As the Giro d'Italia bicycle race sets off in Ireland this weekend, the shadow of doping will not be far behind. In a competition to beat the cheaters, scientists are constantly trying to improve drug testing.
While it can be hard for regulators to keep up with new habits, when an athlete is finally caught doping, the result can be revolutionary.
Performance-enhancing drugs have plagued the sport of cycling for years, with Lance Armstrong at the center of the scandal. But he was not alone.
From 1998 to 2001, Tyler Hamilton was Lance Armstrong's trusted lieutenant on the U.S. Postal Service team, and a member of Armstrong's inner circle.
Hamilton says that for the first two-and-a-half years of his professional career, he raced clean. But a grueling ride in Southern Spain had taken everything out of him. Lying exhausted on his hotel bed, a team doctor offered him something.
"He was concerned, sympathetic, almost fatherly," Hamilton tells NPR's Arun Rath. "He was wearing this fly fishing vest and pulled out a little red egg-shaped capsule, and there it was — a little pill of testosterone."
Hamilton swallowed it, and everything changed.
"Within a couple years, I was up to my neck in doping," he says.
The Doping Arms Race
Not far from the Santa Monica Pier in Los Angeles is the biggest anti-doping lab in the world. The Olympic Analytical Laboratory at the University of California, Los Angeles, performs drug tests for the Olympics, the NBA, MLB, NFL, the NCAA and many other clients who come to them as needed.
"We probably have more urine than anyone in the world," says director Anthony Butch.
The lab tests more than 40,000 samples each year and is packed with millions of dollars' worth of the most cutting-edge scientific gear in existence. They also employ more than 40 top-level scientists to go with it.
There are no signs outside to mark this amazing facility. They prefer to keep it nondescript, because they're developing the latest weapons in what many people call an arms race.
Boxes arrive with glass vials of urine samples from around the world. As the boxes pass through the building, every set of hands they pass through are logged. Like with police evidence, maintaining the chain of custody is essential for security. The samples are wheeled back to the lab where scientists store them in giant refrigerators. The bottles are impenetrable; the only way to open them is to use a machine that cracks the lid.
Just as cyclists like Armstrong and Hamilton were able to keep ahead of the tests for so long, Butch says it's only a matter of time before something new slips by undetected. It can be hard to have a sense if they're winning the war or not.
"If you're a pessimist, you probably believe everybody's doping and nobody's getting caught. Because the positive rate is very, very low," he says. "If you're an optimist, you think that very few people are doping and we're catching them all."
Butch says he falls somewhere in between. He thinks that they are catching some of athletes, but that others are using compounds that the lab can't currently catch. He says every new drug that comes on the scene requires developing a new test, giving athletes who dope a window of opportunity.
"[It] constantly seems like we're running behind the athletes to catch them," he says. "We're getting closer to them. As they change their doping patterns, we can detect lower concentrations, [and] I think we're picking up more cheaters."
The problem, Butch says, is that as new compounds come out, some are extremely difficult to detect, even if you have the technology. For example, there are drugs that stimulate the athlete's pituitary gland to produce more growth hormone.
"These have a very, very short half-life — in the order of minutes," he says. This makes the drug almost impossible to detect. The window for testing is there, he says, but it is getting smaller and smaller as the drugs get more sophisticated.
Testing At The Genetic Level
To latest weapon in the doping wars is being developed by Yannis Pitsiladis, a professor of sport and exercise science at the University of Brighton in the U.K. Instead of looking for drugs in blood, he's looking for the fingerprints that substances leave behind at the cellular level.
With research supported by the World Anti-Doping Agency, Pitsiladis looks at the evidence of doping in the genetic sequence of RNA, the partner of DNA.
"It's at the highest level of sensitivity. Because what we're looking at is the switching on and switching off of genes as a result of taking a particular drug," Pitsiladis says.
Pitsiladis says they develop a genetic profile, or signature, of a particular drug by taking test subjects, typically athletes not currently competing, and administering the drug to them in a controlled environment. They then analyze which genes are being affected by a drug, and use that to create its genetic footprint.
