(from literature gather up to January 2016) From the Anti-Doping Library THE HISTORY OF DOPING AND ANTIDOPING A systematic collection of published scientific literature 2000-2015 Åke Andrén-Sandberg From the Department of Surgery, Karolinska Institutet at Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden CONTENT SUMMARY INTRODUCTION Semantics Overview of doping and anti-doping history Background Fundamental aims of anti-doping Ancient Greek doping 20th century Testing for doping substances in the urine International Olympic Committee (IOC) A continuing challenge: from mushrooms to testosterone German Democratic Republic An international epidemic WADA Blood doping SOME SPECIFIED DATES IN DOPING AND ANTI-DOPING HISTORY Individual cases of certain importance for the history and future Knud Jensen, 1960 Tom Simpson 1967 Ben Johnson 1988 Katrin Krabbe et al Lance Armstrong Maria Sharapova ANCIENT HISTORY OF DOPING AND ANTI-DOPING The first marathon History of sports medicine in ancient Greece Religious ceremonies and athletic competitions Training under supervision Critique of the diet by Hippocrates and Galen Critique of athletics by Philostratus Attempts for performance-enhancing in ancient Greece Dried figs A dangerous game EARLY (MODERN) HISTORY OF DOPING AND ANTI-DOPING First racehorses then strychnine Amphetamines Anabolic steroids Women in sports The first doping in the modern Olympics Olympic nationalism First doping The Olympics 1976-1992 The Second Olympic Games in Athens Football Drug testing Biking Antidoping IAAF banned first Testing Blood doping HISTORY OF TESTOSTERONE AND SOME OTHER ANABOLIC STEROIDS Medical challenges Anti-anabolic castration Castration Organotherapy Scientific exploration of the testes and their function Transplantation of testes in 1786 Transplantation of testes in 1849 More modern transplantation of testes Charles-Edouard Brown-Séquard Birth of endocrinology The Steinach operation Serge Voronoff A Nobel Prize for testosterone research Dubious experiments on prisoners Further research on testosterone Chemical isolation of testosterone A second Nobel Prize for studies on testosterone From German soldiers to Marion Jones Repeated economic success Interests of the pharmaceutical industry A black market Development of new testosterone preparations Stacking and cycling Transdermal testosterone The era of anabolic steroids in doping Bob Hoffman and the Soviet connection An epidemic All sports Science versus ethics Soviet and East Germany Side effects The struggle against the anabolic steroids in sports Laboratory progress Background to T/E ratio US legal actions France and Belgium World Anti-Doping Agency (WADA) History of nandrolone History of aromatase inhibitors History of 5-alpha-reductase inhibitors enzymes (e.g. finasteride) HISTORY OF BLOOD DOPING Semantics Physiological background for blood doping Blood transfusions Research Practical doping Erythropoietin Physiological background Doping with erythropoietin A proxy for failing erythropoietin testing Doping problems in cycling Early testing strategies for blood doping History of detection of recombinant erythropoietin and derivatives Hypotheses on deadly erythropoietin doping practice Sudden deaths in Swedish orienteers Background to the athlete biological passport HISTORY OF DOPING WITH GROWTH HORMONE Physiology of growth hormone in regard to doping Risk of Creutzfeldt-Jakob disease Doped Testing for growth hormone HISTORY OF DOPING WITH OTHER SPECIFIED SUBSTANCES AND METHODS History of doping with human chorion gonadotropin History of doping with insulin Insulin physiology History of doping with caffeine History of doping with ephedrine History of doping with beta2-agonists History of doping with morphine History of doping with cannabis History of doping with xenon History of doping with alcohol History of doping with gamma-Hydroxybutyric acid (GHB) History of doping with ecstacy History of attempts to dope with nutritional supplements History of caffeine-containing nutritional supplements History of doping with creatine History of doping with carnosine History of gene doping Medical history of placebo HISTORY OF THE ATHLETE BIOLOGICAL PASSPORT Semantics Manfred Donike A database since 1989 Longitudinal monitoring DOPING IN THE OLYMPICS The ancient Olympic games The first tests in modern Olympics Doping during the modern Olympics The Olympics in medical journals Canada HISTORY OF WADA World Anti-Doping Agency (WADA) From the homepage of WADA The vision The core values Logo story The agency's history Pre-WADA history Formation of the IOC Medical Commission Formation of the World Anti-Doping Agency The code Definitions National antidoping organizations (NADOs) Formation of Court of Arbitration (CAS) Out-of-competition