Andrew Wakefield & Ignaz Semmelweis: MMR concerns for the UK's GMC

Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
February 04, 2010


Dr. Ignaz Semmelweis (1) was among the first to perceive that birth-related deaths due to puerperal fever were due to a contagion. He dared collect data which indicated the life-saving merit of having physicians wash hands when proceeding from one obstetrical patient to another. He also dared publish his findings, along with admonitions that physicians not in the habit of washing their hands acquire the hand-washing habit. Ultimately, his findings were in "Conflict with established medical opinions" (1) and stand as precedent for how Andrew J. Wakefield, M.D., has been the primary focus of an inquisition by the General Medical Council in the United Kingdom.

In exploring parallels between Semmelweis' career and Wakefield's, several paragraphs from an excellent Wikipedia presentation (1) are illustrative:

"Semmelweis's observations conflicted with the established scientific and medical opinions of the time. The theory of diseases was highly influenced by ideas of an imbalance of the basic "four humours" in the body, a theory known as dyscrasia, for which the main treatment was bloodlettings. Medical texts at the time emphasized that each case of disease was unique, the result of a personal imbalance, and the main difficulty of the medical profession was to establish precisely each patient's unique situation, case by case.

"The findings from autopsies of deceased women also showed a confusing multitude of various physical signs, which emphasised the belief that puerperal fever was not one, but many different, yet unidentified, diseases... Semmelweis's groundbreaking idea was contrary to all established medical understanding.

"As a result, his ideas were rejected by the medical community..." (1)

These aspects of the Semmelweis history can be rewritten in regard to Wakefield:

Wakefield's observations conflicted with the established scientific and medical opinions of the time. Theories of autism causation were strongly influenced by faith in genetics and by a priori certainty that vaccinations played no role in causing some cases of autism [but, eg, see 16-19].

Findings from autopsies and medical profiles of children with autism showed a confusing multitude of various physical signs, which reinforced the belief that autism was neurological even in the presence of associated pathologies. Wakefield's groundbreaking findings of ileal lymphoid hyperplasia and the suggestion that, in some cases, this pathology was related to the MMR vaccine was contrary to all established medical understanding.

Although Semmelweis was dismissed from his position at a teaching hospital, his ideas gradually became accepted (1).  Similarly, as establishmentarian furor arose from the initial Wakefield paper which described gastrointestinal pathologies and which suggested the possibility of an etiologically significant relationship among the MMR, a unique gastrointestinal pathology, and autism in a subgroup of children (2). Indeed, Dr. Wakefield was dismissed from his position at the Royal Free Hospital, even as subsequent studies by him and by others have further documented gastrointestinal pathologies in autistic children (eg, 3-12; see also 13).

Importantly and also parallel to gradual acceptance of Semmelweis's findings, the American Academy of Pediatrics recently gave its approval of gastrointestinal evaluations for autistic children (14-15). The scientific significance of Wakefield et al's original and subsequent findings is conveyed in a brief review following two case presentations, wherein Galiatsatos et al wrote, "One of the earliest studies investigating GI anomalies in autistic children was reported by Wakefield et al...in 1998..." (11; see also 2).

Several issues swirl about Dr. Wakefield: (i) his willingness to explore, document, and report gastrointestinal pathologies in subgroups of autistic children, and (ii) his daring to suggest that vaccinations may have been etiologically significant in regard to some autistic children's gastrointestinal pathology and their regression into autism (2).

Now that The Lancet has now officially retracted (20; see also 22) the 1998 study by Wakefield et al (2), a conclusion seems likely: The Lancet editors retracted Wakefield et al 1998 not because of the findings described therein and subsequently replicated but instead because of the co-authors suggestion that, in a subgroup of children who received the MMR, their regression into autism and their gastrointestinal pathology may have occurred as a result of the way those individual children's bodies responded to the MMR, its live-viruses, and its endogenously induced pulse of interferon gamma (eg, 21).

Thus we return to Wakefield and Semmelweis. Each committed an act of heresy against prevailing medical opinion. In the case of Dr. Semmelweis, data had been collected and eventually published (1), but his tragic flaw became significant when he suggested that doctors ought change their ways. In the case of Drs. Wakefield, Murch, and Walker-Smith, the heresy meriting inquisition lay in daring to suggest that, in some children with autism, the MMR may be been etiologically significant to the child's gastrointestinal pathology and to his or her regression into autism.

