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Wednesday, August 13, 2008

How to Catch Olympic Cheats

Athletes using performance drugs can't stay ahead of detection methods for very long.

By Emily Singer

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Credit: Technology Review

Athletes aren't the only ones racing against the clock this week in Beijing. A team of skilled scientists is working 24 hours a day at a drug-testing lab in Beijing's Olympic Sports Center, analyzing approximately 4,500 blood and urine samples for banned substances. Their work is part of an ever-evolving arms race between scientists and sports cheats who try to stay one step ahead of the latest detection methods.

On Monday, the International Olympic Committee (IOC) announced the first athlete to fail a drug test in Beijing: Spanish cyclist Maria Isabel Moreno, who tested positive for the red-blood-cell-boosting hormone erythropoietin (EPO). But IOC president Jacques Rogge has predicted that 30 to 40 athletes will test positive during the games.

EPO is used therapeutically to treat anemia, but it also boosts blood oxygenation in healthy people, and it has proved troublesome for scientists to detect. For one thing, traces of the drug are quickly eliminated from the body. "When the drug is gone, the urine test becomes negative, but the effect of the drug lasts longer and the athlete is still enhanced," says Don Catlin, founder of Anti-Doping Research, a nonprofit research institute based in Los Angeles that is helping oversee drug testing in Beijing during the games. "Therefore, athletes game the test, trying to figure out the dosing regimens that will keep them beneath the radar."

In an attempt to catch those athletes out, the Olympic antidoping lab has dramatically stepped up testing compared with previous games, conducting 1,000 more tests than in Athens in 2004 and double the number at the Sydney games in 2000. That increase comes largely from greater numbers of tests per sample, rather than from an increase in the number of samples collected.

The IOC and the World Anti-Doping Agency (WADA) are also developing new testing techniques, although they won't give details about any new tests that they plan to run at this year's Olympics. "We need the elements of secrecy to try to be ahead of the game," saysCatlin.

This secrecy won WADA a dramatic victory at the Tour de France last month. Its drug-testing lab caught several cyclists using a longer-lasting form of EPO called CERA. Soon after the athletes were caught, it was revealed that the agency had been working with Swiss drugmaker Roche to develop a test to detect CERA while the drug was still being tested by the U.S. pharmaceutical company Amgen.

Unfortunately, generic versions of the drug are popping up all over the world. And because each has a chemical composition slightly different from the original version, scientists must design a new test for each variety. (Scientists detect the different forms of EPO using a standard laboratory technique called electrophoresis, which separates molecules based on their charge. The man-made versions have a different charge than the peptide made naturally in the body.)

Catlin says that many more versions of EPO are likely to emerge, as well as a related class of drugs called next-generation erythropoiesis-stimulating agents, or ESAs. One of those, Hematide, is already in late-stage clinical trials. "As soon as that's out, it will find its way into the hands of sportsmen and -women," Catlin says.

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Comments

  • Retro Testing
    carlii on 08/13/2008 at 3:31 AM
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    As new tests are developed, do the Olympic Committees have access to the blood samples from prior Olympics?  That is, will we be seeing Olympic metals froms 2008, 2004, and 2000 Olympics later retracted as the drug detection science improves?
    Rate this comment: 12345
    • Re: Retro Testing
      Emily Singer on 08/13/2008 at 9:47 AM
      Technology Review TR Staff
      Biotechnology and Life Science editor
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      Samples collected during the Beijing games will be kept for 8 years so that they can be retested when more sensitive detection methods are developed. I'm not sure about samples from the 2000 and 2004 games.
      Rate this comment: 12345
  • Can these tests determine how old someone is?
    czepp on 08/13/2008 at 2:59 PM
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    If so, then why aren't these tests being used to screen for underage gymnasts?
    Rate this comment: 12345
    • Re: Can these tests determine how old someone is?
      Emily Singer on 08/13/2008 at 3:13 PM
      Technology Review TR Staff
      Biotechnology and Life Science editor
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      No. As far as I know, there are no biological tests to precisely determine age. This column at Slate can tell you more: http://www.slate.com/id/2197365/
      Rate this comment: 12345
  • Those guys are naive
    gabrielg01 on 08/13/2008 at 7:03 PM
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    In the last paragraph there is this quote "The new armamentarium doesn't look for drug X; it looks for the effects of drug X," , and then they conclude that this new approach will catch the "undetectable" drugs.

    First off, looking for biochemical changes and then claiming that drugs were used will be a very contentious issue. Similar changes could be induced with legal drugs, or certain chemical changes in the diet. The accusers will not have a smoking gun but only the smoke. There will doping accusations based on very vague and circumstantial data.

    Second, what makes these people think that the drug effects themselves won't be amenable for cover-up medication?
    Rate this comment: 12345
    • Re: Those guys are naive
      Emily Singer on 08/14/2008 at 10:04 AM
      Technology Review TR Staff
      Biotechnology and Life Science editor
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      It's true, using biological responses to detect drug use will be a very contentious issue and one that is eventually likely to play out in the courts. That's why scientists will need to find markers with a very tight link to the drug -- they are studying drug responses in people of different ages and ethnicities to make sure candidate markers show the same effects in these groups.
      Rate this comment: 12345
    • Re: Those guys are naive
      irreverent on 08/16/2008 at 6:40 PM
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      This strategy is already being used without challenge. For example, hematocrit levels are being used to show blood doping and EPO use in the absence of direct proof of usage. It is extremely difficult to cover up gene expression profiles involving hundreds of genes because they are so unique. It would be the equivalent of trying to cover up your DNA profile. Athletes have been trying to cover up drug use with diuretics for years but they just test for the diuretics instead and catch them that way. What will be really difficult to detect is direct muscle modification by DNA transfer. This cheat has already been shown to work in animal models. Detection would require a muscle biopsy which would not be well accepted by athletes. Another more difficult scenario to control will be the testing and breeding of athletes that are partial myostatin knock outs. These occur naturally and can be easily detected so that unscrupulous countries could breed athletes that have these mutations to great advantage. 
      Rate this comment: 12345
  • AMPK and PPARd Agonists
    tangent on 08/19/2008 at 11:26 AM
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    Does anyone see this paper on last issue of cell?
    "AMPK and PPARd Agonists Are Exercise Mimetics"
    http://www.cell.com/content/article/abstract?uid=PIIS0092867408008386
    The PPARd Agonists definitely is a good drug for cheat!
    Rate this comment: 12345
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