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Rick's Corner

Gene Doping: The Next Balco?

Gene Doping: The next athletic scandal? Twenty years ago, science-fiction writer Isaac Asimov wrote a story called “The Super Runner,” in which he depicted the athletes of the future: gene-modified to have lungs like bellows, bulging muscles, and immensely jacked-up metabolisms that allow them to perform feats of endurance and speed impossible to ordinary humans. Think it’s merely science fiction? Don’t count on it, say scientists on the forefront of research into the limits of human performance. 

Even as the sports world continues to be rocked by the parade of big-name athletes linked to the Balco scandal, sports officials are bracing for the next wave of high-tech cheating: gene doping. For those who haven’t been reading the sports pages, Balco is the Bay Area Laboratory Co-Operative, a California chemical company that allegedly made designer steroids for a Who’s Who of famous athletes. The scandal came to light in 2003 when an anonymous coach mailed a syringe containing an unknown fluid to officials at the U.S. Anti-Doping Agency. The fluid proved to contain a body-building steroid called THG, carefully crafted to be undetectable under conventional tests. 

Although legal investigations are continuing, the THG story is “essentially over” from a scientific perspective, says Donald Catlin, a professor of molecular and medical pharmacology at UCLA. “We know how to find (designer steroids) and deal with them; it’s just a matter of time and energy,” he says. The moment THG came to light, he adds, it immediately went from being the designer-drug of choice to “a dinosaur.” This means that forward-looking drug testers need to be thinking about the future – a domain in which gene doping could put non-enhanced athletes at a tremendous disadvantage. Gene doping isn’t the creation of mutant children by bioengineering them for superstar height, strength, speed or bulk. Rather, it’s a method of altering the genes of adults so their cells do things differently from the way they were programmed at birth. 

Such treatments, called gene therapy when used for legitimate medical purposes, offer promising treatments for inherited diseases, such as muscular dystrophy. But most experts believe it is merely a matter of time before they find an underground market among athletes. Muscular dystrophy is a devastating condition that involves the gradual degradation of muscles, usually due to their inability to manufacture a critical protein. Gene therapists are hoping to use viruses to insert new genes into the cells of the affected muscles, thereby allowing them to function more normally. Similar techniques may someday also be able to offset the muscle atrophy that often accompanies aging. One of the most interesting potential treatments involves a hormone called insulin-like growth factor-1 (IGF-1). IGF-1 encourages the proliferation of “satellite cells,” a type of stem cell found in muscles. These cells can fuse with normal muscle fibers, repairing injury or simply helping the muscle to bulk up – potentially beneficial for both repairing the damage of muscular dystrophy or offsetting the atrophy of old age. 

Sweeney and other researchers have demonstrated that it’s possible to insert the IGF-1 gene into selected muscles of rats and mice, and that when this is done, these cells indeed produce the desired growth factor. In one experiment, researchers inserted the gene into one leg of middle-aged mice but not the others. By the time the mice had aged to the equivalent of octogenarian people, their uninjected legs had lost 25 percent of their strength, but the injected legs were as strong as ever. In another test, the same treatment was given to younger mice, equivalent to humans in their athletic prime. Even in sedentary mice, there was a 15 to 20 percent increase in muscle strength. “It’s the couch potato’s dream,” Sweeney says. For baby boomers hoping to avoid having to use walkers in their old age, this is a wonderful finding, although it will take years of testing to determine whether such fountain-of-youth treatments are free of nasty side effects (such as cancer). But because the mouse experiments used sedentary animals, they didn’t answer the question of whether IGF-1 gives you anything you can’t get by ordinary athletic training. 

