When Olympic medals and multi-million-dollar contracts are at stake, athletes and coaches have been known to resort to drastic measures to strike gold. But as the steroid era evolves amidst increased testing and public hectoring, what other performance booster will enter the ring?

Gene therapy, say a host of researchers, three of whom call for more oversight of the technique's use in athletics. In a commentary published online February 4 in Science, Theodore Friedmann, of the University of California at San Diego in La Jolla, and his colleagues wrote that aside from ethical questions of good sporting practices, many genetic therapies are far from proven: "Although highly effective in some models, these gene therapy techniques are imperfect and still highly risky."

Pressure on athletes to be ever faster, stronger and higher-scoring feeds a fierce field that markets sometimes-suspicious solutions. "Some athletes and coaches will be tempted, prematurely and unwisely, to take advantage of results packaged by some as performance enhancement 'breakthroughs,' even if they are untested in humans and the only 'breakthrough' is faster or stronger mice," the biomedical and genetic researchers wrote.

Indeed, some therapies that are being developed to help people with degenerative diseases and genetic defects live longer and more high-functioning lives might also be used to boost healthy bodies. These include "treatments that regenerate muscle, increase its strength, and protect it from degeneration," H. Lee Sweeney, a physiologist at the University of Pennsylvania School of Medicine who was not involved in the new paper, wrote in a July 2004 article for Scientific American. "Among these are therapies that give patients a synthetic gene, which can last for years, producing high amounts of naturally occurring muscle-building chemicals."

One molecular manipulation in particular, a modulator of peroxisomal proliferator-activated receptor delta, "regulates expression of genes involved in lipid metabolism, energy utilization, and insulin action," noted the authors, and it "increases the production of slow twitch oxidative energy-efficient muscle fibers."

But are these newly developed techniques really being used? Friedmann and his colleagues noted that their concern is far from speculative, pointing to the German track and field coach who in 2006 was found to have tried to get a vector for gene transfer and the genetic juicing from a Chinese lab reportedly offered to athletes before the 2008 Olympics.

Hedging its bets, the World Anti-Doping Agency (WADA), which was established more than a decade ago with initial funding from the International Olympic Committee, put gene therapy on its list of no-no's back in 2004. (Two of the paper's authors have worked with the WADA, and the other works for the American Association for the Advancement of Science, which publishes the journal Science.)

As the race to discover new competitive edges speeds up, so too does the race to detect them. Jacking up genes is "likely to produce broad metabolic, genetic, and proteomic changes," noted the authors. Speedy new sequencing techniques, as are currently used to scan for developmental disorders and other genetic red flags, will likely be able to catch such changes, they wrote.

Although the dangers and dubiousness of gene doping are clear to some scientists, few sports professionals and amateurs have taken a dive into this research literature, cautioned the authors: "Reputable athletes or coaches with little knowledge of genetics are at a disadvantage in assessing 'scientific' claims" of purported performance enhancers.

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