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Originally published October 9, 2005 at 12:00 AM | Page modified October 9, 2005 at 11:39 PM

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Experts predict gene doping is next temptation for athletes

Gene doping will one day allow athletes to push beyond the boundaries of human ability, never mind the rules. And that day is almost here.

Seattle Times staff reporter

Athletes are human guinea pigs, suckers for experiments, all too willing to be poked, prodded and pushed to live up to the credo of a champion — those who take the human body beyond its limits.

And yet we wonder why they sometimes push further than rules allow.

We wonder why they ate ground horse hooves in ancient Greece, why they experiment with everything from coffee to cocaine, why they carry Whizzinators through airports to pass their drug tests.

We ask ourselves: Why can't sports be natural?

Athletes are posed a different question.

How do you want your enhancements: cream or clear?

What they're saying

The think tank: Peter Roby, director for the Center for the Study of Sport in Society.

The U.S. Olympian (turned doctor): Jennifer Devine, Olympic rower and UW graduate.

The insider: This Olympic coach wishes to remain anonymous.

The grieving family: They believe their son killed himself after he stopped taking steroids.

The face: Dr. Gary Wadler, a leading expert whose phone rings constantly.

The educator (former steroids user): Greg Schwab, now principal at Mountlake Terrace H.S.

The Eastern Bloc athlete (turned doctor): Dr. Anna Ragaz swam for Czechoslovakia.

The gene therapist:
Dr. Theodore Friedmann, a leading expert in the field.

The author: Will Carroll wrote "The Juice: The Real Story of Baseball's Drug Problems."

What's clear at this point is sports is entering its most advanced age of enhanced performance. And someday soon steroids will look as outdated as the Model T.

Athletes have changed everything else in order to enhance performance. So it follows that they will eventually change their genes, choosing combinations that suit their sports, making muscles more like outfits and sports more like the science channel. "It has all the potential to make steroids innocuous," says Mike Barnes, director of education for the National Strength and Conditioning Association. "Maybe we'll have this conversation in 10 years, and we won't even mention steroids."

A handful of the 25 experts polled for this series say they believe someone in the athletic world has already tried gene-doping techniques. All 25 say someone in sports eventually will.

Some say gene therapy will be abused by the 2008 Olympics. Others say by 2012.

They know this much: Handlers for athletes have already approached gene therapists and inquired about their methods. What's certain is the inevitability of it all — athletes pushing the human body beyond its limits, in this case, the genetic kind.

"When that becomes accessible — and it will be accessible at some point — it's going to be virtually impossible to continue to fight these drugs," says one Olympic coach, speaking on the condition of anonymity. "When that becomes available, the game is lost."

Welcome to the future of performance-enhancing drugs. Welcome to the next frontier.

Good work, wrong hands

History has taught us that Pandora's box will always open, that advances in medicine inevitably lead to abuse and manipulation. And that's how Dr. Theodore Friedmann became a roundabout figure of importance in the sports world.

Friedmann is an expert on gene therapy, director of the program at UC-San Diego and an advisor to the World Anti-Doping Agency. He has studied gene therapy for 30 years, adding and subtracting genes to try cure Parkinson's Disease, diabetes, arthritis and muscular dystrophy, among others.

But good work often falls into the wrong hands. Especially when technique moves quickly and temptation trumps questions of ethics and unknowns.

"It's very tempting for people who don't appreciate how difficult it is to save a life," Friedmann says.

In terms of genetic limits, athletes are no different than Monday-morning quarterbacks, except that they are typically more genetically endowed. They can only run so fast and jump so high and throw so hard, even with the help of anabolic steroids, then their limits kick in. Limits that can only be changed by altering DNA structure.

Gene doping works by transferring genes directly into human cells to blend into an athlete's DNA. Techniques also can stimulate or block natural chemicals with the same results: increased strength, increased endurance or enhanced muscle growth.

The most common technique for introducing new genes is using harmless viruses.

"They are like moving vans for cargo," Friedmann says.

In this case, the cargo is the gene. The virus is injected, with the gene, directly into tissue, effectively loading athletes with the genes they want, says Kyle Serikawa, a lab manager at the University of Washington who wrote a chapter on genetic doping for the book, "The Juice: The Real Story of Baseball's Drug Problems."

