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 a handful every week—often many more, depending on what is in the news—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.
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 experiment a patient died. In another the therapy worked, but 4 of the 10 human subjects—young children—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 several years, Sweeney, a professor of physiology and medicine at the University of Pennsylvania, and a small cadre of other researchers have learned how to manipulate genes that repair weak, deteriorating, or damaged muscles, bones, tendons, and cartilage in a relatively short time. They can also significantly increase the strength and size of undamaged muscles with little more than an injection. At first the researchers worked with only small laboratory rodents, mice and rats. More recently their efforts have shown promise with dogs. Human testing is years away, but gene therapy has already become a controversy in professional and amateur sports, where steroids, human growth hormone, and other performance-enhancing drugs have been a problem for years. With the Olympics opening in Beijing on August 8, 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 wanted 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 enough 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 at least mimic dystrophin. He settled on a gene that produces insulin-like growth factor 1 (IGF-1), a powerful hormone that drives muscle growth and repair. The IGF-1 gene fit nicely inside a virus and was more appealing because it could potentially treat several kinds of dystrophy. In a series of experiments beginning in 1998, Sweeney and his team at the University of Pennsylvania injected IGF-1 genes into the muscles of mice and rats and watched in wonder as damaged tissue repaired itself.
It’s inevitable that people will use gene therapy for athletics. It’s not clear that we will be able to stop it.
For years afterward, Sweeney spent much of his time scrutinizing the rats and mice he had injected with IGF-1 genes. He put 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 could lift 30 percent more weight, and their muscle mass had swollen by a third—double what his control group of mice (those without IGF-1) achieved with weight training alone. In another experiment Sweeney gave IGF-1 to mice but curbed their exercise. They too bulked up, jumping 15 percent in muscle volume and strength.
Next up for testing were dogs, which come closer than rodents to approximating human biology. The results were similarly striking. Sweeney has now begun developing and testing another type of gene therapy in dogs and comparing its effects to those of IGF-1. The new therapy is based on a protein called myostatin, which normally regulates muscle growth. By dosing dogs with the gene for a myostatin precursor, Sweeney has found he can throw a wrench into the molecular machinery of myostatin signaling, removing a critical check on muscle growth and allowing deteriorating muscles to regain their strength.
On a visit to the University of Pennsylvania, I ask Sweeney to show me his IGF-1 mice. He leads me to a cramped lab where a bubbling tank of liquid nitrogen spews a cold fog across the floor. Rows of transparent plastic containers, each about the size of a shoe box, are stacked on a chrome pushcart, a pungent, musky odor emanating from them. Inside each box are several chocolate-colored mice. Sweeney points out two groups in neighboring containers and asks, “Which set do you think we’ve given IGF-1?” I lean in for a closer look. The mice in the left box look as if they have been watching Buns of Steel videos. Each mouse boasts a rock-hard rump and shockingly large, perfectly chiseled gastrocnemius and soleus muscles (which, in humans, make up the calf). In the adjacent cage, two control mice appear scrawny by comparison. The results are impressive, and I wonder out loud 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.”