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Gene Doping? Cheating in Sports With Gene Therapy

Before the European Championship in 1966, athletes were not tested for drugs that could enhance the performance of an athlete. Yet, by 2015, the World Anti-Doping Agency (WADA) found that out of 283,304 drug tests conducted in the previous year, 3,800 samples contained banned drugs, and more than 10% of elite athletes used performance-enhancing drugs. While most agree that using performance-enhancing drugs can be detrimental to the spirit of sports and unfair to other athletes, what could be said about genetics? After all, genetics are an important determinant in strength, endurance, aerobic capacity, coordination, flexibility and many other traits that are linked to improved athletic performance. With the rise of gene therapy nowadays, some athletes and scientists are exploring the possibility of using this technology to improve the performance of athletes through genetic doping, while others, including the World Anti-Doping Agency (WADA), state that this is unethical and harms the integrity of sports. In the face of modern science and technology, how will this make an impact in modern sport competitions?

Medications

An introduction to doping in sports

Athletes have been using substances to improve their performances since the original Olympic games from 776 to 393 B.C.E, when athletes would use hallucinogenic herbs, fungi, and wine concoctions to improve their speed and endurance. However, in 1904, the first case of using drugs in modern sports competitions became known when marathon runner Thomas Hicks almost died from taking strychnine, a rat poison, and brandy during the St. Louis Olympic games. During the time, there were no rules regarding drug doping, but by 1928, the International Association of Athletics Federation (IAAF) was the first international federation to officially ban doping in athletic competitions, which was defined as, “the use of any stimulant not normally employed to increase the poser of action in athletic competition above the average.”

Soon, other regulatory bodies including the International Olympic Committee began imposing rules on doping, and today, the list of banned substances include anabolic steroids, peptide hormones, metabolic regulators, stimulants, narcotics, and more.

This is Andreas Kreiger, a victim of state-sponsored drug doping in East Germany! Image Source

The dangers of drug doping

There were three main reasons why drug doping is banned, according to WADA. However, arguably the most important reason is the dangers associated with drug doping. In particular, as competitive sports and the Olympics became increasingly influenced by politics, the Soviet Union and East Germany began viewing competitive sports as a way to showcase its influence and power by the 1930s. This led to a mentality and obsession of winning at any cost – oftentimes doping their athletes in order to ensure dominance. But with the fall of the Soviet Union, the extent of doping became well-known to the world as documents were released showing the state-sponsored doping programs. Former athletes had many long-term consequences of drug doping.

To illustrate, in 1986, Heidi Krieger was the women’s shot-put champion from East Germany. At 16 year old, Krieger was given an anabolic steroid called Oral-Turinabol which she was told to be vitamin supplements, but these led her to develop body hair, a deep voice, and masculine features. Eventually, she underwent a sex-change surgery to become Andreas Kreiger after being damaged by the steroids that she was given without her knowledge.

”They killed Heidi… I didn’t have control. I couldn’t find out for myself which sex I wanted to be.”

Andreas Krieger, 1986 women’s shot-put champion and victim of state-sponsored doping by East Germany
The Kalenjin tribe from Kenya produces many of the world’s best runners! Image Source

How your genes determine your athletic success

With the controversies surrounding drug doping, arguments against banning doping state that there are still many ways to enhance performance, such as altitude training, dietary supplements, or carb-loading. Yet, while training and hard work plays a huge role in becoming a successful athlete, there’s also a crucial factor in the success of athletes: genetics. For example, it was found that a Swedish family had a mutation in the EPOR gene, causing them to produce extra red blood cells and improve oxygen-carrying capacity by 25-50%. This family had many champion endurance athletes, including champion cross-country skier Eero Mäntyranta, who won seven Olympic medals in cross-country skiing.

