Innovative Anti Doping Tests

[StyrbjornSterki]

Doping versus anti-doping is its own competition, after a fashion.

One side has a game plan which it is required to both publish in advance to the world at large and to scrupulously abide by.

The other side has every scientific asset as does its opponent. Further, it knows its opponent's plans (because they were required to publish them). Unlike its opponent its game plan is secret and it has neither ethics nor any code to abide by. The only rule they adhere to is this: defeat the anti-dopers.

There is no winning for clean sport under these circumstances.

 

[Aragon]

Even if the blood doping methods would be eliminated one-by-one, there are always some undetectable methods, for instance no present or imaginable direct approach to autotransfusions can' detect direct infusion from an identical twin because there are no storage components in the blood nor blood deterioration, it is just identical red fluid flowing from person A to person B.

Remember when it was said that certain teams were signing riders based on their blood type? Maybe the current 'vogue' for twins - Yates, Oliveira - will spark a new rumour if either of these two blood tests gets off the ground.

There is also a brand new study on the use of low-dose cobalt as stimulant of RBC production, in which there was a small but statistically significant increase in totalHb whereas was no noticeable increase in Vo2Max or performance (the authors of are of the opinion that the improvement was real but gone in the other "noise" in that data).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157393/

This is one the methods of which nobody knows how prevalent it is, I can recall only one athlete having been busted a year or two ago, but I have never read a first-hand account of its use. But if the alternative to rHuEPO is to overdose one's system with all kinds of vitamins and possibly toxic medals, one should at least think how good idea the ban is in the first place.

 

[fmk_RoI]

Cobalt has been in use in horse racing, hasn't it?

 

[Aragon]

Re:

Cobalt has been in use in horse racing, hasn't it?

A large portion of Google hits point to that direction.

The case I had in my mind was Austrian cross-country skier Harald Wurm who got a four-year ban in 2016. From the few news items, I get that there was no positive test but cobalt substance was found from his premises and he admitted having used it as a PED.

https://www.dailymail.co.uk/wires/ap/article-3507714/Austrian-cross-country-skier-Wurm-gets-4-year-ban-doping.html

As far as I can tell, the Wurm case is the only one thus far, but it would be interesting to know how prevalent problem it is today, because while the method of using cobalt to stimulate erythropoiesis has been known since the 1940's, anti-doping specialist Giuseppe Lippi warned about the substance as early as 2005 in one of his papers that many CN readers are familiar with:

https://bjsm.bmj.com/content/39/11/872

 

[veganrob]

Re:

Cobalt has been in use in horse racing, hasn't it?

I wouldn't be surprised. I spent many years in horse racing, !976- early 2000's. I saw and heard of the most outrageous, unethical doping. The horses are guinea pigs for dope. First I heard of EPO use for race horses was around 1990. That's really minor compared to all the other stuff though. Pretty tragic.

 

[Norks74]

Re: Re:

Cobalt has been in use in horse racing, hasn't it?

I wouldn't be surprised. I spent many years in horse racing, !976- early 2000's. I saw and heard of the most outrageous, unethical doping. The horses are guinea pigs for dope. First I heard of EPO use for race horses was around 1990. That's really minor compared to all the other stuff though. Pretty tragic.

Yup it's very true, and horribly unethical. Much more so in my opinion than human doping to win at all costs. At least humans have a choice in the matter.
https://www.telegraph.co.uk/racing/...r-jockey-three-year-bans-doping-horse-cobalt/

 

[fmk_RoI]

Re: Re:

The case I had in my mind was Austrian cross-country skier Harald Wurm who got a four-year ban in 2016. From the few news items, I get that there was no positive test but cobalt substance was found from his premises and he admitted having used it as a PED.

It does seem unusual that we don't have cobalt positives, that the best example is possession and not use. I've vague recollections of cobalt being mentioned around here the odd time, around the time Xenon was in vogue. But like you I don't know of any athletes using it, my knowledge of it call comes from stories about horses.

 

[fmk_RoI]

Re: Re:

Cobalt has been in use in horse racing, hasn't it?

I wouldn't be surprised. I spent many years in horse racing, !976- early 2000's. I saw and heard of the most outrageous, unethical doping. The horses are guinea pigs for dope. First I heard of EPO use for race horses was around 1990. That's really minor compared to all the other stuff though. Pretty tragic.

