A Decade of Doping – and Analytical Advances

In November, after a series of retroactive tests, the World Anti-Doping Agency (WADA) announced that over 70 athletes from the Beijing and London Olympics were guilty of doping violations. The ten-year testing period and increasing sensitivity of analytical tests may help ‘beat the cheats’ (and redistribute a few medals), but they also raise questions and eyebrows. In an article in the New York Times (1), WADA’s Olivier Rabin said, “Science progresses every day. Just over the past probably five years, the sensitivity of the equipment progressed by a factor of about 100. You see what was impossible to see before.”

We asked three doping experts about the balance between analytics and ethics.

The thoughts of... Douwe de Boer

Technical lab expert for Hospital Projects, Department of Clinical Chemistry, Academic Hospital, Maastricht

How is analytical science developing in the sports doping arena?

Detection limits have already been decreasing for several years, making the detection window of the use of doping agents longer and longer. However, what is also contributing to longer detection windows is the discovery of so-called long-term metabolites of the steroids of interest, which may be detected for a longer period although at relatively low concentrations (such metabolites were not discovered previously because of their relatively low concentrations). With today's improved detection limits, their discovery was made feasible and thus their detection in urine samples of athletes is also possible.

Where does the analysis end? 

There is, at this moment, no obvious end to the approach – or at least not until we reach concentrations that can be found in non-athletes; for example, due to contamination of drinking water. Drinking water may contain some doping agents but only at extremely low concentrations. Therefore, we need to have, in principal, a threshold for every doping agent. If the found concentration of a doping agent is below its threshold, no action should be taken against an athlete and if above the threshold, action should be taken.

Is it ethical to analyze – and punish – so many years after the event took place?

Ethical limits certainly are at risk of being violated if an analysis takes place, for example, 10 years after the event. The retrospective analysis can only be justified if the sanction is proportional to the ways that athlete can defend themselves. The longer the retrospective analysis can go back, the more difficult it becomes for an athlete to defend her or himself. The athlete would be forced to keep a personal archive of all kinds of information for a long period (what did I drink and eat, what did I do, when and where for a period of 10 years). If not, an athlete can never defend her of himself adequately. This is also of special relevance, as there is a strong misconception that laboratories never make a mistake. If we increase the period of sanction together with the increase of the period that the retrospective analysis can go back, a fair defense can become impossible and out of proportion in relation to the sanction. Perhaps other policies should be developed.

One solution could be a different approach to collecting evidence. Currently, in sport justice, the doping authorities must collect a minimal amount of evidence, while the accused athlete is supposed to prove her or his innocence with a maximum amount of effort. If this is becoming more difficult for the athletes due to retrospective analysis and is actually out of proportion, we should perhaps require that the doping authorities collect a maximum amount of evidence, like in criminal justice, while the accused athlete should only be required to prove the opposite with the minimal of effort. After all, the increased sanctions are becoming similar to sanctions typically used for criminal justice, justifying a change of approach. Short sanctions justify a maximum amount of effort to prove innocence by the athlete her- or himself, and long sanctions, from my point of view, can only be justified by a maximum amount of effort to prove guilt by the doping authorities. Only this way can we create and restore a fair sanction policy, which is in balance with the situation of the athlete.

Currently, there is an imbalance due to the increase of sanctions and unchanged legal position of the athletes. Moreover, retrospective analysis does not only imply a sanction during several years onwards, it also destroys a complete career backwards. This creates even more imbalance.”

What do you think of this statement from Kasper in the NYT article: “We need to stop pretending sport is clean […] It’s a noble principle, but in practice? It’s entertainment. It’s drama.”  

“Sport is the rewarding of talent, and the application of doping affects this basic principle of sport. Therefore, we should never accept the use of doping (although we should also sanction athletes in a fair, acceptable and proportional way). Otherwise, we may as well skip other sport rules and principles and go back to the old Roman gladiator games, where everything was allowed, so long as it was drama.”

