Somewhere deep inside a forest in central Africa right now, there is a ball python waiting for its next meal.
And waiting.
And waiting.
Pythons can go months — perhaps even longer than a year — without eating. But when they do it is a gourmand’s feast, with the python sometimes consuming a meal equivalent to its entire body weight. Imagine fasting until next Thanksgiving, then hitting up the McDonald’s drive-thru for 300 Big Macs.
Humans would die trying to live this way, but pythons have an extraordinary trick. To deal with all this nutrition at once and the stresses of pumping it through the bloodstream, its organ systems temporarily become HUGE. Its heart expands 25% or more. And, once the meal has been digested and its nutrients distributed, those organs, including the heart, shrink back to normal size without suffering any damage.
When Leslie Leinwand, a powerhouse biology professor and expert in cardiovascular health at the University of Colorado, first read about this, she was giddy.
“I walked out into the lab, and I said, ‘I think we ought to start working on pythons,’” she said. “And people looked at me like, ‘What?’”
Until that point, Leinwand’s lab had been a fairly typical research operation. They worked with mice and rats to solve scientific riddles.
When the snakes finally arrived in her lab — 18 baby pythons in a single pillowcase, which itself was inside a cardboard box that had been shipped from an exotic animal dealer in Oklahoma — Leinwand did question her decision.
“I picked up this pillowcase, and the whole bag is kind of moving,” she said. “And I had a moment where I thought, ‘What have I done?’”
But Leinwand knew that the rest of the animal kingdom held secrets that could benefit human health. Drugs like Ozempic that have revolutionized treatment for diabetes and obesity were developed based on research into Gila monster venom. The venom from deadly sea snails has been studied for potential therapeutic benefit.
So Leinwand plowed ahead. And now her nearly two-decade-long quest to understand python hearts has yielded valuable insights that could one day lead to treatments for multiple kinds of heart disease.
Take, for instance, the python’s expanding-shrinking heart trick. Leinwand and other researchers in her lab have discovered that python hearts are remarkably pliant. Understanding what makes them so could help treat a human condition called cardiac fibrosis — a stiffening of the heart associated with heart disease.
“We would love to know how to make stiff hearts much less stiff,” Leinwand said.
Or what about how a python is able to pump all that sludgy, fat-laden blood through its body following a big meal? A recent study from the lab looked at components of heart muscle cells called myofibrils taken from ball pythons after feeding. (The lab has also studied Burmese pythons, but purchasing and transporting those has become difficult as regulators crack down in response to the species’ invasive rampage across Florida. Those same restrictions mean Leinwand’s students now have to drive new python test subjects back from Oklahoma themselves.)
“We saw something really cool,” said Claudia Crocini, a researcher at Charité – Berlin University of Medicine in Germany who worked on the study while a postdoctoral student in Leinwand’s lab. “These myofibrils after feeding were able to produce a lot more force compared to the nonfed python hearts.”
In other words, python hearts got stronger, something that could help treat human heart conditions involving a weakened heart.
Leinwand is also fascinated by how a python heart grows — when it swells after a meal, doubling the snake’s heart rate, it looks like that of an elite endurance athlete, not like that of someone with advanced cardiovascular disease. Understanding how this happens could lead to treatments for the many human ailments linked to an enlarged, but sick, heart.
And then there’s this little factoid: No matter how much they eat, pythons don’t seem to get heart disease. Leinwand’s tried, in an experiment she half-jokingly calls “‘Super Size Me’ in snakes.” She even tried to publish a journal article with the title “Redefining snake oil.”
“I love that title,” she said. “But they didn’t.”
By now, you may be wondering how serious of a person Leinwand actually is. Interesting research, good sense of humor, but c’mon. Snakes? To treat human heart disease?
But Leinwand may be the most impactful Colorado scientist you’ve never heard of. She has an extraordinary record of turning scientific insights from the lab into actionable treatments that make it to market, where they are helping people live healthier lives.
In 1996, after years of studying a protein called myosin, Leinwand and several colleagues founded a company called Myogen, which eventually developed new drugs to treat a condition called primary pulmonary hypertension. The company sold in 2006 to Gilead Sciences for roughly $2.5 billion.
In 2012, she and several different colleagues then founded a company called MyoKardia to further develop research they had done on a heart disease called hypertrophic cardiomyopathy. The disease — caused by faulty myosin that leads to an enlarged, unhealthy heart — is most famous for causing the death of basketball star Hank Gathers. That company sold in 2020 to Bristol Myers Squibb for $13.1 billion.
Bristol Myers Squibb then got MyoKardia’s invention, a myosin inhibitor called mavacamten, across the finish line for federal approval. The drug is now known by the brand name Camzyos.
“I can’t tell you how gratifying it has been to hear from patients and physicians about this drug and how it’s actually reversing the disease, as opposed to just stopping its progression,” Leinwand said.
There’s still a long way to go before the research on pythons can be turned into treatments for humans. Leinwand and her team need to better identify the exact molecules involved in the beneficial heart processes. They then need to test those molecules in mammals — back to studying mice and rats again.
In the meantime, Leinwand’s past successes have led to uncommon potential sources of funding for a university professor: She’s pitching venture capital firms. But, while the doors may be open, the wallets are less so.
“The answer I got, which people in biotech dread, is that it’s too early,” Leinwand said.
She smiled.
“I could understand why they would think this is a crazy idea.”
But Leinwand, as always, is undeterred. Much like a python, she knows that big things can come along for those with patience.