WHILE track and field athletes compete at the Olympic games this week, genetically engineered mice are also breaking records. The rodents, dubbed 鈥渕arathon mice鈥�, can run almost twice as far as normal mice. Drugs that might have a similar effect are already being tested on people, raising fears that athletes could soon have yet another way to cheat.
鈥淭his is the first animal engineered for increased endurance,鈥� says Ronald Evans of the Salk Institute in La Jolla, California. His team wanted to find out if a protein called PPAR-delta, which is known to help burn fat, also helps fight obesity. In the body, the greatest consumer of fat is the type of muscle that gives athletes endurance, consisting mostly of slow-twitch muscle fibres. Fast-twitch muscle fibre, which is responsible for strength and rapid reaction, is powered mainly by sugar.
Pills that promote slow-twitch muscle activity could help patients with conditions that prevent them from exercising, and help obese people to lose weight. To test this idea, Evans鈥檚 team genetically engineered mice to produce extra PPAR-delta in their muscle. When put on a high-fat diet for 97 days, the engineered mice gained only a third of the weight controls did.
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Increasing PPAR-delta also had a dramatic effect on the composition of muscle itself, doubling the amount of slow-twitch fibres. 鈥淭hese mice behave like conditioned athletes,鈥� says Evans. When tested, the marathon mice were able to run for 92 per cent longer than normal mice and to a maximum distance of nearly 1800 metres, rather than the usual 900.
It is not yet clear if boosting PPAR-delta levels later in life 鈥� or in people 鈥� will increase endurance. But it may not be necessary to resort to gene therapy to find out. A drug that activates PPAR-delta directly, called GW501516, is already being tested on people as a way of lowering cholesterol.
The pharmaceutical company GlaxoSmithKline, which is carrying out the trials, says it has not looked to see if there is any effect on endurance. Evans, however, has already shown the drug causes many of the same changes in muscle cells as those triggered by the higher levels of PPAR-delta in transgenic mice (PLoS Biology, vol 2, p e294). 鈥淚 suspect that animals training with the drug will increase endurance more rapidly,鈥� Evans says. 鈥淭he potential for this to be abused by athletes is real.鈥�
Farnaz Khadem, a spokeswoman for the World Anti-Doping Agency, says she wouldn鈥檛 be surprised if athletes tried taking GW501516 if it became available. 鈥淢ost doping involves a substance developed for therapeutic purposes being used for a sports purpose,鈥� she says. 鈥淢edical science is moving forward, which is good. But it also means we鈥檝e got to be on our toes.鈥