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Too much vaccine/autism monkey business for me to be involved in–but apparently not Laura Hewitson

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Ever since I somehow stumbled into a niche in the blogosphere where I seem to be one of a handful of go-to bloggers for issues having to do with vaccines and the anti-vaccine movement, like Spider-Man I realize that with great power comes great responsibility.

Wait a minute. That beginning was too pompous and pretentious even for me. I know it’s hard to believe, but even Orac has limits when it comes to pretentiousness.

Orac-ian pomposity aside, there are indeed certain topics that I can’t resist. Whether it’s because they intensely interest me or my being an aforementioned “go-to” blogger compels me out of a sense of duty to take them on, take them on I must. Of course, what’s good about such topics is that they generally serve me up custom-made blog material and guarantee that, for a day at least, I have no trouble finding things to write about. Thankfully (or unfortunately–I can’t make up my mind), the anti-vaccine loons at Age of Autism have provided me with perfect material for a Friday in the form of their promotion of a brand, spanking new monkey study that purports to find that vaccines cause autism (or at least disturbing brain changes) in Macaque monkeys. Sadly, but not unexpectedly, this study is not in any sense brand or new, although it may well be spanking. Certainly it deserves a sound spanking, and that’s what it’s going to get right now.

New study shows vaccines cause brain changes found in autism!” proclaim Dan “Where Are The Autistic Amish?” Olmsted and Mark “Not A Doctor, Not A ScientistBlaxill, and the ravening hordes of anti-vaccine loons go wild. Yep, that’s what I’m talking about. Unfortunately.

Yes, the other day Laura Hewitson published as lead author a study in a journal that I had never heard of before (Acta Neurobiologiae Experimentalis) entitled Influence of pediatric vaccines on amygdala growth and opioid ligand binding in rhesus macaque infants: A pilot study. Think of it as Monkey Business in Autism Research, Take 3. But before I go into this study, perhaps it’s a good time to recap Monkey Business in Autism Research, Take 1 and Take 2. Note that this research is the same research that was published in NeuroToxicology last fall and then withdrawn in February in the wake of Wakefield’s disgrace due to his having had his medical license taken away by the General Medical Council in the U.K.

Basically, this “research,” first reported in an abstract at IMFAR back in 2008, is crap science through and through. It suffers from so many methodological flaws that I still marvel that it managed to get through any sort of peer review, much less IACUC review, and its lead investigator has a massive conflict of interest. I once complained about the “studies” that came from these experiments as being what’s known as the “minimal publishable unit” (a.k.a. MPU). In other words, Wakefield and his cronies appeared to be doing one monkey experiment and then chopping it up into as many individual papers as they can. From that, there were the three abstracts at IMFAR, the NeuroToxicology paper–and now this latest atrocity against science.

First, there’s one thing that stood out–nay, leapt out–at me as I read this paper. Do you see it? It’s there in the abstract and it’s there in the paper itself. Andrew Wakefield’s name is not on the paper. In fact, in the Acknowledgments section, we find this curious sentence:

Special thanks to Dr. Andrew Wakefield for assistance with study design and for critical review of this manuscript; and to Troy and Charlie Ball and Robert Sawyer.

Can it be? Andrew Wakefield relegated to a mere “special thanks to” notice tacked onto the end of the mansucript? Remember, Wakefield’s name was featured prominently on the previous incarnations of this study. His fingerprints are all over it. By any rights he should be the senior author on the paper, but he isn’t. I can only guess it’s that the reason is that his name and reputation are so toxic that the appearance of the Wakefield moniker on a submitted manuscript would guarantee that it won’t be accepted even in an apparently bottom-feeding journal like Acta Neurobiologiae Experimentalis. Actually, any journal that would accept a journal article this bad by Wakefield’s protégé, is almost by definition a bottom-feeding journal, but if you have any doubts, check out the rest of the issue, which contains not one but two articles by those masters of autism quackery, Mark and David Geier, originators of the Lupron protocol, not to mention an article by Hitlan and DeSoto. Truly, it’s a cornucopia of bad autism science! Perhaps, as Kev points out, it has something to do with the person who chose the theme of this particular issue of Acta Neurobiologiae Experimentalis, Professor Dorota Majewska. Although I don’t recall having mentioned it before, someone named Professor Majewska signed the original We Support Andy Wakefield petition that I had some fun with a while back.

