How Olympians Could Beat the Competition by Tweaking Their Genes

The next horizon in getting that extra athletic advantage may not be steroids, but gene therapy

The genetic blueprints of an athlete are as important as training. (© Sciepro/Science Photo Library/Corbis)

Take a close look at the athletes competing in this year's Summer Olympic Games in London—their musculature will tell you a lot about how they achieved their elite status. Endless hours of training and commitment to their sport played a big role in building the bodies that got them to the world's premier athletic competition. Take an even closer look—this one requires microscopy—and you'll see something else, something embedded in the genetic blueprints of these young men and women that's just as important to their success.

In nearly all cases, these athletes have realized the full potential laid out by those genes. And that potential may be much greater to begin with than it was for the rest of us mortals. For instance, the genes in the cells that make up sprinter Tyson Gay's legs were encoded with special instructions to build up lots of fast-fiber muscles, giving his legs explosive power out of the starting blocks. In comparison, the maximum contraction velocity of marathoner Shalane Flanagan's leg muscles, as dictated by her genes, is much slower than Gay's yet optimized for the endurance required to run for hours at a time with little tiring. Such genetic fine-tuning also helps competitors in basketball, volleyball and synchronized swimming, although the impact might be much less because effective teamwork and officiating also influence success in those sports.

When the gun goes off for the 100-meter sprint, when swimmers Michael Phelps and Tyler McGill hit the water, when Tom Daley leaps from his diving platform, we see the finest that the world's gene pool has to offer, even though scientists are still trying to figure out which genes those are. Unfortunately, history dictates that we may also see the finest in gene manipulation, as some athletes push for peak performance with the help of illegal substances that are becoming increasingly difficult to detect.

The skinny on muscles
The human body produces two types of skeletal muscle fibers—slow-twitch (type 1) and fast-twitch (type 2). The fast-twitch fibers contract many times faster and with more force than the slow-twitch ones do, but they also fatigue more quickly. Each of these muscle types can be further broken down into subcategories, depending on contractile speed, force and fatigue resistance. Type 2B fast-twitch fibers, for example, have a faster contraction time than type 2A.

Muscles can be converted from one subcategory to another but cannot be converted from one type to another. This means that endurance training can give type 2B muscle some of the fatigue-resistant characteristics of type 2A muscle and that weight training can give type 2A muscle some of strength characteristics of type 2B muscle. Endurance training, however, will not convert type 2 muscle to type 1 nor will strength training convert slow-twitch muscle to fast. Endurance athletes have a greater proportion of slow-twitch fibers, whereas sprinters and jumpers have more of the fast-twitch variety.

Just as we can alter our muscle mix only to a certain degree, muscle growth is also carefully regulated in the body. One difference between muscle composition and size, however, is that the latter can more easily be manipulated. Insulinlike growth factor 1 (IGF-1) is both a gene and the protein it expresses that plays an important role during childhood growth and stimulates anabolic effects—such as muscle building—when those children become adults. IGF-1 controls muscle growth with help from the myostatin (MSTN) gene, which produces the myostatin protein.

More than a decade ago H. Lee Sweeney, a molecular physiologist at the University of Pennsylvania, led a team of researchers who used genetic manipulation to create the muscle-bound "Schwarzenegger mice." Mice injected with an extra copy of the IGF-1 gene added muscle and became as much as 30 percent stronger. Sweeney concluded that it is very likely that differences in a person's IGF-1 and MSTN protein levels determine his or her ability to put on muscle when exercising, although he admits this scenario has not been studied widely.

Slow-fiber muscle growth and endurance can likewise be controlled through gene manipulation. In August 2004 a team of researchers that included the Salk Institute for Biological Study's Ronald Evans reported that they altered a gene called PPAR-Delta to enhance its activity in mice, helping nurture fatigue-resistant slow-twitch muscles. These so-called "marathon mice" could run twice as far and for nearly twice as long as their unmodified counterparts.

This demonstrated ability to tinker with either fast- or slow-twitch muscle types begs the question: What would happen if one were to introduce genes for building both fast- and slow-twitch muscle in an athlete? "We've talked about doing it but have never done it," Sweeney says. "I assume you'd end up with a compromise that would be well suited to a sport like cycling, where you need a combination of endurance and power." Still, Sweeney adds, there has been little scientific reason (which translates into funding) to conduct such a study in mice, much less humans.

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?"


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