The amazing adventures of gene doping man (2008, Jun 21)

The amazing adventures of gene doping manDan Silkstone June 21, 2008 THE breakout star of this year's Beijing Olympics just might be a name you've never heard before.

Ladies and gentlemen, please welcome to the winners' podium . . . Gene.

Gene is neither man nor woman, athlete nor coach.

Gene doping is a sophisticated method of cheating and a phrase you'll be hearing a lot more of soon.

It is the stuff of comic books - superhumans born from laboratory experiments, incredible bulk, designer viruses and alien incursions into human DNA.

If it all sounds a little far-fetched, you haven't been keeping up as science streaks past science fiction.

Many experts believe gene doping is already happening and warn that tinkering with human DNA to boost performance could seriously injure or even kill those who try it.

Oh, and a test to detect it is years away - perhaps as much as a decade.

At stake is the integrity of sport itself.

Only years after Sydney's 2000 Olympics do we realise that the Games some dubbed "friendly" were more like pharmaceutical.

Many of the best-known medallists, particularly in athletics, have handed back their medals as investigation of the infamous BALCO laboratory and other cheat rings uncovered systematic doping.

Since Sydney, the possibilities offered by science have multiplied rapidly.

Now the question is: could the biggest dopes of all, this August, be the hundreds of millions expecting a fair contest? Dr Peter Larkins is a former head doctor for Australia's athletics team and past president of Sports Medicine Australia.

"I think it is happening now," he says of gene doping.

"I can't believe that 10 years after gene therapy has been proven and we have mice that grow muscles twice the size of normal mice and mice that are called marathon mice because they run all day, I can't believe the scientists who have been unethical enough to help athletes cheat for the last 30 years aren't giving that technology to some people.

" Associate Professor Bob Stewart, a drugs-in-sport expert from Victoria University, is also pessimistic.

"We just have to accept the fact that athletes and biochemists are a jump ahead of the WADA (World Anti-Doping Agency) testers," he says.

"In sport, there is enormous incentive to pursue that competitive edge ...

There is no evidence at all that these Games are going to be clean.

The context hasn't changed, the rewards for getting an edge in performance are as high as ever.

The testing is not better for the substances that are out there.

" WADA is taking the threat seriously.

Gene doping has been banned since 2003, when it was still just a fanciful idea.

In the past fi ve years, $8 million has been spent by WADA, fi ghting against it.

Earlier this month, Russia £ once the world capital of state-sponsored drug cheating - played host to the third WADA conference on gene doping.

Warnings rang out that the practice posed a massive threat to the integrity of elite sport as the anti-drug body called for urgent action from the world's scientists.

Dr Olivier Rabin is WADA's science director.

He says his duty is to try to anticipate the future of drug cheating and be ready.

"Gene therapy is currently making huge progress at addressing many illnesses and is better and better mastered by the experts," he says.

"That leads to what we call gene doping.

" Almost all doping originates as legitimate medical treatment.

When technology offers the sick and infirm new ways to rebuild wasted tissue or replace red blood cells, it seldom takes long for rogue scientists and desperate athletes to muscle in on the game.

The gold medal question: is it happening already? "Nobody knows," Rabin admits.

It is a startling admission from the man who is a world expert on the subject.

Rabin says there is no clear-cut evidence of gene doping.

"We have heard rumours.

There is a German coach being investigated.

" German athletics coach Thomas Springstein was sacked by his club in 2006 after he was caught supplying steroids to his athletes.

When Springstein's computer was seized, authorities found emails discussing the purchase of repoxygen - a gene treatment, developed for anaemia, that makes the body produce erythropoietin (EPO).

"We work on the assumption that it will happen one day, if it has not already," Rabin says.

As it waits for a test, WADA has worked hard to build links with the labs developing gene therapy for illnesses such as muscular dystrophy and motor neurone disease.

"Some of them tell us that following scientifi c symposia or workshops, they are being approached by athletes and coaches interested in the technology and asking if it is possible to inject their athletes," Rabin says.

"We have even had a case of a coach approaching a scientist and asking if his whole team could be treated, so we know there is a huge interest from some athletes in this and from the part of the sport community interested in doping.

" Clearly, there are athletes who want gene doping technology.

There are also people who wish to sell it.

It is the scientists who don't talk to WADA who are the most worrying.

Rabin made contact last year with one such lab over the internet.

Posing as an athlete, he purchased repoxygen.

But when the substance was received and tested, it proved to be standard EPO - sold at an inflated price.

There are, Rabin says, trends and fashions in doping.

