Olympic officials, already waging a battle against athletes' use of performance- enhancing drugs, now worry about a new trend: gene doping

By David Kohn
17 aug 2008--Over the past few weeks, even before the torch was lit, dozens of athletes from around the world have tested positive for banned drugs and have been barred from the Beijing Olympics.Sports officials say this shows their new anti-drug attack is working. "The gap between regulators and cheaters has narrowed, and it will continue to narrow," says David Howman, director of the World Anti-Doping Agency (WADA), the international organization that oversees drug testing for the Olympics.WADA and the International Olympic Committee will perform more than 4,500 doping tests during the Olympics, almost 1,000 more than four years ago. TheIOC'sBeijing lab operates around the clock with 180 scientists and staffers. It has added two new tests for human growth hormone and erythropoietin, two previously undetectable drugs that by most accounts have been widely used by elite athletes.Still, that may not be enough.Many knowledgeable observers say that cheating remains rampant, and that athletes, coaches, and trainers - as well as the doctors and scientists they work with - have found new ways to outmaneuver existing tests, and have developed new doping technologies for which no tests exist. The competition in Beijing, they say, will feature hundreds, perhaps thousands, of athletes who have eluded WADA's chemical dragnet."They're ostriches, hiding their heads in the sand," Dr. Mauro Di Pasquale says of WADA and other agencies that oversee testing. A Toronto sports medicine specialist who has decades of experience working with elite athletes, he estimates that more than a third of the 11,000 Olympians in Beijing have used a banned substance in the year or so leading up to the Olympics.He and others say that many key tests have severe limitations. Take, for instance, the test for human growth hormone (HGH): It can only detect the substance in the 24 to 48 hours after the drug is injected. To avoid a positive test, an athlete simply has to stop injections a few days before being tested. That interruption would almost certainly not affect performance because the benefits of HGH, which appears to increase muscle mass and strength, can last for weeks or months. (Athletes can be tested randomly, but these tests are infrequent; in any case, observers say, it is relatively easy to avoid these tests by not answering calls or "going out of town.")Timing is key, says nutrition and training expert Victor Conte: He says athletes generally use performance-enhancers months before competition. "These are training drugs," says Conte, who in 2005 pleaded guilty to conspiracy to distribute steroids as part of the BALCO scandal. "You use them in the offseason, to train better. In-competition, tests are worthless. These athletes aren't dumb."The tests themselves may also make errors. A recent study by scientists at the Copenhagen Muscle Research Center found that the test for synthetic erythropoietin has a high false negative rate; in other words, it lets lots of cheaters through. Known as EPO, erythropoietin is a go-to enhancer for endurance athletes such as long-distance runners and swimmers. It increases red blood cells, making more oxygen available to muscles.Another loophole: Although WADA and its allies test for many steroids such as nandrolone and stanozolol, experts say it is not difficult for a reasonably competent chemist to develop slightly altered "designer" versions. Such compounds have the same effects as the recognized drugs - increased strength and muscle growth - but are invisible to the tests."It's really not that complicated to develop a new steroid," says William Llewellyn, a chemist who is the author of Anabolics, a steroids encyclopedia used by doctors and athletes. He talks regularly with athletes, trainers and coaches, and says it is still possible for athletes in Beijing to evade tests by using designer steroids.Authorities "absolutely have not closed it down," he says.Another potential trick: Athletes may be able to avoid positive tests by taking a cocktail made up of low doses of several drugs, including steroids, growth hormone and EPO, as well as other substances and hormones.Then there are the drugs that are not yet banned. According to several people familiar with doping trends, many athletes are using Viagra, as both a training aid and a performance-booster during competition. The drug works via the same mechanism by which it improves erections: It brings more blood to muscles, says John Romano, senior editor of Muscle Development, a Web site devoted to training and performance enhancement.Howman says WADA knows about Viagra, and is studying it. The agency may ban it in the future, he says.The latest enhancement trend is gene doping. This approach involves injecting the body with a gene that triggers growth in specific tissues such as muscle. Because the muscle increase isn't produced by a foreign substance, but by the body's own genetic instructions, it could be very difficult to detect in a test.So far, research on gene doping has only occurred in animals. But the results have been astonishing. "You can get enormous growth," says Se-Jin Lee, a Johns Hopkins University molecular biologist who discovered the muscle-building gene pathway a decade ago.In recent tests, he's found that with just two injections over two weeks, he can increase muscle mass in mice by 60 percent. This effect occurs with no training at all.He says it wouldn't be difficult to try the approach on humans. "Any small lab out there, even an individual who knows what they're doing, could do this. The technology is relatively straightforward," he says. The estimated cost of such an operation: between $20,000 and $50,000.For an athlete with the opportunity to earn millions, that is a relatively small amount. And this, many observers say, is the crux of the issue: In the end, the battle between cheaters and testers comes down to money. WADA's research budget is about $6 million a year, probably a good bit less than what the other side spends."The bad guys probably have a lot more money to pursue their illicit work than we have to pursue our legitimate work," says Theodore Friedmann, a gene doping expert at the University of California, San Diego. "But it's a noble battle."Lee emphasizes that he has no plans to use his technique on humans, and thinks that doing so would be "nuts," given that the treatment has never been tested in people for either safety or effectiveness.But others may be more audacious. Romano and Di Pasquale say they've heard of several elite athletes who have undergone gene doping treatment, and many observers expect the practice to become widespread. "All the fervor over steroids and HGH will be passe by the next Olympics," says Romano. "Gene doping will take over."WADA agrees. For several years, the agency has been working on tests for gene doping. "Athletes and trainers are all aware of this technology," says Friedmann, who directs the agency's gene therapy research program. "The sporting world is following this at a very high level."Even so, Friedmann is confident. "There's always a clue," he says. "All of these methods have molecular signatures that we will be able to detect."Beyond genes, another booster looms: stem cells. Researchers around the world are growing these malleable cells into all sorts of tissue, from muscle to nerve to bone. In theory, stem cells could be used to augment an athlete in ways similar to gene therapy. Most scientists say stem cell technology isn't yet advanced enough for athletic use. But last month, German journalists released a documentary showing a Chinese doctor offering to inject stem cells into a swimmer for $24,000.Was the doctor making a legitimate offer? "There's no way to know," says Friedmann, "but nothing would surprise me."Di Pasquale, who favors testing, says authorities will always lag behind cheaters. "If the demand is there, you'll always be able to get it. It's just like cocaine and heroin. It will never be under control. WADA will be behind every time."