In addition, it was found that nearly every Male Olympic sprinter and strength athlete that was tested carried the 577R allele, which suggests that this gene plays a crucial role in athleticism. Similarly, despite being a rather small ethnic group in Kenya with around six million people, the Kalenjin tribe in Kenya has won 40% of world class medals for distance running. Because of the Kalenjin peoples’ slim ankles and calves, a trait commonly seen in the Nilotic tribes, this allows their legs to move faster as having less weight away from the center of gravity makes it easier to move. However, this is far from the only reason for Kenya’s domination in running events. The culture of perseverance and working hard, as well as the interest in running among Kenyan youth has also been stated by many Kenyan running champions as the reason for Kenya’s success in running. Currently, there have already been more than 200 gene variants associated with athleticism, such as the “I” gene variant for increased endurance in the ACE gene found in 94% of Sherpas in the Kathmandu Valley of Nepal that was found to increase the chances of successfully climbing a 8,000 meter peak.

The mice were nicknamed “Schwarzenegger mice” because of their increased muscle mass! Image Source

How gene therapy is being used in gene doping

With the discovery and research in gene therapy to treat diseases, many scientists have begun exploring the potential of using gene therapy to enhance athletic performance. In fact, the applications of gene therapy in treating diseases overlap with using gene therapy to improve athletic performance much more than most would expect. For example, in 1998, physiologist H. Lee Sweeney from the University of Pennsylvania School of Medicine and his team inserted the insulin-like growth factor gene (IGF1), a protein that interacts with cells on the outside of muscle fibers to make them grow, using a viral vector into the muscle cells of mice. In young mice, this caused a 15% increase in strength and muscle mass, giving them the nickname “Schwarzenegger mice.” In older mice, these mice had significant strength well into their older years, which is around 20 months old for mice, and also reversed age-related muscle degeneration. While Sweeney intended for his research to help reverse muscle degeneration in patients with Duchenne muscular dystrophy, this didn’t stop athletes and coaches from begging Sweeney to dope the athletes, and he even received a request to dope an entire Pennsylvania junior college team.

“There are animal models which show efficacy and the possibility of this being technically feasible for an athlete to do.” 

Andy Miah, a bioethicist and director of the Creative Futures Institute at the University of the West of Scotland

In addition, gene doping is also capable of changing an athlete’s aerobic capacity. In 2006, a German track and field coach named Thomas Springstein was on trial for doping minors, including attempting to purchase a drug called Repoxygen from a British pharmaceutical company Oxford Biomedica intended to treat severe anemia. Repoxygen injects a gene that stimulates the synthesis of erythropoietin (EPO), which leads to an increase in red blood cells and improves endurance. In fact, the hormone erythropoietin is a common substance for blood doping as a drug, such as in 2012 when cyclist Lance Armstrong admitted to using EPO in all seven of his Tour de France victories. However, while the hormone typically used for blood doping can be detected in laboratory tests, the gene therapy form of EPO, Repoxygen, is impossible to detect.

Nevertheless, this technique of using gene therapy to synthesize EPO is still untested in humans and potentially risky. This is because when macaque monkeys were used to test EPO gene therapy, the concentration of red blood cells became so high that their blood was described as a “sludge.” But soon after, their EPO levels suddenly dropped and they developed severe anemia. The experiment ended shortly after because the scientists had to euthanize the monkeys.

How much are athletes willing to risk to win?

While typical doping methods such as with injections or pills are often dangerous and detectable in laboratory tests, gene therapy is a strategy to edit DNA by inserting new or modified DNA into the patient’s cells. This means that it is not easily detectable through blood tests, and the effects can last for years.

Gene doping is intriguing for many athletes because of the impressive benefits, but this creates a headache for the WADA, who is adamantly against gene doping in sports as they state that this threatens the spirit of sports competition. Currently, organizations including WADA are using significant resources to find methods of detecting gene doping, such as by detecting molecules that interfere with myostatin, which is a growth factor that inhibits the size of muscles, and by detecting plasmid vectors in blood, which is a delivery method for gene therapy. However, if the genetic material is injected directly into the muscle and does not pass the bloodstream, there would be no way to detect gene doping.

