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Nature 414, 569-570 (6 December 2001) | doi:10.1038/414569a

Gene therapy may be up to speed for cheats at 2008 Olympics

David Adam

Athletes may be tempted to genetically modify themselves to boost their performance far sooner than most people realize, researchers have warned.

The idea of sprinters and cyclists injecting themselves with genes coding for hormones that boost the number of red blood cells may sound far-fetched, and the results are uncertain. But some gene-therapy researchers and sports organizations believe that such a genetically modified athlete could mount the winner's podium at the 2008 Olympic Games in Beijing.

If such 'gene doping' did take place, it could be impossible to detect, warns Peter Schjerling, a molecular biologist at the Copenhagen Muscle Research Centre. Speaking at a conference on genes and sport at University College London on 30 November, Schjerling said that artificial genes "can and most likely will be abused by healthy athletes as a means of doping".

Schjerling is not the first to voice concern that unscrupulous athletes might exploit emerging gene-therapy techniques currently being developed to treat conditions such as kidney failure and anaemia. The International Olympic Committee has set up an advisory group on the matter, and says it is closely monitoring progress in gene therapy.

The World Anti-Doping Agency (WADA), a body coordinating a global campaign against the use of banned drugs in sport, is so concerned that it will hold a special conference to discuss the topic in March. (The meeting, at Cold Spring Harbor in New York, was originally scheduled for September, but was postponed after the terrorist attacks on the United States.)

Schjerling says that athletes could target performance-enhancing genes such as those encoding growth factors capable of building muscle strength or widening blood vessels, or a hormone called erythropoietin (EPO) that raises the number of oxygen-carrying red blood cells.

EPO abuse is already thought to be rife in many sports, including cycling — a whole team was expelled from the 1998 Tour de France for using it — but tests have been developed that can find synthetic versions of the hormone injected into the body (see Nature 407, 124; 2000). Introducing the gene coding for EPO would circumvent the tests, however, because the extra hormone produced would effectively be endogenous.

The artificial gene could be delivered to the body in several different ways, experts say. Perhaps the easiest method would be to inject the DNA directly into the muscle. But more efficient techniques using viruses or modified cells from the patient are also being developed.

One problem that currently prevents the clinical use of these techniques is the difficulty of controlling which tissues receive the gene. Schjerling says this would be of little concern to an athlete who just wants a short-term boost in hormone levels. Equally, doubts about whether the genes would keep functioning over time would not concern someone preparing for a one-off event such as the Olympics.

Gene doping of this sort would be difficult to expose. "The DNA of the artificial gene itself can be detected," says Schjerling, "but this requires that the sequence be known and that a sample of the tissue containing it can be acquired."

Even if the risk of detection was small, the risk to the athlete's health probably would not be. This is where the almost fanatical desire of athletes to excel raises problems, according to some of those present at the London meeting. Several cyclists are already thought to have died from EPO use, as the marked increase in circulating red blood cells severely thickens the blood, increasing the risk of clots and strokes.

In animal studies undertaken at the Chiron Corporation in Emeryville, California (S. Zhou, J. E. Murphy, J. A. Escobedo & V. J. Dwarki, Gene Therapy 5, 665–670; 1998), the levels of red blood cells in baboons given experimental EPO gene therapy rose so sharply (from 40 to 75% in 10 weeks) that their blood had to be regularly diluted to keep them alive.

Theodore Friedmann, director of the gene-therapy programme at the University of California, San Diego, and a member of the WADA health, medical and research committee, says gene doping may occur sooner than people think. "The technology needed for a rogue attempt won't take that long to develop," he says. Although he thinks it unlikely that any athlete has yet tried it, he adds: "We all think there will be an attempt to do so."