The cheat gene: Could the next step in sporting fraud come from manipulating DNA?

 

The London Olympics may turn out to be one of the cleanest in history in terms of banned substances – but behind the scenes, scientists fear the next big challenge to fair play in sport: gene doping.

Over the past decade, scientific advances in the understanding of how genes control muscle activity have alarmed experts within the World Anti-Doping Agency (Wada) who believe that using genes, rather than drugs, will be the next way illicitly to boost athletic performance without fear of detection.

Although scientists are unanimous in believing that genetically enhanced athletes did not participate in London 2012, they are almost equally unanimous in saying that there will be an attempt to misuse the technology in a future Olympics.

"Is gene doping currently being practised? We don't have any evidence that it is," says Professor Steve Harridge, an expert on muscle physiology at King's College London.

"But in the future, as gene-therapy techniques become more refined, it becomes more likely, although I think we are many years away from that," he adds.

"The attraction of gene doping is that it is much harder to detect. But there are dangers because you don't know what it is going to keep on doing. The overall control of muscles can be brutally changed by the sudden introduction of a gene," he says.

Other experts believe that gene doping will not be so easily dismissed as too difficult or risky by those who are prepared to go to physical and ethical extremes in order to win medals.

"We don't know that gene doping would work, but it's technically feasible," says Andy Miah, a sports ethicist and director of the Creative Futures Research Centre at the University of the West of Scotland.

"If you look at the investment of the Wada over the past 10 years, this is their key issue, and it has been for a decade. It's hard to argue with the view that is real in a lot of sports," Dr Miah says.

Gene doping is defined by Wada as the non-therapeutic use of genes in order to enhance athletic performance, and the Montreal-based agency, which was set up in 1999, has spearheaded a campaign to develop scientific methods of detecting its illicit use in sport.

The issue took off in 2004 following the publication of studies by Lee Sweeney of the University of Pennsylvania showing that it was possible to create genetically modified (GM) mice with enhanced genes for producing a natural stimulant called insulin-like growth factor (IGF-1) in their muscles.

The enhanced genes increased the muscle strength of the mice by 30 per cent or more, enabling them to run for faster and longer on treadmills compared with ordinary mice.

Dr Sweeney was almost immediately swamped by enquiries from athletes who wanted to get their hands on the technology. It was evident that this type of research was being seen as the next possible stage in the continual evolution of sport doping.

At the time, Dr Sweeney said that the availability of this technology for human use was not going to be anytime soon, but that the temptation for organisations in some countries with the resources and know-how might be too great to resist.

"One can imagine that with enough money you could put together a programme to genetically engineer your athletes and do it in such a way that it would be totally undetectable unless you were to remove tissue from that athlete," Dr Sweeney says.

"There would be nothing in the blood, no signature in the blood or urine to indicate that the tissues had been genetically manipulated," he says.

The GM mice in Dr Sweeney's experiment were modified as embryos and such "germ-line" gene therapy, where genes in every cell of the body are altered, is specifically banned in Britain and many other countries.

However, what concerns Wada is the possibility of adapting gene-therapy technology used in legitimate medicine to modify specific tissues of athletes, such as leg muscles, even though clinical trials on patients have proved largely ineffective and even dangerous.

A year after Dr Sweeney's research emerged, Wada held an international symposium on gene doping in Stockholm, where it became clear that this was the key new area of interest for the anti-doping community.

"Gene doping will in all likelihood soon be with us, and I would not be surprised if the first tentative steps had already been taken," Professor Theodore Friedmann of the University of California, San Diego, told the meeting.

"The genes are available and you make them. All it takes is three or four well-trained post-docs and a million or two dollars," says Professor Friedmann, the chairman of Wada's gene-doping panel and a world authority on genetic engineering.

Since Dr Sweeney's pioneering work of 2004 there have been several further studies showing that it is possible to tweak other genes involved in the metabolic pathways affecting muscle performance.

In 2006, for instance, American scientists at Dartmouth College in New Hampshire showed that it is possible to produce GM mice with a liver gene in their muscles for a substance called AMPK, which boosts concentrations of glycogen, a natural store of chemical energy. These GM mice ran three times as long as ordinary mice without suffering exhaustion.

Two years later, in 2008, scientists at the University of Pennsylvania created GM mice that could run six times farther, simply by altering a gene called interleukin-15R alpha, which shifts how energy is used in the "fast-twitch" muscle fibres.

In the same year, the Salk Institute in California demonstrated how genes and environment can interact in unexpected ways to enhance athletic performance by taking drugs that can "turbocharge" specific performance-enhancing genes.

As in many areas of society where scientific advances can be misused, the regulators are in a constant battle to find ways of detecting the abuses of those intent on breaking the rules.

The evolution of doping

Ancient Greece

The Greeks created concoctions of alcohol and ate hallucinogenic mushrooms and sesame seeds to enhance performance.

Late 19th century

Road cyclists used caffeine mixed with other chemicals, such as ether and nitroglycerine. Others used coffee spiked with cocaine and strychnine.

Cold War-era

First systematic use of anabolic steroids attributed to the Soviet weightlifting teams of the Fifties. The practice spread throughout different sports.

Seventies and Eighties

Blood doping, a process in which an athlete's own concentrated oxygen-carrying red blood cells are reinfused, becomes common.

Turn of the century

With doping as prevalent as ever, the most famous case came with the Balco scandal, which snared dozens of high-profile stars who were using a number of illegal substances.

Will Dean

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