Always seeking new antidoping tools
Detecting gene and other forms of doping is complicated for authorities because they are limited in the types of samples they can take from athletes. They can’t do anything as invasive as muscle biopsies, so they have to rely on techniques that can detect doping in blood and urine. The experts cite the relatively new -omics methods as potential ways to better catch doping. “We believe they are going to be an important component of our arsenal,” says Rabin. “We have different projects looking at all the different levels of -omics.”
Rabin says WADA researchers have some interesting concepts in the works, such as looking for the molecular signatures of doping. “When an athlete dopes with a substance or a cocktail of substances, she or he is looking for a physiological impact. It’s to enhance transfer of oxygen, muscle mass and other different physiological capabilities,” says Rabin. “These create an imbalance in the body’s homeostasis that we believe will be reflected at different -omics levels.” He says a challenge researchers are facing is distinguishing between signatures caused by physical exertion, which elite athletes do intensely, and those signatures caused by doping.
For now, the thinking is that -omics technologies are not quite there yet for antidoping enforcement. Molecular geneticist James Rupert at the University of British Columbia in Canada received WADA funding to explore the possibility of using RNA transcripts to tell if an athlete has doped with EPO. “The test I was proposing would work for any source of erythropoietin, including gene doping,” he says.
But he says his group concluded after preliminary work in mice that there wasn’t sufficiently robust differential gene expression to be detected reliably in urine or blood. Rupert says there probably are differential gene expression patterns at the tissue level, but that doesn’t help antidoping authorities, because they cannot sample tissues. He adds that also compounding the problem is that the genetic variation and background frequencies of people cover a wide range. This is an impediment because “we really wouldn’t have any specificity for our test,” says Rupert. “It’s very important with a doping control test that you have high sensitivity and specificity, because you don’t want to falsely accuse people.”
To better track athletes and understand their individual physiologies, WADA implemented the Athlete Biological Passport program in 2009. The program tracks athletes throughout the year – not just at competitions – to make sure that they are not using performance-enhancing substances or methods. Antidoping authorities take measurements for blood, endocrine and steroid parameters to know what an athlete’s normal physiological range is and to find deviations.
The beauty of the biological passport, says Rupert, is that “you’re serving as your own control … Every time I measure your parameters, I reinforce what I know about you, so it makes my baseline values get better.” The moment an athlete deviates from his or her normal range, it’s a reason to be suspicious. Deviations can occur either because of doping or illnesses. Rupert suggests the biological passport should be expanded to use genetic information, which can help in some cases, such as the Eero Mäntyranta case (see sidebar), to tell genetic outliers from cheating athletes.
Real or fake ability?
With the high stakes of money and fame in sports, doping will remain a fact in years to come. Athletes are desperate enough to try anything. They have scientists and clinicians in their support groups constantly mine the scientific literature, searching for clues about any substance that will improve performance and fly under the radar of the authorities. Even if a compound is shown to change properties of cells in a petri dish in a way that could be interpreted as better performance, some athletes are willing to give it a shot despite the lack of safety data.
“What is scary to us scientists is that some people are ready to take substances without proper clinical trials,” says Rabin. “I worked in the pharmaceutical industry [before]. We took all these precautions to go from animal models to first administrations in humans and then to patients. But then we realized some athletes didn’t even bother to wait. The drug went straight from the test tube to their bodies!”