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April 16th, 2010
04:48 PM ET

More challenges on Wakefield's research

By Madison Park
CNNhealth.com writer/producer

The existence of a gut disease, as described by embattled autism researcher Dr. Andrew Wakefield, is called into question in a new article published Friday in the British Medical Journal.

Wakefield was the lead author of a now-discredited 1998 study which suggested the measles vaccine caused gastrointestinal problems and those GI problems led to autism.  In that piece published in The Lancet, Wakefield, a gastroenterologist had said he discovered a new gut pathology called "autistic enterocolitis."

BMJ: Wakefield’s "autistic enterocolitis" under the microscope

Brian Deer, an investigative journalist challenges this notion in his BMJ article  and  alleges that Wakefield had a "mission,  which was to discover precisely such a disease."  Wakefield was hired by a lawyer to "help launch a speculative lawsuit against drug companies that manufactured MMR vaccine. And the instrument of their attack was to find what he called at the time 'a new syndrome' of bowel and brain disease caused by vaccines," according to the article.  Deer has written extensively on Wakefield for the Sunday Times.

He also reported that the biopsy reports on eight of the 11 children in the study were normal, yet the published Wakefield paper reported that 11 children had “non-specific colitis” - a clinically significant inflammation of the large bowel. The biopsy slides are no longer available for examination.

Autistic enterocolitis has not been accepted into gastroenterology textbooks.

Wakefield’s  study in The Lancet triggered concerns that childhood vaccines cause autism.  Earlier this year, the journal retracted his study after Wakefield was found guilty of acting unethically in conducting his research.

Medical journal retracts study linking autism to vaccine

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soundoff (17 Responses)
  1. brian

    In response to the Lancet article which reviews the evidence that Wakefield predetermined the existence of a new gastrointestinal syndrome without actually having examined any patients, Wakefield said this: "The finding of inflammatory disease of the intestine of autistic children has now been confirmed in 5 different countries."

    There’s an excellent analysis of this “confirmation” here:

    http://justthevax.blogspot.com/2010/02/independent-wakefield-way-really.html

    "So what do we have here? Three (3) genuinely published cases of autistic adults who had consulted a doctor for gastrointestinal problems and were found to have gastrointestinal problems. One conference report from April 2005 that has not gone through peer review and has not appeared in a real journal in the 5 years since the conference. One real study looking at over 50 autistic children which does not confirm Wakefield’s findings. And finally, one study by Wakefield’s buddies in a freshly founded journal run by Andrew Wakefield and his buddies, to say that their buddy Andy was really right all along – how is that for "independent" confirmation?"

    April 16, 2010 at 17:36 | Report abuse | Reply
  2. Matt

    The BMJ article includes a quote from a proposal that Dr. Wakefield and a lawyer submitted to obtain funding for the study. In that proposal, Dr. Wakefield was already claiming that the evidence was "undeniably in favour" of a vaccine injury pathology leading to disintigrative disorder (autism) and enteritis. Before his group started the research, he was already convinced of the result.

    That is just flat out wrong. What an amazing bias to bring to his work.

    April 16, 2010 at 18:49 | Report abuse | Reply
  3. John Stone

    Wakefield's rebuttal can be read here:

    http://www.box.net/shared/zks6g0ekub

    BMJ also published an editorial by Nicholas Wright doubting that Deer's research did anything to disestablish the case for autistic enterocolitis.

    Contributing editor, ageofautism.com

    April 16, 2010 at 19:01 | Report abuse | Reply
  4. Meryl Dorey

    Perhaps Dr Gupta hasn't seen the latest research out of Wake Forest University school of medicine? (http://www.dailymail.co.uk/news/article-388051/Scientists-fear-MMR-link-autism.html) You see, this is a study of 275 children with regressive autism and, though the study is not yet complete, out of 82 children whose gut tissue has been tested, 70 have been found to be harbouring the measles vaccine virus. Not the wild virus – but the vaccine virus.

    Team leader on this study, Stephen Walker, says, "'What it means is that the study done earlier by Dr Wakefield and published in 1998 is correct."

    So before you all start clapping each other on the back and saying – job well done fellas, we've managed to save the MMR vaccine from any and all threats – the cat is out of the bag. Measles vaccine virus in the gut looks like it could very well be linked with both gut and cognitive issues commonly found in regressive autism.

    Meryl Dorey,
    Australian Vaccination Network

    April 17, 2010 at 00:59 | Report abuse | Reply
    • Dave The Happy Singer

      'Perhaps Dr Gupta hasn't seen the latest research out of Wake Forest University school of medicine?'

