IOC hopes to crack down on ‘gene doping’ in 2010 (2008, Jan 6)

IOC hopes to crack down on ‘gene doping’ in 2010
Updated Sun. Jan. 6 2008 9:01 PM ET

CTV.ca News Staff

The International Olympic Committee is hoping a test will be available to expose the next generation of athletes who engage in gene doping.

“Gene therapy–molecular based medicine–is advancing very, very quickly and it is quite possible that there could be breakthroughs in the next couple of years that could be applied to sports by 2010,” Jim Rupert, assistant professor at the University of British Columbia’s School of Human Kinetics told CTV News.

However, the IOC hopes new testing methods will catch those who misuse gene-based medical treatments.

“As we go forward, they are more and more confident that they will have a non-invasive test that will allow us to determine whether or not there has been artificial manipulation,” said Dick Pound, IOC member and former head of the World Anti-Doping Agency (WADA).

Gene therapy has been around for years, but remains largely untested. It involves inserting new DNA into the body’s cells to correct genetic flaws that cause disease.

To increase performance, it is believed that dopers are trying to develop a method for increasing levels of a naturally occurring hormone through genetic manipulation.

“People will be pushing the envelope and looking for an edge, and if you can get a 15 or 30 per cent muscle increase in sports that require explosive strength… it’s clearly something that people will think about,” said Pound.

To ensure athletes end up on the podium fair and square, WADA awarded Jim Rupert a $325,000 grant to come up with a prototype test that will tell the difference between real hormones and those created by gene therapy. Rupert admits this will be difficult.

“Detecting something that’s not supposed to be there is relatively easy. Detecting higher or lower levels of something that’s naturally there is somewhat more challenging,” he said.

Gene therapy revisited (2007, Dec 13)

Gene Therapy, Revisited
By GRETCHEN REYNOLDS
Published: December 13, 2007
In decisions followed closely by experts in performance-enhancing drugs, the Food and Drug Administration and the National Institutes of Health both ruled in the past two weeks that the death of an Illinois woman receiving gene therapy to treat her rheumatoid arthritis was not related to the therapy itself. The woman had developed a life-threatening infection that the regulators decided was due to other drugs she was taking.

As PLAY reported in June, gene doping — or the attempt to alter athletes’ genetic code to make them stronger, faster, bigger, more durable or otherwise inhumanly good — piggybacks on legitimate gene therapy for ideas. Although there are no known cases of gene doping, many drug experts believe that dopers are squirreled away right now in underground labs, consulting published data about gene therapy to create their own home-brewed versions.

Which is why, in theory, the F.D.A.’s findings about the gene trial in Illinois are heartening. Gene therapy, in this case, didn’t kill. Christopher Evans, a professor at Harvard Medical School, who’s preparing his own gene therapy trial for osteoarthritis, speculates that dopers would have been less interested in the women’s death than the promising early results from the trial. “Everything I’ve learned about the psychology of high-performance athletes is that they’ll try anything to get an edge,” he says. Last month, Evans’s gene therapy human trial was pushed back by at least a year, to allow for more safety studies in animals. Gene dopers aren’t likely to be so scrupulous. “Safety,” Evans says dryly, “is not their main concern.”

The Illinois gene therapy trial is expected to resume soon.

the Genathlete study. (2007)

Endothelial nitric oxide synthase gene polymorphism and elite endurance athlete status: the Genathlete study.
via PubMed: triathletes OR triat… by Wolfarth B, Rankinen T, Mühlbauer S, Ducke M, Rauramaa R, Boulay MR, Pérusse L, Bouchard C on 12/11/07

Endothelial nitric oxide synthase gene polymorphism and elite endurance athlete status: the Genathlete study.

Scand J Med Sci Sports. 2007 Dec 7;

Authors: Wolfarth B, Rankinen T, Mühlbauer S, Ducke M, Rauramaa R, Boulay MR, Pérusse L, Bouchard C

In the Genathlete study, we examined the contribution of three polymorphisms in the endothelial nitric oxide synthase (NOS3) gene to discriminate elite endurance athletes (EEA) from sedentary controls (SC). The EEA group included a total of 316 Caucasian males with a VO(2max) >75 mL/kg. The SC group comprised 299 unrelated sedentary Caucasian males who had VO(2max) values below 50 mL/kg. The polymerase chain reaction technique was used to amplify a microsatellite (CA)(n) repeat in intron 13, a 27 bp repeat in intron 4 and a third fragment in exon 7 containing the Glu298Asp SNP. No difference was found between the EEA and SC groups for the 27 bp repeat and the Glu298Asp polymorphism. Chi-square analysis of the overall allelic distribution of the (CA)(n) repeat revealed no significant difference between the two groups (P=0.135). However, comparing carriers and non-carriers for the most common (CA)(n) repeat alleles, we found significant differences between SC and EEA, with more EEA subjects carrying the 164 bp allele (P=0.007). In summary, we found suggestive evidence that the 164 bp allele of the (CA)(n) repeat in intron 13 is associated with EEA status and may account for some of the differences between EEA and SC.

