What first drew you to the field of anti-doping science?
During my undergraduate years, I developed a strong interest in organic chemistry, but I was particularly drawn to analytical chemistry in all its facets. Trace analysis, in particular, fascinated me, and I had the opportunity to work in this area as a student, preparing and analyzing samples for pesticide residues. That was likely where it all began.
At the same time, I became aware of the anti-doping laboratory in Cologne at the German Sport University, where I was – coincidentally – also enrolled as a sport science student. That was when the idea of pursuing my master’s thesis in this field really took shape.
It allowed me to combine two passions – analytical chemistry and sport – in a way I had never anticipated when I first started studying chemistry at the University of Technology in Aachen. And here we are, almost exactly 30 years later.
Looking back, what do you consider your most significant contribution to the anti-doping field?
I would prefer that my peers decide whether I have made a significant contribution to the anti-doping field or not. But I have certainly had the opportunity to witness – and be part of – major developments, including the emergence of new drugs and doping methods, alongside rapid advances in analytical instrumentation, sample preparation, affinity purification, and DNA/RNA technologies.
While new drugs and methods have created opportunities for those seeking to undermine clean sport, analytical approaches have evolved just as rapidly. The ability to combine and apply these tools has led to more powerful, forward-looking, and preventive anti-doping strategies.
Identifying a single, most significant contribution therefore depends very much on the time period in question. If you had asked me 20 years ago, I would have pointed to the development of a method to detect plasma volume expanders used to mask erythropoietin misuse in endurance sports.
A decade later, I might have highlighted work on analyzing and differentiating recombinant peptide-based drugs, such as insulins, in human urine, blood, and dried blood spots using advanced mass spectrometry.
More recently, I would point to the introduction of a first-of-its-kind multiplexed gene doping testing panel, combining PCR and mass spectrometric approaches.
You’ve described doping control as an “arms race.” From an analytical perspective, how has that race evolved over your career?
There have been enormous developments in many respects, and we have learned that the creativity of those attempting to evade detection should never be underestimated. Fortunately, advances in anti-doping research – combined with increasingly sophisticated instrumentation – have enabled accredited laboratories worldwide to develop methods that cover most critical drugs and doping strategies with a reasonable degree of retrospectivity.
One key area of progress has been in understanding drug metabolism and elimination. This has led to the identification of long-term metabolic products of prohibited substances, particularly anabolic-androgenic steroids. When combined with more sensitive chromatographic and mass spectrometric methods, detection windows have been extended from days or weeks to, in some cases, months.
As a result, the use of anabolic agents can now be proven long after drug use has ceased. This has had significant consequences – for example, in re-testing programs where samples from past Olympic Games have been reanalyzed using modern techniques, leading to numerous additional adverse findings and the reallocation of medals.
At the same time, improved analytical capabilities have enabled the detection of next-generation substances, including peptide- and protein-based drugs, as well as DNA- and RNA-derived compounds.
However, the challenge has also grown. Maintaining up-to-date methods that cover all relevant and emerging targets is increasingly difficult – especially when considering substances that were never approved or have been discontinued, but may still be misused.
This raises an important issue: the balance of resources. The costs associated with comprehensive doping control continue to rise, and it is becoming more difficult to maintain parity between the analytical “arms” available to anti-doping laboratories and the evolving strategies of those seeking to circumvent them.
Do you feel anti-doping science is keeping pace with increasingly sophisticated forms of doping – or are there areas where the gap still concerns you?
The continuity and quality of anti-doping research are very impressive, but the field has also become increasingly complex and demanding. It is not an area where progress can slow down – even briefly.
There are many aspects to consider, but one key example is the rapid expansion of modern therapeutics. Many of these are designed to mimic natural biological processes, compensating for deficiencies or regulating the expression of factors that are directly relevant to athletic performance. This presents a major challenge for doping controls.
In such cases, anti-doping science must address not only the analytical chemistry aspects, but also the medical context and the interpretation of results. Generating the necessary data to support reliable detection is both time-consuming and costly. As a result, it must be acknowledged that there are likely periods during which certain forms of doping may go undetected.
This is one of the strongest arguments for long-term sample storage and re-testing programs. With samples stored for up to a decade, re-analysis using improved methods can still lead to actionable findings years after the original test.
What do you see as the most exciting – or most challenging – analytical frontiers right now?
That is difficult to answer definitively. However, one area I find particularly exciting is the investigation of new classes of drug candidates with novel mechanisms of action that may affect athletic performance.
These studies increasingly rely on advanced technologies such as single- or multi-organ-on-a-chip systems, which allow researchers to examine drug metabolism, distribution, and elimination in highly controlled environments. Different routes of administration – such as transdermal, subcutaneous, or intravenous – can be simulated, and the formation of metabolites can be monitored over time.
In addition, the rapidly expanding possibilities for genetic manipulation at both the DNA and RNA level represent both a major challenge and an exciting frontier for analytical chemistry.
The biological passport has shifted anti-doping from substance detection to pattern recognition. Do you see this as the future?
The athlete biological passport has become a central and indispensable tool in anti-doping. Its importance will likely continue to grow over time.
However, it might not replace conventional direct detection methods in the foreseeable future, which provide immediate proof of the presence of a prohibited substance in an athlete’s system.
There’s increasing discussion about fairness. How confident are you in the robustness of today’s anti-doping systems?
This is a very important and complex issue. With the significant improvements in analytical sensitivity, retrospectivity, and comprehensiveness, it is now possible to detect extremely small amounts of prohibited substances – even in cases where an individual may have been unknowingly exposed to pharmacologically insignificant levels.
Various exposure scenarios have been studied and debated, supported by research simulating contamination and investigating drug elimination profiles. For some substances, time- and exposure-dependent metabolic patterns have been identified, which can help result interpretation and decision-making. However, the sheer number of possible real-world scenarios means that not all situations can be fully replicated or understood through laboratory studies alone.
One proposed approach to address this challenge has been the introduction of additional minimum reporting levels. While these exist for certain substances, they are not widely applied – for example, in the case of many anabolic agents. In principle, this could be a viable solution, but it would require sufficiently frequent and comprehensive testing to offset any reduction in analytical retrospectivity.
This is particularly important because anabolic agents are often used during out-of-competition periods, while their performance-enhancing effects can persist for weeks or months after use.
Finally, any discussion must also consider the practical constraints – both the financial limitations of anti-doping programs and the burden that testing places on athletes.
Knowing what you know about doping prevalence, can you still enjoy sport purely as a fan?
Yes, I can – and I continue to believe that the majority of athletes are honest and clean.
Looking ahead, how do you see analytical science shaping the next decade of sport?
The ability to monitor an increasing number of parameters relevant to athletic performance – both nutritional and hormonal – has expanded significantly.
In particular, the growing availability of minimally or non-invasive sampling approaches, such as oral fluid, dried blood spots, and sweat, combined with real-time data acquisition through next-generation wearables, is transforming how data can be collected and used.
These technologies provide athletes, coaches, and support teams with an unprecedented amount of information, with the potential to significantly enhance performance. As physiological markers can be tracked more frequently, athletes and their teams can respond and adapt more quickly – supporting both athlete health and sustained performance over time.
Mario Thevis is Professor for Preventive Doping Research and Director of the Institute of Biochemistry and the Center for Preventive Doping Research, German Sport University Cologne, Germany
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