Yet, the level of sacrifice and risk-taking that athletes were willing to undergo for success may be one of the most surprising findings of all. In the 1980s, Bob Goldman, a doctor and the founder of the U.S. National Academy of Sports Medicine surveyed elite athletes on whether or not they would take a drug that would guarantee them a gold medal at the Olympics but cause certain death in five years. This famous problem, called Goldman’s Dilemma, found that 52% of the elite athletes said yes, and some of the athletes were as young as 16. Goldman repeated his survey every two years for the next decade, and the results were similar every time. However, the results of this study have been disputed by scientists, and many have recreated the survey using different situations, such as regarding legality or fatal complications but not necessarily death.

What will happen to the Olympics in the future?

With the rise of gene therapy, what will happen to sports competitions?

But despite the insistence of preventing gene doping by anti-doping agencies, there are still advocates for gene doping. According to Julian Savulescu, professor of ethics at the University of Oxford, England “genetic enhancement is not against the spirit of sport; it is the spirit of sport.” With further discoveries in gene therapy, what will happen to sports competitions? Once it is proven that gene therapy works in humans and the genetic material injected can get past the body’s immune system, athletes that have undergone gene therapy to improve performance will be difficult, if not impossible, to detect. In an article published in Nature, this means that there will be three potential scenarios in the future.

First, sports competitions, including the Olympics, will continue as it is currently, where the genetically blessed will have a competitive advantage over other players. However, critics of those against gene doping state that there is no way to ban gene doping, and even the chairman of WADA, Gary Wadler, states that this will only be a matter of time as athletes “read the scientific literature and they know what’s cutting-edge—there’s no question about it.” 

Considering that the first Olympics involved white males competing for an olive wreath and now has evolved into a diverse and technologically-advanced competition with equipment and training designed to improve performance, the second solution is to embrace change by allowing athletes to undergo gene doping. This brings up a concerning prospect for the future – what will the future look like if we embrace gene doping? Allowing gene therapy to improve athletic performance will likely lead to gene therapy for non-therapeutic genetic enhancement uses in the general public, which is already being debated with the rise of CRISPR and designer babies. But some say this may be positive for society, as having better, stronger, and smarter people in society means a more productive society overall, while others state that genetic engineering could lead to humans becoming radically different, and also promoting eugenics. 

The third situation involves the use of handicaps, which is already being used for other sports competitions, to help make competitions more fair for those without a genetic advantage. Handicapping in sports assigns advantages through scoring compensation, and this is often used to equalize the chances of winning for less experienced participants. This would be the safest option, because it would increase the opportunities for people who are less genetically blessed, while also reducing the number of people making drastic changes to their body in order to improve their athletic performance. Yet, it would be very difficult to determine the “quality” of an athlete’s genes. After all, due to genetic variety, even gender-verification testing to confirm the sex of female athletes was problematic and eventually abandoned altogether because there was too much genetic variety to accurately use these tests to determine the sex of athletes.

In conclusion…

In the highly competitive world of elite sports, it has been found through an anonymous survey that around ⅓ of athletes at two major track competitions dope to improve their athletic performance. With the rise in gene therapy in recent years, gene doping has been an increasing concern for anti-doping organizations such as WADA, while a promising strategy to improve performance for many athletes as gene doping can be near impossible to determine whether the gene was natural or introduced. Because it’s undoubtedly true that genetics plays a huge role in an athlete’s success in sports, what would be the most reasonable solution to this genetic inequality in the face of gene therapy? Personally, I believe that many elite sport competitions, such as the Olympics, doping, including gene doping, will continue to be banned with no compensation for players that do not carry favorable genes. While this carries a risk of athletes going to extreme lengths to improve their performance, there’s no way to change the fact that genetics plays a huge role in life, including sports, and that’s just how it is.

Note: While writing this article, I’ve been curious about having ‘cheating’ Olympics, where athletes compete to pull the wildest stunts to cheat in the competition – but they must remain undetected. In the end, the athlete with the most elaborate stunt, least suspicion from judges, and highest score wins after they reveal their elaborate schemes. Wouldn’t this be fun to watch? I’d be interested in seeing what creative and sneaky ways people come up with!

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