Pitsiladis says that if everything goes as planned, his test will be ready in a year and a half. He says the beauty of this genetic approach is that it is almost un-cheatable because of the number of genes that the drugs affect.
"There are just far too many genes to try and manipulate, and if you ended up trying to do that, you'll probably end up killing yourself," he says.
'Killing Me From The Inside'
Tyler Hamilton knows all about the race to stay ahead of testing technology. He was winning for a while.
When he began doping, Hamilton was taking EPO, a synthetic form of a hormone that stimulates the creation of red blood cells. Having more red blood cells means more oxygen in the blood and more endurance.
The drug allowed athletes to train harder and longer. In a race like the Tour de France, it was an absolute game changer, Hamilton says.
During this time, Hamilton was passing doping tests. But then tests became more thorough, including tests for EPO. "When we heard that, the doctors came up with a new plan: blood doping," he says.
Blood doping involves athletes taking their own blood or someone else's blood, storing it and then re-injecting it during an event. The action provides a boost of red blood cells, which is great for endurance sports. Hamilton says the U.S. Postal team had its own blood-doping doctor. Ten days into the 2000 Tour de France, they met the doctor in a hotel room.
"He'd put one of those big extraction needles into your arm and fill you back up, so to speak," he says. Typically it would be almost a half-liter of blood injected, he says.
Once, Hamilton accidentally re-infused bad blood, basically giving himself blood poisoning. He had a horrendous fever, and his urine turned black. There was pressure to win and money at stake.
"We created a monster and then ... [the] pressure just got bigger and bigger," he says.
It finally caught up with him when, in 2004, Hamilton tested positive. He was suspended for two years, then returned to racing. After testing positive for a banned substance in 2009, he finally retired.
In 2010, the U.S. government opened a grand jury investigation into Armstrong and the U.S. Postal team.
Witnesses were subpoenaed, including Hamilton, who spent hours on the stand confessing to everything. He says he was told to "tell the truth or go to jail." Hamilton picked the former. He says it was the best thing that ever happened to him.
"It was basically killing me from the inside," he says. "As soon as I started telling the truth, I realized that I'd been protecting this culture for the better part of 14 years, and I realized that that culture was no longer worth protecting."
ARUN RATH, HOST:
It's ALL THINGS CONSIDERED from NPR West. I'm Arun Rath. Earlier this week, just a few miles from NPR West, I found myself standing in front of a row of stainless steel medical-grade refrigerators.
ANTHONY BUTCH: They probably have more urine than anybody in the world.
RATH: That's Dr. Anthony Butch, director of the UCLA Olympic Analytical Laboratory. It is the biggest anti-doping lab in the world. They perform drug tests for the Olympics, the NBA, MLB, NFL, NCAA and many others. They test over 40,000 samples each year. The place is packed with millions of dollars worth of the most cutting-edge scientific gear in existence and more than 40 top level scientists to go with it.
There are no signs outside to mark this amazing facility. They prefer to keep it nondescript, because they're developing the latest weapons in what many are calling a doping arms race. And that's our cover story today.
(SOUNDBITE OF MUSIC)
RATH: When you think of doping in sports today, it's almost impossible not to think of the U.S. Postal Service team that won so many big cycling races. From 1998 to 2001, Tyler Hamilton rode on U.S. Postal. He says that for the first two-and-a-half years of his professional career he raced clean. But one day a grueling ride in Southern Spain had taken everything out of him. Lying exhausted on his hotel bed, a team doctor offered him something.
TYLER HAMILTON: Yeah, one of them came in to check on me, you know, he was concerned and sympathetic, almost fatherly, was wearing this fly-fishing vest and pulled out a little red egg-shaped capsule and there it was. You know, it was like a pill of testosterone.
RATH: Hamilton swallowed it and everything changed.
: Within a couple years I was up to my neck in doping.
