BBC News just made the following announcement:
The doctor who first suggested a link between MMR vaccinations and autism acted unethically, the official medical regulator has found.
Dr Andrew Wakefield's 1998 Lancet study caused vaccination rates to plummet, resulting in a rise in measles - but the findings were later discredited.
The General Medical Council ruled he had acted "dishonestly and irresponsibly" in doing his research.
Afterwards, Dr Wakefield said the claims were "unfounded and unjust".
It's important to note that the council did not rule one way or another on Wakefield's findings, but rather on his research methods (which included paying children at a birthday party for blood samples and conducting unnecessary and invasive medical tests).
The audience at the hearing included a number of Wakefield's supporters, who referred to the process as a "Kangaroo Court." Indeed, Wakefield himself addressed the crowd, telling them:
"The allegations against me and my colleagues are unfounded and unjust and I invite anyone to examine the contents of these proceedings and come to their own conclusions....I want to reassure [my supporters] that the science will continue in earnest."
The politics behind his legal troubles are head spinning, however, I do think he may have been a bit too zealous and stepped over some boundary. Birthday party blood? Certainly that sounds odd, but do we know how much these parents supported him in his efforts and were more than willing to do their part in helping him. We don’t know that the children with gastro problems were given tests that wouldn’t already have “perhaps” been called for, yet again, he may have crossed the line. I haven’t heard that his results were wrong. He found what he found, it hasn’t been said he lied. No one can or should or would reproduce his study, leaving so many” motivated” studies paid for to assure us ,without any science, that he was wrong. Is this any more ethical? I think the “simpsonwood transcripts” disclose enough to stop taking assurances that vaccines don’t cause autism. MMR likely will be found to not be the initiator of autism, possibly it’s an enhancer, in the way that dpt enhances host vs graft.
This is a travesty of justice, and most of the reporting in the news has been abominable. None of the parents of the children Dr. Wakefield treated complained about him. They were just so happy that he was investigating their children’s severe bowel issues. His work has been replicated. He is a responsible competant doctor responding to concerns raised by his patients and their parents. This prosecution is outrageous.
h t t p : / / w w w .ageofautism.com/2010/01/a-short-form-faq-about-the-wakefield-gmc-case.html
h t t p : / / w w w .autismfile.com/
See the movie “Selective Hearing, Brian Deer and the GMC”
at http://www.viddler.com/explore/ziggy/videos/1/
I cannot think of any medically justified reason for giving a child with gastronintestinal problems a lumbar puncture, which is an incredibly painful and potentially dangerous procedure.
Twyla, I have only skimmed the surface on the Wakefield issue, and as I said, the motivation behind Deer and the suit is headspinning. The influences behind Deer, the connections to the courts…it seems all very much designed by powerful people… I didn’t know his study had been replicated..yet it’s always been clear that NO ONE can deny his results as honest and scientific. it appears as a witch hunt in progress.
So far as I know, Wakefield’s results have not been replicated… but perhaps you have citations?
A confounding factor here may be the question of WHO did the replicating. That is, there are researchers who are close to Wakefield whose findings may be questionable because of their relationship. Or there may be studies which suggest that some of Wakefield’s theories may be correct but which don’t literally replicate his work.
Lisa
One of the main findings in Dr. Wakefield’s paper is the presence of inflammation in the bowel, including “lymphonodular hyperplasia”. This was recently replicated in the paper shown below.
I’m not a scientist and not the best person to answer the question of replication, but I’ll do my best to post some more info.
***
Clinical Presentation and Histologic Findings at Ileocolonoscopy in Children with Autistic Spectrum Disorder and Chronic Gastrointestinal Symptoms
Authors: Arthur Krigsman, Marvin Boris, Alan Goldblatt and Carol Stott
Publication Date: 27 Jan 2010
Autism Insights 2010:2 1-11
Arthur Krigsman1, Marvin Boris2, Alan Goldblatt3 and Carol Stott4
1Assistant Professor of Pediatrics, New York University School of Medicine Director of Gastroenterology Services, Thoughtful House Center for Children, 3001 Bee Caves Rd, Austin, Texas, 78746, USA. 2Associate Clinical Professor of Pediatrics, New York University School of Medicine, 550 1st Ave., New York, NY 10016, USA. 3Adjunct Professor Touro College, 27-33 West 23rd St, New York, NY 10010, USA. 4Thoughtful House Center for Children, 3001 Bee Caves Rd, Austin, Texas, 78746, USA.