Serikawa says that when tissues are dissected and examined under a microscope, the effects of gene therapy on muscles can be seen in one to two months. The problem? Those studies didn't say anything about how long it took for physical improvement. As for studies of gene doping in athletes, there are none.

The procedure, according to doctors, is so simple and widespread that a trained college biology student could perform gene transfers. Or an athletic trainer.

"It's not something that's very hard to do, but it's expensive," says Serikawa. "It would cost about $1 million, and it would take a fair amount of equipment. But the technology is very straightforward. If you were in a fully equipped lab, it wouldn't be that difficult."

Endless possibilities

The technology for gene therapy is already here, a tale of mice and men.

In 1997, researchers at Johns Hopkins discovered that if they removed the myostatin gene in mice (the myostatin gene regulates muscle growth), they were twice as muscular as their siblings.

Researchers called these "Schwarzenegger Mice," and they point to research that indicates that blocking myostatin activity may lead to increased muscle mass in humans, too.

Serikawa explains two other examples. One is the story of a German boy with a natural mutation in his myostatin gene. He could hold 6.6-pound dumbbells in his outstretched arms — at the age of 4. Another is the story of Italian cattle who lack myostatin genes — they grow big and bulky, with lots of lean meat.

Last year, cousins to the "Schwarzenegger Mice" were unveiled by researchers at the Salk Institute in San Diego. Their genes were altered to mimic exercise, which boosted endurance and prevented obesity. Researches even took these so-called "Marathon Mice" off their workouts and fed them high-fat diets.

Here's the rub: they didn't gain any weight or lose any endurance.

The possibilities are as endless as they are fascinating. Take EPO, for example, the substance a French newspaper claims cyclist Lance Armstrong tested positive for. EPO (erythropoietin) stimulates bone marrow to produce red blood cells, and the rise in cells increases the blood's ability to carry oxygen. Endurance athletes have long injected themselves with EPO, but what if scientists could locate the gene encoded for EPO production? What if they could turn that gene on and off?

"You would eliminate the need for individuals to inject themselves at all," says Dr. Gary Wadler, the leading expert in the field and a consultant to the World Anti-Doping Agency. "It would make using EPO a lot easier and harder to detect."

Friedmann says insulin growth factor (IGF-1) is another likely target. IGF-1 occurs naturally in cells as a protein that rebuilds muscles. Friedmann says that studies have shown that when rats and mice are injected with the gene for IGF-1, their bulkier muscles contract more easily.

Which leads Friedmann to another rub: IGF-1 is already on the market as a gene-therapy agent.

"One of the things that concerns me is IGF-1 being approved by the FDA for certain legitimate medical uses," Friedmann says. "Off-label uses will inevitably lead to use in people who just want to increase growth factors for muscle. Clearly, that will encourage misuse."

Indeed. Type "myostatin" or "IGF-1" into a common Internet search engine, and you'll yield more bodybuilding sites than medical ones.

Why wouldn't they?

Athletes enhancing their performance are nothing new, just another example of science's great saga, the tug-of-war between technology and temptation.

"The situation with performance-enhancing drugs is very analogous to the situation with nuclear weapons," says Dr. Harrison Pope, director of the biological psychiatry laboratory at Harvard Medical School's McLean Hospital. "There are all kinds of agreements and treaties. And you and I both know countries are going to go out and do it anyway."

Some fans go to NFL games to see hits hard enough to snap bones in half, or to boxing matches to watch fighters draw blood. It's the same principle as drivers who slow down to gauge the aftermath of a car crash — they know they might cringe but do so anyway.

The way some experts see it, the question shouldn't be why athletes abuse their bodies and the rules of sports.

"The question is almost why wouldn't an athlete be tempted to use drugs?" Pope says. "Both the general public and the medical community have tended to underestimate how powerful these drugs are and failed to understand the great advantage athletes have from taking steroids."

Adds Dr. Dan Hamner, a former world-class track athlete and physician in New York: "If people are going to expect these great performances, these falling records, they have to expect that athletes will do anything to get there."

That's why long-distance runners took caffeine in the 1880s to reduce fatigue. That's why Tom Hicks risked his life by taking a perilous mixture of egg whites and strychnine and washing both down with brandy en route to winning the 1904 Olympic marathon.

And ultimately, that's why takers are continually ahead of testers, searching for the next device to enhance performance.

"It's part of the game," the Olympic coach says. "We cannot really eliminate it. These are highly tuned machines that are designed to do things that the human body cannot. It's a risky business. A risky field.

