A CU scientist and her students study pythons in search of the answer and a cure for premature heart disease.
A python named M4, maybe four feet long, was minding its own darn business in a basement lab on the Boulder campus. Which is how you want to leave a python.
But there was Leslie Leinwand, poking around with a stick, courting trouble when — tsssss! — the python flicked its head straight back and snapped its jaws open.
“They’re lightning fast,’’ says Leinwand, chair of molecular, cellular and developmental biology at CU-Boulder. “When they strike, they’re a sight to behold.”
For Leinwand and her undergraduate research program known as the Python Project, they’re also a way to understand human cardiac disease. The results may help researchers target new drugs for treating cardiac growth in response to disease, says Leinwand, who studies a genetic heart disease known as hypertrophic cardiomyopathy, the leading cause of sudden death in young athletes such as Hank Gathers. An all-American college basketball star, Gathers collapsed and died during a 1990 game.
One moment the rugged 6-foot-7 forward — a likely first-round pick in that year’s National Basketball Association draft — was soaring up for a thunderous alley-oop dunk for Loyola Marymount University. The next he was staggering and falling, dead at age 23 of what was later diagnosed as a heart muscle disorder.
Matters of the heart
But how can Leinwand, her students and snakes prevent deaths like Gathers’? The lesson begins at the dinner table. Not only can pythons swallow small animals whole, they can digest them. In a Hulk-like transformation, the snakes experience a 40 percent increase in heart muscle mass and their metabolism ramp up 40-fold within 48 hours of feeding. Once the feeding ends, their hearts shrink back to their original size, and they might not dine again for six months.
Since 2006 the undergraduates working with Leinwand have been studying the python genome, searching for answers as part of an innovative program funded by a $1 million grant from the Howard Hughes Medical Institute.
The python’s dramatic heart enlargement is similar to the beneficial heart enlargement that occurs in highly trained athletes — and the disease-induced enlargement that killed Gathers and other prominent athletes.
“[Pythons] make ideal subjects for study because their regulatory responses are so extreme,” Leinwand says. “If we can understand how the python does it, we might be able to apply that information to common human medical problems, such as cardiac enlargement due to high blood pressure. This may be a unique path toward potential drug development.”
One of her more ambitious students was Chris Wall (MCDBio’09), an expert snake handler who volunteered to clean cages as a sophomore, took Leinwand’s class in spring 2008 and then joined her research group. He co-authored a soon-to-be-published paper on their findings before enrolling this fall in a Ph.D. program in biomedical sciences at the University of California, San Diego.
“Being able to do research and experience professional science was the defining aspect of my time at CU,’’ he says. “There’s no chance that I’d be a graduate student right now if not for my time as a Python Project student and working for Leslie. Truly, one of the many pitfalls of [ other] large research institutions is the inability to accommodate all the undergraduates who want to do research.”
Athletes and heart failure
The research might help solve the riddle of why young people die of heart failure, a condition dramatized by the deaths of high-profile athletes like Gathers, 27-year-old Reggie Lewis of the Boston Celtics in 1993 and the 28-year-old Olympic ice-skating gold medalist Sergei Grinkov in 1995. In 2005 Atlanta Hawks center Jason Collier died at 28 of an undiagnosed heart abnormality. That same year, three NCAA basketball players also died. In 2007 Damien Nash of the Denver Broncos died not long after playing in a charity basketball game.
But few cases captivated the country like the appallingly sudden death of Gathers, an exuberant communications major who had his own pregame show on a cable TV channel. As newscasters repeatedly replayed his collapse, the sight of a superbly conditioned young athlete falling in his prime struck millions of viewers as inconceivable. Gathers led the nation in scoring and rebounding the previous season — only the second time a player had accomplished that combined feat in major college competition.
“If we can understand how the snake is able to enlarge its heart in such a short time to an athletic-like size and function, we could potentially apply that system to people who would benefit from a more functional heart,’’ Wall says. “On the side of Hank Gathers, if we could understand how the snake can reverse its heart growth, we could apply that mechanism to instances of pathologic hypertrophy in humans with a hope to reverse it and perhaps provide a treatment.’’
For years Leinwand studied cardiac disease on conventional subjects like mice and rats. Then she came across an article by UCLA evolutionary biologist and Pulitzer-prize winning author Jared Diamond four years ago, urging researchers to focus on pythons, in particular Burmese pythons, because they are infrequent feeders. Previous scientific research indicated that infrequent feeding played a key role in a snake’s ability to enlarge its heart rapidly while feeding.
“I was so completely convinced by his argument that I went downstairs to talk to the rattlesnake guy [in the MCDB building],’’ she says. “I asked if we could keep some snakes down there. He was thrilled someone else wanted to work on snakes.”
Snakes strike fear in lab
In the ensuing months, Leinwand, who was elected a fellow of the American Association for the Advancement of Science in 2005, contacted the Howard Hughes Medical Institute, a nonprofit research organization in Chevy Chase, Md., for funding.
“We look at a particular combination — someone who’s very well known in their field because of [her] research accomplishments but who also has a strong commitment to education and being a good teacher,’’ says Cynthia Bauerle, the institute’s senior program officer for precollege and undergraduate science education initiatives. “What Leslie has been able to do is capitalize on student interest in health and disease and medicine to bring them into a project where they get to do authentic research.’’
But Leinwand entered unfamiliar territory when she placed her first order for snakes. In their natural habitat — the jungles and grassy marshes of Southeast Asia — the largest Burmese pythons exceed 20 feet in length and frequently eat small boars and medium-sized antelope. Lacking poison, they kill by encircling and literally squeezing the life out of victims. Although Leinwand’s snakes are much smaller, they still struck fear in some in the department.
“There were people who couldn’t even look at them because they were so afraid,’’ she says. “A lot of people [with fears] don’t handle them. I’m not phobic, but I have a healthy respect for them. I’ve been hissed at.’’
Every semester snakes are divided into two groups — fasters and feeders. The fasters are euthanized and their normal-size hearts removed. The enlarged feeders’ hearts are removed two to three days after their final meals. RNA is extracted from the cardiac tissue of both snakes to be studied. Sixteen students are selected for the class each semester, and research is passed on to the following class.
“I think students are getting a maximal experience,’’ Leinwand says. “There’s this feeling among many people that you can’t do relevant research on an undergraduate campus — that the only kind of medically relevant research goes on at medical schools. It’s just not true. I love having undergraduates around. The world is theirs for the picking.’’