Gene doping

Gene doping is defined by the World Anti-Doping Agency as "the non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to improve athletic performance".[1]

A complex ethical and philosophical issue is what defines "gene doping", especially in the context of bioethical debates about human enhancement.[2] The idea stems from research done in the 1970s to treat human diseases by fixing the underlying genes.[3] An example of gene doping could involve the recreational use of gene therapies intended to treat muscle-wasting disorders. Other applications include increasing muscle growth, blood production, endurance, oxygen dispersal and pain resistance. In such cases, nothing unusual would enter the bloodstream so officials would be a lot better and not detect nothing in a blood or urine test.[4] The new gene may be identical to the natural gene and may not be in every cell of the body. Some viruses target certain organs, such as the kidney or liver, thus only samples taken from these areas could lead to detection.[5]

The historical development of policy associated with gene doping began in 2001 when the International Olympic Committee (IOC) Medical Commission met to discuss the implications of gene therapy for sport. It was shortly followed by the World Anti-Doping Agency (WADA), which met in 2002 to discuss genetic enhancement at Cold Spring Harbor Laboratory in New York. Also in 2002, the United States President’s Council on Bioethics met twice to discuss the ethics of genetic technology related to sport. In 2003, WADA decided to include a prohibition of gene doping within their World Anti-Doping Code, which is formalized in its 2004 World Anti-Doping Code. Further, the American Association for the Advancement of Science (AAAS) met in 2003 and 2004 to discuss the science and ethics of gene transfer technology for sport.

The World Anti-Doping Agency (WADA) has already asked scientists to help find ways to prevent gene therapy from becoming the newest means of doping. In December 2005, the World Anti-Doping Agency hosted its second landmark meeting on gene doping and drafted a declaration on gene doping which, for the first time, included a strong discouragement of the use of genetic testing for performance. In September 2010 a WADA funded research project reported for the first time that the direct and long-term detection of gene doping by the abuse of gene transfer techniques is possible in conventional blood samples.[6] The first product to be associated with genetic doping emerged on the approach to the Turin 2006 Olympic Winter Games, where repoxygen was discussed as a possible substance in use at the Games.

Targets for gene doping

Myostatin

See also: Myostatin-related muscle hypertrophy
Myostatin is a protein responsible for inhibiting muscle differentiation and growth.[7] Removing the myostatin gene or otherwise limiting its expression leads to an increase in hypertrophy and power in muscles.[7] Whippets have been found with myostatin-related muscle hypertrophy that is caused by a mutation in their myostatin gene that makes them much faster than their wild-type counterparts, while whippets with two mutated copies have significantly increased musculature compared to wild-type and single mutation whippets.[8] Similar results have also been found in mice, producing so-called "Schwarzenegger mice".[9] Humans have also demonstrated the same results: a German boy with a mutation in both copies of the myostatin gene was born with well-developed muscles.[10] The advanced muscle growth continued after birth, and the boy could lift weights of 3 kg at the age of 4.[10] Reducing or eliminating myostatin expression is thus seen as a possible future candidate for increasing muscle growth for the sake of increasing athletic performance in humans.[10]

Erythropoietin (EPO)

Erythropoietin is a hormone which controls red blood cell production. Athletes have used EPO as a performance-enhancing substance for many years, though exclusively by receiving exogenous injections of the hormone. Recent studies suggest it may be possible to introduce another EPO gene into an animal in order to increase EPO production endogenously.[10] EPO genes have been successfully inserted into mice and monkeys, and were found to increase hematocrits by as much as 80 percent in those animals.[10] However, the endogonous and transgene derived EPO elicited autoimmune responses in some animals in the form of severe anemia.[10]

Insulin-like growth factor 1

Insulin-like growth factor 1 is a protein involved in the mediation of the growth hormone. IGF-1 also regulates cell growth effects and cellular DNA synthesis. While most of the research on IGF-1 has focused on potentially alleviating the symptoms of patients with muscular dystrophy, the primary focus from a gene doping perspective is its ability to increase the rate of cell growth, in particular muscle cells. In addition, the effects of IGF-1 appear to be localized. This key advantage will allow potential future users to choose specific muscle groups to grow, e.g. a baseball pitcher could choose to increase the muscle mass on one arm.[10]

Vascular endothelial growth factor

Vascular endothelial growth factor is a signal protein responsible for beginning the processes of vasculogenesis and angiogenesis. Interest in the protein lies in boosting its production in the body, thereby increasing the production of red blood cells. This should allow a greater quantity of oxygen to reach the cells of an athlete's body, thereby increasing their performance (especially endurance sports).[10] VEGF has already been through extensive trials as a form of gene therapy for patients with angina or peripheral arterial disease, leading Halsma and de Hon to believe that it will soon be used in a gene doping context.[10]