Coincidence? I think not.

Another thing I noticed right away is another odd omission. There is no conflict of interest statement, even though there most definitely should be. As mentioned before, Hewitson has an autistic child who is part of the Autism Omnibus case. This sort of research, if it had been published earlier, could have been used to bolster the complainants’ case. Having been burned two years ago with criticism for not having reported her COI, Hewitson did report it in the 2009 withdrawn NeuroToxicology paper. Now she isn’t reporting it. I wonder why.

Actually, no I don’t.

In any case, on to the present study, which is clearly an offshoot of this earlier work. This is what was found:

Abstract. This longitudinal, case-control pilot study examined amygdala growth in rhesus macaque infants receiving the complete US childhood vaccine schedule (1994-1999). Longitudinal structural and functional neuroimaging was undertaken to examine central effects of the vaccine regimen on the developing brain. Vaccine-exposed and saline-injected control infants underwent MRI and PET imaging at approximately 4 and 6 months of age, representing two specific timeframes within the vaccination schedule. Volumetric analyses showed that exposed animals did not undergo the maturational changes over time in amygdala volume that was observed in unexposed animals. After controlling for left amygdala volume, the binding of the opioid antagonist [11C]diprenorphine (DPN) in exposed animals remained relatively constant over time, compared with unexposed animals, in which a significant decrease in [11C]DPN binding occurred. These results suggest that maturational changes in amygdala volume and the binding capacity of [11C]DPN in the amygdala was significantly altered in infant macaques receiving the vaccine schedule. The macaque infant is a relevant animal model in which to investigate specific environmental exposures and structural/functional neuroimaging during neurodevelopment.

Interesting. Hewitson’s finding claims that animals vaccinated with thimerosal-containing vaccines underwent increases in the size of the amygdala relative to control animals. As always, though, the devil is in the details, and it’s necessary to read the experimental methodology. Note that in this study, as in the previous iterations of this misbegotten study, there was a large mismatch in number between the control group and the experimental group, with four being given saline controls and twelve being given a vaccine “schedule” designed to mimic the vaccine schedule given to children in the U.S. in the 1990s. Hilariously, because all these vaccines are thimerosal-free, Hewitson had to add thimerosal to the vaccines to produce its replication of the vaccine schedule from the 1990s. Of course, because Macaque monkeys mature faster than humans, they received in one year what humans receive in four years.

During this whole period, the investigators then performed MRI and functional MRI, as well as positron emission tomography (PET) scans on the monkeys, which is why I say right here: Don’t get me started on how incredibly unethical Hewitson and Wakefield’s treatment of these poor monkeys. Remember, these monkeys have to be anesthetized every time they undergo a test, and they’re being jabbed with various vaccines or saline solutions all in the service of a highly improbable hypothesis that has been tested time and time again in humans through large epidemiological studies. These aren’t just mice or rats we’re talking about, either. They’re primates and highly intelligent. In fact, I would hesitate even to treat mice this way, and I know our IACUC at my university frowns on experiments that require multiple anesthesias and multiple procedures even on mice.

More interesting is something I found when I read the methods section more closely:

A complete set of MRI data at both T1 and T2 were obtained from 9 exposed and 2 unexposed animals.

And then there was this:

A complete set of PET data at both T1 and T2 were obtained from 9 exposed and 2 unexposed animals.

So let’s see. There were originally 12 exposed monkeys and four unexposed monkeys. That’s bad enough in that the number of monkeys in the control group was so small that it would take a large difference between the vaccinated group and unvaccinated group to produce anything resembling statistical significance. With only two animals in the control group, the situation is even worse. With such a control group, it would be damned near impossible to achieve a result that is statistically significant, and doing statistical analysis on such a data set is an exercise in futility. Worse, no explanation is given for why the three monkeys from the vaccinated group and one monkey from the unvaccinated group weren’t included in the analysis. (One of the monkeys in the unvaccinated control group was apparently excluded for the protocol not being followed.) That’s a rather glaring omission. A glaring omission indeed. If I were reviewing this paper, I would have demanded that the authors explain to me why they left out those monkeys and put a passage in the manuscript describing their rationale. Good thing for Hewitson I wasn’t a reviewer.

