Wednesday 23 May 2012

Jack3d – not worth the risk in all sorts of ways

Dimitar Kutrovsky, the Bulgarian tennis player, has just been found guilty of doping and banned for two years for using a banned stimulant 1, 2. The drug in question is 4-methylhexan-2-amine, (otherwise known as methylhexanamine, 1,3 dimethylamylamine, DMAA, DMP, Forthane or Geranamine amongst other sobriquets). In 2010 it earned the moniker “drug of the year” on Ross Tucker’s science of sport web page 3. As noted in my book, at the time it was in danger of becoming the new nandrolone, in that it was a drug that was triggering a spate of positive doping tests at least in part due to its presence, labeled or otherwise, in supplements taken by athletes.

So what is methylhexanamine? Originally trademarked in 1944 as a nasal decongestant, it was repackaged in 2006 as part of a sports supplement by one Patrick Arnold, the same chemist who synthesized the “undetectable” steroid THG that Dwayne Chambers took. Like most decongestants that are taken to relieve cold or flu symptoms methylhexanamine also has stimulant properties. In some parts of the world, such as New Zealand, it has been used recreationally as a party pill.

Methylhexanamine is an ingredient in many products that claim to improve performance. For example Jack3d – the product Kutrovsky took – is aimed at bodybuilders. It is worth noting that no one has shown any performance benefit for methylhexanamine – in fact I am unaware of any scientific performance study at all on this drug. It was originally “marketed” in part due to its supposed similarity to ephedrine, a stimulant that is now available only on prescription due to concerns about its safety. It is worth noting that, unlike methylhexanamine, the performance effects of ephedrine have been studied but are less than impressive.

The wheels seem to be coming off the methylhexanamine train. Like ephedrine the authorities are concerned about its safety. It seems to be able to restrict blood flow centrally, not just peripherally, with a consequent increase in blood pressure 4. It has recently been banned as an ingredient in supplements in New Zealand. In the USA the influential Food and Drug Administration have not banned it outright, but they have called on the manufacturers to prove it is safe 5; this is likely to amount to the same thing, as supplement manufacturers don’t have the resources or expertise to undertake the relevant clinical trials.

So this drug is on the banned list, it has no proven performance benefits, it is potentially harmful to health and is readily detectable by the anti doping agencies. If I was of a humourous bent I would tell all athletes thinking of using it to Jack it in…….

1 Thanks to University of Essex student, Tom Green, for bringing this story to my attention

Sunday 13 May 2012

Boxing’s latest doping scandal

I am writing from the country that is bringing you the David Haye/Dereck Chisora fight at Upton Park1, courtesy of the world renowned Luxembourg Boxing Federation. It is hard to know what to think about professional2 boxing as a sport. Perhaps its best just to admire its chutzpah in driving through whatever scandal might get in the way of – or in fact enhance – the pot of money at the end of its blood coloured rainbow.

When it comes to drug testing, professional boxing is essentially unregulated. There are usually tests at each fight and sometimes before; the details can form part of the negotiating process. But there is no out of competition testing. Given the length of time between many fights (sometimes as long as six months) it is hard to believe that the sport is drug free. 

The most recent scandal involves US boxer Lamont Petersen. Peterson controversially beat the British boxer Amir Khan to win the WBA and IBF light welterweight titles in December 2011. As part of the rematch scheduled this month the Peterson camp suggested the two fighters agree to voluntary drug testing. Peterson has just failed his test and the fight has been cancelled. The Shakespearean phrase “hoist with his own petard” springs to mind.

The nature of this failed drug testing is intriguing. Let’s leave aside the fact that you have to work quite hard to fail a drug test that you initiated and which you know could only be taken in a short time window. Or the irony that one of the chief supporters of the drug-testing agency used – VADA3 – is Victor Conte, the BALCO chief who supplied the drugs that UK sprinter Dwain Chambers was caught using. What about the science?

