role of gene therapy in sports
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Introduction
Sport has become an important factor in the human lifestyle as it keeps people in good physical condition and it brings nations together; furthermore, it is not something that should be taken lightly. There is a great deal of tough competition in sport and when it comes to world records, the rules and regulations become incredibly strict. When a world record is broken, we need to ensure that the athlete has not been doping to get an advantage over other athletes. A growing concern for the World Anti-Doping Agency is the progression in gene therapy. It has created possibilities of gene doping, which may not be detectable, therefore destroying the element of fairness in sport.
Sport doping
The term, doping , refers to the use of performance enhancing drugs (PEDs) and is used in almost all sports but most commonly in individualistic sports such as athletics, cycling and weightlifting. The use of these drugs is seen as unethical by the majority of the international sports organisations and it is, therefore, banned in certain sports.
In 1928 the International Amateur Athletic Federation (now known as the International Association of Athletics Federations) banned doping amoungst their participants and were the first international governing body of sport to do so, yet we were not technologically advanced during this era and were unable to test for doping. The first tests for performance enhancing drugs were taken in 1966, but the dilemma with the testing was that pharmacology had always progressed faster than the testing and frequently new drugs were being released that were undetectable. Finally, in 1999, the World Anti-Doping Agency was created which lead to a dramatic increase to athletes being caught.
To test for doping a participant is required to provide a urine sample which is separated into two samples, A and B, where sample A is tested first and if a prohibited substance is present, then sample B is tested for confirmation and when confirmed, the participant will be disqualified or will not be authorized to take part in the event. There is however an issue that needs to be faced in near future: the possibility of gene doping by means of gene therapy - and whether or not it is detectable.
Gene therapy
Gene therapy is the process whereby specific genes are inserted into a person s cells with the purpose of combating or preventing particularly a heredity disease an illness that is caused by abnormalities in genes and chromosomes due to mutations. The genes that are inserted will replace the mutated gene with a healthy one or assist in deactivating and fighting the mutated gene. Genes cannot be injected directly into a person s cell. They have to be transported by a vector and the most commonly used vector is a virus. A virus is genetically altered by manipulating its genome to replace disease-causing genes with therapeutic ones. Specific cells are targeted and infected with the virus whereby it unloads its therapeutic genetic material into the cell. The DNA then instructs the cell to produce functional proteins and the cells are restored to its normal state.
The two types of gene therapy include germ line therapy and somatic therapy. The safer option of the two is definitely the somatic therapy. Only specific cells may be targeted and it is short lived because the cells affected by the therapeutic genes eventually get old and die and are replaced with new cells with the original genetic material. This makes it a more conservative approach as it does not affect future generations and if it is not successful its effects will fade out when the cells die, however, if the effects want to be maintained, the dosage must be taken repeatedly during the individual s life span. The distinction between the two therapies is that the germ line therapy involves the infection of sperm, egg or embryo cells whereby the changes become permanent and are passed on to future generations. This can be highly effective if used to eliminate genetic disorders that have been passed down in a family.
Originally gene therapy was studied for the prevention or cure of a disease, however it opens the gates to many other possibilities; possibilities that many athletes are interested in. Somatic gene therapy may be used for gene doping. Although gene therapy is presently in its research and experimental phase, it can be expected to become part of our lives in the near future. According to the article in the time magazine, there have, in the past two years, been breakthroughs in gene therapy.
The breakthrough that has caught the attention of athletes is the one where, through gene therapy, monkeys muscles grew bigger and stronger. This was done within weeks and without the use of anabolic steroids, exercise or genetic engineering. All that was done was an injection of genes directly into the quadriceps of the monkeys and within eight weeks the changes could be observed. As a result of somatic therapy being used, the effects lasted 15 months and returned back to normal. Previously mice were genetically engineered to have an additional follistatin-producing gene, however it was discovered with the monkeys that it is possible to just simply inject genes by using a virus as a vector.
The protein follistatin , blocks the function of myostatin - another protein which holds back muscle growth - therefore if more follistatin is provided there will be less functioning of the myostatin, meaning that muscle growth will not be held back as much as it is originally supposed to, resulting in greater muscle growth. Once the gene coded for follistatin was injected into the muscle and eventually into its nucleus, the muscle itself started producing its own supply of follistatin, which caused muscle fibres to go on growing.
Gene doping
Gene doping is defined as the non-therapeutic use of cells, genes, genetic elements or of the modulation of gene expression, having the capacity to improve athletic performance. This definition originates from the agency that is most concerned for its uses the World Anti-Doping Agency (WADA). The interest in enhancing a sportsperson s performance by genetic is so high in the sports community that gene doping is inevitable.
There are approximately 187 different genes that relate to a persons athleticism and strength, with a specific gene being able to enhance the performance for a particular activity such as running a 2km race. The athlete can be made more efficient by adding copies of certain genes or intensifying or weakening certain genes activities. Scientists are not exactly sure which genes will affect what function of the athlete; however there are genes that are more understood and are in the spotlight for gene doping. One of these is the IGF-1 gene for insulin-like growth factor-1 and this gene s function is to repair and strengthen one s muscles. If one wants an improvement in endurance they would look at the gene for erythropoietin (EPO) which increases the number of red blood corpuscles circulating in their system allowing more oxygen to be carried throughout the body.
