Genetic 'doping'

[dos]

Check this out folks......talk about a big-ass can of worms!

The First Genetically Modified Olympics

Widely expected by 2008, genetic doping could make its first appearance at this year's summer games
By Shannon Klie
Betterhumans Staff
8/9/2004 12:38 AM

Credit: Mehmet Alci
Strong appeal: The potential benefits of gene therapy for athletes are so great that the technology's current risks appear but a minor deterrent

Lee Sweeney is a busy man. Ever since the University of Pennsylvania geneticist discovered that inserting a specific gene could increase muscle performance in rats, he's been swamped by calls and emails begging for treatment. And anyone who doubts that athletes would alter their genes to win gold need only speak with him—if they can reach him. With hundreds of athletes wanting to take part in human trials for the gene therapy, which won't start for at least five years, Sweeney's had little time to speak with anyone, and even had to turn down an interview for this report.

Over the years, many athletes have felt pressure to use banned performance-enhancing drugs, including anabolic steroids, if only to be able to compete with those who are. In an attempt to beat the World Anti-Doping Agency's (WADA) drug tests, some athletes have turned to laboratories that produce and distribute undetectable performance-enhancing drugs. But as science advances, so does the potential for undetectable enhancements, and the next big thing isn't drugs but gene therapy: Manipulating DNA to enhance abilities in a nearly undetectable manner—in essence, changing the body itself to be stronger, faster and overall better for athletics.

WADA and the International Olympic Committee (IOC) have conservatively guessed that some athletes may use gene therapy at the 2008 Olympics in Beijing. "Whether it's a reality in the real world of athletics no one knows yet but we all think it will be a reality in the reasonably near future," says Theodore Friedmann, a member of WADA's health medicine research committee and an expert on gene transfer therapy.

But while the technology is new, and mostly untested on human subjects, athletes are willing to put their lives on the line for the chance to win gold, meaning that genetic doping could become a concern sooner than most people think. "I think it's a concern for this year's Olympics," says Andy Miah, a professor at the University of Paisley, Scotland and author of Genetically Modified Athletes.

Wakeup call

The recent BALCO scandals, says Miah, were a wakeup call that showed there are many forms of performance enhancement that anti-doping authorities know nothing about. American sprinter Kelli White and the San Francisco-based lab BALCO are at the center of this doping scandal, which involves several high-profile members of the US track and field team and their usage of undetectable performance-enhancing drugs. White used a synthetic form of the endurance-enhancing hormone erythropoietin (EPO), which is banned by WADA, to stimulate the production of her body's red blood cells and increase her endurance at last year's track and field world championships. It's a sign of things to come, because soon athletes won't have to take a synthetic compound—they'll be able to alter their bodies' own EPO production using gene therapy.

Gene therapy involves the injection of therapeutic genes into a subject's cells to replace faulty or nonexistent genes or to augment the level of gene activity, which controls how much of a protein—such as EPO—is produced. A vector, typically an altered virus, delivers the genes to target cells.

In 1999, James Wilson and his team at the University of Pennsylvania, in an effort to help kidney patients awaiting transplants, successfully injected parts of the EPO gene into the leg muscles of monkeys to help them maintain a steady supply of red blood cells. Once the technology has been tested on humans, athletes in endurance sports such as cycling and long-distance running could use Wilson's technique to increase their natural production of EPO and give them a nearly undetectable advantage.

Since the EPO discovery, there have been many more genetic breakthroughs with huge implications for sports. Sweeney's gene therapy discovery, which has made him the target of so many athlete inquiries, came earlier this year while looking for a treatment for muscular dystrophy (a disease that causes the progressive degeneration of a person's muscles). Sweeney and his team discovered that by injecting the gene for insulin-like growth factor 1 (IGF-1) into rats, the animals were able to better build and retain muscle. Rats injected with IGF-1 increased muscle size and strength by 15% to 30%, while rats injected with the gene and then put through ladder-climbing exercises doubled their muscle strength. The study results, published in the March issue of the Journal of Applied Physiology, indicate that if healthy people inject IGF-1 their muscles would get stronger without doing additional exercise. And for elite athletes, the benefits could be even more profound, making the effects of training last longer and helping them overcome injury more easily.

