A furor erupted in the world of sports last fall when chemists announced that they had identified a new performance-enhancing synthetic steroid undetectable by standard antidoping tests. Scientists familiar with androgenic steroids and their illicit use in athletics were not at all surprised. "We've known about designer steroids for many years, but up to now we've never been able to prove that someone is actually making them," says Don H. Catlin, a molecular pharmacologist and director of the Olympic Analytical Laboratory at the University of California at Los Angeles. Catlin led the effort to isolate and analyze tetrahydrogestrinone (THG), the compound at the center of the storm. "The fact that we finally characterized one is certainly no reason to celebrate. I'm much more worried about the next THG out there that we haven't found yet."

That's because it is fairly easy for organic chemists to design novel anabolic steroids that standard drug tests would not detect. (Identification depends on knowing the compound's structure beforehand; THG use was discovered only because an anonymous coach sent a spent syringe to U.S. antidoping officials.) All androgenic steroids are based on a chem-ical structure featuring a central complex of four hexagonal carbon rings. Small changes to the molecular groups attached to the periphery of central ring complex yield new derivatives. "Nature has made thousands of steroids, and chemists can make thousands more relatively easily," Catlin comments.

Rogue scientists start with testosterone or its commercially available analogues and then make minor structural modifications to yield similarly active derivatives. The under-ground chemists make no effort to test their creations for effectiveness or safety, of course. Production of a simple new steroid com-pound would require "lab equipment costing maybe $50,000 to $100,000," Catlin estimates. Depending on the number of chemical reactions needed for synthesis, "some of them could be made in a week or two. Others might take six months to a year."

"There are lots of good steroid chemists offshore who gained their expertise developing contraceptives and other hormone drugs decades ago," says Jean D. Wilson, an expert in androgen physiology at the University of Texas Southwestern Medical Center at Dallas. Now that birth-control pills have become a commodity product, "many of these experienced organic chemists are sitting around twiddling their thumbs," he says. "There must be thousands of people in the world who could readily synthesize designer steroids." The THG episode fuels speculation that a net-work of clandestine laboratories exists that develops and produces illegal steroids.

THG's chemical structure is similar to that of trenbolone and gestrinone, both synthetic anabolic steroids banned for athletic use by international sports federations. "Trenbolone is a veterinary drug used by cattle ranchers to increase the size of their stock," Wilson says. It is also popular with bodybuilders, despite toxic side effects. The structure of gestrinone, used to treat endometriosis and related illnesses, differs from that of THG by only four hydrogen atoms. In fact, once Catlin and his U.C.L.A. colleagues had deduced the structure of THG, they re-created it by hydrogenating (adding hydrogen atoms to) gestrinone, which yielded tetrahydrogestrinone.

Besides its novelty, a synthetic steroid's chemical stability under testing conditions also affects its chances of detection. THG tends to break down when prepared for analysis by standard means, which helps to explain why Catlin's team did not identify the compound in its first attempt. The U.C.L.A. chemists isolated THG's signature only after switching to a more sensitive assay process. They used liquid and gas chromatography to fractionate the sample into its molecular constituents; an electron beam then fragmented the separated molecules in a mass spectrometer to produce a spectrum indicating the basic chemical components. The group subsequently developed a urine test for THG, which has been used to finger several well-known sports figures.

Still, the cat-and-mouse game that is athletic drug testing continues. The trouble is that the mice are fast-moving targets that never stop evolving. "We're looking forward for our next research project, and that includes looking for other designer steroids," Catlin reports. Perhaps they can pounce before the mouse disappears.

This article was originally published with the title Doping by Design.

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