Lancet MMR 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 񋌡
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