A gene therapy that appears to bulk up muscle mass and strength in monkeys – reported today in Science Translational Medicine – will undoubtedly raise fresh concerns about the potential for gene doping in sport.

We already know that some athletes use drugs like erythropoietin to increase the amount of oxygen their blood delivers, and steroids to bulk up muscle mass.

The big advantage with gene doping is that it should be harder to detect. That’s because it’s difficult to test for a protein that the body already produces, especially when its levels naturally vary between individuals – which might explain why some people are inherently better at sports than others.

In the new study, Janaiah Kota and colleagues at Nationwide Children’s Hospital in Columbus, Ohio, used gene therapy to add extra copies of the follistatin gene into the leg muscles of monkeys. Follistatin has been previously shown in mice to block myostatin, a protein that decreases muscle mass, resulting in bulked up “mighty mice”.
Monkeys injected with the gene also seemed to bulk up, and when Kota’s team analyzed their leg muscles with a device that measures force, they found that the muscles injected with the follistatin gene were also stronger than normal muscles.

They hope the approach could eventually be used to treat the severe muscle weakness associated with neuromuscular disorders like muscular dystrophy and multiple sclerosis.

Indeed, the drugs companies Amgen and Wyeth are already experimenting with drugs called myostatin inhibitors in humans, with some promising early results.

Such studies have already prompted fears about the potential for myostatin inhibitors to be abused by athletes hoping to gain the competitive edge. If gene therapy can achieve similar outcomes in humans, such modifications will be even harder to detect.

The World Anti-Doping Authority has already prohibited the use of gene doping within their World Anti-Doping code, and while there is currently no hard evidence of athletes using gene doping to improve performance, there are strong suspicions that they will start doing so soon – unless someone figures out a reliable way of detecting it.

Experts believe it is only a matter of time before athletes manipulate their genetic material to gain an unfair advantage despite the current lack of proven cases.
A science journalist, who has published a novel on the theme, and a scientist working in the field of genetics talked to swissinfo about the likelihood and dangers of gene doping in sport.

Since the times of ancient Greece, a minority of athletes have employed a variety of potions to artificially boost their performance. More recently, amphetamines, anabolic steroids and hormones have been the drugs of choice.

The World Anti-Doping Agency (WADA) has recently turned its attention to the threat of gene doping and officially banned the practice in 2003. There have already been suspicions of some athletes using the gene therapy Repoxygen to increase their red blood cell count and thereby allow the body to absorb more oxygen.

Professor Max Gassmann of Zurich University’s Institute of Veterinary Physiology has manipulated the erythropoietin (EPO) gene of mice to produce more oxygen carrying red blood cells – a process that could eventually be transferred to humans.

Gassmann does not think gene doping has infiltrated sport at the moment but believes some people may already be testing its potential, just as beneficial gene therapy is currently undergoing clinical trials.

“I can hardly imagine that we had a gene doping cheat winning at the Beijing Olympics,” he told swissinfo. “But there has been doping throughout history and if gene doping becomes viable then you cannot stop it, because people want to win.”
Fictional leap
Author Beat Glogger has taken the theory a stage further by writing a thriller – “Run For My Life” – about genetically modified athletes. Glogger, also a science journalist, and Gassmann contributed to a Swiss sports ministry document warning about the risks of gene doping.

Scientists have already identified more than 150 genes that potentially influence performance in sports. These include genes that control muscle growth, muscle speed and the production of red blood cells.

“I take the next step into fiction by saying it is possible to manipulate the genes that control speed, power, endurance and even mental strength. These are the four key factors for athletic performance,” Glogger told swissinfo.

There are many cases of people with naturally malfunctioning genes. Most of the time this results in health problems, such as muscular dystrophy, but the rare occurrence of a mutation can also bring benefits.

Finnish cross-country skiing legend Eero Mäntyranta won race after race in the 1960s because of a natural genetic mutation that helped his blood absorb large amounts of oxygen. It would be very hard in future to determine if such a case was caused by nature or gene manipulation, according to Glogger.

“If, after the introduction of the relevant genes, the body produces more EPO or testosterone by itself then you cannot detect it – it looks like you are a natural,” he said.
To die for
However, athletes run a high risk of developing serious diseases such as cancer or even dying if they submit to gene manipulation that is still in the early days of scientific development.

Gassmann’s genetically modified mice live only half as long as other mice. Scientists know how to modify genes and introduce them into the body, but not how to control the behaviour of such genes once they have been implanted.

