Breaking the Code

A few drops of liquid from the inside of a used syringe. That was all Dr. Don Catlin had to work with.

Authorities feared that those few drops were the residue of a new drug -- an illegal drug -- that athletes were taking to make themselves stronger and faster.

When the sample arrived at his laboratory near UCLA, delivered by overnight courier, Catlin set about testing the theory. He started from scratch.

“It’s sort of like the 20 Questions game,” he said. “Is it animal, vegetable or mineral? But in our case, the question is: Stimulant, diuretic or anabolic steroid?”

The next three months played out like a spy novel, albeit one written by a molecular pharmacologist. Through painstaking science, and a little guesswork, Catlin and his team of chemists at UCLA’s Olympic-accredited laboratory determined the substance to be a new chemical entity, the steroid now called tetrahydrogestrinone, or THG.

Catlin had solved an intricate riddle, a feat that earned him worldwide praise. But the accomplishment has left him with mixed emotions.

The discovery appears to confirm a worst-case scenario in sporting circles: That rogue chemists are making designer steroids for the sole purpose of helping athletes cheat and avoid detection.

“This is the first living proof,” Catlin said. “Now we have to face the reality.”

The THG case has triggered a chain reaction.

Using a test created by the UCLA lab, international sports organizations are re-examining hundreds of urine samples kept in storage from recent competitions. So far, four U.S. athletes and a British sprinter have tested positive for THG.

Meanwhile, authorities are focusing on a small company called Bay Area Laboratory Co-Operative, known as BALCO, in Burlingame, Calif.

An anti-doping agency has accused BALCO of being the source of THG. Federal investigators have launched a separate probe reportedly focused on distribution of the steroid and possible violation of tax laws.

Victor Conte, the company’s owner, has denied wrongdoing.

BALCO was previously known for making nutritional supplements favored by an all-star client list. Now dozens of athletes ranging from San Francisco Giant slugger Barry Bonds to boxer Shane Mosley have been subpoenaed to testify before a San Francisco grand jury early next month.

“That’s not good for the sports world,” said Peter Roby, director of the Center for the Study of Sport in Society at Northeastern University. “The concern is that people start to feel like there are no athletes out there doing extraordinary things without performance-enhancing drugs. It taints the accomplishments of a lot” of athletes.

Such is the scandal that came to light in Catlin’s lab. Established in 1982, it tests samples for the NFL, college sports and an alphabet soup’s worth of organizations that govern amateur athletics. As the only Olympic- accredited facility in the nation, it was the first place American sports authorities turned when trouble arose.

Last summer, a man who identified himself as a “high-profile track and field coach” called the U.S. Anti-Doping Agency -- an independent organization that polices amateur sports -- and claimed athletes were using a new kind of steroid. The tipster sent the used syringe to the anti-doping agency’s offices in Colorado Springs.

Because the syringe contained only residue, an agency staff member filled it with methanol, then emptied this mixture into a vial for shipping. As soon as Catlin received the sample, he gathered eight members of his staff for what would be a long, difficult process.

As part of standard procedure, the sample was placed in a gas chromatograph, a computerized oven that heats to more than 300 degrees in 25 minutes. Eventually, the liquid vaporized.

This vapor was swept into a mass spectrometer, where its particles were subjected to an electron beam that produced a “fingerprint” of the molecule.

The chemists soon confirmed they were dealing with a steroid. Precisely what kind? That was more difficult to say.

Any substance, when passed through a mass spectrometer, produces an identifiable peak on a readout. In this case, the sample splintered and appeared as multiple peaks. “We had to sort all that out,” Catlin said.

Over the next few weeks, he accumulated bits of information, glimpses of the mystery steroid.

“You try to piece those together and say, ‘What would the entire molecule look like?’ ” Catlin said. “It’s as if you had a puzzle from a box. You try to put it together so it makes sense.”

Using pencil and paper, Catlin and his crew sketched variations on the basic shape of a steroid -- three six-carbon rings and one five-carbon ring -- trying one alternative after another. They eventually settled on something that looked right, something that made sense.

They synthesized their theoretical drug, in effect mimicking the chemist who created THG. The concoction was put through the gas chromatograph and mass spectrometer, subjected to the same test as the original sample.

The results matched. “We knew we had broken the code,” Catlin said.

