Sports doping experts have been sounding warnings about gene engineering for decades, and its dire implications for clean competition. With the Tokyo Olympics around the corner, Professor David Bishop wonders if gene doping really is sport’s Next Big Thing.
In preparation for the postponed Tokyo Olympics, athletes all around the world are lining up to be injected with genetic material. This genetic material will provide the instructions to produce specific proteins, which will prime the immune system to build the antibodies and T-cells needed to fight off a COVID-19 infection.
However, the modulation of gene expression for therapeutic purposes raises complex questions about whether athletes could use similar techniques to enhance their performances now and in the future.
In the last two decades, every Olympic Games has been preceded by predictions that we may have seen the last Games without gene-altered athletes.
As an exercise and sport scientist, I am driven to discover new ways to enhance human performance using ethical means. This realm raises important questions about what limits should be placed upon performance enhancement strategies available to athletes.
Gene therapy was first tried out on humans in 1990; since then, speculation has grown that genetically modified athletes will soon be the “next big thing” to dominate the sporting world. In 1997, the “father” of genes and sport, Canadian-born Professor Claude Bouchard, suggested that the genetic engineering of super-elite athletes would occur sometime between 2007 and 2012. Since 2003, long before most believed it was possible, gene doping has been banned by the World Anti-Doping Agency (WADA). In the last two decades, every Olympic Games has been preceded by predictions that we may have seen the last Games without gene-altered athletes. But is it technically possible? And do we know which genes to target?
The first known example of a genetic alteration to enhance athletic performance occurred in 1937. That was the year that Eero Mäntyranta, one of Finland’s most successful cross-country skiers, was born. Mäntyranta benefited from a very rare, natural mutation in his erythropoietin receptor (EPOR) gene that caused an increase in his red blood cell mass and an enhanced capacity to deliver oxygen to his muscles. This skier naturally possessed the physiological advantage that endurance athletes try to achieve by training, stays at altitude, blood doping, or the banned administration of erythropoietin (EPO). Gene therapy to modify the erythropoietin receptor gene, and to raise red blood cell levels, could one day be available to athletes not born with this helpful genetic mutation.
These sorts of findings rarely escape the attention of athletes.
Gene transfer to raise erythropoietin production has already been successfully performed in mice and non-human primates. A single intramuscular injection of a viral vector containing additional copies of the EPO gene resulted in almost a doubling of the percentage of red blood cell volume, which was maintained for more than a year.
This potential to use gene therapy to increase the oxygen-carrying capacity of the blood has already caught the eye of some coaches. In 2004, a German track coach attempted to order Repoxygen – an obscure gene-therapy drug being developed to fight anaemia, which he hoped might give his athletes a competitive advantage. It was an historic moment that heralded the dawn of the gene doping era.
It’s going to be a massive challenge, although that hasn’t, and won’t, stop researchers from continuing to try.
Increasing the oxygen-carrying capacity of the blood is an obvious target for gene doping, given its long-established association with endurance performance. However, the steady stream of research describing “marathon” mice, “supermice”, and “Schwarzenegger” mice suggests muscle is likely to be one of the first tissues subject to genetic enhancement.
Genetically engineering mice so that they permanently switched on peroxisome proliferator-activated receptor delta (PPARδ) – a protein controlling the number of type-I or slow-twitch muscle fibres – produced mice that had more slow-twitch muscle fibres and were able to scamper nearly twice as far before exhaustion as their normal littermates. These sorts of findings rarely escape the attention of athletes. In 2013, an international cyclist tested positive for a PPARδ receptor agonist known as GW501516, and sold on the internet and black market as Endurobol. Considering that this is a drug that didn’t proceed past clinical trials due to concerns about cancer risk, it is hard to believe the use of gene therapy to activate PPARδ and other proteins linked to endurance performance would not be tempting to some athletes.
Despite some spectacular findings in the lab with mice, there are still many hurdles to overcome before gene-edited athletes become a reality.
Despite some spectacular findings in the lab with mice, there are still many hurdles to overcome before gene-edited athletes become a reality. The Achilles heel of gene doping is that it is very unlikely that one gene, or even a handful of genes, substantially determines sporting ability. Despite 40 years of research, we still know very little about which genes make a meaningful contribution to sporting success. Any athletic ability is complex, and likely to be influenced by the small, additive effects of many genes, which are further influenced by other genes, environment, development, and random variations. If we can only explain 10% of the variation in something as simple as height, by a combination of 180 gene variants, there seems little hope for completely deciphering the genetic basis of even the most basic athletic ability.
Perhaps the biggest problem, however, is that genetic scientists typically examine tens to hundreds of thousands of people to find which of the approximately 40 million different potential sites of gene variation within 21,000 human genes determine the genetic component of things like height, weight or disease. The pool of elite athletes in any given sport is, by definition, much smaller. Discovering definitive sports genes is going to be a massive challenge, although that hasn’t, and won’t, stop researchers from continuing to try.
Right now, there are no known cases of gene doping being used by athletes. It is technically possible that we have already had gene-doped athletes in the world of sports. If not, it seems only a question of time before the first athletes will seek an advantage by tampering with Mother Nature.
Professor David Bishop is a world leader in muscle exercise. He leads the Skeletal Muscle and Training Research Group at Victoria University, focusing on how diet, exercise and genes interact to regulate skeletal muscle adaptations; he translates this into recommendations for individualised exercise prescriptions to improve health and human performance. He has held numerous leadership positions, including being the youngest-ever president of Exercise & Sport Science Australia (ESSA), when he was lead author on a submission to the Productivity Commission that led to the inclusion of Accredited Exercise Physiologists (AEPs) in Medicare-Plus. He is also assistant editor of the journal "Medicine and Science in Sports and Exercise".