I once did an interview brief for Willy Vlautin's novel Lean on Pete and I think I shocked the presenter by suggesting he ask Vlautin about the descriptions of doping and related cruelty in the book (which is set largely around the tracks in Portland, Oregon), which included vodka (injected) and jet fuel (to burn off nerves). Plus, we also had that Cian O'Connor thing over here, and it's amazing how educted you can become when we're pulling down one of our own (it was like open season, the floodgates opened and all the stuff you couldn't be said because of the importance of Cheltenham and the Curragh just poured out for a few weeks). Other than that, I'm afraid that most of my knowledge of equine doping is about nobbling (which is why horse racing was so early to bring in not just bans for doping, but also actual testing - I have a vague recollection of reading somewhere that in the UK doping the monarch's horses was actually a capital crime, up there with treason, but I've never been able to find out if that was really true or just a bit of bollix).

 

[Aragon]

Re: Re:

It does seem unusual that we don't have cobalt positives, that the best example is possession and not use. I've vague recollections of cobalt being mentioned around here the odd time, around the time Xenon was in vogue. But like you I don't know of any athletes using it, my knowledge of it call comes from stories about horses.

My impression is that there has been barely any published speculation about cobalt use and the method wasn't mentioned in the CIRC-report at all even when GW1506, AICAR and all the other stuff were mentioned of which there is also not that much solid evidence.

The use of rHuEPO was revealed very early on already in 1990 (Rob Pluijmers), so perhaps cobalt culture doesn't exist or the use of PEDs is more secretive now-than-ever because so much of other than AAFs can be used as evidence against the athletes (e.g. USADA vs. USPS).

 

[screaming fist]

Some short reports have been published in the German press regarding the paper about cobalt doping (mentioned above by Aragon - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157393/ ).


Here's a short piece in German: https://www.br.de/nachrichten/sport/wirkt-wie-epo-neue-studie-zu-kobalt-alarmiert-dopingfahnder,RG9kls9

- Doses as high as in supplements are just high enough to significanntly raise hemoglobin production, if an athlete took three or five times the dose they could simulate the effects of a 2000m altitude training of two to three weeks

- There is a test, but it's not WADA-certified so it can't be used to sanction athletes. And allthough cobalt is on the WADA list, no treshold has been established.

- Scientists speculate cobalt doping might have been a thing for 40 years without anybody realising.


I wonder if cobalt might have just replaced EPO as it is relatively safe to use as it's unlikely to be detected. When athletes only can manipulate their blood within the restraints of their biological passport this might be the way to go right now?

 

[Robert5091]

https://bjsm.bmj.com/content/39/11/872

Excessive administration of this trace element (cobolt) also produces goitre and reduced thyroid activity.

Was there not something about people using thyroid medicine? Also was cobolt use not recommended as it's potentially very dangerous?

 

[fmk_RoI]

Going back to Dried Blood Spot testing, which opened this thread last year when USADA were trialling it.

The UCI have been using a Swiss version for their Tramadol testing. Deets are light, all I've seen is this passing reference in May this year:

The UCI – with the support of the Cycling Anti-Doping Foundation (CADF), the independent body mandated to define and lead the strategy on anti-doping testing and investigations in our sport – took samples mainly at the finish line of races. Tests were carried out using the Dried Blood Spots (DBS) reference method. Developed by the Swiss company DBS Systems, sampling kits were used to conduct this minimally invasive test, which involves collecting a small amount of blood from the rider's fingertip.

Daniel Friebe posted a French article earlier today in which Nicolas Leuenberger, of the Swiss Laboratory for Doping Analyses attached to the University Center Romand Medicine Légale, is said to be using the technique to spot O2 vector doping focusing on a specific RNA molecule found only in young blood cells. If Leuenberger's test actually works, as well as speeding up sample collection in the field (and thus reducing costs), it could also be used on stored samples. (The linked article is v light on details and, really, dried blood spot plus RNA is pretty much all there is in it that I could spot.)

Leuenberger's work sounds like a cross between the DBS testing trialled by USADA (using that technique) with the other WADA-funded research that focused on seeking specific markers (eg Christer Malm or Yannis Pitsiladis). Like those other research projects, this has been some time in the building and Google will throw up a few English-language stories about Leuenberger and early versions of this work.

 

[fmk_RoI]

In related news, our good friend Yannis Pitsiladis is yet again close to a soon-to-be-delivered ground-breaking breakthrough:

Pitsiladis and his team specifically examine the behaviour of RNA molecules within the human genome, which transfer – or transcribe, to use the scientific term – instructions from DNA to bodily systems, effectively telling them how to work. This applies to everything from hair growth to the production of red-blood cells.

RNA will respond to whatever factor is working on the body, whether external or internal, including temperature, exercise, altitude and various forms of drugs. “The results have been better than we expected,” Pitsiladis said. “Even the smallest amount of EPO has a significant effect on genetic activity.”

