Aug. 8, 2007 Gene doping has the potential to spawn athletes capable of out-running, out-jumping and out-cycling the strongest of champions. But research under way at the University of Florida could help level the playing field by detecting the first cases of gene doping in professional athletes before the practice enters the mainstream.
In the wake of recent Tour de France drug violations -- and with the 2008 Olympics looming -- the need to stay ahead of the game has never been more evident. That's why the Montreal-based World Anti-Doping Agency, or WADA, charged with monitoring the conduct of athletes, is working with investigators around the globe to develop a test that would bust competitors for injecting themselves with genetic material capable of enhancing muscle mass or heightening endurance.
"If an athlete injects himself in the muscle with DNA, would we be able to detect that?" asked one of France's leading gene therapy researchers, Philippe Moullier, M.D., Ph.D., an adjunct professor of microbiology and molecular genetics at UF and director of the Gene Therapy Laboratory at the Universite de Nantes in France.
Right now the answer is no, he said. But the UF scientists are among several groups collaborating with national and global anti-doping organizations to develop a test that could detect evidence of "doped" DNA.
"WADA has had a research program in place for some years now, to try to develop tests for gene-based doping," said Theodore Friedmann, M.D., head of the agency's panel on genetic doping and director of the gene therapy program at the University of California, San Diego.
It sounds futuristic, but experts say it's only a matter of time. Unscrupulous athletes began showing an interest in gene doping in 2004, when the first reports of muscle-boosting therapies in mice were published by University of Pennsylvania researchers.
Since then, several potential targets of gene doping have emerged, including the gene for erythropoietin, or EPO. A bioengineered version of the hormone, currently on the market, increases red blood cell production in patients with anemia and boosts oxygen delivery to the body. In athletes, this translates to enhanced stamina and a competitive edge.
But because synthetic hormones such as EPO are prohibited by WADA and readily detected through drug tests, performance-driven athletes have begun searching for stealthier and more powerful alternatives.
"The next variation of boosting red blood cell production is to actually inject the EPO gene itself, which would cause increases in red blood cells," said Richard Snyder, Ph.D., an assistant professor of microbiology and molecular genetics at UF and director of UF's Center of Excellence for Regenerative Health Biotechnology. "So the idea is to develop a test that could detect the gene that's administered."
The task isn't easy -- the researchers are faced with a myriad of uncertainties, such as which tissues in the body to sample and how to distinguish a "doped" gene from a naturally occurring form of the gene. Ultimately, the test will compare how many copies of the EPO gene are found in an athlete's body to levels found in the average person who has not been doping.
"Our research aims to develop the ability to detect gene doping, primarily in athletes. But it has a wider purpose, and that's to understand how gene therapies are disseminated throughout the body," added Snyder, whose research stemmed from a cooperative agreement between the UF Genetics Institute and two biomedical research organizations in France: INSERM, the French version of the National Institutes of Health, and the French national blood bank, Etablissement Francais du Sang Pays de Loire. The agreement allows Snyder and Moullier to pool their expertise and resources.
A major objective of the UF-French collaboration is to decipher the structure of AAV, a virus commonly used to deliver genes into the body for therapeutic purposes. Gene "doping" would enter the body through a similar route, but scientists say the two procedures are as different as night and day from a therapeutic standpoint.
"When you use the phrase 'gene therapy' it should be very clear that you're talking about therapy," Friedmann emphasized. "But the same process of transferring genes would also be relevant in sport doping settings. And there you cannot talk about gene 'therapy' -- you can simply refer to the same technology as gene 'transfer.'"
Gene therapy has progressed in leaps and bounds over the years, but the field has proved anything but predictable. Scientists say gene doping will be no different. Current technologies could prove ineffective -- or even lethal -- in humans. When the EPO gene was first introduced into macaques, for example, the animals produced so many red blood cells that their veins clogged, and many eventually died after developing massive allergic responses to the therapy.
"I think many athletes know of the technology. They're aware and they're concerned. WADA's aware and concerned," Friedmann said. "One can overestimate the urgency, or one can be sort of blind to it. But the technology is relatively straightforward and people involved in gene therapy studies could very well see how it could be applied to sport doping."
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