There’s also a disconnect betweent he abstract and what is actually reported in the paper. Let’s reiterate part of what the abstract says:

Vaccine-exposed and saline-injected control infants underwent MRI and PET imaging at approximately 4 and 6 months of age, representing two specific timeframes within the vaccination schedule.

Elswhere in the paper, the authors state:

For the exposed group there was a nonstatistically significant increase in right amygdala volume over time (P=0.16; Table IIa). For the unexposed group there was a significant drop in right amygdala volume over time (P<0.0001; Table IIa).

As Sullivan noted, that’s right: The authors observed a significant decrease in right amygdala volume in the control animals between four and six months of age. In fact, look at the figure that Sullivan relabeled from the paper to make it clearer. This is not a slight degree of shrinkage, either. It’s nearly a 30% shrinkage. Come to think of it, I hope Sullivan won’t mind, but I’m including a thumbnail of his graph with a link to it below:

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Also, as Sullivan points out, in infant monkeys, the amygdala doesn’t shrink. They grow until they reach full size at around 24 months. Yet in Hewitson’s experiments, the amygdala shrank nearly 30% in just two months between four and six months of age, while the sizes of the amygdalas in the vaccinated monkeys appeared to be increasing in size at a slow rate consistent with normal monkeys. Based on such thin gruel, Hewitson tries to argue that the increase in amygdala corresponds to an increase in whole brain size consistent with what has been reported in children with ASD. Yes, that’s the entire argument and those are the purported findings of the paper, and it’s all based on only 11 monkeys.

So what is the likely cause of this finding? Does this mean that saline injections cause the brain to shrink? Of course not. What almost certainly happened is that the control group was so small that by a random fluke of chance Hewitson happened to get two monkeys for whom the average brain volume decreased. This is not unusual or implausible; there’s a lot of variation in brain size, which is why larger numbers are needed to produce any results that can be believed. An N of 2 just won’t cut it. It’s not even clear that an N of 9 would do it either. Certainly I saw no power analyses worthy of the name in the statistics section, and I also saw a whole lot of “not statistically significant” results.

There’s one final observation. Two years ago at IMFAR, Wakefield and Hewitson presented an abstract that was clearly the precursor to this latest paper. At the time the anti-vaccine loons at AoA were kind enough to post the entire text of the abstracts. So let’s take a look:

Pediatric Vaccines Influence Primate Behavior, and Amygdala Growth and Opioid Ligand Binding Friday, May 16, 2008: IMFAR

L. Hewitson , Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA B. Lopresti , Radiology, University of Pittsburgh, Pittsburgh, PA C. Stott, Thoughtful House Center for Children, Austin, TX J. Tomko , Pittsburgh Development Center, University of Pittsburgh, Pittsburgh, PA L. Houser , Pittsburgh Development Center, University of Pittsburgh, Pittsburgh, PA E. Klein , Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA C. Castro , Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA G. Sackett , Psychology, Washington National Primate Research Center, Seattle, WA S. Gupta , Medicine, Pathology & Laboratory Medicine, University of California – Irvine, Irvine, CA D. Atwood , Chemistry, University of Kentucky, Lexington, KY L. Blue , Chemistry, University of Kentucky, Lexington, KY E. R. White , Chemistry, University of Kentucky, Lexington, KY A. Wakefield , Thoughtful House Center for Children, Austin, TX

Background: Macaques are commonly used in pre-clinical vaccine safety testing, but the combined childhood vaccine regimen, rather than individual vaccines, has not been studied. Childhood vaccines are a possible causal factor in autism, and abnormal behaviors and anomalous amygdala growth are potentially inter-related features of this condition.

Objectives: The objective of this study was to compare early infant cognition and behavior with amygdala size and opioid binding in rhesus macaques receiving the recommended childhood vaccines (1994-1999), the majority of which contained the bactericidal preservative ethylmercurithiosalicylic acid (thimerosal).

Methods: Macaques were administered the recommended infant vaccines, adjusted for age and thimerosal dose (exposed; N=13), or saline (unexposed; N=3). Primate development, cognition and social behavior were assessed for both vaccinated and unvaccinated infants using standardized tests developed at the Washington National Primate Research Center. Amygdala growth and binding were measured serially by MRI and by the binding of the non-selective opioid antagonist [11C]diprenorphine, measured by PET, respectively, before (T1) and after (T2) the administration of the measles-mumps-rubella vaccine (MMR).

