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Sunday, November 16, 2008

The doping dilemma

Doping in sport: Impossible to control, time for a new mindset

The issue of doping in sport is (unfortunately) never too far away from the headlines, and as the year winds down, with little in the way of elite sport taking place around the world, it's a chance to reflect on this controversial topic.

That was stimulated by this article, which details the extreme lengths that athletes will go to gain an advantage. The article, published in The Telegraph, explains how Professor Lee Sweeney, an expert in gene-transfer technology, has gained notoriety in the world of sport as a result of the possible application of his research to athletes. Sweeney was one of the scientists responsible for producing the "mighty mice" which are now famous as having super strength and size. In short, read "gene-doping", and you understand why Sweeney is in such high demand.

It's a fascinating article for a number of reasons. It gives a few examples of the lengths coaches and athletes will go to in order to gain a performance advantage, regardless of the risks. One coach offers $100,000 for the mouse-treatment, while another coach requests that his ENTIRE football team be genetically-modified. The fact that this is "only" at high school level is an indication of the extreme lengths that people will go to - how much more so for elite athletes?

These requests apparently come from all around the world, but none are from "big-name sports stars", but usually come from up-and-coming athletes who want to make the big time. In response to this demand, Sweeney is now part of a gene-doping panel on the World Anti-Doping Agency, and will be conducting research to help WADA remain a step ahead of the drug cheats.

Can anti-doping really stay ahead of doping?

That is likely an over-ambitious goal, and elite sport has shown time and again that for the doping authorities to remain AHEAD of the dopers is a near-impossible mission. This year, the world of doping control celebrated when cyclists tested positive for CERA, a third-generation form of EPO, which cyclists were using under the impression that it was undetectable.

We covered that story, and saw how the test was developed thanks to collaboration between WADA and Roche, the pharmaceutical company that produced CERA. A convenenient modification to the compound, in the form of a polyethylene glycol molecule, was the basis of the test. Ricardo Ricco, Emmanuelle Sella, Leonardo Piepoli, Stefan Schumacher, and Bernard Kohl have all tested positive for CERA in recent months, either during the Giro d'Italia, or the Tour de France. CERA was only available in Europe from the beginning of the year, and made its way quickly into the pro-peloton, where that afore-mentioned polyethylene-glycol molecule was thought to make it undetectable.

For once, however, the testers were a step ahead and had managed to develop a test for the drug, which threw up the surprises. More are expected, though one would think that as soon as the cyclists knew the test existed, they'd be off the drug. The point is that the window of opportunity is open for a short time only, and a more "strategic" (read sneaky) approach may be considered in future to catch more athletes!

Perhaps the larger question worth asking, however, is that if CERA is a drug that was used with the wrong impression that it was undetectable, how many more might exist where the athlete is actually right, and the drug is undetectable? The anti-doping authorities were quick to pat themselves on the back and hail this as a victory and a giant leap forward. They'd do well to remember that for every one drug they can test for, there may well be many others they cannot.

The premature celebrations don't serve any purpose in the long run. Let's not forget that had it not been for a jealous coach and an anonymously handed-in syringe, we might still be celebrating Dwain Chambers and Marion Jones' sprinting exploits...THG was only discovered "by accident" and thanks to coach-jealousy, and it blew open a can of worms so vast that it still seems to throw up revelations today. This should serve as a reminder to the authorities that they are nowhere near to winning the war, despite winning this particular battle.

The Telegraph article has some interesting insights in this regard. It leaves behind Professor Sweeney and his gene-doping requests, and talks about French scientists who have received similar visits and requests from athletes. Professor Philippe Moullier is currently working on gene-therapy to help patients with anemia (currently he works with monkeys), and he received a visit from ex-Tour de France cyclists who said they represented an anti-doping agency and wished to find out about his research.

Upon telling them that the research was only in its infancy, they said that the riders would not care, and that "there are kids in the Tour de France who would do anything just to have the most advanced technology." That again highlights the intensity of the battle that anti-doping agencies are fighting.

