Another concern is that the vector virus might run amok. Scientists believe that is what happened during a 1999 French gene therapy trial on a group of 10 young children with X-SCID, an immune deficiency disorder known as boy-in-the-bubble syndrome. Researchers engineered a virus to carry a replacement gene to repair the immune systems of the sick children. The technique cured nine of them, and scientists initially deemed the trial an overwhelming success. Nearly three years later, however, doctors diagnosed two boys in the study with T-cell leukemia. Two more leukemia cases have since come to light; one patient has died. Somehow the virus carrier—not the replacement gene—had managed to touch off the blood disease, an international medical team reported in 2003. A parallel study in England initially looked more promising, but recently leukemia struck one of its participants as well.
Those incidents sparked widespread condemnation that stifled nascent research initiatives. The climate for gene therapy research has since begun a slow rebound. A variety of human trials are now under way with tighter safeguards, but most experiments are confined to animals.
Beyond the medical and regulatory setbacks, the largest roadblock to commercializing the technology is money. For years Sweeney’s efforts to launch dog studies were thwarted by a lack of funding. Human trials are even costlier, so for now, Sweeney says, IGF-1 and myostatin gene therapies remain on the distant horizon. He nonetheless keeps a list of telephone numbers from desperate parents who have contacted him.
Meanwhile, amateur athletics is trying to come to grips with gene doping. Every few years the World Anti-Doping Agency hosts a symposium where scientists, regulatory officials, and athletes gather to discuss gene doping. Theodore Friedmann, who directs the program in human gene therapy at the University of California at San Diego, spearheaded the first of these workshops six years ago. “People intent on subverting gene therapy will do so,” says Friedmann, who has advised the National Institutes of Health and congressional leaders on gene-related issues. “The technology is too easy. It’s just graduate student science.”
That bothers Arne Ljungqvist, the World Anti-Doping Agency’s health, medical, and research committee chairman, who doles out several million dollars in grant money every year to research groups looking at gene doping and its detection. Additionally, Friedmann, who chairs the agency’s antidoping panel, is working to establish testing protocols. “So far the results are sitting in the form of research advances,” he says, “but not in the form of real detection methods.” One concept is to hunt for what Friedmann calls physiological fingerprints. Introducing foreign genes into muscles, he says, “is going to produce changes in the way muscles secrete things into the blood and, therefore, into the urine.” In the same way breast and colon cancer alter the pattern of proteins in the bloodstream, genes linked to IGF-1 or EPO will, in theory, leave traces. Surveillance organizations like the U.S. and world antidoping agencies “will look for those signatures and patterns that can be tied, with confidence, to the existence of a foreign gene,” Friedmann says. Although it may be years in development, Friedmann envisions a noninvasive imaging device akin to an X-ray that detects bits and pieces of leftover viruses used to introduce performance-enhancing genes.
Ironically, the misuse of gene doping in sports is more clearly defined than its proper use. When physicians begin curing athletic injuries with gene therapy, the boundaries of healing and enhancement will blur. “There will be a fuzzy line between what is a medically justifiable treatment of injuries and what is performance enhancement,” Friedmann says. “There is nothing terribly noble about an athlete destroying a career with an injury if one can medically prevent or correct it. I would be hard-pressed to say that athletes are not eligible for this or that manipulation. It has always been obvious that there are therapeutic-use exceptions. There is no reason to think that therapeutic-use exceptions would be disallowed for genetic tools.”
That, of course, opens the door for abuse. In some instances, athletes would require only minuscule improvements to nudge them into the winner’s circle. “Olympic athletes don’t need to see a drastic change,” Huard says. “Sometimes the gold medalist is only a fraction of a second over the silver.” It would be very easy for a team physician to surreptitiously let therapeutic genes continue working for a few hours, days, or weeks after an officially sanctioned treatment ends.
With no viable testing mechanism on the horizon, it is possible that at least one of the 10,000-plus Olympic competitors in Beijing this summer will have experimented with gene doping. “Nothing would surprise me,” Friedmann says. For the time being, though, gene doping is not only illegal but also unsafe and probably ineffective. “If it’s done now,” he says, “it will certainly be done badly.”Additional reporting by
