Wakefield’s “autistic enterocolitis” under the microscope
BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c1127 (Published 15 April 2010) Cite this as: BMJ 2010;340:c1127
All rapid responses
I can assure Clifford Miller I am not confusing different issues, but
remain very focused on the topic under discussion.
Those with autism do develop bowel disorders, but all the available
evidence has shown that there is no particular form of gastrointestinal
disease specific to autism such as "autistic enterocolitis"(1).
I remain open to the possiblitiy of future studies demonstrating just
such a pathology, but at the present time there is absolutely no credible
evidence. This fact will not alter, no matter how much Mr Miller resorts
to quoting red herrings about urinary metabolites, or mentioning
irrelevant items that appear in the Daily Telegraph.
I prefer to remain informed by scientific evidence, and not to
swallow whatever journalistic opinion is pumped out by the media. I would
have thought that this would have been a lesson well learned over the last
10 years or so of the Wakefield debacle.
(1) Evaluation, Diagnosis, and Treatment of Gastrointestinal
Disorders in Individuals With ASDs: A Consensus Report.
http://pediatrics.aappublications.org/cgi/reprint/125/Supplement_1/S1
Competing interests:
None declared
Competing interests: No competing interests
Re: Wakefield’s Lancet Paper Vindicated – [Yet Again]
Editor,
The deregistration of Dr Wakefield and Professor Walker-Smith is
beginning to look more like a Conspiracy than a Stuff Up.
None of the accusers have attempted to explain the profound metabolic
changes in the urine of MMR treated children reported by Wakefield et
al{1} and now confirmed.[2]
Surely the GMC should have asked their experts if Methylmalonicacid
urea could cause Cobalamine deficiency and Autism.
" In infants, cobalamin deficiency may present as failure to thrive,
developmental delays or regression, progressive or persistent neurologic
disorders, or hematologic changes" [3 ]- precisely what one would expect
in children with gastrointestinal symptoms with "Autism Spectrum Disorder
and Language Regression".[4].
It's time for the Truth.
Michael Innis
References;
1. Wakefield, AJ, Murch SH, Anthony A, Linnell J, et al; Ileal-
lymphoid-nodular hyperplasia, non-specific colitis, and pervasive
developmental disorder in childrem The Lancet vol 351; 1998
2. Children with autism have a different chemical fingerprint in
their urine than non-autistic children, Imperial College News Release
Thursday 3 June 2010,
3. Bjørke-Monsen AL, Torsvik I, Sætran H, Markestad T,et al; Common
Metabolic Profile in Infants Indicating Impaired Cobalamin Status Responds
to Cobalamin Supplementation PEDIATRICS Vol. 122 No. 1 July 2008, pp. 83-
91 (doi:10.1542/peds.2007-2716)
4. Valicenti-McDermott MD, McVicar K, Cohen HJ, Wershil BK et al;
Gastrointestinal Symptoms in Children with an Autism Spectrum Disorder and
Language Regression. Pediatric Neurology vol 39 2008; p392-98.
Competing interests:
I have reported adverse vaccine reactions previously
Competing interests: No competing interests
I am grateful to Dr Peter Flegg for his response [1]. Dr Flegg appears to confuse and conflate two very different issues.
The issue to which these responses are directed is an article [2] which quoted this statement "Researchers at the Royal Free Hospital School of Medicinemay have discovered a new syndrome in children involving a newinflammatory bowel disease and autism2". It is beyond question that bowel disease and autism are now clearly linked and the original Royal Free hospital's findings as published in 1998 in The Lancet have been replicated by numerous papers internationally as cited in the footnotes here [3].
It also seems that Dr James Le Fanu appears as unconvinced by the GMC panel's decision on Walker-Smith, Wakefield and Murch as he is that the MMR vaccine is not implicated as a causal agent of autistic conditions.
Writing today in The Telegraph Dr Le Fanu states "the General Medical Council's recent ruling to strike professors Andrew Wakefield and John Walker-Smith off the register had the fingerprints of the medical establishment all over it." ....... "It seems only sensible, given this moral confusion that would portray a decent and honest man as deceitful and exploitative, to reserve judgment about the GMC's verdict and to speculate what lies behind it. Leaving aside the question of whether the MMR vaccine is implicated in this form of autism – as the parents' accounts would certainly suggest – it is perhaps not unreasonable to detect the hidden hand of those powerful forces for whom the crushing of a professional reputation is a price worth paying for the continuation of the ever-expanding child immunisation programme.": The hidden hand of powerful forces: James Le Fanu, 07 Jun 2010.
Competing interests:
None declared
Competing interests: I am grateful to Dr Peter Flegg for his response [
Mr Miller needs to be rather more critical and less credulous before
he leaps to the conclusion that any and every newly published paper about
the gut and autism somehow automatically verifies Wakefield's discredited
hypothesis.
Let's be clear on what this study(1) reveals. It looked at urinary
metabolite differences between autistic children, their siblings, and
other age matched controls. The changes found suggest autistic children
(and their non-autistic siblings) have differences in bowel flora
metabolism.
