The fight against doping – is the testing working?

When you study chemistry at school, you learn that litmus will go blue in alkaline solutions and red in acidic solutions and many people wrongly assume that drug testing is equally black or white.

Recently published was a very disturbing article (http://labtimes.org/labtimes/issues/lt2013/lt01/lt_2013_01_18_23.pdf) in which four Norwegian biochemists outlined a number of deficiencies in the methods used by the World Anti-Doping Agency (WADA) to detect the performance-enhancing drug CERA (Continuous Erythropoietin Receptor Activator), specifically relating to the failed test for this banned substance by the Norwegian race-walker Erik Tysse.

Tysse was banned for two years from all competition and organised training, however the compelling evidence presented by the authors makes me believe that this was an unjust and unwarranted punishment. I worry that he is not the only one to have suffered such a fate of wrongful conviction and what is perhaps equally worrying is that if WADA’s tests can produce false-positives, then they must surely also be letting some cheats slip through by producing false-negative results.

How can WADA get it wrong?

The Science

CERA is fundamentally hard to detect. EPO is a naturally produced hormone that triggers the production of red blood cells– CERA is a synthetic variant of EPO, designed to mimic the action of EPO. They are very similar in size and shape; in fact they have identical amino acid sequences. The one difference between them is that they have different post-translational modifications; meaning different chemical groups are added to the protein. In this case, CERA is pegylated, whilst EPO is glycosylated, leading to a difference in charge between the two.  This difference should, in theory, allow the tests to distinguish between EPO and CERA, as CERA should appear more basic and EPO more acidic. However, during the preparation and purification of the samples it is possible for one or more of the acidic groups attached to EPO to be removed, thus causing natural EPO to appear more basic. This makes it essentially indistinguishable from CERA.

The Bureaucracy

After testing positive, Tysse’s case was brought before The Tribunal of the Norwegian Confederation of Sports. The judge in this case openly admitted that much of what was discussed “went over his head”. When the case hinges on jargon like “negatively charged sialic acid unit” and “N-glycosylation states” it is clear that an unscientifically trained judge is unable to make a fully informed decision. Yet Tysse was still found guilty.

After appealing this decision, Tysse then went to the Court of Arbitration for Sport (CAS). In this second case, the data provided to the CAS by WADA was deliberately presented in a misleading way- that favoured the conclusion that CERA was present. The figures presented to the court were a cut-and-paste job. Reference bands taken from one gel were aligned next to Tysse’s samples from a separate gel. The relative sizes of the bands were also changed- with the image of Tysse’s sample being enlarged 40%. This data would be laughed out of my Monday morning lab meeting, with some serious questions asked, but it is easy to understand how those not familiar with the relevant techniques might readily accept the “expert opinion”.

What Next?

These decisions cannot continue to be made by people that lack the qualifications to interrogate the data presented to them; the presence of an independent panel with a basic understanding of the science behind the testing would have prevented this from slipping through. These decisions have destroyed an athlete’s career and thrown their life into turmoil, so we must do more to get them right.

Doping is the single biggest problem facing sport today, but as with all criminal cases, you are innocent until proven guilty. Cases such as this make a mockery of the whole system.

The testing laboratories must maintain the highest professional standards with strict protocols for the collection, transport, and analysis of samples, a scrupulous chain of custody and accurate application of fixed standards for the evaluation of doping evidence—with the anonymity of the athlete guaranteed at all steps of the process. Only then can we have full confidence in WADA.