
Gene doping is the hypothetical non-therapeutic use of
gene therapy
Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells.
The first attempt at modifying human DNA ...
by athletes in order to improve their performance in those
sporting events
Sport is a physical activity or game, often competitive and organized, that maintains or improves physical ability and skills. Sport may provide enjoyment to participants and entertainment to spectators. The number of participants in a ...
which prohibit such applications of genetic modification technology,
and for reasons other than the treatment of disease. , 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
Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...
and
protein biosynthesis
Protein biosynthesis, or protein synthesis, is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the produc ...
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.
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
Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in tertiary structure, molecular structure to insulin which plays an important role in childhood growth, and has Anabolism, anabolic effects in adults. In the ...
that was much stronger than normal mice, even in old age, preclinical studies published in 2002 of a way to deliver
erythropoietin
Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in th ...
(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
The World Anti-Doping Agency (WADA; , AMA) is an international organization co-founded by the governments of over 140 nations along with the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against d ...
(WADA), the
International Olympic Committee
The International Olympic Committee (IOC; , CIO) is the international, non-governmental, sports governing body of the modern Olympic Games. Founded in 1894 by Pierre de Coubertin and Demetrios Vikelas, it is based i ...
, and the
American Association for the Advancement of Science
The American Association for the Advancement of Science (AAAS) is a United States–based international nonprofit with the stated mission of promoting cooperation among scientists, defending scientific freedom, encouraging scientific responsib ...
, 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.
[Wells DJ. 2008]
"Gene doping: the hype and the reality"
Br. J. Pharmacol. nternet154:623–31.
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
Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in tertiary structure, molecular structure to insulin which plays an important role in childhood growth, and has Anabolism, anabolic effects in adults. In the ...
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.][Gretchen Reynolds for The New York Times. June 3, 2007]
Outlaw DNA
/ref> 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
Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
.[
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
Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in th ...
(EPO) as a potential treatment for anemia
Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
.[ The scientists from that company also received calls from athletes and coaches.][ In that same year the ]World Anti-Doping Agency
The World Anti-Doping Agency (WADA; , AMA) is an international organization co-founded by the governments of over 140 nations along with the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against d ...
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
Human enhancement is the natural, artificial, or technological alteration of the human body in order to enhance physical or mental capabilities.
Technologies Existing technologies
Three forms of human enhancement currently exist: reproductive ...
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 effectively 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
The American Association for the Advancement of Science (AAAS) is a United States–based international nonprofit with the stated mission of promoting cooperation among scientists, defending scientific freedom, encouraging scientific responsib ...
focused on the issue.
Research published in 2004 showed 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
Peripheral artery disease (PAD) is a vascular disorder that causes abnormal narrowing of arteries other than those that supply the heart or brain. PAD can happen in any blood vessel, but it is more common in the legs than the arms.
When narr ...
.
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.[Gallagher, James. (2 November 2012]
BBC News – Gene therapy: Glybera approved by European Commission
BBC. Retrieved 15 December 2012.
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
Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in th ...
, insulin-like growth factor 1
Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in tertiary structure, molecular structure to insulin which plays an important role in childhood growth, and has Anabolism, anabolic effects in adults. In the ...
, human growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
, myostatin, vascular endothelial growth factor
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors ...
, fibroblast growth factor
Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by the macrophages. They are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in ...
, endorphin
Endorphins (contracted from endogenous morphine) are peptides produced in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in the pituitary gland of the brain. Endorphins are endogeno ...
, enkephalin and alpha-actinin-3
Alpha-actinin-3, also known as alpha-actinin skeletal muscle isoform 3 or F-actin cross-linking protein, is a protein that in humans is encoded by the ''ACTN3'' gene (named sprinter gene, speed gene or athlete gene) located on chromosome 11. Al ...
.[
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
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders are ...
, 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
Alpha-actinin-3, also known as alpha-actinin skeletal muscle isoform 3 or F-actin cross-linking protein, is a protein that in humans is encoded by the ''ACTN3'' gene (named sprinter gene, speed gene or athlete gene) located on chromosome 11. Al ...
is found only in skeletal muscle
Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...
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
Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA, double-stranded non-coding RNA, non-coding RNA, RNA molecules, typically 20–24 base pairs in length, similar to microR ...
.[
]
Myostatin
Myostatin is a protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
responsible for inhibiting muscle
Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...
differentiation and growth. Removing the myostatin gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
or otherwise limiting its expression leads to an increase in muscle size and power.[ This has been demonstrated in ]knockout mice
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
lacking the gene that were dubbed " Schwarzenegger mice". Humans born with defective genes can also serve as "knockout models"; a German boy with a mutation in both copies of the myostatin gene was born with well-developed muscles. The advanced muscle growth continued after birth, and the boy could lift weights of 3 kg at the age of 4.[ In work published in 2009, scientists administered ]follistatin
Follistatin, also known as activin-bindings protein, is a protein that in humans is encoded by the ''FST'' gene. Follistatin is an autocrine glycoprotein that is expressed in nearly all tissues of higher animals.