Results: Compared with unexposed animals, significant neurodevelopmental deficits were evident for exposed animals in survival reflexes, tests of color discrimination and reversal, and learning sets. Differences in behaviors were observed between exposed and unexposed animals and within the exposed group before and after MMR vaccination. Compared with unexposed animals, exposed animals showed attenuation of amygdala growth and differences in the amygdala binding of [11C]diprenorphine. Interaction models identified significant associations between specific aberrant social and non-social behaviors, isotope binding, and vaccine exposure.

Conclusions: This animal model, which examines for the first time, behavioral, functional, and neuromorphometric consequences of the childhood vaccine regimen, mimics certain neurological abnormalities of autism. The findings raise important safety issues while providing a potential model for examining aspects of causation and disease pathogenesis in acquired disorders of behavior and development.

Note that we appear to have had a mass exodus of authors from this study Note also the emphasized sentence.

That’s right. Back then Hewitson was reporting that the amygdalas of the infant monkeys were not growing normally in the vaccinated group. There were also 13 monkeys in the vaccinated group and three in the unvaccinated group, truly the incredibly morphing expermental groups. It looks to me as though some hypothesis rearrangement intervened here. Apparently between 2008 and 2010, someone read some research suggesting larger brain sizes were characteristic of autism and ASD. Either that, or I can’t help but ask Hewitson: How could this have happened? Were you incompetent then analyzing your data or are you incompetent now? OK, I admit it. It’s a trick question. The two aren’t mutually exclusive, and Hewitson appears to have been incompetent both then and now, in my not-so-respectfully insolent opinion. The study didn’t have enough monkeys, particularly in the control group, to come to any conclusion worth having any confidence in whatsoever.

What a horrific waste of primates!

Naturally, none of this stops Wakefield’s cheerleaders over at the anti-vaccine crank blog Age of Autism from promoting this study to the hilt, even going so far as to cite Wakefield’s discredited “monkey business” study as though it showed anything other than no real difference between the groups and were a different study altogether, rather than just another appendage of the same incompetent experiment. In the comments we’re treated to examples of conspiracy mongering so hilarious that I laughed out loud at a couple of them, in particular this one by Jeff C.:

…this will be dismissed by the medical establishment as a study conducted by known “anti-vaccine nuts” published in some “third-rate, foreign journal”. They’ll say, “Why isn’t it published in a reputable, mainstream journal? How do we know the peer review was adequate?”

Of course, they control the “mainstream” journals, they control peer review, and would never let a study like this see the light of day. The system is rigged, and they’ll use that to discredit or stifle any study not to their liking.

The only way to break the dam is to keep studies like this coming. In the meantime, we need to get the word out on this one.

Actually, were it not for the abuse of primates, a part of me would hope the anti-vaccine movement keeps studies like this coming. Nothing destroys their scientific reputation faster than such mind-meltingly awful science. It’s so bad that each study like this can only guarantee further scientific marginalization of these cranks. It also provides excellent blog fodder, although too much risks frying my fragile eggshell mind.

Too bad it’s such a crime that so many monkeys had to give their lives in the service of such bad science. Blog fodder and discrediting the anti-vaccine movement aren’t worth the loss of primate life.

More reading on this terrible study:

  1. Terrible Anti-Vaccine Study, Terrible Reporting (crossposted to Science-Based Medicine)
  2. The genie is out of the bottle: vaccines cause autism
  3. The genie is out of the bottle. Part II – more genies, more bottles

ADDENDUM

Geez, the comments are getting worse:

The increased head size is likely caused by heavy metal interference with apoptosis (programmed cell death) which is the brain’s way of modelling itself into an optimum configuration. My older autistic son had a remarkably large head as a toddler which is now a more normal size as a teenager.

Let’s see, he’s mastered the science-y sounding jargon but clearly has no clue what it means. Truly, here we see an example of a little knowledge being a dangerous thing.

ADDENDUM #2

If you want to know how bad this study is, consider the fact that homeopaths like it.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

177 replies on “Too much vaccine/autism monkey business for me to be involved in–but apparently not Laura Hewitson”

I suspect the 2 control monkeys were exposed to conversations between anti-vaxers, which clearly explains the brain shrinkage.

Seriously, though, the figure is striking. If they actually believed those results, wouldn’t it be the case that the amygdala shrinks substantially in the average unvaccinated child? Surely, this should not be difficult to confirm.

