The chime on H. Lee Sweeney’s laptop dings again—another e-mail. He doesn’t rush to open it. He knows what it’s about. He knows what they are all about. The molecular geneticist gets dozens every week, all begging for the same thing—a miracle. Ding. A woman with carpal tunnel syndrome wants a cure. Ding. A man offers $100,000, his house, and all his possessions to save his wife from dying of a degenerative muscle disease. Ding, ding, ding. Jocks, lots of jocks, plead for quick cures for strained muscles or torn tendons. Weight lifters press for larger deltoids. Sprinters seek a split second against the clock. People volunteer to be guinea pigs.
Gene therapy could do for athletes what photo manipulation has done for this runner. But performance-enhancing drugs would undermine amateur athletics, which by definition are supposed to show how far natural skills can be advanced, says Richard Pound, president of the World Anti-Doping Agency. “I want athletes,” he says, “not gladiators.” |
Sweeney has the same reply for each ding: “I tell them it’s illegal and maybe not safe, but they write back and say they don’t care. A high school coach contacted me and wanted to know if we could make enough serum to inject his whole football team. He wanted them to be bigger and stronger and come back from injuries faster, and he thought those were good things.”
The coach was wrong. Gene therapy is risky. In one recent experiment, a patient died. In another the therapy worked, but 2 of the 10 human subjects—infants—got leukemia. To some, such setbacks are minor hiccups, nothing to worry about if you want to cure the incurable or win big. In the last few years, Sweeney, a professor of physiology and medicine at the University of Pennsylvania, and a small cadre of other researchers have learned how to create genes that repair weak, deteriorating, or damaged muscles, bones, tendons, and cartilage in a relatively short period of time. They can also significantly increase the strength and size of undamaged muscles with little more than an injection. So far, they have worked with only small laboratory rodents—mice and rats. Clinical trials on larger animals, like dogs and cats, are currently not being funded. Human testing is years away, but gene therapy has already become a controversy in professional and amateur sports, where steroids, human growth hormones, and other performance-enhancing drugs have been a problem for years. With the Olympics opening in Athens on August 13, the subject is only going to get hotter. “It’s the natural evolution of medicine, and it’s inevitable that people will use it for athletics,” Sweeney says. “It’s not clear that we will be able to stop it.”
Sweeney became interested in gene therapy in 1988, shortly after scientists pinpointed the gene responsible for Duchenne muscular dystrophy. He decided to find out if there was a way to counteract the disease genetically. Children with muscular dystrophy lack the gene required to regulate dystrophin, a protein for muscle growth and stability. Without dystrophin, muscle cells atrophy, wither, and die. Sweeney’s plan was to introduce the dystrophin gene by hitching it to the DNA of a virus that can transport genes into cells. As it turned out, viruses were too small to carry that gene. So Sweeney began searching for a smaller gene that would fit inside a virus and at least mimic dystrophin. He settled on a gene that produces insulin-like growth factor (IGF-I), a powerful hormone that drives muscle growth and repair. The IGF-I gene fit nicely inside a virus and was more appealing because it could potentially treat several kinds of dystrophies. In a series of experiments beginning in 1998, Sweeney and his team at Penn injected IGF-I genes into mice and rats and watched in wonder as damaged muscle tissue repaired itself.
Today Sweeney spends much of his time scrutinizing the rats and mice he has injected with IGF-I genes. He puts them through a rigorous exercise program, strapping weights to their hind legs and repeatedly prodding them up a three-foot-high ladder. After two months, the rodents can lift 30 percent more weight, and their muscle mass has swollen by a third—double what his control group of mice (those without IGF-I) can achieve with weight training alone. In another experiment Sweeney gives IGF-I to mice but curbs their exercise. They too bulk up, jumping 15 percent in muscle volume and strength.
On a recent visit to Penn, I asked Sweeney to show me the mice. He led me to a cramped lab where a bubbling tank of liquid nitrogen spewed a cold fog across the floor. Rows of transparent plastic shoebox-size containers were stacked on a chrome pushcart, a pungent, musky odor emanating from each box. Inside were several chocolate-colored mice. Sweeney pointed out two groups in neighboring pens and asked, “Which set do you think we’ve given IGF-I?” I lean in for a closer look. The mice in the left box no doubt have been watching Buns of Steel videos. Each mouse boasts a rock-hard rump and shockingly large and perfectly chiseled gastrocnemius and soleus muscles (which, in humans, make up the calf). In the adjacent cage, two control mice look scrawny by comparison. The results are impressive and make me wonder just how easy it would be for someone to reproduce Sweeney’s results in a human. “I wouldn’t be surprised if someone was actively setting up to do it right now,” he says. “It’s not that expensive, especially if you are just going to do it to a small population of athletes.”