Judging from the uncritical news coverage, one would imagine this
study has identifed a diagnostic test for autism that can be used early
enough in life to help "prevent" autism. But this is not what the authors
say. They specifically state that the differences demonstrated might be
the result of autism, rather than a predictive biomarker for its
development. In other words, it may just be a coincidental marker, and be
quite irrelevant in terms of the pathogenesis of autism. Indeed the
authors are quite clear that they were merely looking for biomarkers of
autism, and drew no conclusions about any putative role the gut might have
in the development autism. The changes found may indicate underlying
metabolic differences between autistics and non-autistics, but the fact
that this may manifest in the way the authors found in no way implicates
extrinsic gut damage (eg measles virus) as the crucial pathogenetic
trigger.
The authors also state that biomarkers found during established
disease vary considerably from those found in early disease, so their
findings would not necessarily be replicated if one analysed infants who
were showing very early autistic changes. They also stated that larger
longitudinal studies need to be performed to clarify this.
None of these conclusions has any relevance to the concept from
Wakefield that vaccine measles virus (and only MMR vaccine virus at that,
but not monovalent vaccine measles or natural measles virus) damages the
gut to cause lymphonodular hyperplasia and colitis, leading to a leaky gut
which allows possible neurotoxins to enter the portal circulation and
subsequently cause autism.
There are also a number of caveats about this paper. The study used
age matched controls, but there was no attempt to match for the most
relevant overiding driver of bowel flora differences, namely their diet.
Diets of children with established autism can differ radically from the
normal, for many reasons. Cases and some controls came from South
Australia, but the other controls came from Switzerland. Although there
were no apparent metabolic differences between controls from different
countries, one wonders why additional controls had to be recruited from a
different hemisphere.
In addition the paper showed that the non-autistic siblings of autism
cases had a similar metabolic profile. Why was that? Three possible
reasons spring to mind: Either there were no real differences between any
of the groups and the biomarkers are not that discriminating, or the
siblings were also latently autistic (but for some reason not manifesting
this yet), or the differences are more consistent with another factor such
as diet. Of the three possibilities, the last looks to be the likeliest to
me.
I think we need to see followup and extension of this work before it
is clear whether it indicates a consistent and reproducible biomarker for
autism, and considerably more work to understand what this means in terms
of pathogenesis. It is sad to find this study is yet another straw that
Wakefield's supporters are desperately grasping at in their attempts to
vindicate him.
(1) Urinary Metabolic Phenotyping Differentiates Children with Autism
from Their Unaffected Siblings and Age-Matched Controls.
Ivan K. S. Yap, Manya Angley, Kirill A. Veselkov, Elaine Holmes, John C.
Lindon, and Jeremy K. Nicholson.
Journal of Proteome Research 2010; 9:2996–3004.
Competing interests:
None declared
Competing interests: No competing interests
The citation and link to the abstract of the just published research from Imperial College [noted by Jenny H Allan's Response [3]] appears to support just such a claim.
The Imperial College, London research's remarkable specificity appears to support the Wakefield, Walker-Smith et al original finding and takes the matter significantly further. "People with autism are also known to suffer from gastrointestinal disorders and they have a different makeup of bacteria in their guts from non-autistic people. Today's research shows that it is possible to distinguish between autistic and non-autistic children by looking at the by-products of gut bacteria and the body’s metabolic processes in the children's urine. The exact biological significance of gastrointestinal disorders in the development of autism is unknown" [4]
[1] Gastrointestinal disorders common in individuals with ASDs Dr Peter Flegg Consultant Physician Blackpool BMJ Responses 26 May 2010
[2] Gastrointestinal disorders common in individuals with ASDs - John A. Dodge, Hon Prof of Child Health, University of Wales Swansea - BMJ Responses 27 May 2010
[3] Wakefield’s Lancet Paper Vindicated – [Yet Again] Jenny H Allan BMJ Responses 4 June 2010
[4] : Children with autism have a different chemical fingerprint in their urine than non-autistic children, Imperial College News Release Thursday 3 June 2010, "Urinary Metabolic Phenotyping Differentiates Children with Autism from Their Unaffected Siblings and Age-Matched Controls," Journal of Proteome Research, published in print 4 June 2010. [Added 5 June 2010]
Competing interests:
None declared
Competing interests: Evidence from emerging papers suggests in support of the 1998 Lancet published finding of Walker-Smith, Murch Wakefield et al that Dr Flegg may not be correct in suggesting that children with regressive autism or indeed any form of autism do not have a unique, specific and distinctive form of bowel disease [1]. Professor Dodge may also therefore be premature in agreeing with Dr Flegg that no-one has claimed this. [2]
Recently published research findings from a joint study conducted by
researchers at Imperial College London and the University of South
Australia acknowledges that persons with autism are also known to suffer
from gastrointestinal disorders. These researchers have now devised a
simple urine test to diagnose autism in young children. This was based on
the researchers' findings of differences within the gut flora and
metabolic functions of children with autism. It is also tacitly
acknowleged by these research scientists,(and presumably the entire
medical establishment)that early intervention can enormously improve the
prognoses for these children. As Lorene Amat, from the Autism Treatment
Trust, also suggests, via her response to Brian Deer's article, these
children have been badly let down and neglected due to the UK medical
establishment's ostrich like denials and vilification of Wakefield, Walker
Smith and Murch who were all concerned with helping and treating our
affected children. As Lorene Amet says 'It is time to move on'.
