Drugs that enhance exercise could be a boon for fighting obesity and diabetes, but they could also give athletes an unfair advantage over their competition. Like some existing doping practices—such as injecting red blood cells and taking erythropoietin (EPO), both of which increase the oxygen-carrying capacity of the blood—a PPARdelta stimulator could help athletes run, ski, or pedal farther by helping them use more oxygen. PPARdelta wouldn't alter the blood composition directly, but it would enable muscles to consume more oxygen. "There are two concerns," says Evans. "Using the gene as the doping agent and using the drug as the doping agent." Genes injected into the tails of mice can get into cells and become active, suggesting that athletes could use the PPARdelta gene directly. Gene doping isn't widely practiced, but since 2003 the World Anti-Doping Agency (WADA) has included gene doping among its banned substances and practices, and Evans is working with WADA to develop a test for both the PPARdelta drug and the gene. (The International Olympic Committee founded WADA in 1999 to coordinate anti-doping efforts across all sports; many sports federations and national Olympic committees have adopted WADA's anti-doping code.) Drugs that target PPARdelta aren't commercially available, but several pharmaceutical companies are pursuing such pills for lipid-related diseases. Once on the market, they would undoubtedly hold appeal for reprobate athletes looking for a shortcut to the winner's podium. Because no one has tested PPARdelta drugs in human performance, Evans isn't sure how they would stack up against other doping methods. But eventually someone will make the comparisons—or even test for synergisms. Says Evans: "Lots of people ask me what would happen if you take this drug with EPO." —R.J.D.

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