For daring publish the findings (2) and to state the MMR-gut-autism relationship as a possibility, and for refusing to recant, Dr. Wakefield has become a hero to many parents who witnessed their child develop gut pathologies and regress into autism soon after receiving the MMR vaccination.

A petition - actually a letter - in support of Dr. Wakefield and to the United Kingdom's General Medical Council can be viewed and signed online. Comments from signers can be viewed by clicking on a "comments" link below the thermometer-like icon.

To read and sign Dr. McCandless letter to GMC, in support of Andy Wakefield, M.D, go to this link:
http://tinyurl.com/yacv2xp
In the right portion of the page is a link via the word letter. Click on that link to read the entire letter and to sign it if you're so inclined.


References:

1. Ignaz Semmelweis
http://en.wikipedia.org/wiki/Ignaz_Semmelweis

2. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children
Wakefield AJ et al.
Lancet. 1998 Feb 28;351(9103):637-41.

3. Enterocolitis in children with developmental disorders
Wakefield AJ et al.
Am J Gastroenterol. 2000 Sep;95(9):2285-95.

7. Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism
Furlano RI et al.
J Pediatr. 2001 Mar;138(3):366-72.

8. The significance of ileo-colonic lymphoid nodular hyperplasia in children with autistic spectrum disorder
Wakefield AJ et al.
Eur J Gastroenterol Hepatol. 2005 Aug;17(8):827-36.

9. Immune activation of peripheral blood and mucosal CD3 lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms.
Ashwood P, Wakefield AJ.
J Neuroimmunol. 2006 Apr;173(1-2):126-34.

10. Are there more bowel symptoms in children with autism compared to normal children and children with other developmental and neurological disorders?: A case control study
Smith RA et al.
Autism. 2009 Jul;13(4):343-55.

"There was a significant difference in the reporting of certain bowel symptoms (constipation, diarrhoea, flatulence) and food faddiness between the autism group and the mainstream school control group... It would appear, however, that this is not specifically associated with autism as bowel symptoms were reported in similar frequency to a comparison group of children with other developmental and neurological disorders."

11. Autistic enterocolitis: Fact or fiction?
{excellent, brief overview}
P Galiatsatos, A Gologan, E Lamoureux
Can J Gastroenterol. 2009 Feb;23(2):95-8.
http://www.pulsus.com/journals/abstract.jsp?sCurrPg=journal&jnlKy=2&atlKy=8619&isuKy=837&isArt=t

12. Clinical Presentation and Histologic Findings at Ileocolonoscopy in Children with Autistic Spectrum Disorder and Chronic Gastrointestinal Symptoms
Arthur Krigsman, Marvin Boris, Allan Goldblatt and Carol Stott
Autism Insights 2010:2 1-11; 27 Jan 2010
http://www.la-press.com/clinical-presentation-and-histologic-findings-at-ileocolonoscopy-in-ch-a1816

13. Gastrointestinal pathologies in autism: Did Mayo's Ibrahim and colleagues err?
Teresa Binstock, Jan 31, 2010.
http://www.generationrescue.org/binstock/100131-autism-gastrointestinal-misleading-study.htm

14. Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report
Buie T et al.
Pediatrics 2010;125:S1–S18.
http://pediatrics.aappublications.org/cgi/content/full/125/Supplement_1/S1

15. Recommendations for Evaluation and Treatment of Common Gastrointestinal Problems in Children With ASDs
Buie T et al.
Pediatrics 2010;125:S19–S29
http://pediatrics.aappublications.org/cgi/content/full/125/Supplement_1/S19



16. Thimerosal exposure in infants and neurodevelopmental disorders: an assessment of computerized medical records in the Vaccine Safety Datalink
Young HA, Geier DA, Geier MR.
The George Washington University School of Public Health and Health Services
J Neurol Sci. 2008 Aug 15;271(1-2):110-8.
$ http://linkinghub.elsevier.com/retrieve/pii/S0022-510X%2808%2900157-3

