'Frustrating' delays for promising biomarker-based assay


A biomarker-based test has been developed to detect athletes that have used banned drugs long after the compounds themselves become undetectable - but it won’t be approved in time for the Beijing Olympics.

The World Anti-Doping Agency (Wada) currently relies on directly detecting banned substances to catch those taking performance-enhancing drugs. Sophisticated analytical techniques combining liquid or gas chromatography with mass spectrometry, as well as immunoassays, continue to be developed to detect banned drugs. However, many substances fall to undetectable levels within hours of being swallowed or injected.

One such compound is growth hormone (GH), a protein produced naturally by the body but abused by athletes to boost skeletal muscle tissue while reducing body fat, which becomes undetectable by immunoassay within 36 hours. Prior to the 2000 Sydney Olympics, an international team of scientists identified two protein biomarkers, IGF-I and P-III-P, whose levels are directly elevated by GH injection, and remain high for several weeks. Since 2000, further studies have confirmed that the biomarkers remain valid across different ethnic groups, and that their levels are not affected by injury.

However, the test is yet to be implemented. The commercial immunoassay used in the study to detect IGF-I is no longer made, and Wada is yet to develop its own. 

’There’s been a little bit of frustration that the work we’ve done has not led to the test being accepted for the Olympics,’ says Richard Holt of the University of Southampton, UK, who has led much of the validation work. ’But you can understand there’s some caution to ensure that once the test is implemented you won’t run into legal difficulties - we’re not the ones who’d have to foot the legal bill.’

Holt’s studies do prove that biomarkers are a valid way to detect banned drugs, says Phil Teale, who works on drug detection at Quotient Bioresearch near Newmarket, UK. Teale has been involved in a project to identify further GH biomarkers, and says the team has developed a way to quantify more accurately biomarkers using mass spectrometry, potentially avoiding the need for a bioassay. ’The mass spectrometry approach also means you can look for several proteins in the same assay,’ says Teale.

A further benefit of biomarker detection is that cheats will find them difficult to mask, says Holt. British sprinter Dwain Chambers, currently fighting a lifetime Olympic ban after testing positive for the banned steroid tetrahydrogestrinone in 2003, has revealed that he was taking seven prohibited substances, some of which mask the effects of performance enhancers. However, suppressing biomarker levels would mean suppressing part of the anabolic effect the athlete was trying to obtain, says Holt.

Anecdotal evidence suggests that the next challenge for testers will be to identify cheats using gene doping to boost their levels of certain performance-enhancing hormones. Using genes to increase local hormone production within the muscle wouldn’t necessarily increase hormone levels in the bloodstream. 

James Mitchell Crow