Testimony of Dr Andrew J Wakefield MB MS FRCS FRCPath

Committee on Government Reform

June 2002

Mr Chairman and members of the Committee,

 Before bringing you up to date with the research linking MMR vaccine to regressive autism I will put the record straight with respect to Dr Gershon’s testimony last year on the molecular detection of measles virus in the laboratory of Professor O’Leary. Dr Gershon’s testimony was false in relation to a number of assertions, whether or not his testimony constituted perjury or simply sloppy science. It is not my wish to take up valuable time in this hearing with the details of Dr Gershon’s unacceptable errors. All correspondence and raw data have been provided to the ranking majority and minority members. Merely by way of illustration, he stated that tissues from experimental animals not infected with measles virus were positive in Professor O’Leary’s lab. In fact they were all entirely and consistently negative on repeat testing. Dr Gershon’s behaviour was a disgrace. I would level the same charge at anyone who relies or has relied in any way upon this testimony. I am not surprised that Dr Gershon turned down the offer to appear before this committee. Had he done so, I am sure he would have enlightened the Committee, somewhat belatedly, as to any proprietary rights his wife might have in the Merck chickenpox vaccine patent. 

The current sate of the science:

The association between MMR vaccine, autism and intestinal inflammation was first suggested by my group from the Royal Free Medical School in 1998 in a paper published in the Lancet. The same research team, in collaboration with Professor John O’Leary and Dr Simon Murch from the Royal Free Hospital, has since shown in a comprehensive series of eight peer-reviewed scientific studies that the major findings of our original study were correct. These papers are listed as an appendix.

The sum of the research by my group and our collaborators, taken together with additional work by independent physicians and scientists in the United States has now confirmed the following facts.  

• Children with regressive autism and intestinal symptoms have a novel and characteristic inflammatory disease of their intestine (1-4).

• This disease is not found in developmentally normal control children (2-4).

• This disease is entirely consistent with a viral cause (5-8).

• This disease may be the source of toxic damage to the brain (9).

• Measles virus has been identified in the diseased intestine in the majority of children with regressive autism studied, precisely where it would be expected if were the cause of the intestinal disease (5,8).

• These children, who suffer the same pattern of regressive autism and intestinal inflammation, come from many countries including the US and Ireland where they have been investigated and biopsied independently.

• Measles virus has been found in only a small minority of developmentally normal children (5).

• The measles virus in the diseased intestine of autistic children is from the vaccine (11).

• Children with regressive autism appear to have an abnormal immune response to measles virus (1a,2a)

• These findings are entirely consistent with parental reports that their normally developing child regressed into autism following exposure to MMR vaccine (1,11).  

Confirmation of intestinal findings

Other researchers in the US have confirmed the presence of intestinal inflammation in children with regressive autism (3a & see testimony of Dr A. Krigsman MD) and, independently, the link with measles virus in children who were given the MMR vaccine (12,13).

 Measles virus sequencing

Most significantly, a study due to be presented at the Pathological Society of Great Britain and Ireland, in Dublin at the beginning of July has confirmed that the measles vaccine virus is present in the diseased intestinal tissues of children with regressive autism.

 The Dublin researchers headed by Dr John O’Leary, Professor of Pathology at Trinity College Dublin, examined viral genetic material from intestinal biopsies taken from 12 children with gastro-intestinal disease and an autistic spectrum disorder. The viral genetic material had already been identified as measles in a study published in January in Molecular Pathology. Using state of the art molecular science the samples from these twelve children have now been characterised as from vaccine strain measles virus. This investigation continues. These data constitute a key piece of evidence in the examination of the relationship between MMR vaccine and regressive autism.

 Re-challenge and biological gradient effects for MMR/MR vaccines

A further key piece of evidence comes from examination of “re-challenge” and “biological gradient” effects for possible vaccine-related adverse events.

 Re-challenge refers to a situation where re-exposure of an individual to an agent (e.g. vaccine) elicits a similar adverse reaction to that seen following the initial exposure. The secondary reaction associated with re-challenge may either reproduce the features associated with the primary challenge, or may lead to worsening of the condition that was provoked or induced by the initial exposure.

 During the course of our clinical investigation we have observed that some children who received a second dose of MMR, or boosting with the combined measles rubella (MR) vaccine, experienced further deterioration in their physical and/or behavioural symptoms following re-exposure. In a report of April 2001, the Vaccine Safety Committee of the US Institute of Medicine (IOM) stated that, in the context of MMR vaccine as a possible cause of this syndrome, “challenge re-challenge exposed would constitute strong evidence of an association”[1].

 In the context of adverse vaccine reactions, a biological gradient refers to an increasing severity of, or increased risk of developing, a particular disease outcome. More severe bowel disease in children with regressive autism who had received more than one MMR/MR would be an example of this.

 We have undertaken systematic evaluation of re-challenge and biological gradient effects in children with regressive autism who have undergone investigation at the Royal Free Hospital.

  “Exposed” – children with normal early development & regressive autism who had received more than one MMR/MR - were compared with age and sex matched “unexposed” – children with normal early development & with regressive autism who had received only one MMR but otherwise similar baseline characteristics to the exposed group. Comparisons included: secondary (2^o) developmental/behavioural regression; 2^o physical deterioration, prospective, observer-blinded scores of endoscopic & microscopic disease severity.

