Lewis Wolpert: 'Could gene technology be used illegally to increase an athlete's performance?'
Wednesday 04 August 2004
Sporting ability offers a fascinating insight into the complex relationship between nature and nurture - between the characteristics one's body has because of its genes, and those it has due to training.
Sporting ability offers a fascinating insight into the complex relationship between nature and nurture - between the characteristics one's body has because of its genes, and those it has due to training. There are many elements involved, but muscle and blood are, for athletes, fundamental. And it raises the question: could gene technology be used, illegally, to increase an athlete's performance?
A medical journal has just described the case of a child with greatly increased muscle mass because of a mutation in a gene called myostatin. Myostatin is responsible for a protein that is a negative regulator of muscle mass. Mice that have had this gene deleted become muscle-bound titans.
The four-year-old with the mutation in the gene is unusually strong. His mother, who carries a similar gene, was a professional athlete and other members of the family also possess great physical strength. More generally, second-and third-generation professional athletes are not that rare and could owe their abilities in part to variants in genes like myostatin. One such family is rumoured to include a European weightlifting champion.
Another example of a gene involved in muscle development that could offer an advantage to sprinters is the gene that codes for fast muscle fibres. An unusually high number of sprinters have copies of this gene, and this is particularly true of female sprinters who have two copies of the gene. Muscle mass normally declines with age and lack of use has a similar effect, as was so clearly demonstrated with astronauts working in the absence of normal gravity. A special feature of our muscles that are used for common movements is the presence of satellite cells that lie on the outside of the muscle membrane.
These are muscle-specific stem cells, and when they divide their offspring fuse with the muscle and contribute to its growth. A factor that stimulates the division of these satellite cells is insulin-like growth factor. When this substance was introduced into the muscles of the limbs of young mice, the rate of muscle growth was greatly increased.
This was not done by simply injecting the factor since it would disappear within a few hours. The technique was based on introducing the gene for the growth factor which should then result in it being produced for the life of the cell into which it was introduced. This was done by putting the gene into a virus that infects muscle cells, and then injecting the virus into the muscles of the young mice.
It is not just muscle mass or the rate of contraction that are important for athletic performance, as endurance is essential for many competitive sports. Endurance is partly dependent on the amount of oxygen reaching the muscles, and is carried there in the red blood cells. Another factor, erythropoietin, promotes the production of red cells. It was found that a Finnish cross-country skier and gold medallist at the 1996 Winter Olympics had a mutation that caused an excessive response to erythropoietin. Several members of his family were also champion athletes.
A synthetic form of erythropoietin has been developed to treat anaemia and it has also been used by some athletes to improve performance, as in the 1998 Tour de France. More dramatically, the British cyclist David Millar has just confessed to its use. There are also dangers if the gene that codes for the factor is introduced, as experiments on animals found that the blood-cell count rose to the extent that the blood became so thick that it almost stopped flowing. Nevertheless there will undoubtedly be ways of doing this in a safe way in the future.
But this raises some tricky questions about the ability to detect whether an athlete has had genes for insulin-like growth factor or erythropoietin or a block to myostatin introduced into their muscles - otherwise known as gene doping. Detection could not only be very difficult but might require removal of pieces of muscle for testing, which few athletes would accept.
Such examples are only a tiny selection of some 90 potential genes associated with improved athletic performance. Another issue entirely is whether tests for such genes will be used in the future to screen the genetic makeup of children in order to see if they should be encouraged to pursue certain sports. The prospect of testing children for the genes of sporting prowess raises different ethical issues other than simply ensuring fairness in sport.
Professor Wolpert is professor of biology as applied to medicine at University College London
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