Wakefield and MMR: New Revelations

November 13, 2011 at 5:01 pm (Anti-Vaccination) (, , , , , , , , , , , , )

A guest blog post from a UK Doctor

New revelations and implications about Andrew Wakefield’s research work.

For anyone who doesn’t know about the ramifications of the Andrew Wakefield saga, here is a brief recap. In 1998 he published a paper in the Lancet journal along with 11 colleagues, detailing bowel changes found in a sequence of children supposedly consecutively referred to his department of Gastroenterology at the Royal Free Hospital in London. The suggestion was that these children’s parents had noticed behavioural or gastrointestinal abnormalities within a very short interval following MMR vaccination. The inference drawn was that MMR might damage the bowel, leading to neurological changes of autism. In a press conference called after the paper was published, Wakefield expressed no faith in the MMR vaccine, and called for single measles vaccines to be used as an alternative.

The media picked up on and widely publicised this dangerous and erroneous message, and soon MMR vaccination rates were falling, from a high of 92% in England in 1998 to around 80% in 2003, well below the levels needed to maintain herd immunity for measles. Matters began to unravel for Wakefield in 2004, following the revelations from a freelance journalist, Brian Deer, who exposed Wakefield’s financial conflicts. 10 of Wakefield’s co-authors, who were unhappy with the linkage drawn to MMR and who were seemingly kept in the dark about Wakefield’s numerous ties with antivaccine litigants and other fatal conflicts of interest, issued a “retraction of interpretation” of the paper.

Formal investigation processes were started by the UK General Medical Council in 2007, and Wakefield and two research colleagues were brought before the GMC on charges of medical misconduct. In 2010 Wakefield was found guilty on all charges and struck off the medical Register, although he refused to acknowledge any culpability and continued to attempt to link vaccines with bowel disease and autism, despite the total lack of any corroborating scientific evidence.

In January this year, Brian Deer published further evidence about the study in the BMJ in a series of articles entitled “How the case against the MMR vaccine was fixed”, which questioned the histological evidence used by Wakefield to show the children in his study suffered from colitis (bowel inflammation). Based upon evidence from the GMC hearings and new evidence from Brian Deer’s investigations, the BMJ described Wakefield’s study as an “elaborate fraud”, and the original publication of the study was formally retracted in full by the Lancet.

Now there have been some new revelations as revealed in this week’s BMJ. It appears that whilst attending a “vaccine safety” conference in the Caribbean last year, Wakefield gave records of the histological gradings used on all the subjects to a fellow conference attendee, David Lewis. Presumably he felt the reports might exonerate him from any responsibility in writing a paper where the reported normal pathology findings somehow changed into “abnormal” findings by the time the paper was submitted, and published. In fact they do nothing of the sort. The pathology grading scores were passed on to the BMJ by Lewis, and the BMJ then sent these out for independent analysis by a panel of expert pathologists.

The results of their review are devastating for Wakefield and his pathologist co-authors. In the majority of cases, bowel biopsies were graded as normal or “non-specific”, in other words there was no evidence of significant colitis (which is what was claimed in the published article). The independent review by the BMJ’s pathologist concurs that these gradings indicate no evidence for colitis. One professor comments:

“We came to an overwhelming and uniform opinion that these reports do not show colitis. Findings for all but one child represent changes within the normal appearance of bowel biopsies, and the changes reported for this child do not amount to colitis. The grading sheets make no provision for quantitative analysis, and the sheets themselves fall far below the standards expected for a research study.

We saw no evidence of enterocolitis, either histologically or in assumed association with reported endoscopic findings of ileal lymphoid nodular hyperplasia, which is a normal feature of young children that sometimes persists into adulthood. In my opinion, and that of those to whom I spoke, there is no justification whatsoever for calling this an enterocolitis.”

So two questions arise. Firstly, who could have changed the interpretation of these negative biopsies and turn them into reports apparently showing active colitis?
And secondly, why did the pathologists who initially correctly graded the biopsies as being “normal” or “non specific” agree to put their names to a paper where the reports were altered to read that they showed major pathological changes?

