also, what are the signals that tell the heart to go back down to a normal size?"
Answering such questions might offer insights into how to stop or even reverse problematic heart growth in people.
Yuxiao Tan, a molecular biologist at CU Boulder who was supervised by Leinwand, has revealed another important insight in a soon-to-be published study. "Their heart can not only become bigger," he says, "but their cardiac muscle cells also increase in numbers after they eat."
It's different in humans. "When people suffer a heart attack," explains Tan, "they end up getting a scar over their heart because our heart muscle cells aren't able to proliferate and repair the scar."
The research in Leinwand's lab is still underway, but it's possible that pythons may carry the clues for how we might remodel human hearts to improve our own cardiac health at different stages of life.
Of muscles and molecules
Another line of investigation that these researchers are pursuing is related to the python's apparent ability to resist muscle atrophy.
Take Agrapina, Maas' pet python. Even after months of not eating and barely moving, when she caught site of the rat he offered her, "she was strong enough to then constrict it completely. She was fully capable," he says. "She had lost very little muscle tone despite all that time fasting."
"I know of no other creature that can do this kind of fasting without losing muscle function," says Leinwand. She believes this ability could one day lead to treatments for people dealing with muscle atrophy as they age.
And Leinwand says the snake's digestive processes have something to teach us as well, pointing to the countless small molecules produced as the animal breaks down a meal. "I think that this could be what we call a gold mine."
Indeed, Leinwand coauthored a paper, published this spring in the journal Nature Metabolism, with collaborators from a variety of institutions, describing a molecule coursing through the blood of both Burmese and ball pythons that surged a thousand times after feeding.
"If I were a betting person," says Leinwand, "I'd bet that something that changes a thousand-fold is probably doing something important."
The study confirmed her suspicion. Gugel says the molecule, which is called pTOS, appears to act as an appetite suppressant by targeting the hypothalamus in the brain.
"When we give this molecule to obese mice, they eat less and they lose weight," he says.
Jasmin Camacho, an evolutionary biologist at the Stowers Institute for Medical Research, applauds the python work as another way of looking in unexpected places for potential drugs and cures. "By going to this extreme animal, that molecule was expressed at a higher level in a way that it just stood out," she says.
Camacho, who wasn't involved in the python research, studies bats that she thinks might hold secrets for fighting diabetes since they can consume large amounts of nectar without any apparent health problems.
"Evolution's been running natural experiments for hundreds of millions of years," she says. "So by studying these adaptations, we start to think of other ways that our bodies can work."
Animal-inspired renaissance
GLP-1 weight loss drugs, like Ozempic, came out of research on the venomous gila monster lizard. Gugel hopes for a similar trajectory for the new molecule that the python studies uncovered.
"I think that there's big potential in the market for a drug that specifically can inhibit appetite in the brain to help people with weight loss," he says.
To that end, Gugel, Leinwand, Martin, and Jonathan Long of Stanford University have formed a company called Arkana Therapeutics to develop this and other discoveries into new drugs and treatments. They hope to look beyond pythons to other overlooked species, Martin says.
Ashley Zehnder is the CEO of Fauna Bio, a company that searches for disease resistance therapies among mammals equipped with unique adaptations. She says the approach that Leinwand's team at CU Boulder is taking could expand the drug discovery palette.
"You can find these really potent bioactive molecules in these extreme species," she says, "because they were evolutionarily perfected, and we can use that for medicines."
There are challenges to this approach, naturally, says Zehnder, including learning how to care for the animals in the lab and having to figure out their complex inner workings from scratch.
But the payoff, Zehnder argues, could be potential cures for our afflictions drawn from the great tree of life. "I think there's a lot that we can learn by putting ourselves back in that evolutionary tree and saying, 'what can we learn from these other animals?,'" she says.
"And I think what it will do at the end of the day is make us really greatly appreciate the value of that diversity."
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