The most important element in achieving athlete compliance with anti-doping rules is the certainty of detection. Thus, scientific research plays a mission critical role in achieving clean competition. Many factors contribute to the advances in detection. Incremental advances in the ability to detect prohibited substances and methods, and identification of long-lived metabolites continue to lengthen detection windows. While the athlete biological passport hematological and steroidal modules hold great promise, experience shows that new research is needed to improve the sensitivity and specificity of the approach for current doping techniques. Indirect detection strategies using biomarkers or transcriptomic techniques have been increasingly investigated. The incorporation of more cost-effective sampling strategies using dried blood and plasma spots, oral fluid, and breath analysis show great promise toward increasing the number of tests while remaining within testing budget constraints. Despite the importance of research to ensuring rule compliance, a major challenge for anti-doping research is achieving and maintaining sufficient funding in the reality of the myriad of new substances introduced for disease treatment but abused for performance enhancement. In addition, obtaining metabolism and population reference range data, particularly for new drugs or designer drugs that have not obtained approval for administration to human subjects, remains a significant problem. Nevertheless, research continues to contribute important data to support anti-doping efforts.
Despite being prohibited by the World Anti-Doping Agency (WADA), blood manipulations such as the use of recombinant human erythropoietin and blood transfusions are a well-known method used by athletes to enhance performance. Direct detection of illicit blood manipulation has been partially successful due to the short detection window of the substances/methods, sample collection timing, and the use of sophisticated masking strategies. In response, WADA introduced the athlete biological passport (ABP) in 2009, which is an individualised longitudinal monitoring approach that tests primarily haematologic biomarkers of doping in order to identify atypical variability in response(s) in athletes, highlighting a potential doping violation. Although the implementation of the ABP has been an encouraging step forward in the quest for clean/drug-free sport, this detection method has some limitations. To reduce the risk of being detected by the ABP method, athletes are now resorting to microdoses of prohibited blood boosting substances to prevent abnormal fluctuations in haematologic biomarkers, thereby reducing the sensitivity of the ABP detection method. Recent studies from numerous laboratories, including our own, have confirmed the potential of transcriptomic microarrays, which can reveal distinct changes in gene expression after blood manipulations, to enhance the ABP. There is, therefore, an urgent need to intensify research efforts that involve transcriptomics and other state-of-the-art molecular methods, collectively known as “omics”, e.g., proteomics (proteins) and metabolomics (metabolites), in order to identify new and even more robust molecular signatures of blood manipulation that can be used in combination with the ABP and, intriguingly, even as a stand-alone test.
Clarity about the ethical justification of anti-doping is essential. In its absence, critics multiply and confusion abounds. Three broad reasons are typically offered in anti-doping's defense: to protect athletes' health; to promote fairness; and to preserve meaning and values in sport - what the World Anti-Doping Agency (WADA) Code refers to as the spirit of sport. Protecting health is itself an important value, but many sports encourage athletes to take significant risks. The case against doping is buttressed by concern for athletes' health, but it cannot be the sole foundation. Promoting fairness is vital in all sports as the metaphor of the level playing field attests. But playing fields can be leveled by providing performance-enhancing drugs to all competitors. When doping is prohibited, fairness is aided by effective anti-doping. But the fundamental justification for anti-doping is found in the meanings and values we pursue in and through sport.
The advent of gene transfer technologies in clinical studies aroused concerns that these technologies will be misused for performance-enhancing purposes in sports. However, during the last 2 decades, the field of gene therapy has taken a long and winding road with just a few gene therapeutic drugs demonstrating clinical benefits in humans. The current state of gene therapy is that viral vector-mediated gene transfer shows the now long-awaited initial success for safe, and in some cases efficient, gene transfer in clinical trials. Additionally, the use of small interfering RNA promises an efficient therapy through gene silencing, even though a number of safety concerns remain. More recently, the development of the molecular biological CRISPR/Cas9 system opened new possibilities for efficient and highly targeted genome editing. This chapter aims to define and consequently demystify the term "gene doping" and discuss the current reality concerning gene- and cell-based physical enhancement strategies. The technological progress in the field of gene therapy will be illustrated, and the recent clinical progress as well as technological difficulties will be highlighted. Comparing the attractiveness of these technologies with conventional doping practices reveals that current gene therapy technologies remain unattractive for doping purposes and unlikely to outperform conventional doping. However, future technological advances may raise the attractiveness of gene doping, thus making it easier to develop detection strategies. Currently available detection strategies are introduced in this chapter showing that many forms of genetic manipulation can already be detected in principle.
