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The Honolulu Advertiser
Updated at 11:26 a.m., Tuesday, May 13, 2008

Report: Gene doping is next frontier of performance enhancers

By Sam Mellinger
McClatchy Newspapers

Scientists have seen the future of sport. It involves mice that can lift three times the average, humans that can run 90-minute marathons, and ligament tears that can be fixed by injection.

It is genetic engineering, therapy and doping, and it is the arrival of the bionic athlete. At the extreme, this is either the advancement or end of the human race. At the minimum, it is the unavoidable change to the way our sports—baseball, football, the Olympics, you name it—are played.

They used to talk about this in whispered tones, with only the occasional mention in mainstream media. Five years ago, the experts said gene doping wouldn't be a concern for another five years. More and more, that sci-fi, futuristic threat is now.

"The upcoming Olympics," says Ron Evans, a genetics professor at the Salk Institute, "it's probable that right now, someone is training on this."

Evans knows. He led a team of geneticists who created "the marathon mouse," a rodent that ran twice as long as normal mice with one-third of the weight gain.

The goal of Evans' work is to cure obesity, diabetes, certain kinds of heart disease, and all sorts of noble endeavors. But you know who calls him? Athletes. Coaches. Even a horse trainer.

A couple of snapshots:

A German track coach charged with supplying steroids to underage athletes is proven in court to have the knowledge and desire to purchase Repoxygen, a substance that activates a gene that stimulates the body's production of red blood cells. One cell biologist refers to this as the "crossing of the Rubicon" into the world of gene doping.

China holds science fairs in which it shows off rabbits with human ears, and a mutant fish that matures into adulthood in half the time, setting off alarms around the globe about what else that country may be up to.

This is not the apocalypse of life as we know it. Genetic engineering's base is in saving lives, which it has done already. Children suffering severe anemia have already benefited from still-risky experimental treatments that injected genes to boost red blood-cell production.

But this could be the apocalypse of sports as we know it. The abuse of this technology may forever change our games. This is real, experts say. It's happening soon, if not already.

The competition may be drifting to labs in a way that could make BALCO look quaint. Gene doping has the potential to have much more impact on sports than steroids or HGH ever did .

"Absolutely," says Gary Green, a UCLA physician who advises Major League Baseball on its drug policy. "It could really redefine everything we think about sports. You could end up with 10 different competitions, the genetically natural and the genetically unnatural. It's a really dangerous thing."

Your local grocery store sells the benefits of gene therapy. Those greenhouse tomatoes, the ones that are smooth and plump and beautifully red even out of season? Yeah, they've been genetically altered.

The world of genetic engineering creates possibilities for all sorts of medical miracles. There are between 250,000 and 300,000 ACL injuries per year in America—the vast majority away from professional sports—and they may soon be treated with an injection that would heal the ligament. No more surgery.

Researchers at Baylor used genetic modification to boost the size of pigs by 20 percent while cutting down on fat and avoiding the debilitating side effects produced by more traditional treatments.

It's not a huge leap to see the potential gold mine here for athletes.

"Whether it is promoting an endurance-enhancing gene or increasing muscle mass," says Andy Miah, a Scottish doctor and expert in bioethics. "There are many applications, but no direct ways to test for it."

To get an idea, consider the case of Eero Mantyranta, a three-time Olympic gold medalist for Finland in cross-country skiing in the 1960s.

He was accused of blood doping—even back then—but was proven to have a natural genetic mutation that gave him more red blood cells than the average person. More cells to carry oxygen from the lungs means more aerobic stamina.

Mantyranta's case illustrates the difficulty of catching dopers, because some of these mutations can happen naturally. They can also happen through genetic alteration, giving athletes superhuman physical ability.

"You take a normal human," says Theodore Friedmann, a board member for the World Anti-Doping Agency health medicine research committee, "and you make him better than normal."

If confined to natural training, elite athletes are said to be now using 99 percent of their natural physical capacity, compared to just 75 percent in 1896, the year of the first modern Olympics . Given those parameters, academics say there would be no new world records after the year 2060.

But that's in a world with no genetic engineering. Scientists think a series of gene-doping breakthroughs could boost endurance by up to 10 percent and, according to one study, allow a runner to complete a marathon in 90 minutes—more than a half-hour faster than the current world record.

Consider that your favorite basketball and football players could enhance their genes to become faster, stronger, even taller, avoid the natural slowing down that comes with age—and do it with virtually no risk of being caught by a drug test.

LeBron James could be dunking into his 50s, Josh Beckett dropping nasty curveballs 20 years from now, and Brett Favre making broadcasters coo in the year 2025.

Scott Rodeo is an orthopedic surgeon at the Hospital for Special Surgery in New York. His work centers on using gene therapy to treat the recovery of rotator cuff tears. His team has completed work on sheep, but if it goes where they hope, this is literally life-changing stuff for baseball pitchers everywhere.

"The healing between tendon and bone is a slow process," Rodeo says. "What we're doing, this could potentially hasten recovery time. You could certainly diminish the failure rates, which are distinct."

There is an unavoidable ethics question here. It's the kind of thing that physicians and philosophers could spend days debating, with no consensus.

What if doctors say your child will grow to be 4 feet tall, but a genetic alteration could make your kid 5-2? Wouldn't you take it? So how long before someone wants their 6-2 son to be 6-8 and play college ball?

Molecular genetic engineering holds the most promise in curing muscular dystrophy in children. So how long before those same effects are used by an athlete to accomplish what otherwise wouldn't be possible?

We utilize all kinds of enhancement already, from pills that make us feel better to plastic surgery that makes us look better. Genetic alteration may provide the same benefits, only without the drugs or risk of surgery.