We can only make a highly educated guess as to the answer to the first question. Perhaps Dr Wakefield, as principal author of the study, who had a vested interest in proving his hypothesis that MMR caused bowel damage and autism, is the likeliest culprit.

As to why the pathologists who co-authored the paper allowed their names to be linked to it, who knows? In academia, one can see the desire to publish research papers is sometimes overwhelming, and might distort otherwise reasoned and rational thought processes. The pressure to get one’s name on a prestigious paper might be enough to make someone turn a blind eye to different emphases or interpretations within a study, or bow to any pressure was brought to bear upon anyone “rocking the boat” by questioning the interpretation of the biopsy results.

Now the BMJ is calling for an independent enquiry into the whole affair, specifically to see whether any underlying institutional research misconduct is revealed at University College London (which took over the Royal Free), and if necessary a Parliamentary inquiry.

This is important. This is not just about Wakefield, it goes to the heart of all studies done by all researchers everywhere. It is vital that those putting their names to research have fully accepted and agreed the content of the research paper and are willing to stand by it. It is imperative that researchers are not pressurised into acceding to the views of other coauthors if they disagree with the study conclusions, interpretation, or the way in which their own work has been presented for publication.

Perhaps one way to ensure that this happens is for every author on a paper to explicitly state that they are in full agreement with all aspects and conclusions of the paper, and that should the paper be found wanting in any aspect of its research methodology or its conclusions, then all authors will accept the ramifications on an equal basis, with no-one being afforded to option of saying “Oh, I just did some statistics, I never actually helped write the study”.

Let’s hope an independent investigation helps reveal the scenarios where any institutionalised misconduct is likely to happen, and that appropriate safeguards can be put in place to preserve the integrity of scientific research and research governance. And let us not fool ourselves that episodes like this Wakefield farrago are rare aberrations, since they are unlikely to be so. Hopefully some good will come out of this whole tawdry episode, and UK research will emerge stronger than ever.

And finally, it would be quite wrong for me to end without quoting one delicious vignette from the BMJ editorial concerning Wakefield’s original 1998 Lancet publication:

“The paper’s first sentence reads: “We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder.” The only truth in this sentence is that the patients were children.”

Ouch! That one’s gotta hurt.

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48 Comments

  1. Alan Henness said,

    Wondering how Wakefield’s supporters are going to be able to contort this one…

  2. mike ward said,

    I love that end bit!!!!

  3. Cybertiger said,

    The ‘UK doctor’ dribbled,

    “Let’s hope an independent investigation helps reveal the scenarios where any institutionalised misconduct is likely to happen, and that appropriate safeguards can be put in place to preserve the integrity of scientific research and research governance.”

    One thing is certain about this ‘guest blogger’, who ever he is, is that he’s a priceless pompous prat.

  4. Cybertiger said,

    The puddled professor piddled out the following priceless poppycock,

    “We came to an overwhelming and uniform opinion that these reports do not show colitis.”

    And the overwhelming and uniform opinions came without looking at a single histological slide. You can’t make this stuff up!

  5. pv said,

    A fool wrote, “And the overwhelming and uniform opinions came without looking at a single histological slide. You can’t make this stuff up!”

    But if Saint Andy of Wakefield presents it in his defense, without a histological slide, that would be ok. You can make that stuff up.

    The idiot ex-GP of Flitwick has been at the meths again and spews forth a stream of ad homs.

  6. Chris said,

    Mr. Henness, they will carry on as before blindly believing everything Wakefield tells them. All they can do is try to smear Brian Deer, oblivious to the fact that even without the fraud a small case series really proved nothing,

    There is more here, with some interesting observations that John Stone was given a comment to post at Nature:
    http://biologyfiles.fieldofscience.com/2011/11/oh-what-tangled-web-we-weave.html

  7. Cybertiger said,

    @Chris

    The evidence suggests that you may be a little dim-witted.

    But you are right; a case series lies at the bottom of the traditional hierarchy of evidence, and proves absolutely nothing. This may be why Wakefield et al stated in their [retracted] paper,

    “We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described.”