PMID: 18067521 [PubMed - as supplied by publisher]

Engineering a win (2007 Oct)

Engineering a win
Issue 17 of Cosmos, October 2007 <http://www.cosmosmagazine.com/issues/2007/17/>
by Dominic Cadden
<http://www.cosmosmagazine.com/node/1669>
Sporting prowess at the flick of a gene? In the race to be the best, some athletes are even prepared to toy with their DNA.

Doping in sport is big business. Fierce competition drives athletes to extreme measures to improve their performance, while sports institutions employ ever more comprehensive tests to screen for the most commonly abused steroids and drugs.

The next paradigm in doping for those who can afford (and stomach) it may lay in illicitly manipulating their own DNA for a range of benefits, from increased stamina and reduced fat to larger muscles. ‘Gene doping’ exploits the ability to splice or ‘cut and paste’ useful genes resulting in athletic benefits ˆ and unknown side effects ˆ that last a lifetime.

A substance linked to gene doping was first detected at the 2006 Winter Olympics and there’s now concern the practice could be used in the 2008 Beijing Olympics.

Gene doping is a spin-off from gene therapy, which is being investigated to treat hereditary disorders such as cystic fibrosis by replacing a patient’s faulty genes with functional ones. Doctors have had some success with transferring genes into harmless viruses, which are injected into the body. With luck, these viruses replicate within target cells and copy themselves into the body’s strands of DNA.

“The skills involved aren’t that difficult,” says Daniel Eichner, scientific manager for the Australian Sports Anti-Doping Authority in Canberra. “There are scientists who are willing to do anything for money, and a lot of athletes are willing to put their body on the line, no matter what the danger.”

Even in medical gene therapy, however, two major dangers exist. The first is the risk that a manipulated gene can’t be controlled or turned off. The second is that gene therapy could trigger cancer. One seemingly successful French trial for treating severe combined immunodeficiency disorder was halted in 2002 when some of the 11 patients developed leukaemia. However, despite the risks, the temptations will be hard to resist.

Since the full publication of the human genome in 2004, a handful of the 25,000-odd genes detected so far have been found to have some role in athletic performance. One example is the IGF-1 or insulin growth factor gene, says geneticist Damien Abarno of the University of South Australia in Adelaide. Scientists have already had some success getting this gene to ‘take’ in animals and, unlike steroids, “it increases the number of muscle cells, not just the size of them,” he says.

And there are many more genes that could be useful to athletes. Boosting the expression of the gene for MGF, or mechano-growth factor, could limit fatigue and improve muscle repair. The AMPK gene affects how muscles accumulate glycogen, and therefore impacts endurance. The ACE-1, or angiotensin-converting enzyme gene, can be deleted for increased strength or inserted for greater endurance, and has an effect on blood pressure and how muscles use oxygen.

Only a few of these genes have been extensively tested for side effects. However, animal trials with one gene called HCP have highlighted some of the potential risks. One common method of improving performance is increasing red blood cell numbers, which boosts the transport of oxygen from the lungs to the muscles, improving stamina and performance. The conventional method of boosting red blood cell count is with the hormone erythropoietin (EPO), although this is now easily screened for in athletes. Similar effects can be gained by inhibiting the function of the gene HCP, which itself regulates blood cell distribution. However, trials in monkeys were unsuccessful, and often fatal, says Albarno. “The problem was that the [red blood cell count] increased rapidly up to levels where it turned the blood to jelly.”

This side-effect was avoided with a different gene therapy treatment, for anaemia. Tested in 2002, but never produced commercially, Repoxygen works by increasing levels of the body’s own EPO. This, in turn, boosts red blood cell production, but only in response to very low levels of oxygen that might be experienced with anaemia or during intensive exercise.