Peterson tested positive for “synthetic” testosterone, an anabolic steroid.  This is the same compound that Floyd Landis  - the disgraced Tour de France winner – was banned for.

Why testosterone? Well testosterone is the human anabolic steroid. Although it is not the optimum steroid to take for performance, athletes use it in the hope that it can’t be distinguished from natural testosterone in a doping test.

Why synthetic? Purifying natural testosterone from human or other animals would be extortionately expensive (in the book I note the heroic attempts in the 1930s to isolate testosterone; the starting materials varied from 20 kg of bulls’ testicles to 15,000 litres of German policemen’s urine). Nowadays a steroid from soya beans called Diosgenin can be purified cheaply in large quantities – this can then readily be turned into testosterone in a chemistry laboratory.

The problem for Peterson is that – even though its molecular structure and muscle building activity is identical to the testosterone we produce in our own bodies – the synthetic version contains a clue as to its specific plant origin. This clue is the carbon isotope ratio (CIR). Carbon is the atom that is the backbone for all the molecules in our bodies. Mostly it has a mass of 12 (C12). But a small percentage of carbon atoms are heavier, with a mass of 13. (C13). We get all our carbon from the food we eat. So the ratio in our body is the average of all the plants we have eaten (either directly or via the plants that the animals we eat have themselves eaten). The normal human ratio is 98.9% C12 and 1.1% C13. But soya beans have a slightly different ratio of 99.0% C12 to 1.0% C13.

A machine called an isotope ratio mass spectrometer can measure this ratio in the testosterone from an athlete’s urine sample. Hence the presence of the banned synthetic testosterone can be detected over and above the body’s normal testosterone. A CIR test is expensive and is only done by WADA for confirmation when testers are already suspicious of a sample (as was the case for Floyd Landis4). But VADA pride themselves on doing this test on all samples. This is the test that tripped Peterson up.

Could Peterson have avoided being caught by the test? Yes, if he paid someone to make testosterone from a human or animal starting material.  But this would be extortionately expensive. There is one other possibility. As it is the presence of two different carbon ratios that is the clue to the doping, changing your diet might fool the test. First the good news I’ve passed the test; now the bad news, I had to eat only soya beans for the three months before……..

1.   Upton Park is the current home of West Ham football club who won the original bid to take over the Olympic Stadium. In my fantasy alternative universe with a two-year time lapse the fight could have been the first post Olympic event in this stadium.

2.   In contrast Olympic boxing (the 3 round version) has to obey all the WADA drug testing rules.

3.  VADA uses WADA approved laboratories so the test result itself is robust

4.  Click here for a nice link to the Landis case.

Saturday 5 May 2012

Presbyterian minister and blood doping

Another minister and doping story (see my April 23 blog), but this time the minister is of the religious persuasion.

Anti-doping agencies have a “strict liability” rule. If a drug is in your body you are guilty. The authorities don’t have to prove how it got there. Therefore “false positive” tests are a huge problem in developing a new test. The example I give in my book is of a test for gene doping that is accurate 999 out of 1,000 times. This is much better than the usual statistical tests that scientists use. If the 1 in 1,000 chance is of missing a cheat (false negative) this might be acceptable. However, it is unacceptable if the 1 in 1,000 chance is of catching an innocent (false positive). This is because doping tests are not used to confirm whether someone is cheating; in this case a 1 in 1,000 error would probably be considered “beyond reasonable doubt” by a jury. Instead they are the primary way of catching someone in the absence of any other evidence. A statistical calculation shows that for a 1 in a 1,000 chance of a false positive result, it would only take on average 693 tests to convict an innocent person. To put this in context, London 2012 will conduct over 6,000 drug tests.

We can relate this idea to our own lives by thinking of what might happen when we see a doctor. Say she gives us a test for a fatal disease that affects 1% of the population. The test is 99 percent reliable; so 99% of people who have the disease test positive and 99 percent of those are healthy test negative. The doctor gives you a test and it comes back positive. How worried should you be? How likely are you to die? The immediate thought is that you are 99% likely to die. Start writing your will and putting your affairs in order now. In fact the answer is that your doom is only 50% likely. You still have a chance.