The battleground is too vast to police using "classic" methods

But perhaps the most telling point, which is really my opinion, and is not really covered in the article, is that the battleground is too vast for agencies like WADA to try to police using "classical" means. The concept that one can appoint a small group of scientists to a doping panel, and have a very narrow hierarchy where a few experts are responsible for overseeing the strategy and tactics of WADA is a very outdated one.

Whether it's a Professor Sweeney in Pennsylvania, or Professor Moullier in Nantes, or any one of the countless other scientists who are doing work on doping (either gene-doping or classical), it is simply impossible to monitor and manage all of them. For every Prof Sweeney who is drafted onto a doping panel, there could well be thousands of scientists who are not. Trying to control this simply cannot work in an archaic, pyramid structure which awards research funding to the select few who have the right contacts and obtain the right profile.

Flawed testing, but WADA's blind eye fails to advance progress

This is a job for everyone, and WADA and every anti-doping agency would do well to remember this. Unfortunately, they rarely do. This is best demonstrated by the example from earlier this year, when a Danish research group, working independently, decided to "test the testers" and evaluate how effective WADA's testing labs were in detecting EPO use. The results of that research are summarised in the figure below.

The study, in case you missed it, gave research volunteers EPO and then sent collected samples to two different WADA laboratories for testing. The result was that the labs did OK on the first round (during the period of "boosting") with Lab A producing a 100% positive record, and Lab B getting 7 "suspicious" samples, but one negative. But during the maintenance phase, only two out of 24 samples tested positive for Lab A, while Lab B failed to find a single positive or suspicious sample.

In response to this result, which was actually published in a scientific journal, the Scientific Director of WADA said "I have never seen such a drastic situation as the one reported in this article".

Well, Dr Rabin and WADA, you have now. Because the paper is there for all to see. Yet WADA came out and defended their testing process, despite having been dramatically shown-up by an independent research group. Given the stakes in the battle and the enormity of the fight against doping, the Danish research helped show that the current anti-doping process is not foolproof (in fact, it's seriously flawed), and dismissing it serves little purpose, other than to signal to athletes that your chances of getting caught are not as high as they should be. Therefore, use drugs, you might just get away with it.

Wada does, incidentally, do its own evaluation of the labs, but the results are never published, and no "data-sharing" policy exists. The organization is set up very much like the classic "business", where a select few make all the decisions, control all the funding and pull all the strings, as they see fit. What this does (apologies for the management speak) is reduce the rest of the world (all 99.999%) to onlookers, rather than fostering what has been called a "knowledge economy", where everyone shares in data and expertise is maximized. Tall, narrow pyramids are not the way to fight the anti-doping battle, because the "opposition", the dopers, are diffuse, spread out and impossible to control.

The Wikinomics of anti-doping

Rather, the work of EVERYONE should be embraced, in a kind of "wikinomics" fashion, where the sharing of information, in a fully-transparent system should be promoted. The "wikinomic" concept, incidentally, holds that "mass collaboration" may hold the answer to solving the kinds of problems faced by anti-doping authorities. It is the title of an excellent book, well worth reading, and a particularly interesting website.

I really do beleive that an astronomical collaboration approach to the fight against doping is required - the details will be difficult to work out, but only when thousands come together to pull in the same direction, can we expect the testers to catch the dopers. The first step should be to make fully transparent the blood profiles of riders, the processes followed and the funding process. Of course, people will gasp and balk at this notion, just as they would for any other example of mass collaboration (read the book "Wikinomics" for some of them).

But the fight against doping will only be won when far more people are involved on the side of the testers. Currently, no incentive exists for those people to collaborate, but the incentive to cheat is huge - $100,000 for experimental methods, for example.



Anonymous said...

Hi Ross and Jonathan !

Thanks for the article, its a very important subject. Just a few remarks:

1-Unfortunately, you cite and highlight the wrong article as an example. To make your story complete, you should not ommit to the readers the fact that the study published by Lundby et al. lacks the most basic principles of science, its almost as bad as the famous Coyle paper you commented on. So go and read the published comments from the labs involved and see for yourself...

