Doping and Diagnostics

‘Top athletics coach Alberto Salazar faces doping claims’ BBC
‘Chris Froome wins Tour de France 2015: Doping claims dampen the mood as Brit triumphs’ The Independent
‘'One in three medal winning distance runners this century are guilty of doping' according to reports’ The Telegraph
‘Athletics faces new doping crisis after ‘biggest leak’ of test results’ The Guardian
‘More than one in 10 athletes could be doping - Wada chief’ BBC

Looking at the headlines above, it would appear that the world of sport has been gripped by one doping scandal after another in 2015.  Athletics and cycling in particular have come under heavy scrutiny on several occasions, with numerous reports calling into question the integrity of the sports.

In June, following a BBC investigation, Alberto Salazar, the famous American coach of British star Mo Farah, was accused of violating anti-doping rules, particularly in regards to Farah’s American training partner, Galen Rupp, who is accused of taking a prohibited substance at only 16. Chris Froome powered his way to an emphatic second Tour de France victory last month, but did so amid allegations of doping – chemical or otherwise – and some rather unpleasant treatment from a few spectators. And ahead of the 2015 World Championships in Athletics beginning this Saturday in Beijing (and the prospect of a highly anticipated head-to-head showdown with poster-boy Usain Bolt for the title of sprint king), the dominance of twice-banned American Justin Gatlin has led to increased scrutiny on how supposed drugs cheats are dealt with in athletics, particularly as Gatlin has set the fastest five times this year, including a personal best, at the age of 33.

The biggest story of all came only this month, however, when the entire athletics world was rocked by claims of alarmingly widespread doping after the Sunday Times and a German broadcaster obtained access to 12,000 blood tests from 5,000 athletes between 2001 and 2012. Following analysis of the leaked database, it is alleged that:

-          1 in 3 medals won in endurance events at and Olympics and World Championships between 2001 and 2012 were won by athletes with suspicious test results
-          10 medals at London 2012 were won  by athletes with suspicious test results
-          1 in 7 of the athletes named in the files have recorded blood tests that were ‘highly suggestive of doping’
-          7 London marathons in 12 years were won by athletes with suspicious test results

It is clear, therefore, that there is a battle taking place in sport, particularly in athletics and cycling, to maintain clean and fair competition. And at the forefront of this fight against doping is in vitro diagnostics.

The array of drugs used by athletes to enhance their performance is vast, as demonstrated by the list of prohibited substances and methods, released annually by the World Anti-Doping Association (WADA) in an attempt to keep up with the ever-evolving world of doping. The largest class of performance-enhancing drugs are anabolic steroids, accounting for 48% of the ‘Adverse Analytical Findings’ in 2014, followed by stimulants, which make up 15%. Narcotics, peptide hormones and beta-2 agonists are also used, whilst 13% of suspicious results are due to diuretics, banned since they are masking agents used to get rid of traces of other drugs.

Manipulation of blood and blood components are also prohibited. Known as blood doping, some athletes will boost the concentration of red blood cells in the blood, increasing the amount of oxygen that can be transported to muscles. This can be achieved by injecting red blood cells from either a donor (homologous transfusion) or previously harvested from an athlete’s own blood (autologous transfusion), or, alternatively, drugs such as erythropoietin (EPO) can be used to artificially increase the number of circulating red blood cells.

The history of diagnostic test use in an effort to combat doping is remarkably recent.  The UCI (cycling) and FIFA (football) were the first to introduce doping tests at their World Championships in 1966, with the Olympics in Mexico and Winter Olympics in Grenoble following in 1968. In the early 1970s, however, the use of anabolic steroids was widespread as there was no way of testing for them until 1974, whilst the fight against EPO was made difficult by the lack of a reliable testing method all the way until 2000.

Whilst more effective test methods in the 1990s led to a remarkable drop in the level of top results in some sports, the rapid progression in pharmacology, poor international cooperation and a lack of unified standards meant that the effectiveness of anti-doping measures was limited. Only following a Tour de France scandal in 1998, which highlighted the need for an independent international agency, was WADA established (in 1999) and a united diagnostic approach to doping to sport began. There are now 35 laboratories around the world accredited to conduct human doping control sample analyses, with the aim of keeping sport clean and fair.

Testing itself is usually carried out on a urine sample, with techniques such as chromatography (gas chromatography, HPLC) and mass spectrometry used to test the samples for prohibited substances, whilst blood testing is becoming more and more common as attempts to tackle ‘blood doping’ are increased. The advent of ‘biological passports’ in recent years has greatly aided testing, allowing doping violations to be indirectly detected through variations from an athlete’s normal levels rather than attempting to detect the doping substance or method itself. The first example of this technique was the measurement of the testosterone to epitestosterone ratio (T/E) introduced at the beginning of the 1980s, since administration of exogenous testosterone does not affect the level of epitestosterone, an inactive epimer of testosterone. If the T/E ratio is over 4:1, carbon isotope ratio (CIR) testing (explained in this infographic by The New York Times) is used to confirm whether the testosterone is natural or synthetic.

The main advantage of ‘biological passports’ is that, regardless of how quickly new drugs are developed, human physiology remains the same and variations from an individual’s ‘norm’ can be more easily recognised. This is vital since new drugs today are produced at an unprecedented rate, meaning there is often a delay of several years between the availability of a new drug and the application of an effective diagnostic test for that drug. Cycling introduced biological passports in 2008, with 26 riders being found positive for EPO during the first three years; athletics followed suit in 2009, and football at the 2014 World Cup.

Innovation truly is key when it comes to diagnostics in doping, since new drugs and methods are constantly being developed to avoid the tests. Most recently, the emergence of gene doping has presented a new challenge to the anti-doping community, meaning more work has to be done so that testing can keep up. Since 2001, WADA has committed $60 million for research to develop new and improved detection methods, issuing a call for research proposals every year. Research often focuses on the search for new specific markers that indicate non-normal physiology, although just as new types of drug emerge every year, it is hard to predict from where the next breakthrough will come. What is clear though is that in vitro diagnostics will continue to lead the fight!

(Thumbnail Photo: AFP via The Telegraph)


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