Abstract
Background: Children with developmental disorders experience chronic gastrointestinal symptoms.
Aims: To examine the nature of these gastrointestinal symptoms and histologic findings in children with autism spectrum/developmental disorders and ileocolonic disease.
Methods: Chart review. 143 autism spectrum/developmental disorder patients, with chronic gastrointestinal symptoms, undergoing diagnostic ileocolonoscopy.
Results: Diarrhea was present in 78%, abdominal pain in 59% and constipation in 36%. Ileal and/or colonic lymphonodular hyperplasia (LNH), defined as the presence of an increased number of enlarged lymphoid follicles, often with hyperactive germinal centers, was present in 73.2%. Terminal ileum LNH presented visually in 67% and histologically in 73%. Colonic LNH was multifocal and presented histologically in 32%. Ileal and/or colonic inflammation presented in 74%, consisting primarily of active or chronic colitis (69%). Ileal inflammation presented in 35%. Presence of LNH significantly predicted mucosal inflammation. Patients with ileal and/or colonic LNH had lower mean/median age than those without; patients with ileal and/or colonic inflammation had lower mean/median age than those without. There was a significant association between ileo and/or colonic inflammation or LNH, and onset of developmental disorder; plateaued or regressive onset conferred greater risk than early onset.
Conclusions: Patients with autism or related disorders exhibiting chronic gastrointestinal symptoms demonstrate ileal or colonic inflammation upon light microscopic examination of biopsy tissue. Further work is needed to determine whether resolution of histopathology with appropriate therapy is accompanied by GI symptomatic and cognitive/behavioral improvement.
Twyla – I’m no scientist either, but what confuses me about this and Wakefield’s work is…
The charts reviewed in the above abstract ONLY included kids who were actually suffering from serious GI symptoms for which they were undergoing invasive evaluation. So of course those kids would have GI symptoms (as would every other kid who was in the hospital for GI symptoms).
Similarly, Wakefield being a gastroenterologist would naturally see only children with significant GI symptoms. I say “significant” symptoms, because if the symptoms were mild they would probably be treated by a general pediatrician.
What am I missing here??
Lisa
Dr. Wakefield speaks for himself quite eloquently here:
h t t p : / / w w w .rescuepost.com/files/autismfile_us33-wakefield.pdf
h t t p : / / w w w .rescuepost.com/files/autism-file-usa34-wakefield-2.pdf
Gonzalez, L., et al., Endoscopic and Histological Characteristics of the Digestive Mucosa in Autistic Children with gastro-Intestinal Symptoms. Arch Venez Pueric Pediatr, 2005;69:19-25.
Balzola, F., et al., Panenteric IBD-like disease in a patient with regressive autism shown for
the first time by wireless capsule enteroscopy: Another piece in the jig-saw of the gut-brain syndrome? American Journal of Gastroenterology, 2005. 100(4): p. 979-981.
Krigsman, A., et al., h t t p : / / w w w .cevs.ucdavis.edu/Cofred/Public/Aca/ Web Sec.cfm?confid=238&webid=1245 (last accessed June 2007) (paper submitted for publication)
Balzola, F., et al., Autistic enterocolitis: Confirmation of a new inflammatory bowel disease in an Italian cohort of patients. Gastroenterology 2005;128(Suppl. 2);A-303.
Galiatsatos, P., et al., Autistic enterocolitis: Fact or fiction. Canadian Journal of Gastroenterology. 2009;23:95-98.
Lisa, the point here is to study children who have autism and serious GI issues. These studies (e.g. the Wakefield et al 1998 Lancet study and the recent Krigsman et al study excerpted above) do not address the question of what percentage of children with autism have GI issues compared with children without autism. These studies do NOT claim that most or all autism cases are caused by the MMR, nor that most or all autism cases are caused by IBD, nor that all children with autism have IBD.
