May 31, 2002, Friday London Edition 2
Gene doping threatens to Transform Sport: In the Final Part of our Series, Geoff Dyer and David Firn Examine the Dangers to Sport from Medical Advances
By GEOFF DYER and DAVID FIRN
In academic circles, they are known as the "Schwarzenegger mice", laboratory animals whose bodies have expanded rapidly after the injection of a gene that causes muscles to grow.
The mice are the first stage in a medical breakthrough of enormous potential, the development of treatments that coax the bodies of seriously ill patients with degenerating diseases to recreate the damaged tissue. In the sporting world, however, these bionic mice present a much darker threat. Gene therapy, the transfer of different genes into the bodies of patients, could also be used to improve athletic performance substantially. And it could be undetectable.
"If it does take off, sport as we know it will disappear," says Dick Pound, president of the World Anti-Doping Agency (Wada), a body set up by the International Olympic Committee after a doping scandal in cycling four years ago. If gene therapy were used widely, some sports could be reduced to a manufactured spectacle of freakish stunt men rather than a genuine contest of equals.
Or in 20 years athletics could become more like motor racing, where it is the engine and technical knowledge of the team as well as the driver's ability that wins grands prix.
Of such a scenario Mr Pound warns: "We might as well all play video games. Parents will not let their children go into sports."
Scientists more skilled
Gene therapy is one of the technologies at the forefront of the rapidly expanding field of genetic engineering.
By injecting synthetic genes, which make the proteins that are the basis of many medical treatments, researchers hope to uncover cures for diseases stretching from cancer to haemophilia. Despite a public relations disaster two years ago when a patient died in clinical trials and many experiments had to be halted, scientists in the field are growing more optimistic.
They have become more skilled at using viruses to direct the genes into cells without being rejected by the body's immune system. A number of trials involving human beings are now under way. Within a few years, treatments for some diseases could be on the market.
Yet while the treatments are still in the research labs, the potential uses in sport of gene therapy have long been apparent.
At the 1964 Winter Olympics in Innsbruck, Eero Maentyranta of Finland won two gold medals in cross-country skiing.
It later emerged he had a genetic mutation that increased the number of red blood cells in his body. As they are the cells that transfer oxygen to the rest of the body, his capacity for aerobic exercise was much higher. The human body creates erythropoetin, known as Epo, which regulates the creation of red blood cells. But Maentyranta's genes lacked a switch to turn off Epo production.
A synthetic version of Epo has revolutionised the treatment of anaemia, but it has also been abused by a number of sportsmen to boost their stamina, notoriously in the 1998 Tour de France when one team was thrown out of the race and two top cyclists admitted taking the drug. Now researchers are working on a gene therapy treatment, which would deliver the Epo gene into patients' cells - in effect recreating Maentyranta's genetic make-up. As a result, patients would not need regular injections of Epo.
The other most interesting area for athletes is the genes that affect muscle growth. Geoffrey Goldspink, a scientist from the Royal Free and University College Medical School in London, is developing one treatment for muscular dystrophy, a fatal wasting disease. It uses a gene called MGF - Mechano-growth factor - a naturally occurring hormone produced after exercise that stimulates muscle production. MGF falls as we age, which is one reason why we lose muscle mass as we get older, Professor Goldspink says. A treatment to build up muscles would allow people to remain independent for much longer.
"We can put this gene into a mouse's muscle and increase its mass 20 per cent in two weeks," Professor Goldspink says. Full-scale trials in humans could begin in under two years.
Lee Sweeney, a leading US researcher in the field of IGF-1, another muscle-building hormone, has produced similar results on laboratory mice. He believes the gene insertion technique could produce an equally impressive effect in humans.
"For athletes there would be the additional benefits of a greater response to training; the muscles would heal rapidly following injury; and the strength and speed would be preserved as the person aged," says Professor Sweeney of the University of Pennsylvania.
But Werner Franke, a molecular biologist, who played a leading role in uncovering East Germany's systematic use of anabolic steroids in the 1960s and 1970s, is sceptical about the threat posed by gene doping.
"I think it's barking up the wrong tree," he says. Doctors would not only need to be able to turn the gene on in specific muscles to have any effect, they would have to turn it off again to avoid detection. Professor Franke says the IOC is exaggerating the threat of gene doping to win credibility after failing to crack down on conventional doping in the past. "The IOC failed to act in the past and has not been willing to admit it," he says.
"Gene doping is a potential issue, but I see extreme difficulty in the
fine-tuning," he says. "Why use the Epo gene when the (safety of using) the
protein is so well understood? It would be so expensive and so much more
hazardous."
But Professor Goldspink says it is inevitable these new therapies will be used by athletes. He has been approached by Kenyan athletes worried they will lose their dominance in long-distance running as their government would not be able to afford the gene technology.
"Once they are available, they will be obtained and misused (by athletes). There's no doubt about that, and it will make the Olympic Games meaningless," he says. The Olympics would become the "Growth Hormone Games".
Risk of cancer
Gene therapy will present huge risks for athletes, however.
Too much Epo can cause the blood to thicken, which increases the risk of heart seizure or strokes. Families with the same genetic mutation as Maentyranta often have a record of heart problems, researchers say.
Muscle producing hormones such as IGF-1 increase the risk of cancer and heart disease. And even then, the impact on the athlete is still unknown.
"Maybe with growth hormone the muscles would start to tear. There is so much that we do not know," says Theodore Friedmann, director of gene therapy at the University of California at San Diego. "Any athlete tempted to put himself in the hands of a doctor doing gene therapy would be putting himself in considerable danger."
The situation is even more difficult for the sports authorities because many scientists believe it could be near impossible to detect gene therapy in athletes.
"It is going to be very tough," says Joseph Glorioso, an academic at the University of Pittsburgh. "To really prove the existence of the protein, you need to do a biopsy, which is unwieldy to say the least and an unreasonable thing to do to athletes."
There is some potential that imaging technology can be developed, whichwould allow drug-testers to analyse the molecules. If the scanners allowed scientists to observe the way that the synthetic gene reacted with the target cells, this would be of great interest to researchers and to regulators.
However, this type of scanning might involve the introduction of the sort of contrast liquid into the body of the athlete that is used to detect tumours or heart disease, which can be unpleasant.
"Sooner or later, you are going to have to put something into the body of the athlete to detect if there is molecular activity," says Dr Friedmann. "No sensible athlete would allow this to happen, nor would a trainer let it happen." But Professor Goldspink says the task of detecting the genes is difficult but not impossible. There are tests that can spot the subtle differences in the proteins that are made as a result of gene doping, as the proteins produced after gene therapy are different from the "natural" versions.
Gene doping, however, would be much easier to detect if biotechnology companies incorporated so-called marker genes into the treatments. "But that inevitably makes the treatment less effective, so there is an ethical problem," he says.
Sports administrators are trying to raise the issue of gene therapy before it becomes reality. Wada organised a conference this year to discuss possible abuse in sports and detection methods. Scientists, meanwhile, have already warned that a "black market" could develop for their treatments.
Wada's Mr Pound says: "The Olympic movement has let the drugs problem get away from them. They are now trying to get the genie back in the bottle."
He says he is "sanguine" about the prospects of having good detection methods by the time gene therapy becomes more widely available. "With genetics we are trying to get ahead of the curve." Previous articles in the series were published on May 29 and May 30
Copyright 2002 The Financial Times Limited / Financial Times (London)