It was Repoxygen that German athletics coach Thomas Springstein was accused of attempting to obtain prior to the 2006 Winter Olympics in Turin, Italy. Springstein and another trainer in Germany are under investigation by the World Anti-Doping Authority (WADA), which outlawed gene doping in 2003. The WADA is now working with geneticists to find effective screening techniques.

“Close to US$8 million has been spent in the WADA research program for gene doping, representing a significant portion of the entire budget,” says geneticist Theodore Friedmann at the University of California in San Diego, USA, and chair of WADA’s gene doping panel.

One proposal has been to genetically map athletes and then periodically re-screen them to detect changes, says Robin Parisotto, a Canberra-based consultant to Sport Knowledge Australia, who helped establish a test for blood doping with EPO. “But when do you do that? Before they become elite athletes, as a child, or soon after birth?” Parisotto asks.

Friedmann says that scientists working under the WADA banner have studied a number of the side effects that occur with changes to genes and to metabolism. If researchers can put these together to create a ’signature’, eventually it may be possible to detect this signature in saliva samples, he says. “In exactly the same way that DNA technology has added so much in forensic science and crime detection, it will add very powerful new tools to detect doping.”

With the 2008 Beijing Olympics looming, the clock is ticking to find tests capable of detecting the practice.

“Realistically, it will be very difficult to have a test up and running before Beijing”, says ASADA’s Eichner. But this doesn’t mean GM cheaters will manage to remain undetected ˆ WADA rules allow samples to be tested for up to eight years after an event.


Dominic Cadden is a freelance science and physiology writer based in Sydney, Australia.

Anti-doping agency developing test for genetic cheating (2007, Nov 1)

Anti-doping agency developing test for genetic cheating
Thu Nov 1, 9:54 PM ET

The World Anti-Doping Agency is working with scientists to develop tests to battle genetic cheating, which it believes could become possible in five years, its chief said in an interview published Friday.

Dick Pound, WADA’s outgoing chairman, told the Financial Times business daily that genetic manipulation could eventually dwarf drugs-based cheating in sports.

“We are working with them (scientists) to have a non-invasive (test) ready by the time these techniques are being used,” Pound said, telling the paper he was convinced scientists would make genetic manipulation an option for athletes in five to six years.

Pound said that scientists had told WADA that they had already received inquiries from athletes and coaches about how genetic manipulation would work, and how it could affect performance.

The FT said that such testing is at such an early stage that scientists are still conducting laboratory experiments on rats.

Pound also said that the recent case of American Olympic gold medallist Marion Jones admitting she took performance-enhancing drugs had helped push the US Olympic Committee to take a harder line against drugs-based cheating.

“US professional sports are in a combination of denial and responding with the absolute minimum they think they have to do to keep Congress off their backs. It is only legislation that gets their attention,” he said.

“It is very hard to quantify the scale of the (drugs cheating) problem. Some countries understand the problem, but don’t know how to go about solving it. Some are still trying to pretend there is no problem.”

Warning on genetic cheating in sports (2007, Nov 1)

Warning on genetic cheating in sports
By Roger Blitz in London
Financial Times
updated 7:43 p.m. CT, Thurs., Nov. 1, 2007
Genetic manipulation will eventually dwarf drug-cheating as the main issue to confront sports, the outgoing chairman of the World Anti-Doping Agency said on Thursday.

Dick Pound said he was convinced scientists would make genetic development available to athletes within five or six years, allowing them to enhance performance by bulking up their bodies by up to 30 per cent.

Mr Pound, who leaves the sports doping monitoring body at the end of the year after six years at the helm, said Wada had begun contact with leading global scientists and was running several research projects about genetic manipulation.

He said that scientists were telling Wada that they were already receiving inquiries from coaches and athletes about how genetic manipulation could improve performance – even though research is still at a stage where scientists are working in laboratory conditions with rats.

“We are working with them to have a non-invasive [test] ready by the time these techniques are being used,” he told the FT.

Sports are grappling to protect their integrity following a series of high-profile drug scandals. Athletics has been rocked by the admission by US athlete Marion Jones, an Olympic champion in Sydney in 2000, that she took performance-enhancing drugs. Cycling’s Tour de France endured another year of drug scandals, prompting team disqualifications and the desertion of several sponsors.

Mr Pound, who was attending an FT sports industry conference, said he believed the Marion Jones case had helped harden the mood of the US Olympic Committee after assuming for years that drug-cheating in athletics was a problem only for other countries.