2- Anti Doping is not so far off the pace. A shift of paradigm is taking place as not the abused substance itself is to be detected in all cases, but its effects. That is for example what the biopassport is looking for. I am sure that this and similar approaches are the future of anti-doping and that they will come off the ground in the near future. Anti Doping will come closer to forensic science.

P.S: And, for example, all this genetic monkey EPO doping is detectable.. Search PubMed for "Lasne F" and you will see ;-)

Keep up the good work !

Ross Tucker and Jonathan Dugas said...

Hi Anonymous

Thank you for the comments. It's great to have such informed and constructive "criticism", a real addition to the site, so thank you.

Perhaps you would care to elaborate here on those "flaws" in the study? I'd gladly publish and debate them in the name of the very "open data sharing" concept I'm speaking of! I'll certainly investigate, but it would be good if you'd elaborate yourself, under what anonymity or name you wish to.

Second, on the biological passport issue, yes, you're 100% right. I considered (and in fact had even writted) a section on it, but in the interests of length, cut down on that section. But you're quite right, the passports will make an impact. I'd like to see those be ever more "open", it's exactly what is needed. It seems to me, then, that the fight against doping is evolving into a much more strategic battle, where as you rightly point out, the battle is fought with pre-emptive testing, monitoring and tracking. If that's done, then yes, the war is gradually being won. What concerns me, however, is that the progress is too slow (as is typical of a narrow "beauracracy") and the target will move. That's why I'd advocate a more inclusive fight. But, perhaps that's happening and you are one of those who'll make it happen!

Finally, as for the genetic monkey EPO issue, agreed, the example was really given more for the fact that cyclists are looking for any edge they can obtain, and not so much for the specifics of the science.

I'm going to post a short note at the end of the post to tell readers to check out your comment, because it's very valuable.

Thanks once again!


Anonymous said...

Hi Ross and Jonathan,

Thanks for the reply. I think everybody should be able to make his/ her own opinion on the article by reading the comments ("letters") on the JAP website, which are available for free online. I will just cite the conclusion of one of these comments (from M. Saugy et al, the guys from the Lausanne Lab who were strongly involved in developing the CERA test that caught the cheaters at this years Tour de France..):

"...In conclusion, for all the previous mentioned reasons, the published results cannot be credited with any scientific credibility and demonstrate of a great lack of knowledge of the authors regarding the EPO detection method and more generally of the whole anti-doping procedures. This publication has to be considered as a major offense to the scientists working since years to help the sports authorities to efficiently deal with doping in their disciplines."

Another comment on the passport:
As Anne Gripper, the UCI Anti Doping Manager stated in a recent interview, the evidence gathered by the passport has to be rock solid, as riders will go to court and try to challenge the findings in every possible aspect, ranging from preanalytics to analyser calibration etc. The first cases that go to court are the ones that are most important, as they are landmark cases in sports jurisdiction and will be the example for many other sports. So we better be sure! It is moving forward, no worries. But we must not hurry, just to get some results. We need results that stand in court !!

Cheers :-)

Ross Tucker and Jonathan Dugas said...

Hi again anonymous

Thanks for the follow up. I'm sure (and hope) that a good many readers will take you up and read those letters in the journal. My personal take is that our site's very existence is to not require that, because a vast majority of people don't want to go and read journals, free or not. We could just as easily post links to the abstracts of every scientific article we've ever done, and I like the idea of discussing and translating those debates for non-scientists, and then sharing opinions through this platform. But I'll certainly be one of those to read up on it, and post, time-permitting (posting frequency has been a challenge lately, as you may have noticed!!!)

Your second point is absolutely crucial. There's been a great deal of talk about life-bans for drug offenders, but what people miss, and what you've highlighted, is that to increase the punishment, you have to simultaneously increase the accuracy of the process by which offenders are caught. Otherwise, the authorities would be setting themselves a bar that is too high for them to clear. Effectively, eagerness to increase punishment would make it less likely that they can act. So the quote you provided is absolutely vital, and thank you for that insight.


