In what may prove to be a significant advance in the campaign against sports doping, City of Hope researchers have developed a new method of detecting performance-enhancing anabolic steroids, including so-called “designer steroids” that may escape current testing methods.
Authorities have long based their efforts to find evidence of doping through chemistry, with labs searching an athlete’s blood or urine for chemical compounds known to enhance performance. But designer steroids such as THG -- the substance at the center of the BALCO doping scandal -- are crafted to be invisible because authorities don’t know to look for its particular chemical markers.
The new strategy moves away from chemistry -- to biology. And, according to experts, the City of Hope research is at the leading edge of a wave of biology-based testing advancements that may one day show testers if genes have been manipulated for athletic exploits.
All anabolic steroids, researchers have learned, function by interacting with an internal switch at the cellular level called an “androgen receptor.” The new test detects any compound that turns on that receptor, even if the compound is unfamiliar to anti-doping authorities. A “eureka moment,” Dr. Barry Forman, an expert in genetics who led the research on receptors, said of adapting it for the anti-doping campaign.
Results of the new testing strategy were published in the Oct. 21 edition of the peer-reviewed journal Nuclear Receptor Signaling. The non-profit City of Hope, based in Duarte, is widely considered a leading medical research and treatment center. A post-doctoral fellow, Xiaohui Yuan, performed many of the experiments in Forman’s lab.
Researchers and doping experts say the need for new strategies is keen. The BALCO case showed how easy it is to tweak a molecule or two in a known steroid and come up with a new one, THG; testers knew nothing about it until a track coach sent in a sample.
As BALCO defendant Victor Conte put it last month upon being sentenced in federal court in San Francisco to eight months’ confinement: “Even the so-called gold-standard anti-doping programs designed for Olympic-caliber athletes are ineffective, let alone the more inept programs that exist in professional sports.”
And, as the journal article describing Forman’s research put it, “The full extent of the current problem [of sports-related doping] is not fully known because the only designer compounds that can be identified are those where there was a ‘whistle-blower’ who alerted authorities.”
Don Catlin, the head of the Olympic-accredited lab at UCLA who led the team two years ago that identified THG, said Forman’s research holds considerable promise for anti-doping authorities.
It may be some time, perhaps several years, before it is put into practical application, Catlin cautioned. Moreover, Forman’s focus so far has been on blood while many doping tests involve urine; the use of blood can be problematic for athletes with cultural sensitivities to the loss or use of blood from the body. And so far, the new strategy applies solely to anabolic steroids, not to a wider range of illicit substances.
Still, Catlin said, “He’s got something and he should be congratulated for that.”
Olivier Rabin, science director at the Montreal-based World Anti-Doping Agency, called it “a very interesting tool for the future.”
WADA, which since 2001 has committed more than $21 million to researching anti-doping methodologies, is helping to underwrite two projects like Forman’s, in Germany and in the Netherlands. WADA is eager, among other things, to know whether the notion can be extended to urine, an issue Rabin said shouldn’t be difficult to solve.
The long-term importance of the City of Hope research, Rabin said, is that it underscores a “different philosophy” in anti-doping research.
A primary concern among anti-doping authorities is the use of genetics to boost performance -- which authorities have said is perhaps just a few years away. Using the example of genetic strands injected into an athlete’s muscles to make them bigger, Rabin said, “We may not be able find the gene.”
But, he said it’s quite another matter to search for “the consequences of this modification, this manipulation. So in a sense we’ve got the ... possibility to approach the scientific determination of a doping violation from a different way.”
He emphasized that such biology-based tests probably would never completely push aside chemistry. Referring in particular to Forman’s research, he said, “Like many additional tools, it’s not as if the telephone came and replaced mail. Or e-mail came and replaced mail. I think it’s an additional tool, a very useful tool within our arsenal of tools that we want to use in the future to detect doping.”
Anabolic steroids are synthetic forms of the hormone testosterone. They come in tablets, creams or injections and are illegal to use without a prescription. Athletes are tempted to use them because they not only help them grow bigger and stronger, they help speed recovery from hard workouts.
Under the current testing model, known steroids are put on a banned list. In testing athletes’ urine samples, authorities then search for chemical structures of familiar compounds, such as Stanozolol.
The discovery of that substance caused Canadian sprinter Ben Johnson’s disqualification at the 1988 Summer Olympics and reportedly led to the suspension during the 2005 baseball season of Baltimore Oriole slugger Rafael Palmeiro.
Forman said the androgen receptor is one of about 50 known receptors; some 35 have no known drug or hormone associated with them. Such receptors are called “orphan receptors,” and they have emerged as the focus of Forman’s research.
“We want to find new hormones because we think they’re important, particularly for diseases including diabetes and heart attacks,” Forman said.
Forman said the idea that his research could have a sports application occurred to him as he heard a news report about BALCO on his car radio.
“With all the publicity about designer steroids, it occurred to me that it’s the same question.
“In one case, we want to find the natural hormones the body makes to bind -- to activate -- orphan receptors. In the case of the doping scandals, we want to find these new drugs that athletes use to activate to the androgen receptor.”
It took only months to adapt his research for possible use in ferreting out steroids, he said. “It didn’t take too much tinkering,” he said. “We had developed expertise in this [research] for other receptors. It was easy to apply it.”
The new strategy, he acknowledged, applies so far only to anabolic steroids and the androgen receptor. For instance, human growth hormone, another performance aid that has traditionally proven difficult to detect, activates a different receptor, Forman said, adding, “This really wouldn’t have any impact on that [receptor] whatsoever.”