"In medicine, such risks are accepted by patients and by the profession that danger is being undertaken for purposes of healing and preventing pain and suffering," Friedmann says. "If those same tools when applied to a healthy young athlete were to go wrong, there would be far less ethical comfort for having done it. And one would not like to be in the middle of a society that blindly accepts throwing [erythropoietin (EPO)] genes into athletes so they can have improved endurance performance." EPO has been a favorite target for people interested in manipulating blood production in patients with cancer or chronic kidney disease. It has also been used and abused by professional cyclists and other athletes looking to improve their endurance.
Another scheme has been to inject an athlete's muscles with a gene that suppresses myostatin, a protein that inhibits muscle growth. With that, Sweeney says, "you're off and running as a gene doper. I don't know if anyone is doing it, but I think if someone with scientific training read the literature they might be able to figure out how to succeed at this point," even though testing of myostatin inhibitors injected directly into specific muscles has not progressed beyond animals.
Myostatin inhibitors as well as EPO and IGF-1 genes have been early candidates for gene-based doping, but they're not the only ones, Friedmann says. The vascular endothelial growth factor (VEGF) gene instructs the body to form signal proteins that help it increase blood flow by sprouting new blood vessels in muscle. These proteins have been used to treat macular degeneration and to restore the oxygen supply to tissues when blood circulation is inadequate. Other tempting genes could be those that affect pain perception, regulate glucose levels, influence skeletal muscle adaptation to exercise and aid respiration.
Games at the 2012 Olympics
Gene manipulation is a big wild card at this year's Olympics, Roth says. "People have been predicting for the past several Olympics that there will be gene doping at the next Olympics, but there's never been solid evidence." Gene therapy is often studied in a medical context, and it fails a lot of the time, he notes. "Even if a gene therapy is known to be solid in terms of treating a disease, when you throw it into the context of athletic performance, you're dealing with the unknown."
The presence of gene doping is hard to detect with certainty. Most of the tests that might succeed require tissue samples from athletes under suspicion. "We're talking about a muscle biopsy, and there aren't a lot of athletes who will be willing to give tissue samples when they're getting ready to compete," Roth says. Gene manipulation is not likely to show up in the blood stream, urine or saliva, so the relatively nonintrusive tests of those fluids are not likely to determine much.
In response, WADA has adopted a new testing approach called the Athlete Biological Passport (ABP), which will be used at the London Olympics. Several international sporting authorities such as the International Cycling Union have also begun to use it. The key to ABP's success is that, rather than looking ad hoc for a specific agent—such as EPO—the program monitors an athlete's body over time for sudden changes, such as a jump up in red blood cell count.
Another way to detect the presence of gene doping is to recognize how the body responds to a foreign gene—notably, defense mechanisms it might deploy. "The effect of any drug or foreign gene will be complicated by an organism trying to prevent harm from that manipulation," Friedmann says—rather than from intended changes induced by EPO, for example.
The Olympic games make clear that all athletes are not created equal, but that hard work and dedication can give an athlete at least an outside chance of victory even if competitors come from the deeper end of the gene pool. "Elite performance is necessarily a combination of genetically based talent and training that exploits those gifts," Roth says. "If you could equalize all environmental factors, then the person with some physical or mental edge would win the competition. Fortunately those environmental factors do come into play, which gives sport the uncertainty and magic that spectators crave."