LONDON There have been "marathon mice", "Schwarzenegger mice" and dogs whose wasted muscles were repaired with injected substances that switch off key genes. It may not be long before we get the first genetically modified athlete.
Some fear the use of gene therapy to improve athleticism is already a reality. But since sports authorities' drug testing methods still lack the sophistication needed to pick up gene doping, its status remains unclear.
What is certain, from scientific studies and from surveys of elite sports people, is that it is technically feasible to use genetic modification to improve sporting performance, and that some athletes are prepared to risk their lives if they could be guaranteed to win gold medals.
Officially, UK Anti-Doping, the body which oversees the control of performance enhancing drugs in Britain, says genetic manipulation as a form of performance enhancement "is currently a theoretical rather than a proven issue".
But Andy Parkinson, UKAD's chief executive said: "I wouldn't be surprised if someone out there is trying to do it, and I think that's very worrying."
The World Anti-Doping Agency (WADA) says it is ploughing "significant" money and resources into research into finding ways to detect genetic enhancement of athletes.
NEW GENETIC MAKE-UP
Gene doping - in which DNA is introduced into the body using an inactivated virus or by other means - could alter a person's genetic make-up and improve athletic performance by increasing muscle growth, blood production, endurance, oxygen dispersal or pain perception.
Since it cannot be detected, no one really knows whether athletes are using it or not.
Chris Cooper, a professor of sports and exercise science at Essex University and author of a book called "Run, Swim, Throw, Cheat" thinks it is "hugely unlikely anyone is gene doping" and says the focus should be on people who use well-known performance enhancers like anabolic steroids and blood doping.
However, emails that surfaced during a trial of a German track and field coach Thomas Springstein in 2006 showed that people behind some athletes were at least thinking about genetic modification as a way forward.
Scientists who lead the field in developing gene therapy techniques in laboratory animals have also reported being inundated with enquiries from sports people keen to know more.
"There are animal models which show efficacy and the possibility of this being technically feasible for an athlete to do," said Andy Miah, a bioethicist and director of the Creative Futures Institute at the University of the West of Scotland.
The drug mentioned in the 2006 German court case was Repoxygen - a gene therapy developed by the British biotech Oxford Biomedica (OXB.L) as a treatment for severe anaemia.
The company has since pulled the plug on developing the product as it seemed unlikely to be profitable as a medicine.
Yet an email written by coach Springstein to a Dutch doctor suggested some in the sports world were already keen.
"New Repoxygen is hard to get," Springstein wrote. "Please give me new instructions soon so that I can order the product before Christmas."
Repoxygen is based on a direct injection of an inactivated virus carrying the gene for EPO, or erythropoietin, a hormone beloved by athletic dopers seeking to artificially boost their red blood cells and aerobic capacity.
Repoxygen is just one of a number of scientific developments that caught the eye of potential sports dopers.
Lee Sweeney, a professor at the University of Pennsylvania in the United States, has pioneered research into gene transfer technology and developed various super-sporty lab mice to test its potential.
In 2007, while researching possible ways to restore muscle growth in patients with muscular dystrophy, Sweeney and his colleagues created mice in a lab who continued to have enormous muscles and significant strength into old age.
The super mice were created by injecting normal mice with a virus containing the gene for insulin growth factor 1, or IGF-1, a protein that interacts with cells on the outside of muscle fibres and makes them grow.
They were nicknamed "Schwarzenegger mice" after the American bodybuilder and film star-turned politician. Scientists later reported success in treating dogs with wasted muscles with the same therapy.
These experiments followed hot on the heels of "marathon mice", which hit the headlines in 2004 after researchers genetically engineered the lab animals by tweaking a gene called PPAR-delta.
The scientists found the genetically engineered mice could run twice as far as normal mice, and they stayed lean even when they were fed on a high-fat diet.
"So there's a technical precedent for this (performance enhancing genetic modification), but it's still uncertain quite how it would effect humans," said bioethicist Miah.
"And of course there are uncertainties about how those animals are effected in other ways - does it effect their fertility? Their longevity?"
In his book, Cooper relates the tale of an experiment conducted by Jim Wilson, one of Sweeney's colleagues at the University of Pennsylvania, who tested EPO gene therapy in macaque monkeys.
It initially worked as expected, increasing oxygen transport in the monkeys' blood. But the high concentrations of EPO soon produced so many red blood cells that the blood became like sludge and needed to be thinned at regular intervals.
Then the monkeys' EPO levels suddenly plummeted, leading to severe anaemia and forcing the scientists to end the experiment and euthanise the animals.
"These studies show that of all the doping techniques we are talking about ... gene doping is currently by far the most technically difficult and risky to attempt," Cooper writes.
GOLD MEDALS - TO DIE FOR?
Yet while such potentially life-threatening and unknown side effects are a major concern for people seeking to develop medicines to treat sick patients, would-be genetically modified Olympians may take a different view.
Experts said that to evaluate whether something as risky and unproven as gene doping is being tried in sports, it's important to see just how far athletes might go in pursuit of gold medals.
A frequently-cited survey in the world of sport gives a bleak picture. In it, Chicago-based Bob Goldman, a doctor and founder of the U.S. National Academy of Sports Medicine, asked elite athletes in the 1980s whether they would take an enhancement which guaranteed them gold medals but would also kill them within five years. More than half said yes.
"I was shocked to see that out of 198 world-class athletes, 52 percent would be willing to give up their life for five years of an undefeated run of wins," Goldman told Reuters during the 2004 Olympic Games in Athens.
He repeated the survey every two years for the next decade and the results were always the same - around half of the athletes polled were ready to die for gold. "Some of the athletes are only 16-years-old," Goldman said. "To be willing to die at 21 is a serious psychological mindset."
While no-one can be sure if genetically modified Olympians are swimming in pools or running on tracks right now, the lure of winning gold may make athletes more willing than most to take a dangerous genetic leap into the unknown.
"That's partly why the world of sport is so concerned," said Miah. "They know that if athletes had something that would give them the opportunity to win medals, but would kill them 5 years later, many of them would take it.
"This is a community of high risk takers."
(Editing by Michael Holden)
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