There are a subset of people with autism who have very severe IBD issues. Leaving aside questions of epidemiology and whether these issues affect everyone with autism, these two studies are studying individual children to try to understand the health issues that affect them.
Lisa, you often speak about the importance of identifying and studying subsets of people with autism, as autism is a broad diverse spectrum. Studying children with autism and severe GI issues — many of whose parents report these issues began shortly after the MMR vaccine — is study of one subset — one important subset.
And apparently the specific finding of “lymphoid nodular hyperplasia” was novel and not seen in patients without autism.
For a text of the Lancet paper, see:
http://www.autismresourceconnection.com/documents/Ileal-colonic-lymphoid.pdf
P.S. And although this is a study of a specific subset, understanding the mechanisms involved could possibly shed light on other subsets. It may be that much autism is a result of neuroinflammation — immune systems gone awry — encephalitis — whether caused by thimerosal, aluminum, environmental mercury, other environmental toxins, multiple viruses injected in a vaccine, other vaccine ingredients, or inherent immune system abnormalities impacting the brain and nervous system.
A study widely reported as contradicting Dr. Wakefield et al’s findings actually supports them.
Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study
Mady Hornig et al
http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0003140
“The sample was an age-matched group of US children undergoing clinically-indicated ileocolonoscopy. Ileal and cecal tissues from 25 children with autism and GI disturbances and 13 children with GI disturbances alone (controls) were evaluated by real-time reverse transcription (RT)-PCR for presence of MV [measles virus] RNA in three laboratories blinded to diagnosis, including one wherein the original findings suggesting a link between MV and ASD were reported.”
“Prior to examination of study samples, performance of the four different primer sets (two for H gene, two for F gene) was evaluated for the 12 cloned target regions using synthetic RNA standards. A lower limit of detection of 50 RNA molecules per reaction was confirmed for each primer set in all laboratories.
“All laboratories correctly identified all positive controls using pre-established criteria for positivity (positive results in at least two of three wells with at least one of the primer pairs for F and one of the primer pairs for H). All laboratories correctly identified all negative controls.”
“Analyses in all three laboratories found two ileal biopsy samples with MV F gene and H gene RNA: one from a boy in the AUT/GI group, the other from a boy in the control group. Real-time RT-PCR indicated a range of 2–7 molecules per PCR reaction, corresponding to approximately 50–500 MV RNA molecules per 100 ng of total RNA extract (Table 3). Sequence analysis confirmed that products of these samples were authentic…
“Both subjects with positive samples had reactive lymphoid follicles (RLF). In the AUT/GI subject, RLF were present in both small and large intestine; the control had RLF restricted to colon. Endoscopy revealed inflammation in both subjects: the case had nonspecific gastritis; the control had acute distal esophagitis.”
This paper confirmed that:
- Measles virus can persist in the GI tract. This was accompanied by intestinal inflammation in both affected children; the inflammation was more widespread in the child with autism.
- The results from the lab which had been used by Dr. Wakefield et al were consistent with the results from the other two labs.
But then the authors draw conclusions based on statistical reasons, which seems quite odd in a study only involving 25 cases with autism & GI issues, and 13 controls with GI issues but no autism. They say that since one of each (a case and a control subject) had persistent MV infection, and the others did not show MV infection, that argues against a causal connection between vaccine induced MV infection in the gut and autism.
These conclusions seem odd and quite illogical because:
- It was years since the measles vaccine, and it is quite possible that the vaccine could have caused an ongoing inflammatory process without there necessarily being continuous detectible measles infection. What if there is an autoimmune aspect to this inflammatory process, where the intestinal cells look to the sensitized immune cells like either the virus in the vaccine or some other vaccine ingredient (such as eggs)? We do not understand how vaccines disrupt the immune and digestive systems.
- This is such a small group. How can conclusions be drawn based on percentages? And, it is quite possible that some people have IBD without autism, and/or IBD/autism with causes other than the MMR. Diversity of etiology does not argue against some people with autism having an etiology that involves MMR reaction and ongoing inflammation in the intestines. The fact that one of the 25 children with autism/IBD in this study showed ongoing measles infection in the gut supports the possibility of an MMR-IBD-autism mechanism.
