Gene manipulation will have its most significant impact in treating diseases and promoting health rather than enhancing athletic abilities, although sports will certainly benefit from this research. Scientists are already studying whether gene therapies can help people suffering from muscle diseases such as muscular dystrophy. "A lot has been learned about how we can make muscles stronger and bigger and contract with greater force," says Theodore Friedmann, a geneticist at the University of California, San Diego, and head of a gene-doping advisory panel for the World Anti-Doping Agency (WADA). Scientific studies have introduced IGF-1 protein to mouse tissue to prevent the normal muscle degradation during aging. "Somewhere down the road efforts could be made to accomplish the same in people," he adds. "Who would not stand in line for something like this?"
Gene therapy has already proved useful in studies unrelated to muscle treatment. In December 2011, for example, a team of British researchers reported in The New England Journal of Medicine that they were able to treat six patients with hemophilia B—a disease in which blood cannot clot properly to control bleeding—by using a virus to deliver a gene enabling them to produce more of the clotting agent, factor IX.
Despite experiments with IGF-1 and MSTN protein levels in mouse muscle, identifying which genes are directly responsible for athletic prowess is a complicated matter. "What we've learned over the past 10 years since the sequencing of the human genome is that there's a heck of a lot more complexity here than we first envisioned," says Stephen Roth, a University of Maryland associate professor of exercise physiology, aging and genetics. "Everybody wants to know what are the genes that are contributing to athletic performance broadly or muscular strength or aerobic capacity or something like that. We still don't have any hard targets solidly recognized by the scientific community for their contribution to athletic performance."
By 2004 scientists had discovered more than 90 genes or chromosomal locations they thought were most responsible for determining athletic performance. Today the tally has risen to 220 genes.
Even with this lack of certainty, some companies have already tried to exploit what has been learned so far to market genetic tests they claim can reveal a child's athletic predispositions. Such companies "are sort of cherry-picking some literature and saying, 'Oh, these four or five gene variations are going to tell you something,'" Roth explains. But the bottom line is the more studies we've done, the less certain we are that any of these genes are really strong contributors by themselves."
Atlas Sports Genetics, LLC, in Boulder, Colo., began selling a $149 test in December 2008 the company said could screen for variants of the gene ACTN3, which in elite athletes is associated with the presence of the protein alpha-actinin-3 that helps the body produce fast-twitch muscle fibers. Muscle in lab mice that lacks alpha-actinin-3 acts more like slow-twitch muscle fiber and uses energy more efficiently, a condition better suited to endurance than mass and power. "The difficulty is that more advanced studies have not found exactly how loss of alpha-actinin-3 affects muscle function in humans," Roth says.
ACE, another gene studied in relation to physical endurance, has rendered uncertain results. Researchers originally argued that people with one variant of ACE would be better at endurance sports and those with a different variant would be better suited to strength and power, but the findings have been inconclusive. So although ACE and ACTN3 are the most recognized genes when it comes to athletics, neither is clearly predictive of performance. The predominant idea 10 or 15 years ago that there might be two, three or four really strong contributing genes to a particular trait like muscular strength "is kind of falling apart," Roth says. "We've been realizing, and it's just been borne out over the past several years, that it's not on the order of 10 or 20 genes but rather hundreds of genes, each with really small variations and huge numbers of possible combinations of those many, many genes that can result in a predisposition for excellence.
"Nothing about the science changed," he adds. "We made a guess early on that turned out not to be right in most instances—that's science."
WADA turned to Friedmann for help after the 2000 Sydney Summer Olympics after rumors started flying that some of the athletes there had been genetically modified. Nothing was found, but the threat seemed real. Officials were well aware of a recent gene therapy trial at the University of Pennsylvania that had resulted in the death of a patient.