    However, the case series is often considered to be hypothesis generating: this may be why at the end of their [retracted] paper, Wakefield et al stated,

    “We have identified a chronic enterocolitis in children that may be related to neuropsychiatric dysfunction. In most cases, onset of symptoms was after measles, mumps, and rubella immunisation. Further investigations are needed to examine this syndrome and its possible relation to this vaccine.”

  8. Cybertiger said,

    @Chris, one of the dim-witted disciples of McScience

    Professor (Dame) Trisha Greenhalgh is a very important GP and ever so scientific. She wrote an awfully clever book called, ‘How to Read a Paper: the basics of evidence-based medicine’. I don’t suppose you’ve read it.

    While she acknowledged that the case series provides weak scientific
    evidence, Professor Greenhalgh, in her book, gave a good example of the case series providing an early warning of vital importance to science and public
    health,

    “A doctor notices that two babies born in his hospital have absent limbs (phocomelia). Both mothers had taken a new drug (thalidomide) in early pregnancy. The doctor wishes to alert his colleagues worldwide to the possibility of drug-related damage as quickly as possible.”

    (Dame) Trisha went on to say that “anyone who thinks ‘quick and dirty’ case reports are never scientifically justified should remember this example.”

  9. Chris said,

    Hmmm, since the paper actually said “We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described.” … then why is there all this fuss?

    If it was not in the paper, what evidence did Wakefield have to suggest parents use separate vaccines and not any of MMR vaccines the twelve children had received. Did he use data from the USA where an MMR vaccine had been used since 1971? Is there evidence that those gastrointestinal/autism issues were seen in American children in the 1970s and 1980s, and where is it?

    And exactly which MMR vaccine was the study on? One of the three used in the UK before 1992, or the one used after 1992?

    And, yes, I agree it is hypothesis generating. But brings about another question, why did Wakefield refuse the Royal Free’s offer to conduct a larger study? If he wrote further investigation was required, why did he not do it?

  10. pv said,

    As I said,
    “The idiot ex-GP of Flitwick has been at the meths again and spews forth a stream of ad homs.”

    Boringly, boringly boring and predictable.

  11. Ben said,

    ” It is imperative that researchers are not pressurised ” don’t you mean “pressured”? They would explode otherwise.

  12. Cybertiger said,

    Of course, jdc523′s guest blogger is not the only priceless prat in the UK,

    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)71125-9/fulltext?version=printerFriendly

    If only the fat lady of MMR had stuck to singing, making cabinets, inventing nappies and having Gordon Brown’s babies.

  13. deetee said,

    Chris, that is really fascinating about John Stone.

    It is quite clear he was posting a comment sent directly to him by David Lewis with instructions to send it to Nature and to pretend it was all Stone’s own work. Yet Stone miserably failed to even get this simple task right, despite 2 attempts at doing so.

    Pehaps Cyberpussy can inform his close friend who the prat really is.

  14. deetee said,

    “The paper’s first sentence reads: “We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder.” The only truth in this sentence is that the patients were children.”

    And if I were the GMC, I’d ask to see the originals of the study childrens’ birth certificates.

  15. Wakefield and MMR: New Revelations | Vaxfax monitor | Scoop.it said,

    [...] Wakefield and MMR: New Revelations A guest blog post from a UK Doctor New revelations and implications about Andrew Wakefield’s research work. For anyone who doesn’t know about the ramifications of the Andrew Wakefield sag… Source: jdc325.wordpress.com [...]

  16. Chris said,

    I see Cybertiger did not even attempt to answer my questions.

    I really want to know what evidence Wakefield used when he announced at the 1998 press conference that the MMR should not be used, but to only use single vaccines. Despite a version being used safely in the USA since 1971.

    I also want to know why he did not take up the Royal Free’s offer to do a larger study.

  17. deetee said,

    Chris, you won’t get an answer, not even an argumentum loquator cum inconsequentia (though he might try his usual argumentum ab contumelias).
    ;)

    It is patently clear that the announcements given by Wakefield at the press conference had nothing to do with the Lancet paper, since as you say there was zero evidence to implicate MMR.