The statistical tests that are used to make these calculations are based on Bayes's theorem. Thomas Bayes was an 18th century English mathematician and Presbyterian Minister based in Tunbridge Wells in Kent. In an essay published posthumously he devised a theory that used prior knowledge of a distribution to determine the likelihood of a subsequent event being correct.

What has this got to do with doping? Well Bayesian probability underpins the test for blood doping used in the athlete’s blood passport1. Upon being enrolled in the passport program, the athlete gives blood regularly. At first it is assumed that his blood parameters are the same as the general population. As more tests are taken a statistic is calculated that is biased towards the individual parameters of the specific athlete. The athlete becomes his own control. If his blood deviates from his own normal readings, such as might happen following EPO doping or a blood transfusion, he can fail a doping test even if no specific doping product is found in the blood.

This is not an academic question. Last week saw the very first successful prosecution of a runner for blood doping via the use of a biological passport. A four-year ban2 was given to the Portuguese marathon runner, Helder Ornelas, solely for anomalous readings in his blood passport during the 2010 season.
We may be entering a new era in anti-doping (although see my April 3 blog for a different view).

1 you want to find out more about the biological passport and Bayesian theorem in layman's terms, check out these links:  Biological Passports; Bayesian probability.

2  At 38 years old any ban effectively ends Ornelas’s career. The unusually long ban for a first offence in this case suggests that the authorities may be trying for a deterrent effect; they want the dopers running scared of the passport system. 

Tuesday 1 May 2012

How long should “drugs cheats” be banned?

The British Olympic Association’s (BOA) attempt to keep its lifetime Olympic ban for athletes – in contradiction to the rules of the World Anti Doping Agency (WADA) – was decisively rejected by the Court of Arbitration for Sport yesterday. The BOA had to pay the costs of arbitration.

As I predicted it ends in the defeat that most expected (see my blog of March 12). I can’t say I am too unhappy about this. One of the best features of the current anti doping system is that we have a worldwide body that everyone signs up to. If one country has a different sentence or interpretation of the rules, whether more or less lenient, then they still have to tow the party line. As I describe in my book, at one time or another, many countries – the UK included – have been accused of being too lenient about the results of positive drug tests. We need a standard body to ensure a level playing field; otherwise there will be anarchy. Of course the correct thing for the BOA to do is to campaign to change WADA’s sentencing rules, as it now seems to be doing. Whether it has any political capital left to succeed in this is a moot point.

But the more interesting question is what should the ban be? Two years, four years, life? In my last blog I made the case for a long ban. But there are pragmatic reasons to go for a shorter term. One is that it might encourage cheats to come forward and give evidence against others in the system. But perhaps a more compelling argument is that two years may be the maximum ban that will stand up in court given our current testing regime. After all a ban prevents someone earning a livelihood in their chosen profession; whatever length it is, this is a pretty severe punishment. So you have to be sure of your conviction. My suspicion is that there would be even more appeals against positive tests if the bans were longer. These appeals might also have more chance of success, forcing WADA to prove how a compound got into an athlete’s system, rather than the athlete having to prove their innocence (as is the case now). The more severe a sentence, the more lawyers get involved. Just think how much more legal expense there is in the USA with a death penalty compared to a life sentence. So a longer ban might, perhaps counter-intuitively, result in fewer cheats getting caught.

I am a scientist, not an athlete, nor a sports administrator. My views on the length of ban matter no more than those of any other fan. But for what it is worth I am a pragmatist as heart. I favour the system that has the best chance of catching the most people, not one that inflicts the largest penalty once they are caught. I think fear of getting caught is a better deterrent than fear of the length of a punishment – both in life and in sport.

Of course the main winners in this story are the lawyers who have hoovered up a fraction of the BOA and WADA’s budgets. But that’s a story for another blog…….