In 1982 Isaac Asimov wrote a classic short story about genetically-engineered athletes with giant lungs, capable of running fifty miles an hour. Asimov’s “Super Runners” are still entirely science fiction, but the intrusion of genetic technology into sports is not. In fact, Turin may be one of the last Olympics in history where athletes are tested only for drugs. “Gene doping,” the next frontier of illicit technologic performance enhancement, is already coming into view — and it may someday prove nearly impossible to control.
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Gene doping is a variant on the fondest medical dream for genetic engineering: human gene therapy. Simply put, genes control the manufacture of the proteins that underlie all of the human body’s functions. Missing or malfunctioning genes thus account for countless varieties of human ills, and the hope is that someday by replacing or repairing those miscreant genes, a wide range of illness and disability can be cured or controlled. But just as gene therapy promises to restore normality to the infirm, it also carries the potential to give super powers to those who are already entirely fit.
Work in therapeutic gene therapy was how “gene doping” first reared its head, seven years ago, with the work of H. Lee Sweeney at the University of Pennsylvania. Sweeney was investigating ways that gene therapy might help people with muscular dystrophy, or elderly patients whose muscle mass has dangerously declined. Sweeney created a synthetic gene that promotes an insulin-like substance encouraging muscle cell growth, and used a tiny virus to carry the gene into the muscles of laboratory mice. The mice muscles grew 15 to 30 percent larger than normal — even though the mice had no exercise. And when middle-aged mice with the genetically-enhanced musculature grew to old age, they retained their megamuscles.
As soon as Sweeney’s work was published, athletes and their coaches began to call. Of course, the safety and efficacy of Sweeney’s work isn’t even sufficiently established to use in the chronically ill, much less those interested in the technique for sport. (Sweeney has only now expanded his work to dogs.) It wasn’t long, however, that additional gene therapy research drew more attention from athletes. Se-Jin Lee, a Johns Hopkins researcher, accelerated muscle growth in mice by blocking the gene that produces a protein that limits muscle growth. (Children with this rare mutation naturally can be exceedingly strong for their age.) Another researcher genetically modified the fat-burning abilities of mice muscles to significantly increase endurance.
The World Anti-Doping Agency — the Olympic Committee’s watchdog for such matters — is already funding work on detecting genetic modifications, but it’s much trickier than merely sniffing out illicit drug use. The compounds that the added genes produce are generally identical to what the body already produces, and the viruses used to insert the new genes are also widely found in humans. While there may be some promising — and very expensive — potential solutions on the horizon, at present most researchers say that the only sure way to detect genetic manipulation would be an actual needle biopsy of each athlete’s muscle tissue. That’s likely to be a non-starter for even the most dedicated Olympian.
The technology used in gene doping is already well within the skill-set of thousands of laboratories around the world. The bigger question is who would actually take the risk. Early attempts at legitimate human gene therapy have had mixed results; in 1999 an 18-year-old boy died days after receiving a genetic injection intended to cure an inherited liver disease. More recently in France, gene therapy seemed to cure the “boy in a bubble” immune deficiency syndrome in a group of youngsters — but then three of them developed leukemia. Performing gene doping could be malpractice or potentially murder; receiving it would be an enormous gamble.
One 2003 experiment should be particularly worrisome to would-be gene dopers. The work attempted to genetically increase the level of erythropoietin in rhesus monkeys. EPO is a hormone that encourages red blood cell formation and is used clinically to treat diseases like anemia. It is also notoriously abused by athletes to improve endurance in events like cross-country skiing or cycling. The genetic modification in some of the monkeys worked very well — so well in fact that it thickened their blood to the point it required dilution for the creatures to survive. In other monkeys their own immune systems attacked the novel EPO (as well as their natural EPO) leading to severe anemia.
So what kind of trainer and athlete would engage in such an experiment? Perhaps one whose country was bent on winning at any cost — think of the former East Germany’s steroid binge during the 70’s and 80’s. Find another totalitarian country with similar aspirations, and that’s not a bad first candidate. (For starters, perhaps we should ask the South Koreans to keep an eye on their cousins to the north now that they’ve agreed to compete as a single team.)
Gene doping may still be a few years off, but as soon as it starts, the issues will grow remarkably complex. What about athletes who use legitimate gene therapy to repair injuries? That technology may be essentially the same as gene doping. And if gene doping can be detected, what should the penalty be? Currently WADA suggests a two-year suspension for first time drug users, but the results of a single gene doping could last for years, or even a lifetime. And finally, some thinkers are already suggesting that it may be impossible to prevent genetic manipulation and we should view such “transhumans” as just another class of competitor that has simply chosen an unorthodox training regimen.
There’s one aspect of genetic technology, however, that has already appeared in sports— and it’s not only legal, it’s sold on the Internet. For a year now, the Australian genetic testing company Genetic Technologies Ltd. has been offering a DNA test that detects variations in the ACTN3 gene. This gene produces a protein that enhances the operation of so-called “fast twitch” muscle fiber, the kind involved in activities like sprinting or power lifting, as opposed to endurance sports like marathons. In one variation of this gene, the production of the protein is repressed, so that while muscles remain normal, they have much less of this fast twitch enhancer.
Everyone has two copies of the gene, one from each parent, so it’s possible to have one, two or no “repressed” versions of the ACTN3 gene. In a study of 300 elite level athletes, including 50 Olympians, every single one of the sprint/power athletes tested had at least one “normal” copy of the ACTN3 gene. That means that all were producing at least some of the fast-twitch protein enhancer in their muscle fibers. On the other hand, endurance event athletes were more likely to have two copies of the “repressed” variant, suggesting that the absence of the fast-twitch protein may have supported the development of slower, more efficient muscle fiber.
Genetic Technologies cautions that the test, so far sold only in Japan and Australia for about $100, doesn’t predict whether anyone is going to be a champion; far too many other factors are involved in that. Rather, it’s intended to help experienced athletes choose what events they should train for — and shouldn’t, the manufacturer cautions, be used to pressure kids into one sport over another.
On the other hand, knowing what activities one has a proclivity for might well be helpful for young athletes — or better, knowing which activities won’t be fruitful. I spent years as a kid trying without success to become a faster swimmer for short-distance events; it might have been a relief if my coach could have simply told me, “Son, your chart says you’ve got two repressed ACTN3’s. Ever hear of a triathlon?”
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