From viruses to competitive sports. While still in their infancy, gene doping techniques are already threatening to penetrate Olympic sports. Why are they feared so much and why do some see great promise in them?

While the runners in the Olympic games prepare to take their places at the start line, a race no less significant is taking place behind the scenes. The competitors: scientists and doctors who are developing new methods and new drugs to enhance athletes’ performance are up against authorities and doctors fighting to identify these artificial interventions, which are at times dangerous to athletes’ health. The current main player in this drugs race is ‘gene doping’ – a technique designed to enhance the body’s natural abilities by manipulating the genetic material itself.

The idea of gene doping was conceived in 1970, following an innovative approach developed in medicine and research. The idea was to treat human diseases that have a genetic background by inserting the 'healthy' version of the defective gene into the body’s cells, a method called 'gene therapy'.

The field of gene therapy is based on the idea that defective and disease-causing genes in our body can be fixed. All that needs to be done is to insert the functional gene into a neutralized virus and let the virus do its trick by infecting the cells of the body and injecting the healthy gene into them. And as for the rest, the body will manage everything on it’s own.

While this sounds rather simple at first glance, in practice it is actually a very complicated process, requiring an in-depth understanding of all the possible implications of inserting a foreign gene into our body and disrupting its intracellular balance. Failed past attempts, some of which even ended in the death of patients in clinical trials, prevented the field from blossoming and becoming a leading method for curing human diseases.

Even though there still remains a long way to go for gene therapy to offer any practical benefit, the fear that athletes would use gene therapy techniques to enhance their performance has been present for quite some time. As early as 2003, the World Anti-Doping Agency (WADA) has issued a ban on gene doping, declaring it an illegal manipulation in competitive sports, further extending this ban in 2018 to include all forms of gene editing. 

Sought-after genes

Some argue that all forms of competitive sports will be using gene doping as an integral part of athletes’ routine training within less than ten years. Genes that are likely to be in the limelight of gene doping techniques are those associated with areas such as muscle growth and contraction, pain endurance, blood production, pain perception and muscle oxygen supply.

Labs whose research focuses on genes associated with these fields have already caught the eye of many athletes. One of these labs is that of Professor Lee Sweeney from the University of Pennsylvania in the United States, whose research focuses on Duchenne muscular dystrophy (DMD) – a genetic disease affecting the functionality of the body’s muscles. Sweeney and his colleagues discovered that the underlying genetic defect in patients results in the dysfunctionality of an important protein called dystrophin, which is essential for muscle function. In addition, the researchers found that a protein, called IGF-1, can cause muscle growth when bound to muscle cells.

Using genetic tools, the researchers were able to insert the gene encoding for IGF-1 into mice that constitute a model for the study of DMD, which exhibited Duchenne-like symptoms. The result was the creation of what became known as the “Schwarzenegger mice” (named for the famous bodybuilder), with a 40 percent increase in muscle mass. Sweeney said in an interview that “when the mice became the equivalent of senior citizens (which for mice is about 20 months of age), they were still as strong and fast as they had been when they were young”. With such results, it’s no wonder that Sweeney began to receive requests from athletes to inject them with the 'magic gene'.

This research is only one example out of many. Researchers from the Salk Institute for  Biological Studies in California injected mice with a gene that encodes a protein responsible for burning cellular fat, which allowed them to run twice the distance that regular mice could run. Although the study was originally carried out for medical purposes, many athletes have their gaze fixed on this study, hoping to join the ‘marathon mice’.

Additional genes, such as erythropoietin (EPO) which is responsible for red blood cell production, or VEGF, responsible for the production of new blood vessels in the body, have also become prominent candidates for use in gene doping. Considering the fast rate of progress in medical and biological research, this list is only expected to grow over time.

Biological hacking

Genetic engineering is becoming increasingly cheaper and more common nowadays, so much so that any person with basic knowledge and experience in biology can order any substance he wants on the internet and download the software required to carry out independent genetic experiments. Scientists and ‘biological hackers’ say they have many inquiries from athletes or coaches, looking to acquire tools for gene doping.

Although so far, no actual gene doping has been documented in sports, evidence of preliminary attempts undertaken in this direction does exist. An athletes coach in Germany was caught and charged with attempts to acquire a genetic element that contained the erythropoietin gene (EPO). This element was developed to enhance the production of blood cells in patients with serious diseases, such as certain types of cancer and chronic kidney disease. Evidence of the coach’s efforts to acquire this genetic element was discovered in his email account. This was not the only case. Slightly prior to the Beijing 2008 Olympic Games, a German investigative reporting team broadcast a television show about a Chinese scientist who offered genetic manipulation services for athletes.

Taking preventative measures

If attempts at gene doping have already taken place, perhaps someone has already succeeded at it? As of today, there is no clear evidence that gene doping has infiltrated the world of competitive sport, but even if not, it is only a matter of time until it does. The World Anti-Doping Agency has already approached scientists and has been funding scientific research on methods for detection of gene doping, with the goal of finding ways to prevent gene doping from becoming the next big hit for athletes willing to do anything to enhance their performance.

Developing tests to detect illegal usage of gene doping is not at all a simple matter, and it is, in fact, unlike any other tests existing today. In gene doping, a new gene is inserted into the cells of the body, enabling them to produce proteins and other substances that could improve the athlete’s performance. In most cases it will be very difficult to distinguish between the proteins naturally produced by the body and those produced as a result of a gene insertion.

It is a widely held view that the methods for detecting gene doping should focus on monitoring metabolism, the genetic and protein makeup of each athlete and to try and detect unusual changes in them. However, different factors, which are dependent on age, sex and the physical abilities also need to be considered, since humans also change naturally. In addition, one needs to keep in mind that top athletes have outstanding genetics, extraordinary skills and exceptional physical abilities to begin with.

A study published back in 2011 offers a new method for detecting gene doping. The researchers focused on detecting the genetic component used to insert the foreign gene. Since the structure of this component is different from the structure of our DNA, the researchers were able to develop a method sensitive enough to detect whether such a component exists in an athlete’s blood. However, this method also has its limitations and a one hundred percent success rate cannot always be guaranteed.

The next big thing in sports?

The world of sports and science has not reached a consensus regarding gene doping. Some believe it is best to allow genetic manipulations, so that athletes are evaluated according to their performance abilities, their spirit and perseverance, and not only on maximization of their inborn genetic potential. Julian Savulescu, a professor of ethics at the University of Oxford  in the United Kingdom, argues that "genetic enhancement is not against the spirit of sport; it is the spirit of sport". Others think that this is an ethical problem, which perverts the potential capabilities of medicine and science and exploits them unfairly, and of course, endows the treated athletes with an unfair advantage over their peers. 

Beyond the ethical questions, gene doping also poses significant medical risks. In an experiment in which researchers injected monkeys with the EPO gene, the production of blood cells in the monkeys increased to such an extent that the researchers had to constantly draw blood from them to prevent a stroke. Later in the experiment, when the monkeys' immune system began to function, they surprisingly developed anemia.

These challenges are likely the reason why doctors and scientists are not yet able to bring gene therapy into practical use. Much work still remains in order to develop consistent methods for genetic manipulation of humans, under international ethical standards. Until that day arrives, we are not likely to see many cases of gene doping in sports.