Action For Autism

MMR not linked to Autism

Have we finally turned a corner with the MMR/Autism scare? News reports today are almost unanimous in heralding the latest piece of research to find no evidence of a connection between the MMR vaccination and autism. One or two papers are grudging in their acknowledgements and turn to long time critics of the MMR vaccine like JABS spokesperson Jackie Fletcher and Dr Richard Halvorsen, a supplier of single vaccines for “balance.”

But the consensus seems to be that the MMR scare has run its course. This is the latest and largest case control study to look for evidence of the persistence of measles virus or elevated levels of measles antibodies in the blood of autistic children.

The results are reassuring. Researchers found no significant difference between autistic children, children with learning difficulties and typical controls. When they looked at differences within the autism group they got the same result. Children with childhood autism [ICD-10 classification equivalent to DSM-IV autistic disorder] showed no significant difference from children with other autistic spectrum disorders. It was the same when they compared regressive to non-regressive autism.

Having read the study I can see no obvious confounds that should undermine our confidence in its conclusion that:

No difference was detected in the distribution of measles antibody or in measles virus in ASD cases and controls whether the children had received the first, second or both MMR vaccinations. This remained true when the analysis was restricted to ASD cases with a history of regression. Only one child had symptoms of possible enterocolitis, and this child was in the control group.

Opponents of the MMR vaccine have, nevertheless, raised a number of objections. My favourite is Jackie Fletcher who is quoted by the BBC as saying that:

It is making a leap from having the actual data on the antibodies and saying MMR does not cause autism.

This shows a serious misunderstanding of the basic tenets of scientific proof. The authors are not saying that MMR does not cause autism. They are saying that they found no evidence to support the hypothesis that MMR causes autism and that we have an accumulation of data that suggests otherwise. The difference is that we do have “the actual data.” In the absence of any “actual data” that suggests otherwise there is no reason to give the MMR hypothesis any consideration at all.

Other critics of the paper have tried to question the data. John Stone has responded on a number of comments sections to alleged a high dropout rate. Either he misunderstands the process or he is being dishonest. This study took advantage of a larger study by Baird et al in order to focus on MMR. Parents all knew that the focus was on the MMR. Out of 1770 initial subjects selected for screening 735 declined or failed to complete the screening. After screening 255 of the remaining 1035 were selected for in depth assessment. John Stone is comparing the final study group with the initial sample. And, given that the researchers informed parents that the study was about the MMR vaccination, it is extremely unlikely that parents who believed that MMR was implicated in their child’s autism would withdraw.

There was a significant withdrawal at the next stage when 100 subjects either declined to provide or were unable to provide a suitable blood sample. Again, it is extremely unlikely that parents who believed that MMR was implicated in their child’s autism would withdraw at this stage. And most of the withdrawals were of children with learning difficulties but no autism.

Another objection is the use of blood tests rather than biopsies or lumbar punctures to obtain CSF samples. These are highly invasive procedures that are only indicated when there is clinical benefit to the child. It would be unethical to subject children to unnecessary and potentially risky medical procedures purely for the purposes of research. And such procedures are unnecessary unless you believe that measles virus and antibodies mysteriously vanish from the blood of autistic children when they enter the gut or the CSF. The authors clearly state that:

Measles virus replicates in a range of cells during infection, including the upper respiratory tract, intestinal cells, several T cell lineages and macrophages. Replication occurs for similar periods in these different sites. An earlier study had suggested detectable virus using PCR in PBMCs from children with ASD. We used PBMCs in this study as a proxy for gut mucosal cells, which were not obtained for ethical reasons.

The earlier study they cite was:

Kawashima H, Mori T, Kashiwagi Y, et al. Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism. Dig Dis Sci 2000;45:723–9.

If you visit Springerlink you learn that the fifth named author was Andy Wakefield. Critics cannot have it both ways. If Baird is wrong to look for measles virus in blood how can Wakefield be right to do the same thing? Or is Baird being criticized, not because she used the wrong method, but because she got the wrong results?

Another potentially valid criticism is that 255 is too small a number to reveal the small numbers of children who may have had an adverse reaction. But all the case studies purporting to find measles in the blood had considerably less subjects. It is quite possible for autistic children to have adverse reactions to vaccines just like other children. It is quite possible for them to have elevated levels, just like other children. In fact Baird et al. found three children with abnormal results on. They suggest:

two possible explanations for the finding of one RT-PCR-reactive sample in 98 cases of ASD and two in the 90 TD children. Immunity to measles is not always complete and measles genome has been detected in the PBMCs of asymptomatic people during measles epidemics. C2 and D6 measles genotypes were detected in the UK population before 2002. The finding may also be due to laboratory cross-contamination, which can be problematic with RT-PCR assays.

So will this study end the controversy? Probably not. As the Guardian leader writer put it today

So the evidence is now clearer than ever that the causal link does not exist. The reality, however, is that this may not alter the views of some who still insist MMR is a threat, for their thinking was never scientific and so is not amenable to the developing facts.

There are those who are instinctively hostile to technology, who always want to believe that modern medicine will do harm. Then there are those who want to believe that the state is a pernicious conspiracy, bent on endangering children. Last, but not least, are those with a vested interest in continuing to spread the mistrust. Dr Andrew Wakefield led the original research postulating the link, and he is currently before the General Medical Council on various charges, some relating to whether his work has been financed in ways that could have compromised his objectivity. Whether that charge is upheld or not, it is already clear that much of the media has stoked up unfounded fears on the irresponsibly selfish grounds that sensationalism sells.

The Guardian is not completely blameles in all this but it has a better record than its sister paper, the Observer. The important thing is that the majority of the media are finally reporting the science and turning their backs on the MMR circus.

February 6th, 2008 Posted by Mike | Andrew Wakefield, Autism, MMR, vaccines | 11 comments