      That story is from 2006. Do you ever stop lying? #StopAVN

      July 30, 2010 at 05:25 | Report abuse |
  5. Robert McMaster

    More Witch Hunt Science from doctors with a cure for nothing. British medical authorities are terrified that people will have the nerve to doubt the miserable outcomes and inflated costs of their way of milking autism. The very idea that what you eat could might have pathological consequences is obviously nonsense. Slag such rubbish immediately lest the matter be objectively investigated. Roll out the Swift Boat crowd and slag all who dare to say differently.

    April 17, 2010 at 14:33 | Report abuse | Reply
  6. Martha Moyer

    My son, age 36, has had severe behavior and bowel issues all his life. As a child he constantly was trying to put his hands in his rear end and would literally paint the walls with feces. Was he telling me something? He couldn't talk. He did sometimes do huge bowel movements so he had potential for training and when placed in an institution was doing well until the institution found out that they wouldn't get paid to work with his bowel issues. His training stopped. This was never told to me. He had a major bowel impaction which has caused complete loss of bowel control. His bowel muscles and nerve endings are shot. We use a devise, similar to an enema for toileting three times a week ( http://www.piemed.com ). This is so sad as he needs complete one on one care for the rest of his life. I do not feel this has any relationship to vaccines. I believe this has to do with autism and the lack of understanding of the bowel process. I also feel this has a genetic and disease component.

    April 18, 2010 at 02:04 | Report abuse | Reply
  7. FreeSpeaker

    Ms. Dorey seems to have an alternative definition for "latest". A simple reading of the dates of the comments shows that this article stems from 2006. A search of PubMed fails to show that this has been published in the past three years. The Wakefield apologists are desperate.

    April 19, 2010 at 11:09 | Report abuse | Reply
  8. brian

    Meryl Dorey asked, “Perhaps Dr Gupta hasn't seen the latest research out of Wake Forest University school of medicine? “Dorey referred to an abstract presented at the IMFAR meeting in April of 2005, in which the authors presented preliminary results that indicated the presence of measles RNA in bowel tissue samples taken from children with ASD that remains quite at odds with other work in this area.

    It’s interesting to see “the latest research” cited as support for Wakefield’s thoroughly-refuted MMR-autism idea. That work, from Dr. Walker’s group at Wake Forest, was reported at a conference five years ago, and the reason it remains unpublished is almost certainly due to the fact that what Walker et al. reported as positive results were almost certainly FALSE positives, just as the similar work reported earlier by Wakefield and his collaborators was beyond question due to false positives: the test designed to detect measles RNA in the samples actually produced positive results if no RNA was present (that is, the test tube contained reagents only, but no sample) and others have shown that the test reagents with human DNA in the samples.

    In the Omnibus Autism Hearings-related decision on the Hazlehurst appeal, the Special Master referred to this preliminary and still unpublished work:

    “ . . . [Walker’s colleague] acknowledged that the preliminary data from the study was “not useful at this time” (Cedillo Tr. at 682), declined to draw any conclusions about the biological significance of the Walker group’s findings (Cedillo Tr. at 682), and identified what respondent describes as several significant drawbacks to the study, including that the experiments had not been “blinded”28 and had lacked negative controls.”

    The question regarding the linkage of measles or the MMR vaccine is a hot topic. If Walker had had any real evidence to report, he would have published by now. That idea is dead, dead, dead, and citing never-published work performed over five years ago shows just how dead it is.

    April 19, 2010 at 12:21 | Report abuse | Reply
  9. tonylurker

    Latest research out of Wake Forest? That was presented at a conference in 2006 and has yet to be published in a real journal. The unpublished version was used in the Omnibus hearings and was not found to be persuasive.

    April 19, 2010 at 12:29 | Report abuse | Reply
  10. brian

    Of course it’s worth noting that the report of a more recent, definitive attempt to replicate Wakefield’s work (which included Wakefield’s former business partner and collaborator as a co-author) concluded:

    "The work reported here eliminates the remaining support for the hypothesis that ASD with GI complaints is related to MMR exposure. We found no relationship between the timing of MMR and the onset of either GI complaints or autism. We also could not confirm previous work linking the presence of MV RNA in GI tract to ASD with GI complaints.”

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526159/

    [Correction: I wrote above that Walker’s poster was presented at IMFAR in April of 2005; of course the conference was actually in June of that year.]

    April 19, 2010 at 13:23 | Report abuse | Reply
  11. brian

    One more thing: Although Wakefield is of course keenly aware of the court of public opinion, in science he seems to have moved on from his failed “chronic measles infection (e.g., with the MMR vaccine strain) causes gut inflammation which somehow leads to autism” hypothesis to an understanding more in line with the the evidence.

