The Future of Doping in Sport
For the longest time, I thought that it was a losing battle. The dopers would always outfox the anti-dopers. It was simply a matter of resources – anti-doping agencies are generally poorly-funded and have to operate within the bounds of very strict rules and regulations. They have to be very sure about a person before they can bring a case against them, and even then, they had to come up against lawyers and convince judges who had no knowledge of the inner workings of elite sport, or of medicine. Athletes (at least in big-money sports) on the other hand have at their disposal far more resources, not to mention the fact that large-scale organized sport is a huge and very wealthy (entertainment) industry which takes good care of its investments, if you catch my drift.
But this belief has changed. Why has it changed? It has changed because things are actually changing for the better, but also and not insignificantly, because I lived with a very talented analytical chemist for a year. Not only can I now give her PhD presentation word-for-word, but I have learned a great deal about analytical chemistry techniques – not just the chemistry, but the actual means by which chemists detect things. Xenia’s thesis was about Fluorinated Compounds, and without going into too much detail about those (click the link if you would like to know more), part of the challenge of the research was detecting very small amounts of those chemicals in food. It doesn’t take a genius to see how this kind of knowledge can translate to detecting performance-enhancing drugs in a person’s body, either through a urine sample or a blood sample.
For a very long time, there was only testing at competitions. This was very easy to get around – simply don’t dope during competition. Any good athlete knows that most of the important work is done in the years and months leading up to a major competition and doping during that time is a very effective way to get a performance advantage on the day of the competition when you would present for a test and be clean. They eventually got around this by introducing out-of-competition testing, which is exactly what it sounds like. When done properly, at random times an agent from a nation’s anti-doping agency would show up at your door and demand a sample. This makes it exponentially more difficult to carry out any kind of systematic doping regime. There are, of course, ways to get around this and there are flaws in the system (which I cover in more detail in my previous article about doping in sport), but the most obvious way to circumvent this is to take a drug for which no test exists. For a very long time, there was no test for EPO and indeed, a sample from the first year that Lance Armstrong won the Tour de France was later found to contain it so this avenue seems thoroughly explored.
It is at this point where I usually throw my arms in the air and give up hope on there ever being “clean” sport. Sure, you can keep people’s samples for a long time and hope that the number of substances which are being tested for expands enough to catch them before it becomes prohibitively expensive to store so many old samples, but that’s not a great way to be. The next significant advance was the introduction of the biological passport. This is simply taking a blood sample and monitoring a number of parameters. We know enough about our biology to know what the “normal” bounds for these biological markers are, and also how much those markers can fluctuate. The beauty of this system, is that you don’t actually have to detect any performance enhancing substances to be able to catch a drug cheat. The test measures the effect of those substances on your own body (and they do have an effect – otherwise nobody would take them).
At the same time, that can be problematic. In my previous article on doping in sport, I mentioned speed skater Claudia Pechstein. To their credit, speed skating introduced the biological passport at exactly the right time to remove her from the Vancouver Olympic Winter Games in 2010. Rumour has it that her biological markers were all over the place, and that everyone kind of knew that she was on the juice. However, since they never detected a banned substance in her blood, they could never pin anything on her. When the passports were introduced, she was instantly pegged and banned for two years. She filed an injunction which allowed her to skate for just long enough to make an attempt at qualifying for the games, but the damage had already been done, and she missed out. However, the court case dragged on, and it went all the way to the Court of Arbitration for Sport in Lausanne (sport’s highest court – that’s not a joke) where it was argued that she had a rare genetic condition which caused her markers to be what they were. Then it was proposed that her father be tested, and if his biological markers were similarly zany, then she should be let off the hook. They eventually got around to testing him, sure enough his markers were similarly strange, and since no banned substances were ever detected in her blood or urine, she launched an appeal through the Swiss Federal Supreme Court. Thankfully, the court eventually rejected the appeal, and upheld the ban, proving that lawyers aren’t all bad.
Perhaps she does have a rare genetic condition, after all, Olympic athletes, especially gold medallists, are genetic freaks… but I don’t buy it. This is just a little bit too weird. The genetic condition cited was a special kind of blood anaemia – a type which would make your blood less able to carry oxygen than a normal person’s. Five Olympic gold medals, two silvers, and two bronzes, spread over five Olympic Games (six if she had managed to make it to Vancouver, and she was plenty good enough to do it) is not the skating resumé of a “normal” person, much less someone with anaemia. After serving her ban, she won a bronze medal in the 5000m at world single distance championships in Heerenveen at the age of 41, and continues to perform well at the highest level of competition. Of course, the fact that catching someone with the biological passport doesn’t require the detection of banned substances can be problematic. There will always be some latitude for appeal, and maybe we will magically learn that high performance athletes have an unusually high frequency of rare genetic conditions.
So this is where my new knowledge of analytical chemistry comes into it.