To determine whether IGF-1 gene doping might truly be a magnet for cheaters willing to risk their health in pursuit of athletic glory, Sweeney repeated the experiment, this time with rats. He forced the animals to climb ladders with weights tied to their tails, in an effort to simulate human workouts. The findings were dramatic. In control animals that were not subjected to the ladder-climbing workouts, the gene-doped legs again got 15 percent stronger. But in animals that received both the injection and the exercise, the doped legs grew 30 percent stronger. By comparison, the equally well-exercised, non-doped legs gained only 14 percent in strength. In other words, gene doping had more than doubled the effectiveness of the athletic rats’ training. IGF-1 doping is merely one possible form of gene doping. Another approach would be to boost the muscles’ metabolism by increasing their component of mitochondria, the cellular powerhouses that burn fat and carbohydrates to produce fuel for exercise. More mitochondria would mean more energy, and presumably greater speed and endurance, without the need to bulk up. Or, it may be possible to tinker with a hormone called myostatin, which has the opposite effect as IGF-1. Its purpose is to keep you from growing larger muscles than you actually need – important to our distant ancestors, who would have had to forage for extra food if their bodies bulked up too strongly. There is a breed of cattle called Belgian Blues that has unusually large, lean muscles because the animals produce lower-than-normal amounts of myostatin. Myostatin-inhibiting drugs are already under development for use in treating muscular dystrophy, and Sweeney’s team has experimented with gene-doping techniques to inject a myostatin-inhibiting gene into the livers of mice, causing all the muscles of their bodies to grow like those of Belgian Blue cattle. 

Nobody has a clue what side effects this would have in humans – but if it makes stronger mice, it’s likely to be tempting to the next generation of Balcos. Sweeney predicts that myostatin-inhibitors will be the next designer drug on the cheating athlete’s shopping list. Gene-doping the liver to produce drugs such as myostatin inhibitors will be no harder to detect than conventional forms of drug administration, such as pills or injections. That’s because, in order to reach the muscles, these compounds must pass through the bloodstream, where they will show up on blood tests. Much more difficult to detect will be IGF-1 gene doping or other techniques that work directly within the muscles, bypassing the bloodstream. Detecting this type of cheating might well require a biopsy of the affected muscles – a considerably more invasive (and painful) test than current drug tests. 

As far as anyone knows, gene doping hasn’t yet hit the athletic world. But in 2002, Richard Pound, president of the World Anti-Doping Agency, says he received his first inquiry from a concerned coach. And Theodore Friedmann, a medical professor at UCSD, notes that the necessary techniques are already within the reach of the average molecular biology graduate student. If a well-funded national sports program made a concerted effort, as the East Germans did with steroids during the Cold War, Sweeney believes that gene-doped athletes could be a threat in the 2008 Beijing Olympics. Pound thinks it’s more likely not to be a problem before 2012 but notes that this makes the threat no less real. “What’s important is that we don’t lose track of it,” he says. “I want gold medals given to athletes, not their gene engineers.” “It’s scary to think that there would be coaches and athletes who would do that,” says Bob Williams, a Portland, Ore., coach who in 2000 trained Lisa Nye for a world record in the women’s 3,000-meter steeplechase. Williams thinks that the most likely motivator will be the lure of big bucks for top-performing athletes and their agents. “The Olympic Games is one thing,” he says, “but making money is more powerful for athletes who’ve lost focus on why we’re doing this.” 

Beyond that lies the question of whether the practice ever can be effectively banned. Thomas Murray, president of The Hastings Center, a leading bioethics think tank, points out that athletes are accustomed to manipulating their bodies in all kinds of ways to achieve maximum performance. Dietary supplements, minutely planned diets, high-tech equipment – all of these are an accepted part of sports. Some athletes now go so far as to live in low-oxygen “altitude tents” designed to mimic the effects of living on mountaintops, without ever leaving the comforts (and training facilities) of home. Sweeney suggests that in the long run, society’s attitude toward gene doping will depend on how widely the same techniques are used by nonathletes. If a treatment is used only rarely, to cure a disease such as muscular dystrophy, athletes will most likely be prohibited from using it. But if the population at large is using something like IGF-1 to slow the normal effects of aging, it may well become an accepted method of boosting athletic performance. Sweeney also notes that genetic profiling of elite athletes will probably demonstrate that they already carry unusual genes. For example, weight lifters may be genetically like Belgian Blue cattle – with naturally low levels of myostatin that make it easier for them to bulk up. Once such factors are identified, he asks, is it fair to insist that other athletes not be allowed to give themselves the same genetic advantage? “It’s not a question I’d like to answer,” Sweeney says. 

But someday, probably before Isaac Asimov’s story is another 20 years older, it’s exactly the type of question that anti-doping authorities will indeed be forced to answer. 

© 2004 by Richard A. Lovett. All rights reserved.

See this at http://running.richardalovett.com. If people want to come to my site, that’s great.


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