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Scientists racing to catch gene-doping athletes

LONDON (AP) _ Scientists are racing to develop a test to catch athletes who try to boost their performance by manipulating their own genes.

Though there is no proof that gene doping is already occurring, researchers say they would like to be ready ahead of the 2008 Beijing Olympics. Gene doping is an illegal spin-off of gene therapy, which typically alters a person's DNA to fight diseases like muscular dystrophy and cystic fibrosis.

Detecting such minor genetic changes within the human body's own structure is like looking for the proverbial needle in a haystack. While no commercial test exists to identify gene doping, scientists are exploring various hypotheses they hope will soon pan out.

Even if a test does not become available until after the Olympics, authorities have the power to test samples taken from the competition for up to eight years after the events have taken place.

``The approach to detect gene doping is coming,'' said Dr. Theodore Friedmann, a gene therapy expert at the University of California, San Diego. ``No one should think that they will be able to hide the evidence of a genetic change.''

At the World Anti-Doping Association, researchers are trying to track the immune traces left by the viruses commonly used in gene doping. Gene transfers are most effectively performed with viruses, which have first had any dangerous properties removed. In most cases, viruses tend to leave behind incriminating antibodies.

``The body reacts to the presence of any viruses and develops an immune response that can be monitored,'' said Dr. Olivier Rabin, WADA's science director.

Because it is virtually impossible to identify the individual gene altered, researchers are also focusing on the secondary impact such changes would provoke.

``If you perturb a biological system, you'll get all kinds of changes in the homeostasis to keep it functioning,'' Friedmann said.

Friedmann and his colleagues are researching a gene doping test in mice that attempts to identify the molecular changes following a gene mutation.

``We're finding families of genes that unexpectedly change in response to an alteration at the genetic level,'' Friedmann said. ``Those genes can constitute a molecular signature for the system having been disturbed.''

Identifying this genetic signature would be like catching a gene-doping athlete red-handed.

Not knowing precisely which genetic changes to look for complicates scientists' search for a test. But it also poses a serious health risk to the athletes who may be tempted to modify their genes.

Traditional drug doping enhances the body's potential dramatically _ but is still bound by the body's own limits. In contrast, gene doping removes these limits altogether.

``You're changing the blueprint of what Mother Nature intended,'' said Dr. Todd Schlifstein, an assistant professor at New York University School of Medicine. Such a radical step, Schlifstein says, may have unexpected and unpredictable medical consequences.

This has already been seen in athletes who have illegally increased their levels of repoxygen, which gives the body the gene needed to produce erythropoietin (EPO), a naturally occurring hormone that stimulates the production of red blood cells. Having more red blood cells can increase an athlete's stamina since the cells carry oxygen. But red blood cells are also thicker than regular blood cells.

``Having extra red blood cells can make your blood sludge. The body wasn't made to have its underlying mechanism changed,'' Schlifstein said, adding that an athlete with excess levels of red blood cells is susceptible to a clot, stroke or heart attack.

The precision required in gene therapy also means there may be significant risks if the gene is not re-inserted correctly.

``If the gene happens to hit some oncogenes, it could send a message to other cells to become cancer cells,'' Rabin said.

In cases where growth hormones are stimulated, it is also possible that very early cancers, which may not yet have been detected, could have their growth dramatically accelerated.

Because gene transfer is still very experimental, there are significant risks for anyone modifying their own genes.

``In the name of healing, patients and doctors may accept the risks if there is a chance that the patients will recover,'' Friedmann said. ``But in the name of changing the outcome of a sporting event, it would be tragic to see a healthy, young athlete be harmed by manipulating his genes.''
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