Cheating athletes want the latest, undetectable substances.

Ultimately, though, athletes are not stupid.

"They will use a drug if they believe it will work and they believe they are not going to get caught.

If it does work, they will keep going.

" How close are we to a test? Larkins says "about 10 years" but Rabin says preliminary work shows gene doping does leave a detectable "signature".

"It is clear today that we do not have a test and are still at a research level. But things can move fairly quickly ∑ it could be weeks or it could be years."

Australia is at the forefront of the search.

In a laboratory at the quaintly named National Measurement Institute in Sydney, Dr Kerry Emslie and her team are working hard. "It is a needle in a haystack we are looking for. It is not easy," she says.

Emslie says a reliable test is probably years away but thinks the signs are encouraging. She wrote a paper last year for the Government, assessing the potential threat posed by gene doping. Lose the initial fight, she warns, and as technology improves, we will see more and more genetic manipulation and enhancement.

So how does it work?

First, the gene that governs a certain desirable function is isolated ˜ the source is usually another person. Then, in a laboratory, it is amplified ˜ made more powerful. The gene is then inserted into a viral vector, a virus that has had the harmful part of its structure deactivated but which retains the ability to penetrate and colonise human cells. It is a sort of biological Trojan Horse.

Adenovirus ˜ a common cause of respiratory problems ˜ is most often used but other viruses such as herpes simplex or even HIV are being looked at. The vector is injected into the athlete and begins to take over cells. Once inside, the altered gene becomes part of the cell's DNA and recodes it to behave differently ˜ producing, for example, more and stronger muscle or creating EPO, which in turn creates more red blood cells.

The virus colonises cells at the same rate it would if carrying disease. Once the gene is embedded, it will be expressed. There is no turning back.

Emslie thinks the viral vector leaves a trace that could be the basis for a test. But so little of the vector is required to start the process that searching for it is extremely difficult. Another option is to search for the body's immune reaction to the virus. At the moment, the only way to test for genetic manipulation is to take a muscle biopsy ˜ an invasive procedure that athletes would never submit to.

The search is annoyingly slow. Anyone charged with doping will automatically challenge the finding in court and a testing regime considered untried or experimental would not withstand legal scrutiny. While the cheats may gamble with untried and cutting-edge technology, the drug testers must be certain.

Rabin says that as testing for synthetic EPO gets better, the focus of cheats will shift to gene doping. Currently, athletes must be tested soon after administering EPO. When they remove themselves to distant training locations, they are hard to uncover. But WADA has been cracking down on such practice and is now forcing athletes to continually disclose their whereabouts. Time is running out for the EPO cheats.

Dr Harry Rothenfluh is national testing manager for the Australian Sports Anti-Doping Authority. He says the lack of a test does not give potential gene dopers a free pass. "Finding a test is going to be a real challenge but we also have intelligence functions looking at information coming in and seeking information."

The organisation now has an intelligence staff of six scientists and former law enforcement people. They trawl internet sites where athletes seek information, forge close ties with labs and try to predict where illegal medical technology might be found. "We aren't just relying on testing because we don't know how far away a test will be."

If this brave new world all sounds a little Frankenstein, Larkins says we should have seen it coming. "We've always known genetics determines talent and genetic selection of athletes has gone on since the 1960s," he points out.

Ian Thorpe endured a doping scandal in 2007 because his natural production of hormones was abnormal. Thorpe was a genetic freak. It's easy to see how a rival might be tempted to cheat. No matter how hard you train, the Thorpes of this world have an inbuilt genetic advantage. Why not redress that imbalance?

Larkins says it is a tragedy for sport and a danger for its future that we simply will not know until years after Beijing who, if anyone, was cheating.

"If anyone performs too well in Beijing, the cloud will be over them for the next 10 years. Every fantastic performance now is tainted ∑ it is a really sad thing for sport."

Blood samples taken during the Games will be frozen for eight years and retested once new detection methods are developed. A star two months from now could be unmasked as a cheat two years hence.

Because of the cost and scientific complexity, it is unlikely that huge numbers of athletes are gene doping. But, as the BALCO case showed, it is those near the top who have the most reason to use such methods and the best means of accessing them.

There are plenty of ethical problems with gene doping. But far more pressing are the medical questions surrounding the embryonic science. Experiments and trials over the past decade have demonstrated an impressive capacity to retool human bodies by tinkering with DNA. They have also uncovered some terrible side effects.

