Action For Autism

Autism Omnibus: MMR - the evidence.

Throughout the entire Autism Omnibus Proceedings (OAP) the decision about whether or not vaccine strain measles virus had caused autism depended on a simple, verifiable fact. Could the petitioners show that vaccine strain measles virus had persisted in the bodies of autistic children? Special Master Hastings who heard the initial test case of Michelle Cedillo devotes 45 pages of his Decision to reviewing the evidence for this. (pages 40 -85)

Specifically, the petitioners’ primary expert concerning the causation of autism,  Dr. Marcel Kinsbourne, made it clear that his opinion in any individual case would depend upon the existence of a reliable laboratory finding of persisting vaccine-strain measles virus in the body of the individual in question. (Tr. 1180A, 1183A, 1196A.) Similarly, the petitioners’ primary expert concerning the causation of chronic gastrointestinal dysfunction, Dr. Arthur Krigsman, also specified that his opinion in any individual case would depend upon the existence of such a reliable laboratory finding of persisting vaccine-strain measles virus in the individual. (Tr. 531-33A, 538A.)

A Reliable Test for Persistent Measles Infection?

A logical consequence of this is that petitioners would have an interest in establishing the reliability and validity of the testing carried out by Professor O’Leary’s team at the Unigenetics Laboratory in Ireland on biological samples taken from Michelle Cedillo and other autistic chidren. Equally, the respondent would wish to challenge its reliability and validity. In addition to the testing carried out for the purpose of litigation the O’Leary lab had also carried out testing for research that was peer reviewed and published in academic journals. Of particular relevance was the paper by Uhlmann et al (2002) in which O’Leary’s team utilized the same PCR techniques that were used to test Michelle Cedillo’s sample.

In order to find measles RNA in the tissue samples they had to use a technique known as polymerase chain reaction (PCR). In PCR testing you use a primer that is known to react with your target material to amplify the target material, in this case measles RNA. But you have to perform additional tests to ensure that your primer is identifying measles RNA and only measles RNA. You have to determine that your primer is specific to the task and that there are no false positives.

When D’Souza et al (2006) tested autistic children’s blood for measles RNA using the same methodology as described in the Uhlmann paper they found lots of measles. They found it in the autistic children and the non-autistic controls. So they performed additional tests which filtered out most of the false positives. Then they carried out a “gold standard” test known as sequencing which eliminated all seven of the nine remaining samples which were able to be successfully sequenced. They concluded that none of their samples contained measles virus. They also concluded that the Uhlmann study was equally unlikely to have detected measles RNA because the primer was not specific enough to distinguish measles RNA from human DNA.

There is an obvious problem with applying the D’Souza findings to the Uhlmann study and by extension, to the reliability of the O’Leary lab in relation to Michelle Cedillo. De Souza found measles in nearly all their samples. If O’Leary was similarly unreliable why didn’t they find measles in their non-autistic control group?

Three expert witnesses for the respondent: Drs. Bustin, Rima and McDonald- offered a possible explanation. All agreed that procedures at O’Leary’s lab were error prone and liable to contamination and false positives. Dr. Bustin and Dr Rima also found evidence of alterations to laboratory records which, according to the testimony of Dr Bustin, were certainly improper and perhaps fraudulent. There were other problems.

For example, sometimes the guidelines of the testing equipment manufacturers were not followed, which could erroneously make negative results appear to be positive results and disregard for accepted procedures that seemed calculated to deliberately generate false findings of measles virus in some cases.

This led Special Master Hastings to note that

Dr. Bustin’s testimony suggested the possibility that the Unigenetics personnel might have been deliberately using incorrect settings on their testing machine, in order to generate “positive” results that might support the MMR/autism causation theory. (Tr. 2009-11A.)

Dr McDonald stopped short of alleging deliberate fraud but concluded that

I have had the opportunity to examine the majority of those so-called positive in cell-PCR slides and discovered worrying discrepancies between the methodologies reported in the Uhlmann et al paper and what was actually done in the lab. The technique is completely unreliable with an unacceptably high experimental failure rate, many of the control sections were destroyed during the processing, the wrong technical controls were being used, and the claims of positivity or negativity were subjective and spurious. In cell-PCR does not detect measles virus in the lymphoid tissue of children with autism.

In the face of detailed and damning testimony like this the assertions of the petitioners’ witnesses that they were satisfied with the reliability of the testing carried out at the O’Leary lab were not persuasive.

Shooting the messenger

Although the petitioners had failed to provide any evidence for persistent measles virus they still defended the hypothesis by criticizing those studies like D’Souza that called the hypothesis into question. This has been a common feature of both the Omnibus proceedings and the wider debate about vaccines and autism. The vaccine blamers seem to operate on the totally unscientific basis that once they have presented a plausible hypothesis it is up to their critics to provide proof positive that the hypothesis is false and any perceived flaws in these critics’ arguments are assumed to strengthen the hypothesis. I am sure there is a name for this sort of logical fallacy. The only thing that can strengthen a hypothesis is data.

Nevertheless, Dr Hepner for the petitioners

stated that the failure of the Afzal and D’Souza studies to replicate the findings of the Uhlmann study was probably due to two factors. First, in those Afzal and D’Souza studies, the authors tested certain blood cells of the children, not intestinal tissue as did the authors of the Uhlmann article. Second, the Afzal and D’Souza studies tested autistic children, but not autistic children with gastrointestinal dysfunction as was the case with the Uhlmann testing. (Ex. 63, pp. 4-5; Tr. 629A-31A.)

