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A scientific glimpse into a perpetual battle

In the 1960s Summer Olympic Games in Rome, Danish cyclist Knud Enemark Jensen collapsed during a road race and died of an alleged overdose of amphetamines and a vasodilator that he took as performance enhancers. The case raised an international discussion that swelled into the very first doping scandal. The war on doping had officially begun.
Story By; Marianna Tampere

Intentional improvement of performance has been used by athletes throughout sports history. Some ancient Greek champions are believed to have boosted their performance at the time of the original Olympic Games between 776 BC and 393 AD. They would eat sheep testicles in the hope to gain strength and virility or drink stimulating mushroom and herbal mixtures that were often hallucinogenic or poisonous. Even in modern times athletes have been willing to risk their health and life for gold. When physician and publicist Bob Goldman asked elite athletes if they would take an illegal drug that would guarantee victory in every competition but kill them after 5 years, more than half said yes. In the time from 1982 to 1995, he regularly repeated the study, but continued to find the same sad result.   

Motivated by Jensen’s death, modern anti-doping enforcement was established in 1967, albeit with immense limitations due to initially poor methods of analysis. The Olympic Games Medical Commission introduced its first drug testing at the 1968 Winter Olympics in Grenoble, France, and later that year at the Summer Olympics in Mexico City. The first athlete to be tested positive and disqualified was Swedish pentathlete Hans-Gunnar Liljenwall for alcohol use, which he explained as “two beers to steady the nerves”. In 1999, the World Anti-Doping Agency (WADA) was established as an independent international organization to regulate, promote and monitor the fight against doping in sports. Frankly, nobody knows how many athletes really dope, but the leaks hint at a widespread problem. Thrilling moments of victory are sometimes overshadowed by ugly headlines covering yet another doping scandal. According to a WADA statistics from 2015, the disciplines with the highest number of violations were bodybuilding, athletics and weightlifting with an average of 250 rule violations per year.

The doping classics

Over the years, the battle between dopers and anti-doping agencies has been following a consistent pattern: new doping substances are continuously being synthesized and new deceitful techniques are being developed. Eventually, they end up on WADAs ever-growing list of prohibited compounds and methods. The list is regularly updated as new and better detection methods are being developed and implemented.

Athletes have been willing to risk their health and life for gold

Drugs that boost the production of muscle mass, stimulate alertness or increase oxygen availability in the blood are all doping classics that have been around for a long time. Anabolic-androgenic steroids (AAS) such as Stanozolol have skeletal muscle building (anabolic) and masculinizing (androgenic) effects. AAS include androgens like testosterone and its synthetic analogues, hundreds of which were developed during the 1950s. When AAS bind androgen receptors, they activate downstream signaling pathways in cells that increase protein synthesis and prevent muscle breakdown, resulting in the growth of muscle mass. Taking AAS increases strength up to 20% within 10 weeks with most significant improvements in bench press, explaining the heavy use of AAS by weightlifters. However, AAS consumption comes with numerous side effects that depend on the dosing and length of drug abuse: masculinization of women, feminization of men, immune system and growth problems, just to name a few. Moreover, a 2007 study has revealed frightening long-term damage to mental and physical health of Eastern German athletes and their children after 20 years of state-organized doping with AAS.

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Amphetamines such as Dexedrine have crossed over to sports from the military in the early 1950s and since then have been widely used due to their stimulating effects on both a physical and a cognitive level. These drugs are banned only during competitions. At therapeutic doses, amphetamines improve endurance, alertness and reaction time via the neurotransmitter dopamine. Amphetamines increase synaptic levels of neurotransmitters, such as dopamine, by releasing them from neurons and by blocking their reuptake from the synapse. Again, the list of unwanted side effects is long, including serious addiction, cardiovascular, sexual and psychiatric consequences.   

Perhaps the most widely-known doping substance, erythropoietin (EPO), is a hormone that is naturally produced in the kidneys to promote red blood cell production in bone marrow when the body senses low blood oxygen and iron levels. Since it became possible in the late 1980s to synthesize the hormone in cell culture using recombinant DNA technology and make it more stable than its natural counterpart, EPO has led to a doping revolution in endurance sports.

Those fighting against doping are naturally at a disadvantage because when testing for performance enhancers one needs to know what to look for

What makes EPO so attractive for sportsmen is that the increased number of red blood cells directly correlates with an increased performance because there is more oxygen available to the body. On the other hand, EPO misuse can lead to stroke, blood clotting and autoimmune diseases. EPO has been banned since the 1990s, but a validated test was not implemented until 2000. The test detects EPO in blood or urine by isoelectric focusing that separates natural and synthetic EPO (among other proteins) based on their electric charges, followed by Western blot detection.

The majority of other doping substances, including amphetamines and AAS, are analyzed by accredited laboratories in the urine by means of separation based on chemical properties using gas chromatography, followed by detection on a mass spectrometer using their mass-to-charge ratio. Unfortunately, cheaters have taken a step further to gain competitive advantage. They would use, for instance, diuretics and other masking agents to increase urine production and thereby excretion of prohibited drugs. Therefore, most diuretics have found their way onto the blacklist, too.

The times, they may be a-changin’

Those fighting against doping are naturally at a disadvantage because when testing for performance enhancers, one needs to know what to look for. Moreover, no individual test can detect all banned substances. Despite the challenging battle, the goal of having doping-free sports competitions drives anti-doping agencies to persevere. Since 2001, WADA has supported research with 69 million USD to develop and improve detection methods and study emerging doping threats, such as gene doping. Recently, WADA introduced a novel strategy called “Athlete Biological Passport” (ABP). The principle is to monitor various biological parameters from blood and urine over time in order to indirectly reveal the effects of doping, rather than detecting the substance itself. The first “Hematological module” of the ABP, implemented in 2009, looks at a panel of blood biomarkers for the detection of blood doping. The second “Steroidal module”, applied in 2014, focuses on urine parameters aiming to reveal AAS usage. Over time, the ABP has been significantly improved and serves as a valuable tool to indirectly detect doping with substances that have not yet made it into the banned list.

Cheating in sports has been around for centuries, and the continuous arms race between the two sides will probably go on. However, there seems to be a change happening in athletes’ mindsets. In a recent repetition of Goldman’s survey, only 6% of athletes answered they would take doping that would make them win but eventually kill (in absence of legal consequences) – in stark contrast to the original study. This is perhaps the true measure of the impact and achievements of WADA and the anti-doping movement. So, let’s hope that the power of science will eventually lead the clean and fair sport to the win.

This article was previously published in Medicor 2017 #2
Proofread by: Zach Chia

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