Increasingly, researchers are uncovering the genetic basis of athletic excellence. Last year, for example, Kathryn North at the Children's Hospital at Westmead in Sydney, Australia discovered that the ACTN3 R allele occurs more frequently in sprinters, while the X allele occurs more frequently in endurance athletes. ACTN3 R yields the protein a-actinin-3, which North and colleagues conclude activates the "fast-twitch" muscles that give people extra power for brief and vigorous bursts of activity. "Our findings in ACTN3 genotype suggest individuals have a genetic predisposition that affects muscle performance," says North. While there's currently no gene therapy treatment involving ACTN3, if one were developed it could have the potential to enhance athletic ability in humans. And the discovery could also help guide the choices of young athletes in determining events for which they're best suited.

Such research has made the prospect of genetic doping a near-term concern for the IOC. This March, Bengt Saltin, a member of the IOC science committee, cut the expected timeline for athletes to use gene therapy in half after Sweeney released the results of his IGF-1 research. Instead of 10 years, as the IOC medical commission chair Arne Ljungqvist estimated last year at an anti-doping conference in Sweden, Saltin said that athletes could attempt gene doping in the next four years—in time for the 2008 Olympics. As researchers make more discoveries, the timeline could shorten even more.

Regulating the inevitable

Despite all the research, however, gene therapy is still potentially deadly. An American patient in a gene therapy trial for a liver disorder died, for example, and two European children treated with inserted genes for immune deficiency developed leukemia.

For at least the next four years, the risk to athletes attempting to gene dope will still be very real, according to Shawn Winnett, communications coordinator at the Australian Sports Drug Agency. "Even by 2008 the technology would be raw and could lead to disastrous health effects in offending athletes," says Winnett. According to Friedmann, these risks are only tolerable if one is treating an already life-threatening disease. "To expose healthy young athletes to those risks at the moment is foolhardy and unethical," he says.

To address the risks, countries have set up regulatory mechanisms. The US Food and Drug Administration (FDA) and the National Institute of Health (NIH), for example, have extensive oversight mechanisms for gene therapy. But such mechanisms are often limited. While the US mechanisms come into play when an institution receives federal money for genetics research, for example, they don't apply to private companies. "To their credit, nonacademic centers have voluntarily gone through the NIH oversight system because it's in everybody's best interest to do things right at the outset of a new field," says Friedmann.

Richard Pound, WADA chairman, says that the existing protocols, in all countries, are very strict and that only projects with therapeutic applications are approved for clinical trials. "Of course, the vast majority of drugs used in doping were originally designed for therapeutic usage," says Pound.

Protocols or not, the risks associated with gene therapy in its current incarnation, as well as the risks of breaking regulations, might not be enough to deter some people from setting up black market labs to provide genetic enhancement for a fee. Sweeney told USA Today in March that some athletes would be willing to spend US$100,000 for a new set of muscles and that much money is very attractive, especially to scientists in the former Soviet Union who have lost most of their research funding.

But black market labs could be built pretty much anywhere. Friedmann points out that in the 1980s people thought the Soviet Union would be the first to develop undetectable steroids but the San Francisco-based BALCO proves that Americans are just as likely to do so. "Black market labs could be any place where there's money, technology, sport pressure and a will," says Friedmann. "That doesn't exclude anybody as far as I can tell." Pound agrees and says that this kind of illicit work for personal gain seems to be a function of human nature. "We will just have to do what we can to detect the labs and get them closed," he says.

It could take anywhere from $100,000 to a million dollars to set up a black market gene therapy lab. All the general approaches are published in the scientific literature and most graduate level molecular biology students could perform the procedures. However to devise a first class, ethical clinical program would be difficult and expensive, and it would involve restrictions that would take years to satisfy. "To do it right would be difficult and very expensive," says Friedmann. "To do it wrong would be easy and cheap."

So WADA, the IOC and various national anti-doping agencies are preparing for the inevitable: when the threat of gene doping becomes a reality in international sports. In an effort to stay ahead of the quickly advancing technology, WADA added cellular and genetic forms of doping to its list of banned substances and methods last year.

Gene therapy, however, is nearly impossible to detect because it works at a cellular level to augment the body's natural cellular processes. Currently a muscle biopsy is the only viable test for genetic manipulations, and then only for genetic therapies that act directly on muscles, such as the IGF-1 treatment. "Muscle biopsies in general have been used in clinical settings," says Friedmann. "But clearly no athlete is going to do that, nor should they be pressured to do something that invasive."

