Wakefield was right! Or not

Autism-bacteriaAndrew Wakefield is a figure who polarises opinion.

To quacks, cranks, and especially antivaccinationists, he is a Brave Maverick Doctor who blew the whistle on the vaccine industry and found the One True Cause of autism.

To the reality-based community he is an unethical quack, struck off for dishonesty and conducting invasive experiments on vulnerable children without proper consent or ethical oversight, reviled for publishing fraudulent research without declaring massive conflicts of interest, and demonised as a significant cause of a resurgence in measles leading to permanent harm and even death.

You might be able to guess which camp we fall into.

Antivaccinationists desperately want Wakefield to be right, even though he wasn’t. So any study showing any kind of link between intestinal disorders and autism is portrayed as vindication, regardless of the actual facts.

In this short piece WDDTY seek to vindicate Wakefield by reference to a study, Reduced Incidence of Prevotella and Other Fermenters in Intestinal Microflora of Autistic Children, Kang et. al., PLoS ONE, 2013; 8: e68322.

“We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described” – Wakefield et. al, 1998

The first thing to note is that the PLoS ONE article does not cite Wakefield’s work. Some will think this is because Wakefield is a pariah, others will know that his work has been retracted so won’t be cited, but the real reason is that the finding has absolutely nothing to do with Wakefield’s hypothesis.

Say it quietly, but the first part of maligned doctor Andrew Wakefield’s theory about the MMR (measles–mumps–rubella) vaccine and autism has been proved right: autistic children do have low levels of three critical bacteria in their gut.

No! Not even close. Wakefield’s claim was that autism is caused by “autistic enterocolitis” triggered by the MMR vaccine. You don’t have to take my word for it, the full text is available on The Lancet website (free registration required). No part of Wakefield’s paper is in any way supported by the new work!

Doctors know that autistic children usually have a range of gut problems, so researchers at Arizona State University decided to find out if it was more than a coincidence. They analyzed the gut flora of 20 autistic children aged between three and 16 years and compared them with samples from 20 typical non-autistic children. The autistic children had fewer types of gut bacteria in general and were also low in three critical varieties: Prevotella, Coprococcus and members of the Veillonellaceae family. Of these, Prevotella species are the most important as they play a vital role in gut interaction.

This is entirely unrelated to Wakefield’s claims, which in any case were admitted in the paper (though not by implication in his grossly irresponsible press statement) not to be provably causal:

“We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.”

The triggers were identified as MMR in eight cases and measles infection in one. And the claims were quite specific:

Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with agematched controls (p=0·003), low haemoglobin in four children, and a low serum IgA in four children.

The research was funded by a payment of £55,000 to the Royal Free Hospital by a firm of lawyers engaged in preparing a suit against the manufacturers of the MMR vaccine. It subsequently emerged that a further £400,000 had been paid to Wakefield himself. The lawyers also recruited some of the children in the study. None of this was declared in the published output.

It has also subsequently emerged that the PCR tests that Wakefield claimed identified measles virus in the gut of autistic children, was the result of contamination.

So Wakefield’s thesis was:

  • Autism is caused by enterocolitis
  • This enterocolitis is triggered by the measles virus

Both of these claims are wrong. And the PLoS ONE study does not in any way challenge that. In fact even Wakefield’s own original paper does not support it, it contains the following statement:

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

The PLoS ONE paper does not find evidence of measles virus in the gut, or of a form of enterocolitis. It doesn’t use the term enterocolitis. the signature features claimed by Wakefield et. al include lymphoid nodular hyperplasia and aphthoid ulceration. Neither of these is mentioned in the PLoS ONE paper. The PLoS ONE paper mentions PrevotellaCoprococcus, and unclassified Veillonellaceae. Wakefield et. al. make no mention of these, its only mention of bacteria is screening for evidence of campylobacter, salmonella, shigella and yersinia – in other words specifically ruling out bacteria as a cause of the purported enterocolitis. No mention is made of the level or makeup of gut flora.

It does not claim to find a causal relationship, in fact it states that:

[T]he direction of causality among interconnected pathophysiological factors (e.g., autistic symptoms, diet patterns, GI symptoms, and gut microbiome profile) is still unclear

It does not identify a distinct “autistic enterocolitis”, but a “relatively low level” of gut flora, specifically a reduction in diversity.

It concludes:

In summary, we demonstrated that autism is closely associated with a distinct gut microflora that can be characterized by reduced richness and diversity as well as by altered composition and structure of microbial community. Most notably, we also discovered that the genera PrevotellaCoprococcus, and unclassified Veillonellaceae were significantly reduced in autistic children. Unexpectedly, these microbial changes were more closely linked to the presence of autistic symptoms rather than to the severity of GI symptoms and specific diet/supplement regimens. Despite limited information on the direction of causality among autism, diet, GI problems, and microbiome profiles, the findings from this study are stepping-stones for better understanding of the crosstalk between gut microbiota and autism, which may provide potential targets for diagnosis or treatment of neurological as well as GI symptoms in autistic children.

To infer from this that Wakefield is in any way vindicated, is to engage in wishful thinking of the most fanciful kind. The two are related only in as much as they both involve the gut – and given the drivers for Wakefield’s work this is almost certainly pure coincidence.

What Doctors Don't Tell You
Why don’t doctors tell you that new research vindicates Andrew Wakefield?

Because it doesn’t.

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