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The Future
DAVID EPSTEIN
March 17, 2008
Think performance enhancers are a problem now? Welcome to the era of the genetically engineered superathlete
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March 17, 2008

The Future

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

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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.

Since the gene genie escaped from the bottle a decade ago, researchers have discovered dozens more genes that appear to affect athletic performance. This is old news in the rodent community. Scientists have created mice whose bodies are flooded with oxygen-carrying red blood cells, creating greater endurance. Other mice have been engineered to produce extraordinary amounts of growth hormone, while still others metabolize fat and carbs in such a way that they can live like couch potatoes yet run like marathoners.

Significant safety hurdles remain before gene therapy is widespread for humans. The most efficient means of delivering a synthetic gene is by attaching it to a virus that shuttles it into human cells. Viruses are great at that. They can also trigger the immune system in a way that can lead to fatal results. In 1999 Jesse Gelsinger, an 18-year-old with a rare liver disease who had volunteered for a gene-therapy trial, died from a massive immune response to the virus used in the treatment. And the dangers extend beyond the immune system. In a gene-therapy trial in France, 12 boys were successfully treated for X-linked severe combined immunodeficiency, commonly known as Bubble Boy syndrome, but at least three of them developed leukemia.

One delivery method—flushing the bloodstream with the desired gene—is simple enough, says Sweeney, that it could be achieved by a clever undergrad in a molecular biology lab. The method is not very efficient and hasn't been thoroughly tested, but it hints at the possibilities for the spread of gene tampering in sports. Despite the unknowns and the dangers, chances are good that someone at the Beijing Olympics in August, someone willing to weigh his or her mortality in gold, will have undergone gene transfer in an attempt to enhance performance. "Even when I tell them it's not safe," Sweeney says, "some athletes are willing to try anything."

The signs are ominous. In January 2006, during German track coach Thomas Springstein's trial on charges of providing performance-enhancing drugs to minors, evidence emerged indicating that Springstein had attempted to procure Repoxygen, a gene-therapy drug developed to treat anemia by prompting cells to produce EPO and, in turn, red blood cells. (He was found guilty of giving illegal substance to minors and received a 16-month suspended sentence.) In addition, Mauro Di Pasquale, the 1976 world powerlifting champion and an Ontario physician who has written several books on sports doping, says he knows that athletes are experimenting with gene doping, with the help of Chinese doctors and researchers.

Human data relating to myostatin has been hard to come by. Soon after his discovery, Lee attempted to identify potential test subjects with natural mutations in their myostatin genes. He placed an ad in Muscle and Fitness, and close to 1,000 muscle-bound men and women responded. But after collecting samples from 150 of them, he has yet to find a single one with the myostatin mutation he had engineered in his mice.

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