Its primary function is the b ...
via gene therapy to the quadriceps of non-human primates, resulting in local muscle growth similar to the mice.[
]
Erythropoietin (EPO)
Erythropoietin
Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in th ...
is a glycoprotein
Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
that acts as a hormone
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
, controlling red blood cell production. Athletes have injected the EPO protein as a performance-enhancing substance
Performance-enhancing substances (PESs), also known as performance-enhancing drugs (PEDs), are substances that are used to improve any form of activity performance in humans.
Many substances, such as anabolic steroids, can be used to improve ath ...
for many years (blood doping
Blood doping is a form of Doping in sport, doping in which the number of red blood cells in the bloodstream is boosted in order to enhance athletic performance. Because such blood cells carry oxygen from the lungs to the muscles, a higher concentr ...
). When the additional EPO increases the production of red blood cells in circulation, this increases the amount of oxygen available to muscle, enhancing an athlete's endurance. Recent studies suggest it may be possible to introduce another EPO gene into an animal in order to increase EPO production endogenous
Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell.
For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...
ly. EPO genes have been successfully inserted into mice and monkey
Monkey is a common name that may refer to most mammals of the infraorder Simiiformes, also known as simians. Traditionally, all animals in the group now known as simians are counted as monkeys except the apes. Thus monkeys, in that sense, co ...
s, and were found to increase hematocrits by as much as 80 percent in those animals. However, the endogenous and transgene
A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
derived EPO elicited autoimmune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease" ...
responses in some animals in the form of severe anemia
Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
.
Insulin-like growth factor 1
Insulin-like growth factor 1
Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in tertiary structure, molecular structure to insulin which plays an important role in childhood growth, and has Anabolism, anabolic effects in adults. In the ...
is a protein involved in the mediation of the growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
. Administration of IGF-1 to mice has resulted in more muscle growth and quicker muscle and nerve regeneration.[ If athletes were to use this the sustained production of IGF-1 could cause heart disease and cancer.][
]
Others
Modulating the levels of proteins that affect psychology are also potential goals for gene doping; for example pain perception depends on endorphins and enkephalins, response to stress depends on BDNF
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...
, and an increase in synthesis of monamines could improve the mood of athletes.[ Preproenkephalin has been administered via gene therapy using a replication-deficient ]herpes simplex virus
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are two members of the Herpesviridae#Human herpesvirus types, human ''Herpesviridae'' family, a set of viruses that produce Viral disease, viral infections in the majority of humans. Both HSV-1 a ...
, which targets nerves, to mice with results good enough to justify a Phase I clinical trial in people with terminal cancer with uncontrolled pain.[ Adopting that approach for athletes would be problematic since the pain deadening would likely be permanent.][
VEGF has been tested in clinical trials to increase blood flow and has been considered as a potential gene doping agent; however long term follow up of the clinical trial subjects showed poor results.][ The same is true of ]fibroblast growth factor
Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by the macrophages. They are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in ...
.[ ]Glucagon-like peptide-1
Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and cer ...
increases the amount of glucose
Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
in the liver and has been administered via gene therapy to the livers of mouse models of diabetes and was shown to increase gluconeogenesis
Gluconeogenesis (GNG) is a metabolic pathway that results in the biosynthesis of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In verte ...
' for athletes this would make more energy available and reduce the buildup of lactic acid
Lactic acid is an organic acid. It has the molecular formula C3H6O3. It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as wel ...
.[
]
Detection
The World Anti-Doping Agency
The World Anti-Doping Agency (WADA; , AMA) is an international organization co-founded by the governments of over 140 nations along with the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against d ...
(WADA) is the main regulatory organization looking into the issue of the detection of gene doping.[World Anti Doping Agency]
Gene Doping
Page archived January 7, 2016 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
Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell.
For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...
and recombinant proteins.
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.]
First generation of gene doping detecting methods
Gene doping detection idea started in 2004 when WADA has put gene doping in the banned list and started investigating a new method that can detect the inserted transgenes.
The first generation of gene doping detection techniques used PCR tests that targets the transgenes’ sequences. It can be obtained from a blood sample which will contain endogenous and transgene DNA since a small amount of the transgene will leak into the bloodstream. It can be easily distinguished from endogenous DNA because it lacks introns since the transgene will most likely use cDNA that is obtained by reverse transcriptase from RNA, which has removed its intones though RNA splicing
RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcription (biology), transcript is transformed into a mature messenger RNA (Messenger RNA, mRNA). It works by removing all the introns (non-cod ...
leaving only exon-exon junction that include only the coding sequences and some important sequences like promoters since the viral victors has a limited capacity. Therefore, PCR can target these exon-exon junctions as a unique sequence that is not present in gDNA
Real time PCR
PCR has many applications in molecular biology field including DNA analysis. The main purpose of PCR is to amplify and double the DNA sequences exponentially.
In gene doping detection, If the sequence started to amplify producing an exponential graph, then the test is positive and indicates the presence of the gene in the sample obtained from that person. But if the sequence didn't amplify and a linear graph was produced, then the test is said to be negative and the targeted DNA sequence was not present in that person's sample.