I’m sorry, I don’t have time to summarize these studies but only to list them. I have to go cook GFCF food now, and read aloud a Percy Jackson book…
Horvath K., et al., High prevalence of gastrointestinal symptoms in children with autistic spectrum disorder (ASD). J Pediatr Gastroenterol Nutr 2000, 31:S174.
Melmed, R., et al., Metabolic markers and gastrointestinal symptoms in children with autism and related disorders. J Pediatr Gastroenterol Nutr 2000, 31:S31–S32.
Horvath, K. and Perman, J., Autistic disorder and gastrointestinal disease. Current Opinion inPediatrics 2002, 14:583–587.
Furlano, R., et al., Quantitative immunohistochemistry shows colonic epithelial pathology and γδ-T cell infiltration in autistic enterocolitis. J Pediatrics 2001;138:366-372.
Torrente, F., et al., Enteropathy with T cell infiltration and epithelial IgG deposition in autism. Molecular Psychiatry. 2002;7:375-382. And Torrente, F. et al., Focalenhanced gastritis in regressive autism with features distinct from Crohn’s and helicobacter pylori gastritis. Am. J. Gastroenterol. 2004;4:598-605.
Ashwood, P. et al., Intestinal lymphocyte populations in children with regressive autism: Evidence for extensive mucosal immunopathology. J. Clin. Immunol. 2003;23:504-517.
Ashwood. P., et al., Spontaneous mucosal lymphocyte cytokine profiles in children with regressive autism and gastrointestinal symptoms: Mucosal immune activation and reduced counter regulatory interleukin-10. Journal of Clinical Immunology. 2004:24:664-673.
Wakefield, A., Enterocolonic encephalopathy, autism and opioid receptor ligands. Alimentary Pharmacology & Therapeutics. 2002;16:663-674.
Uhlmann, V., et al., Potential viral pathogenic mechanism for new variant inflammatory bowel disease. Molecular Pathology 2002;55:84-90.
Sabra. A., et al., Ileal-lymphoid-nodular hyperplasia, non-specific colitis and pervasive developmental disorder in children. The Lancet, 1998;352:234-235.
Sabra, A., et al., Linkage of ileal-lymphoid-nodular hyperplasia (ILNH), food allergy and CNS developmental: evidence for a non-IgE association. Ann Allergy Asthma Immunol, 1999;82:8.
Valicenti-McDermott M., et al., Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease. Developmental and Behavioral Pediatrics. 2006;27:128-136.
Richler, J., Luyster, R., Risi, S., Hsu, Wan-Ling, Dawson, G., Bernier, R., et al., Is there a ‘regressive phenotype’ of autistic spectrum disorder associated with the measles-mumps-rubella vaccine? A CPEA study. Autism Dev. Dis. 2006, 36:299-316.
Sandler, R., Short-term benefit from oral vancomycin treatment of regressive-onset autism. J. Child Neurol. 2000;15:429-435.
Parracho, H., Differences between the gut flora of children with autistic spectrum disorders and that of healthy children. Journal of Medical Microbiology. 2005;54:987-991.
See Barbara Loe Fisher’s commentary “Vaccines: Doctor Judges & Juries Hanging Their Own” at:
http://www.nvic.org/NVIC-Vaccine-News/January-2010/Vaccines-Doctor-Judges-Juries-Hanging-Their-Own.aspx
The important part of this story should be the satisfaction of the parents of these children, none are looking to find fault with Wakefield, contrary they all seem pleased with his efforts. While those that have ties to Glaxo are processing their complaints, and using court systems for gain, there is nothing that suggests his findings were WRONG! Where is the outcry against all of the false science, the studies that are done by drug companies and conveniently signed by those that never had a testtube in the game, just “sign off” scientists. This is being ignored, it’s time to expose this more than questionable practice and stop vilifying those such as Wakefield.
Twyla – you are a national treasure! Thanks for the info and citations.
You’re sooooo right – there should be more focused research on those affected with GI SSx — especially those with regressive-onset rather than congenital-onset (both cohorts should be studied, but they should be grouped to see if there are differences).
There are other comorbidities that should be studied vis ASD (again, with separate cohorts for regressive / congenital and controls).