The effect is so marked that, by examining the change in the genetic signatures over time, Pitsiladis is able to estimate when the blood was manipulated and roughly on what scale doping is taking place. “The athletes who are cheating will follow carefully tailored regimes, taking the drug at certain points in their training and at certain intervals,” Pitsiladis said. “If we can begin to establish the pattern then we are a step closer to catching them.”

Oh, and bonus link for another thread: Pistaldis and the sub-two hour marathon. A man's gotta eat and you can't dine out on the one soon-to-be-delivered ground-breaking breakthrough forever.

(Soz peeps, I've nothing against Pistaldis, but the UK media just lap the guy up every few years just cause he's based in a UK uni and it's become a bit of a joke.)

 

[fmk_RoI]

Some comments on DBS from a wide-ranging and sometimes interesting interview with USADA science director Matt Fedoruk. First, some basic intro stuff to catch folk up:

We started looking into technologies that were being developed here in the U.S. that allowed us to collect blood more easily in a noninvasive way, more athlete-friendly collection devices. And we stumbled upon a couple of companies that have been working on these devices that essentially collect a small amount of blood from the capillary blood beds in your skin. You put these devices on your arm or your leg or some other area of your body that has good perfusion, and you press a button and a small amount of blood can be collected.

One of them is Seventh Sense Bio[systems]. They’re an outfit out of Boston. They’ve developed this device called TAP, which stands for touch activated phlebotomy. That’s the main device we’ve been testing. And there’s another device called Tasso that works under a very similar principle but isn’t quite as painless as the TAP device. We’ve been piloting both of those devices just to see how they work and what the benefits and limitations of them are.

And this on the shades of Theranos that some of us automatically think of when we see DBS mentioned:

We need to be really careful. One, you can’t overpromise, and two, that the science needs to be vetted properly in order to make sure that the methods work properly. I think that’s where Theranos fell over, is that they were promising this revolutionary technology, but yet in practice the science didn’t fit and they weren’t actually measuring what they said they were, and the number of analytes they were promising in a single spot was grossly overestimated. That’s why having multiple entities working on the dry blood spot, making sure that we roll it out to our athletes, that we’re publishing in peer reviewed journals, that this stuff is transparent is really important.

One interesting change of tone in the interview is on the use of algorithms and AI, which could mean that USADA are finally listening to Greg LeMond on the need to look at performance indicators and not just biomarkers:

We have a great opportunity in delivering a higher level of sophistication through understanding of things like athlete performance and developing more sophisticated mathematical algorithms to predict when an athlete’s performance trajectory is either peaking too early or going too steep compared to their past performances. There’s a lot more that we could be doing as an anti-doping community and taking those cues from other industries that we’re starting to look into: things like artificial intelligence and machine learning are areas that the consumer industry and the insurance industry and others are using already. How can we learn how to use them more effectively in anti-doping?

The rest of the interview is worth atleast glancing over, it covers familiar stuff (Russia, gene doping) but there's nuggets of info in it, I think.

 

[fmk_RoI]

USADA science director Matt Fedoruk mentioned in the interview above the possibility of using AI to some degree. WADA today announced three AI-related projects they've funded:

* The first is a one-year project exploring possible techniques for the analysis and application of AI to detect the use of prohibited substances or methods to circumvent anti-doping rules. If the results are promising, they will be compared with those obtained using traditional statistical methods, such as the adaptive model currently used for the Athlete Biological Passport.

* The second is a two-year project that aims to quantify the risk of doping in athletes through the application of AI and, as a result, to develop an algorithms-based sampling and testing strategy.

* The third project is a two-year study of the perceptions of different stakeholders regarding the use of AI and its benefits in the context of anti-doping and to guide dialogue between WADA, other anti-doping organizations, athletes and the general public.

 

[proffate]

The biggest issue with an AI approach is that you need lots of training data. For example AI is a powerful tool for self driving cars, but only after you have driven thousands or millions of miles around a city to train that AI.

In this case, that means the system would need many passports (where a "passport" is a collection of metrics over time associated with a single athlete) and for each one, a decision, i.e. "doped" or "clean". I don't think that exists because any training set would have many false negatives (passports associated with a doped athlete who had never been caught, falsely marked as clean) and because the size of the set of true positives (athletes with passport data who are known to have doped) is exceedingly small.

IOW, AI is not going to solve the problem that we don't truly know what a doped passport looks like.

