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Saturday 11 September 2010

Peer Review fails again

Zahler I have written earlier on the connexion between vaccines and autism, expressing my desire to see more research before reaching a conclusion. Just seeing research, however, is not sufficient; it must be evaluated. This is supposedly the task of Peer Review, which is thought to ensure that no pseudoscience makes it into print in the scholarly journals. Note that Richard Horton, editor of The Lancet, wrote this about the peer review process (but not in his own magazine!):
We know that the system of peer review is biased, unjust, unaccountable, incomplete, easily fixed, often insulting, usually ignorant, occasionally foolish, and frequently wrong.
Perhaps nowhere has this process been demonstrated to have utterly failed more than in the case of Andrew Wakefield, who has been ostracized from the medical community over the publication (in The Lancet) of his study of the link between autism and the MMR vaccine. The first set of allegations against him (half of which were dismissed as unfounded), and his response, can be seen at this link. The 143-page fact sheet from the preliminary license revocation hearing of 3 of the article's authors (released this past January after 2½ years of investigation) can be found here.

As nearly as I can figure out, the only piece of evidence collected by Dr. Wakefield's team that is actually disputed is the condition of the children's intestines, and--what do you know--the original records have disappeared. This is how the Lancet article reads:

Findings
Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were nofocal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children.
The article concludes:
We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described. Virological studies are underway that may help to resolve this issue. If there is a causal link between measles, mumps, and rubella vaccine and this syndrome, a rising incidence might be anticipated after the introduction of this vaccine in the UK in 1988. Published evidence is inadequate to show whether there is a change in incidence or a link with measles, mumps, and rubella vaccine. A genetic predisposition to autistic-spectrum disorders is suggested by over-representation in boys and a greater concordance rate in monozygotic than in dizygotic twins. In the context of susceptibility to infection, a genetic association with autism, linked to a null allele of the complement (C)4B gene located in the class III region of the major-histocompatibility complex, has been recorded by Warren and colleagues. C4B-gene products are crucial for the activation of the complement pathway and protection against infection: individuals inheriting one or two C4B null alleles may not handle certain viruses appropriately, possibly including attenuated strains. Urinary methylmalonic-acid concentrations were raised in most of the children, a finding indicative of a functional vitamin B12 deficiency. Although vitamin B12concentrations were normal, serum B12 is not a good measure of functional B12 status. Urinary methylmalonic-acid excretion is increased in disorders such as Crohn’s disease, in which cobalamin excreted in bile is not reabsorbed. A similar problem may have occurred in the children in our study. Vitamin B12 is essential for myelinogenesis in the developing central nervous system, a process that is not complete until around the age of 10 years. B12 deficiency may, therefore, be a contributory factor in the developmental regression. We have identified a chronic enterocolitis in children that may be related to neuropsychiatric dysfunction. Inmost cases, onset of symptoms was after measles, mumps, and rubella immunisation. Further investigations are needed to examine this syndrome and its possible relation to this vaccine.
One thing that greatly complicates the discussion is the latitude with which a diagnosis of Autism is dispensed. I read a billboard just the other day, that every 20 minutes another child is diagnosed with autism (where--in the hospital emergency room?). Yet the same child, with the same symptoms, can be diagnosed either with autism or pervasive development disorder, just on the basis of either not wanting to hurt the parents' feelings on the one hand, or qualifying for taxpayer-funded intervention on the other. It has become a political diagnosis as much as a medical one.

The research I have seen definitely points in the direction of a 3-fold link between:

1) Reaction to the MMR shots
2) Verbal and social regression around age 18 months
3) Casein and gluten allergy with cerebral symptoms

But millions of children being diagnosed with autism spectrum disorder don't necessarily show this triad of symptoms. If meaningful research is to be done, children that show this triad must first be segregated from the great mass of those labeled with ASD.

In the mean time, informed parents will continue to do their own research and work out their own treatment regimens. Classic autism is clearly both preventable and treatable. If existing treatments don't work in any given case, it only shows that more study needs to be done.

6 comments:

  1. And what do you think of the research in the book: Unraveling the Mystery of Autism and Pervasive Developmental Disorder: A Mother's Story of Research & Recovery, by Karen Seroussi?

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  2. I just read a synopsis Karen's story. She mentions Wakefield's research as validating her own. Wakefield's research is now so tainted that it will have to be done all over again to gain any credibility. Seroussi's still stands. I spoke to a child psychiatrist recently about autism and noticed that she chose her words very carefully in stating that on the whole, there is no documented link between vaccination of a population and the rate of autism in that population. Then she segued into the Wakefield/Lancet fiasco, as if that settled the matter. I was encouraged that in her own mind at least, she was still open to the implications of more research.

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  3. But have you read her book? They actually cured their child of Autism! Whatever sources they used, it lined up with their hypothesis, and they cured their child.

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  4. No, I don't have the book. All the autism cures I'm aware of included a GFCF diet--in some cases, that's all it took, along with enzyme supplementation. A whole industry has now arisen to supply the enzymes.

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  5. Yes, exactly, the GFCF diet. But that would prove the theory of the measles cells adhering to the walls of the colon, as explained in the book.

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  6. Actually, all sorts of autism cures are emerging these days, diet still being the most (or only) affordable one. And research is ongoing regarding the link to measles particularly:
    http://www.ncbi.nlm.nih.gov/pubmed/15694999?dopt=Abstract
    http://www.ncbi.nlm.nih.gov/pubmed/7760985?dopt=Abstract
    http://www.ncbi.nlm.nih.gov/pubmed/7541036?dopt=Abstract

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