To detect doping with EPO, urine samples collected from athletes are tested by WADA-accredited laboratories. In recent years, however, the test’s reliability has been seriously and credibly questioned by scientists from the Copenhagen Muscle Research Center in Denmark in a 2008 article published in the Journal of Applied Physiology.
The researchers injected eight males who were recreational athletes with EPO and collected urine samples before the injections on eight more occasions. They then sent two identical sets of samples to two separate, WADA-approved testing labs. The results proved widely divergent, with one lab detecting numerous positive results and the other detecting no positive results.
Drug companies that produce EPO have helped antidoping laboratories develop direct tests based on minute differences between the recombinant molecules and the natural form. But, as athletes increasingly obtain knock-offs produced in China and India with subtle biochemical differences, testers have trouble staying ahead in the race. To date, only costly and time-consuming isoelectric focusing techniques can distinguish among glycosylation patterns on these molecules and distinguish among recombinant and endogenous forms of EPO.
Martial Saugy, Ph.D., the director of the Swiss Laboratory for Doping Analyses, and his team have developed another testing technique. Instead of looking for drugs or minute traces of their breakdown products in blood and urine, they pioneered the “biologial passport,” which builds up a profile of an individual over time, trying to detect biochemical changes that indicate doping.
Since 2008, Dr. Saugy’s laboratory and the International Cycling Union (UCI), cycling’s international federation based in Aigle, Switzerland, have created biological passports for hundreds of professional cyclists, some containing data from dozens of blood draws.
Rather than ordinary spot-testing approaches that look for unnatural ratios between biological constituents in a single sample or for direct chemical evidence of known doping agents, the passport allows investigators to find deviations from the rider’s test-established norm that might result from doping, even if the specific drug or tactic remains unknown.
For example, the test will look at reticulocyte formation (level of immature blood cells) to determine whether accelerated or decellerated reticulocyte production is occuring. According to Michael Ashenden, Ph.D., a sports scientist and a member of the independent board UCI has assembled to evaluate the profiles, each member of the group can examine whatever markers he or she chooses in blood profiles.
“I tend to scrutinize reticulocyte [immature red blood cell] values,” Dr. Ashenden said, “to see if there are any signs of accelerated or decelerated reticulocyte production.” An acceleration, he says, might point to use of EPO to increase red blood cell production, while a decrease indicates that the athlete just stopped using EPO or recently took a transfusion of stored red blood cells, the process for which the term “blood doping” was coined.
The main benefit of the passport, Dr. Elliott remarked, is that it serves as a warning to athletes that, behind the scenes, they are being watched. As doping practices continue to become more sophisticated, WADA says it will further develop and refine this passport strategy to monitor a selection of an athlete’s biological parameters over a period of time, ideally throughout his or her career, to detect abnormal variations.
Dr. Elliott noted that a critical element to managing the risk that a drug will be used for sports doping remains the development of detection assays even before a drug is launched. And while this year’s relatively longer race times in the Tour may signal diminished use of doping, the ultimate disincentive may prove to be a real fear of getting caught by newer, better testing.