Muscle Boy

"This report is significant because it shows for the very first time conclusively that myostatin does play an important role in regulating muscle growth in humans, as we already knew to be the case in both mice and in cattle," says Lee, who is a co-author of the report.

Schuelke says the mutation is "probably quite rare and we were just happy to find it." He says other scientists have searched for myostatin mutations in samples of athletes and so far failed to find any.

Lee says that DNA tests showed the German boy's mother, a former professional sprinter, lacks one copy of the gene, while the child lacks both copies. "If you lack just a single copy of the myostatin gene, you have increased amount of muscle, but not as much as if you lack both copies," says Lee. "So in other words, the effect of myostatin is almost certainly dose-dependent; that is, if you have some function, then you have a certain amount of muscle, and if you have a reduced amount of that, then you have even more muscle."

This means that therapies that even partially block the effect of myostatin could increase muscle strength. "It certainly makes us very optimistic in terms of further pursuing this area of research for the treatment of muscle-wasting diseases," says Lee.

Wyeth pharmaceutical company recently started Phase I clinical trials of a myostatin blocker to treat muscle-wasting diseases. In Phase I trials the drug is tested for safety in healthy adults.

Genetically engineered mouse

Schuelke says the boy seems healthy and with clothes on "you wouldn't notice him walking down the street. But his bare muscles are much more prominent and he has much less subcutaneous fat" than a normal child. "So far he is well, we've checked him regularly," says Schuelke, "but there are diseases that show up later in life, so we can't predict" his future health since he is the first proven human case.

Clouding the Doping Debate

Schuelke says in addition to DNA testing, researchers at Wyeth Pharmaceuticals developed a test for detecting myostatin in human blood. "Testing for myostatin in humans is much more difficult than in animals, because humans have much lower circulating levels" of myostatin, Schuelke explains.

Could athletes suspected of using performance-enhancing drugs use such a test to prove they are natural? "We can now measure it in an athlete and get a number, but what do we compare it to?" says Schuelke. "We first have to establish what's normal to know what an athlete's values mean." He says he's working with the Wyeth scientists to collect samples to determine that.

University of Pennsylvania gene therapy researcher Lee Sweeney, whose own studies on mice convinced him that athletes may be tempted to tamper with their own DNA, worries that the new genetic therapies will find their way into professional sports. He wrote in the July issue of Scientific American about the "natural advantage" the myostatin mutation provides.

"There are going to be people who are carrying these mutations that give them unusual athletic abilities without the need to do the same level of training as an average person," he says. "If I was a weightlifter and competing against someone who is not making any myostatin because of a mutation in his genes, then I think I might want to file a protest that that person has an unfair genetic advantage even though they inherited it."

In fact, Sweeney predicts that as gene therapy becomes widespread it could be tougher to argue that athletes shouldn't have access to it. "I think as this becomes more widely known that athletes are competing against people who have naturally occurring mutations that are clearly a genetic advantage to them, that they're going to say that this gene enhancement or gene doping is not an unfair thing," he says. He predicts some will argue "'it's unfair to not let me have it because now I'm competing against people whose parents gave them these things naturally, and mine didn't, and…I want the same enhancement in my genes so that I can actually compete with them in a fair manner'. Then the debate becomes really cloudy and interesting for the bioethicists."

This research appeared in the June 24, 2004 issue of the New England Journal of Medicine, and was funded by Helft dem Muskelkranken Kind (Hamburg, Germany) and National Institutes of Health (NIH).