As the steroid controversy continues to rage through the sports world, a Penn professor is researching a new type of gene therapy that could potentially represent the next wave of performance-enhancing treatments.
Spurred by watching elderly family members lose their strength, Physiology Department Chairman Lee Sweeney has devised a way to inject genes that promote muscle growth into animals. In theory, a similar procedure could promote muscle growth in humans -- an effect which could help those afflicted with muscular dystrophy and other types of muscle-degenerating diseases.
However, he notes that these therapies could be used to enhance muscle growth in a healthy individual as well.
"These things could be abused by people just looking to enhance their sports performance," Sweeney said, adding that he believes that within the next five years athletes will be attempting to gene dope.
Although Sweeney has said that he does not believe gene-doping will hit the American market nor make a major impact globally for at least 20 years, he believes that the 2004 Games in Athens will have been the last Olympics untainted by genetically enhanced athletes.
As regulations within the United States will make it extremely difficult for any athlete to gain access to the therapy here, Sweeney believes that unregulated clinics in third-world countries will offer athletes the opportunity to gene dope.
"It's just going to take one person with the money and scientific know-how," Sweeney said, citing former BALCO executive Victor Conte as an example of somebody who undertook this sort of initiative. Conte researched undetectable designer steroids for a variety of high-profile athletes.
"We do know by experience that there are people out there who are ready to do whatever [it takes] to help athletes cheat," World Anti-Doping Agency spokesman Frederic Donze said.
"You have different kinds of new ways of cheating. Gene-doping is definitely one major concern."
Although the technology has only been tested on lab mice, gene-doping does appear to have a clear demand among athletes. Sweeney said that he has repeatedly been e-mailed by anonymous athletes inquiring about the cost and availability of gene therapy.
"I had one high school football and high school wrestling coach approach me," asking for the therapy for their entire teams, Sweeney said.
One of the most ominous implications of gene-doping is that it will be difficult to test for. Sweeney predicted that gene-doping will only be detectable through muscle biopsy and not the more standard blood and urine samples currently used to test athletes.
Donze said that the agency is taking steps to prevent gene-doping in athletes before it starts. WADA is currently funding five research projects in an effort to find a way to detect gene-doping through means other than muscle biopsy.
Theodore Friedman -- a gene therapist at the University of California, San Diego and one of the recipients of WADA funding -- believes that the detecting technology is not far behind the gene-doping technology.
"The technology [to test using blood samples] will be there, sooner or later," he said. "It may take some time, it may be very quick."
But because of its current undetectable nature, gene-doping raises serious ethical considerations as its development continues.
Paul Root Wolpe, senior fellow at the Penn Center for Bioethics, believes that the values surrounding gene therapy's general use should be held distinct from those regarding gene-doping by athletes.
"The day the announcement [about Sweeney's work] came out, people started speculating about its enhancing effects," Wolpe said. "That's not the whole story here."
"The thing about sports that we always have to remember is that there is no right or wrong in sports; sports is a convention" Wolpe added. "We could allow or not allow any technology."
According to Wolpe, gene-doping might prove to be a safer technology than steroids in the long run.
"Steroids, as male hormones, increase aggression. But increasing your muscle mass does not, in and of itself, make you aggressive."
But the idea to promote muscle mass via gene therapy has broader ethical implications when it comes time to inject these genes into humans. For now, Sweeney and his colleagues have only been testing muscle-promoting genes in mice and rats, with dogs next on the list of animal subjects.
Although Sweeney observed no harmful side effects in his lab mice, the possible side effects in humans give rise to serious moral questions.
"The only reason that this technology probably won't be an ethical monster is because it will be tested first for a muscle-wasting disorder," Wolpe said.
But while it may be worth it for people suffering from muscle depletion, athletes have more to lose because of the medical risks associated with gene therapy.
"The risk/benefit ratio is appropriate in certain diseases," Friedman said. "In sport, there are only risks."
"It's pretty clear to me that both the athletes and the elderly don't care about long-term effects," Sweeney said, adding that elderly patients don't need to worry about them, but athletes should.
According to Sweeney, human trials are likely to begin "in the next year or two."
Wolpe also feels that widespread innovations in gene therapy are inevitable.
"Barring harms," he said, "I'm not sure that these major technologies should be stopped."
But these harms were clearly manifested six years ago in a tragic incident here at Penn.
Eighteen-year-old Jesse Gelsinger, a Penn student who suffered from a rare liver disorder, died as a result of being injected with a gene during a gene therapy experiment at Penn's Institute for Human Gene Therapy.
In response, the Food and Drug Administration temporarily shut down all gene therapy trials at the University and cited the IHGT for numerous violations.
What happened with Gelsinger illustrated the inherent danger of gene therapy trials and had a ripple effect throughout every lab involved in gene therapy research.
But with such promising results from Sweeney and his colleagues, proponents of gene therapy are trying to put distance between the Gelsinger case and today.
In any case, gene therapy is a reality that is looming relatively near on the horizon. It has great potential to help those with degenerative muscle diseases, but also presents a number of ethical and medical questions, especially regarding gene-doping with athletes.
"I think an athlete is going to try it in the next five years," Sweeney said. "But I don't know if it's going to be successful."