It is very important for the genes to be deposited into the correct cells; otherwise muscle enhancing genes may end up producing growth proteins in the eyes which could alter the patient s vision. Luckily scientists have methods of directing the genes into the right cells. They can do so by injecting the genes straight into the muscle so that the genes enter the muscle cells only. Genes can also be controlled so that they can enter cells but only activate in the desired cells. A carefully chosen virus may be used that infects only certain parts of the body. Scientists also believe that they can engineer a gene so that it will only function when a drug is taken that triggers it off. The injected new genes will enter the nucleus (the cell is transduced) and either linger freely amoungst the chromosomes or it will shove into and become part of a chromosome. The difference lies in the fact that when the cell divides through the process of mitosis, the gene that is part of the chromosome divides with it and becomes part of two new daughter cells, whereas the genes that are roaming freely in the nucleus will die when the division takes place. The transduced cells will obey the new genetic instructions and synthesise proteins accordingly.
It is exciting to fantasise about the greatness that can come from gene doping for athletes, but when reality kicks in we must know that there are certain concerns about possible health issues. Taking human experimentation into account, genes have only been transferred in the purpose of making diseased people healthy; not making healthy people improve. Doping has only been tested on animals and even some animals experienced unfavourable side effects. Numerous athletes are interested in the EPO gene for more oxygen to be circulated. However, in an experiment of doping healthy monkeys with the EPO gene, their blood became dangerously thick and the scientists had to bleed the monkeys to prevent a stroke and heart failure. In the end the best thing to do was to put the monkeys out of their suffering through euthanasia.
There are many hopes that there will be a breakthrough in gene therapy for cancer to be cured, but what hasn t been thought of much is the dangers of gene therapy in doping. An athlete expecting an enhancement may end up with cancer instead. It is possible that the genetic modification triggers off a cancer gene or hinders a cancer suppressing gene, resulting in a tumour. An experiment on five children turned out to be a failure when they were treated with gene therapy to treat their immunodeficiency and the genes were inserted into the chromosome in the wrong place, turning on cancer cells, and the children were left with leukaemia.
It is also possible that a patient s immune system reacts; causing inflammation, fever or a possible severe reaction that could be fatal. This was witnessed when a gene was injected into a monkey where it produced the incorrect EPO protein which is naturally made in the liver and the monkey s system attacked both EPOs leaving the monkey without red blood corpuscle production. The end result was fatal. Doctors are incapable of taking a gene out of a cell, therefore if something does go wrong, there is nothing that can be done to stop it. It is also unknown as to what will happen to a treated patient when they get old, because gene therapy is still young. All that can be confirmed now is that presently gene doping is not safe, but it is expected to be safe in a few years to come.
Detection of gene doping
Performance enhancing drugs and blood doping is tested and detected through blood or urine samples. Techniques known as gel electrophoresis and isoelectric focusing are used to distinguish the EPO hormone that is naturally present in an athlete s urine to the almost identical EPO hormone that is present due to doping. If the gene for EPO is injected into an athlete it is indistinguishable from its natural counterparts and will not be detectable in a urine or blood sample because nothing unusual enters the bloodstream. Although gene doping is not yet available, it has been prohibited by the World Anti-Doping Agency (WADA). If it was readily available today there is a certainty that it would be used because at present there are no methods of detecting it, which is why WADA has already asked scientists to come up with safe methods of testing to detect it.
Firstly a deep concern is the availability of gene doping and whether or not it may be secretly in use presently. The chances are slim, yet possible. Human gene products haven't been approved for sale by the U.S. Food and Drug Administration (FDA), therefore it would be illegal if it were in one s possession. Any experiments involving humans must be authorised by the FDA and the National Institute of Health, and currently only humans in desperate need of treatment may be experimented on, however, uses other that aren t therapeutical are disallowed. Officials are concerned with the possibilities of scientists accepting bribes that are able to prepare genes in a laboratory, but nothing can be done to stop it if done so discretely.
It is possible to detect gene doping in an athlete, however, it can only be done if the specific enhanced muscles were known (but an athlete would have to tell you, which is unlikely) and results would only come after a sophisticated study in a laboratory. The chances of it being successful are slim because of the uncertainties of which tissue in the body needs sampling, which is where the problem lies. If the tissue is found, the test will compare how many copies of the doped gene are found in the athlete to the common number found in an average person who hasn t been doping. An idea of detection involved not looking for the drug, but looking for its effect on the body. The positive point on this method is that it would not only be used for detection of gene doping, but for all kinds of doping.
The body can be examined for an immune reaction, which could be triggered off by the use of a virus as a vector in gene doping. The antibodies that are produced to fight a virus can stay in a person s blood for up to six whole months. Researchers are trying to image transgenic proteins and injected genes inside the body of an athlete which could detect modifications within a muscle. Currently this may be done with radioactive tracers which are safe but would cause an inconvenience to athletes. Scientist are in the process of testing methods on mice to detect changes in blood, urine or saliva, but an athlete s average ranges still need to be discovered through numerous tests and samples.
All over the world scientists are working hard on discoveries in gene therapy. Whether it be for therapeutical means, gene doping, or detection of gene doping, they are working in full throttle. When gene therapy has its final breakthrough it is expected to have a larger impact on our world than the industrial revolution. Due to all this focus on gene therapy and information from scientists, gene therapy can be expected in a few years time. It will be used in sport, however, by the time it is available, methods of detection will almost be ready to combat it and provide fair competition. As there has been a lag phase of detection of doping as to when the doping is released, so it will too happen with gene therapy. Athletes and audiences should decide what they value in sports and whether allowing gene doping would dissolve those aspects. That will help us decide where to draw the line , says Thomas Murray, president of the Hastings Center, a non-profit bioethics institute in New York.