Prior to the formation of the World Anti-Doping Agency (WADA), the fight against doping in sport was not unified; instead, it relied on individual approaches established by various stakeholders to make it effective. The scandal of the Festina Affair, during the Tour de France 1998, and other drug doping scandals revealed the ineffectiveness and inadequacy of such an approach. The resulting media scandal raised public authorities' awareness about the necessity to deal with doping in sport with a harmonized and a more effective approach. The International Olympic Committee interceded and convened a World Conference on Doping, bringing together all parties involved in the fight against doping. As a result, WADA was established on November 10, 1999, in Lausanne to promote and coordinate the fight against doping in sport internationally. In this regard, the World Anti-Doping Code (WADC or the Code) is the core document harmonizing anti-doping rules and regulations within sport organizations and public authorities. The Code was instrumental in introducing the concept of "nonanalytical" rule violations, which are emphasized within the revised 2015 Code. Nonanalytical rule violations allow anti-doping organizations (ADOs) to apply sanctions in cases where there is no positive doping sample, but where there may still be evidence that a doping violation has occurred. This recognition of "nonanalytical" rule violations by WADA is the concrete result of taking into account lessons learned from prior infamous doping scandals. Thus, intelligence gathering, particularly through cooperation with global law enforcement agencies, is a key tool in the fight against doping. The 2015 Code and the international standards on testing and investigations establish and implement intelligence gathering as part of ADOs' routine activities in the fight against doping in sport.
The challenges facing modern anti-doping analytical science are increasingly complex given the expansion of target drug substances, as the pharmaceutical industry introduces more novel therapeutic compounds and the internet offers designer drugs to improve performance. The technical challenges are manifold, including, for example, the need for advanced instrumentation for greater speed of analyses and increased sensitivity, specific techniques capable of distinguishing between endogenous and exogenous metabolites, or biological assays for the detection of peptide hormones or their markers, all of which require an important investment from the laboratories and recruitment of highly specialized scientific personnel. The consequences of introducing sophisticated and complex analytical procedures may result in the future in a change in the strategy applied by the Word Anti-Doping Agency in relation to the introduction and performance of new techniques by the network of accredited anti-doping laboratories.
The list of prohibited substances and methods (the List) is the international standard that determines what is prohibited in sport both in- and out-of-competition. Since 2004, the official text of the List is produced by the World Anti-Doping Agency (WADA), the international independent organization responsible for promoting, coordinating, and monitoring the fight against doping in sport. Originally based on the prohibited lists established by the International Olympic Committee, the List has evolved to incorporate new doping trends, distinguish permitted from prohibited routes of administration, and adjust to new analytical and pharmacological breakthroughs. In this chapter, the elements that compose the List as well as the updates over the years are presented.
For decades, drug testing has been the main instrument at the disposal of anti-doping authorities. The availability in the 1980s of substances identical to those produced by the human body, including the "big 3" (erythropoietin, testosterone, and growth hormone), necessitated a new paradigm in anti-doping. The athlete biological passport (ABP) is a new paradigm, complementary to traditional drug testing, based on the personalized monitoring of doping biomarkers. Athletes who abuse doping substances do so to trigger physiological changes that provide performance enhancement. The ABP aims to detect these changes through its 3 hematological, steroidal, and endocrine modules. Any deviation of a biomarker from what is expected in a healthy physiological condition can be attributable to doping or a medical condition, which, interestingly, is also the criterion used to define a banned substance. Recent advances in proteomics and metabolomics offer immense opportunities to enhance the ABP. The ABP shares multiple aspects with the present customization of health care and personalized medicine.
In sport, a wide array of substances with established or putative performance-enhancing properties is used. Most substances are fully acceptable, whilst a defined set, revised annually, is prohibited; thus, using any of these prohibited substances is declared as cheating. In the increasingly tolerant culture of pharmacological and technical human enhancements, the traditional normative approach to anti-doping, which involves telling athletes what they cannot do to improve their athletic ability and performance, diverges from the otherwise positive values attached to human improvement and enhancement in society. Today, doping is the epitome of conflicting normative expectations about the goal (performance enhancement) and the means by which the goal is achieved (use of drugs). Owing to this moral-functional duality, addressing motivations for doping avoidance at the community level is necessary, but not sufficient, for effective doping prevention. Relevant and meaningful anti-doping must also recognise and respect the values of those affected, and consolidate them with the values underpinning structural, community level anti-doping. Effective anti-doping efforts are pragmatic, positive, preventive, and proactive. They acknowledge the progressive nature of how a "performance mindset" forms in parallel with the career transition to elite level, encompasses all levels and abilities, and directly addresses the reasons behind doping use with tangible solutions. For genuine integration into sport and society, anti-doping should consistently engage athletes and other stakeholders in developing positive preventive strategies to ensure that anti-doping education not only focuses on the intrinsic values associated with the spirit of sport but also recognises the values attached to performance enhancement, addresses the pressures athletes are under, and meets their needs for practical solutions to avoid doping. Organisations involved in anti- doping should avoid the image of "controlling" but, instead, work in partnerships with all stakeholders to involve and ensure integration of the targeted individuals in global community-based preventive interventions.
