HIRED MUSCLE: H. Lee Sweeney's work on modifying genes to increase muscle strength puts his services in high demand from the athletic community.
Lee Sweeney

It's an Olympics year, which means that Lee Sweeney's phone is ringing off the hook. Athletes call him three or four times a day asking for help, offering him money. They're persistent, practically begging, but he always says no.

After all, Sweeney is not an athletic coach; he is a soft-spoken physiologist at the University of Pennsylvania School of Medicine, and he is developing treatments that could stop age-related muscle decline. But "things that make the muscles healthy when you're older are going to make them healthier when they're young," Sweeney concedes, and athletes know it—which is why they want to be his guinea pigs.

Sweeney's work attracts athletes not just because he helps muscles function better—it's also because he focuses on gene therapy, a medical approach that inserts new or modified genes into patients' cells. It has not quite proved itself clinically yet, but gene therapy directly modifies DNA—so theoretically, treatments can persist for months, years or even for life. Its effects are more subtle and consistent than traditional pill-popping or daily injections. And because doctors can insert the genes directly into the tissues that need them, gene therapy should have fewer side effects than other treatments and is not detectable in the bloodstream.

What athlete wouldn't want a performance booster that is hard to detect, lasts a long time, and has few side effects? That is precisely why "gene doping," the use of gene therapy for enhancement purposes, is becoming such a headache for the World Anti-Doping Agency (WADA), the independent international agency that monitors sports doping. The Montreal-based watchdog organization has held three international meetings on the topic since 2002, focusing on how to both prevent and detect the practice. (So far, they have not gotten far with either.) According to WADA chairman Gary Wadler, gene doping is simply a matter of time: Athletes "read the scientific literature and they know what's cutting-edge—there's no question about it," he says.

Sweeney's work has been popular with athletes for a decade. In 1998 he and his colleagues published a study in the Proceedings of the National Academy of Sciences USA in which they used a common virus to insert the gene for insulinlike growth factor 1, or IGF1, into the DNA of muscle cells of young and old mice. Doing so increased muscle mass and strength by approximately 15 percent in young mice and reversed age-related muscle changes in old mice, making them 27 percent stronger than they were before.

These "Schwarzenegger mice," as the press referred to them, instantly propelled Sweeney to science stardom. Soon after, his phone started ringing. One of his first requests was from a football coach at a Pennsylvania junior college who wanted Sweeney to dope his entire team. Of course, he said no.

Sweeney is also developing gene therapies that inhibit the function of myostatin, a growth-regulating protein that counteracts the effects of IGF1. The absence of myostatin not only increases musculature but also sheds fat, because myostatin plays a role in fat deposition. Sweeney is using viruses to insert inhibitors of myostatin into healthy dogs as well as those that suffer from a form of muscular dystrophy. Because muscle tissue turnover in muscular dystrophy is so high, he inserts the gene into the liver, where it is made into a protein and excreted into the blood, which then travels to and modifies the muscles.