Saturday, November 20, 2010

A Look at Drug Use in Sports

On November 10, 2010 I was fortunate enough to sit in on Dr. Thomas C. Werner's lecture titled "Performance-Enhancing Drug Use in Sports: Catching the Cheaters (Sometimes)" at USI.  Werner, a Professor Emeritus at Union College in Schenectady, NY, is currently traveling around the country as part of an American Chemical Society effort to promote an understanding of drug usage in sports.

Werner combined his expertise in analytical chemistry (PhD MIT '69) and his interest in sports to produce an informative lecture outlining the history of drug usage in sports dating back to the 1940's. He prefaced his talk by emphasizing the high profile of drug usage as it has ruled sporting news in recent years. Werner discussed usage and screening of amphetamines, synthetic anabolic steroids, human growth hormones, and erythropoietin (EPO).  This blog entry is based on the eight pages of notes I wrote while Werner talked.

Who sets the rules used to define and monitor performance enhancing drug (PED) usage in sports?  The World Anti-Doping Agency (WADA) was created (coincidentally on Nov. 10) in 1999. Many governments and world sporting organizations, including the International Olympic Committee (IOC), back and fund WADA.  Individual governments create their own agencies like the one created in the US (USADA).  Sports leagues such as the MLB, NFL, NBA, NHL, and NCAA have created their own sets of rules.  Furthermore, 145 nations have ratified the 2004 UNESCO treaty against drug usage in sports.

What follows is a brief layman's analysis of the primary types of PEDs used and the screening processes used by the above agencies to detect the PEDs.

Amphetamines are powerful stimulants used to treat such problems as sleep disorders, asthma, and ADHD.  Amazingly, a 2009 study showed that these drugs are used by MLB players at a rate more than twice that of normal society.  Amphetamines can be detected in urine, even though finding them has been compared to "finding a needle in a haystack."   They are separated through gas and liquid chromatography before being detected using mass spectroscopy.  The identification is based on the known retention time of the amphetamines in mass spectrometers.

Synthetic Anabolic Steroids can be used to build lean body mass, especially muscular tissues.   More than sixty of these steroids are on the list of substances banned by WADA.  These exogenous steroids are derivatives of testosterone that can be detected in urine.  Though used for decades by athletes competing in a wide range of sports, anabolic steroids came to world focus after Canadian sprinter Ben Johnson was stripped of his 1988 Olympic Gold Medal and 1987 100-meter world record for using stanolozol.

An analysis of MLB players hitting 50 or more home runs in a season reveals interesting data.  From 1920 to 1995 the feat was accomplished 1 in 4 years.  From 1996 to 2002 there was an average of 2.4 batters reaching that number of homers each year.  Finally, from 2003 to 2009 there was an average of 0.71 batters hitting 50 or more homers.  It is widely believed that the high level of home runs hit during the 1996-2002 time period were due to the use of the BALCO-produced "cream" and "clear" by MLB players.  The "cream" was a testosterone-based cream used in conjunction with the "clear," an anabolic steroid tetrahydrogestrinone (THG).  THG was a tetrahydrated form of steroid that long avoided or "cleared" screening by anti-drug agencies because the clear did not show the peaks that analytical instruments were looking for and because the combination of the cream and the clear prevented upsetting the natural ratio of testosterone and epitestosterone, which could also be detected by analytical instruments.  The decrease in MLB home runs that occurred after 2002 aligned with the discovery of the cream and the clear.

Human Growth Hormones (hGH) are used to treat growth hormone deficiency and growth disorders.  hGH promotes repair, regrowth, and regeneration in all types of cells.  Screening cannot detect exogenous forms of this polypeptide hormone in urine and a sufficient screening method for its detection in blood was not developed until 2004.  This method involves the use of an anti-body hGH to capture hGH and before another detection particle is attached.  The resulting charged complex is then detected when it produces a light flash in an analytical instrument.  The intensity of the flash is used to measure the level of hGH in the blood sample.

Erythropoietin (EPO) plays a key role in regulation of red blood cells (RBCs).  Exogenous EPO is used to treat anemia brought on by kidney diseases or cancer treatment.  Synthetic EPO (rEPO) can increase the RBC by 5-10%, making it the drug of choice for endurance athletes who rely on RBCs to carry oxygen to muscle cells. rEPO is detectable in urine, but only for a short period of time due to the presence of proteases.  Athletes use microdoses that are undetectable within 24 hours.  Many of the 80+ EPO biosimilars fail standard EPO isoelectrofocusing (SDS-PAGE) tests.  The difficulty in screening for synthetic EPO made it the first "blockbuster" biopharmaceutical drug.  Usage of rEPO has reached world wide attention due to its detection in a wide range of Olympic athletes and Tour de France cyclists. 

The ratio of red blood cell volume to total blood volume is known as hematocrit.  After extensive evaluation, WADA set the allowable hematocrit limit at .50 or 50%, since it is extremely rare for humans to have higher levels.  Some sports have implemented a longitudinal biomarker system known as a Biological Passport to monitor hematocrit over time.  This long-term, multi-test system allows for the creation of a hematocit baseline in athletes which can be used to indicate blood manipulation.  Though the Biological Passport cannot be used to determine if an athlete is using PEDs, it can initiate closer scrutiny that can then produce positive tests for PEDs.  International cycling and skiing unions are already using this system to test athletes.

Dr. Werner concluded his lecture by stating that there is currently debate about the efficacy of drug screening.  While the screening processes are limiting PED usage, they are quite costly to sporting organizations and governments.  Furthermore, knowledge of the screening is likely causing cheaters to continually develop new molecules to replace the detectable ones.

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