Friday, 21 October 2016

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 2nd. 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 …….”

Wednesday, 31 August 2016

Bloody Olympics: Rio, 2016, and the history of illegal blood doping

The below is a reprint of a bog I wrote for Oxford University Press to coincide with the Olympics. Nothing new really, but it was nice to put things in a historical context. To see the original story (with pictures) go to http://blog.oup.com/2016/08/rio-2016-history-blood-doping/

Throughout history blood has been imbued with magical properties. Drinking blood was viewed as a source of power for many mythical beasts centuries before the invention of the modern vampire myth. In Greek mythology Odysseus can revive the dead by giving them blood to drink. But all blood is not the same – the blood from the veins on the left side of the snake-headed Gorgon Medusa is deadly, that from the right side is life-giving. In 1489 the Italian philosopher Marsilio Ficino, proposed that drinking the blood of healthy young men could rejuvenate the sick and elderly. Indeed it seems that an attempt was made to cure Pope Innocent VIII of his stroke by giving him blood from three ten year old boys. More dramatically the Hungarian princess and serial killer, Countess Elizabeth of Bathory, was alleged to have drained all the blood from over 600 young girls to feed her restorative blood baths.

Drinking fresh blood was supposed to give you strength, maybe eternal life if you were a vampire. Even in the post-enlightenment age, the first blood transfusions had nothing to do with the modern notion of enhancing oxygen supply; instead they were supposed to heal by replacing old bad blood with strong healthy animal blood.

Sport has long had a fascination with blood. The blood of the Roman gladiators, moppped by a sponge from the arena, fed a profitable business; perhaps the athlete’s ultimate commitment to promoting their brand? Today blood is even more relevant to sport. Indeed arguably its use and abuse in sport today has come close to destroying the Olympic movement.

The modern fascination with blood in the Olympics arose from the new discipline of sports science in the 1960s and 1970s.  A key driver was the 1968 Mexico City Olympics where physiologists recognized the difficulty of getting sufficient oxygen to tissue in the rarefied 2km high air. Red blood cells transfusions increase the amount of oxygen given to people suffering from trauma or anaemia. It was therefore argued that healthy athletes could be given “excess” blood to increase their ability to deliver oxygen to tissue, and hence enhance their performance in endurance sport?

Scandinavian scientists were first to prove this - in 1972, Bj√∂rn Ekblom at the Institute of Physiology of Performance in Stockholm, showed a 25% increase in stamina after a transfusion. It was subsequently alleged that Scandinavian athletes were putting this laboratory method into practice. Lasse Viren won double gold medals on the track in 5,000m and 10,000m at the 1972 and 1976 Olympics. Unproven allegations of blood doping dogged Viren, who always denied them claiming that altitude training and “reindeer milk” were the keys to his enhanced performance. Some of his teammates did later confess to blood doping, however, most notably Kaarlo Maaninka at the 1980 Olympics. Maaninka received no sanction, which might surprise today’s readers given that blood doping is one of the main reasons we will not see the Russian track and field team competing at these Olympics. However, although in the 1970s and 1980s blood doping was viewed as morally dubious, it did not break any rules. The anti doping effort of the time focussed more on amphetamines and anaboloic steroids.

This would change in the 1980s. The LA Olympics in 1984 was the watershed event. There was extensive use of blood transfusions including by several members of the highly successful US cycling team. Again no rules were broken, but the IOC had had enough and banned blood doping in 1985. However, they had no way of testing for this form of cheating, so it presumably continued in secret. In fact the ready availability of genetically engineered EPO in the late 1990s, a difficult to detect drug that increases the number of red blood cells more gradually and naturally than a blood transfusion, undoubtedly increased the use of banned methods. I could fill most of the rest of this article with a list of Olympic athletes who are confirmed or strongly suspected of using EPO and/or blood transfusions to aid their performance.

So where are we now? Blood is a part of the Olympics and always will be. Whilst not imbuing you with the mythical life giving properties of Odysseus, optimizing your number of red blood cells is a key part of success in endurance events. I can guarantee that every medal winner in a long distance endurance event will have had their blood measured frequently by support scientists to conform the success of their training program, whether that program uses permitted (altitude training, sleeping in low oxygen tents) or banned (EPO, blood transfusion) methods.

So much for Rio, what about PyeongChang and the Winter Olympics? This is, if anything, an even richer source of stories than the summer games.  There are claims of athletes chosen for ski teams solely so that are the right blood group to donate blood to their team leader; in 2006 a disgraced ex Austrian ski coach crashed his car into a roadblock in the Italian alps, whilst attempting to escape the police. But that’s a blog for two years time ……..

Rio Olympics 2016 and doping stories

Most of the interest for me happened pre the Games of course and the "will they, won't they" allow Russia to compete saga. Not surprisingly during the games my TV and radio interviews weren't about science, but about athletes response to other athletes. The extent of finger pointing was unusual for the Olympics,  but less extreme than has happened at some other events e.g. Paula Radcliffe unfurling her "EPO cheats out" banner at the 2001 World Championship [1]. Still it was the Olympics so news outlets inevitably focussed on incidents such as the finger wagging between Yulia Efimova and Lilly King [2]. Until of course the light relief/black comedy provided by Ryan Lochte and his co-conspirators [3].

