Another Wakefield paper pulled?

By Grant Jacobs 13/02/2010 8


In recent news the Lancet article by Andrew Wakefield that, in part, lay behind the MMR vaccination scare in the UK and elsewhere was retracted subsequent to a ruling by the UK General Medical Council’s Fitness to Practise Panel. (‘In part’ because mainstream media reportage and Wakefield’s statements to the media and public also played a role–arguably the larger role–in creating the scare.)

(Source: wikipedia)
(Source: wikipedia)

The latest news is that Neurotoxicity has withdrawn a recent paper titled Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing Hepatitis B vaccine: Influence of gestational age and birth weight in which Andrew Wakefield is the senior author.

Details as to the reason behind the withdrawal are not yet available to the best of my knowledge.

Withdrawal, as opposed to retraction (like the earlier Lancet paper), is for papers that have only been released in preliminary form, what is referred to as “articles in press”. (Many journals now release these on-line in advance of formal publication release, in the form of ’advance publication in press’ papers.)

While details as to the withdrawal are not known, Elsevier’s withdrawal policy states:

Article Withdrawal: Only used for Articles in Press which represent early versions of articles and sometimes contain errors, or may have been accidentally submitted twice. Occasionally, but less frequently, the articles may represent infringements of professional ethical codes, such as multiple submission, bogus claims of authorship, plagiarism, fraudulent use of data or the like.

and further elaborate:

Article Withdrawal

Articles in Press (articles that have been accepted for publication but which have not been formally published and will not yet have the complete volume/issue/page information) that include errors, or are discovered to be accidental duplicates of other published article(s), or are determined to violate our journal publishing ethics guidelines in the view of the editors, may be ’Withdrawn’ from ScienceDirect. Withdrawn means that the article content (HTML and PDF) is removed and replaced with a HTML page and PDF simply stating that the article has been withdrawn according to the Elsevier Policy on Article in Press Withdrawal with a link to the current policy document.

Considering that this article has previously been criticised on-line (see Footnote, below), one would likely suspect that objections to the work have been raised with the editors of the journal, possibly in the light of the recent General Medical Council’s ruling and Lancet paper withdrawal, or possibly to the institutions associated with the work.

Given that this study apparently–I have to go on the word of others here–was to examine a putative (to Wakefield) link between thimerosal and autism(-like) symptoms, I’m not surprised. I’ve written previously about the putative autism–vaccine (or thimerosal) link; there are now a good number of large studies disproving such a link.

Furthermore, I’m curious as to how these researchers obtained permission to use the Macaque monkeys in their research. Surely a decent ethics committee would have ruled against the study on the basis that a proposed thimerosal–autism link has insufficient plausibility to justify the use of the animals? (But then, being a computational biologist as opposed to an experimental biologist, I never get to face these committees myself so I don’t have first-hand experience of them.)

Footnote: Since writing the above, it’s come to my attention that Orac has, as always, beaten me to it (sigh). In particular, note that he has written a series of articles examining this study. I would suggest those interested in what might lie behind this withdrawal to head over his way and read his take on this and the series of articles he has previously written about this study. It‘s interesting that he suspects that Wakefield to have been the source of the withdrawal.

Another informal criticism is in this blog article, whose author is also the author of the up-coming The Complete Idiot’s Guide to College Biology. You’ll need to look for the passages in the middle of the article, as the article refers to other studies, too. My impression is that this criticism isn’t of the body of the paper, but abstracts for the same study that appeared on the SafeMinds website, who have since pulled that article off their website.

Update: For those not up with the state of play, it would seem that Wakefield has resigned from Thoughtful House.


Other articles on Code for life:

Lancet formally retracts Wakesfield paper

Autistic children and blood mercury levels

Genetic tests and personalised medicine

Monday potpourri: maps, malaria in the USA, cholera in Dunedin and vaccines

Map shows New Zealand with lowest death rate on earth in 1856, over 11 in 1000 dying

Deleting a gene can turn an ovary into a testis in adult mammals


8 Responses to “Another Wakefield paper pulled?”

  • Dear Mr. Jacobs:

    Since Sciblogs is devoted to “science” I respectfully suggest that the issues related to the Journal of Neurotoxicology withdrawal of the Macaque vaccine study should be grounded on methodology and not selective ethics. You speculate that ethics approval was unlikely for a study testing the effect of thimerosal on monkeys. You base your comment on the ethical impropriety of performing thimerosal studies because of lack of plausibility of the connection of thimerosal to neurodevelopmental injury. This view, however, flies in the face of multiple studies of thimerosal and its ethylmercury component. While epidemiology has been inconclusive in its look at thimerosal the population studies of thimerosal have merely been inconclusive in finding an association. They are not negative studies (as Verstraeten, the author of the the U.S. based study said in a letter to Pediatrics). It is worth noting that the IOM itself said in 2001 that the hypothesis that thimerosal in vaccines is linked to neurodevelopmental disorders is plausible. This is before the IOM’s 2004 rejection of an association with “autism” (not neurodevelopmental disorders.) The 2001 conclusion was based on presentations that included one by the longtime editor of Environmental Health Perspectives, the respected NIEHS U.S. government/NIH publication. His opinion is that thimerosal can and does cause neurodevelopmental injury.

    There are many studies that show a likely biological connection between thimerosal and neurodevelopmental disorders. For example, a researcher who now is an the scientific advisory Board of the Autism Science Foundation, DiCicco-Bloom, published a study several years ago linking methylmercury to autism. Other research by him and others has shown deleterious effects of mercury exposure during development. See, Carratù et al. Prenatal Methylmercury Exposure: Effects on Stress Response During Active Learning. Bulletin of Environmental Contamination and Toxicology (2008) vol. 81 (6) pp. 539-542. The same researchers have published studies showing that methylmercury causes damage to the hippocampus in rats. See, Methylmercury selectively alters neurogenesis in the neonatal rat hippocampus. International Journal of Developmental Neuroscience. Volume 24, Issue 8, December 2006, Page 589

    Now, those studies involve methylmercury and we can all agree that the toxicokinetics and other characteristics of methylmercury are different from ethylmercury contained in thimerosal (e.g. longer blood half-life for methylmercury). But what is not acknowledged is that the small amount of research of thimerosal and ethylmercury has strongly suggested that it is much MORE toxic than methylmercury because it readily partitions into inorganic mercury, that is not readily excreted once it lodges to the brain. In fact, research by the same authors cited above show that thimerosal is about two times more toxic than methylmercury in the way, for example, it inhibits DNA synthesis. There is also a body of work showing that thimerosal provokes strong autoimmune reactions to individuals who are sensitive. It is clear, therefore, that the body of research in animals in this area is compelling.

    The question I have is why the thimerosal research in this area is not acknowledged? Why is science not pursuing the hypothesis, clearly plausible based on research, a very small portion of which I have cited, that thimerosal and its component ethylmercury is more, not less, toxic to developing humans, than methylmercury, which has been openly studied much more closely?

    Given the body of research why would it be “unethical” to pursue such research in primates? What is your basis to say the Neurotoxicoloy paper was withdrawn because of lack of ethics, other than pure speculation.

    Putting aside the vaccine-autism controversy, which is highly politicized – and polarized – and has been relegated to competing debating points, wouldn’t anyone devoted to science welcome honest and open research of the effects of thimerosal on the developing brain? This is especially important because the developing brain of many children to this day is exposed to thimerosal and ethylmercury by injection.

    Putting all this in context is the fact that, with respect to epidemiology, the area that you claim has “asked and answered” these issues has not even examined whether exposure to thimerosal in vaccines is associated with regressive neurodevelopmental disorders. Please do not take my word for that assertion – the statement was made by one of the leading and most respected epidemiologists in the world – who wrote/edited the leading textbook on the subject for graduade students.

    As a blogger devoted to an honest examination of science I urge you and the editors of this blog to consider that because of the politicization of the vaccine-autism controversy there is an effort to suppress science in the area of thimerosal that may threaten certain valued public health policies.

    We will have to wait for an explanation of the strange and abrupt withdrawal of the primate paper that looked at vaccines and thimerosal. The fact that a committee in the UK has condemned Dr. Wakefield on matters completely collateral to the substance of his research that was published 12 years ago, is emphatically not a compelling reason to withdraw and suppress completely different research recently completed at universities in the United States.

