The next step in doping (2008, Jul 27)


Sunday Focus | The next step in dopingBY LINDA ROBERTSON Imagine the Olympics of the future, perhaps the New Delhi Games of 2040. Then, as now, some athletes will cheat to win gold medals. Picture discus throwers with custom-built arms. Or swimmers with modified legs. Or marathon runners with enriched blood. Or gymnasts and basketball players with injury-proof joints. Or archers with brains designed for hyperconcentration. No longer will they rely on such primitive substances as steroids or worry about drug tests. They will be able to alter their own DNA.

Is this science fiction? It's called gene doping, and it might make its debut at the Beijing Olympics.

The science of implanting genes to boost the body's performance has been called the next frontier in illicit sports doping. Unless it already is happening.

''I predict multiple people will win in Beijing who have been gene-doped,'' said John Leonard, executive director of the American Swimming Coaches Association in Fort Lauderdale. ``It's not just experimental. It's been in use for four years.''

Other doping experts doubt the problematic technique of gene transfer has worked on any athlete. But the World Anti-Doping Agency, which banned gene doping in 2004, believes it is a threat to the integrity of sports and is trying to develop a detection test.

''We have no evidence that people have tried it successfully,'' WADA science director Olivier Rabin said. ``We've heard rumors. We investigate, but so far it's led nowhere.''

EASILY AVAILABLE

The technology, explained in numerous scientific articles, is available and relatively easy to implement, although the dangers include heart attack or cancer. Not just Olympians but pro baseball, football and basketball players and athletes in other major sports would benefit from increased strength and endurance. Throughout history, unethical athletes have shown a willingness to be guinea pigs if it meant the difference between winning and losing.

''Thousands of labs around the world with reasonably trained people in molecular biology have the capability,'' said Dr. Theodore Friedmann, a gene therapy expert at the University of California-San Diego. ``There is so much money in sports. Put a couple unscrupulous people together, and it wouldn't surprise me if an athlete attempted gene doping.''

H. Lee Sweeney is a scientist at the University of Pennsylvania researching cures for muscle-wasting diseases who used growth hormone to bulk up his ''Schwarzenegger mice'' and is now increasing muscle mass in dogs by 20 percent by inhibiting myostatin production. He has been contacted by various athletes, coaches and trainers, mostly in football, weightlifting and body building.

''The inquiries never stop,'' Sweeney said. ``They ask if they can be treated. They're ready to volunteer for any experiment. Some even say they'll pay me.''

No wonder because gene doping has potential to not only be effective but invisible. Why inject synthetic EPO to increase red blood cell production when you can inject the EPO gene itself? Athletes wouldn't have to bother with detectable drugs if their own cells could be stimulated to produce a natural stream of performance-enhancing proteins.

Gene doping is the bastardization of gene therapy, which is used to change traits in diseased people. This is how it works:

Human DNA is made up of 20,000 genes. They contain codes that tell cells how to function. To worm a gene into the body, a virus, like the one that causes colds and pink eye, is hollowed out and implanted with new genes for, say, stronger muscles or super-oxygenated blood. The ''vector virus,'' a little bag of protein with the gene inside, is then injected into target tissue, where it attaches to cells and dumps in the gene. The cells with new DNA replicate.

VARIETY OF USES

''Viruses can be engineered to express a whole variety of genes,'' said Dr. Richard Snyder, associate professor of molecular genetics and microbiology at the University of Florida and director of the Center of Excellence for Regenerative Health Biotechnology. There are genes to improve reaction time and increase alertness, although tinkering with cognitive functions is farther down the road, Snyder said.

A Harvard professor has located a gene that he hopes would prevent osteoarthritis and create sturdier joints. He has tested it on lame horses.

A simpler, cheaper but uncontrollable method would involve injecting a piece of DNA into a muscle to prod the pituitary gland to release growth hormone.

''It worked pretty well in pigs, which they grew faster so they could take them to market faster,'' Sweeney said. ``But they didn't want these pigs to live for 20 years. You can turn the gene on, but what happens if you can't turn it off?''

The first sign that gene doping wasn't just a Frankensteinian fantasy came before the 2006 Torino Olympics. E-mails found during an investigation of German track coach Thomas Springstein detail his efforts to obtain Repoxygen, developed to treat anemia, then taken off the market. It helps the body produce EPO.

