Other abused biological molecules include synthetic versions of human growth hormone and luteinizing hormone, which is involved in testosterone production. These hormones present challenges in detection to antidoping researchers. “Our job is always to differentiate between the naturally circulating substance from the doping agent. Whatever is identical to the human body is very difficult for us to identify and to prove that this substance was a misuse of a drug rather than a natural variation,” says biochemist Mario Thevis at the German Sport University. Most of the methods for detecting doping rely on chromatography and mass spectrometry.
Drugs available on the market aren’t the only headaches for antidoping authorities. A major component of the antidoping efforts is developing detection methods for pharmaceuticals not yet on the market. Thevis gives the example of selective androgen receptor modulators, which are a new type of anabolic agents in phase III clinical trials. They stimulate growth of muscle and bone. The potential drugs already are being abused, says Thevis, pointing to the case of Jamaican 400-meter runner Bobby-Gaye Wilkins, who was banned from the world championships in Doha in 2010 after she tested positive for a selective androgen receptor modulator called Andarine. That case, says Thevis, “demonstrated we are not chasing ghosts. We are going after drugs that are not yet approved for the market but are definitely being misused by elite athletes.”
The BALCO scandal of 2003 illustrated that some athletes were willing to take drugs that federal agencies and antidoping authorities didn’t even know existed. BALCO was a company that illicitly provided athletes with a substance known as “the clear” that was later identified by Catlin’s group to be the molecule tetrahydrogestrinone. THG is an anabolic steroid that binds to the androgen receptor to boost muscle mass. Federal law-enforcement authorities eventually caught a number of athletes who used it, including British 100-meter sprinter Dwain Chambers, American sprinter Marion Jones and MLB player Barry Bonds.
Blood and genetic tricks
Blood doping is another matter: Cheating athletes get clinicians in their entourages to dupe the hemoglobin count test by adjusting their red blood cell counts before and after competition. In some cases, authorities track the volume percentage of red blood cells. In a tricky manipulation, cheaters increase their red blood cell counts by taking drugs like EPO during the off-season. They withdraw the hemoglobin-rich blood and refrigerate it. When competition season starts, once the antidoping inspector leaves with blood samples from the athletes for testing, the cheaters transfuse the stored blood back into their bodies and head out to compete loaded with extra hemoglobin. After the competition, they quickly withdraw some blood to bring their red blood cell count back to normal and wait for the antidoping inspector to do the post-competition test. Just as with some synthetic hormones, there isn’t a good way to tell apart stored red blood cells from ones that are currently circulating in the bloodstream to catch blood doping.
Genetic manipulations have been on WADA’s radar screen for a decade, although no athlete has yet been caught using them. Gene doping is essentially the flip side of gene therapy. Gene therapy has made recent gains in treating illnesses like genetic-based severe combined immunodeficiency disease and Leber congenital amaurosis, a retinal disease that progresses to total blindness by adulthood.
Because of gene doping’s growing potential, WADA’s science director, Olivier Rabin, says the agency has been proactive against its exploitation. “If an athlete were ever to be in a position to add an extra gene of EPO or growth factor, they can gain a significant advantage,” he says. “We believe that this technology one day will be an option for some athletes who will not hesitate to consider it.”
Gene doping is certainly attractive to manipulate muscle, blood and pain-perception systems –”anything that enhances the ability to train and to deliver blood to exercising tissues and to increase endurance or explosive muscle function,” says Theodore Friedmann at the University of California, San Diego, a gene therapy expert who helped to establish the organization’s research program in the area.
He says while gene doping isn’t yet reality, “there have been some high-profile instances of very prominent athletic trainers making attempts to obtain genetic tools, like the viral vectors that express transgenes.” Friedmann cites the 2006 case of a German trainer, Thomas Springsteen, who was arrested and brought to trial for making attempts to obtain Repoxygen, a drug that was in preclinical trials to put an erythropoietin gene into patients suffering from bone marrow failure from chronic kidney disease or cancer.