If I were reviewing this paper, I would have demanded that the authors explain to me why they left out those monkeys and put a passage in the manuscript describing their rationale.

The explanation may be easier than we think. Maybe… and this is just my opinion (and not that of anyone who pays me a miserable wage for a living)… Maybe they took out those monkeys which would have proven their theory wrong? I used to do that (hide evidence of my mistakes) all the time WHEN I WAS FOUR YEARS OLD (which is the level of maturity I get from anti-vaxxers who keep complaining to my employers about me).

Not that I’m bitter or anything.

Hmm…perhaps the missing 2 control monkeys showed greater increases in amygdala volume than the exposed monkeys. Those two were the ones used in the earlier paper, while the two that showed a decrease were used for this one? Just throwing out ideas.

First it goes down… then it goes up…

…amazing how that happens if you have no control sample to speak of.

Add one… lose one… …whoops…

Dear me.

As Sullivan’s post that Orac linked to makes clear (including showing the normal developmental plot of amygdala volume in the macaque from someone else’s study), the “results” they report for the vaccinated group exactly parallel the normal expected timecourse. So, er, no effect of vaccines, then.

It would be hilarious if it weren’t so thoroughly dire.

Anyway – different point. Orac didn’t say, I presume since it is obvious to those who have followed this stuff, but the pattern of repeat invasive investigations under general anaesthetic/sedation parallels what Wakefield & friends did to their ASD child patients back in the day – also under, er, rather ethically dubious circumstances.

Nice.

Interesting analysis. Even a non-researcher such as myself recognized the low N as a significant problem.

If I encountered a result so unexpected with N=2, I would most definitely added subjects and repeated the experiment. I hope the peer review will look into that aspect and the others ORAC pointed out but I also see that as a collosal waste of time, money and primates.

Without having easy access to the information, doesn’t the exposed group’s growth match normal development? A boondoggle to prop up a fraud.

The authors observed a significant decrease in right amygdala volume in the control animals between four and six months of age.

Why do the authors care that there was a significant change within one group? Surely their results depend on there being a significant difference between the vaccinated and non-vaccinated samples. Looking at the data in the paper, it’s clear why they are harping on this – it’s their only significant result. That large gap between vaccinated and non-vaccinated samples in the above graph is not statistically significant (p=0.82).

The only reasonable conclusion they can draw from this data is that there is no difference between the vaccinated and non-vaccinated samples. Can’t say I’m surprised to see them pick out the one significant anomaly and ride it for all it’s worth though.

Typo alert: “There’s also a disconnect between he abstract“. “he” should be “the”.

And if the study had any clinical significance, rather than indicating that vaccines caused brain growth, it would indicate that vaccines prevented brain shrinkage.

A control group of just 2 animals? Is that a sufficient control group for ANY experiment?

Oh my, monkey brains growing as monkey brains should. Film at eleven. That entire statistics section was a complete waste of space, not to mention complete hand-waving, science-y sounding tripe.

I can only hope that this group is never allowed near animals again for this vapid experimentation. The University of Pittsburgh should be ashamed of themselves for allowing this unnecessary sacrifice of monkeys.

I just skimmed the paper (I don’t know how Orac can read things like this in detail). There were a few other problems I noticed.
First, they do not report the image resolution for either the MRI or PET data. The PET data has a reference to the protocol they used, but I’d still like confirmation about resolution used for this study. The image quality looks good, but when you’re talking about volume of interest sizes, this is an absolutely essential parameter to list.

Another major lapse is they gave no indication that the person drawing the volumes of interest was blind to the populations. (i.e. when they were drawing the volumes did they know if they were working on a vaccinated or unvaccinated money?) Lack of blinding should also have been a flat out rejection. Frankly, I think this is a bigger deal than the removed monkeys because an unblinded person can always go back to the data and adjust the volume sizes accordingly (sometimes by accident, but this is an issue of practice of science beyond ethics) At minimum, they should have reported on the drawing method used and given some evidence that the person drawing the volumes could consistently repeat the results.

OK, I just have to ask…

What’s the relevance of the Page/Beck (or Beck/Page, depending on your guitar god preference) Yardbirds photo?