The main story in my opinion though was the IPC being brave enough to ban Russia completely from the Paralympics. The world didn't end and the ban was even upheld by the Court of Arbitration for Sport.  This rather put the lie to the IOC's passing of the buck to the national sporting organisations with its ridiculous one week timescale and wilful misreading of the nature of the McLaren WADA report [3].

I didn't get asked much about the IPC decision  though I did try to bring the contrast with the IOC into some of my interviews. Still I am now really looking forward to the Paralympics. Not clean, but cleaner......

[1]  https://www.theguardian.com/sport/2001/aug/10/athletics1

[2] http://www.independent.co.uk/sport/olympics/rio-2016-yulia-efimova-and-lilly-king-show-how-swimmings-code-of-honour-is-shot-to-pieces-by-ioc-a7179891.html

[3] http://www.breitbart.com/video/2016/08/22/john-oliver-destroys-ryan-lochte-labels-him-americas-idiot-sea-cow/

[4] https://www.theguardian.com/sport/2016/aug/04/richard-mclaren-ioc-wada-russia-rio-2016-

Friday, 11 March 2016

Sharapova, Pound and Seppelt: Tacking Doping in Sport 2016

I’ve just come back from this two-day conference at Twickenham stadium. To get there I waited once again at the bus stop I used to spend my teenage life hanging around – a situation made me feel both strangely young and old at the same time. But what of the conference? You might expect a set of talks from regulators and lawyers to be dry and drab. However, at times more sparks flew than even at the most vitriolic academic meeting. Actually the latter are usually sedate – though intellectually stimulating events – with tempers and egos well in check (at least until the bar opens).

So what caused the fuss at Twickenham? Surprisingly it wasn’t the Maria Sharapova meldonium affair. This just led to incredulity as to how someone would keep taking a drug – for whatever reason – when it was so clearly advertised as coming on to the banned list and an effective test had clearly been developed. The fact that Sharapova has been joined by 99 other athletes in the space of a few months suggests either a massive breakdown in anti doping education or a significant level of stupidity amongst dopers.

So who did get everyone excited? Not Dick Pound for once with his usual erudite exposition of Russia’s recent failings. Not even Jonathan Taylor from Bird & Bird who did his best to wind up – well everyone really. No they were both upstaged by the showing of Hajo Seppelt’s new ARD documentary; this revealed that banned coaches were still active in Russia. He followed this up with some direct barbs at the WADA president, Sir Craig Reedie, accusing him of firing one of his top investigators and having a conflict of interest between his role at WADA and the IOC (where he is a Vice President).


I felt a little bit sheepish giving my own talk immediately after Hajo’s Tour de Force. Especially as what I was talking about essentially amounted to studying not doping. I discussed whether much of doping’s effectiveness could be due to the power of the placebo effect i.e. the athlete runs faster because they believe they have a secret advantage. This contrasts with the nocebo effect, where the athlete runs slower because they believe their opponent is doping and hence can’t be beaten. The problem is to do the definitive placebo doping study I would need to give EPO to a elite athletes whilst telling them I was giving them a meaningless injection. This would reveal exactly how much of EPO’s benefit is due to its biological, rather than its psychological effect. But it is hard to see a research ethics committee agreeing to this level of deception. Such a pain when morality gets in the way of a good piece of science!

Wednesday, 9 September 2015

Paula Radcliffe, Sky News and me


What I feared from my last blog has come true. It looks as if athletes are going to be “forced” by media (or political!) pressure to reveal their blood passport data – well every athlete who is successful in a high profile sport at least. In this context I was interviewed after Paula Radcliffe on Sky News this afternoon. When I finished the interviewer thanked me, but said it was all very complex. Such a response would normally indicate I had failed as a science communicator. In this case I think I succeeded in getting my point across. Interpreting anomalous athlete biological passport data is non trivial. That is why it requires three experts to agree in a blind test (not knowing who the athlete is). Simple analysis can work on large data sets to indicate the potential scale of a doping problem. It can’t be done to scapegoat an individual.

Thursday, 20 August 2015

Doping at the World Athletics Championships – part 1

My title indicates that I think these championships might take up more than one of my blogs! Indeed the Sunday Times/IAAF doping story has already messed up my holiday. I was pestered by well meaning journalists while visiting Yorkshire. Fortunately I was for the most past saved by dodgy mobile phone signals and an absence of Wifi. I did, however, make an exception to talk to Radio 5 live Drive and Radio 4 pm in the BBC radio car parked in the local pub car park. What could be more surreal?

It has been hard commenting on the leaks given the fact that the various protagonists (IAAF and the Sunday Times/ ARD/WDR) have access to the data but have released only a very limited amount into the public domain. The IAAF has indicated they will eventually publish a “prevalence study” sometime in the future. Whether this will go so far as to make comparisons between countries and whether it will also be possible to compare individual sporting events remains to be seen. These of course are the highlights of the leaks, but realistically might be excluded in an academic type report.