But he said US professional sports continued to show a blinkered attitude. “US professional sports are in a combination of denial and responding with the absolute minimum they think they have to do to keep Congress off their backs. It is only legislation that gets their attention,” said Mr Pound.

The fight against drug cheats would be improved by speeding up the process of drug testing by sporting bodies, he added. But he agreed that individual sports and their federations only tended to crack down on their stars after the painful experience of a high-profile scandal.

“It is very hard to quantify the scale of the problem. Some countries understand the problem, but don’t know how to go about solving it. Some are still trying to pretend there is no problem. It will be a combination of passage of time and a willingness to assume responsibility,” Mr Pound said.

He added that the Beijing Olympics next year would be equipped with state-of-the-art anti-doping testing, but Wada remained short of funds with an overall annual budget of $23m.

Copyright The Financial Times Ltd. All rights reserved.

Gene doping could replace performance-enhancing drugs, experts predict (2007, Oct 23)

Gene doping could replace performance-enhancing drugs, experts predict

By Morgan Ashenfelter

(AXcess News) Washington – Performance-enhancing drugs are nothing new in professional sports, as recent scandals with Major League Baseball, the Tour de France and Marion Jones attest. But members of medical and policy making communities are worried about a new technology called gene doping, which modifies genes regulating specific traits.

“The sports industry is a small window into an entire realm of non-medical testing that we need to consider how to regulate,” said Mark Rothstein, director of the Institute for Bioethics, Health Policy and Law at the University of Louisville School of Medicine. He and three other members of a panel spoke on Monday.

The focus of the panel, put on by the Hastings Center and the American Association for the Advancement of Science, was the effects gene doping and genetic testing could have on athletes and how it should be regulated.

“The science is inevitable,” said Dr. Theodore Friedmann, professor of pediatrics at the University of California, San Diego. “The time is not too early to think about policy and ethical issues.”

In the sports world, gene doping would be the use of genes instead of drugs to enhance performance. Scientists have identified genes that control blood production, muscle growth and fast and slow twitch fibers, which determine muscles’ ability to work at a high intensity or steady endurance. If an athlete has a lower amount of a certain gene in his or her body, a doctor could inject the athlete with more of that specific gene.

Genes are also affected by environment and development over time, meaning scientists may not be able to modify the genes that could enhance an athlete’s performance.

But that’s a risk most professional athletes are willing to take, said John Feinstein, National Public Radio sports commentator and the author of several sports books.

“The pressures on athletes, the fact that there’s always someone right behind you and the amount of money encourages them to take the risk,” Feinstein said. “To athletes, succeeding at their sport is worth the risk to their health, to be labeled as a cheater and of being caught.”

Thomas Murray, president of the Hastings Center, a bioethics research institute, said in the short run, education is the most important.

“In the next several years, it is much more likely athletes will hurt themselves because no one knows exactly how to regulate certain genes,” Murray said. “In the long run, sports bodies will have to do the most in terms of policy, but there will be some room for Congress.”

Genes, which are made up of DNA, can be likened to instructions that contain a person’s physical and functional traits. When a problem exists within DNA, a mutation occurs in the gene, which affects whichever trait it controls.

Through gene therapy, doctors can target specific, problematic genes by injecting a virus into the person’s body. The virus has been stripped of its disease-causing materials and instead carries a human gene that is mutilated or missing in that person. When the virus multiplies, the new, healthy gene will have different traits than the one it replaced.

In athletes, the injections could add traits that didn’t exist before or reinforce existing traits.

Because the technology is so new, risks are high. Many patients who undergo gene therapy to cure life-threatening diseases die from contracting other diseases, such as leukemia. Friedmann encourages the use of gene therapy only for patients with life-threatening mutations, not for healthy athletes.

“Gene therapy is an immature technique, still,” Friedmann said. “It’s experimental medicine.”

Murray said that one protection would be to discourage gene testing, at least on children.

Gene testing analyzes a person’s DNA to look for a number of specific traits, such as cognitive ability, addiction, sexuality and coordination. What Rothstein is concerned about is parents using genetic testing to place children on a certain life path, including sports. He cited Genetic Technologies, an Australian company, which offers such tests.

“It is an incorrect notion, genetic determinism, to think that genes are immutable,” Rothstein said.

Genetic Technologies’ test analyzes a person for disease susceptibility, identity and sports performance, specifically ACTN3, which controls fast twitch fibers.