🙂

@bsci, they claimed that “all image analysis was undertaken in an observer-blinded fashion.” However, others knew of the vaccination status of the animals. It’s no wonder that no decent journal would want to touch this.

@Scottynuke,
Good question. When I read the title, I expected a picture of the Monkeys but when that didn’t work out no matter how hard I squinted, I just skipped to the words…

there was a nonstatistically significant increase in right amygdala volume over time (P=0.16; Table IIa)

That alone made me facepalm. Repeat after me: there is no such thing as a nonstatistically significant increase. And even if they did increase, like Orac said, how do we know that’s not just normal development? Such a precipitous drop in the “control” group certainly isn’t “normal.”

I mean, I know it’s a third-rate journal and all, but c’mon, people this is Peer Review 101, here.

@ Scottynuke, MikeMa,& T.Bruce ( and Orac) : Oh, we are showing our age!( but that’s ok) Alternate reaction : “But *why* is he not showing a photo of the _Arctic_ Monkeys?” (current hot band ; one dates current “it” girl)

Yeah… I was kind of wondering if Orac thought those were the Monkees.

-RR-

“Oracian pomposity aside, …”

What an awesome paragraph! How do you pronounce Oracian (assuming it’s or’-ack): or’-ack-shun or or’-ack-en?

Nit-pick: eliminate the comma between brand and spanking.

I’m hung up on the choice between “Too Much Monkey Business” and “Not Enough Monkeys” as a slogan for the antivax movement.

Both hit the mark.

I do believed the necropsies were preformed on the wrong primates.

Unfortunatly adding 5 more would have only confounded the results further as the amygdala size plummeted.

“For the exposed group there was a nonstatistically significant increase in right amygdala volume over time (P=0.16; Table IIa). For the unexposed group there was a significant drop in right amygdala volume over time (P<0.0001; Table IIa).”

Wait, I don’t understand. Notwithstanding the bizarre wording of “a nonstatistically significant increase” (which I’ve never seen used in psychometric or med ed journals), the low sample size, the conflicts of interest, et – isn’t the conclusion of this that the researcher did NOT find the effect they claim they found? The amygdala volume in the treated group did not show a volume increase that was statistically significant. Therefore you fail to reject the null hypothesis and say that you cannot say that the treatment had an effect. Period.

It seems they’re trying to claim that amygdalas are supposed to shrink, not grow, and amygdalas that grow are indicative of ASD – but they haven’t shown here that a significant growth occured. They cannot claim to have observed ANY reliable change on the part of treated animals. And, frankly, I find it hard to believe that they actually found a significant change downwards with the control group, given an N of 2.

How did this get past a peer reviewer? Unbelievable. My intro Biostats students would have caught this.

Look, I know threadjacking is a faux pas, but I’m honestly confused here… (at least I’m not making an “Old Spice” TV commercial reference to Orac’s reply) 🙂

It’s the Yardbirds, obviously, but where’s the “monkey business” link? Am I that oblivious to the Yardbirds’ discography? Has Hewitson finally gone “Over Under Sideways Down” or something? Can’t get to Youtube from this PC, so I can’t access McNeely’s suggestion.

It’s the Yardbirds, obviously, but where’s the “monkey business” link? Am I that oblivious to the Yardbirds’ discography?

Apparently the answer to your question is, “Yes.”

Too bad Jeff C missed entirely what we’d say: it’s not where it was published, but how awful the science is. But alas, apparently “they” control peer review, so the conspiracy theory must be that their “science” is such that no matter how good it is it will be dismissed as shoddy. Theirs truly is a world where black is white, up is down, and cats and dogs are living together.

Scotty, think Chuck Berry cover. Everyone and their brother has done it. So you could say there’s been too much…

Theirs truly is a world where black is white, up is down, and cats and dogs are living together.

Let’s hope they don’t cross the streams.

This “study” is very similar to the “baby haircut” one.

They get a spurious result on the control group, and they redefine the study accordingly.

“Autism causes hairs not to bind mercury”

“Vaccines causes babies brains not to shrink”

…maybe one of their 2 control monkeys got ill because it was not vaccined ?