testing History of therapeutic use exemptions (TUE) Anorchia Aplastic anemia Congenital adrenal hyperplasia (CAH) and hypogonadism Stimulation medication Danazol Glucocorticoids and diuretics Beta-blocker Recognising the concept of TUEs More recent Olympic Games Legislation Courtroom, economics and anti-doping USA Industrialized doping Laboratory testing Adverse findings 2005-2011 from the Doping Control Laboratory of Athens The 2005 WADA list The 2011 WADA list The 2012 WADA list The 2013 WADA list Category 0 Monitoring program The 2014 WADA list Erythropoesis-stimulating agents Amendment to the 2014 Prohibited List Implementation of the World Anti-Doping Code 2015 Non-approved substances Important persons in anti-doping Richard W Pound Arne Ljungqvist EFFECT OF INTERNATIONAL RESULTS DURING THE ANTI-DOPING ERA Influence on world records in running by doping and anti-doping testing World records in running as indication for doping in the elite Prediction of further improvements (year 2002) 100 meter and 5000 meter 100 meter in Olympic Games REFERENCES SUMMARY Semantics Throughout history, athletes have sought to improve their performance through dietary and medical help. Doping is the use of banned pharmacological substances or metods with the unique aim of improving physical performance, sometimes even to the price of serious adverse effects on health. Doping is as old as sport itself. The word itself is likely derived from the Dutch word, dop, the name of an alcoholic beverage made from grape skins and used by Zulu warriors to enhance their prowess in battle – however, first of all a drink used as a stimulant in South African ceremonial dances. The term “doping” progressed into mainstream use in the early twentieth century, originally referring to drugging of racehorses. However, what substances and methods that should be regarded as ”doping” is still a matter of opinion, and it must be understood that the definitions of doping is dependent on time and who make the proposal. Morover, there are differences regarding definitions also depending on in which situation doping is discussed: - The international sports federations relies on WADAs list which is updated yearly - National laws which is different in different countries and usually only concerns hormones (amphetamines etc are dealt with by other laws) and are updated with many years delay - The public, including the mass media, which is very moralistic and nationalistic and swings from one opinion to the other with little time delay In this booklet: doping = substances and methods on the WADA list In the 1980s, Jean D Wilson citing the singularity of androgen receptor, suggested that androgenic and anabolic activity of androgens could not be dissociated. Therefore, he and others have argued that the term androgenic-anabolic steroid is a misnomer and should be abandoned. By laymen the use of androgenic anabolic steroids are usually shortened to “steroids”, which for the fundamentalistic chemist of course is very incorrect. In this booklet it is used the middle way, which means “anabolic steroids or AS (sometimes AAS)” – right or wrong, that is what is commonly use in the anti-doping vocabulary. Ancient Greek doping The practice of enhancing performance through foreign substances or other artificial means is as old as competitive sport itself. As early as BC 776, the Greek Olympians were reported to use substances such as dried figs, mushrooms, and strychnine to perform better. 19th and 20th centuries The modern era of doping dates to the early 1900s, with the illegal drugging of racehorses. Alfons Bukowski (1858-1921) is commonly regarded as the pioneer of anti-doping research. In 1910, he developed a method to detect alkaloids in horse saliva. One hundred years later, this is a good moment to remember Bukowski, an outstanding Polish pharmacist, often mistakenly represented in world literature as a Russian chemist. It is also an occasion to mention that the real driving force in the history of doping were events related to horse rivalry. In modern times, there is a correlation between the discovery of a drug and its use in sports. During the end of the 19th Century and the beginning of the 20th Century, new illicit substances were incorporated into sport. In 1896, Arthur Linton, a Welsh cyclist, died under the influence of stress and speed ball (cocaine + heroin) during the Tour de France. In 1904, and he has the dubious distinction of being the first known person to die from such drug abuse. The first documented case of drug use in the modern Olympic Games took place when Thomas Hicks, a marathoner, nearly died from a mixture of brandy and strychnine. With the advent of modern pharmacology in the early 20th century, many athletes began to experiment