Cheating athletes manipulate
various aspects of molecular biology
and medicine to improve their performance.
As London gears up for the 2012 Summer Olympic Games, cheating athletes and antidoping officials continue their game of hide-and-seek. Doping is as old as sports itself, but the past few decades have seen the phenomenon grow more sophisticated. As our understanding of molecular biology, biochemistry, pharmacology and medicine improves, athletes become even more cunning in their exploitation of advances in these fields.
Enhancing sporting prowess goes back to the ancient Greeks, who used special diets and concoctions to improve their athletic abilities. In the 19th century, cyclists and other endurance athletes dabbled in molecules like strychnine, caffeine and cocaine. But doping exploded in the 20th century with advances in molecular biology and pharmacology. The Danish cyclist Knud Enemark Jensen died during competition at the 1960 Rome Olympic Games after taking amphetamines. With the introduction of synthetic anabolic steroids for increasing muscle mass in the 1960s, sporting authorities knew they had to take action. Testing for stimulants began in 1967; in the 1970s, the International Olympics Committee started to test for anabolic steroids.
These days, testing for performance-enhancing substances and techniques is routine and has a unified front. The World Anti-Doping Agency, established in 1999, is an independent foundation of the IOC. It works with intergovernmental organizations, governments, public authorities and other public and private entities to stay at the forefront of the fight against sports doping. WADA has research programs to support investigations into ways molecular biology, biochemistry, analytical chemistry and pharmacology can be applied to fight doping. It also maintains an extensive list of prohibited substances and methods for performance enhancement.
Abuse of biological molecules and drugs
Medicines, designer drugs and biological molecules are popular in the doping world despite the fact that authorities have safeguards in place for most of them. A classic example is erythropoietin, known as EPO. It’s a glycosylated protein hormone that stimulates bone marrow to produce red blood cell precursors. In the 1980s, the biotechnology company Amgen introduced the first synthetic version of EPO, called Epogen (1). The drug was designed to treat anemia in patients suffering from chronic kidney disease and other illnesses that cause a drop in red blood cell count.
But cheating athletes immediately saw the drug’s potential to increase their blood’s oxygen-carrying capacity during competition. Twenty-six years after the introduction of Epogen, synthetic variants of EPO still dominate the list of preferred doping agents. “EPO continues to be a problem because it’s so potent and works so well,” says sports doping expert Don Catlin at Anti-Doping Research. So many cyclists were caught doping with EPO and other drugs during the 1998 Tour de France that the media dubbed that year’s competition the “Tour de Shame.”
A detection method for EPO based on isoelectric focusing exists (2). But as Catlin notes, “There is a variety of ways to hide [EPO] and stay underneath the radar.” The method looks for the differences in glycosylation that make endogenous and synthetic versions of EPO migrate slightly differently on the gel. The biggest limitation of the test is that it can detect a synthetic EPO only if the drug is taken within two to five days of testing. The testing is also time and labor intensive, for it takes 48 hours to complete and is finicky. “In that context, it’s not the greatest test in the world,” says Catlin. “But it keeps nailing a small percent of those who are using EPO.”
Testosterone, an anabolic steroid, is another popular drug for abuse. Catlin’s group developed a carbon isotope ratio mass-spectrometric analytical approach in the 1990s to catch it (see sidebar). The test snagged U.S. sprinter Justin Gatlin, who won gold medals in the 2004 Games, and 2006 Tour de France winner Floyd Landis. Major League Baseball player Ryan Braun was accused of testosterone doping earlier this year but had his positive test result overturned in court when his legal team argued that his urine sample had not been handled according to protocol.