Game-changer: The long push to end blood transfusions in sport

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Tuesday, July 25, 2007: The world of cycling and the Tour de France were plunged into controversy with the news that Alexander Vinokourov had tested positive for a blood transfusion. The Astana team leader had crashed heavily on stage five of the race, losing time, and struggled in the days after that. His general classification dreams were over, yet he roared back into the headlines by winning the stage 13 time trial.

The performance was a dominant one, with Vinokourov pummelling runner-up Cadel Evans by no less than one minute 14 seconds. He went on to take a second stage victory two days later, but any celebrations were short-lived. The Kazakh was tested after his time trial success and, four days after that, the shockwaves hit the Tour: traces of another person’s blood had been found in his system. He was out of the race.

Predictably, Vinokourov insisted on his innocence. Unpredictably, his team gave a ludicrous reason for the positive test. It suggested that his stage five crash and the cuts he suffered to his knees may have caused the unusual blood readings. Quite why that fall would lead to someone else’s blood cells being in his system was never satisfactorily explained, and he was handed a ban for a homologous blood transfusion.

Yet Vinokourov wasn’t the first to have broken the rules in this way. In 2004 Tyler Hamilton was snared for a homologous blood transfusion and, several weeks later, his-then Phonak teammate Santiago Perez was also caught out.

Coincidentally – or maybe not – Vinokourov’s teammate Andrey Kashechkin also tested positive in the same way days after his compatriot. At the time, speculation was rife that both pairs of teammates may have accidentally transfused each other’s blood. This was never proven, but blood bags may conceivably have been mixed up.

Whatever happened, though, riders got the message: the test for homologous blood doping was an impressive one, and not to be messed with.

But that wasn’t the end of the problem.

Vinokourov during his ill-fated time trial.

Detecting the undetectable

What to do when you can’t transfuse someone else’s blood? Why, use your own. It might seem astonishing but, a full fourteen years after a test was perfected to detect the shenanigans that Vinokourov, Hamilton and others got up to, there is still no way to directly screen for autologous blood transfusions.

Providing the red blood cells being reintroduced are your own, providing you don’t transfuse so much as to trigger a biological passport violation, there is little chance of being caught.

Because of this shortcoming, riders such as Lance Armstrong and his US Postal/Discovery Channel teammates were able to exploit transfusions for many years.

That was the case in the mid 2000s. Worryingly, that method is still undetectable now.

Christer Malm is trying to change this. The Swedish scientist is Professor in Sports Medicine at Umeå University and CEO of the company ProTest Diagnostics. He has been working for many years on the answer to an important question: how to be able to definitively prove that an individual has had a blood transfusion.

Malm spoke to this writer several years ago about his research, and hoped then that a test could be developed sooner rather than later. Since then the solution hasn’t been found, but he feels he is getting closer. ProTest Diagnostics has an investor on board, has received funding from WADA and the Swedish innovation agency and has made some good progress.

The company’s early research saw the team administer transfusions to subjects, who showed a 17 percent increase in both VO2 Max and also in time to exhaustion. However, the transfused group’s blood readings were not sufficiently different from a non-treated group to illustrate that they had received blood. The conclusion from that? Regarding the biological passport as the solution to blood doping is a mistake.

“I think from that study it’s fair to say that if you know what you’re doing, you can probably cheat without a terribly high risk of being caught,” Malm tells CyclingTips.

“If you do it wrong or too close to testing, or if you use a high dose of EPO, then of course you change your concentrations of red blood cells and concentrations of haemoglobin. And that’s definitely going to show up on the passport. But I also think if you know what you’re doing, you can fly under the radar.”

That echoes what other anti-doping researchers such as Micheal Ashenden have said. The biological passport is a useful tool, but isn’t sufficient precise to catch careful blood dopers. And, even if it was, the consensus is the high budget challenge by Roman Kreuziger may have made authorities much less likely to take passport cases.

The number of those cases has plummeted in recent years. Because of this, it underlines even more clearly the need for a direct test.