Orac, this is a great takedown…but there is a bigger picture to consider here: this paper was published in an autism-focused special issue of Acta Neurobiologiae Experimentalis. Seriously, check out the other papers in Volume 70, Number 2 (2010)

Turlejski K.
Focus on autism – editorial comment (pp: 117-118)

Pisula E.
The autistic mind in the light of neuropsychological studies (pp: 119-130)

Kawa R., Pisula E.
Locomotor activity, object exploration and space preference in children with autism and Down syndrome (pp: 131-140)

Cubała-Kucharska M.
The review of most frequently occurring medical disorders related to aetiology of autism and the methods of treatment (pp: 141-146)

Hewitson L., Lopresti B., Stott C., Mason N.S., Tomko J.
Influence of pediatric vaccines on amygdala growth and opioid ligand binding in rhesus macaque infants: A pilot study (pp: 147-164)

DeSoto M.C., Hitlan R.T.
Sorting out the spinning of autism: heavy metals and the question of incidence (pp: 165-176)

Geier D.A., Audhya T., Kern J.K., Geier M.R.
Blood mercury levels in autism spectrum disorder: is there a threshold level? (pp: 177-186)

Schultz S.T.
Does thimerosal or other mercury exposure increase the risk for autism? A review of current literature (pp: 187-195)

Majewska M.D., Urbanowicz E., Rok-Bujko P., Namysłowska I., Mierzejewski P.
Age-dependent lower or higher levels of hair mercury in autistic children than in healthy controls (pp: 196-208)

Geier D.A., Kern J.K., Geier M.R.
The biological basis of autism spectrum disorders: Understanding causation and treatment by clinical geneticists (pp: 209-226)

Schultz S.T.
Can autism be triggered by acetaminophen activation of the endocannabinoid system? (pp: 227-231)

Kazek B., Huzarska M., Grzybowska-Chlebowczyk U., Kajor M., Ciupińska-Kajor M., Woś H., Marszał E.
Platelet and intestinal 5-HT2A receptor mRNA in autistic spectrum disorders – results of a pilot study (pp: 232-238)

See any familiar names and pet hypotheses in there? I do…

It looks like this journal, or more specifically the journal’s editor, Kris Turlejski, may have become a sympathetic party to the Mercury Militia.

Let me also state, for the record, that I am embarrassed to have mis-spelled my own pseudonym…

I blame my normal-sized amygdala.

You know someone is going to have to conduct a more thorough study with a statistically significant number of animals to refute this. That means several more primates are going to be sacrificed to satisfy the delusions of these people.

I feel bad after euthanize rats and mice in our animal work. I simply couldn’t work with monkeys; I don’t think I could handle it emotionally.

On the Yardbirds,

maybe it’s because the study is on the Shape of Things like monkey’s brains.

http://www.bing.com/videos/watch/video/yardbirds-shape-of-things/7e0931695d0bdd7d2bd27e0931695d0bdd7d2bd2-70545441702?q=Yardbirds&FORM=VIRE2

Or, maybe these are the results when you do your research Over Under Sideways Down.

http://www.bing.com/videos/watch/video/over-under-sideways-down-yardbirds-page/f604e76a23390fafd13ef604e76a23390fafd13e-165672780975?q=Yardbirds&FORM=VIRE4

Too Much Monkey Business was a Chuck Berry song.

A reader at AoA asked: “If no one has studied non-human primate amygdala development, how do we know what ‘normal’ is? Is it normal to have a decline in amygdala size during development?”

In reply, another reader simply provided a link to the abstract of the paper Sullivan pointed out. [Payne C, Machado CJ, Bliwise NG, Bachevalier J. Maturation of the hippocampal formation and amygdala in Macaca mulatta: A volumetric magnetic resonance imaging study. Hippocampus. 2009 Sep 8]

Since that paper showed that the conclusions of the Hewitson paper (which relied on an anomalous, probably scatter-related decline in amygdala volume in the tiny control group while vaccinated macaques developed normally) are utter nonsense, it’s not surprising that the post was quickly deleted. Olmstead and Blaxill can’t handle the truth.

@John Harrold

You know someone is going to have to conduct a more thorough study with a statistically significant number of animals to refute this.

Not really. As Sullivan pointed out (Orac provided a handy link), the increasing size of the amygdala observed in the experimental group kinda matches the increasing size of the amygdala in macaques in general, based on a study of macaque hippocampal formation and amygdala maturation from 2009 that looked at a similar number of monkeys. If anything, the control group’s shrinkage is the anomaly in this study.

Thanks for the links, Orac. You are of course welcome to anything I blog.