RATH: He began taking a synthetic form of a hormone that stimulates the creation of more red blood cells. More red blood cells means more oxygen in the blood, more endurance. Athletes refer to the drug by its shortened name, EPO.
: Edgar Allan Poe as we called it. You were able to train harder, longer. In a race like the Tour de France, absolute game changer.
RATH: Now you have to understand, this whole time he's passing doping tests but eventually the tests for EPO became more thorough.
: When we heard that, the doctors came up with a new plan, blood doping.
RATH: A new plan for them but an old technique. Blood doping involves athletes taking their blood or someone else's blood, storing it, then re-injecting it during an event, again providing a boost of red blood cells, great for endurance sports. Hamilton says U.S. Postal had their own blood doping doctor. Ten days into the 2000 Tour de France, they met the doctor in a hotel room.
: He'd put one of those big extraction needles into your arm and fill you back up, so to speak. And typically it would be about 450 cc's of blood.
RATH: Almost a half liter. During the 2004 Tour de France, Hamilton accidentally re-infused bad blood, basically giving himself blood poisoning. He had a horrendous fever and his urine turned black. But there was pressure to win and money at stake.
(SOUNDBITE OF TOUR DE FRANCE RACE)
UNIDENTIFIED MAN: ...a physical and mental delivery here by Lance Armstrong to all of his rivals in the Tour de France. He is just going faster and faster and faster...
: You know, we won the tour in '99 with Lance. It was a huge story. I mean, it was a worldwide story. We created a monster and then it was like pressure just got bigger and bigger.
RATH: It caught up with him and in 2004 he tested positive. Hamilton was suspended for two years and blacklisted from the sport. In 2010 the U.S. government opened a grand jury investigation into Armstrong and the U.S. Postal team. Witnesses were subpoenaed including Hamilton, who spent hours on the stand confessing to everything.
: As soon as I started to tell the truth I realized that I'd been protecting this culture for the better part of 14 years. And I realized like that culture was no longer worth protecting.
RATH: Former professional cyclist Tyler Hamilton. Back at the UCLA Olympic Analytical Lab, they're racing to keep up with the cheaters. It never stops. New samples arrive all the time. The latest shipment of boxes comes in, glass bottles of urine samples from around the world. As the boxes pass through the building, every set of hands they pass through are logged. Like police evidence, maintaining the chain of custody is essential for security.
The samples get wheeled back to the lab where scientists store them in giant refrigerators. Dr. Anthony Butch pulls out one of the glass bottles ready to be entered into the system. The bottles are the extreme end of tamper proof. They can only be opened by crushing the lid, and that requires a special machine.
Here they're using the latest techniques to detect drugs like EPO and practices like blood doping. Still, just as athletes like Armstrong and Hamilton were able to keep ahead of the tests for so long, Dr. Butch says it's only a matter of time before something new comes along. It can be hard to have a sense if they're winning the war or not.
BUTCH: Are you an optimist or a pessimist? If you're a pessimist, you probably believe everybody's doping and nobody's getting caught because the positive rates are very, very low. If you're an optimist you think that very few people are doping and we're catching them all. Well, I'm kind of somewhere in between. I think we're catching some of them but some of them are using compounds that are escaping our ability to catch them at this particular point.
RATH: He says every new drug that comes on the scene requires developing a new test, giving athletes who dope a window of opportunity.
BUTCH: We're getting closer to them. As they change their doping patterns we can detect lower concentrations. I think we're picking up more cheaters. The problem is with new compounds as they come out, things that are extremely difficult to pick up, even if you have the technology.
RATH: Like drugs that stimulate the athlete's own pituitary gland to produce more growth hormone.
BUTCH: And these have a very, very short half-life in the order of minutes.
RATH: Making the drug almost impossible to detect.
The testing is out there. It's just the window of detection becomes smaller. So they're getting much more sophisticated.
WARREN CORNWALL: It's a constant arms race.
RATH: That's reporter Warren Cornwall. He's written a lot about the science of doping. At the level of the fan, why should we care about this?