Some of this has been done, but too much $$$ has been siphoned off and wasted on dead-end genetic research because of the stubborn establishment’s insistence that this is a “genetic” disorder.
Lisa – you should get a copy of the Zimmerman book. I’m not sure what you think about the role of “environmental factors” in the pathogenesis of ASD (I think I know what you think, but I won’t put words in your mouth). But I believe you would come away from reading the Zimmerman book with a conviction that (1) there is a real increase in ASD, and (2) it is not “genetic”, it’s largely environmental with a number of genetic susceptibility factors.
ASD is not a “genetic’ disorder in the sense that most people think of “genetics”. It is not an autosomal disorder like sickle cell, PKU, etc. There may be 10 to 100+ genetic and epigenetic factors (SNPs, CNVs, methylation & sulfation changes to gene expression, etc.), with no single factor being either necessary or sufficient to cause ASD in any individual. Ergo, environment environment environment.
You can read the Zimmerman book for free on ScribeD (sp?).
Very best regards,
-Bob
ou will have a much different outlook.
I agree with Bob, Twyla brings great facts into the discussion.
I believe, as Bob, that autism is environmental, however, I do believe the bulk of recent (90″s) cases were caused by (one) exposure. Whether that exposure was a synergistic effect of antigen, thimerosal, aluminum, etc.or the effect of any one of those, it was vaccine. I think the information found in the Simpsonwood transcripts coupled by what was gleaned in the Puerto Rico aluminum vaccine transripts has proven this.
So far as I know, Wakefield’s results have not been replicated… but perhaps you have citations?
Hornig tried, but failed to replicate Wakefield’s results in 2008, using three different labs, including the one used by Wakefield.
Hornig, of course, is Dr. Mady Hornig, whose 2005 “Rain Mouse” study is frequently misinterpreted by anti-vaccine activists. She dosed mice with thimerosal and looked for signs of autism. Her study concluded there were none.
Barbj, you are also a national treasure!
I do agree with you, actually. I believe my son’s regression was triggered by his vaccines (or that the vaccines were a substantial factor).
We have to make “baby steps” to get people to understand FIRST that the pathogenesis is environmental, and then SECOND to find the environmental culprit(s).
First, you need convincing data.
Hi Lisa,
I think the whole topic can be helpful for parent’s trying to understand the situation.
Following the science is difficult for a lot of people. Look at the examples given above that are incorrectly claimed to support/replicate Wakefield’s findings.
This isn’t a criticism of the average parent, rather it seems self-evident that non-scientists are going to have problems following complex scientific arguments.
On the other hand, many of the ethical issues in the GMC decision are so much more accessible for the average person.
Simple example:
1 Wakefield had been funded for two years by lawyers when the Lancet paper was submitted,
2 The Lancet’s policy was very clear; all sources of funding must be disclosed in writing to the journal
3 Wakefield’s written disclosure did not include the lawyer funding
That was easy: a simple look at the documents demonstrates that he was not truthful to the journal and in fact violated important ethical safeguards.
The only interesting part left is to watch how the Wakefield supports are spinning the story and ruthless avoiding the basic facts.
W&N
Barbaraj,
The parental satisfaction with Wakefield argument is a red herring.
The allegations were things like Wakefield lied to the ethics committee or lied to the journal etc.
Parental satisfaction provides zero information on these sorts of issues.
On the other, one interesting detail to emerge was that Wakefield’s contract explicitly stated that he couldn’t treat patients.
Why? What had he done? Why aren’t the parents that are so satisfied with his treatment demanding answers?
W&N
Hi Twyla
The only travesty I see is the propaganda put out by Wakefield’s supporters.
E.g.
http://www.nvic.org/NVIC-Vaccine-News/January-2010/Vaccines-Doctor-Judges-Juries-Hanging-Their-Own.aspx
With nonsense like this it seems inevitable that people will question BLF’s integrity.
It just doesn’t seem possible that a person could honestly
believe this.
I have a request for you.
One of your examples offered in support of
Wakefield was:
Clinical Presentation and Histologic Findings at Ileocolonoscopy in Children with Autistic Spectrum Disorder and Chronic Gastrointestinal Symptoms
Please take 1 minute and review the history of the journal (from its website) and then answer this question:
do you honestly believe that they are not playing you for a fool?