"If you're a philosopher," Friedmann says, "you might ask, `If we accept it through pills, why don't we accept it through genes?' And the answer isn't absolutely clear to me."

In the sporting world, there are plenty of examples of dependence on engineering: race cars, golf clubs, even baseball bats. Maybe it shouldn't be a surprise that someday—today? — our athletes will be engineered, too.

The effects here go way past sports, straight into everyday life. Should parents be able to choose the sex of their baby? What about hair color? Eyes? Physical attributes like height and build?

Medical researchers have come to expect that their advancements, aimed at treating disease, will eventually be used for less-than-noble purposes. After all, AIDS patients sometimes sell their prescription HGH to bodybuilders.

But sports leagues and organizations are scrambling to come up with answers to how they can deal with a problem that is potentially more pervasive and less detectable than anything we've seen involving steroids and HGH.

"We're going to have to start looking at patterns, rather than just what's there at this present time," says John Lombardo, a 30-year veteran of sports medicine and the NFL's advisor on performance-enhancing drugs. "You look at what somebody's pattern or profile does over years, then use that as a mechanism. Not just a positive test, but be able to say, `Well, this is altered and this doesn't happen naturally.' "

Nine Paris boys were diagnosed with the same fatal disease as the Texas Bubble Boy. Beginning in 1999, doctors experimented and gave each boy transplants of his own bone marrow cells corrected by a gene transfer.

All immediate indications were positive. After about three years, one had developed a leukemia-like disease. Three months after that, another. Both boys died, sending emergency halts to other gene therapy projects around the world.

So it doesn't take Friedmann long to answer what the dangers are that we're working with.

"Death," he says. "Death is a danger. You don't play with these methods."

This is a dangerous spot we're in right now, where there's enough knowledge to mess with genes but not enough history to know what the effects will be. Experimentation right now could be fatal.

They say the technology is so immature that the only certainty here is that something will go wrong. Deaths are the price of progress when trying to treat fatal disease, but hardly justified when trying to improve athletic performance.

One experiment involved altering the genes of monkeys to boost their red blood cells, which allowed them to test off the charts in endurance tests. Unexpectedly, and without warning, the floor fell out of monkeys' blood production and they eventually died of anemia.

There is no "off switch" in much of what these gene alterations do. Which is why one scientist warned athletes to only genetically enhance the muscles they don't really want, so that the flesh could be cut out if it grows too big or too fast or both.

In time, genetic engineering may very well be safer than steroid or HGH use. But that time is not now, not yet.

"I think if athletes really paid attention to what it means to change a gene," Lombardo says, "they'd be very hesitant to do it. At least the state of the art right now. Most of the studies have been done in medical conditions, and most of them haven't been real successful."

The future of gene engineering is the future of sports, and vice versa. As Rodeo says, "you're talking about the next frontier of doping."

There is no way of knowing just where this is going, but already there are people trying to figure out how we'll deal with it all once it's here. Since there would be no drug to test for, some want in-depth DNA and gene readings done early on athletes to establish known baselines.

There are calls for strict governmental oversight, medical tags on gene alterations that would show up in tests, or just regulation—not prohibition.

Others say forget that, let's create two divisions: the natural and the enhanced. Kind of like in bodybuilding.

"Athletes are already posthuman cyborgs and we celebrate this," says Miah, the Scottish doctor. "It is likely that greater use of this technology will seep into other aspects of culture, as we begin to embrace more and more enhancements.

"Sports might soon become peculiar for resisting such developments and, in the meantime, will be placing athletes at greater risk by forcing them to enhance behind closed doors."

Miah has studied the trend of performance enhancers in sports and says one of the favorite lines of leagues and sports organizations is to acknowledge a pending threat, but say it's still down the road.

That's essentially what Green and Lombardo—the doctors working with MLB and the NFL, respectively—said in separate interviews for this story.

Evans and other experts say the future is closer to now, if it hasn't already arrived. Evans has been approached too many times by too many people in sports to think it isn't possible that a gene-altering version of BALCO is up and operating somewhere, working to unleash a new generation of superior athletes.

Parents, coaches and athletes themselves want to know as much as they can about the process and the benefits and the risks. Knowing that gene alteration is still—at best—in its adolescence and potentially fatal doesn't seem to scare anyone.

After a recent speech, Evans was approached by a college basketball player he didn't want to identify. These weren't surface, just-to-understand-better questions, either. And this athlete is not alone in his curiosity and willingness.

"They're not embarrassed by asking," Evans says. "If they think someone's cheating, and they have to race against that person, that's a decision they have to make. And it's not an obvious decision for athletes.

"Look, it's definitely early. But the games are on. Athletes are emerging in their awareness.

HOW GENE DOPING WORKS

Experts say gene doping is the next great threat to professional sports, and that the impact could far outweigh what we've seen with steroids and HGH. Here are three ways doctors say athletes could abuse the technology:

Injection of a gene to boost production of the hormone erythropoietin, known as EPO. This increases red blood cell production, which increases aerobic capacity. The procedure is meant for patients who suffer severe anemia, but could also benefit healthy athletes—and is why some predict a 90-minute marathon.

Insertion of muscle-building genes into muscle cells. This is the method designed for those with conditions like muscular dystrophy but, again, can be abused by healthy athletes to target specific muscles they want to enhance. Like a sprinter's legs, a linebacker's chest or a pitcher's arm.

Insertion of genes to grow new blood vessels. This treatment is mostly for elderly people with arterial disease. The new gene would boost production of new vessels, which would provide more oxygen and other nutrients to the tissues of athletes. This is the part that would give muscles, lungs and the heart more stamina, both in the short and long term.