 

[fmk_RoI]

Back to Yannis Pitsiladis. Looks like his gene-based test for blood-doping is going to be a thing during the countdown to Tokyo. For each Games this millennium, gene-doping has been the Games's ghost of Christmas Future but now it looks like the IOC is trying to change the script. Thomas Bach is bigging up Yannis Pitsiladis yet again being close to being on the edge of a soon-to-be-delivered ground-breaking yet-to-be-validated anti-doping breakthrough:

“With research on genetic sequencing progressing well, this new approach could be a groundbreaking method to detect blood doping, weeks or even months after it took place,” Bach told the World Conference on Doping in Sport in Katowice, Poland.

“If approved by the World Anti-Doping Agency such gene testing could be used at the Tokyo Olympics. These new methods will again strengthen deterrence. We want the cheats to never feel safe, anytime or anywhere.”

And even it the validation somehow cannot happen in the nine months between now and the Games - nine months? Tons of time! - the IOC wand to use Pitsiladis to scare athletes straight:

Even if the test is not validated in time for Tokyo 2020, the IOC intends to store more samples so they can analyse them in the future. “This will add to the fact the pre-Games testing programme will be the most extensive programme ever, aimed to maximise both detection and deterrence,” Bach said.

Okay, come on, put your vote where your faith is and we'll check back in come July: sad-face this post if you reckon there's no way in hell Pitsiladis can get his test validated before Tokyo, thumbs-up if you actually believe it's a goer.

Me:

 

[86TDFWinner]

It is also interesting that in 1976 the Le Monde journalist was quite convinced that blood doping was going on in the pro cycling when the issue wasn't discussed that much in the media.

If I shall have the opportunity, I will ask some information from the people themselves because I have been working on an essay/article series on the origins of blood doping that might see the light of the day in a few months in which I have incorporated some new material from Sweden sources.

Didn't Anquetil and Merckx pretty much admit to some form of doping?

 

[myrideissteelerthanyours]

Didn't Anquetil and Merckx pretty much admit to some form of doping?

Merckx had a positive /w a one month suspension and he later on had one of those weak confessions where they say: I did something wrong. I trusted a doctor.

Anquetil refused to even denounce doping. He definitely admitted to taking amphetamines.

 

[fmk_RoI]

USADA's got a new saliva test:

https://ufc.usada.org/oral-fluid-collection-testing/

A major benefit of oral fluid testing is that it has the potential to detect in-competition prohibited substances, such as stimulants or cannabinoids, very close to their use and/or exposure. Accordingly, this may minimize the potential scenario where a substance prohibited in-competition only, that was used out-of-competition, would be detected during an in-competition test.

(Fun bit of anti-doping history for you: testing is commonly thought to date back to the 1910s, when Polish pharmacist Alfons Bukowski developed a saliva test for horses.)

 

[Aragon]

Haven't seen this program mentioned yet at the Clinic, but "Partnership for Clean Competition" has its podcast which features (among other topics) interviews now-and-then researchers who develop tests for anti-doping purposes such as a dried blood spots, OMICS approach to detect blood doping etc:

Anti-doping Podcast - Partnership for Clean Competition

More Podcasts Below Support This Podcast Interested in sponsoring the Anti-Doping Podcast or have a guest recommendation? Support the Anti-doping Podcast Interested in sponsoring the Anti-Doping Podcast or have a guest recommendation?

cleancompetition.org

Very accessible and has some interesting topics, but I can't say I learned that much from the handful I've listened thus far, e.g. the AMGEN scientist who developed rHuEPO even mentioned something about having heard rumours of cyclists using the hormone in the late-1980s and it would've been interesting to know where the rumours originated from etc. instead of him spending minutes to tell the details of the ABP program.

 

[Nomad]

Haven't seen this program mentioned yet at the Clinic, but "Partnership for Clean Competition" has its podcast which features (among other topics) interviews now-and-then researchers who develop tests for anti-doping purposes such as a dried blood spots, OMICS approach to detect blood doping etc:

Anti-doping Podcast - Partnership for Clean Competition

More Podcasts Below Support This Podcast Interested in sponsoring the Anti-Doping Podcast or have a guest recommendation? Support the Anti-doping Podcast Interested in sponsoring the Anti-Doping Podcast or have a guest recommendation?

cleancompetition.org

Very accessible and has some interesting topics, but I can't say I learned that much from the handful I've listened thus far, e.g. the AMGEN scientist who developed rHuEPO even mentioned something about having heard rumours of cyclists using the hormone in the late-1980s and it would've been interesting to know where the rumours originated from etc. instead of him spending minutes to tell the details of the ABP program.

There was evidence of rHuEPO use at both the Calgary & Seoul Olympics. Perhaps experimental use starting in the 1988 cycling season?