    Here’s what Wakefield wrote last year in a rather obscure new journal, Biomarker Insights:

    “Genetic analysis suggests that as many as 15 genes might be involved in Autism Spectrum Disorders (ASD) . . . Based on neurobiological findings and location within a chromosome 7q31 autism candidate gene region, Campbell et al analyzed the MET receptor tyrosine kinase gene in a family based study of autism and found a functional variant of MET with autism with a calculated relative risk of 2.27 . . . In the central nervous system, MET contributes to development of the cerebral cortex and cerebellum. Abnormal MET/HGF [hepatocyte growth factor] signaling in the cerebral cortex results in atypical interneuron migration . . . and reduced interneurons in the frontal and parietal regions of cortex. In the cerebellum, aberrant signaling causes decreased proliferation of granule cells and reduction in the cerebellar size, particularly in the vermis. Both of these aberrations are consistent with those observed in brains of individuals with autism . . . Neuropathological findings in autism indicate altered organization of both the cerebral cortex and cerebellum, both of which are disrupted in mice with decreased MET signaling activity . . . Increased risk for autism . . . may impart, particularly in individuals with severe GI disease, shared etiology of a parallel, although independent, disruption of brain and peripheral organ development and function.”

    Wakefield is clearly interested in finding a GENETIC explanation for autism with concurrent GI disease.

    April 19, 2010 at 14:04 | Report abuse | Reply
  12. Carol

    But here's part of what Nicholas Wright has to say in evaluating Deer's case against autistic enterocolitis:

    "So, does autistic enterocolitis exist? Children with autism often have chronic diarrhoea, bloating, abdominal pain, distension, and abnormal stool consistency.10 A cross sectional study that compared children with autism with matched controls and children with other developmental disabilities found that 70% of children with autistic spectrum disorder had a history of gastrointestinal problems, compared with 28% of controls (P<0.001) and 42% of those with other developmental disabilities (P=0.03).11 Certainly something seems to be going on. Moreover, several articles describe the association between inflammatory pathology and autistic spectrum disorder 3 Many of these have been heavily criticised5 and defended,3 and the role of chronic constipation and other associated conditions in causing the changes recorded in these patients has been much debated.5 10"

    As he notes, something seems to be going on.

    April 19, 2010 at 22:25 | Report abuse | Reply
  13. Carol

    And I think everybody knows that there is a genetic component to autism. Not everybody develops autism. Boys develop it with much greater frequency than girls.

    Those with genetic susceptibility are more vulnerable to the environmental insult or insults with which we are now bombarded.

    April 20, 2010 at 12:46 | Report abuse | Reply
  14. FreeSpeaker

    Carol, did Wright control for all the wacky diets desperate parents try after being persuaded by those who still do not have a clue?

    April 20, 2010 at 12:50 | Report abuse | Reply
  15. FreeSpeaker

    I am still waiting for clear evidence that any environmental factor plays a part in developing Autism.

    April 20, 2010 at 13:39 | Report abuse | Reply
  16. brian

    The fact that some children with ASD have gastrointestinal problems does not do anything at all to support either Wakefield’s hypothesis or the existence of the syndrome he allegedly found in 11 of 12 children (only 8 of which were referred with gastrointestinal problems).

    Wakefield had proposed that inflammatory bowel disease in general and Crohn’s disease in particular were caused by measles virus; he then, before he examined any of the 12 Lancet children, extended this to include chronic infection with measles virus as the cause of both GI problems and startling (within an average of 6.5 hours of receipt of the vaccine!) neurological deterioration.

    There are better, genetic explanations. Wakefield recently published an article related to the MET mutations as a cause of both ASD and gastrointestinal problems. The MECP2 mutations that are associated with Rett Syndrome (which causes dramatic deterioration after a period of apparently normal development) is also associated with gastrointestinal problems; the MECP2 gene product, which frequently is aberrantly expressed in the brains of individuals with ASD, also regulates the expression of diverse genes throughout the body. Many other genes may be involved: In general, it’s not unreasonable to think that some mutations that affect neurodevelopment would also affect the gastrointestinal tract, which is, after all, replete with nerves. This evidence for genetically-determined neurodevelopmental problems that may also affect the gut is entirely separate from Wakefield’s idea that chronic measles infection increased gut permeability and allowed toxic substances to reach the brain to cause ASD–an idea that has been repeatedly and convincingly refuted.

    April 20, 2010 at 15:09 | Report abuse | Reply

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