    If we are truly devoted to science I submit that transparency must prevail. The recent revelations in Australia of the publication of a fake journal paid for by Merck and published by Elsevier (publisher of the Lancet –Wakefield- study and Neurotoxicology – the withdrawn Macaque study- should draw scrutiny of the question of whether there is something other than science at play in the suppression of controversial research.

    Sincerely,

    Robert J. Krakow
    Disclosure:
    I am an attorney who represents children with vaccine injuries in litigation.

  • “The fact that a committee in the UK has condemned Dr. Wakefield on matters completely collateral to the substance of his research that was published 12 years ago, is emphatically not a compelling reason to withdraw and suppress completely different research recently completed at universities in the United States.”

    A nifty straw man argument. Is anyone really arguing that all of Wakefield’s work should be suppressed because of the GMC comments on “collateral matters”?

    By the way Mr. Krakow, scientifically-minded persons would argue that selection bias would have fairly direct scientific relevance to the substance of the 1998 research.

  • Do’C:

    You characterize any and all arguments that displease you as “straw man” arguments. It was the lead post on this blog that speculated that ethical flaws caused withdrawal of the macaque paper from Neurotoxicology. It is that suggestion to which I am responding. Far from erecting a straw man I am questioning baseless assertions found here and almost everywhere in the media when Dr. Wakefield is discussed.

    I have not observed anyone arguing that all of Wakefield’s work should be suppressed. Surely that argument would be too nakedly biased for pursuit by those who wish to suppress Dr. Wakefield’s challenge to medical and public health orthodoxy.

    Selection bias? The 1998 Lancet paper was a case series of children referred by medical practitioners. A case series is not a novel event for a medical journal. It is accepted as one method for revealing data that my point to novel hypotheses. There was no pretense by the Dr. Wakefield or the other researchers that the study subjects for the 1998 Lancet paper were blindly selected. Parents came to him with their children upon the medical referral with well documented complaints about onset of bowel disease symptoms post-MMR vaccination. Those parents maintain their claim to this day, and for the most part credit Dr. Wakefield for leading their children to treatments that have improved their quality of life. The paper was transparent about this and never suggested something more, except to call for further scientific inquiry.

    I can see from your comments here and elsewhere in your blogosphere that it is you, Do’C, who is well-practiced at constructing straw men.

    With respect to Grant Jacobs’s notification to readers of this blog that I have a long history of writing to bloggers in this “manner” – do I detect that you have some objection to the “manner” of my posts. If so, please advise me where I may have offended you or your readers. I am surprised because I support my assertions and go to some lengths to maintain a respectful tone. That I have been outspoken on this issue for some time is true, but I would expect that as someone devoted to “science” you would welcome a respectful test to your assertions. Am I mistaken about this?

    Please let me know if you discover the reason why Neurotoxicology withdrew the Primate paper.

  • “The 1998 Lancet paper was a case series of children referred by medical practitioners. A case series is not a novel event for a medical journal. It is accepted as one method for revealing data that my point to novel hypotheses. There was no pretense by the Dr. Wakefield or the other researchers that the study subjects for the 1998 Lancet paper were blindly selected. Parents came to him with their children upon the medical referral with well documented complaints about onset of bowel disease symptoms post-MMR vaccination.”

    Mr. Krakow, a denoted “selection bias” would compromise blind study, which is not the case here as you point out. However, bias in the process of selection relative to the paper’s premise, can also affect the substance of the study. If the study premise is something along the lines that kids had post MMR GI problems, and the study claims to provide insight via case series methodology to study those particular types, it’s a potential problem.

    Certainly you’ve read the GMC decision?

    “Having regard to its findings in relation to Child 1, 9, 5 and 10, namely that these children were admitted to undergo a programme of investigations for research purposes, and that they all lacked a history of gastrointestinal symptoms, the Panel is satisfied that these referrals did not constitute routine referrals to the gastroenterology department… In reaching its decision, the Panel concluded that your description of the referral process as “routine”, when it was not, was irresponsible and misleading and contrary to your duty as a senior author.”

    – Page 46

  • The State of Play? For you it may be all play and games Mr. Jacobs. For parents of autistic children, and the children themselves, it is anything but play.

    Any chance you will be publishing your insights into the causes of autism disorders anytime soon or will you be too busy playing?

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