By Rasmus Damsgaard, MD, PhD
I am aware of a handful of athletes with urine samples that contain artificial EPO (erythropoietin).
Science is engaged in an arms race with drugs cheats
Nevertheless, these samples have been declared "negative" - the athletes have not even been accused and maybe never will.
Right now these athletes participate on the highest international level against their fellow
There are at least three issues, which are strong proof of previous artificial EPO administration.
First of all, the EPO urine analysis must show "EPO bands" that differ from the "natural bands" - the bands representing the hormone produced by the person's own body.
Secondly, these "natural bands" are usually non-existing, when artificial EPO has been administered - a result of a decreased production of the body's own EPO.
That's the way the body works; when a drug is administered, the body puts its own production on a hold. The phenomenon is also known as "negative feedback".
Thirdly, a suspicious blood profile is a strong indicator of whether the production of red blood cells is stimulated or inhibited in an unnatural way.
Hamster or ill?
All three issues are present in the five samples of concern. Surprisingly, the criteria set by World Anti-Doping Agency (WADA) are so narrow that none of the tests were able to be declared positive.
These highly suspicious samples have primarily all been declared "negative" by WADA accredited laboratories.
Nevertheless, it is obvious just by looking at the results that the EPO bands are far away from the bands representing natural EPO.
In addition, these samples show no signs of natural produced EPO - the "natural bands" are simply non-existing. This could either be due to kidney failure (natural EPO is produced in the kidneys) or - if I may be so blunt - maybe the athletes descend from hamsters?
That is, the majority of artificial EPO is produced in hamster cells, making this artificially-produced hormone different from natural human EPO.
The majority of artificial EPO is produced in hamster cells, making this artificially produced EPO different from natural human EPO
The EPO bands in these highly suspicious samples are indistinguishable from the hamster hormone bands - ergo the athletes must be hamsters!
Another possibility is, as already mentioned, that they suffer from chronic renal failure, having their blood rinsed by dialysis and being in a life-long treatment with artificial EPO.
Obviously, being a kidney patient is not consistent with being a world-class athlete.
In addition, the blood profiles of these athletes indicate that the production of red blood cells on certain occasions has taken place with an un-physiological high rate.
This is illustrated by the large proportion of young red blood cells (the reticulocytes) in the blood. In a healthy individual, the proportion of reticulocytes makes up around 1% of the total population of red cells.
Sometimes minor increases or decreases are observed, but the proportion almost always lies within the range of 0.2-2.0%.
When a low reticulocyte proportion is present in the blood, the athlete is either ill not
able to participate in competitions or has an unnaturally large amount of red blood cells circulating in the blood stream.
A large amount of red blood cells increases the thickness of the blood, which results in an increased risk of thrombosis.
This is sensed by the body, which subsequently decreases its own production of red blood cells resulting in a decrease in the proportion of reticulocytes.
On the contrary, if the proportion of reticulocytes is large, the body's production of red blood cells is "working over time".
This is observed after large blood losses have taken place e.g. in connection with certain serious pathological conditions or after major high impact accidents.
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Another potential scenario is that blood is withdrawn and kept stored in a blood bank for subsequent reinfusion - also called autologous blood transfusion - or during artificial EPO administration.
It is essential for the interpretation of these results to know that not only do the proportion of reticulocytes in the blood samples from these athletes exceed the 2.0% limit, but this level is far greater than the reticulocyte levels seen in previous as well as subsequent samples from the same athletes.
In these samples the level was around 1%, which, as previously mentioned, is a normal level in a healthy individual.
But why do neither the WADA accredited laboratories nor WADA themselves declare the samples "positive"? Despite numerous enquiries, WADA refuses to make any changes.
The simplified "legal answer" from WADA and the laboratory is that they are not in possession of the specific kind of artificial EPO that the athletes have used.
As long as the kind of EPO is unknown, there will be no positive test results. WADA has promised that as soon as they track the right EPO, the samples will be declared positive.
The problem is that nowadays a large number of illegal laboratories in, for example, China, Russia and India produce a wide range of different "unknown" EPO types the so called EPO "biosimilars".
It is self-evident that tracking down and subsequently analysing all these different black market EPO types is impossible. For example, at least 20 different kinds of EPO are circulating on the black market, which WADA may not be in possession of. Then again, the numbers of non-certified EPO types may be in the hundreds.
Another issue that needs to be addressed is that the international sports federations (IF's) do not automatically receive a detailed EPO test result.
The only test result received is whether the test is "negative" or "positive". A complete description of the test result is only delivered on request from the IF's.
If the federation does not use blood profiles, it is impossible to track down a positive sample declared negative by the laboratory.
Dr Damsgaard says he knows of samples that contain artificial EPO
Bearing this in mind, one can't stop thinking of how many positive EPO urine tests you would find if the door to the databases of the laboratories suddenly turned wide open.
To sum up, we are looking at a handful of test results showing unnatural EPO bands, lacking the normal EPO bands. In addition, blood tests from the same athletes show significant increases in the production of red blood cells.
WADA exhibits a limited interest in using the lack of natural EPO bands as an additional deteriorate fact.
Neither does it seem to bother them that the blood profiles look like they originate from people who either have lost two litres of blood or have taken an overdose of EPO in their treatment of their non-existent chronic renal failure.
External experts have had a look at the results and the conclusion is univocal; the athletes have been using artificial EPO. But WADA's strict criteria for a positive test keep the federations from sanctioning the athletes.
While WADA and the accredited laboratories travel around the world in their search for new EPO types, the cheaters keep doping, earn a big price and sponsor money and we - the anti-doping experts - fear not to get funded for our next research projects if we were to tell the world what we know!
There are ways to catch or convert the cheaters. First of all, blood profiles must be implemented in all relevant sports federations. Large, unnatural deviations from the individuals' own previous tests results should lead to a "no start" sanction for a given period.
Not before the blood profile has returned to normal is the athlete allowed to compete again. In addition, blood tests should be used to target urine samples.
Then WADA's criteria of a positive EPO urine test should be re-evaluated. Instead of defining a specific signature for each and every different kind of EPO, the definition of a "normal test result" should be developed.
Every test result deviating from this "negative reference" should be considered positive. An alternative approach is to arrange a meeting, where the suspected athlete, a representative from the sports federation and an external anti-doping expert should attend.
Factors like illnesses, genetic factors, strenuous exercise and so on, which could explain the suspicious results, should be disclosed.
In truth, this meeting should be arranged with the sole objective to show the athlete that the federation knows what is going on, and make it clear that from now on the athlete will be tested excessively.
Although the possibilities are plenty, but not exhausted, they will not be realized until the day the highest authorities stop limiting the anti-doping work and instead extend it.
Until that day, I would dare to say, it is the authorities and not the athletes that are responsible for the doping problems in today's sport.
Dr Rasmus Damsgaard runs the anti-doping programme for the International Ski Federation and for the Astana Cycling team