"We're pushing the human body, and we're pushing the human spirit. And we're trying to see how far it goes."

To that, Wadler responds: "I'm sure that there's virtually nothing people have not manipulated if they thought it would enhance performance. Nothing would surprise me."

The problem, according to many experts, is the system itself, which is designed to assume the guilt of athletes, to chase them and drag them into testing.

And any athlete who is not what Dr. Charles Yesalis calls an "absolute moron" will pass the tests anyway.

"Drug use is so widespread now," says Yesalis, a doping expert from Penn State University, "I don't think your average reader has a clue. Drug testing is there to make the few remaining naïve journalists and fans think that sports are clean."

And that's the problem with gene therapy — it challenges the system at its core. What happens when sports can't test for performance enhancement? What happens when all the current testing — mostly through blood and urine samples — becomes irrelevant?

"We put so much stock in improving the testing program and having more tests, that when we lose testing as a tool, we're going to be screwed," says Will Carroll, author of "The Juice," a book that looks at baseball's drug problems.

Friedmann says that sports' governing bodies and anti-doping administrations are working with gene therapists to develop tests for the inevitable abuse of gene therapy.

"It will happen," he says. "I'm quite confident."

But there are currently none in place. Altered genes won't show up in a blood or urine test. Two methods proposed by Serikawa would require constant blood testing to monitor unusual changes in protein levels or sequencing part of an athlete's genome to compare their expected levels of gene expression to what's actually going on in their blood.

Gene doping would show up on a muscle biopsy. But Serikawa and Friedmann find that scenario unlikely because testers would have to stab a biopsy needle into an athlete's flesh in order to take a piece close to a millimeter in diameter. That would, at once, invade privacy and affect performance.

"I've earned my cynicism doing this for 29 years," Yesalis says. "Drug use in sports has been a constant epidemic since the last quarter of the 19th century. It's never stopped, despite all the PR statements from sports federation officials. It's just been there. And in many sports, like cycling or track, it's been super-sustained at high levels. We're just starting the anabolic steroid era in baseball, even though it's 10 years old.

"And we haven't even seen gene therapy yet."

Deadly consequences

That, Friedmann says, is precisely the problem. Researchers don't know — and won't know because it's illegal to conduct clinical gene-therapy trials for enhancement purposes — what altered genes will do to a healthy human body. Potential side effects are a mystery.

Friedmann points to a recent French study that included 15 children with severe immune deficiencies similar to the "Bubble Boy Syndrome." Researchers were able to insert the normal gene, and the children's immune systems were totally restored. Some of the children have lived more than six years after the one-shot treatment.

What happened next should serve as a warning to the sports world. Silent tumor genes were kicked off by the introduction of the gene, and three of the children in the study developed leukemia.

"People who use these methods will not be interested in the study," Friedmann says. "They are interested in doing it. Along the way, there will probably be some very serious and adverse events and people will die and things will go wrong probably more than they go right at first."

Those are exactly the results that worry sports' governing bodies. Results that include athletes dying in competition.

"That's what they are afraid of," the Olympic coach says. "They don't want to become a stage for gladiators. They don't want people dying in front of thousands. They're afraid that's what sports will become. But I don't think they have any idea about how we don't arrive there."

No stopping progress

Hamner, the New York physician who was once a competitive runner, is now in his mid-60s, and says he takes testosterone once a week. He says it makes him feel like he's 35 again.

He's not against taking performance-enhancing drugs under the correct medical supervision, and he points to surveys that show fans are more concerned with athletes' salaries and off-the-field conduct than they are with performance-enhancing drugs, and, soon, gene therapy.

So Hamner puts all of that together and offers a unique proposal. Two leagues. One clean. One dirty.

Is this what sports have come to?

"It sounds complicated, but it's the only way to level the playing field," Hamner says. "Or else you're going to have cheating. You always will."

Yesalis, again donning his cynic's cap, says, "That is terribly naïve. A great example to show why that would fail is amateur bodybuilding. Even when there is no money at stake, you have people who lie about their drug use for a $5 trophy."

Suckers for experiments. Pushed and poked and prodded. Here comes the next era of enhancement, and with it, the next generation of guinea pigs.

Welcome to the next frontier.

Greg Bishop: 206-464-3191 or gbishop@seattletimes.com

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