Monday, February 1, 2010

"Independent" the Wakefield way (really something for the fail blog)

One of the claims that keeps reappearing in the comments sections under articles covering the GMC ruling on Andrew Wakefield and colleagues is that

The key finding (chronic colitis found in ASD children) of Dr. Wakefield's early case report published in The Lancet in 1998 HAS been independently confirmed by medical researchers in five different countries.

That is a very significant claim. After all, independent confirmation of a recent finding, would make the validity of a finding more likely, and if 6 independent laboratories found the same gut changes in autistic children, then then likelihood that this was a) a fluke or b) made up by Andrew Wakefield would be drastically reduced.

Finally, one of those commenters has posted those ‘independent confirmations’ – so I thought it might be worth having a look at them.

Krigsman, A. (Assistant Professor of Pediatrics, New York University School of Medicine Director of Gastroenterology Services), et al.,Ileocolonoscopy in Children with Autistic spectrum Disorder and Chronic Gastrointestinal symptoms. Autism Insights 2010:2 1-11.

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.

Balzola, F., et al., Autistic enterocolitis: Confirmation of a new infammatory 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.

Let’s look at number 1, Krigsman et al. The name sounds vaguely familiar. In fact, anyone who has read a little about the MMR-autism affair will know Arthur Krigsman as the clinical director of Thoughtful House, which happens to be the same Texas Clinic out of which Andrew Wakefield practises. One editor of “Autism Insight”, the journal in which this “independent confirmation” was published, is Andrew Wakefield (another one the senior author of the study, Carol Stott). Gosh, I bet peer review was harsh for this one.

Gonzales et al, number 2, has been published in Arch Venez Pueric Pediatr” which stands for Archivos Venezolanos de Puericultura y PediatrĂ­a. It was a bit tricky to get my hands on the paper, especially since the citation was not quite right, but I did manage and was not surprised to find that indeed the authors cannot replicate Wakefield’s 1998 “findings” of a distinct autistic enterocolitis, although they do report a higher incidence of gastrointestinal problems in their autistic group.

Balzola et al, number 3, is a case report of one adult autistic patient with inflammed bowel.

Similarly, Balzola et al, number 4, is a meeting abstract that never saw the light of day as a peer reviewed study.

Autistic enterocolitis: confirmation of a new inflammatory bowel disease in an Italian cohort of patients.
Federico Balzola, Clauser Daniela*, Alessandro Repici, Valeria Barbon, Anna Sapino***, Cristiana Barbera**, Pier Luigi Calvo**, Marina Gandione*, Roberto Rigardetto*, Mario Rizzetto.

Dept of Gastroenterology. University of Turin. Molinette Hospital Turin, Italy

*Dept of Neuropsychiatry for Children. University of Turin Regina Margherita Pediatric Hospital, Turin, Italy ** Dept of Pediatric Gastroenterology. University of Turin Regina Margherita Pediatric Hospital, Turin, Italy *** Dept of Biomedical Science and Human Oncology University of Turin

Although the causes of autism are largely unknown, this long-life developmental disorder is now recognised to affect as many as 1 to 500 children. An upper and lower intestinal disease has been recently described in these patients (pts) in spite of gastrointestinal symptoms have been reported by the parents back more many years. This disorder comprising ileo-colonic lymphoid nodular hyperplasia (LNH) and chronic inflammatory colonic disease was called autistic enterocolitis: an association between autism and bowel disease was then proposed.

Nine consecutive male pts (mean age 18 years, range 7-30 years) with a diagnosis of autism according to ICD-10 criteria that showed chronic intestinal symptoms (abdominal pain, bloating, constipation and/or diarrhoea) were enrolled. After routinely blood and stool tests, gastroscopy and colonoscopy with multiple biopsies were performed under sedation. A wireless enteroscopy capsule was also performed in 3 adult pts.

Anemia and fecal blood positive test were found in 2 pts and 3 pts, respectively. Gastroscopy revealed mucosal gastritis in 4 pts, esophagitis in 1 and duodenitis in 1 pts. Histological findings showed a chronic inflammation of the stomach and duodenum in 6 pts (66%) but inconsistent with celiac disease. Macroscopic mucosal abnormalities (aphtoid ulcerations and loss of vascular pattern) were found in 1 pts (11%) at colonoscopy and a LNH in the terminal ileum in 4 pts. (44%) Microscopic colitis with intraepithelial lymphocytes and eosinophils infiltrations, mucosal atrophy and follicular hyperplasia was histologically present in all the pts (100%) whereas a chronic inflammation with iperemia and villous shortening of the terminal ileum was shown in 6 (66%) pts. The wireless capsule revealed areas of bleeding or patchy erythema, mucosal erosions and ulcers in both jejunum and ileum in 1 patients whereas a particular chronic jejunum and ileal erosive pattern was evident in the other two.