    Indeed, his advice to have single measles vaccine seems highly illogical, since he was trying to implicate not MMR as the cause of the autistic bowel problems, but specifically *measles virus* from the vaccines. So why recommend measles vaccine at all? To do so would be nonsensical if the measles virus was the culprit as he supposedly thought.

    Instead, I think Wakefield was deliberately trying to muddle the distinction between his Lancet research work on the one hand, and his ongoing litigation work against MMR and the incorrect notion that kids might be harmed if they developed what was a rare, mild and inconsequential complication (meningitis) from the Urabe strain mumps virus in the MMR vaccine on the other. He merely wanted to say something bad about the evil MMR, so used the press conference as an opportunity to do so. But the Urabe strain MMR had been withdrawn in 1992, and the problem (meningitis) had not been reported since.

  18. Cybertiger said,

    The original pompous prat has arrived in town. Dr. DeeTee, I presume. How’s the weather in Blackpool?

  19. jdc325 said,

    @Cybertiger – you may not have noticed, but Chris said this earlier today: “I see Cybertiger did not even attempt to answer my questions.”

    Are you going to attempt a response?

  20. Cybertiger said,

    Medical evidence guru, Professor (Dame) Trisha Greenhalgh, has always shovelled sh*t for a living and is now hailed as the champion dung spreader.

    Of course, Dr Godlee is not the only prat to sit atop the medical establishment muck heap.

    In April 2004, the dim-Dame deposited a hot, steaming turd over at Deer Brian’s place (aka http etc, briandeer.com). The prof’s droppings were an allegedly scholarly appraisal of the ‘case series’ paper by Wakefield et al. The daft-Deer loved the fragrance and the noxious poop secured pride of place on the site for more than six years. The Department of Health website – home to Professor (Sir) David Salisbury – even directed people to Brian’s pad,

    http://briandeer.com/mmr/lancet-greenhalgh.htm *

    Wakefield’s paper did not state a research hypothesis so the clever professor made one up. She then went on to state that the study design – a descriptive report on only 12 children – was incapable of proving the hypothesis that had never been stated. Were the study’s conclusions supported by the data? The data supported Wakefield et al’s conclusions, but not the dim-Dame’s made up hypothesis, of course.

    Prof Trish is the original embarrassing body. Yuk!

    * Trish’s crap analysis has now been pooped from Brian’s place. Perhaps the embarrassment finally became too much.

  21. Cybertiger said,

    Chris innocently asked,

    “I also want to know why he did not take up the Royal Free’s offer to do a larger study.”

    Why would Wakefield – or any reasonable scientist – want to do a study under the direction of a mercenary to**er like Professor (Sir) Mark Pepys?

    And the cleverly dim-witted Chris also asked,

    “I really want to know what evidence Wakefield used when he announced at the 1998 press conference that the MMR should not be used, but to only use single vaccines. Despite a version being used safely in the USA since 1971.”

    You could read Andrew Wakefield’s book, ‘Callous Disregard: autism and vaccines – the truth behind a tragedy’. Or this video might be a help,

  22. Chris said,

    Actually, ex-Dr. Tiger, I want the peer reviewed articles from PubMed that Wakefield used as evidence. Just post a list of those articles that pre-date 1998 that show concerns from any MMR, especially those in the USA starting in 1971. Since you are so intimate with the details, you can just list the journal, title, date and authors of the papers used by Wakefield to as evidence for his proclamation.

  23. Chris said,

    You might find this useful, it discusses the flaws with Wakefield’s reasoning:
    MMR vaccine—worries are not justified.

    What is interesting is that Wakefield was never really aware there were multiple versions of MMR vaccines. The biggest difference was which mumps strain was being used. The UK MMR vaccines withdrawn in 1992 were those with the Urabe strain of mumps, due to slightly increase in meningitis.

    The single mumps vaccine parents were sold post 1998 were not approved for use in the UK, and more than likely were the Urabe strain.

