Gene doping at Torino?

With the Torino Winter Olympics due to kick off on Friday (February 10), anti-doping authorities are still hoping that the spectre of gene doping -- the misuse of gene therapy to boost athletic performance -- will not cast its shadow over the competition. However, a recent court case in Germany appears to suggest otherwise.Gene doping is a cause for concern among those who want to keep sports clean because it is potentially hard to detect. Until very recently, experts had spoken about it as something that would happen in the future. But in recent days, a German court hearing evidence in the trial of a running coach accused of giving performance-enhancing drugs to young athletes was told that a search of his Email inbox turned up references to a product called Repoxygen.Repoxygen, developed by UK firm Oxford Biomedica, delivers the gene for erythropoietin to muscle cells in a vector configuration that brings the gene under the control of an oxygen-sensitive gene switch. In one Email, the coach, named Thomas Springstein, wrote that "new Repoxygen is hard to get. Please give me new instructions soon so that I can order the product before Christmas," according to German news service Deutsche Welle.Repoxygen is still in preclinical development, according to the Oxford Biomedica Web site. The company's representatives have said Springstein did not receive the product from the company.Regardless of whether Springstein actually administered the product to an athlete, gene doping will assuredly be a reality sooner rather than later, said Theodore Friedmann, head of the gene doping panel for the World Anti-Doping Agency (WADA). "It's almost an irrelevant question whether it's being done at the moment," he told The Scientist. "The technology is getting to the point that someone is going to do something silly."The untested nature of many gene transfer technologies means they could pose serious threat to the safety of athletes, Friedmann said. "None of these systems are well enough characterized to know what their impact will be. The danger to the athletes far exceeds the level of knowledge needed to do this safely."WADA was created by the International Olympic Committee in 1999 to maintain an international anti-doping code, coordinate testing of athletes, and fund scientific research to develop new detection methods. Since 2002, growing concern about the possibility of gene doping has prompted it to spend some $3 million on the field. In 2003, WADA added gene doping to the list of banned substances and procedures in its World Anti-Doping Code. It is also included in the International Olympic Committee's anti-doping rules for the Turin games.Olivier Rabin, the agency's science director, said athletes are most likely to use gene technologies that offer them the same kind of benefits as banned drugs. "Boosting of oxygen transfer and muscle mass building are definitely two of the key areas of gene doping, as indicated by the abuse of pharmaceutical drugs by some athletes for those purposes today," Rabin said.Geoffrey Goldspink from University College London is one researcher whose work on gene therapy for muscle mass has already brought him unwanted attention from the sporting world. He and his colleagues are developing a treatment for muscle wasting diseases that involves transferring the gene for mechano growth factor, using a plasmid vector. In mouse studies, the gene triggered a 30% increase in muscle mass within weeks, suggesting the treatment could be more potent than anabolic steroids.Goldspink said he is frequently contacted by people from what he calls the "sports counter-culture," who want him to supply them with his technology. He forwards such Emails to WADA, but acknowledges it wouldn't be impossible for a lab elsewhere to produce it themselves. "It's not rocket science to make genes," he said. "Many graduates in biochemistry can make them if they're experienced enough."As a result, WADA and other anti-doping agencies are working on developing ways to detect athletes who have misused gene technology, including mass spectroscopy approaches that can distinguish between endogenous and introduced growth factors, tomographic detection of mRNA being formed in unusual tissues after gene transfer, and microarray searches for alterations in the expression profile of certain genes. Rabin said that WADA does not announce which substances and methods are detectable, but did acknowledge that gene transfer generally produces effects that are measurable in the body. "So yes, there could be ways to detect some forms of gene doping now," he told The Scientist.And even if gene therapy techniques are not currently viable, he added, use of gene doping could still come back to bite athletes in years to come. "Whatever happens in Turin," he said, "athletes' samples will be stored for several years and may be re-analyzed in the future once new doping substances and methods can be detected. The World Anti-Doping Code provides for an eight-year statute of limitations."Stephen Pincock Stephen.pincock@journalist.co.ukLinks for this articleTorino 2006 https://www.torino2006.org"German coach suspected of genetic doping," Deutsche Welle, February 3, 2006. https://www.dw-world.de/dw/article/0,2144,1890782,00.htmlRepoxygen https://www.oxfordbiomedica.co.uk/repoxygen.htmTheodore Friedmann https://biomedsci.ucsd.edu/faculty_descrip.asp?id=43World Anti-Doping Code https://www.wada-ama.org/rtecontent/document/code_v3.pdfThe International Olympic Committee anti-doping rules applicable to the XX Winter Olympic Games in Turin, 2006 https://www.wada-ama.org/rtecontent/document/IOC_AntiDoping_Rules_05.pdfG. Goldspink, "Age-related muscle loss and progressive dysfunction in mechanosensitive growth factor signaling," Annals of the New York Academy of Sciences, June, 2004. PM_ID: 15247032

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