These preliminary data are strongly consistent with previous descriptions of autistic enterocolitis and supported a not-coincidental occurrence. Moreover, they showed for the first time a small intestinal involvement, suggesting a panenteric localisation of this new IBD. The treatment to gain clinical remission has still to be tried and it will be extremely important to ameliorate the quality of life of such pts who are likely to be overlooked because of their long-life problems in the communication of symptoms.

These findings do not support a distinct pathology unique to autism. Additionally, Wakefield's original claim was essentially, 'MMR vaccination, then appearance of gastrointestinal symptoms, then regression into autism'. So not only was Wakefield's original claim roundly disproven, but Balzola et al.'s findings do not indicate anything remotely descriptive of Wakefield's original claim. This abstract also remains just that, i.e. an abstract presented at a meeting 5 years ago and has not gone through any peer-review, nor publication.

Finally, number 5, Galiatsatos et al., is a case report, featuring two adult patients with gastrointestinal problems and an ASD diagnosis. The authors call for “more investigations” in their discussion.

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?!

Edited on 19 January 2011 to add a find that Sullivan from LBRB led me to - it appears that the 2007 and 2008 tax forms (990) from Thoughtful House mention a "VENEZUELA COLLABORATION" under the projects they fund - a bit of thoughtful googling produced this gem

Gastrointestinal Pathology in Autism Spectrum Disorders: The Venezuelan Experience by Lenny G. Gonzalez, MD

Meet Lenny Gonzales, another Wakefield "buddy".


  1. That's pathetic, isn't it?

    And you know, those adults with the gastro issues might indeed have gastro issues in relation to being autistic to some extent. Being an autistic adult is stressful. IBS, for example, is probably common among autistic adults. What they need is go talk to a real doctor, learn to manage their stress, and so forth. Not woo.

  2. Thank you, Catherina and Science Mom. I have no background in science and am bewildered by all the claims and citations constantly thrown around on the web. Your clear and thorough posts have helped me a lot. Also, thank you for providing links to the studies you discuss!

  3. I am so absolutely thrilled that you did this. I have been reading about the "replicated trails" too and was going to look into it. You saved me the hassle. These people sure can trumpet the science that they don't even understand or look into. What a disaster.

    What do you think of the relationship between maternal age and autism? That seems interesting to me. Certainly the correlations are there- maternal age and autism incidence is a much tighter correlation than vaccine frequency and autism. Also, states with lower age maternal births also have lowest autism levels (but probably the worst surveillace too).

    Great post.

  4. Thanks for this. I am jealous because I didn't do it first (or at all)!

    I've reposted it to LeftBrainRightBrain:

  5. We know that Wakefield and his conspirators ran many more than 12 children through the week of horrors at the Royal Free Hospital. But on the 12 reported on, none of them were diagnosed with Crohn's or UC. And it had serious ethical issues.

    Krigsman's paper reported on data gathered at a New York hospital which denied Krigsman permission to do colonoscopies on autistic kids for research purposes and denied him the right to use the data he had gathered because of consent form concerns.

    Krigsman got around that by using a commercial IRB and carefully limiting what they could comment on. A decent journal should have rejected this weaseling around the hospital IRB. Or they should have required Krigsman to detail the history of his research. Krigsman's report on 143 consecutive case of autism and bowel problems is amazing to me. He never mentions finding Crohn's or UC in any of them.

  6. Also of note is that there was at least one specific effort to duplicate Wakefield's findings, using (iirc) the same lab and even some people who had been inclined toward the Wakefield viewpoint - and even this totally failed to show what Wakefield insisted he'd found.

  7. Hi, can I please ask what the correct citation for Gonzales et al was? I've got the other four, and if you could please provide an accurate reference or direct link to this one I'd really appreciate it.

    Thanks, Tom.

  8. Tom, that is the correct citation for the Gonzalez et al. paper. Is there something else you are looking for?

  9. Oh, okay, I was just unable to find it in PubMed. I'll go through the journal.


  10. Looks like they forgot to focus on some of the available studies, here???? No prove ever, no connection to vaccines, right? Thats what you must and want to believe.

    Callous Disregard Research References

    Biomedical Treatment in Autism (ASD)


    1. That is so sweet, anon - more Wakefield buddies and Wakefield himself supporting Wakefield.. many of those, we have addressed in the follow up post to this:

      But if you think one of those papers lends particularly strong support of Wakefield's core idea (that vaccines cause gut issues that cause/trigger autism), then feel free to describe which and how. Linking to Wakefield's website doesn't count ;)

  11. It looks like a visit from Lowell Hubbs, who has been banned from a hospital campus, believes in conspiracy theories, convicted for theft and drunk driving, and more!