And while accessing substances from a legitimate laboratory is one method of gene doping, once research is published, it can be relatively simple for others to "follow the recipe" and replicate gene treatments in secret labs.

"Doing this is much more complicated than injection of EPO," Rabin says. "We know that from experiments conducted on animals that if you cannot regulate correctly expression of the EPO gene, then you die. Your blood becomes so thick that it coagulates."

If you think that is enough to scare athletes away, think again. Rabin estimates that during the late 1990s, when EPO abuse was in an early phase, 20-30 young cyclists died from the substance. "We know people will take the risk . . . when you are an athlete in your 20s, you feel invincible."

ASADA's Rothenfluh says human trials of gene therapy are still in the early stages and it is vital that athletes realise the danger. "There have been some pretty high-profile cases. A young man in the US died as a result of his body reacting to the virus inserted and there were some kids in another trial for whom the treatment accidentally activated leukaemia. There are some pretty major risks but the lesson of history is some athletes won't care."

Rothenfluh says there is a quantum leap between traditional drug cheating and gene doping. With traditional doping, an athlete can stop taking the drug if harmful side-effects become apparent. Quit taking steroids, EPO or human growth hormone and there's a fair chance your body will recover. "But once you've put a gene inside a viral vector into your system, it is not really possible to get it back out."

Larkins also fears the consequences. "You are manipulating your cells' biology at a micro level," he says. "In the studies of this, more mice die than actually survive."

But the mice that do survive have 30% bigger muscles, more power and more strength, he says, or can run all day without ever training.

Victoria University's Stewart says the effect of gene doping on the coming Games is uncertain, but says gene doping, coupled with next-generation EPO products, means there is now a distinct gap between the cheats and the testers.

He proposes a radical solution ˜ opening the doors to supervised and controlled doping. "It's really a matter of finding policy measures that aren't as punitive and are based around education, harm-minimisation and protecting the health and wellbeing of athletes and not worrying too much whether someone has an unfair advantage.

"As fans, we pretend and fantasise about naturally gifted athletes and sheer hard work but we already use genetics to identify athletes for sports, then we target them and train them up and feed them specific diet. There's not much accident in it."

It's an interesting idea but unlikely to happen soon and it hardly seems fair to the overwhelming majority of athletes who do not cheat. Instead, it seems, we are in a new era where gold medals will be provisional and world records arrive with asterisks attached.

It's not ideal to catch drug cheats years after the event, WADA says. But it is better than not catching them at all.

Gene genie is out of the bottle, and cheats may escape Dan Silkstone June 21, 2008 "It is clear today that we do not have a test and are still at a research level. But things can move fairly quickly ∑ it could be weeks or it could be years."

Australia is at the forefront of the search.

In a laboratory at the quaintly named National Measurement Institute in Sydney, Dr Kerry Emslie and her team are working hard. "It is a needle in a haystack we are looking for. It is not easy," she says.

Emslie says a reliable test is probably years away but thinks the signs are encouraging. She wrote a paper last year for the Government, assessing the potential threat posed by gene doping. Lose the initial fight, she warns, and as technology improves, we will see more and more genetic manipulation and enhancement.

So how does it work?

First, the gene that governs a certain desirable function is isolated ˜ the source is usually another person. Then, in a laboratory, it is amplified ˜ made more powerful. The gene is then inserted into a viral vector, a virus that has had the harmful part of its structure deactivated but which retains the ability to penetrate and colonise human cells. It is a sort of biological Trojan Horse.

Adenovirus ˜ a common cause of respiratory problems ˜ is most often used but other viruses such as herpes simplex or even HIV are being looked at. The vector is injected into the athlete and begins to take over cells. Once inside, the altered gene becomes part of the cell's DNA and recodes it to behave differently ˜ producing, for example, more and stronger muscle or creating EPO, which in turn creates more red blood cells.

The virus colonises cells at the same rate it would if carrying disease. Once the gene is embedded, it will be expressed. There is no turning back.

Emslie thinks the viral vector leaves a trace that could be the basis for a test. But so little of the vector is required to start the process that searching for it is extremely difficult. Another option is to search for the body's immune reaction to the virus. At the moment, the only way to test for genetic manipulation is to take a muscle biopsy ˜ an invasive procedure that athletes would never submit to.

The search is annoyingly slow. Anyone charged with doping will automatically challenge the finding in court and a testing regime considered untried or experimental would not withstand legal scrutiny. While the cheats may gamble with untried and cutting-edge technology, the drug testers must be certain.

