The most effective treatment--the drug and exercise combination--seems to work by reprogramming muscle metabolism. Mice that ran and took the PPARδ-activator compound gained 38 percent more slow-twitch muscle fibers than their sedentary counterparts, which were comparable to control mice, and showed a unique pattern of gene expression that partially mimicked that of exercise. "It looks like they've been able to make fast muscle fibers act more like slow muscle fibers, which have a greater capacity to use fats as fuel," says William Evans.

Scientists don't yet know if the drugs will have the same effects in humans. (The PPARδ activator has been in clinical trials for obesity and cholesterol regulation, but results have not yet been released.) If the drugs are successful, William Evans says, these compounds might be most useful for someone "who needs to lose a lot of weight or who is at risk of diabetes. It may make doing regular submaximal endurance exercise seem easier to people who don't do exercise." However, he says, "if, as I suspect, people look at it as a substitute for exercise, that would be bad news indeed."

With their endurance-enhancing properties, the compounds also have a high potential for abuse by athletes. Ronald Evans and his team are already working with the World Anti-Doping Agency to develop tests to detect one of the drugs. However, it's unclear whether such drugs would boost performance in a well-conditioned long-distant runner. "Endurance runners already have 80 to 90 percent slow-twitch fibers," says William Evans, who biopsied world-class endurance runners several years ago. "So if this drug makes fast-twitch fibers behave like slow-twitch fibers, it's unclear if it would have any effects."