Commentary: Can Drug-Busters Beat New Steroids?

It's scientist vs. scientist as the Athens Olympics approach

Don H. Catlin is in an arms race. His lab at the University of California at Los Angeles processes tests that determine if athletes are using body-enhancing drugs. Recently, his team rushed to develop a test for an exotic steroid that builds muscle but doesn't exist in nature. Demand for "designer steroids" is surging, the tools to create them are widespread, and the designers are rolling in dough. Unfortunately, the same can't be said for scientists trying to combat doping. Without major infusions of cash, the drug dealers will maintain the upper hand. "It's a nasty problem," Catlin says.

The drug Catlin encountered last year is an anabolic steroid called tetrahydrogestrinone (THG). It doesn't show up in standard urine tests -- and indeed, the compound is shrouded in mystery. On May 19, sprinter Kelli White was banned from competition for two years after admitting she had used undetectable performance-enhancing drugs. The U.S. Anti-Doping Agency (USADA), an independent body created by the U.S. Olympics Committee that manages all Olympic drug testing for American athletes, built its case against her using documents seized from BALCO, a San Francisco company charged with selling THG.

Likewise, the USADA could try to bar track star Marion Jones from competing at the Olympics. Jones, who has not tested positive for any steroid, has said she will sue if she is barred. Still, the USADA could act based on evidence allegedly pointing to a connection between Jones and executives of BALCO.

Regardless of how that plays out, THG has just a bit part in this drama. Drug testers assume that there are dozens of designer steroids for sale, or in the labs. After all, designing them doesn't require a PhD in chemistry: Take a standard steroid, tweak a few carbon, oxygen, or hydrogen atoms, apply trial and error, and you could get a drug that no test will catch.

The arms race is bound to intensify. Many drug testers believe that within a few years, desperate athletes will try to alter their genes so that they don't need designer drugs. It's not sci-fi: Gene-therapy techniques that some biotech companies are developing to fight cancer and other diseases could be adapted to this end. Rogue doctors might, for example, inject an athlete with a virus rejiggered to deliver the gene that makes erythropoeitin (EPO) -- a protein that boosts the production of oxygen-carrying red blood cells. Right now, there is a test to detect synthetic versions of the protein, which some athletes take to improve their stamina. But if gene therapy were used to prime the body's natural EPO production, tests might not spot it.

What's especially frightening about the emergence of new doping methods is that athletes who use them may be putting their lives on the line. Underground manufacturers of designer steroids don't go through the normal U.S. Food & Drug Administration testing rigmarole to prove the drugs are safe. Furthermore, athletes who take performance-enhancing drugs often receive doses that are 10 to 100 times higher than normal therapeutic doses. At such high levels, steroids can cause blood clots, heart attack, stroke, and liver cancer. EPO, taken in excess, literally turns the blood to sludge, with the obvious consequences of heart attack and stroke. Gene manipulations could aggravate such dangers, as the technology is still experimental.

Scientists enlisted by anti-doping agencies are trying to stay a step ahead of the cheaters. At the University of California at San Diego, a team led by Theodore Friedmann, a pediatrics professor, is searching for tiny changes that occur in the body when it is exposed to certain genes. "In this hypothesis, when you inject one gene, the body turns on and off a whole other set of genes," Friedmann says. "That might present a protein signature," which drug-testers could spot in a blood sample.

Detecting successive generations of designer steroids will require a different type of sleuthing. Doping experts estimate that the common steroid testosterone alone could be refashioned into many synthetic variants. UCLA's Catlin believes he could design a battery of tests that would pick up most potential clandestine steroids -- even before anyone knows they're being abused. But it won't be easy. Computerized equipment that tests urine for steroids must be programmed to look for each specific subtype of steroid. That means Catlin's scientists would have to create all the potential new steroids in the lab, rigorously characterize the properties of each one, then feed the information into the testing machines.

It's not technology that is holding back the anti-doping campaign, but lack of funding. The USADA budgets only $2 million a year for its drug battle, with typical grants ranging from $50,000 to $250,000 and running for three years or less. "That's about enough to buy paper, rubber bands, and some Scotch tape," says Charles Yesalis, professor of health and human development at Pennsylvania State University and a sports historian

When Yesalis gives talks on drug testing, he ends by showing a slide of a dog chasing its tail. It's an apt image. Without financial support from deep-pocketed donors, such as the giant companies that sponsor major sporting events, scientists who are trying to combat doping will never sprint past drug dealers -- or athletes who are willing to risk their health in the quest for the next gold medal.

By Arlene Weintraub

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