Andrew said...

Does there exist, or has anyone proposed, an anonymous report system that athletes could use to help keep authorities more aware?

In US aviation there is the ASRS. It's run by a neutral party and allows pilots to submit reports on safety incidents, not for criminal prosecution but to gather data for studying safety issues.

I could see such a system having value in the anti-doping effort. Do you think this would work?

Ross Tucker and Jonathan Dugas said...

Hi Andrew

Thanks for the email. I think that's the kind of thing it might take. In the book "Wikinomics", the best example I can recall is of a mining company in Canada which decided that instead of keeping all of its information secret (its geological profiles, maps, soil analysis), it would publish it and make it accessible to anyone. This is understandably a radical notion - for a company to reveal its IP is a huge step.

The response was overwhelming - the company received hundreds of tips and suggestions about where they should next mine and drill, including some computer generated models that the CEO said he would never have been able to produce in his lifetime. The result was that the mine grew its revenue by an enormous amount in no time at all. The point is that when information is shared, potential for change exists.

And on the doping front, I don't think that exists on a large enough scale. There are "transparent" systems within teams, but as Jonathan has written in the past, this is a misnomer, because when the teams create their own doping controls, they still control the data and its flow. So it's not truly "open-source". I believe, like you, that a fully open-source method would help. Quite how to do this is difficult to know, without knowing the minute details. But I'm fully sold on the idea of "mass collaboration", I think it's teh way forward. And it's happening for the dopers, and therefore might be a necessity for the anti-doping controls.


Jamie said...

People found guilty of doping should be taken into the streets and shot!!!

They are a disgrace to all that sport stands for.


Unknown said...

First off, CERA was not engineered to be detectable in any way, the company announced and sampled the drug to a-d authorities well before releasing it to the market.

CERA is a bad choice for doping in general, because it works somewhat like injectable steroids(estherified testosterone...) which are released steadily over time. Inject today, the drugs work slowly for 2-3 weeks, but are also detectable for 2-3 weeks because they maintain constant levels in the bloodstream. You need drugs that are "consumed", or assimilated if you like, very rapidly, NOT slow release ones. Take t-patches and gels, or classic EPO for example. You get peak levels of the respective hormone soon after use, than levels fade rapidly. Once bound to their receptors in the tissues, they set the wheels in motion, so to speak, and for a considerable amount of time. Zig-zag between doping tests you expect, make yourself unavailiable on the day of your meeting with the nurse, and just watch out for negative feedback, and other things that hint to doping.

That being said, a bit of philosophy now. A-d testing is quantitative, unfortunately. WADA needs to show to the world just how effective tests are, with a quantitative approach, of course. Find out what quantities of the regular doping products you can get away with, and how they affect performance.

This way you can prove that doping doesn't work... or maybe that it works so well it's improbable to be "elite" and "clean" simultaneously.

All for the better knowledge of the millions watching.

Ross Tucker and Jonathan Dugas said...

Hi Mircea

No one said CERA was engineered to be detectable. That was widely reported, but not by us. So you haven't read quite accurately what we wrote about it.

As for the point of it not being useful, you're quite right. Once it became known that it was detectable (which, you'll recall, most thought it wasn't), then it suddenly fell a few notches. But an undetectable drug, regardless of its use or assimilation, is a very attractive proposition.

I don't know enough of the pharmacokinetics and mode of action to debate whether the effects of CERA are long-lasting, or whether it's the drug itself. If it's teh drug, then of course, being detectable made it instantly a bad drug to use. If it's the effect, then it is different.

But regarding the burden on WADA to prove testing, you're 100% right. That would be a real step in the right direction. My argument is that the whole world needs to prove it, not just WADA. Why task one organization - let everyone do it. Down here in Cape Town, we'd love to do that research, and could, barring the obvious ethical concerns. So open it up, science will find that if the incentive exists...