This was not like previous busts. Historically, cheaters have used existing drugs that were designed for medicinal purposes but served a dual purpose in sport.

Anabolic steroids, for instance, build muscle mass in patients suffering from a variety of ailments. Healthy athletes have used them to grow stronger and train harder. This unintended use has been linked to long-term health consequences, including liver toxicity and infertility in men. In many cases, it has also been outlawed in sports.

Cheaters have not been deterred. For instance, they have sought obscure drugs that are harder to detect.

THG appears to be the next step. According to the World Anti-Doping Agency, it is the subject of no existing literature. Authorities suspect its creator began with gestrinone -- a steroid used to treat endometriosis -- and tweaked the formula.

“What we have uncovered appears to be intentional doping of the worst sort,” USADA Chief Executive Officer Terry Madden said last month. “This is a conspiracy involving chemists, coaches and certain athletes using what they developed to be ‘undetectable’ designer steroids.”

At the very least, THG “is right up there on the creativity scale,” said Steven Ungerleider, an author who wrote about the state-sponsored East German doping program of a generation ago.

Catlin said he doesn’t know whether the steroid was designed to disintegrate in testing or whether that was simply a coincidence. Either way, after making his identification, he had more work to do.

First, he turned his work over to the USADA, which commissioned an independent lab to verify the results. Then, he set about devising a test in which THG would not break apart in a gas chromatograph.

Catlin eventually found an additive that stabilized the molecule. This process has been adopted by labs around the world.

But even as some anti-doping authorities hail the THG discovery as a turning point in their fight against cheaters, others are taking a wait-and-see attitude. Craig Kammerer, who helped found the UCLA lab and is now an independent researcher, offers a cautionary tale from the 1996 Olympic Games in Atlanta.

Several athletes tested positive for a little-known stimulant called bromantan. They did not challenge the results. But they did go to the international Court of Arbitration for Sport to argue there was insufficient scientific evidence that the drug enhanced their performances.

As a member of the testing team, Kammerer scrambled to find research that would show bromantan had given them an unfair advantage. He dredged up a series of documents from bygone research.

“They were all in Russian,” he said. “The courts threw it out.”

Now Kammerer wonders whether THG -- with no literature -- will face similar challenges.

BALCO owner Conte, while denying he was the source of the steroid, hinted as much in a recent e-mail to the Los Angeles Times: “How can Dr. Don Catlin at UCLA make statements about the substance that has been named ‘THG,’ such as ‘Users will become bigger and stronger,’ when there has not been a single scientific study that has ever been conducted on the substance?”

The Food and Drug Administration recently supported the conclusion that THG is an anabolic steroid. Catlin expresses no doubt: “We know what we have here.”

Dr. Charles Yesalis, a Penn State professor and expert in the field, offers conflicting proposals for combating cheaters.

He suggests that the U.S. and world anti-doping agencies funnel more research dollars into facilities such as the one at UCLA.

The second involves an important trend outside the laboratory.

In 1998, French customs found a stash of performance-enhancing drugs in the car of a trainer for the well-known Festina bicycle racing team. Two years later, just before the Sydney Games, Australian customs caught an Uzbekistan Olympic official with quantities of the banned human growth hormone.

Similarly, THG might have gone undetected without the tipster’s help.

“Instead of giving so much money to drug testing, perhaps undercover sting operations would be a more fruitful strategy,” Yesalis said.

Catlin agrees that enforcement is crucial. But given his training and livelihood, he also sees great possibilities in the lab.

Proponents of testing have long insisted that, given $100 million and five years, chemists could devise a foolproof process. The THG case offers a limited example -- the UCLA lab was able to devote staffing because of a $100,000 grant from the USADA.

Now, Catlin dreams of more money and a new research campaign.

He figures that anyone inclined to create a performance-enhancing drug would probably start with one of two dozen or so steroids already proved to work.

Given resources, his staff could make like the cheaters, tweaking known drugs into new shapes and devising tests to render these creations useless.

“You have to be on top of this,” he said. “You need to be thinking like someone who’s trying to cheat the system.”

This is the bittersweet side of the victory. Finding THG suggests that more undetected designer steroids are out there.

“To me, all of this is detectable and preventable,” he said. “But it’s a messy, messy business.”