DENY, DENY, DENY. Gene doping: the future of theatre?

Deny, Deny, Deny is written by Jonathan Maitland and is due to open at the Park Theatre, London on November 2^nd. I was the scientific advisor for this play, which deals with a female sprinter tempted into experimenting with gene doping. I wrote a short piece for the program notes, which I reproduce below [note that the last line does not mean I particularly think any athlete is currently gene doping, although this possibility can’t be ruled out entirely].

“In 2006 anti doping agencies got the information they had always feared.  Police raiding the home of famous German athletics coach, Thomas Springstein, found this email on his computer: The new Repoxygen is hard to get. Please give me new instructions soon so that I can order the product before Christmas.” Repoxygen was an experimental drug developed by UK biotechnology company Oxford Biomedica. It was designed to treat anaemia by injecting extra copies of the human erythropoietin (EPO) gene.

EPO is a small protein that increases the number of oxygen carrying red blood cells in the body. Activating the EPO gene increases the levels of EPO protein, increasing the number of red blood cells, enhancing oxygen delivery and improving performance in long distance “aerobic” sports. Clean athletes try to increase their own levels of EPO by altitude training. Others, like the cyclist Lance Armstrong, injected synthetic EPO directly - a process explicitly banned by the World Anti Doping Agency. Synthetic EPO is detectable, albeit with difficulty. It also needs multiple injections. How much better coach Springstein thought to inject the EPO gene itself? This gene would continue to make increased undetectable levels of EPO, creating a gene doped super athlete!

We don’t know whether Springstein ever got hold of his black market Repoxygen. We do know that Oxford Biomedica stopped making it; a combination of poorer than expected animal trials and the ready availability of new versions of cheap, synthetic EPO protein made further development uneconomic. Market forces, rather than the vigilance of anti doping agencies saved the day for clean sport in this instance.

Gene doping sits at the heart of Deny, Deny, Deny. So what is it and is the plot scientifically feasible? Gene doping is the bastard child of gene therapy. It uses the same molecular tools but aims at different outcomes. Whilst gene therapy attempts to cure genetic diseases such as cystic fibrosis and thalassemia, gene doping aims to improve how well elite athletes can run, swim or throw.

In the 1970s gene therapy was touted as heralding a new age of medicine. Is gene doping a similar game changer in sports cheating? The basic science is scarily cheap. You can teach students the principle in a school project and even get them to make a “dummy” gene construct. There is an analogy here with nuclear weapons. Everyone knows the basic theory of how to make one. But the problem - and expense - lies in the fine details of the engineering. In gene therapy the multi million pound expense is not in creating the new gene, but in making the final product effective and safe. As a result there are only a handful of genetic diseases that are currently treated by gene therapy; the cost of gene therapy per patient runs into the hundreds of thousands of pounds.

It is easy to envisage gene doping increasing the speed of female sprinters. It would only require injecting a gene that causes a slight increase in levels of testosterone – the natural male anabolic steroid - to increase female muscle mass and enable a sprinter to power to victory in the 100m or 200m. But given the costs is gene doping too expensive and impractical to be successful without the backing of Big Pharma or a rogue state? I think not. If you had “looser” ethics and were willing to trade off safety for low cost and high performance, it is easy to envisage an unscrupulous coach persuading a scientist to inject a gene that would increase the performance of a female sprinter. Perhaps they already have …….”