* Animal experiments show gene therapy can boost performance
* Gene doping likely to be dangerous and risky in humans
* Tests can't detect it, so status of gene doping unclear
LONDON, Aug 7 (Reuters) - 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 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.
MARATHON MICE
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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