Recombinant human erythropoietin in sports: a review

Erythropoietin is an endogenous hormone of glicoproteic nature secreted by the kidneys and is...

www.scielo.br

 

[Aragon]

If we are to believe that what is written is true without taking a look into the sources quoted, then Francesco Moser was perhaps the first rHuEPO-user according to the CIRC-report (pp. 30-31):

Francesco Moser twice broke the hour record in 1984, reportedly helped by Dr Francesco Conconi and Dr Michele Ferrari. Francesco Moser is reported to have admitted using – at the time not illegal – blood transfusions in 1999, however in 2014 he apparently stated that: “…There wasn’t any blood transfusions, before the first or second attempt. The benefits of altitude were enough”. Seized documents from Dr. Francesco Conconi in proceedings against him apparently however showed that Francesco Moser had been treated with EPO around that time.

 

[fmk_RoI]

If we are to believe that what is written is true without taking a look into the sources quoted, then Francesco Moser was perhaps the first rHuEPO-user according to the CIRC-report (pp. 30-31):

Really is the wrong thread to be having this discussion again but: obviously Moser couldn't have used EPO in 1984. I think it's well known - as "known" as this can be in the face of omertà - that Moser's tenth-anniversary 1994 Hour rides were EPO-fuelled. That CIRC was inaccurate with its historical 'research' ... look, about the only good thing in that report is the way it highlighted how doping is defined by those talking about it, that for some it's puritanism for others it's simply not getting caught. For much of the rest, CIRC was badly written scuttlebutt.

WRT the EPO guy and the 'rumours' about its use in the 1980s. When did he say he heard these rumours? If in the 1980s, it's one thing, if later, well, there's lots of rumours about EPO use in the 1980s and this becomes like a self-referential Wiki claim eating itself. If it was contemporaneous rumours, well we know that EPO was being talked about in news reports from the Calgary Olympics. We know that Les Earnest was expressing an interest in it that same year. And we know that Søren Kragbak has said there was an attempt to recruit Dutch Danish cyclists in 1989. So, rumours of use in the 1980s: we know they exist.

 

[Aragon]

I have had only a precursory look at the article and haven't read it in too much detail yet, but here is a brand new article about a relatively new approach to detect autotransfusions:

https://cyclingtips.com/2018/08/game-changer-the-long-push-to-end-blood-transfusions-in-sport/

The research has been going on for a few years and while the approach has had some problems and there hasn't been (yet) a breakthrough, I know for sure that none-other-than Dr. Björn Ekblom (who "developed" blood doping in the late-1960's) is about 100 % certain that the method will eventually catch the blood dopers.

The breakthrough paper is going to be published relatively soon and a non-edited version is available here:

DETECTION OF AUTOLOGOUS BLOOD DOPING

Objectives Autologous blood transfusion (ABT) enhances athlete’s performance, is banned as doping by the World Anti-Doping Agency (WADA). Currently, there is no implemented detection method for ABT. Transfusion of one’s own, long-term cryopreserved red blood cells (cryo-RBC) immediately...

www.medrxiv.org

The authors claim that by focusing on differences between frozen vs. non-frozen RBCs, with their model, they can detect 100 % of autotransfusers (some for up to 5 weeks after the treatment) who use cryopreservation (-80 degrees C) with no false positives, when the control group has been sea level, high altitude and hypoxic chamber athletes.

According to the authors, this is an real breakthrough because they maintain that refrigerated blood is not a viable option for the following reasons:

Because cold-stored (+1º to +4ºC) blood is viable for a maximum of 42 days, during which time the athlete’s physical performance is compromised from blood donation, and erythropoietin is readily detected the blood doping method of choice for cheating athletes is transfusion of one´s own, long-term cryopreserved red blood cells.

Even when one should add ABP-fluctuations after blood donation roughly a month before reinfusion, I wouldn't be top convinced about this, because under the current ABP-system, even cryopreservation doesn't allow enormous transfusions without inducing fluctuations in Hb, Ret-% and OFF-Score.

In addition, an athlete can take certain precautions when donating blood the usual way not to affect the ABP-module or training capacity before the grand competition, such as:

• elevating Hb mass via microdosing of cobalt/EPO before blood donation --> blood loss shouldn't affect ret-% count that much because the post-donation Hb-level is closer to normal than it would've otherwise have been.
• Using the blood "refreshing" method (donate a bag, donate 2 bags a month later after which you infuse the old bag etc...) described by Hamilton, Landis et al, but only using something like ½ blood bags instead of a full bag --> Hb fluctuations affecting training status and ABP-module should be less than 5 %.