The purpose of this chapter is to provide an overview of the philosophical and ethical underpinnings of anti-doping policy. The nature of sport and its gratuitous logic is explored. The doping rules in sport, such as the Prohibited List, are ways of drawing a line to facilitate a certain sort of competition. Sports can be understood as a means of testing the natural physical abilities of the athlete, combined with the hard work they put into improving their performance. A test promoted by the anti-doping laws. Permitting certain forms of performance enhancement would threaten the special nature of such a test. Doping can be seen as a threat to the integrity of sport, not just because of the rule breaking doping currently entails. The chapter explores the ethical issues that arise with such forms of enhancement, such as fairness, harms to health, and indeed a refusal to accept human limitations. Finally, the criteria upon which a substance or method may be prohibited by the World Anti-Doping Agency (WADA) is addressed. The 3-part criteria, concerning (1) enhancement, (2) health, and (3) the spirit of sport are described, and literature that takes a critical line is addressed. Particular reference is made to the public health agenda explicit within anti-doping policy.
Traditionally, research in anti-doping has been stimulated by the need for technological improvements to accommodate the expansion of the list of prohibited substances and methods. Nevertheless, in recent years, anti-doping found itself at a crossroads due to the increasing complexity and constant refinement of doping methods. As illustrated by the 2012 USADA (United States Anti-Doping Agency) versus Lance Armstrong case, a change in paradigm was necessary. The exploration of new scientific avenues to understand the mechanisms of doping and pinpoint its practice was most needed to allow designing more efficient preventive or disruptive strategies. In this context, and at the time of writing in 2017, transposing the concept of forensic intelligence to anti-doping was identified as a promising approach to address the different aspects of doping, from the individual athlete to organized doping and trafficking of substances in a proactive rather than a reactive way. Indeed, collection, structuring, and logical processing of multiple sources of information, and not strictly results of bioanalytical testing of urinary and blood samples, can bring additional value to detect and describe potential, emerging, or existing doping issues. This anti-doping intelligence can provide anti-doping authorities and relevant stakeholders with timely, accurate, and usable information for decision making to solve, reduce, and/or prevent doping-related activities. The integration of intelligence to complement other anti-doping approaches is a potentially major step forward in the development of more effective and robust anti-doping strategies.
The introduction, in 2004, of the World Anti-Doping Code and a standardized "prohibited list" of substances and methods proscribed in sport represented a consistent, international response to the escalating challenge of drug misuse in contemporary sport. Simultaneously, it was recognized that athletes experiencing illness or injury might legitimately require the use of "prohibited" medications or procedures, and the concept of the "therapeutic use exemption" (TUE) was introduced. The mechanisms of the TUE process are carefully defined and described in a specific WADA "international standard" (IS). As a consequence, anti-doping organizations (ADOs) were empowered to establish "Therapeutic Use Exemption Committees" (TUECs) whose membership and responsibilities were clearly delineated in the IS, and to whom an athlete and treating physician(s) could make appropriate application for a TUE. A careful review of such an application by a TUEC panel of physicians might allow permission for an otherwise prohibited course of treatment, provided that appropriate criteria had been met. Sport physicians have a clear responsibility to ensure accurate and complete documentation of the clinical circumstances requiring a TUE when completing such applications. Typically, applications for consideration by TUECs are forwarded to a national ADO, but depending on an applicant's level of competition, it may become necessary to involve an international federation or major event organization (e.g., International Olympic Committee, or Commonwealth Games Federation). Such organizations may receive, review, and grant TUEs specific to the competitions over which they preside. Increasingly, there is recognition of TUEs granted by other ADOs. However, this is not always the case; in certain circumstances, the decisions of other TUECs to grant or deny an application may be appealed. The advent of the TUE process ensures that an athlete with a genuine medical condition that necessitates the use of a prohibited substance or procedure can apply for permission to use such treatments and is not denied access to competition or training.