Lance Armstrong – and then-teammate Floyd Landis – used blood transfusions for years without detection.

And yet, that hasn’t been easy to find. Early on, researchers tried a different approaches to try to detect transfusions. One approach was to look for traces of the softeners which were used in the blood bags, phthalates, but once this method became public athletes knew that they could simply switch to other types of storage for blood.

Genomics was another avenue explored, as was an examination of immune system responses after transfusions.

Those efforts haven’t paid off, leaving Malm and his team with their own novel approach. “We use proteomics, looking at proteins, or fractions (peptides) for profiling of the blood,” he explains. “We have conducted tests on maybe 50 people now. We did a real good study up in northern Sweden and now we are working with a hospital in Stockholm. We’ve done another set of transfusions looking at white Caucasian males and it seems it works.”

Getting the test closer to approval and implementation has required Malm and his team to assess the effects of high altitude on the test, as well as determining how exercise and gender differences can also affect the results. At this point in time, they are concentrating on assessing what, if any, effects different genetics have on the outcome.

“The aim is to test African, Asian and Indian populations, from a genetic point of view,” explains Malm. “We need to make sure other populations don’t give different results.”

The importance of this is to ensure that the test results can be stood over, both ethically and legally. “It’s okay if we only detect half or a third of the doped athletes, as long as we have no false positives,” he says. “Because false positives would be devastating, if you accuse someone of doping who is actually clean.”

Anti-doping scientist Christer Malm
That leads Malm and his team on to the next stage in the test’s development. “The major challenge we have now is to get a lot of clean subjects. To find elite athletes that we can be certain are not doped,” he says. “In other words, volunteers who can say, ‘look I’m not doped, you can take a blood sample,’ but who are still elite athletes.”

Once the test is perfected, he feels it will play an important part in policing sport. “The test picks up autologous blood transfusions. We should be able to detect fairly small amounts, although we are still working out how long after a transfusion it works. For example, if you take a unit of blood a long time before the test, will it be able to trace this?

“Also, if you take a microdose of blood, how small a dose can be detected? We don’t know this yet, but we are working on it.”

What’s clear is that Malm believes the test will become more sensitive and more precise over time. He says that will be achieved “when you move from the screening method [currently] being used down to using only a few biomarkers.” That fine-tuning is currently part of the team’s work and something which will strengthen the power and reach of this anti-doping measure.

‘A game-changer’

Robin Parisotto has played a crucially important role in anti-doping during his career, including the development of the first-ever tests for EPO in 2000. He was also one of the founding members of the UCI’s biological passport programme.

He believes the test being developed by Malm and his team has the potential to be a hugely important addition.

“A couple of years ago, I reviewed the application of grant for that research,” he told CyclingTips recently. “That application was basically posting a proof of concept study which showed they could definitely detect autologous blood doping based on proteomics.

“In a sense, what that means is that when genes express their proteins, that will be due to some effect on the gene. The effects on genes are produced by things like drugs, the environment, diet, pollutants, even exercise. So if you measure those proteins that those genes are actually expressing, you can sort of create a picture….

“You can say, ‘okay, so this picture is typical of someone who has been taking a headache pill, or insulin, or rheumatoid arthritis drugs, or has been at altitude for six weeks. Or is on a high-fat diet.’ You can build these pictures. And what this particular researcher has done is actually given a cohort of athletes autologous blood that’s been collected and then frozen and then brought out and given in small doses back to them over a six-week period.

“The proof of concept studies shows they have been absolutely able to differentiate those athletes who had been blood doped compared to athletes who had nothing done it. To my mind, it was probably the study that had the most potential to really tackle autologous doping.”

What Parisotto saw was an early version of the test, and a lot of work has been done on it since. But even then, he was clear how big a deal the test could be.

“If that proof of concept is validated, it certainly is a game changer,” he said. “Because then no amount of marginal gains or microdosing is going to hide it.”