In the shadowy subculture of sports doping, underground websites and black market labs advertise gene therapies for sale. WADA's Rabin posed as an athlete and ordered what was touted to be Repoxygen from a company in Southeast Asia. Tests showed it was synthetic EPO.

SUSPICIONS

In the TV documentary ''Doping in the Middle Kingdom,'' broadcast Monday on Germany's ARD network, a journalist posing as an American swimming coach was offered stem cell treatment for his athlete by a Chinese doctor for $24,000. During the segment, filmed by hidden camera inside a Chinese hospital, the doctor recommended ''four intravenous doses, 40 million stem cells, perhaps twice that, the more the better'' over two weeks.

''Quite frankly, this surpasses my worst fears,'' WADA's Patrick Diel told the filmmakers, who also interviewed a Chinese swimmer, now coaching in South Korea, who said the 1988 and 1992 Chinese swimming teams were fueled by steroids.

Fort Lauderdale's Leonard, a watchdog for swimming, has heard of alleged gene doping during his travels in China. Many in his sport are curious about the fate of the so-called ''Baby Army,'' a group of young swimmers from Hunan Province posting world-class times and the ''lost children'' from that group who are training in secrecy. He said the country, given its totalitarian government, well-funded sports school system and sophisticated sports science program, has the means, the will and the numbers to try new treatments.

''China is obsessed with athletic success, and there are huge political, economic and personal ramifications,'' Leonard said. ``In China's system, athletes aren't always able to say no.''

But China has made much-publicized bans on athletes who have tested positive and crackdowns on companies distributing doping products. Sweeney believes China wouldn't risk the embarrassment of hosting anything other than the ''Clean Games'' it has promised. The International Olympic Committee will conduct 4,500 tests for banned substances, a 25 percent increase over 2004 and a 90 percent over 2000.

However, Sweeney also believes an ambitious centralized government may not be able to resist the temptations of gene doping.

''If the East German sports machine was still in place, they could perfect gene doping,'' he said. ``Who would have dreamed up BALCO? Athletes are crazy and will try anything if they have someone to help them.''

But he doesn't believe gene doping would work now, at least not without serious health consequences. Most of the hundreds of gene therapy trials over the past 20 years have been unsuccessful or inconclusive, with a few striking breakthroughs, such as one for treatment of childhood blindness.

''It's a difficult and controversial field,'' Friedmann said. ``If anyone proceeded on an athlete it would be malpractice. Things can and will go wrong.''

SERIOUS SIDE EFFECTS

Monkeys injected with EPO genes developed blood the consistency of sludge. Some had clots, strokes and heart attacks. In others, bone marrow shut down and they died of anemia.

The ''marathon mice'' created at the Salk Institute died young. Other animals developed huge muscles that caused tendons, ligaments and bones to snap.

''Race horses are bred for traits of speed and power, but with no trait for bone strength they shatter those spindly legs,'' Friedmann said.

In France, three boys who had gene therapy for immune deficiencies got cancer.

''We've seen several cases of leukemia where the inserted gene hit a cancer-regulating cell,'' Rabin said.

In the U.S., a boy who volunteered for a study on genetic liver disease died.

''If gene therapy worked as well on humans as it does on monkeys or dogs it would be thriving,'' Sweeney said. ``The problem is that humans have an immune reaction to the virus vectors. Gene doping would be like an organ transplant. . . . It's heavy duty.''

To deter cheaters, WADA aims to have gene doping tests ready by 2012 for the London Olympics and for major sports leagues.

At Snyder's lab in Gainesville, research funded by WADA is focused on a blood test that would distinguish between the genes a person is born with and extra, ectopically introduced genes.

Friedmann's tests would find the antibodies that react to the viruses or identify a molecular signature for genetic changes.

Friedmann and WADA know they are in a race against ingenious dopers.

By the time a method or substance gets unmasked -- such as BALCO's ''designer'' THG -- another is in vogue.

''I love the beauty of sport,'' Friedmann said. ``But when the competition is not between athletes but between their molecular biologists and the technological companies behind them, that is not pretty.''