March 21, 2008

The Wakefield Witch-Hunt

The Wakefield witch-hunt
Friday, 21st March 2008
The Spectator

A couple of days ago, yet another story appeared claiming that fresh research had shown that there was no link between the MMR vaccination and autism. This new research was said to have shown that, contrary to the claims made by Dr Andrew Wakefield, the surgeon at the centre of the MMR scare, there was no relationship between gut problems and autism, the core of his concerns. It also claimed that the discovery furthermore damaged the related theory that a gluten-free diet could help children with autism.

Dr Hilary Cass, from Great Ormond Street, said: ‘It is very distressing to have a diagnosis of autism, a lifelong condition.Many families are driven to try out interventions which currently have no scientific basis. For example, advocates of the leaky gut hypothesis offer children a casein and gluten-free diet which as yet lacks an evidence base.’

This particular observation is a telling indication that this study bears little relation to reality. For there are countless families whose autistic children’s suffering from gut problems has only been eased, and their autistic symptoms improved, by the introduction of precisely such a diet. ‘No evidence base’? Tell that to those families. It is their lived experience.

Second, despite the way this was presented in the media this is not a new piece of research at all. It is instead a recycled version of a study by Baird G. et al, published in the Archive of Diseases in Childhood on February 5 and reported in the press around that time. The study drew the following response from Andrew Wakefield:

…The study is severely limited by case definition in the context of the crucial ‘possible enterocolitis’ group. For inclusion in this group they required the presence of two or more of the following five current gastrointestinal symptoms:

* current persistent diarrhea (defined as watery/loose stools three or more times per day >14 days),
* current persistent vomiting (occurring at least once per day, or more than five times per week),
* current weight loss,
* current persistent abdominal pain (3 or more episodes [frequency not specified by authors] severe enough to interfere with activity);
* current blood in stool;


* past persistent diarrhea >14 days’ duration, and excluding current constipation.

We have over the last 10 years evaluated several thousand children on the autistic spectrum who have significant gastrointestinal symptoms. Upper and lower endoscopy and surgical histology have identified mucosal inflammation in excess of 80% of these children. Almost none of these children with biopsy-proven enterocolitis would fit the criteria set out above. Firstly, these children rarely have vomiting, current weight loss (as opposed to failure to gain weight in an age-appropriate manner), or passage of blood per rectum. The requirement is thus narrowed to a child having two of two relevant symptoms – current persistent diarrhea and current abdominal pain according to their criteria, plus a past history of persistent diarrhea excluding current constipation.

The requirement for the current presence of these symptoms, for 14 or more days continuously, shows a singular lack of understanding of the episodic, fluctuating, and alternating (e.g. diarrhea/constipation) symptom profile experienced by these children. In our experience, ASD children with histologic enterocolitis typically have 1 to 2 unformed stools per day that are very malodorous and usually contain a variety of undigested foodstuffs. This pattern alternates with that of “constipation” in which the unformed stool is passed after many days of no bowel movements at all, and with excessive straining. This group is entirely overlooked by the arbitrary criteria set forth in their paper. With respect to diarrhea and constipation, a detailed discussion of stool pattern in these children is available1 which further highlights the shortcomings of the above criteria. Moreover, the interpretation of pain as a symptom in non-verbal children, as it often manifests as self injury, aggressive outbursts, sleep disturbances, and abnormal posturing, is notoriously difficult. This interpretation requires an insight based upon the correlation of symptoms, histological findings, and response of symptoms to anti-inflammatory treatment. There is no evidence in the Baird et al. paper that these crucial factors were taken into account. This study’s inappropriate symptom criteria would explain the discordance with other reports that have revealed a high prevalence of significant gastrointestinal symptoms in general autism populations2,3.

It is surprising that Dr Peter Sullivan, a co-author on the paper, who presumably provided the above gastroenterological criteria, was not aware of the aforementioned limitations. In his role as a Defendant’s expert in the UK MMR litigation, he will have had access to the clinical records of autistic children with the relevant intestinal symptoms and biopsy-proven intestinal inflammation.

We suggest that the authors might wish to reflect on the ethical implications of setting the bar too high for the investigation of such children by ileo-colonoscopy, with the attendant risk of missing symptomatic, treatable inflammation.

Since the relevant MMR/autism children are considered to be those with regression and significant gastrointestinal symptoms, the appropriate stratification for between-group analyses of measles virus antibody levels has not been conducted; therefore the paper is difficult to interpret, adding little if anything to the issue of causation. Moreover, it is a major error to have presumed that peripheral blood mononuclear cells are a valid ‘proxy’ for gut mucosal lymphoid tissues when searching for persistent viral genetic material.

A further major problem in this study is the number of children who dropped out or who were unable to provide adequate blood samples. We know nothing about either the 735 children who were lost at stage two, or the 100 children for whom blood samples were not available. At the very least, we should be told whether the children who dropped out were likely to be representative of those who stayed in, with regard to the key issues of interest.

For reasons that will emerge in the near future, it would be of interest to know whether siblings of autistic children were included in either of the two control groups. This information is not provided.