Malm and his team are excited by what the test appears to be able to do, but there are several steps left to achieve. They have to finish the study on how different genetic populations respond to the test. They also need to run the research on a large number of known clean athletes. Both of those steps are part of the current validation phase, and are being done to ensure that there won’t be any false positives down the line.

After that, the test will be scrutinised by others, including WADA itself. Legal experts would likely also need to look at it in order to make sure it will stand up in court cases.

But, providing things all go to plan, it should move forward for use in the world of sport. How long could that take? Malm isn’t sure. “You would have to ask WADA what the timeframe would be,” he said. “If we had the product ready, we would then have to see how much further testing will WADA want or need to do before they can actually implement this.

“I know that there are two levels. They have a kind of an observation phase. If there is a new test that they want to try, they can have it on like an observation mode for it for some time. They collect data and then before they implement it as a test, they actually can take legal actions.

“I’m just speculating now, but if they take it in for a year or two years to monitor athletes and then after that if they can say that it only seems to detect a true transfusion subject and not giving false positives, then they would move it to a live test, so to speak. They could use that test to cut off athletes and use in court.

“I realise that there is a legal aspect to this that we don’t deal with right now. I’m sure the lawyers would ask critical questions to make sure the test is accurate.”

There have been tests for EPO since 2000; at this point in time, autologous transfusions, another method of blood doping, cannot be detected.

‘There could be a very big effect on sport’

Eighteen years ago, Parisotto’s crucially important EPO test was introduced in time for the 2000 Olympic Games in Sydney. The next Games are two years away and it is certain that some athletes will intend using transfusions to try to cheat the system.

Is it possible that this test could be in place in time for the Games? Well, Malm and Pro Test Diagnostics want and need their own side of things to be completed by mid 2019. That would then mean that WADA would have a year to have things in place for the next Games.

“From our perspective, as the producers and developer, we will be done before then,” he says. “If it’s possible for WADA to implement that for the next Olympics, I don’t know. But we’re not going to need two years. That’s for sure.

“Our timeline kind of ends next summer. If it’s not if it’s not up and running then, maybe never will be,” he says, pointing out one concern. “I mean, we have worked on this for a long time and we have hit a lot of bumps on the road. It looked easy from the beginning, then it was looked impossible, and then we realized what we had to do.

“We are close to getting where we need to be, but it has taken a long time. We have limited resources, of course. We are only a few people working on this in the company.”

Blood doping has existed for a long, long time in sport. The Finnish endurance runner Lasse Viren is rumoured to have used the practice to win Olympic gold in 1972 – it wasn’t banned at the time – and it is likely that it was used by some in pro cycling during that same decade. Since then, it is likely that numerous races across numerous sports have been won by those artificially jacking up their aerobic systems.

Given the long history of transfusions in sport, it is obvious just how crucial it is to finally have a test to detect this form of blood doping. Malm believes it could have a profound effect.

“We know if this works it’s going to be a big thing in the news and the sporting world. I know that. We also know that there could be a very high number of positives. There could be a very big effect on sport.”

But he remains cautious, underlying the need that everything works out as planned.

“We worked on it for a long time and I’m not jumping up and down just yet. We have to see it work. It does looks very, very promising. But I think also if we are not done in a year, I think we are going to run into financial issues. We are already going for a long time, and I think we have exhausted the resources.

“But we are relatively confident we will get there. Absolutely. And so is our investor. WADA must be too. They gave us a grant, they approved our report a few weeks ago.”

Given the long wait for such a test, it would be a tragedy for sport if funds dried up before the first autologous blood transfusion detection method was introduced. It would be a tragedy for fans, for those who want to see clean competition. It would also be a tragedy for the cyclists and athletes who want to compete in an ethical way.

Rumours of blood doping have existed for half a century. Vinokourov was snared a full eleven years ago, yet there is still a huge shortcoming in the testing system. Everyone who values clean sport will welcome this hope on the horizon.

As Parisotto said, it should be a game-changer. Here’s hoping it is.

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