I am not a scientist. But it seems self evident to me that if measles virus is persisting in the gut of autistic children and infecting their brains it would be remarkable if it was not also found in their blood. And D’Souza did carry out a further study on intestinal material with similar results. Furthermore the architect of the MMR/autism hypothesis, Andrew Wakefield, took part in a study that used PCR to detect measles RNA in the blood of autistic children.

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.

The second criticism, that other researchers have not tested autistic children with GI dysfunction and this explains their failure to detect measles in the children, misses the point that D’Souza did find measles when he used the same techniques as the O’Leary team but these were false positives. Where is the data to support the petitioners’ case? It is not enough to query the studies that contradict your hypothesis. You need some positive evidence as well. The best that Dr Hepner could do, apart from defending the Uhlmann study, was to point to research of her own that has still not been published so we only have her word for it.

Finally, Dr. Hepner pointed to a study that is currently in progress, conducted by herself and several others, to which I will refer as the “Walker study.” She stated that the “preliminary data” from that study “present another step in support” of the proposition that the measles virus persists in the intestinal tissue of autistic children. (Ex. 63, p. 5; Tr. 634A-35A.)

Absence of Evidence

The petitioners not only failed to provide any reliable evidence for persistent measles infection. They also neglected to provide any evidence that the measles they thought they had detected was vaccine strain measles. This surprising omission drew this comment from Special Master Hastings.

The petitioners in this case, of course, need to demonstrate not only that Michelle Cedillo and other autistic children have persisting measles virus in their bodies, but that such persisting measles virus is vaccine-strain measles virus, i.e., derived from an MMR vaccination rather than from the natural, “wild” form of measles virus. The Uhlmann article, however, does not even purport to show that the measles virus, which was claimed to have been found in the children’s biopsies, was vaccine-strain measles virus. Similarly, the specific Unigenetics test of Michelle Cedillo’s tissue purported to identify only measles virus, not vaccine-strain measles virus.

The fact that the petitioners were unable to provide any evidence that vaccine strain measles virus had persisted in Michelle Cedillo or any other child for that matter left them trying to argue that the hypothetical possibility that MMR could cause autism was more probable than not. (The fifty percent plus a feather argument)

Hypothesis versus data

Case reports often suggest a hypothesis that has the power to explain novel situations. Autism emerged from case studies published contemporaneously but independently by Kanner in the USA and Asperger in Austria. But many hypotheses are generated in science and only those that are supported by data from systematic investigations will prosper. The MMR/autism hypothesis has been around for at least ten years since Wakefield’s paper in the Lancet. Unfortunately for the petitioners, most of the data has piled up against the hypothesis, as was evident from the proceedings in the Vaccine Court.

Vaccines have not always been with us and many parts of the world still do not have adequate supplies. So the obvious question is, “In the absence of vaccines does wild strain measles virus cause autism?” The answer is no. Measles virus can persist in the body and it has been known to infect the brain, often with fatal consequences. But there is no evidence that it has ever caused autism.

Perhaps the vaccine strain, because it is weaker than the wild strain, could cause autism instead of killing you. It could enter the brain, cause an inflammatory reaction and the resulting brain damage could cause autism. Perhaps. But the argument is very weak. Inflammation is associated with some cases of autism. Measles can cause inflammation. But it is quite a stretch to speculate on that basis that vaccine strain measles infection causes an inflammation that leads to autism. Special Master Hastings actually described the petitioners’ theory as speculative and dismissed it because of expert testimony like this on page 89 of Cedillo.

• This “is not biologically plausible.” - Dr Griffin.
• It would require a “new biology.” - Dr Ward.
• It “does not follow any [known] biologic model of a measles infection of the brain” - Dr Wiznitzer.
• “We understand especially what measles virus may or may not do within the nervous system,” and that knowledge is incompatible with the theory that the persisting measles virus would cause autism. - Dr Rust.

Rectifying an anomaly

And that is it really. A biologically implausible theory with no factual evidence to support it was allowed to drag on for seven years. The costs must run into millions of dollars. The real cost is in the damage this case has done to confidence in vaccines.  Vaccine preventable diieases are making a comeback and measles is leading the way.  There is also the cost to the families who believed this theory and, in addition to the legal expense that many will have incurred, there are the medical costs of  the remedies sold to them by the same quack doctors who promoted the theory in the first place.

I am also struck by a curious anomaly. The petitioners’ case has always stressed that it is persistent vaccine strain measles virus that is causing autism. Because they thought they were detecting measles RNA in children many years after their vaccination they argued that it was the persistence that led to autism. This suggests a chronic, debilitating effect rather than an acute episode leading to immediate regression. Yet the petitioners argued for just such an acute episode within days of the vaccination in the case of Michelle Cedillo.

If that was the case there was no need to prove the persistence of measles virus. It did not need to persist in order to have the stated effect within the time frame as described by Dr Kinsbourne. Readers may recall that for years prior to joining the Omnibus Proceedings, the Cedillo family and their principle expert witness, Dr Kinsbourne, believed that Michelle had suffered a table injury. That is, she had suffered a recognized injury as a result of MMR vaccination. It is quite feasible that such a claim would have been accepted and Michelle would have won a settlement.

I see no way to rectify this particular anomaly in Michelle’s favour. But I do hope that when they decide on costs, the special masters take into account the quality of legal work and the standard of the expert testimony offered and match the payments accordingly. My next post on the Omnibus will look at some of these so-called experts, notably Krigsman and Bradstreet, in more detail.

March 11th, 2009 Posted by Mike | MMR, autism Omnibus, science, vaccines | 7 comments