Professor Jeremy Nicholson et al 'Autism finding could lead to simple
urine test for the condition.' Journal of Protoeme research' Press release
3-Jun-2010. (Daily Mail, Daily Telegraph, Eurek Alert etc.)
Competing interests:
Grandson with autism and bowel problems
Competing interests: No competing interests
Declan Fox asks 'What about the children?' What I would like to ask
is why have neither the GMC and BMJ nor anyone else within the UK medical
establishment asked this question before? Surely these twelve Lancet
children should have been 'central' to any investigation about whether
autistic enterocolitis or any other bowel syndromes exist as a condition
specifically associated with autistic persons?
My Grandson was not one of the original Wakefield twelve; he was part of a
later group of children treated at the Royal Free Hospital by Professors
Walker Smith and Murch. My daughter was told that he had exactly the same
bowel condition as the rest.
My Grandson is now seventeen and will soon become a voting adult. Yes, he
still suffers a lot of pain and discomfort from his bowel problems and yes
he is still autistic. (Both of these conditions are life long ones; there
is presently no cure). Fortunately he is a very high functioning
Asperger's autism case and is now becoming only too well aware of the
injustices that have been done to him by a very uncaring NHS system which
seems less concerned with his wellbeing than in following a government
imposed politically correct agenda.
My Grandson now lives in Scotland and regularly attends both neurological
and gastro clinics. His epilepsy is very well controlled and monitored by
the neurologists; his autism needs have been left to the education
department. The doctors in the gastro clinics take one look at his
casenotes and run scared at the sight of the dreaded names 'Walker Smith'
'Murch' and horror of horrors, 'Wakefield'!! Officially his impacted bowel
is 'chronic constipation' for which he is prescribed an assortment of
laxative bottles. We have learned from experience how to best ameliorate
his condition using dietary interventions. He is a lovely young man and we
are all very proud of him.
Competing interests:
Grandson with autism
Competing interests: No competing interests
Declan Fox wonders at the fate of the children that Wakefield
studied. They may all be chronically constipated, but the medical
community will never really know if constipation was their true fate. Of
course, there were never just twelve children studied by Wakefield and his
colleagues. In a statement published in the Lancet in March 2004,
Professor John Walker-Smith indicated that a further forty children had
been investigated, thirty-nine with the syndrome reported, before the
retracted paper was published. Walker-Smith went on to say,
“The children were all investigated specifically and exclusively by
clinical need to determine whether bowel inflammation was present that
could then be appropriately treated”. [1]
Perhaps they all turned out to be constipated kids. Who knows?
In February this year, a few days after judgment had been passed on
Wakefield and Professors Walker-Smith and Murch, a paper destined to be
published in ‘Neurotoxicology’, another Elsevier journal, was suddenly
withdrawn. The subjects of the study (co-authored by Andrew Wakefield)
were twenty nursery-reared rhesus macaque infants. [2] The fate of these
infants now appears to have been struck from the scientific record. What
scientist will dare follow up on the twenty, tiny rhesus monkeys? And
isn’t Dr Fox being a little naïve in wondering what happened to the fifty-
two Wakefield children?
[1] A statement by Professor John Walker-Smith. The Lancet, Volume
363, Issue 9411, Pages 822 - 823, 6 March 2004.doi:10.1016/S0140-
6736(04)15709-7.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)15709-
7/fulltext
[2] Accepted Manuscript. Title: Delayed Acquisition of Neonatal
Reflexes in newborn Primates receiving a Thimerosal-containing Hepatitis B
Vaccine: influence of gestational age and Birth weight. Authors: Laura
Hewitson, Lisa A. Houser, Carol Stott, Gene Sackett, Jaime L. Tomko, David
Atwood, Lisa Blue, E. Railey White, Andrew J. Wakefield.
http://www.rescuepost.com/files/hewitson-et-al-09-primate-hbv-study.pdf
Competing interests:
None declared
Competing interests: No competing interests
In all the reports and correspondence about this sad affair, I have
read nothing about the fate of the children Wakefield studied. Has there
been any kind of follow-up, medical or GI? Did they in fact go on to
develop any kind of chronic colitis? Or was it all down to chronic
constipation?
Yours etc
Declan Fox
Competing interests:
None declared
Competing interests: No competing interests
Re: The consensus on bowel disorders in autism.
Editor,
While Peter Flegg thinks Clifford Miller "resorts to quoting red
herrings about urinary metabolites" others, including me, think the
demonstration of urinary metabolites such as Methymalonic acid is AN
IMPORTANT CLUE to an understanding of the pathogenesis of pervasive
developmental disorder in children.
On the strength of the finding in the urine Wakefield et al; pointed
out that "B12 deficiency may therefore, be a contributory factor in
developmental regression", ---red herring or pearls before swine?
Michael Innis.
Competing interests:
None declared
Competing interests: No competing interests