8.3 MMR and the Medical Research Council
Fitzpatrick, M. (2004) Chapter 8 ‘The Lancet Paper’ taken from MMR and Autism: What Parents Need to Know, London, Routledge. Copyright © 2004 Michael Fitzpatrick.
Although the Royal Free press conference projected the MMR-autism debate onto the national stage, and Dr Wakefield gained a growing status among anti-immunisation campaigners and parents of autistic children, he made little headway in convincing his medical and scientific colleagues of his case. In March 1998, at the request of Sir Kenneth Caiman, Chief Medical Officer, the Medical Research Council (MRC) convened an ad hoc group of 37 experts, drawn from the spheres of virology, gastroenterology, epidemiology, immunology, paediatrics and child psychiatry, to review the associations suggested by the Royal Free team between measles virus and MMR on the one hand, and between inflammatory bowel disease and autism on the other (MRC 1998). The group's meeting was chaired by the pathologist Professor Sir John Pattison (a veteran of the mad cow crisis); Dr Wakefield and epidemiologist Scott Montgomery (one of the Royal Free team) attended the meeting to present and discuss their case.
The group first considered the laboratory evidence produced by the Royal Free group for the hypothesis that measles virus caused inflammatory bowel disease and noted that ‘the most sensitive molecular genetic techniques were negative in the hands of all groups’ (MRC 1998: 2). They emphasised that further studies ‘must involve independent laboratories testing the same specimens, using full controls and a range of techniques with agreed experimental protocols’ (MRC 1998: 2). When considering the epidemiological evidence claimed to link viral infections and inflammatory bowel disease, the group found no correlation between measles or mumps infection alone and Crohn's disease and ulcerative colitis. The experts agreed that there was some correlation between the occurrence of measles and mumps infection within the same year and the later incidence of inflammatory bowel disease. However, they considered existing studies limited and recommended further examination by independent groups.
On autism, the group considered the Lancet paper and emphasised the point that autism commonly becomes apparent in the second year of life – at around the time children receive MMR. However, the group insisted, ‘such coincidence does not imply a causal link’. They pointed out that, whatever the trends in the incidence of autism, they bore no relationship to the Introduction of MMR. They considered that the proposed ‘leaky bowel’/opioid excess mechanism was ‘biologically implausible’ (MRC 1998: 3). They further pointed out that the supposedly distinctive pattern of ‘lymphoid nodular hyperplasia’ identified by the Royal Free group was a common and benign condition in children. Finally, it was argued that the findings of abnormally low levels of some immunoglobulins (IgA) in four out of the twelve children was a simple error resulting from the use of adult normal ranges (when using appropriate paediatric ranges, only one child had a low IgA level) (Richmond, Goldblatt 1998).
After a day-long meeting the experts concluded that there was no current evidence linking MMR and autism. They thought that ‘it would be surprising if the link had not been noted in other countries with good diagnostic facilities for autism where MMR has been widely given for many years’ and suggested that ‘further research on an international basis would settle this matter’ (MRC 1998: 3). The expert group advised the Chief Medical Officer that there was no reason for a change in current MMR vaccination policy, as had been recommended by Dr Wakefield. However, they proposed more research on both inflammatory bowel disease and autism. These Conclusions were sent in summary form to every doctor in the country in a letter from the Chief Medical Officer on 27 March (Caiman 1998).
Dr Wakefield later complained that he felt he had been ‘set up’ at this meeting (Mills 2002: 17). He claimed that the 37 experts had all been ‘picked by the government’ and that he and Dr Montgomery had had to face them ‘alone’. He felt that a nine-hour meeting fell short of the detailed scrutiny he had hoped for.
Following the March 1998 meeting, the MRC set up an expert subgroup to steer and monitor research in inflammatory bowel disease and autism. This subgroup included leading figures in the relevant disciplines and it invited other specialists to attend particular meetings: these included Dr Wakefield, and his co-authors Professor John Walker-Smith and Dr Simon Murch. In its report in April 2000, the subgroup noted further evidence from the Royal Free group of ‘a classic pan-colitis associated with severe constipation and immune dysregulation in a group of children with developmental disorders’ (MRC 2000, Wakefield et al 2000).
This study compared a series of 60 ‘consecutive’ cases of ‘autistic enterocolitis’ (including the orginal 12), with a control group of 37 developmentally normal children undergoing ileo-colonscopy. Given the controversy still raging around the Lancet paper, it was curious that the new study included no information about MMR or any other immunisation history. The study confirmed ‘an endoscopically and histologically consistent pattern of ileo-colonic pathology’ in ‘a cohort of children with developmental disorders’ (Wakefield et al 2000: 2294). It also recorded results of investigations suggesting minor immunological abnormalities. The authors described a subtle ‘new variant’ inflammatory bowel disease, lacking the specific features of either Crohn's disease or ulcerative colitis. They again drew attention to the association of this pattern of bowel disease with ‘a developmental disorder that was associated with a clear history of regression’ – a loss of skills after a year or more of normal development. They concluded that ‘this syndrome [autistic enterocolitis] may reflect a subset of children with developmental disorders with distinct etiological and clinical features’ (Wakefield et al 2000: 2294).
This study was open to the same charges of selection bias as the Lancet paper. It was also criticised on the grounds that the control group was not properly matched for age. Apart from providing a fuller picture of the supposed new syndrome of ‘autistic enterocolitis’, it added little to the continuing MMR-autism controversy. The MRC report concluded that ‘the case for “autistic enterocolitis” had not been proven’ (MRC 2000: 4). It commented that the Royal Free studies had been performed in a ‘self-selected group of patients and the histological finding of ileal lymphoid-nodular hyperplasia may have been secondary to severe constipation’ (MRC 2000: 4).
The subgroup concluded that, in the 18-month period following Dr Wakefield's Lancet paper, ‘there had been no new evidence to suggest a causal link between MMR and inflammatory bowel disease/autism’ (MRC 2000: 5). It conceded that much remained unknown about these conditions and that MRC support for research in these areas, particularly inflammatory bowel disease, was weak. It made a series of specific recommendations for future research.