I heard through some chemistry friends that Alberto Contador’s blood tests, apart from occasionally turning up clenbuterol also contained small amounts of phthalates (plastic softener). Where do these plastics come from, you ask? Take a look at the bag in the picture above. The amount of clenbuterol found in Contador’s sample was very low, far too low to have a performance-enhancing effect (and it would seem careless that a rider would take such an easily-detectable substance during the tour). It’s far more likely that he had taken it during training, and there was a small amount of it left when he removed some of his own blood for blood doping later (which also explains the plastic softener in his blood). The contaminated beef story is total bullocks, since clenbuterol is banned in the EU and all of the randomly-tested beef in Spain contained none.
That’s where the future of anti-doping lies – in detecting the things that happen around the doping itself. Luckily, the methods available for detection have expanded significantly and we are now at a point where we can really begin to envision a world of sport that is doping-free.
In the past, the only tool available to anti-doping chemists was called “target analysis”. It is simply looking for specific things. You were only able to test for things which you knew the chemical structures of. Now we have non-target analysis.1 That means that you don’t need specific “targets” – this method detects everything. Of course, in a blood or urine sample, one can expect to find a LOT of things, and most (if not all) of those things will not be performance-enhancing. For example, if you eat a lot of microwave popcorn, you can expect to find trace amounts of fluorinated compounds in your bloodstream, or if you drink a lot of bottled water, you’ll find bits of plastic from the bottles (most of that stuff is completely harmless, by the way… ok… not fluorinated compounds, they’re endocrine disruptors, but that’s a completely different discussion). To filter the information overload that non-target analysis would give you, there is a tool called “semi-target analysis” whereby the chemical signatures of known ions are extracted.
Now you’ll still have signs of a whole lot of things you don’t know about which might be irrelevant to your doping-search, but here’s where we can be very clever. You can take these results and store them in much the same way that the biological passport works. Then, in subsequent tests, you can use a computer to superimpose the results and look for differences. When used in combination with the biological passport, this could prove to be the ultimate tool. The biological passports are already a really excellent idea, but they suffer from the problem of not being able to detect anything directly, but instead reveal anomalies in an individual’s biological markers. With this additional chemical analysis, we can “pair up” abnormal fluctuations in biological markers with differences in results between tests. We have now narrowed the field so-to-speak, and have only a small number of “suspicious” chemicals to isolate.
But then what? You have a suspicious fluctuation in the biological passport – one whose chances of occurring naturally are one in a million – but the people in the decision-making bodies of sports often flunked mathematics, so they don’t even know what that means. Next, you have the one or two chemicals we isolated which correspond in the time-series to those abnormal fluctuations. If any of those chemicals are known doping agents, then it’s game-over. But what if there’s a new designer drug, one that has been purposefully manufactured so as to be unrecognizable to anti-doping authorities? What then?
In that case, we have an ace in the hole. It comes from the world of toxicology and goes by the name of “in-vitro toxicological screening”.2 What does it do? This tool is primarily used to test chemicals (e.g. food colouring) to determine whether or not they are harmless, and determine whether or not they have biological effects. What do I mean by biological effects? I mean questions like – are they endocrine disruptors? do they activate certain protein receptors? do they stimulate so-and-so system in the body. It is obvious why toxicologists would be interested in a test like this, and it should be obvious why a test like this would be of interest to anti-doping authorities.
So now, not only can we detect the effects of a doping substance on the body using the body’s own biological markers, not only can we now detect ANY anomalous “new” chemical in the blood corresponding to these fluctuations, and not only are these tests sensitive enough to detect the plastics used in the bags used for doping, now we can EVEN isolate those substances and determine the mechanisms by which they act on the body and improve performance. In my previous article about drugs in sport, I said that in the long-term, it would eventually disappear because ultimately it was driven by money in sport, and money in sport only would push people to take these enormous health risks if there was a lot to be gained – for example if you lived in poverty, or were from a country with gross income inequality. However, as Lance Armstrong has shown us, there will always be psychologically “different” people who are basically sporting-sociopaths who will convince themselves of anything, tread on anyone, and possess a desire to win which defies what we might think of as “rationality”. In any case, thanks to science, and with the help of some very nifty (and expensive) new technology, we may finally be able to end doping in sport once and for all. Obviously, human ingenuity seems boundless, and it would be easy to believe that eventually somebody will figure out a way around these methods. However, the lengths to which you would need to go, and the expense you would need to bear to cheat the system would be so great that not only would it not be worth it, but such an effort would be impossible to hide from the world.
If anyone has good contacts, or knows “the right people” to contact about how to test and then eventually implement such a system please get in contact with me (I have a few contacts in WADA, but not many, I’m just getting started here).
- non-target analysis is done by high resolution accurate mass spectrometry, coupled to chromatography (gas, liquid, or electrophoretic) ↩
- in-vitro tests require high concentrations, so the isolation step is important. It must be isolated and concentrated – concentrated so that the amounts in the test are high enough to be effective, and isolated so that other substances in the blood don’t interfere. There are many ways to do this, e.g. sample preparation using solid phase extraction, and then isolating the chemical on a sample preparation fractional column ↩
I thoroughly enjoyed this one – not so much for the sports, nor the chemistry, but the thought process itself.
I’m sure I’ll find these Ideas handy for my own research sometime soon – thanks!