CORNWALL: If you take away restrictions on doping, essentially a sport becomes a battle between who has the best chemists and biologists to prevail. And that takes the heart out of it. I know personally for me, I mean, I'm a cyclist and a triathlete and I have videotapes of just about all the Tours de France that Armstrong won just for motivation. But I don't really watch them anymore.
RATH: Cornwall has found a reason for optimism, a scientist who's developing the ultimate weapon to end the doping wars. Instead of looking for drugs like EPO in the blood, he's looking for the footprints they leave behind at the molecular level. His name is Yannis Pitsiladis, a professor of sport and exercise science at the University of Brighton.
With his research supported by the world anti-doping agency, Pitsilatis looks at the evidence of doping in the genetic sequence of RNA, the partner of DNA.
YANNIS PITSILADIS: It's at almost at the highest level of sensitivity because what we're looking at is the switching on and the switching off of genes as a result of taking a particular drug. We develop this profile or signature of a particular drug and then that's what we try and find.
RATH: So at this genetic level there's a molecular footprint left behind?
PITSILADIS: That's the idea, yes. We can find consistently in everyone we have tested up until now; we find the same molecular signature to the same drug.
RATH: So how do you learn to recognize what the signature of a particular drug is at this genetic level?
PITSILADIS: OK. So what we've done up until now is we've actually taken volunteers, healthy volunteers who are athletes typically who are not permitted to actually compete during the trial because obviously they would have an unfair advantage because they take a banned drug.
RATH: You're having them dope.
PITSILADIS: Well, I wouldn't use the word dope here because they're basically agreeing to do this, but they're taking the same kind of drug that athletes in the past and now may be taking but under controlled conditions. So we administer the drugs, so we're present when the drug is being injected. And then go into the laboratory subsequent to that and look at the genes that are being expressed. And doing that we've identified these molecular signatures of, in this particular case, the drug EPO, erythropoietin.
RATH: With this test, how long are you able to trace the effects of the drugs?
PITSILADIS: So far we've achieved a four-week identification, which is fabulous. The current detection window is typically 48 hours after taking an injection of EPO. Four weeks is an incredible improvement compared to what we had up until now.
RATH: In terms of things that could generate false positives, are there things that you might misidentify as a signature for one of these drugs that's actually from something else?
PITSILADIS: Yes. And the most important one is going to altitude, especially middle- and long-distance athletes, endurance athletes will spend a significant amount of time often living for prolonged periods of time in training at high altitude. And the changes which occur when you go to altitude, for example increase in red blood cells so you can carry more oxygen, these are the same kind of effects the drug that they tend to take also produces.
So we've got to make sure that going to altitude, while it still has a similar effect on the red blood cells, isn't having the same molecular response. My prediction based on the work that we've done to date is that none of these confounders will have anywhere near the same kind of molecular signature as the particular drug of interest.
RATH: You're testing with your subjects with already existing substances that we know about. Say though, in six months something else comes on the market, there is some new molecular footprint. You have to spend the time learning that new signature, right?
PITSILADIS: Absolutely. Athletes that are currently doping should actually be having sleepless nights because the bottom line is those samples that you collected for anti-doping purposes are being stored. So we can go back to those samples, apply these molecular signatures as we develop them and be able to identify them even years after they've done this.
So the beauty of this kind of approach, this kind of molecular signature approach is that it's almost uncheatable in the sense that there are so many genes that are being switched on that if you wanted to manipulate the test, you couldn't do it because there's far too many genes to try and manipulate. And if you ended up trying to do that you'll probably end up killing yourself.
RATH: Yannis Pitsiladis, professor at the University of Brighton. Warren Cornwall says a test like this where RNA sequences could be examined months or years after the fact for previously unknown drugs could finally give authorities a decisive edge in the doping arms race. Dr. Pitsiladis says that if everything goes as planned, his test will be ready in a year-and-a-half.
(SOUNDBITE OF MUSIC)
RATH: This is NPR News. Transcript provided by NPR, Copyright NPR.