http://www.thelancet.com/journal/vol359/iss9307/full/llan.359.9307.editorial_and_review.20100.1

 

Editorial

 

Time to look beyond MMR in autism research

Is the measles, mumps, and rubella (MMR) vaccine safe? Yes, acceptably so, is the only conclusion possible to reach in the face of the totality of the epidemiological evidence. There are no substantiated data to suggest that the MMR vaccine causes autism, enterocolitis, or the syndrome first described by Andrew Wakefield and his colleagues in The Lancet in 1998. New research from some of the same authors as the 1998 Lancet report, in conjunction with a Dublin group led by Prof John O'Leary, has been published early online in Molecular Pathology. Fragments of the measles virus genome are reported in 75 of 91 children with ileal-lymphoid-nodular hyperplasia, enterocolitis, and developmental disorder, compared with five of 70 control children. But, crucially, these data do not support any link to the MMR vaccine, since no vaccine-specific strain data are presented for measles, mumps, or rubella. This latest twist has prompted Prof John Walker-Smith to end his silence since the publication of the first 1998 paper, of which he was the senior author. In this week's Correspondence columns (see page 705), Walker-Smith endorses the use of MMR, and calls for an independent research agenda into the causes of the bowel and behavioural disorders in this small and select group of children.

Sadly, a balanced scientific debate has given way to personal attacks and unreasoned demands for single vaccines. Public faith in the MMR vaccine has been eroded, leading to falls in its uptake and now outbreaks of measles in the UK. Unless public opinion swiftly changes, measles, mumps, and rubella cases will become commonplace, with their resultant deaths and sometimes serious morbidity, mirroring the pertussis vaccine scare in the 1970s. Doctors need to present all of the evidence to parents to allow them to make informed decisions, and that evidence comes down in favour of MMR.

But the debate also needs to move beyond the safety of MMR. What of autism and the burden it brings to children and parents? As Walker-Smith highlights, these children are ill-served by the current fear that MMR causes autism. The UK Department of Health announced last week that £2·5 million was to be given to the Medical Research Council to support autism research, following publication of the MRC's report on autism in December, 2001, which documents that six per 1000 children under 8 have an autism-spectrum disorder. Whether the actual number of cases is increasing or whether this high prevalence is due to increased awareness will be an important area for future research.

What is clear from the MRC report is just how much is unknown about the physical and psychological abnormalities that may underlie autism, let alone the possible causes. Functional brain-imaging studies have shown underactivation in areas associated with planning and control of complex actions, and in areas linked with processing socioemotional information. Brain neurotransmitter abnormalities have been reported. Psychological theories focus on social understanding, control of behaviour, and ability to focus on detail, but there are large gaps between theory and practice. A genetic component to autism-spectrum disorders is established, and the search for autism-susceptibility genes is underway. But the complexity of the autism-behavioural phenotype and the lack of knowledge about the developmental processes that are disrupted in autism are hampering molecular research. In addition to infections, prenatal exposure to drugs, perinatal complications, and diet have all been suggested as environmental triggers of autism, but independent replication will be critical in establishing whether any of these factors is relevant.

In 1998 in The Lancet, calling for an effective pharmacovigilance system for detecting vaccine-associated adverse events, Robert Chen and Frank DeStefano said "Without such a system, vaccine-safety concerns such as that reported by Wakefield and colleagues may snowball into societal tragedies when the media and the public confuse association with causality and shun immunisation". Unfortunately, this is exactly what has happened with MMR. In addition to such a system, a clear research agenda into the causes, developmental abnormalities, and treatments of the autism-spectrum disorders is needed.

The Lancet

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