Clinical Presentation and Histologic Findings at Ileocolonoscopy in Children with Autistic Spectrum Disorder and Chronic Gastrointestinal Symptoms doesn’t even mention the word “measles”, which is strange for a paper that was written for the sole purpose of burnishing Wakefield’s image.
Measles virus was only part of Wakefield’s paper. The paper documented intestinal inflammation.
Indeed, it’s precisely the lack of specifity to the Wakefield paper that has allowed people to claim any paper which has found GI issues in people with autism as ’supporting Wakefield’.
I’ve even recently seen someone who is usually rather reasonable reference a much larger paper that found no relationship between onset of bowel symptom and behavioural symptoms, yet this was touted as supporting Wakefield anyway.
Papers that find GI issues in people with autism do not support Wakefield, as Wakefield’s hypothesis was that GI issues have a aetiological or causative relationship to onset of behavioural changes.
Papers which simply state “Some people with autism can also have other conditions” is in no way similar to the hypothesis laid out in the 1998 paper.
dedj – I think the reality is that some folk will cite such articles as “proof” of a causal relationship.
That is… a finding that plastics used in baby bottles could be toxic PROVES that plastic causes autism…
or a finding that mercury rates are high near a town with a high number of children with autism proves that the mercury caused the autism.
It’s certainly possible that there’s a causal effect. But the research being used to “prove” the causal effect simply doesn’t do that!
Lisa
Again, this paper by Dr. Wakefield et al was a “case series”, which is defined as follows:
“Case series studies describe the experience of a single patient or a group of patients with a similar diagnosis.
These types of study, in which typically an astute clinician identifies an unusual feature of a disease or a patient’s
history, may lead to formulation of a new hypothesis… At that time an analytic study (most frequently using
a case-control approach), can [then] be done to investigate possible causal factors.”
- from Hennekens C., Buring, J. (1987) Epidemiology in Medicine. Mayrent, S.L (Ed.), Lippincott, Williams and Wilkins
This study did not pretend to prove that all autism is caused by IBD, and it specifically stated that they did not prove that MMR causes autism. This paper gathered information on 12 patients which could be used to form and further investigate hypotheses. Instead of building on the information gleaned from this study, every effort has been made to shut down further investigation that could possibly show a link between the MMR, IBD, and autism.
Some people seem to believe that first epidemiological studies are published in peer reviewed journals proving something, and only after that can we believe it and study it further. The thought process appears to be that until such epi studies are published, we should ignore all other evidence, including what parents and practitioners have witnessed, and in depth study of individual patients. With this rational, we would never learn anything new.
Scientists start by gathering evidence – including “anecdotal evidence” and various sorts of medical data – to form hypotheses and then further investigate. The published peer reviewed studies don’t spring out of thin air. And epidemiology often only provides clues, and is not the only valid type of science.
Indeed, relying only on epidemiological evidence would result in a limited exploration of the issue.
That the 1998 paper did not attribute all autism to IBD/GI is not an issue and could be considered irrelevant to the discussion of whether discovery of GI issues in people with autism “would support the hypothesis that the consequences of an inflamed or dysfunctional intestine may play a part in behavioural changes in some children.”
Although the Wakefield paper is very loose and non-specific in it’s discussion (which didn’t make any sense when I first read it, but certainly does now – it’s an excellent CMA and so ambigious it could be used to support practically anything) one thing is clear – the paper does not merely describe GI issues in people with autism, but postulates that GI issues are contributory ro behavioural changes. In the context of the paper, ‘behavioural changes’ are identified as meaning developmental regression.
Papers supporting the hypothesis of a shared gut/autism aetiology, do not support Wakefield 1998.
Papers supporting adversive behaviour as a result of GI distress, do not support Wakefield 1998.
Papers indicating excess prevalance of GI issues in people with autism, without correlation between onsets, do not support Wakefield 1998.
Only papers indicating that GI issues preceed, and are implicated in, developmental regression in a subset of children, are supportive of Wakefield 1998.
Wakefield 1998 contained a lot more than merely “We found the symptoms in these people”. Sticking to the content of the actual paper under discussion would be preffered in future.
