Juhtiv dopinguekspert ei kiida heaks Veerpalu testimist (lisatud 19 juunil)

[Palun andestage mu natuke vigase väliseestlaskeele eest]

Saatsin 13 aprillil kirja juhtivale kasvuhormooni eksperdile, professor Peter Sonksenile, ja sain huvitavat ja positiivset vastust. Edastasin seda Eesti Suusaliidule aga nüüd tuli mõte et võiksin seda ka avalikustada.

Professor Sonksen oli esimene maailmas kes leidis, et kasvuhormoonil on efektid ka täiskasvanutel ja peetakse üheks maailma juhtivaks selle alla eksperdiks. Tema on ka uurinud dopingu testimist ulatuslikul määral ja on arendanud testi kasvu hormooni dopimise kontrollimiseks.

Sonksen kinnitas mu arvamust, et WADA (maailma dopinguassotsiatsiooni) test pole piisavalt uuritud selleks, et saab seda kasutada dopingi testimiseks. Ta vastab jaatavalt mu küsimusele kas on mõeldav, et kõva pikka-ajaline trenn võib muuta kasvuhormooni isoformide suhted (selle suhte määramine on keskne WADA testis). Ta kinnitab ka mu arvamust, et grupp mida on uuritut (20) on suurel määral liiga väike. Sonksen arvab, et grupp peaks olema üle  20 korda suurem, selleks et võimaldada testi usaldusväärsuse määramist.

Järeldus

On tehtud Veerpalule ülekohut, kasutades teaduslikult ebapiisavalt uuritud testi, millel võib olla teatud nõrkused. Testi usaldusväärsust saab alles kindlaks määrata palju ulatuslikuma testimise läbi. Nõrkused võivad olla sellised, et annavad valet tulemust just nende tingimuste puhul mille all testiti Veerpalut. Ei ole, tänapäevase teadmise seisuga, õigustatud järeldada selle testi alusel, et ta on ennast dopinud.

Allpool mu kiri koos tema vastustega, märgitud [Sonksen]. Olen märkinud tähtsad kohad punasega.

KIRJAVAHETUS PROFESSOR PETER SONKSENIGA

In a message dated 13/04/2011 14:28:37 GMT Daylight Time, Jaan Suurküla writes:

Dear Professor Sonksen,

I have some questions regarding the validity of WADAs GH isoform-based doping test.
I am an Estonian physician investigating the doping case of the skier, World and Olympic champion Andrus Veerpalu. You may know that he recently failed the doping test of WADA based on GH isoform analysis using monoclonal antibiodies.
I have doubts about the credibility of the “validation paper” of the WADA scientists, based on research on recreational athletes (High-Sensitivity Chemiluminescence Immunoassays for Detection of Growth Hormone Doping in Sports,http://www.clinchem.org/cgi/content/full/55/3/445)?
4 of 7 authors of this validation paper, are owners of the test or its distribution company and one is an employee of tthat company. Two are also tied to WADA, This non-independent study seems to be the only published validation paper.  
QUESTION 1:
a)  Do you consider such a paper a reliable scientific validation document?
[Sonksen] It is a peer-reviewed publication in an established journal
 
