Think performance enhancers are a problem now? Welcome to the era of the genetically engineered superathlete

After discovering how myostatin affects muscle, Lee was flooded with inquiries from athletes. Simon Bruty/SI

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By David Epstein

I am one of the most avid sports fans you'll find," Se-Jin Lee says. It's true. He'll watch anything. Basketball. Football. Fútbol. Billiards on channel seven-hundred-whatever. As a graduate student in the '80s Lee used to sit in his car in the driveway with the radio on to listen to the games of faraway baseball teams. Even now, in his lab at Johns Hopkins Medical School in Baltimore, he easily rattles off the NCAA basketball tournament winners in order from 1964 to 2007. And, like anyone who values fair competition these days, he's disturbed by the issue of performance-enhancing drugs in sports.

Why, then, is Lee working to usher in technology that will make even today's most inventive doping methods look primitive? A professor of molecular biology and genetics, the 49-year-old Lee studies genes that tell muscles what to do -- genes that he knows how to change. As clever as chemists are in altering steroid molecules to avoid detection (recall BALCO's THG, a.k.a. "the Clear"), those designer drugs can be spotted once antidoping agencies know what to look for. Even human growth hormone will be detectable soon, after a valid blood test becomes commercially available. But if athletes develop ways to alter their genes, the very blueprints for their own muscles, there may be no test of blood or urine that can pick that up.

Lee is pushing the frontier of genetic research into muscle building because the same breakthroughs that could boost performance in sports might also bring about a medical revolution. Advances could not only mitigate the effects of diseases like muscular dystrophy but also give senior citizens back their strength -- which, often, would amount to giving them back their lives.

In 1995 in his lab on North Wolfe Street, Lee and two colleagues identified the function of myostatin, a protein that tells muscles when to stop growing. It does so, scientists believe, by signaling "satellite cells," or stem cells that lie dormant around the muscle until they're needed to build or repair it. Experimenting on mice, Lee inactivated both copies of the gene in the animal that code for myostatin. The result: Over four to six weeks the rodents developed twice their normal muscle mass without a formal exercise regimen. After Lee's results were published in 1997, he was awash in e-mails from people with muscle-wasting disease (no surprise) offering themselves as subjects for human experiment. He got similar offers (surprise!) from bodybuilders and athletes. Imagine: double the muscle mass. Could he do to them what he had done on the mice?

Some of the athletes barely knew what they were inquiring about. They'd ask Lee where they could purchase some myostatin. "Of course, they didn't want myostatin," he says. "They wanted to block it." But if they could block it with a synthetic gene, the alteration would be a part of their DNA, and it would last for years at the center of their cells. The most straightforward way of detecting the new gene would be to remove a piece of the muscle and probe for it, a procedure most likely too invasive for widescale use. It would be enough to make one long for the simplicity of the steroid era.

The year after Lee's mice results went public, H. Lee Sweeney, a physiology professor at the University of Pennsylvania, published a paper detailing his own mighty mice, which he had injected with a gene engineered to produce a muscle builder called insulin-like growth factor (IGF-1). Sweeney, too, was inundated with inquiries from athletes. He says a high school football coach and a high school wrestling coach volunteered their entire teams as guinea pigs.

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