DAY 1. IT’S ALL ABOUT MOLECULES IN A TOOLBOX! A. Defining the context and demystifying molecular biology We all have a plan ! Every science is based on some general model that makes it possible to do research and make discoveries. This is of course true for modern biology which is built on what is known as the Central Paradigm of Molecular Biology. Performance, doping and anti-doping as biological phenomena Rigorous, scientific, and simple definitions of key concepts necessary for literacy in doping biology and anti-doping sciences. What are molecules & Co? Everything you wanted to know about molecules and how they come together to build the living world, but never had the chance to ask. What is a cell? A logical, no-nonsense model of how molecules come together to form a cell and how they work together and deliver performance. B. Targets of doping What is a doping molecule and a doping method? The whole doping / anti-doping field seen from the point of view of molecules. Muscle cells How do they work? Where do they come from? What do they need to work? What can alter their performance? Nerve cells How do they work? Where do they come from? What do they need to work? What can alter their performance? The brain The whole is more than the sum of its parts… and the brain as an organ proves ! What are the essential features of brain biology that make it such an important target for performance enhancement? Blood What do different blood cells do? Where do they come from? What do they need to work? What can alter the performance of blood? Help Dr Jekyll, the doping expert Targets of doping and doping molecules are all it takes to start building a doping plan. Can you help Dr Jekyll help his team win, no matter at what cost? C. Anabolism and catabolism: the ying and yang of performance Where do molecules come from? We ingest nutrients, our body produces its own molecules, and we can take drugs… A molecular overview of anabolism and the principal modes of action of drugs. Where do molecules go? An overview of catabolism and excretion. Molecules… gone with the wind? Not exactly. The dynamic body map of molecules At the end of the day, we will construct the athlete’s body as a interconnected network of performing molecules! DAY 2. SCIENCES IN DOPING AND ANTI-DOPING A. The essentials of biology relevant to doping We will begin the day by a quick review of all the concepts presented during day 1 and necessary to understand sports performance at the molecular level and how it can be enhanced legitimately and illegitimately. B. Biotechnology for doping… and everything else The "biotech revolution" started some 20 years ago with the production of fully human complex biological molecules in simple microorganisms thanks to recombinant DNA technology. We have just begun to reap the benefits from this formidable new technology… and society hasn't even started answering the fundamental questions it raises, in particular in the field of performance enhancement. To address this complex issue, biotech literacy is essential. In this section of the course we will explore the following key concepts and methods in this new science: recombinant DNA technology and cloning, chemical synthesis, microbial fermentation, mammalian cell culture, stem cell therapies, gene therapies and protein and cell engineering. C. Biotechnology against doping The major part of the second day shall be devoted to a detailed exploration of state-of-the-art diagnostic techniques used in the fight against cheating athletes, including: Gas chromatography and liquid chromatography (GC, LC) Mass spetcrometry (MS) Isotopic ratio mass spectrometry (IRMS) Electrophoresis and isoelectric focusing (IEF) Western blotting, Enzyme-linked immunosorbent assay (ELISA) Fluorescence activated cell sorting (FACS) Whenever possible we will link the laboratory diagnostics and related tasks to real world examples (such as CAS doping cases) that will illustrate the essential strengths and weaknesses of each technique and what can go wrong in the entire process of a testing campaign. C. What makes good anti-doping science? As a conclusion to day 2, we will recapture the essential scientific methodology needed to build up a solid case for the fight against doping. Key notions in diagnostics such as sensitivity, specificity, negative, positive controls, statistical data treatment and good laboratory practice will be presented in the context of an "ideal" anti-doping testing scenario. DAY 3 - WADA PROHIBITED LIST: A SCIENTIST'S AND ATHLETE’S VIEWS The major part of the third day will be devoted to exploring the WADA prohibited list with the eyes of a scientist and of an athlete, using the information and tools acquired during the first two days of the course. By doing so, the participants will consolidate their knowledge and have the opportunity to ask scientifically sound questions. Typical issues we may address include the following: Molecular properties of the prohibited substance or method, effects on performance and health, adverse interactions, cocktails… The modes of action of the prohibited substance or method, its metabolism, modes of administration, reasons for therapeutic exemption, associated masking methods… Current and future detection methods, window of detection, false positives and negatives, specificities, sensitivities and other limitations of detection methods… Brand names, generics, history of development, IP and legal issues, related substances… Of course, these explorations cannot be comprehensive. However, participants will have the opportunity to customize this part of the course and to apply their newly gained literacy skills to start making more sense of the scientific foundations of the WADA prohibited list. Whenever possible we will link selected prohibited substances or methods to real life doping cases emphasizing aspects that are the most relevant to doping/anti-doping. The overall objective is to analyze the complete chain of custody in doping control for a better understanding of the roles played by all stakeholders and to explore “what if” scenarios to better understand risk assessment and management of uncertainties. C. From reading the WADA prohibited list to making decisions To wrap-up the exploratory work above, we will link the information in the WADA prohibited list to Dr Jekyll’s doping plan as a means to consolidate all the knowledge gained in the course and put it to use in the context of performance enhancement. In parallel, we will build an anti-doping decision-making tree which highlights the main scientific certainties and uncertainties in the use, misuse and detection of prohibited substances and methods. C. Out-of-competition testing The design and implementation of an effective out-of-competition testing campaign is one of the main challenges faced by anti-doping officials today. We will attempt to provide scientifically sound, rational answers to the essential questions in OOC testing: who to test, when, for which prohibited substances and methods and why? In spite of the complexity of the task, the emerging concept of intelligence testing, borrowing on key notions and methods developed in health prevention campaigns and public health in general, paves the way to effective OOC testing methodologies. D. The future of the fight against doping Doping is like any other recurrent epidemic of some non-infectious disease: it will never be fully eradicated. If so, the objective is to find the most effective and efficient manner to contain the phenomenon (keeping sports clean), while minimizing adverse side effects (high costs of all kinds, suffering, sensationalism, bad press). Primary prevention (lifelong dissuasion) and secondary prevention (targeting doping controls in an individual athlete) may well be the key to effective doping control. Such an approach implies longitudinal individual and collective follow-up of athletes and the existence of a genuine biological passport. Understanding the scientific foundations of what may be ultimately the only definitive answer to the doping epidemic will conclude the last day of the course.
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