“Whatever you put into the body is hard to control. If you realise it is no good then it is almost impossible to stop, and that is what could happen with gene cheating athletes,” Gassmann said. “It is easy to switch on a light but much more complicated to dim it.”

One method of controlling modified genes is to develop drugs that act like on and off switches, but this process is still in its infancy.

“Gene doping could be undetectable and it could improve performance but you could also die,” Glogger warned. Just like the characters in his book.

swissinfo, Matthew Allen in Zurich

By A.J. Perez, USA TODAY
WASHINGTON — From East German swimmers in the 1970s, to sprinter Ben Johnson in the 1980s, to clients of the Bay Area Laboratory Cooperative (BALCO) in recent years, athletes have sought an edge in a lab.
In the future, that lab might not produce a steroid or human growth hormone but genes that, for example, could alter the webbing of a swimmer’s hands and feet.

“We already have webbed hands and feet,” said Andy Miah, a lecturer at University of the West of Scotland. “It would just be a little bit more. What … could the world of sports do about that? Absolutely nothing, nor should they be able to.”

Gene doping, considered by many experts to be the next frontier for athletes seeking a biologic edge, was the central theme Thursday at a forum hosted by the American Enterprise Institute, a conservative think tank. The presenters agreed that doping on the cellular or molecular level likely is years away, and Miah was in the minority when it came to how it should be handled by sports governing bodies.

The World Anti-Doping Agency, which sets the rules on banned substances for Olympic sports, has outlawed gene doping — even though there’s no evidence it exists in sports, nor is there a test to detect it.

“It’s going to be difficult (to detect), but we will succeed in the long run,” said Theodore Friedman, a professor at the University of California-San Diego. “Whether WADA is ahead of the curve or not, time will tell. …You’re going to be looking for changes in a cell, not testing for a drug.”

Friedman said gene therapy is “an immature field” that’s had some “highly publicized setbacks” in treating disease. Still, U.S. Anti-Doping Agency CEO Travis Tygart said it’s good that the topic is getting attention before it becomes an issue in sports.

“This discussion is miles ahead of where we were pre-BALCO, when people were questioning the need for out-of-competition testing or research,” Tygart said. “It would be naive to think the demand is not there. If you rely on the experts who study the issue, we’re still several years away from it being a legitimate risk.”

Edwin Moses, one of the best hurdlers in history, said athletes likely won’t look to gene doping until they’re forced to.

“Most guys are still going to be using the (usual) techniques,” Moses said. “They will continue to be doing it as long as there are no tests used to detect it. Some will always (cut corners). It’s like those who drink and drive and think they can get home without getting caught. Whether it’s drugs or cheating for an exam, there are always going to be people who cheat.”

Then there’s the even more far-reaching notion of prospective parents potentially altering embryos to bring out the attributes more likely to produce an elite athlete.

“The direct manipulation of embryos or fetuses is far off in the future,” said ethicist Thomas Murray, president and CEO of the Hastings Center, a bioethics research institute. “I can’t imagine finding a good argument for parents to be allowed to do that. But if they did it anyway, what would we do to their children? It’s a disturbing prospect.”

The ministers “acknowledge that there is a problem of corruption, match fixing and illegal betting in sport and invite sports organisations to investigate the situation and, where appropriate, identify the problems”.

The Council of Europe is invited to draw up a draft recommendation which could form the basis of a new convention on these issues and help increase integrity controls.

In particular, the ministers ask the Council of Europe to address emerging challenges such as genetic engineering in sport.

Doping refers to the use of performance-enhancing drugs, which is forbidden by organisations that regulate sport competitions. It is widely seen as unethical by most international sports organisations as it damages health and undermines the equality of opportunity of athletes.

A major new ethical challenge in the fight against doping is the use of genetic engineering, declares the resolution.

Gene doping can enhance athletic performance without being detected in blood and urine tests. The issue is currently being addressed in bioethical debates about human enhancement.
“One of our main priorities should be well prepared to react quickly to new ethical challenges,” agreed Birgitta Kervinen, president of the European Non-Governmental Sports Organisation (ENGSO).

The resolution on pan-European sport cooperation invites the Council of Europe to consider ways of increasing its cooperation with the European Union.

“I believe that it is the clear interest of EU members and non-members alike to avoid any developments which would introduce duplication and weaken pan-European arrangements for a better and healthier sport across the continent and beyond,” said Maud de Boer-Buquicchio, deputy secretary-general of the Council of Europe.

The resolution on autonomy and sport reflects concerns that stakeholders have over the growing commercialisation of sport and the effects it has on the autonomy of sports movements.