  24. Cybertiger said,

    Chris offers convincing evidence that the dim get dumber and solid proof that he/she’s a pudding.

  25. Martin said,

    “As to why the pathologists who co-authored the paper allowed their names to be linked to it, who knows?”

    You could include in your list that the co-authors didn’t bother to check the paper at all, rather than that they semi-knowingly turned a blind eye. After all, whose job is it to check? What form should those checks be? Who checks that the checks have been done? As you say, this goes to the ‘heart of all research everywhere’, but it’s just another example of why this way of disseminating knowledge is not trustworthy.

  26. Cybertiger said,

    @Martin, yet another brainless prat

    “You could include in your list that the co-authors didn’t bother to check the paper at all, rather than that they semi-knowingly turned a blind eye.”

    Have you got a shred of evidence to back up that slur?

  27. draust said,

    On the subject of “Saint Andy’s” attack on MMR at the press conference, and how pre-planned it was, I always found this letter from Wakefield’s mentor Prof Roy Pounder, [one of the documents Brian Deer presumably got from the Royal Free under FoI], quite revealing. Note it was written six weeks before the press conf/publication.

    I have wondered about Prof Pounder’s role in the whole farrago, which has never been properly explained. I would hazard a guess he is one of the ‘senior RFH people’ Godlee was referring to in her editorial. An interesting point is that Pounder was a co-author on virtually everything Wakefield published on MMR and inflammatory bowel problems up to the Lancet paper, on which his name did not appear, even though (as the letter shows) he was clearly involved in what was going on.

  28. Chris said,

    Or Dr. Pounder was taken in by Wakefield psychopathic charm, and really did not understand the actual lack of data in that paper. Amazing that no one realized that an MMR vaccine had been in use in many parts of the world since 1971.

    For those who wish to get a lovely virtual Christmas gifts for Wakefield fanboys (like Cybertiger), please consider getting them this Quaction figure.

  29. Cybertiger said,

    Yesterday, the editor of the BMJ provided readers with treat in corrupt and contorted publishing ethics. There was something of the ‘James and Rupert’ in her offering,

    http://www.bmj.com/rapid-response/2011/11/15/re-pathology-reports-solve-%E2%80%9Cnew-bowel-disease%E2%80%9D-riddle

    To quote the best bit,

    “The second point is that, even if we had concluded that we were obliged to obtain consent, we reasonably anticipated that we would have been unable to obtain it. The BMJ is not and never has been in contact with the patients or their families to the extent that, apart from one parent who has written to us, we don’t know their identities. Furthermore, given (a) the fact that most of the families of the patients in question are known to be dedicated supporters of Andrew Wakefield and opponents of Brian Deer and his work and (b) the tenor of the articles that we were proposing to publish alongside David Lewis’s letter, we reasonably believed that even if we could establish contact with the patients or their families, we would not obtain consent.”

    And then lady of the MMR goes on to say,

    “Third, we considered that there was an overwhelming public interest in publication of the grading sheets and the data they contained …”

    Eh? Overwhelming public interest? Surely the only interest comes from pedantic prats like jdc352 and hateful village-idiots like dr. deetee from Blackpool.

  30. Cybertiger said,

    It is obvious that the public interest would be well served by subjecting dr.deetee to a thorough forensic psychological investigation.

    http://www.thinktwice.com/ploys.htm

    The investigating authorities will no doubt be able to report a full house of ploys deployed by this mean spirited consulting physician from Blackpool.

  31. deetee said,

    Interesting that out of the tactics mentioned in that article, most of them can be applied to Dr Wakefield.

  32. Chris said,

    It was still just a case study of 12 children. And among them there could be up to four different MMR vaccines used (three from the UK, and one American child). There was absolutely no reason it should have been given any weight whatsoever.

    Also, where is the evidence that what was claimed by Wakefield, his fanboys and fangirls started in the USA in 1971?

  33. Cybertiger said,

    “It was still just a case study of 12 children … There was absolutely no reason it should have been given any weight whatsoever.”

