A recent issue of the journal Acta Neurobiologiae Experimentalis (ANE) focused upon autism. Not just autism, but autism causation with papers on vaccines, acetaminophen and, of course, mercury. The idea for this focus edition came from Professor Dorota Majewska who holds the EU Marie Curie Chair at the Institute of Psychiatry and Neurology in Warsaw, Poland. The authors for this focus issue are largely the same as those from a conference Prof. Majewska organized in 2008, Autism and Vaccinations .
The recent paper by DeSoto and Hitlan, Sorting out the spinning of autism: heavy metals and the question of incidence, is basically a review article. It has been touted as support for the mercury hypothesis with a commonly quoted phrase,
Fifteen were offered as evidence against a link between exposure to these metals and autism. In contrast, a sum of 43 papers were supporting a link between autism and exposure to those metals
That said, I was planning to avoid the recent DeSoto and Hitlan paper. It isn’t really new (adding to the number of articles on toxins and autism without adding to the knowledge base). I was going to avoid the paper, that is, until Prof. DeSoto gave an interview for the Age of Auitsm blog. I don’t understand why the Age of Autism considers Prof. DeSoto to be an expert on so many areas of autism and the environment. The breadth of her work is not great. Below is an exchange which shows what I mean. Prof. DeSoto was asked to comment on the recent study by Hewitson et al., comparing vaccinated and unvaccinated monkeys.
Q: There is a study published in Acta Neurobiologiae Experimentalis alongside yours that deals with vaccinated and unvaccinated primates. Do you have a reaction to the study or its conclusions?
Dr. DeSoto: All the primates were vaccinated, the difference was whether there was a heavy metal additive. This is a potentially important study. There are a few weaknesses that prevent strong conclusions. The size of the control group is small (apparently n=2). Given that rhesus neural development within the brain region of interest is not all that well documented, a larger control group would have been desirable. This weakness is acknowledged by the authors.
Isolating the infant monkeys shortly after birth is a significant change from normal environment. The severing of the maternal bond and being raised essentially alone (only visual contact was maintained with the peer infants) affects every aspect of development – including neural development. There is evidence that brain volume is specifically affected by isolation. The rearing situation in the study, in my mind, is not very comparable to normal development, especially if the outcome of interest includes brain volume.
That said, this is the only study that has compared the net effect of multiple vaccination additives on brain development. Above all, I have to editorialize and say this seems difficult to understand (that is – why is this the only study?). If some scientists and some parents question the safety of the vaccine schedule, such studies as this one are the way to investigate the concerns.
Now, the one study that exists (even if there are caveats that go with pilot research) suggests there are differences. Whether one is of the opinion that individually testing vaccines is as good as testing the combined effect or not – at this point it is imperative that additional studies be conducted on the additive effect of the full vaccine schedules.
To be clear and to repeat, if one thinks that the vaccines with additives given in close succession have no effect on neural development– this ought to be established empirically. One thing that I noticed in the study is the main effect for difference in brain volume (no time effect). It should be noted that this suggests the early administration of additive-containing vaccine (first four rounds) was a culprit of interest.
Prof. DeSoto did not take a careful look at the Hewitson et al. study. How do I know this? In the above interview, DeSoto states:
“All the primates were vaccinated, the difference was whether there was a heavy metal additive”
The paper states, “”Four infants were assigned to the unexposed study group and received saline injections according to the schedule in Table I”“. The differences included the heavy metal additive, as well as all the ingredients that make a vaccine differ from saline.
What amazes me is that the interviewer at the Age of Autism missed that as well. Even though AoA has touted the Hewitson study greatly, they don’t appear to have read it closely.
This is not a minor detail. It is key to the study design and conclusions.
Given that rhesus neural development within the brain region of interest is not all that well documented
I think that Prof. DeSoto can be excused for not realizing that there is a study tracking the development of precisely the amygdala in macaques. This is because Hewitson et al. did not include that reference (which was easily found in a pubmed search).
“The size of the control group is small (apparently n=2)”
The control group was 4. One was excluded for “scheduling reasons” and the other for unknown reasons. This was a major problem with the study. Fatal, one might say, as the brain sizes of the control group didn’t grow between the two time periods tested (about 4 months and about 6 months of age) for the monkeys. At the same time, their amygdalas shrank. This was a big warning sign that something was amiss with the control subjects, but this was ingored by Hewitson, et al.. Based on this faulty premise, Hewitson et al. claimed that the brains and amygdalas of the vaccinated monkeys were on an abnormal growth path. It is amazing that Prof. DeSoto missed that.
A fact that I am not surprised that Prof. DeSoto missed is that in a previous IMFAR abstract on this group, Hewitson et al. came to the exact opposite conclusion: that the brains of the vaccinated monkeys did not grow as fast as the unvaccinated monkeys.
Back to the recent DeSoto and Hitlan paper. They make the following statement:
It is worth noting that there have been only three empirical articles directly comparing those with and without an ASD on mercury levels in the body to a control group of normally developing matched controls that report that report no link (Ip et al. 2004, Soden et al. 2007, Hertz-Piciotto et al. 2010). While, the most recent article appears to be the strongest, lacking any obvious errors or flaws (we think that this recent article does provide at least some legitimate evidence contradicting the hypothesis that autism and heavy metals are linked), the other two are seriously flawed.
In the end, this mention of the Hertz-Picciotto study is why I decided to write about the DeSoto piece, and in the process bring in the interview.
Part of what made the Hertz-Picciotto study strong was the fact that they controlled for fish consumption. Correct me if I am wrong, but I believe this is something that Ip did not do, nor did DeSoto and Hitlan in their re-analysis. I don’t see mention of fish consumption in the recent DeSoto and Hitlan paper.
Again, I’ll point out that the analysis by EpiWonk was thorough and clear. I wish he had published it. I don’t think consider fish consumption to state that the DeSoto/Hitlan re-analysis of the Ip data is likely not thorough enough to make the conclusions they draw.
The fact of the matter is, the Ip data just aren’t that profound. It was worthwhile to do a re-analysis given the errors in the Ip dataset and paper. But it was three years ago that DeSoto and Hitlan did their re-analysis. In the meantime, Hertz-Picciotto et al. have a better dataset and a more thorough analysis.
DeSoto and Hitlan editorialize a bit in their paper:
If a person has publicly staked his/her career on a certain position being right, it may become harder to keep a truly open mind, even when new data become available and even when the original intent was to be objective. A way this bias might manifest itself is an overstatement or slight misstatement of results. We feel that both sides have been guilty of this, and this happens when a person becomes so confident in the correctness of his/her own view that he/she no longer reviews evidence to the contrary. Unconscious bias may exist even in the best scientists.
This begs the question of whether DeSoto and Hitlan are as guilty of those they chide. Re-analyzing the Ip data is not staking their career on a certain position. Repeatedly publishing on such a limited dataset does make this reader start to question whether some piece of their reputation is now tied to this position. With apologies to Prof. DeSoto, but the fact that her misimpressions of the Hewitson et al. paper are skewed towards the mercury hypothesis makes me wonder even more.
The autism research community needs to have fresh eyes looking at questions and data. DeSoto and Hitlan did well to reanalyze the Ip data once the mistakes were shown. They just appear to this observer to have (a) overstated the interpretation of their analysis and (b) gotten very quickly in to exactly the sort of rut they accuse others of being in.
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<a href="http://leftbrainrightbrain.co.uk/2010/08/prof-desoto-discusses-mercury-and-autism/">Prof. DeSoto discusses mercury and autism</a>