As a general observation, this paper contributes nothing to the issue of causation, one way or another. Case definition alone is likely to have obscured the relevant group of autistic children. The study tells us nothing about what actually happened to the children at the time of exposure. We are increasingly persuaded that measuring things in blood many years down the line tells us very little about the initiating events in what is, in effect, a static (non-progressive) encephalopathy unlike, for example, subacute sclerosing panencephalitis, which is a progressive measles encephalopathy. The gut is a different matter, and analysis of mucosal tissues has been very informative, since here, in the relevant children, active ongoing, possibly progressive [AV1]4, inflammation has been identified.

None of Wakefield’s pointers to the irrelevance of or inadequacies in the Baird research was included in the news stories. Nor do these stories refer to other research studies which show a higher rate of gastro-intestinal problems among children with autistic-spectrum symptoms. The recycling of the Baird study was but the latest in a steady drip-feed of such items which appear to be part of a concerted campaign to ensure that the General Medical Council hearing into the conduct of Wakefield’s research, which is shortly due to resume, takes place in as prejudiced an atmosphere as possible. No stone is being left unturned by the medico-political establishment and its creatures in the media to ensure that this doctor is destroyed.

As I have repeatedly said, I have no idea whether Wakefield is correct or not in his concerns about the possible adverse effects of the MMR vaccine on a small sub-set of vaccinated children. Nor do I know whether any of the charges being levelled against him at the GMC has any legs. But I do believe — as I wrote in my series of articles on the subject for the Daily Mail in 2003 here, here and here — that many of the statements made by the Department of Health and medical establishment about the ‘proof’ of the vaccine’s unchallengeable safety are deeply misleading. And I also believe, having spoken to many parents of such children, that their experiences simply cannot be dismissed as they have been by the medical establishment. No-one has ever suggested that the MMR vaccine causes all or most of the incidence of autism. If Wakefield is correct, it is only a small proportion of children whose immune systems may be unable to cope, for whatever reason, which makes them particularly vulnerable to such ill-effects. And contrary to the message being pumped out by the medical establishment that the vaccine has been proved to be safe — by studies which are all either flawed, inadequate or irrelevant — the fairest and most accurate thing to say is that the jury is still out.

One of the most reprehensible weapons being wielded in the witch-hunt against Wakefield is the claim that anyone who gives any credence whatever to his concerns is responsible for the incidence of measles amongst children whose parents are as a result too frightened to give them the MMR vaccination. There are two obvious points to make in response to this piece of moral blackmail: 1) the whole panic could have been avoided by offering single measles, mumps and rubella jabs rather than the triple MMR, and 2) it is surely just as important as avoiding cases of measles mumps and rubella to avoid causing the kind of catastrophic damage to the brain and gut displayed by the children at the heart of this controversy.

And there is a further and quite appalling point to note. This whole saga started because parents of such children found that their family doctors were dismissing out of hand their children’s gut and brain problems, accordingly refusing to alleviate their suffering. Now, as a direct result of the animosity towards Wakefield that has been whipped up — and the fear that any doctor who suggests he might be right will similarly find him or herself at the receiving end of the medical establishment’s fist — children exhibiting this combination of gut and brain damage are finding it difficult to obtain treatment.

Another letter to the Archive of Diseases in Childhood from John Stone, the parent of an autistic child, makes terrifying and distressing reading:

In this regard it is worth noting the recent warning of the National Autistic Society (NAS):

‘The National Autistic Society is keenly aware of the concerns of parents surrounding suggested links between autism and the MMR vaccine. The charity is concerned that the GMC hearing, and surrounding media coverage, will create further confusion and make it even more difficult for parents to access appropriate medical advice for their children. It is particularly important that this case is not allowed to increase the lack of sympathy that some parents of children with autism have encountered from health professionals, particularly on suspected gut and bowel problems. Parents have reported to the NAS that in some cases their concerns have been dismissed as hysteria following previous publicity around the MMR vaccine. It is crucial that health professionals listen to parents' concerns and respect their views as the experts on their individual children…’

The NAS warning relates to the GMC hearing involving doctors Wakefield, Walker-Smith and Murch which is set to resume on 25 March approaching. I do not think it is being unduly cynical to query the publication of this study at the present time as a media event, bearing in mind that it seems to have been carried out five or six years ago. Moreover, the study has once again been promoted as refuting the Wakefield hypothesis when it in fact tests for a possibility that had not been proposed. Meanwhile, the plight of autistic children with gastro- intestinal symptoms is excluded both from the study and public attention, as if they did not exist. The NAS statement warned of ‘creating further confusion’ and this is precisely what this study and its media exposure has done.

As the resumption of the GMC hearing draws nearer, one has to ask whether this will serve the cause of truth and justice and the relief of suffering — or is it instead merely a show trial which will bring about the precise opposite?

1 comment:

Ivar T said...

It has been reiterated that the study doesn't say anything about the benefit of diet.

They just found that the peptide in urine tests can't determine whether a diet would have any benefit.