The study evaluated possible associations between neurodevelopmental disorders (NDs) and exposure to mercury (Hg) from Thimerosal-containing vaccines (TCVs) by examining the automated Vaccine Safety Datalink (VSD). A total of 278,624 subjects were identified in birth cohorts from 1990-1996 that had received their first oral polio vaccination by 3 months of age in the VSD. The birth cohort prevalence rate of medically diagnosed International Classification of Disease, 9th revision (ICD-9) specific NDs and control outcomes were calculated. Exposures to Hg from TCVs were calculated by birth cohort for specific exposure windows from birth-7 months and birth-13 months of age. Poisson regression analysis was used to model the association between the prevalence of outcomes and Hg doses from TCVs. Consistent significantly increased rate ratios were observed for autism, autism spectrum disorders, tics, attention deficit disorder, and emotional disturbances with Hg exposure from TCVs. By contrast, none of the control outcomes had significantly increased rate ratios with Hg exposure from TCVs. Routine childhood vaccination should be continued to help reduce the morbidity and mortality associated with infectious diseases, but efforts should be undertaken to remove Hg from vaccines. Additional studies should be conducted to further evaluate the relationship between Hg exposure and NDs.

17. Hepatitis B triple series vaccine and developmental disability in US children aged 1-9 years
 Gallagher C, Goodman M. Toxicol Environ Chem 2008 90(5):997-1008.
{free online}
http://fourteenstudies.org/pdf/hep_b.pdf

This study investigated the association between vaccination with the Hepatitis B triple series vaccine prior to 2000 and developmental disability in children aged 1-9 years (n = 1824), proxied by parental report that their child receives early intervention or special education services (EIS). National Health and Nutrition Examination Survey 1999-2000 data were analyzed and adjusted for survey design by Taylor Linearization using SAS version 9.1 software, with SAS callable SUDAAN version 9.0.1. The odds of receiving EIS were approximately nine times as great for vaccinated boys (n = 46) as for unvaccinated boys (n = 7), after adjustment for confounders. This study found statistically significant evidence to suggest that boys in United States who were vaccinated with the triple series Hepatitis B vaccine, during the time period in which vaccines were manufactured with thimerosal, were more susceptible to developmental disability than were unvaccinated boys.

18. Hepatitis B vaccination of male neonates and autism
[conference abstract as published]
CM Gallagher, MS Goodman, Graduate Program in Public
Health, Stony Brook University Medical Center, Stony Brook, NY
Annals of Epidemiology, p659
Vol. 19, No. 9 Abstracts (ACE) September 2009: 651–680.

PURPOSE: Universal newborn immunization with hepatitis B vaccine was recommended in 1991; however, safety findings are mixed. The Vaccine Safety Datalink Workgroup reported no association between hepatitis B vaccination at birth and febrile episodes or neurological adverse events. Other studies found positive associations between hepatitis B vaccination and ear infection, pharyngitis, and chronic arthritis; as well as receipt of early intervention/special education services (EIS); in probability samples of
U.S. children. Children with autistic spectrum disorder (ASD) comprise a growing caseload for EIS. We evaluated the association between hepatitis B vaccination of male neonates and parental report of ASD.
METHODS: This cross-sectional study used U.S. probability samples obtained from National Health Interview Survey 1997–2002 datasets. Logistic regression modeling was used to estimate the effect of neonatal hepatitis B vaccination on ASDrisk amongboys age 3–17 years with shot records, adjusted for race, maternal education, and two-parent household.
RESULTS:Boyswho received the hepatitis B vaccine during the first month of life had 2.94 greater odds for ASD (nZ31 of 7,486; OR Z 2.94; p Z 0.03; 95% CI Z 1.10, 7.90) compared to later- or unvaccinated boys. Non-Hispanicwhite boys were 61% less likely to have ASD(ORZ0.39; pZ0.04; 95% CIZ0.16, 0.94) relative to non-white boys.
CONCLUSION: Findings suggest that U.S. male neonates vaccinated with hepatitis B vaccine had a 3-fold greater risk of ASD; risk was greatest for non-white boys.

19. Generation Zero
{FOIA-based analysis of CDC's 1999 thimerosal findings}
Blaxill M, Safeminds 2004
http://www.safeminds.org/research/library/GenerationZeroPowerPoint.pdf

20. Retraction—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children
The Editors of The Lancet
http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673610601757.pdf

21.
Kinetics of immunologic responses after primary MMR vaccination.
Pabst HF et al.
Vaccine. 1997 Jan;15(1):10-4.

22
. An Interest in Conflict? The ‘conflict of interest’ policy of the General Medical Council and the fitness to practice hearing of Dr. Andrew Wakefield, Professor Walker-Smith, and Professor Simon Murch
by Martin J. Walker, MA
© Copyright 2009, Medical Veritas International Inc. All rights reserved.
http://www.medicalveritas.com/images/00211.pdf



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