In the fight against doping, creating a level playing field across all sports is very challenging from a legal perspective. A harmonized approach presupposes first and foremost a supreme regulatory authority on a global level. This task cannot be attributed to the public sector, because there is no supranational authority of public international law capable of dealing with it. Thus, responsibility has to be assumed by a private law entity. This in turn requires complicated contractual agreements by which duties and responsibilities are transferred from the individual to the national level and from there to the top of the pyramid. In practice, this process is not only difficult and cumbersome, it also leads to an accumulation of power at the top of the sports pyramid that must be contained by organizational checks and balances, such as access to justice and the rule of law, accountability, transparency, and possibilities for the respective stakeholders to partake in the decision-making process. The weighting of all these different aspects is demanding and further complicated by the regulatory reach of the various national lawmakers. Since national laws differ considerably and a harmonized legislative approach is nowhere near in sight, a global approach in the fight against doping must push back national laws and legal concepts as much as possible. The purpose of this chapter is to give an overview on all these legal challenges.
The pillars of anti-doping are detection, deterrence, and prevention. Detection takes the form of testing for banned substances. Deterrence builds on testing and gathering evidence. Athletes who test positive are exposed to penalties. The main tool of prevention is education. Education takes many forms and can be implemented in many ways. This chapter addresses the nature and challenges of current anti-doping education. Firstly, general goals of education and their connection to sport are discussed. Secondly, three normative interpretations of sport are presented, and their implications for anti-doping education are examined. Instrumentalist interpretations and interpretations with emphasis on performance and enhancement challenge the anti-doping campaign. A human excellence interpretation is advocated in which anti-doping is considered a consistent and integral part of sport. Thirdly, future challenges for anti-doping education are reflected upon.
This chapter addresses both the development and substance of the World Anti-Doping Code, which came into effect in 2003, as well as the subsequent Code amendments, which came into effect in 2009 and 2015. Through an extensive process of stakeholder input and collaboration, the World Anti-Doping Code has transformed the hodgepodge of inconsistent and competing pre-2003 anti-doping rules into a harmonized and effective approach to anti-doping. The Code, as amended, is now widely recognized worldwide as the gold standard in anti-doping. The World Anti-Doping Code originally went into effect on January 1, 2004. The first amendments to the Code went into effect on January 1, 2009, and the second amendments on January 1, 2015. The Code and the related international standards are the product of a long and collaborative process designed to make the fight against doping more effective through the adoption and implementation of worldwide harmonized rules and best practices.
The fight against doping in sport as we know it today commenced by the creation of the International Olympic Committee (IOC) Medical Commission in 1961 following the death of a Danish cyclist during the Rome Olympic Games the year before. After a slow start, the fight got under way as from the early 1970s under the leadership of the IOC and of the International Association of Athletics Federations. Despite a lack of understanding and weak support even from the sports community, a series of measures were taken during the 1970s and 1980s which still form cornerstones of today's anti-doping strategy. In addition to information and education campaigns, the most important examples are the introduction of procedural rules for doping controls, the establishment and follow-up of a list of prohibited substances and methods, the accreditation of doping control laboratories, the introduction of in- and out-of-competition testing, rules for therapeutic use exemption, and the introduction of blood sampling. During the 1990s, the anti-doping fight gained increasing support both inside and outside the sport community. In order to harmonize the wide variety of rules that had developed both in sport organizations and at the domestic level and to promote anti-doping activities, the World Anti-Doping Agency (WADA) was jointly created by the Olympic movement and the public authorities in 1999. WADA is today carrying on the fight supported by the universally accepted WADA Code and an International Anti-Doping Convention under UNESCO.
This paper addresses practical and ethical considerations regarding genetic tests to predict performance and/or risk of exercise-related injury or illness. Various people might wish to conduct sport-related genetic tests for a variety of reasons. For example, an individual might seek personal genetic information to help guide their own sport participation. A sports coach might wish to test young athletes to aid team selection or individualize training. A physician might want to predict the risk of injury or illness in athletes and advise regarding selection or preventative measures. An insurance company might seek to estimate the risk of career-threatening injury for athletes based partly on genetic information. Whilst this information is, in part, encoded in our DNA sequence, the available tests allow generally only a poor prediction of the aforementioned variables. In other words, the current genetic tests and analysis methods are not powerful enough to inform important decisions in sport to a substantial degree. It is particularly disappointing that more than half of the commercially available genetic tests related to exercise and sport do not appear to identify publicly the genetic variants they assess, making scrutiny by academic scholars and consumers (or their representatives) impossible. There are also challenging ethical issues to consider. For example, the imposition of genetic tests on individuals (especially young people) by third parties is potentially susceptible to abuse. Scientists and practitioners should understand the limitations of the tests currently available, the ethical concerns and the importance of counselling before and after testing so that they are only used in a responsible manner.
