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Researchers cite dangers of gene doping in sports

Dr. Jim Wilson never intended to create supermonkeys.

A pioneer in genetic engineering, he was experimenting with a way to insert single genes into muscle cells, a technique that could eventually be used to treat a variety of genetic illnesses. He chose a gene that boosts levels of erythropoietin, or EPO, a key hormone in the production of oxygen-toting red blood cells and a convenient marker to measure the success of his experiment.

But EPO has long had another claim to fame. Its synthetic version, created in the 1980s to treat anemia, is one of the most notorious performance-enhancing drugs in competitive sports, able to increase endurance by raising the oxygen supply to muscles.

In less than two weeks, many of Wilson's rhesus monkeys had red-cell counts greater than those of world-class runners who train at high altitude. By three weeks, they had a higher concentration of red cells than even the worst EPO abusers in sports.

As the sports world vainly struggles against the epidemic of illegal drugs, science has already opened the door to the next frontier in fraud -- gene doping. By introducing specific genes, the experimental technology has created bigger muscles, faster metabolism and greater endurance in laboratory animals. Hidden in cells, gene enhancements in humans would be much harder to detect than drugs.

"We know that gene therapy at some point will be abused," said Olivier Rabin, the director of science for the Montreal-based World Anti-Doping Agency.

There is no evidence that any athlete has tried genetic alteration, but the agency added it last year to the international list of "banned methods" and has begun funding research to detect gene abuse. The temptations for athletes are high. But they are not without risks. For example, all eight monkeys in Wilson's experiment are dead.

Wilson, a boyish-looking professor of medicine at the University of Pennsylvania, knows the highs and lows of gene therapy, a field barely three decades old.

He led one of the earliest trials in humans -- an effort to introduce genes to cure cystic fibrosis. But in 1999, he found himself at the center of gene therapy's biggest disaster. Jesse Gelsinger, an 18-year-old from Tucson, with a rare liver disorder, enrolled in one of Wilson's clinical trials. He received a genetic injection, which his body rejected. Four days later he was dead.

The Food and Drug Administration, which ruled that Wilson should have stopped the experiment sooner, moved to bar him from leading human trials.

Despite the setback, Wilson and other scientists kept pushing ahead. There have been nearly 1,000 gene therapy clinical trials worldwide, and the field remains one of medicine's best hopes in the fight against disorders such as diabetes and Parkinson's disease.

The problem is that the interactions among genes are still poorly understood and the therapeutic genes do not always land where scientists intend.

In humans, success has been limited and sobering. The most-cited example is the treatment of a fatal immune disorder known as X-linked SCID -- or "bubble boy disease" -- in 10 children in France. Eight recovered. Two developed leukemia after the new gene landed in a dangerous spot.

It could be decades before viable therapies are on the market. Most clinical trials are conducted on terminally ill patients seeking a last resort.

Despite the risks, it didn't take long for sports officials to recognize the potential for athletes to abuse genetic technology. "We know that some athletes are willing to take very high risks to enhance their performance," Rabin said.

If the athletes had seen Jim Wilson's monkeys, perhaps they would think twice.

In four of the monkeys, the red cell counts began to reach dangerous levels within a month, thickening their blood, and increasing their risk of stroke. The animal handlers had to insert needles in the monkeys' forearms -- twice a month, on average -- to thin their blood.

In the other four monkeys, EPO levels began to fall sharply. Their bodies had identified the EPO produced in the muscle cells as a foreign invader and mounted an immune response. They also became severely anemic. Wilson had no choice but to put them to sleep.

The other four monkeys were kept alive for more than a year to monitor their EPO production. Then, they also were euthanized.

"It's hard for me to believe," Wilson said, "that [any athlete] would try to do this."

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