    Hurrah! Give the guy a Nobel prize for his stunning quick-wittedness.

  34. Cybertiger said,

    “Interesting that out of the tactics mentioned in that article, most of them can be applied to Dr Wakefield.”

    Whoopee! Give the quack a Nobel prize for stunning originality.

  35. Cybertiger said,

    Whoops, sorry … my mistake … I meant the igNoble for the prize ducks who quack so pathetically … it’ll be Andrew Wakefield who’ll get the real Nobel.

  36. Chris said,

    Okay, so what? You seem too enamored with it. And there have been no replications. Don’t bother with the Gish Gallop on Wakefield’s webpage, it is worthless. There was an honest attempt, but as you can tell from the title it shows Wakefield was wrong:

    Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study.
    Hornig M et al.
    PLoS ONE 2008; 3(9): e3140 doi:10.1371/journal.pone.0003140

    Now where is that evidence that what Wakefield and friends found existed in the USA starting in 1971?

  37. Chris said,

    Oh, and more reasons showing that Wakefield has independently replicated.

  38. Chris said,

    Erg, error… the last sentence shows that Wakefield has not been independently replicated. He is still wrong, wrong, wrongety wrong.

  39. mike ward said,

    Cybertiger – have you not thought of seriously reconsidering your debating tactics after they cause you work problems? At one time I thought you could have a point about statins but lost interest when you started hurling continuous insults like this

  40. pj said,

    To be fair, it has been known for quite some time that these histology findings were being over interpreted:

    “Significant bias was introduced to the studies from the Royal Free by the interpretation of histological changes seen in normal lymphoid follicles as pathology…It is also disturbing that the investigators have not attempted to re-inforce the histopathological diagnosis of enterocolitis by having the slides examined in an open forum by independent pathologists, especially since another small series has found no abnormalities…

    There is no evidence from the papers discussed above that a significant number of autistic children have ‘enteritis’, i.e. inflammation of the small intestine. The only consistent abnormality seen in these children may be ILNH, but we have explained why this finding is not unexpected in constipated individuals…”

  41. Cybertiger said,

    @mike ward, tuneless chorister for the goon show

    What have my opinions on statins – whatever they are – or however they’re phrased – got to do with the price of fish? And I naively thought you sciencey types looked dispassionately at the evidence, and only the scientific evidence. Idiot!

  42. Cybertiger said,

    Come on, give us a song: what do the goon show choristers think of this recent letter to the BMJ? Or is it all a bit too sciencey?

    http://www.bmj.com/content/343/bmj.d6985?tab=responses

    The choristers = UK doctor, dr. deetee of Blackpool, Chris & mike ward (aka dim and dumber) and jdc352, tweeting twitterer.

  43. Cybertiger said,

    Of course the chorister line up also includes, UK scientist, dr.drippy draust, pj the tittish banana-pyjama, Martin, that other brainless twat, and pv the poppycock prat.

  44. Cybertiger said,

    Of course the lead singers in the cabaret are Deer & Godlee (aka dr.evadne and dame hilda unhinged).

    http://gaia-health.com/gaia-blog/2011-11-18/another-nail-in-the-coffin-of-the-case-against-wakefield-pathologist-speaks-out/

  45. Chris said,

    Ex-Dr. Struthers, what evidence do you have that the autism issues with the MMR vaccine started when it was introduced in the USA in 1971?

    And why do we care what you think?

  46. Mike Ward said,

    Cybertiger – who would have won in a fight between you and that guy you threatened? You lost your job over it so you must have thought about it. Satisfy my curiosity as I have given up getting any sense out of you

  47. Cybertiger said,

    Dim & Dumber are singing for their supper. Twits.

  48. Chris said,

    So, you won’t answer my question? Why? You are calling me dim, then do try to educate me by answering my question.

    Just list the title, journal, date and authors of the papers written before 1997 that show there was a problem with the MMR causing autism in the USA starting in 1971. Surely, you know where Wakefield came up with his evidence to support his statements in the press release that were not evidence in his Lancet paper.

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