So what can be said and how does it relate to the upcoming World Athletics Championships in Beijing? Well, starting with a selfish note, I am pleased that the 1500m final in the women’s 2005 World Athletics championships is finally getting the “recognition” it deserves [1]. In the opening pages of my book I note that, far more than Ben Johnson’s 100m run in the Seoul Olympics, this race deserved the moniker of the dirtiest race in history [2]. My comment that the first five athletes to cross the line were alter found guilty of doping (admittedly in later tests) has now been backed up by anomalous blood readings taken at the time of the events.

It is worth noting that the winning time in this infamous race was over a second slower slower than when the clean athlete, Kelly Holmes, won the 1500m Olympics title a year earlier. This brings me to my first substantive point. An anomalous blood reading does not mean someone is necessarily doping. And even if they are doping it does not mean that they won the race because they were doping. Although there is good evidence in the scientific literature that increasing your total haemoglobin levels increases athletic performance, there are sparingly few results in elite athletes (where performance effects of ergogenic aids naturally become smaller in size). Even the studies that have been done rarely use a proper randomised placebo controlled design. There is no control for the placebo effect. The importance of this cannot be underestimated; a placebo effect is likely to be doubly powerful when taking a banned substance as these are assumed to be especially powerful. Interestingly a recent randomised blind trial on elite cyclists surprisingly showed no effect of altitude training and suggested previous positive results might be mostly down to placebo [3].  “Unfortunately” it will be almost impossible to do a similar study using EPO or blood doping due to ethical constraints surrounding giving people potentially harmful drugs. Worse still the definitive study would involve giving someone the drug and actively telling them they are getting a placebo [4]; even using microdoses of EPO this would be a real ethical minefield.

My second substantive point relates to the success, or not, of the blood passport program introduced in athletics by the IAAF in 2009. Clearly this has resulted in a significant number of suspensions. But has it affected the number of people doping? In cycling there seems to be a clear effect [5]. This was shown by the drop in the number of cyclists showing abnormally high or low levels of young red blood cells called reticulocytes (a recent blood transfusion will likely give a low number and an injection of a high dose of EPO a high number). The blood doping expert Michael Ashenden was reported in the Sunday Times as saying that “despite the introduction of the biological passport, analysis of the data shows nearly 70 athletes with suspicious blood test results still escaped censure” [6]. This my be so, but it would be very interesting to see his detailed analysis of whether there was any change at all from 2009-2012.

The relevant data outlining the effect of blood doping on the performance of elite athletes is hidden from the average scientist in the secret files of doping athletes and their coaches. Still my “not too controversial” personal view is that blood transfusions and high dose EPO genuinely provide a performance benefit in elite athletes. I am currently less convinced that micro dosing of EPO, of the type designed to fool the biological passport, is as effective. It is unlikely to create a situation where a clean athlete cannot win a race against a doper. It is also possible that just by forcing the athletes to change doping strategies to avoid detection, you make that doping less effective.

In the worst-case scenario portrayed by the Sunday Times 30% of successful athletes had anomalous blood readings and so might have been doping; but this still means that 70% of athletes with “normal” blood readings managed to beat these dopers. Doping is best seen as one part of a complex set of factors that lead to a gold medal. It is only occasionally in sport that we see situations where it is inconceivable that a clean athlete could beat a doper – the most notable being the period in the 1970s and 1980s when female athletes were dosing with large amounts of anabolic steroids. The Tour de France in the Armstrong years may well be another example.

My final point relates to one I was questioned by on BBC radio recently. Should athletes reveal their own passport data? Even the athletes themselves are divided on this [7, 8]. But I feel the cat is out of the bag now. Anyone with a normal score is going to shout it from the rooftops. Those with anomalies will be shamed for not revealing them – unless they have a really clear explanation to hand. Anyone not revealing their scores will be assumed to be hiding their data because they are doping. My major concern is that the internet will fill up with well-meaning and not so well-meaning amateurs who will be able to “prove” that someone is doping from their passport score.

We have seen this effect with performance data in cycling for a number of years now. The most recent example was the accusations of doping against Chris Froome in the Tour de France in the complete absence of any analytical doping data [9] or any intelligence about dodgy practices garnered from fellow team members [10]. Another example: the UK 400m runner Roger Black is one of those now calling for athletes to reveal their passport data [7]. Yet I remember him telling me he was once confronted by a member of the public who said he could tell he was cheating just by looking at some of the times he had posted. As Paula Radcliffe [8] said you can never prove you are not doping.

I suspect blood passport scores such as reticulocyte count, red cell volume and haemoglobin concentration will soon become as well known to the world of online sport comment as performance measures such as peak power, VO2 max and lactate threshold are now. In the conclusion of my book I said “When it comes to making practical and ethical policy there is a devil in the scientific detail that is absolutely required if we are to make informed moral and political choices.” In athletics and doping the time of science is upon us now.