One day last year, a dejected cardiology research fellow in Leslie Leinwand's lab sought her out. He could not begin his experiments to test the role of estrogen in hypertrophic cardiomyopathy, a genetic form of heart disease that leads to thickening of the walls/chambers of the heart, because none of his mice were showing any symptoms of the disease.
The only thing he had done differently with the mice, he told Leinwand, was to switch them from their usual soy-based diet to a comparable milk-based diet. He did so because a colleague mentioned that soy, with its large concentration of plant estrogens, might confound the estrogen experiment.
"When I expressed amazement and excitement at how the change in diet could have such a profound effect on disease, he quickly went from being despondent to realizing that he had found something he was not expecting that would take him in a new direction," Leinwand recalled. "That's something I love about science."
Leinwand's lab also recently found that mice with hypertrophic cardiomyopathy could reverse some aspects of the disease if they were allowed to exercise at will on a wheel in the cage. This suggests that people who have the same genetic mutation as those in Leinwand's mice might be better off with mild exercise rather than leading a sedentary lifestyle that is usually advised by their physician.
Human clinical trials are the final arbiter of the implications of mouse studies, but discoveries like these help non-scientists appreciate the potential relevance of scientific research to their lives. As an HHMI professor, Leinwand plans to take advantage of this natural interest in health and disease to design a new undergraduate course, public lecture series, and teacher workshops called "From Bench to Bedside: the Role of Science in Medicine."
"I've lined up a bunch of stellar faculty who are good speakers," said Leinwand, who is the chair of molecular, cellular and developmental biology at the University of Colorado at Boulder,. "We're going to cover everything from tissue engineering of artificial joints to microbial communities in different disease states, such as ulcers and cystic fibrosis." HHMI investigator Kristi Anseth, for example, will discuss her engineering of artificial joints, and National Academy of Sciences member Norman Pace will share his famous experiment in which a new technique for analyzing bacteria without culturing them produced a shocking revelation of the diversity of microbes living on shower curtains and in hot tubs.
Leinwand's students will also do research using a colony of green and brown Burmese pythons housed in the basement of the psychology department. There, a postdoctoral fellow who used to be afraid of snakes will supervise a half-dozen undergraduates seeking to understand how a python's heart balloons within 48 hours of eating and then reverts to pre-meal size after the food is digested—a question for which no one yet knows the answer. "It seems almost impossible that this can happen," Leinwand said.
To track down the molecular mechanism of snake heart enlargement, the students will learn to develop cDNA libraries, copies of most or all of the DNA sequences within a given cell or organism—vital data in molecular biology research—and organize them using bioinformatics tools. Pretty much anything the students learn will be new information, because virtually nothing is known about the snake genome. Understanding the growth and regression of the python heart could shed light on beneficial and harmful heart enlargement in people and lead to new ideas for drug therapies. "Students get really excited about research like this, as opposed to following a lab manual," Leinwand said.