“This won’t affect the 2008 Olympic Games,” Murray said. “But companies will soon be peddling gene doping, and there will be willing and eager athletes as customers.”

Source: Scripps Howard Foundation Wire

Benefits of genetic research in sport (Miah, 2007)

Benefits of genetic research in sport
Submitted by harminka on Fri, 2007-09-14 13:29.
Posted under:
<http://www.huliq.com/tags/sport>
Genetic research into athletic ability should be encouraged for its potential benefits in both sport and public health, a leading group of scientists meeting at the University of Bath said today.

However, ethical concerns, such as whether seeking information about differences between ethnic groups could be perceived as racist research, need to be properly addressed, they warn.

Their recommendations are published in a ‘position stand’ on genetic research and testing launched at the British Association of Sport & Exercise Sciences annual meeting today.

They call for more genetic research in the sport and exercise sciences because of the anticipated benefits for public health, but want researchers to take a more active role in debating the implications of their work with the public.

“If a powerful muscle growth gene was identified, on the one hand this could help develop training programmes that increase muscle size and strength in athletes, but even more importantly the knowledge could be used to develop exercise programmes or drugs to combat muscle wasting in old age,” said Dr Alun Williams from Manchester Metropolitan University, one of the report’s authors.

“We, as scientists investigating genetics, acknowledge a public concern about some genetic research and we believe scientists need to engage in public in debates about the potential benefits of their research.

“Research into the athletic success of East African distance runners or sprinters of West African ancestry might be perceived as unethical.

“But understanding the limits of human exercise capacity in sport could lead to the development of treatments for a range of diseases like cancer and cardiovascular disease.”

The potential applications of genetic testing in sport and exercise also raise some ethical concerns, for example in identifying potential athletic ability before birth.

An Australian company already offers the first genetic performance test (for the ACTN3 gene) which has been linked to sprint and power performance.

The report authors are sceptical about whether this test is useful but anticipate that more advanced versions of these tests will be available in future.

“We are not yet at a point where we can identify a potential future Olympic champion from genetic tests but we may not be very far away,” said Dr Williams, who wrote the report with Drs Henning Wackerhage (Aberdeen University), Andy Miah (University of Paisley), Roger Harris (University of Chichester) and Hugh Montgomery (University College London).

They highlight two dangers of genetic performance tests. Firstly, genetic performance tests might later be linked to disease. For example, a muscle growth gene may later be linked to cancer growth.

“Not all people may want to know, while young that they are at increased risk of cancer by early middle age, but they might inadvertently become aware of that just because they had a ‘sport gene’ test,” said Dr Williams.

Secondly, genetic performance tests can be performed even before birth and this may lead to the selection of foetuses or to abortions based on athletic potential.

The report recommends genetic counselling and that the testing should be confined to mature individuals who fully understand the relevant issues.

Genetic tests might also be used to screen for health risks during sport such as genes that are linked to sudden cardiac death.

Genetic tests for sudden cardiac death are already available but the report recommends that such testing should not be enforced on athletes.

Problems with mandatory testing are highlighted by the case of the basketball player Eddy Curry, who had an irregular heart beat.

Curry was asked by his club, the Chicago Bulls, to perform a predictive genetic test for a heart condition. The athlete refused and was traded to the New York Knicks who did not make such a demand.

In future, genetic tests might be used to identify those that respond with the biggest drop in cholesterol, blood pressure or glucose to exercise.

In a personalised medicine approach, such tests could be used to select subjects for therapeutic exercise programmes but scientists are concerned that this might undermine the ‘exercise for all’ message that already seems difficult to get across to the public.

The authors say that genetic testing might also be used to detect gene doping, which may be a real threat by the time of the London Olympics in 2012, or to show that positive doping tests are the result of a genetic mutation in an athlete.

The report recommends that genetic testing should be used for anti-doping testing as long as the genetic samples are destroyed after testing.-University of Bath

Genetics, Bioethics and Sport (Miah, 2007)

Miah, A. (2007) Genetics, Bioethics & Sport, Sport, Ethics and Philosophy, 1(2), 146-158

Gene Doping: A Review

Gene Doping: A Review

of Performance-Enhancing Genetics

Gary R. Gaffney, MD, Robin Parisotto, BA

0031-3955/07/ 2007 Elsevier Inc. All rights reserved.

doi:10.1016/j.pcl.2007.04.004 pediatric.theclinics.com

Pediatr Clin N Am 54 (2007) 807–822