Rabin says that as testing for synthetic EPO gets better, the focus of cheats will shift to gene doping. Currently, athletes must be tested soon after administering EPO. When they remove themselves to distant training locations, they are hard to uncover. But WADA has been cracking down on such practice and is now forcing athletes to continually disclose their whereabouts. Time is running out for the EPO cheats.

Dr Harry Rothenfluh is national testing manager for the Australian Sports Anti-Doping Authority. He says the lack of a test does not give potential gene dopers a free pass. "Finding a test is going to be a real challenge but we also have intelligence functions looking at information coming in and seeking information."

The organisation now has an intelligence staff of six scientists and former law enforcement people. They trawl internet sites where athletes seek information, forge close ties with labs and try to predict where illegal medical technology might be found. "We aren't just relying on testing because we don't know how far away a test will be."

If this brave new world all sounds a little Frankenstein, Larkins says we should have seen it coming. "We've always known genetics determines talent and genetic selection of athletes has gone on since the 1960s," he points out.

Ian Thorpe endured a doping scandal in 2007 because his natural production of hormones was abnormal. Thorpe was a genetic freak. It's easy to see how a rival might be tempted to cheat. No matter how hard you train, the Thorpes of this world have an inbuilt genetic advantage. Why not redress that imbalance?

Larkins says it is a tragedy for sport and a danger for its future that we simply will not know until years after Beijing who, if anyone, was cheating.

"If anyone performs too well in Beijing, the cloud will be over them for the next 10 years. Every fantastic performance now is tainted ∑ it is a really sad thing for sport."

Blood samples taken during the Games will be frozen for eight years and retested once new detection methods are developed. A star two months from now could be unmasked as a cheat two years hence.

Because of the cost and scientific complexity, it is unlikely that huge numbers of athletes are gene doping. But, as the BALCO case showed, it is those near the top who have the most reason to use such methods and the best means of accessing them.

There are plenty of ethical problems with gene doping. But far more pressing are the medical questions surrounding the embryonic science. Experiments and trials over the past decade have demonstrated an impressive capacity to retool human bodies by tinkering with DNA. They have also uncovered some terrible side effects.

And while accessing substances from a legitimate laboratory is one method of gene doping, once research is published, it can be relatively simple for others to "follow the recipe" and replicate gene treatments in secret labs.

"Doing this is much more complicated than injection of EPO," Rabin says. "We know that from experiments conducted on animals that if you cannot regulate correctly expression of the EPO gene, then you die. Your blood becomes so thick that it coagulates."

If you think that is enough to scare athletes away, think again. Rabin estimates that during the late 1990s, when EPO abuse was in an early phase, 20-30 young cyclists died from the substance. "We know people will take the risk . . . when you are an athlete in your 20s, you feel invincible."

ASADA's Rothenfluh says human trials of gene therapy are still in the early stages and it is vital that athletes realise the danger. "There have been some pretty high-profile cases. A young man in the US died as a result of his body reacting to the virus inserted and there were some kids in another trial for whom the treatment accidentally activated leukaemia. There are some pretty major risks but the lesson of history is some athletes won't care."

Rothenfluh says there is a quantum leap between traditional drug cheating and gene doping. With traditional doping, an athlete can stop taking the drug if harmful side-effects become apparent. Quit taking steroids, EPO or human growth hormone and there's a fair chance your body will recover. "But once you've put a gene inside a viral vector into your system, it is not really possible to get it back out."

Larkins also fears the consequences. "You are manipulating your cells' biology at a micro level," he says. "In the studies of this, more mice die than actually survive."

But the mice that do survive have 30% bigger muscles, more power and more strength, he says, or can run all day without ever training.

Victoria University's Stewart says the effect of gene doping on the coming Games is uncertain, but says gene doping, coupled with next-generation EPO products, means there is now a distinct gap between the cheats and the testers.

He proposes a radical solution ˜ opening the doors to supervised and controlled doping. "It's really a matter of finding policy measures that aren't as punitive and are based around education, harm-minimisation and protecting the health and wellbeing of athletes and not worrying too much whether someone has an unfair advantage.

"As fans, we pretend and fantasise about naturally gifted athletes and sheer hard work but we already use genetics to identify athletes for sports, then we target them and train them up and feed them specific diet. There's not much accident in it."

It's an interesting idea but unlikely to happen soon and it hardly seems fair to the overwhelming majority of athletes who do not cheat. Instead, it seems, we are in a new era where gold medals will be provisional and world records arrive with asterisks attached.

It's not ideal to catch drug cheats years after the event, WADA says. But it is better than not catching them at all.