 In a preliminary analysis exposed children scored significantly higher than unexposed children for:

(i)                 secondary regression on the basis of analyses performed at the different levels, including : 

• parental history 

• excluding those whose secondary regression occurred following publication of the 1^st suggested MMR-autism link in 1998; and,

• inclusion of only those for whom independent corroborative evidence of secondary regression was obtained from the records;

(ii)            secondary physical symptoms;

(iii)            presence of severe ileal lymphoid hyperplasia; and,

(iii)            presence and severity of acute mucosal inflammation.

 No measures of disease were worse in unexposed than exposed children.

 These data identify a re-challenge effect on symptoms and a biological gradient effect on severity of intestinal inflammation that provide evidence of a causal association between MMR and regressive autism in these children.

 I have repeatedly requested a meeting with Sir Liam Donaldson the UK’s Chief Medical Officer to discuss the situation. His response has been to refuse to meet, but instead to demand that we send him the children’s samples. He has provided absolutely no indication, in terms of scientific protocol, how he would proceed to analyse these samples. He has, as far as I am aware, no ethical approval for analysing these samples. He may be reassured to know that independent testing is being conducted and that as part of the litigation process in the UK, the Defendants are being provided with identical samples for independent analysis.

 The last seven days have seen a report, in the journal Clinical Evidence, publicised as “new research” disproving any links between autism and the MMR vaccine.  The authors specifically excluded clinical research into bowel disease, immune disorders and other documented features of autism that may relate to a viral cause. They do not cite any of our publications beyond the initial study of 12 children in 1998. In fact, the Clinical Evidence paper was no more than a review of the epidemiological studies, including the Davis study that will be critically reviewed during this hearing, that have already been dismissed as irrelevant by an independent review commissioned by the Institute of Medicine in the US.

Key Publications by Wakefield/O’Leary  groups

1.        Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, et al. Ileal LNH, non-specific colitis and pervasive developmental disorder in children. Lancet 1997; 351: 637-641.

2.        Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, Davies S, et al. Enterocolitis in children with developmental disorder. American Journal of Gastroenterology 2000; 95:2285-2295

3.        Furlano RI, Anthony A, Day R, Brown A, McGavery L, Thomson MA, et al. Colonic CD8 and ?d T cell infiltration with epithelial damage in children with autism. Journal of Pediatrics  2001;138:366-372

4.        Torrente F, Machado N, Ashwood P, et al. Enteropathy with T cell infiltration and epithelial IgG deposition in autism. Molecular Psychiatry 2002;7:375-382

5.        Uhlmann V., Martin CM., Shiels O., Pilkington L., Silva I., Lillalea A. Murch SH., Wakefield AJ., O’Leary JJ. Potential viral pathogenic mechanism for new variant inflammatory bowel disease. Molecular Pathology. 2002;55:1-6

6.        Kawashima H., Takayuki M., Kashiwagi Y., Takekuma K., Hoshika A., Wakefield AJ. Detection and sequencing of measles virus from peripheral blood mononuclear cells from patients with inflammatory bowel disease and autism. Digestive Diseases and Sciences. 2000;45:723-729

7.         Wakefield AJ and Montgomery SM. Measles, mumps, rubella vaccine: through a glass, darkly. Adverse Drug Reactions & Toxicological Reviews 2000;19:265-283.

8.         Wakefield AJ and Montgomery SM. Autism, viral infection and measles mumps rubella vaccination. Israeli Medical Association Journal 1999;1:183-187

9.        Wakefield AJ, Puleston J., Montgomery SM., Anthony A., O’Leary JJ., Murch SH. Review article: the concept of entero-colonic encephalopathy, autism and opioid receptor ligands. Alimentary Pharmacology and Therapeutics 2002; 16: 663-674

10.    Shiels O., Smyth P., Martin C., O’Leary JJ. Development of an allelic discrimination type assay to differentiate between strain origins of measles virus detected in intestinal tissue of children with ileocolonic lymphonodular hyperplasia and concomitant developmental disorder. Pathological Society of Great Britain and Ireland. Journal of Pathology. 2002 .A20

11.    Wakefield AJ, Anthony A. Clinical characteristics of children with autism and entero-colitis comparing recipients of one and more than one measles-containing vaccine (submitted).

 Publications by others

1.      a. Singh V., Lin S., Yang V. Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autism. Clinical Immunology and Immunopathology. 1998:89;105-108

2.      a. Singh VK. Neuro-immunopathogenesis in Autism. 2001. New Foundations of Biology. Berczi I & Gorczynski RM (eds) Elsevier Science B.V. pp447-458

3.      a. Horvath K, Papadimitriou JC, Rabsztyn A, Drachenberg C, Tildon JT. Gastrointestinal abnormalities in children with autism. Journal of Pediatrics 1999; 135: 559-563

 

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[1] Stratton K., Gable A., Shetty P., McCormick M. Immunization Safety Review: Measles-Mumps-Rubella Vaccine and Autism. National Academy Press. Washington DC. 2001. www.iom.edu/imsafety