Expert verdict: Race to keep pace with sports cheats

Aug 5 2008 by Our Correspondent, Huddersfield Daily Examiner

The Olympic Games begin on Friday and the world's analytical chemists will lead the battle to catch the drug cheats. Roger Jewsbury, Head of the Department of Chemical and Biological Sciences in the School of Applied Sciences at the University of Huddersfield reports.

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.

Of all the records that may fall at the Beijing Olympic Games, which start on Friday, athletes will hope at least one stays unbroken: the number of competitors testing positive for drugs.

Only an optimist would bet against it and, unfortunately, it is likely that by the closing ceremony there will be more than the record number caught in the 2004 Athens games, having to swap the trip of a lifetime for a trip to a lawyer.

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.

But this is a constant battle as the cheats try to stay one step ahead.

Drug use in 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.

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-born runner Diane Modahl, banned in 1994, 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 two 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 last year and in a second appeal this year.

Dwain Chambers, the 100 metre sprinter who also briefly had trials for the Castleford Tigers rugby league team earlier this year, recently 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, over one hundred 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 focusing.

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, but rest assured that the analytical chemists are doing what they can to catch the cheats.