The thoughts of... Herman Ram

Director, Doping Authority, the Netherlands

How is analytical science developing in the sports doping arena?  

The 98 new cases after reanalysis of samples from the Beijing and London Olympic Games are clear examples of progression. Great progress has been made in the equipment for LC-MS and GC-MS, but it is true that basically all procedures have developed, although in different ways. For instance, EPO is nowadays detected by applying two completely independent methods (IEF and SDS-PAGE), instead of one.

Where does the analysis end? 

Currently, thresholds are only set for substances that are either endogenous or (in low quantities) present in our natural environment. The lower LODs lead, on the one hand, to more detection of deliberate doping use (for instance micro-dosing and detection after a longer time span), but this development also leads to a rise of cases in which there is no intentional use of doping substances (contamination of food supplements being the most common example of this). Several possible approaches to this latter problem are being discussed, including the introduction of thresholds for more (or even all) substances, and the issuing of a warning in cases wherein a low concentration of a substance is detected (and only starting disciplinary proceedings when a similar situation reoccurs). None of these suggestions are, however, expected to be put into the rules any time soon.

Is it ethical to analyze – and punish – so many years after the event took place? 

The use of doping is unethical, not the detection thereof. There is a clear Statute of Limitations in the rules (presently 10 years) and analytical scientists should do their best to detect doping use within that period. After the Statute of limitations, no disciplinary proceedings can be started, of course (and rightly so).

What do you think of this statement from Kasper in the NYT article: “We need to stop pretending sport is clean […] It’s a noble principle, but in practice? It’s entertainment. It’s drama.” 

Mr. Kasper seems to throw in the towel, thus abandoning all athletes who want to compete clean. Sport isn’t clean, and it will never be completely clean (and I myself certainly have never stated otherwise). But although the fight against doping is far from perfect, it is our duty to protect clean athletes to the best of our abilities. Allowing doping for the sake of the entertaining qualities of sport is an unacceptable infringement of athletes’ rights.

The thoughts of... Francesco Botrè

Professor, Department of Experimental Medicine, Sapienza University of Rome, Italy

How is analytical science developing in the sports doping arena?

It is not only the technology that gets progressively better (i.e. in terms of the performance of the analytical instrumentation used by the anti-doping laboratories); it is also, if not mainly, a deeper knowledge of the pharmacological profile of the prohibited drugs. The isolation of a previously unknown metabolite can prolong the window of detection of a given drug over a very long period – even longer than the one achieved by targeting an ‘old’ metabolite using newer instrumentation. The same holds true for the study of drug interactions (those who use doping seldom use one drug only). In other words: it is not simply analytical chemistry, but rather a combination of biochemistry, pharmacology, organic chemistry, protein chemistry, molecular biology (including, of course, analytical chemistry).

Where does the analysis end?

There is no end from a merely analytical point of view; clearly, the discrimination between an actual doping offense (i.e. intentional intake) and accidental doping is increasingly difficult as the detected concentration of the prohibited drug/metabolite decreases. Supplementary information may be necessary below a certain concentration value. At the same time, the issue of ensuring long term retrospective detectability of specific drugs could be overcome by a more frequent testing of the athletes. Should an athlete be tested, let's say, every other week, it would be no longer necessary to ensure a LOD allowing the detection of a drug taken six months earlier...”

Is it ethical to analyze – and punish – so many years after the event took place?

I would like to reverse the question here: if you trained hard and performed at your best, but you still lost a medal against a competitor using doping, would you not be happy to have ‘justice’, even after 8-10 years? Nonetheless, I understand this is more a legal and ethical issue rather than a merely scientific one.

What do you think of this statement from Kasper, in the NYT article: “We need to stop pretending sport is clean […] It’s a noble principle, but in practice? It’s entertainment. It’s drama.”

The doubt arises if you consider sport mostly as an attraction, entertainment, drama, or business. Instead, doping has to be fought with consideration for the primary goals, which are: the protection of fair play, of the athletes' health, and, overall, of the ethical value of sport.