Next generation sequencing
With the limitation of the first-generation detection methods, it was important to develop a new method that overcomes the previous failures with a high accuracy and can detect the manipulation in DNA sequences that could evade to be detected by PCR methods.
The solution was using Next Generation Sequencing (NGS) method that can determine the nucleotide
Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
orders of the whole genome or targets the exon-exon junctions in transgene and compare it with reference gene sequence. This method is fast accurate and is getting cheaper by the time and has opened a new field in science that wasn't possible before like sequencing the whole genome sequencing.
DNA sequencing
DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, thymine, cytosine, and guanine. The ...
was established in the 1970s with the two-dimensional chromatography and kept improving until 2001 with the completion of human genome project
The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying, mapping and sequencing all of the genes of the human genome from both a ...
which costed about three billion dollars and required 15 years to finish sequencing the whole genome. However, with nowadays sequencing technology, whole genome sequencing
Whole genome sequencing (WGS), also known as full genome sequencing or just genome sequencing, is the process of determining the entirety of the DNA sequence of an organism's genome at a single time. This entails sequencing all of an organism's ...
(WGS) takes only a single day and costs around a thousand dollars. Moreover, a new sequencing technology is under development that will cost only 100 dollars for WGS.
There are many NGS techniques that are used in DNA sequencing but the most used method is the one done by illumina
Research
A 2016 review found that about 120 DNA polymorphisms had been identified in the literature related to some aspect of athletic performance, 77 related to endurance and 43 related to power. 11 had been replicated in three or more studies and six were identified in genome-wide association studies, but 29 had not been replicated in at least one study.
The 11 replicated markers were:[
;Endurance:
* ACE Alu I/D (rs4646994) (Called ACE I)
* ]ACTN3
Alpha-actinin-3, also known as alpha-actinin skeletal muscle isoform 3 or F-actin cross-linking protein, is a protein that in humans is encoded by the ''ACTN3'' gene (named sprinter gene, speed gene or athlete gene) located on chromosome 11. All ...
577X
* PPARA rs4253778 G,
* PPARGC1A Gly482;
; power/strength markers:
* ACE Alu I/D (rs4646994) (called ACE D)
* ACTN3
Alpha-actinin-3, also known as alpha-actinin skeletal muscle isoform 3 or F-actin cross-linking protein, is a protein that in humans is encoded by the ''ACTN3'' gene (named sprinter gene, speed gene or athlete gene) located on chromosome 11. All ...
Arg577
* AMPD1 Gln12
* HIF1A 582Ser
* MTHFR rs1801131 C
* NOS3 rs2070744 T
* PPARG 12Ala
The six GWAS markers were:[
* CREM rs1531550 A,
* DMD rs939787 T
* GALNT13 rs10196189 G
* NFIA-AS1 rs1572312 C,
* RBFOX1 rs7191721 G
* TSHR rs7144481 C
]
Ethics of gene doping
The World Anti-Doping Agency
The World Anti-Doping Agency (WADA; , AMA) is an international organization co-founded by the governments of over 140 nations along with the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against d ...
(WADA) determined that any non-therapeutic form of genetic manipulation for enhancement of athletic performance is banned under its code. There are guidelines to determine if said technology should be prohibited in sport: if two of the three conditions are met, then the technology is prohibited in sport (harmful to one's health, performance enhancing, and/or against the "spirit of sport").
Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.
The high risks associated with gene therapy can be outweighed by the potential of saving the lives of individuals with diseases: according to Alain Fischer, who was involved in clinical trials of gene therapy in children with severe combined immunodeficiency, "Only people who are dying would have reasonable grounds for using it. Using gene therapy for doping is ethically unacceptable and scientifically stupid." As seen with past cases, including the steroid tetrahydrogestrinone ( THG), athletes may choose to incorporate risky genetic technologies into their training regimes.[
The mainstream perspective is that gene doping is dangerous and unethical, as is any application of a therapeutic intervention for non-therapeutic or enhancing purposes, and that it compromises the ethical foundation of medicine and the spirit of sport.][ Others, who support ]human enhancement
Human enhancement is the natural, artificial, or technological alteration of the human body in order to enhance physical or mental capabilities.
Technologies Existing technologies
Three forms of human enhancement currently exist: reproductive ...
on broader grounds, or who see a false dichotomy
A false dilemma, also referred to as false dichotomy or false binary, is an informal fallacy based on a premise that erroneously limits what options are available. The source of the fallacy lies not in an invalid form of inference but in a false ...
between "natural" and "artificial" or a denial of the role of technology in improving athletic performance, do not oppose or support gene doping.
See also
* Doping in sport
In competitive sports, doping is the use of banned athletic performance-enhancing drugs (PEDs) by athletes, as a way of cheating. As stated in the World Anti-Doping Code by WADA, doping is defined as the occurrence of one or more of the anti-d ...
* Human genetic enhancement
* Stem cell doping
References
''attribution'' contains text from Human genetic enhancement as of 17:03, 26 October 2020
{{DEFAULTSORT:Gene Doping
Applied genetics
Doping in sport