He ultimately hopes to use mass spectrometry, the gold standard in analytical chemistry, to detect all forms and variants of EPO with a single test. Mass spec measures the unique spectral profiles generated by different molecules, giving an unambiguous method of detection. While the technique is already used to detect other banned drugs, the chemical structure of the EPO molecule makes it difficult to measure using traditional mass spectrometry. “It is a complex drug with glyco groups hanging off it,” says Catlin. “We have to get rid of these groups or find a way to characterize the whole intact molecule.”
Another significant challenge for the antidoping authorities is human growth hormone (hGH). This drug is virtually identical to the most common form of growth hormone produced naturally by the body. It is made by inserting the human gene for the growth hormone into bacteria.
The current test for hGH was first used at the 2004 games in Athens, and it will be used more broadly in Beijing. The test analyzes the ratio of different forms of the hormone in the blood. “If an athlete uses recombinant hGH, which is identical to the major isoform of natural hGH, the ratios that normally occur are influenced and significantly altered,” says Mario Thevis, a professor of preventive doping research at the German Sport University Cologne. “This can be measured and visualized, and enables the detection of hGH misuse.” Thevis is also working on a more sensitive test that can detect different varieties of hGH.
And while WADA prefers to stay mum on the specific details of new tests currently under development, the agency has disclosed details of a broader new approach that might overcome some of the challenges associated with detection of EPO and hGH. Using new technologies, such as microarrays, which can simultaneously measure changes in the expression of thousands of genes, proteins, and other biomarkers, scientists can quickly search for biological changes induced by such drugs. “The new armamentarium doesn’t look for drug X; it looks for the effects of drug X,” says Theodore Friedmann, a physician scientist at the University of California, San Diego, who is working with WADA. Thanks to this approach, altering a drug so that it becomes invisible to testing will no longer be possible, he says.