Actually, sticking to discussion of the charges (which is the topic of this thread) would be preferred in future, assuming such a thing is possible.
Here is the discussion section of the 1998 Lancet paper:
Discussion
We describe a pattern of colitis and ileal-lymphoidnodular
hyperplasia in children with developmental
disorders. Intestinal and behavioural pathologies may
have occurred together by chance, reflecting a selection
bias in a self-referred group; however, the uniformity of
the intestinal pathological changes and the fact that
previous studies have found intestinal dysfunction in
children with autistic-spectrum disorders, suggests that
the connection is real and reflects a unique disease
process.
Asperger first recorded the link between coeliac disease
and behavioural psychoses.4 Walker-Smith and
colleagues5 detected low concentrations of alpha-1
antitrypsin in children with typical autism, and
D’Eufemia and colleagues6 identified abnormal intestinal
permeability, a feature of small intestinal enteropathy, in
43% of a group of autistic children with no
gastrointestinal symptoms, but not in matched controls.
These studies, together with our own, including evidence
of anaemia and IgA deficiency in some children, would
support the hypothesis that the consequences of an
inflamed or dysfunctional intestine may play a part in
behavioural changes in some children.
The “opioid excess” theory of autism, put forward first
by Panksepp and colleagues7 and later by Reichelt and
colleagues8 and Shattock and colleagues9 proposes that
autistic disorders result from the incomplete breakdown
and excessive absorption of gut-derived peptides from
foods, including barley, rye, oats, and caesin from milk
and dairy produce. These peptides may exert centralopioid effects, directly or through the formation of
ligands with peptidase enzymes required for breakdown
of endogenous central-nervous-system opioids,9 leading
to disruption of normal neuroregulation and brain
development by endogenous encephalins and endorphins.
(cont.)
(cont.)
One aspect of impaired intestinal function that could
permit increased permeability to exogenous peptides is
deficiency of the phenyl-sulphur-transferase systems, as
described by Waring.10 The normally sulphated
glycoprotein matrix of the gut wall acts to regulate cell
and molecular trafficking.11 Disruption of this matrix and
increased intestinal permeability, both features of
inflammatory bowel disease,17 may cause both intestinal
and neuropsychiatric dysfunction. Impaired enterohepatic
sulphation and consequent detoxification of compounds
such as the phenolic amines (dopamine, tyramine, and
serotonin)12 may also contribute. Both the presence of
intestinal inflammation and absence of detectable
neurological abnormality in our children are consistent
with an exogenous influence upon cerebral function.
Lucarelli’s observation that after removal of a provocative enteric antigen children achieved symptomatic
behavioural improvement, suggests a reversible element
in this condition.13
Despite consistent gastrointestinal findings,
behavioural changes in these children were more
heterogeneous. In some cases the onset and course of
behavioural regression was precipitous, with children
losing all communication skills over a few weeks to
months. This regression is consistent with a disintegrative
psychosis (Heller’s disease), which typically occurs when
normally developing children show striking behaviour
changes and developmental regression, commonly in
association with some loss of coordination and bowel or
bladder function.14 Disintegrative psychosis is typically
described as occurring in children after at least 2–3 years
of apparently normal development.
Disintegrative psychosis is recognised as a sequel to
measles encephalitis, although in most cases no cause is
ever identified.14 Viral encephalitis can give rise to autistic
disorders, particularly when it occurs early in life.15
Rubella virus is associated with autism and the combined
measles, mumps, and rubella vaccine (rather than
monovalent measles vaccine) has also been implicated.
Fudenberg16 noted that for 15 of 20 autistic children, the
first symptoms developed within a week of vaccination.
Gupta17 commented on the striking association between
measles, mumps, and rubella vaccination and the onset of
behavioural symptoms in all the children that he had
investigated for regressive autism. Measles virus18,19 and measles vaccination20 have both been implicated as risk factors for Crohn’s disease and persistent measles
vaccine-strain virus infection has been found in children
with autoimmune hepatitis.21
We did not prove an association between measles,
mumps, and rubella vaccine and the syndrome described.
Virological studies are underway that may help to resolve
this issue.
