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Olympic athletes: Performance-enhancing epigenetics?

                                      
With the coming of the Winter Olympics in PyeongChang later this week, I thought it would be interesting to take a look at a brief history of the use of performance-enhancing drugs in athletic competitions. In view of a paper published in Nature this week titled “Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy”, I ask the question: Does this mean once a cheat always a cheat?

Let's look back at the original ancient Greek Olympics. The only thing deemed unethical was fixing the contest. Historical evidence indicates Greek Olympic athletes consumed excessive amounts of meat beyond their normal diet. They experimented with herbal medicines to enhance athletic performance. Some even went as far as eating animal testicles in search of potency.

You can well imagine that Roman gladiators needed to use stimulants and hallucinogens just to enter the ring.
Any fatigue or prior slight injury could be fatal.

In the late 19th century competitive French cyclists were known to chew on coca leaves to fight fatigue and hunger. In the early days of the modern Olympic movement, athletes were known to have their own secret mixes of strychnine, heroin, cocaine and caffeine sometimes developed by the coach or the team. The first actual rules against doping in sport came in 1928 when the International Association of Athletics Federation (IAAF) prohibited doping by athletes.

We are led to believe that during the second World War, American, British, German and Japanese armed forces all used amphetamines to counteract fatigue, give them an elevated mood and heighten performance. By the 1950s athletes were also routinely using amphetamines.

Russian weightlifters were using testosterone as early as 1954 and US weightlifters began experimenting with anabolic steroids. The Food and Drug Administration approved steroids for sale in the US in 1958.

On August 26th, 1960 the first Olympic athlete died in competition due to doping. Danish cyclist Knut Jensen collapsed and died during a race. Autopsy results revealed the amphetamine Ronicol was to blame.

The British cyclist Tommy Simpson was named BBC Sports Personality of the Year in 1965. His motto was “if it takes ten to kill you, then take nine and win". When he died in the 13th stage of the Tour de France in 1967, his death created pressure for sporting agencies to take action against doping. In 1967, the International Olympic Committee (IOC) established a medical commission to fight doping.

The first compulsory doping controls at the Winter Olympic Games took place in 1968 at Grenoble, France. Anabolic steroids were added to the IOC banned list in 1975 and the first testing for steroid abuse took place at the 1976 Montreal Olympic Games.

Many Canadians will remember the thrill of seeing Ben Johnson cross the finish line first to win a gold medal at the 1988 Seoul Korea Olympic Games. They will also remember the disappointment when he was stripped of the medal the next day for testing positive to stanozolol, a prohibited anabolic steroid.

In 1999 the World Anti-Doping Agency (WADA) was established. This created an independent International anti-doping agency to be in place for the 2000 Olympics in Sydney, Australia. WADA banned gene doping in 2003. By 2004 WADA took control of the prohibited list from the IOC. In 2006, US President Bush signed a law banning gene doping in sports. This effectively prohibits the use of genetic modification for performance enhancement in any American athletic competitions.

A long-term study done in 2007 examined former German athletes and their children. Forty years after doping, one quarter of the athletes in the study had developed some form of cancer. One third had attempted or had thoughts of suicide. The risk of miscarriage and stillbirth was 32 times higher than the normal population and some of the children born had physical deformities or were mentally handicapped. A very high price to pay for Olympic glory.

The number of professional road racing cyclists that have been involved in doping is so great that an entire new history line would need to be prepared. Two words summarize this controversy: Lance Armstrong. I could also have substituted the names of Floyd Landis or Alberto Contador. All three of these individuals have had major cycling titles taken away due to doping.

Russia has its own major issues with competitors being banned and with reports of state-sponsored doping. These are currently in the news and represent another major chapter in Olympic doping history.

Where does the paper published in Nature this week titled “Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy” fit into this discussion? This is a big research project with eleven contributing authors led by Robert A. Seaborne of Keele University, Staffordshire, UK. Prior studies had shown that in-vivo mouse skeletal muscle possesses a memory from the anabolic growth steroid sex hormone, testosterone. Further research also suggested that large scale epigenetic modifications can occur very rapidly in skeletal muscle.

Seaborne’s group examined untrained male subjects who went through an exercise training period, a layoff period and then a return to the exercise. In terms of applying these results then we must be cautious since some studies note differences between elite athletes and weekend warriors. But let’s assume that these results apply to all. The results reported in Seaborne’s paper show that epigenetic changes target the loci associated with cellular growth and can lead to enhanced gene expression when exposed to later life anabolic encounters. The interpretation is that there is an epigenetic memory of earlier muscle growth.

Here is what we need to think about. If it is possible to create epigenetic muscle memory with exercise, is it also possible that muscle built up through the use of steroids will also have this same epigenetic memory? If an athlete has been caught doping, how long a suspension would be needed to make any difference if the epigenetic memory is still there? What about abusing steroids as a teenager, then becoming a ‘clean’ athlete going on to Olympic success?

I think that this new paper adds a completely new layer of complexity to drug screening at the Olympics. Regardless, I will continue to enjoy the competitions, trusting the majority of Olympians follow their oath:
We promise to take part in these Olympic Games, respecting and abiding by the rules and in the spirit of fair play. We all commit ourselves to sport without doping and cheating. We do this, for the glory of sport, for the honour of our teams and in respect for the Fundamental Principles of Olympism

Links of interest:
          History of Performance Enhancing Drugs in Sports
          Seabourne’s paper

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Olympic athletes: Performance-enhancing epigenetics?

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