The Burmese python is one of the largest snakes in the world. But despite its intimidating appearance, it has a heart. And that heart may provide clues to researchers in developing drugs that help counteract the effects of heart disease.
Last week I talked with Dr. Leslie Leinwand, professor of Molecular, Cellular and Developmental Biology at the University of Colorado. Leinwand sometimes has as many as 60 pythons in her lab, where she also teaches a research lab course called the Python Project. Excerpts of our conversation are below.
What is it about pythons that make them a good model for studying heart disease in humans?
Most of us in academic settings usually study mice and rats. In this case, pythons sounded extremely exotic. What Diamond had described was a phenomenon that I didn’t know anything about. Being a heart person, I zeroed in on a couple properties of these snakes. Diamond had shown that pythons were infrequent feeders; they can live for nine to 12 months without eating anything. They don’t lose muscle mass--which is what happens when mammals fast--so I was interested in that. But what really intrigued me was that when they do eat, they eat a huge meal. And in order to digest it, their organs—except for the brain--increase in size, stay big for a few days and then go back down again after the digestion process.
Diamond’s work had shown that when you look at insulin levels and lipid content of their blood—in you or me or a mouse--those levels would be toxic. But the pythons are completely oblivious to those levels. So I wanted to understand how the snake can do this—have their organs grow and then how they can get rid of that extra tissue. Our hypothesis was that the enlargement of the heart would be akin to that of a highly trained athlete, like Michael Phelps or Lance Armstrong. So we hypothesized that the python does this, but in 24 to 36 hours.
Your heart can also get bigger in an unhealthy way, through genetic disease or a lifetime of high blood pressure that’s not treated. So we thought if we could understand how the python does this over and over again throughout its life, it might lead to therapeutic solutions .
We would like to be able to develop a pharmaceutical that could potentially counteract a disease state and make a more healthy heart. I think everyone knows that exercise is a good thing; but some people simply can’t exercise.
You are working with a local biotech company on this?
Yes, a very small company, Hiberna Corp. I’m one of its founders. It was founded on the biology of extreme organisms. Pythons and organisms that hibernate are two examples.
There are people working on bears, but not at this company. That would be more of a challenge for me than pythons. There’s a hibernating ground squirrel that the company is working with.
So what happens next with the pythons?
We have a paper in the works. The idea is to find out if we can do similar processes in mammals and whether we could develop a drug that could work in mammals that would mimic some type of beneficial cardiac growth.
And the drugs would counteract the effects of heart disease?
They would try to reverse that by promoting good processes as a surrogate for very vigorous exercise.
So it would be like giving them a little bit of Phelps or Armstrong.
Did you have any reservations about working with pythons?
Not really. You have to be respectful that these are very large snakes, so you handle them carefully. Generally when we study them they are four to five feet--a young adult. Pythons are among the longest lived and biggest snakes in the world. If you feed them continuously instead of fasting them like in the wild, they just keep on growing. Twenty to 30 feet not uncommon. That would be a challenge to work with.
How many do you have in the lab?
At any given time about 20, but we’ve had as many 50 or 60.
Where is their natural habitat?
Mostly in India and what used to be Burma. Now there’s an infestation of the Florida Everglades. It’s a disaster because they don’t have any predators. They are eating everything in sight and growing like crazy, choking out local species.
Anything else I should know about them?
We developed a research lab course called the Python Project. Students take it for credit and get a real life research experience. Kids get a lot more interested in science if they can actually do it versus just read it. We’ve had this course for five years and we have 16 undergrads each semester. Instead of having a TA teach it, we have post-doctoral fellows teach it, so students get great high-level instruction on this interesting biological program.
Howard Hughes Medical Institute developed the Professors Program—so I got a grant from them for what would otherwise be a pretty expensive course to run.
How helpful are the undergrads with the research?
Incredibly helpful. Sometimes lab courses are out of a manual and you already know what the result is. And they’re bored. But as soon as the students realize they are generating data that no one has generated before they're really excited.