Boffins catching up with drugs runners

Roger Jewsbury, Head of Department of Chemical and Biological Sciences, at the University of Huddersfield, looks at doping in sport.

A team of analytical chemists at the Winter Olympics in Vancouver are working around the clock analysing some 2,000 urine samples.

And with nearly two-thirds of analyses now completed, no-one has yet been shown to have enhanced their performance with prohibited drugs, although some had been banned before the Games started.

The Olympic creed may say that it is more important to take part than to win, but sponsorship deals and national pride demand more — winners and world records.

Along with the training and preparation, some athletes will either have chosen or have been pressured into choosing to take performance enhancing drugs.

Only analytical chemists can prevent the athletes obtaining an unfair advantage and possible damage to their longer term health. But this is a constant battle as the unscrupulous try to stay one step ahead.

Drug use at the Olympics is nothing new. Records from second century Greece show that in the original Olympics, athletes used potions made from anything from mushrooms to ground asses’ hooves to improve their performance.

These days, the World Anti-Doping Agency (WADA) produces a prohibited list, updated regularly, for all sports. The list is comprehensive covering anabolic (body-building) steroids, hormones and diuretics. Stimulants and narcotics are banned during competitions.

Analytical chemists can detect very low levels of prohibited substances or their products in the body (known as metabolites) but difficulties arise from the use of substances already present, from the use of unexpected compounds that the analysts are not looking for and from the detection of levels so low that they may be arising from other causes.

For example, it is now possible to detect such low levels of cocaine that they could have arisen from someone handling contaminated bank notes (and most are as we discovered in last Friday’s Chronicle) and then putting their fingers in their mouth.

Samples taken are either urine or blood and because of their significance, a false positive could destroy an athlete’s career, they should be treated like forensic samples.

The sample collection procedure involves splitting the sample into two (A and B samples) followed by a screening analysis and then a specific analysis of the A sample.

The B sample which can be used for confirmation is stored at -20°C to avoid changes on storage.

Manchester runner Diane Modahl, banned in 1994 after being accused of taking testosterone, was cleared after it was admitted that the B sample had been incorrectly stored by a Portuguese lab.

Testosterone is a naturally occurring hormone (in both men and women) which builds muscle mass, enhancing speed.

After the US cyclist Floyd Landis made a spectacular recovery in the 17th leg of the Tour de France a few years ago, his urine sample showed high levels of testosterone.

Epitestosterone, a natural inactive isomer of testosterone, occurs at similar concentrations in the body. WADA advise that if the ratio of testosterone to epitestosterone is more than 4:1, then synthetic testosterone is likely to be present.

In the case of Landis, that ratio was 11:1. To prove that synthetic testosterone is present, the analytical chemist has to be clever. Synthetic testosterone is made in a lab from different starting materials to those used in the body. The carbon atoms in the molecules are a mixture of isotopes with slightly different weights.

The ratio of these isotopes will vary with the source of the testosterone, so by comparing the ratio in testosterone and in epitestosterone, the use of synthetic hormone can be verified. Landis did challenge his conviction but it was upheld.

Dwain Chambers, the 100 metre sprinter who also played briefly for the Castleford Tigers, unsuccessfully challenged his lifetime Olympic ban following a two-year ban for taking an anabolic steroid. He is said to subsequently have admitted to various other offences including the use of EPO, which had not been detected.

EPO (erythropoietin) is a natural hormone which stimulates the production of the red blood cells. A genetically engineered version is available to treat anaemia, but is of interest to athletes because increasing the number of red blood cells increases the oxygen carrying capacity of the body.

Regular testing is required for EPO, as the added EPO is lost from the blood in a matter of days, whereas the beneficial effects last for several weeks. It is a very large molecule, more than 100 times larger than testosterone for example, and exists as a mixture of several similar forms, so the methods for detection of simpler drugs cannot be used.

Synthetic EPO has slightly different molecular forms to the natural EPO and detection methods include separating those forms into a characteristic pattern using a technique known as isoelectric focussing.

Aware of the method of analysis, some labs are now modifying the engineered EPO specifically to make it harder to distinguish from the natural product.

The next step may be the use of gene therapy, still being developed for medical treatment, to produce drugs such as EPO directly in the body to make them even more difficult to distinguish from the naturally occurring compounds.

Where there is a demand, there will always be unscrupulous manufacturers who will satisfy the market.

Rest assured, the analytical chemists are doing what they can to catch the cheats.