b) Do you consider the number of tested subjects (10 men and 10 women injected with GH, plus 10 untreated healthy reference subjects) sufficient for providing reliable results?
[Sonksen] It was sufficient to convince the reviewers that the method is valid but insufficient to validate a test before implementation for forensic testing
b) As there appears to be no other published validation papers, do you consider this test scientifically validated to such an extent that it is justified to use it for checking doping?
[Sonksen] No
QUESTION 2: Do you consider the testing on recreational athletes after a short peroid of exercise a sufficient basis for validation of the test. More specifically, do you think these results are relevant for professional athletes doing weeks of high intensity endurance excercise?
[Sonksen] They are relevant but more data would be needed before I would be satisfied
QUESTION 3: More specifically:
a) Is it conceivable that prolonged or intense exercice may alter the physiology and biochemistry in such a way that it might affect the pattern of isoforms? 
[Sonksen] It is conceivable
b) can it be excluded that injection of HGH during such excercise may have a different effect on the incretion of HGH from the pituarity than the injection  in persons not doing prolonged endurance training.
[Sonksen] No
c) If this so, do you think this might influence the test result significantly, making it unreliable?
[Sonksen] It is possible
Addition: I just got a reference that might indicate that heavy endurance training can change the isoform ratio: Zarrineh, F., F. Salami, H.N. Bakht, M. Salavati and M. Hedayati, 2009. Effect of acute and chronic aerobic training on plasma GH isoforms concentration in pubertal and pre-pubertal male athletes. J. Applied Sci., 9:13, 2469-2474. (http://scialert.net/abstract/?doi=jas.2009.2469.2474)
QUESTION 4:
a) Is it sufficient to base the test on a only four  monoclonal antibodies (mAbs)?
[Sonksen] They were selected from a larger collection
b) I have proposed a hypothesis that there may be minor, perhaps epigenetic variations in the structure of GH such as to influence its configuration much enough to make the WADA mAbs less responsive or unresponsive to the presence of pitGH. I am aware of major genetic variations (causing dwarfism), but I suppose minor alterations may not be known, because they may not cause any trouble. What do you think about this hypothesis?
[Sonksen] It’s a hypothesis and as such needs testing before it can be accepted or rejected
c) If this is conceviable, might such an alteration jeopardize the result, causing misleading info about the ratio between recombinant GH (recGH) and pitGH?
[Sonksen] Conjecture
d) If so, do you think the number of subjects in the validation study is large enough for excluding the possibility of such variations? In additiion to the 20 participators of the WADA validation study, blood from two “cohorts” German blood donors was used as a reference group to find out the “normal” recGH/pitGH ratio.
e) Do you find it satisfactory that the size and ethnicity of the blood donor reference groupwas not declared?
[Sonksen] I would like to have seen a larger collection of elite athletes as a reference group – we used >800 in GH-2000
f) If you think there might occur genetic variations that could affect the test, how large reference group size would you think is required and what is the importance of including different ethnicities?
[Sonksen] Practicality limits size – 500 would be a more realistic figure and ethicity effects should be excluded
5. I have proposed a hypothesis that intense oxidative stress may cause damages to HGH that change its configuration so as to make the HGH isoforms less recognizable by the mAbs. It seems likely that a rise of free radicals to a high level may appear after several days of intense endurance training because of the exhaustion of antioxidative defences that such activity may bring about. Statistically, as far as I can see, significant damge to HGH molecules would be quite likely considering the very small numbers of HGH molecules compared to the large number of free radicals. What do you think about this hypothesis?
[Sonksen] It’s a hypothesis
And if this occurs, might it, in principle, affect the measured isoform ratio so as to yield misleading results?
[Sonksen] First the hypothesis needs testing
  
QUESTION 5: Why do you think this test would be “as difficult to defend?” according to  the following quote attributed to you one year ago in an internet source:

“I don’t know why they chose the isoform. I think they thought this was a more direct test than our marker method. I think that they were, ah, too thick to understand it. They weren’t experts in the field, and they don’t really understand it. The isoform test would be every bit as difficult to defend in court as our method.” (Source: “Experts Question WADA Blood Test for HGH“)

In other words, what weaknesses do you find in this method? 
[Sonksen] There is insufficient peer-reviewed scientific literature to support it being introduced – in my opinion. I understand that they have more unpublished results that WADA has reviewed. I do not believe IOC or WADA undertook sufficient ‘due diligence’ before they decided to back the isoform method rather than that proposed by GH-2000 

With collegial greetings,
Jaan Suurküla, M.D. (retd)
Tallinn, Estonia
Peter SonksenPeter Sonksen MD FRCP FFSEM(UK)
Emeritus Professor of Endocrinology St Thomas’ Hospital and King’s College, London
Visiting Professor Southampton University

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