The race to improve human performance with drugs is on.
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Engineering the DNA to Build the Ultimate Athlete

Here on the seventh floor of the University of Pennsylvania's Clinical Research Building, biologist H. Lee Sweeney is preparing to genetically reengineer mice that could become something close to the world's greatest athletes. If all goes well, these mice will have muscles that aren't only bigger and stronger than normal, but more fatigue-resistant, a cross between a powerlifter and a marathoner. "If someone had the resources," Sweeney says, "they could do something like this now. The only thing preventing it from happening the way EPO happened is that you need very qualified technical help to do this. But with the way funding for science is going...."

This, potentially, is the dark side of the next wave of performance enhancement. While Sweeney's work is nothing but admirable – he's looking for new therapies to treat degenerative diseases like muscular dystrophy – if the antidoping authorities fail to keep pace, athletes may find rogue scientists able to inject them with extra copies of human genes essential to performance. The genes, piggybacked onto viruses, will be incorporated into the athlete's own DNA, programming his body to build more muscle or to develop more aerobic capacity, without the injections of synthetic boosters like steroids or EPO.

In the late 1990s, Sweeney created a small media stir when he unveiled a bunch of hypermuscular mice, quickly dubbed "Schwarzenegger mice," that he had injected with an extra copy of a gene that produces a growth factor called IGF 1 – which promoted an Arnold-like physique. (A Pennsylvania junior-college football coach contacted Sweeney about procuring some of the experimental product so that he could begin injecting his players.) Practically from that moment on, sports-science insiders have predicted the imminent arrival of gene doping in sports. The future took awhile to get here, but in the past year, several of Sweeney's Penn gene-therapy colleagues have successfully treated genetic diseases in humans, and one research group in Ohio has begun to treat muscular dystrophy with the therapies that he pioneered.

Sweeney's new research project reads like a blueprint on how to construct the perfect all-purpose athlete. He will insert a gene in his mice that blocks the action of myostatin, a protein that limits growth in muscle tissue. He will also insert a gene that pumps up the production of PGC1 Alpha, a signaling protein involved in muscular endurance. More PGC1 Alpha means more energy being produced in the mitochondria, the cell's power plant, which means more capacity to go long and hard. In specialized athletes, these two different power systems are at war with each other. A marathoner's muscles grow into superefficient mitochondrial powerhouses but become physically smaller and less capable of short, intense contractions. The powerlifter gets essentially the reverse effect. "What if you start hammering both of these pathways?" Sweeney asks. "What does the muscle do with that information? Does one system become dominant, or does it integrate the two the way you can with exercise, when you combine weightlifting with endurance running? Maybe we're making a middle-distance runner." Or a basketball or a soccer or a tennis player.

By midsummer, Sweeney will begin injecting the mice with the two genes and putting them through a kind of mouse Olympics to measure their performance: how long they can run on the treadmill (endurance); how long they can hold on to a wire (strength). If they perform like champs, no doubt a certain class of sports trainer will notice. Sweeney himself takes the long view. "I think if these kinds of therapies become widespread," he says, "you're not going to be able to deny the athletes. They'll say, 'If everyone else can do it, so can we, and as long as it's safe, who cares?'"

Juicing the Weekend Warrior

While world-class jocks have to be vigilant about not running afoul of their sports' doping guidelines, no restrictions inhibit the amateur. Dr. Florence Comite, endocrinologist and prominent Manhattan anti-aging physician, combines liberal prescriptions of hormones with a state-of-the-art sports lab to get optimal performance from her clients. Comite and her associates design workouts, put together nutrition and supplement packages, and subject clients to a battery of tests to make sure they hit their performance marks. Her primary weapon – detailed in her forthcoming book, 'Keep It Up: A Bold New Formula to Expand a Man's Physical and Mental Power for Life' – is pushing up testosterone levels. For middle-aged men, she does this not with the patches and gels you see shilled on TV, but with regular injections of a hormone, HCG, which stimulates testosterone production. And she's learned to leverage men's competitiveness to improve their health. In her lab is a whiteboard ranking patients' top scores on a handful of physiological measures. "Some of these guys are in the top 99th percentile for VO2 max for 20-29 year olds," an associate, Steven Villagomez, says. "And they're almost 60."