WADA and the United States Anti-Doping Agency (USADA) are researching and developing new genetic approaches, such as imaging and molecular methods, to detect evidence of genetic enhancement, but Pound would like to be able to do more. "I would like to make genetic manipulation for performance enhancement illegal," he says, "as well as being prohibited within the rules of sport."

Legalize it?

Not everyone agrees with Pound, however. Some want to see gene therapy become a useful and legitimate training tool for athletes.

Miah, the author of Genetically Modified Athletes, says that the IOC can't treat genetic modification as it does other forms of doping. "It's not sufficient simply to prohibit this technology in sport," says Miah, "and hope that will be the end of the issue." Given the threat of black market labs and the lack of a valid method of detection, Miah says that prohibition isn't the best option. "Increasingly, genetic modification will be seen as a valuable aspect of our society," says Miah, "promoting health and benefiting humanity."

Miah points out that genetic modification is just one more tool at athletes' disposal, no different than an altitude chamber that increases the concentration of their red blood cells to improve their endurance. He says the criteria for distinguishing between fair and unfair technologies haven't been addressed by international sport bodies since the beginning of the anti-doping movement 40 years ago.

Some argue that genetic manipulation undermines the anti-doping position that doping creates an inequality amongst competitors. There are natural variations in genes among people and allowing athletes access to gene therapy could actually level the inherently uneven playing field. This argument, however, rests on there being equal access to gene therapy. Even if international sports authorities agreed that gene therapy is a valid treatment and training option for athletes, the therapies, as with other medical treatments, would be under the jurisdictions of individual countries. And access to medical treatment is rarely fair and equitable. "This unfairness will be replicated in genetic delivery and gene therapy settings," says Friedmann. "The distribution of the therapies will be inequitable."

Some gene therapy, however, will almost certainly be accepted. Gene therapy will likely soon be a legitimate treatment option for a variety of injuries such as muscle, tendon and nerve damage—all of which afflict athletes—and it would be unfair to deprive athletes of effective therapies. So if WADA persists in banning genetic enhancement, it will have to develop a list of tests and regulations to delineate between treatment and enhancement, just as it did with banned drugs. Friedmann expects that WADA will make some of the genetic technology available to athletes through therapeutic exemptions. "But when athletes take advantage of these kinds of therapies," he says, "it should be done openly and in full view of the regulatory bodies in sport."

But while Friedmann thinks that it's inevitable that genetic therapies will be incorporated into international sports, he worries about their effect on the nature of sport. He says that instead of a feat of athleticism being the result of skill, training and dedication, in the future people will wonder if it's a simple product of bioengineering. "It's a threat to sport as we know it," he says.

Miah disagrees, and says that in some ways genetic enhancement is actually consistent with the nature of sport. "Elite sport is premised on performance enhancement," he says. "Sport is a technology and genetic modification is consistent with its most basic values."

Love the last quote....."genetic modification is consisitent with its most basic values"?! WTF?!

[Jean-Paul]

Good lord! My first thought is that I am not really surprised, but the implications are scary. Not just because of what it does to athletics, but its such a Pandora's box for us to mess with our own genitics like this. If you change someone at the genetic level, doesn't that also change their genetics if they breed? And athletes aren't going to be the only ones wanting to afford such treatments.

Some of the possibilities are cool though... What if they discover a method for turning off the gene that controls how we age? I don't know that I would want to turn myself into some kind of mutant athlete, but if I could extend my lifespan by 100 years or more that would be pretty cool. Imagine not having to follow the typical formula of getting out of highschool, going straight to college just so you can go straight into a job where you have to work until you can retire so you have a little free time and some money while you wait to die. Instead you can change careers every 20 years and have a lot more time to travel.

[russ]

If you change someone at the genetic level, doesn't that also change their genetics if they breed?

I don't know much about the details of gene therapies, but I think that this type of therapy attempts to insert the new gene into specific cell lines. I doubt that a gene targeted towards muscle growth would find it's way into reproductive cells. I could be wrong on this one, though.

What if they discover a method for turning off the gene that controls how we age?

If you can pick out the biotech company that develops that particular technology and buy some stock early on, you'll never need to work again regardless of how long you live [img]tongue.gif[/img]