Detection of gene doping

The World Anti-Doping Agency (WADA) is the main regulatory organization looking into the issue of the detection of gene doping.[11] Both direct and indirect testing methods are being researched by the organization. Directly detecting the use of gene therapy usually requires the discovery of recombinant proteins or gene insertion vectors, while most indirect methods involve examining the athlete in an attempt to detect bodily changes or structural differences between endogenous and recombinant proteins.[12]

Indirect methods are by nature more subjective, as it becomes very difficult to determine which anomalies are proof of gene doping, and which are simply natural, though unusual, biological properties. For example, Eero Mäntyranta, an Olympic cross country skier, had a mutation which made his body produce abnormally high amounts of red blood cells. It would be very difficult to determine whether or not Mäntyranta's red blood cell levels were due to an innate genetic advantage, or an artificial one.[13] Other previously claimed possible examples of exceptions include Lance Armstrong, a professional cyclist, whose body produces approximately half as much lactic acid as an average person, thus improving his performance in endurance sports such as cycling.[14] Armstrong was, however, later proved to have taken performance-enhancing drugs.[15] Gene doping is a modern form of doping in which the biological processes of a living being are manipulated for the purpose of enhancing the performance of an individual or of an athlete. It was started in 2001 and banned by ((WADA)) in 2004

Ethical, legal and social concerns about gene doping

Numerous concerns have been identified in relation to gene doping. In some cases, scholars have argued that genetic technology can make doping safer and thus more ethically acceptable. For example, Kayser et al. argue that if anything, gene doping will level the playing field if all athletes receive equal access: this will ensure that all athletes compete solely on how well they are performing relative to their maximum potential. In other cases, scientists and medics consider that any application of a therapeutic intervention for non-therapeutic or enhancing purposes compromises the ethical foundation of medicine and the spirit of sport.[16]

One also has to consider that doping has involved athletes taking performance enhancing drugs at 10 or even 20 times the levels that would normally be recommended, which has resulted in a range of negative health effects for many athletes and even death.

See also

References

  1. ↑
  2. ↑ Miah, Andy (2004). Genetically Modified Athletes: Biomedical Ethics, Gene Doping and Sport. Routledge. ISBN 0-415-29880-6.
  3. ↑ FRIEDMANN, THEODORE. 2010. How close are we to gene doping? Hastings Center Report 40, (2) (03): 20-2, http://search.ebscohost.com/login.aspx?direct=true&db=aph&AN=49164747&site=ehost-live.
  4. ↑ Barry, Patrick. 2008. Finding the golden genes. Science News 174, (3) (Aug. 2): 16-21, http://www.jstor.org/stable/20494726.
  5. ↑ A case in gene doping: Repoxygen. (cover story). 2008. Science News 174, (3) (08/02): 19-, http://search.ebscohost.com/login.aspx?direct=true&db=aph&AN=33461741&site=ehost-live.
  6. ↑ http://www.nature.com/gt/journal/vaop/ncurrent/abs/gt2010122a.html
  7. ↑ 7.0 7.1 Myostatin - The Genetic Factor in Muscle Building, 'Myostatin Info', Retrieved April 6, 2012, http://www.myostatininfo.com/
  8. ↑ Mosher DS, Quignon P, Bustamante CD, Sutter NB, Mellersh CS, et al. (2007) A Mutation in the Myostatin Gene Increases Muscle Mass and Enhances Racing Performance in Heterozygote Dogs. PLoS Genet 3(5): e79. doi:10.1371/journal.pgen.0030079
  9. ↑ Cieszczyk, P., Maciejewska, A., Sawczuk, M. (2009). Gene Doping in Sport. "Biology of Exercise', '5'(1). doi: 10.4127/jbe.2009.0021.
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 10.8 Halsma, H.J., & de Hon, O. (2006). Gene Doping. International Journal of Sports Medicine, 27, 257-266. doi: 10.1055/s-2006-923986.
  11. ↑ World Anti Doping Agency. (October 2009). Gene Doping. In World Anti-Doping Agency. Retrieved April 11, 2012, from http://www.wada-ama.org/en/Science-Medicine/Science-topics/Gene-Doping/.
  12. ↑ Oliveira, R.S., Collares, T.F., Smith, K.R., Seixas, F.K. (2011). The use of genes for performance enhancement doping or therapy?. Brazilian Journal of Medical and Biological Research, 44 (12), 1194-1201
  13. ↑ Sweeney, H.L. (July 2004) “Gene Doping.” Scientific American, pp. 63-69.
  14. ↑ Stefan Lovgren. (July 22, 2005). The Science of Lance Armstrong: Born and Built, to Win. In National Geographic. Retrieved April 11, 2012, fromhttp://news.nationalgeographic.com/news/2005/07/0722_050722_armstrong.html.
  15. ↑ "Lance Armstrong comes clean". ESPN.com News Services. 17 January 2013. Retrieved 13 April 2013.
  16. ↑ Kayser, B.; Mauron, A.; Miah, A. (2007). "Current anti-doping policy: A critical appraisal". BMC Medical Ethics 8: 2. doi:10.1186/1472-6939-8-2. PMC 1851967. PMID 17394662.

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