If there is a causal link between measles, mumps, and
rubella vaccine and this syndrome, a rising incidence
might be anticipated after the introduction of this vaccine
in the UK in 1988. Published evidence is inadequate to
show whether there is a change in incidence22 or a link
with measles, mumps, and rubella vaccine.23 A genetic
predisposition to autistic-spectrum disorders is suggested
by over-representation in boys and a greater concordance
rate in monozygotic than in dizygotic twins.15 In the
context of susceptibility to infection, a genetic association
with autism, linked to a null allele of the complement (C)
4B gene located in the class III region of the majorhistocompatibility complex, has been recorded by Warren and colleagues.24 C4B-gene products are crucial for the activation of the complement pathway and protection against infection: individuals inheriting one or two C4B null alleles may not handle certain viruses appropriately, possibly including attenuated strains.
(cont.)
(cont.)
Urinary methylmalonic-acid concentrations were raised
in most of the children, a finding indicative of a
functional vitamin B12 deficiency. Although vitamin B12
concentrations were normal, serum B12 is not a good
measure of functional B12 status.25 Urinary
methylmalonic-acid excretion is increased in disorders
such as Crohn’s disease, in which cobalamin excreted in
bile is not reabsorbed. A similar problem may have
occurred in the children in our study. Vitamin B12 is
essential for myelinogenesis in the developing central
nervous system, a process that is not complete until
around the age of 10 years. B12 deficiency may,
therefore, be a contributory factor in the developmental
regression.26
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.
Addendum:
Up to Jan 28, a further 40 patients have been assessed; 39 with the syndrome.
http://www.lifehealthchoices.com/images/lancetwakefield.pdf
***
Sounds like a very thoughtful and logical discussion to me.
Apparently the London Times retracted the part about “dishonest”.
http://www.cryshame.co.uk/
The Times only retracted the part about calling Murch and Walker-Smith dishonest. Wakefield’s reputation remains intact.
It was totally unneeded to copy and paste the entire discussion, especially as you failed to substantiate in any way, shape or form your interpretation of it. Quoting a passage or paragraph is fine. Quoting the entire section and then failing to state which bits lead to your conclusion and why, is just wasteful, rude and makes you look a bit careless. Although it’s not a big issue in this discussion, it would be best if you were to be more considerate towards other readers in the future.
“Sounds like a very thoughtful and logical discussion to me.”
Even if that were true, (it is a rather plain discussion, with various bits thrown in) it does not change the required findings that a study would need to support Wakefield 1998. Wakefield 1998 does not merely report on GI findings in people with autism, but puts forward a correlation between GI issues and behavioural changes. Any ’suppoting’ study would have to do the same, or very similar.
As said, at least one of the list of studies ’supporting Wakefield’ that have been spammed about this place and others, directly stated that it found no such relationship.
Friends: I hate to say it, but we seem to be slipping fast into personal accusations and flaming.
I don’t want to close this thread, but please, if possible:
1. refrain from personal remarks
2. try to keep posts relatively brief (that is, short enough to fit in one comment post)
Thanks all!
Lisa
Hi Twyla,
I take it that you will not look at the journal that published:
Clinical Presentation and Histologic Findings at Ileocolonoscopy in Children with Autistic Spectrum Disorder and Chronic Gastrointestinal Symptoms
And tell us if you think this is “honest science”?
W&N
White&Nerdy, Your don’t have the grace to state your thesis but it appears to be basically that a group of like-minded people get together to found a journal and publish some of their own papers therein (which the establishment journals are strongly hostile to). And “~therefore~” that journal and all the contained papers can be written off as just part of a dishonest conspiracy.
The slight problem with this thesis of yours is that just about all scientific journals and institutions start off in that way, or eventually end up becoming that way. The GMC is not some neutral body but a part of a whole cliquey authoritarian establishment closing ranks against someone who speaks “inappropriately”. As for the BMJ’s latest parade of allegations from Brian Deer, the BMJ has form for extreme dishonesty. It published a huge pack of lies in an “obituary” against Prof David Horrobin, which brought about 100 complaints about the wanton falsehoods in that pile of lies specially cooked to order. So it’s the BMJ of which I wouldn’t believe a word I read therein.