For Heart Health, Snake Oil

By Cayte Bosler
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(AP)

A python, though firmly high on the food chain due to its size (up to 30 feet long), sometimes doesn't eat for a year or more. The snake has a peculiar biological mechanism to compensate for its sometimes prolonged fasting periods. After a meal, the mass of a python’s heart doubles within a day, and the triglycerides in its bloodstream increase fifty-fold. Its metabolism and production of insulin and lipids skyrocket.

Then, the python’s organs shrink back to their original size without losing newly generated muscle mass. A well-muscled heart allows the python to survive until the next unforeseen feast.

Leslie Leinwand, a molecular biologist at the University of Colorado at Boulder, began investigating this adaptation in 2005, dubbing her research team the Python Project. Leinwand and her team are looking into the potential implications of mimicking the organ growth, or hypertrophy, of the python.

When she told her colleagues she was ordering a crate of baby Burmese pythons for her lab, they thought she’d lost her mind. But she is not the first scientist to call for investigation in an increasingly popular area of science called “extreme biology” for clues to human health.

Jared Diamond, famous evolutionary biologist and geographer, highlights the python's organ growth in a 1998 Nature magazine article. Leinwand's lab shares data—and pythons—with Diamond’s colleague (and co-author on the Nature article) Stephen M. Secor of the University of Alabama. The snakes are rumored to glide freely around Secor’s lab floor.

According to the Centers for Disease Control and Prevention, heart disease is the leading cause of death in the United States. In 2005, the University of Colorado molecular biology research lab was working on defining what happens to the human heart as it gets bigger in instances of athletics, heart disease, genetic disease, and high blood pressure. Leinwand’s intent from the get-go was to derive a drug for curing and preventing heart disease by studying the pythons and their enlarged hearts. 

The University of Colorado’s Molecular, Cellular and Developmental Biology research lab has long studied heart function. In 2013, Leinwand won the Bonfils Stanton Award in Science and Medicine for heart research.

“To determine what exactly is causing the enlargement of the python's heart we experimented by transfusing plasma from an [unfed] snake to another snake with no changes to speak of. Then we transfused plasma from a fed snake to a starved snake and its heart grew bigger,” Leinwand says.

The team identified three catalytic key fatty acids in the plasma of fed pythons: myristic acid, palmitic acid, and palmitoleic acid. This specific combination is the magic cocktail for tissue growth and a key discovery for the Python Project.

Dr. Cecilia Riquelme, an original team member of the Python Project, first called for experimentation to see the effect of python plasma on mammalian cells.

“I thought she would get discouraged. I thought it was too big of a leap.” Leinwand chuckles, remembering the conversation.

Riquelme didn't listen. She conducted an experiment in which she dropped snake blood on mice cells. Observing the cells’ reactions, she discovered the fatty acid combination indeed enlarges a mammalian heart.

Since the discovery the lab continues to test on healthy mice, pre-treating them with the discovered fatty acid combo, referring to it offhandedly as “snake oil.”

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Dr. Leinwand with python. (Courtesy Leslie Leinwand)

"The first step is to do no harm. And the effects so far have only been beneficial. By beneficial I mean the heart is larger morphologically, and geometrically. We can also look inside the heart to make sure we aren't triggering any disease pathways. We can measure that in a lot of different ways and we haven’t seen any evidence intracellularly that we are activating anything harmful," Leinwand says.

The next step is to determine if the fatty acid combination will reverse the progression of an already established heart disease.

“Next we will do three things: Simulate a genetic heart disease model, cause a heart attack, and give the [mice] high blood pressure with a surgical intervention,” Leinwand says.

If the snake oil works, the team plans to experiment on larger mammals like dogs, and finally move to a volunteer human population.

There are healthy and unhealthy ways for human hearts to grow—some diseases and congenital heart problems involve abnormally large, but defectively functioning hearts. A stellar athlete, by contrast, can develop a larger-than-average, well-functioning heart.

“Michael Phelps has a huge heart,” Leinwand explains. During prolonged periods of intense dynamic physical activity, human hearts can increase in size by 30 to 40 percent. “Athlete's heart is associated with improved cardiovascular biology and physiology. We can look to known literature that we have generated to understand when heart growth is healthy or not,” she says. “I like to think of it in terms of signaling molecules: Red means stop and green means go. It sounds trite, but it’s accurate. The molecules signal the heart to stop growing, to grow in a good way, or grow in a bad way.”

The goal of the drug is to build healthy muscle around the heart, in the same way a python is able to rapidly build healthy heart mass. Leinwand mentioned that the drug could treat diabetes, high blood pressure, and obesity—additional healthy heart mass could make exercise possible for those unable to work out due to their condition, and lower the risk of heart attacks.

Leinwand says the biggest holdup for her work is not the state of the science, but a lack of funds. Experimenting is expensive, and her original funds—from the state of Colorado’s health department and the Howard Hughes Medical Institute—are dwindling. The National Institute of Health is reviewing Leinwand’s application for a large grant.

 When budgets are tight, which they now, getting funding agencies to go out on a limb has been hard,” Leinwand says. “The venture capitalists we've approached are fascinated by the biology and the story, but they are nervous. When I first started doing this I felt like I was getting chewed up and spat out. The amount of aggression is huge. You walk in and everyone is sitting at the table already skeptical. Then you get a thick skin about it. Now I’m used to it, so I shrug it off.”

But Leinwand says she has garnered only encouragement from colleagues and neighboring departments.

“People love this. I've been working in heart disease for 25 years and I've never gotten so much positive feedback from colleagues. The University of Colorado benefits from these projects, including the eventual sale of the drug. This university is very entrepreneurial. They like faculty to seek out patents.”

Leinwand established biomedical company, Hiberna Corporation of Boulder, in 2008, to manufacture the snake oil drug. She says she expects it to hit the market as soon as 10 years from now.

Not everybody is fanatic about Leinwand making unconventional use of pythons. After pictures of Leinwand holding her pythons started surfacing, letters from PETA showed up on her desk.

"They contact me and say I shouldn't do these experiments. They say no animal research is justified."

Her response to the animal rights organization cited academic research demonstrating animal research that has led to helpful medications. She received no reply.

Using animals to develop pharmaceuticals is not unprecedented—an anticoagulant called Draculin comes from bat saliva and Cone snails are used in the development of non-addictive chronic pain medicines.

“My investigation of heart disease involving extreme biology phenomena is still considered nontraditional research and instruction,” Leinwand says. “Anytime you do anything out of the box people are skeptical and critical."

This article available online at:

http://www.theatlantic.com/health/archive/2013/10/for-heart-health-snake-oil/280172/