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.