gene doping gene doping gene doping is the hypothetical non-therapeutic use of gene therapy by athletes in order to improve their performance in those sporting events which prohibit such applications of genetic modification technology, and for reasons other than the treatment of disease. as of april 2015, there is no evidence that gene doping has been used for athletic performance-enhancement in any sporting events. gene doping would involve the use of gene transfer to increase or decrease gene expression and protein biosynthesis of a specific human protein; this could be done by directly injecting the gene carrier into the person, or by taking cells from the person, transfecting the cells, and administering the cells back to the person. part of a series ondoping in sport substances and types anabolic steroids blood doping gene doping stem cell doping mechanical doping technology doping cannabinoids diuretics painkillers sedatives stem cell doping stimulants beta2-adrenergic agonist clenbuterol ephedrine epo human growth hormone methylhexanamine sarms stanozolol tetrahydrogestrinone terminology abortion doping biological passport blood-spinning doping test performance-enhancing drugs repoxygen stem cell doping whizzinator history olympics tour de france (1998, 1999, 2007) auto racing balco scandal clemson university steroid scandal u of south carolina steroid scandal dubin inquiry association football china east germany russia united states festina affair floyd landis case game of shadows juiced l.a. confidentiel lance armstrong history of allegations doping case operación puerto operation aderlass doping in american football steroid use in baseball barry bonds perjury case mitchell report biogenesis scandal doping-related lists doping cases in sport athletics cycling doping at the olympic games doping at the world championships in athletics stripped olympic medals stripped european athletics c'ships medals drugs banned from the olympics mlb players suspended for doping mlb players in the mitchell report anti-doping bodies world anti-doping agency international testing agency list of national anti-doping organizations australian sports anti-doping authority french anti-doping agency national anti-doping agency russian anti-doping agency uk anti-doping united states anti-doping agency the historical development of interest in gene doping by athletes and concern about the risks of gene doping and how to detect it moved in parallel with the development of the field of gene therapy, especially with the publication in 1998 of work on a transgenic mouse overexpressing insulin-like growth factor 1 that was much stronger than normal mice, even in old age, preclinical studies published in 2002 of a way to deliver erythropoietin (epo) via gene therapy, and publication in 2004 of the creation of a "marathon mouse" with much greater endurance than normal mice, created by delivering the gene expressing ppar gamma to the mice. the scientists generating these publications were all contacted directly by athletes and coaches seeking access to the technology. the public became aware of that activity in 2006 when such efforts were part of the evidence presented in the trial of a german coach. scientists themselves, as well as bodies including the world anti-doping agency (wada), the international olympic committee, and the american association for the advancement of science, started discussing the risk of gene doping in 2001, and by 2003 wada had added gene doping to the list of banned doping practices, and shortly thereafter began funding research on methods to detect gene doping. genetic enhancement includes manipulation of genes or gene transfer by healthy athletes for the purpose of physically improving their performance. genetic enhancement includes gene doping and has potential for abuse among athletes, all while opening the door to political and ethical controversy. history of gene doping the history of concern about the potential for gene doping follows the history of gene therapy, the medical use of genes to treat diseases, which was first clinically tested in the 1990s. interest by the athletic community was especially spurred by the creation in a university lab of a "mighty mouse", created by administering a virus carrying the gene expressing insulin-like growth factor 1 to mice; the mice were stronger and remained strong even as they aged, without exercise. the lab had been seeking treatments for muscle wasting diseases, but when their work was made public, the lab was inundated with calls from athletes seeking the treatment, with one coach offering his whole team. the scientist told the new york times in 2007: "i was quite surprised, i must admit. people would try to entice me, saying things like, 'it'll help advance your research.' some offered to pay me." he also told the times that every time similar research is published he gets calls and that he explains that, even should the treatment became ready for use in people, which would take years, there would be serious risks, including death; he also said that even after he explains this, the athletes still want it. in 1999, the field of gene therapy was set back when jesse gelsinger died in a gene therapy clinical trial, suffering a massive inflammatory reaction to the drug. this led regulatory authorities in the us and europe to increase safety requirements in clinical trials even beyond the initial restrictions that had been put in place at the beginning of the biotechnology era to deal with the risks of recombinant dna. in june 2001, theodore friedmann, one of the pioneers of gene therapy, and johann olav koss an olympic gold medallist in speed skating, published a paper that was the first public warning about gene doping. also in june 2001, a gene therapy working group, convened by the medical commission of the international olympic committee noted that "we are aware that there is the potential for abuse of gene therapy medicines and we shall begin to establish procedures and state-of-the-art testing methods for identifying athletes who might misuse such technology". research was published in 2002 about a preclinical gene therapy called repoxygen, which delivered the gene encoding erythropoietin (epo) as a potential treatment for anemia. the scientists from that company also received calls from athletes and coaches. in that same year the world anti-doping agency held its first meeting to discuss the risk of gene doping, and the us president's council on bioethics discussed gene doping in the context of human enhancement at several sessions. in 2003, the field of gene therapy took a step forward and a step back; first gene therapy drug was approved, gendicine, which was approved in china for the treatment of certain cancers, but children in france who had seemingly been effective treated with gene therapy for severe combined immunodeficiency (non-human) began developing leukemia. in 2003 the balco scandal became public, in which chemists, trainers and athletes conspired to evade doping controls with new and undetectable doping substances. in 2003 the world doping agency proactively added gene doping to the list of banned doping practices. also in 2003, a symposium convened by the american association for the advancement of science focused on the issue. research published in 2004 showing that mice given gene therapy coding for a protein called ppar gamma had about double the endurance of untreated mice and were dubbed "marathon mice"; those scientists received calls from athletes and coaches. also in 2004 the world anti-doping agency began to fund research to detect gene doping, and formed a permanent expert panel to advise it on risks and to guide the funding. in 2006 interest from athletes in gene doping received widespread media coverage due its mention during the trial of a german coach who was accused and found guilty of giving his athletes performance enhancing drugs without their knowledge; an email in which the coach attempted to obtain repoxygen was read in open court by a prosecutor. this was the first public disclosure that athletes were interested in gene doping. in 2011 the second gene therapy drug was approved; neovasculgen, which delivers the gene encoding vegf, was approved in russia to treat peripheral artery disease. in 2012 glybera, a treatment for a rare inherited disorder, became the first treatment to be approved for clinical use in either europe or the united states. as the field of gene therapy has developed, the risk of gene doping becoming a reality has increased with it. agents used in gene doping there are numerous genes of interest as agents for gene doping. they include erythropoietin, insulin-like growth factor 1, human growth hormone, myostatin, vascular endothelial growth factor, fibroblast growth factor, endorphin, enkephalin and alpha-actinin-3. the risks of gene doping would be similar to those of gene therapy: immune reaction to the native protein leading to the equivalent of a genetic disease, massive inflammatory response, cancer, and death, and in all cases, these risks would be undertaken for short-term gain as opposed to treating a serious disease. alpha-actinin-3 alpha-actinin-3 is found only in skeletal muscle in humans, and has been identified in several genetic studies as having a different polymorphism in world-class athletes compared with normal people. one form that causes the gene to make more protein is found in sprinters and is related to increased power; another form that causes the gene to make less protein is found in endurance athletes. gene doping agents could be designed with either polymorphism, or for endurance athletes, some dna construct that interfered with expression like a small interfering rna. myostatin