It is very difficult to discuss this paper calmly. The science is so remarkably bad. Mark Blaxill and Dan Olmsted either didn’t read it or they didn’t understand it–or they don’t care.

This is a waste of time, money and laboratory animals. It is totally irresponsible to hype this nonsense and inflame and upset parents.

This paper would be a joke if it weren’t for the harm it is causing.

Well, more pure Wakefield. The manipulation of controls has been his hallmark for 20 years. As is the absurdity of the ultimate claims. Invariably, it’s too many parents blaming the vaccine, too many samples coming up positive for measles, too many monkeys with evidence of gross brain damage.

I guess they just can’t help themselves. Greed is in the nature of the cheat.

– Oh, and let’s not forget Carol Stott, who sets the benchmark for the calibre of these people:

http://briandeer.com/mmr/carol-stott.htm

Well, who could hope to match an all-knowing plexiglass box of lights in listing the Yardbirds’ various covers?

I sit corrected. 🙂

And Hewitson’s babblings don’t even rate being called a “study,” but never mind, I’ll sit quietly in the corner now. 🙂

@scottynuke: don’t feel bad. I can’t access youtube at work either and had no idea what Orac was talking about either. (Yes, I am musically illiterate, why do you ask? My husband nearly left me when I admitted I had no idea Eric Clapton was a member of a band called Creem ?Cream?)

@squirrelelite: Thanks for the Yardbirds/Chuck Berry info. As I noted above, I had no idea.

This seems to be a repeated trend. If the data don’t support your position, make up data that do. That’s how Wankerfield started; it was prominently on display during the Omnibus trials; and now this.

I loathe PETA’s methods and support ethical animal studies but shouldn’t someone give them a link to this paper? The waste of primates is appalling.

Mike,

PETA as capital punishment? If you oppose the death penalty, then you should also oppose PETA.

Acta LineHookAndSinka has an impact factor of 1.33 – publishing this load of vaxaloon crap is going to catapult them into new heights! There is no one I know on the editorial board. Sad.

@Todd W.
The only thing about PETA I ever liked was the use of Dominique Swain as a naked spokesperson. That was it. Other than that, they’re just as diluted as our “friends” at “that other blog”… you know? The one that thinks itself a “newspaper”?

“What almost certainly happened is that the control group was so small that by a random fluke of chance Hewitson happened to get two monkeys for whom the average brain volume decreased. ”

You’re being too generous Orac. There is a clear pattern of behavior here. In each and every “study”, different permutation of similar “experiments” all seem to point to the same conclusion. Even if obvious problems are apparent with her methodology, they all seem to designed to imitate the childhood vaccine schedule and produce the same result: childhood vaccines clearly cause changes that are observed in autistic individuals. I’m going to go out on a limb here and cite fraud. If someone else can replicate the results, I will apologize and will stand corrected. Luckily for her, no one will bother (or is in a position) to use macaques to follow up on highly questionable research.

The cost of demonstrating fabricated/falsified data is too high in this case. I’m sure that factors into her experimental designs and her conclusions.

MI Dawn writes:

My husband nearly left me when I admitted I had no idea Eric Clapton was a member of a band called Creem? Cream?

Interesting you should bring up Clapton – he was a member of the Yardbirds, but had left by the time of the band photo above. The guitarists in the lineup above include at far left Jeff Beck, and Jimmy Page second from right. (Though they’re both guitar gods, you may not be familiar with Beck. Page, on the other hand, was later a member of a little group you might have heard of called Led Zeppelin.)

John Harrold

I feel bad after euthanize rats and mice in our animal work. I simply couldn’t work with monkeys; I don’t think I could handle it emotionally.

I know animal research is a necessary evil, but I can’t believe they were allowed to make these monkeys suffer for such a horrid study.

I think it would stand to reason; the only ethical reason for doing a study with primates is if there were a genuine demonstrable benefit to humans.

Of course, being a layperson I have never had to experiment on animals. But when I went on Wikipedia and looked up “rhesus macaque” it was exceedingly sad to think of what happened to these infants for no good reason.

An interesting anomaly:

Look at Figure 2 on page 153 of the study. The top row are PET and MRI scans of one of the non-vaccinated monkeys, while the bottom is of a vaccinated monkey. I noticed several things. First, the activity in the PET decreased everywhere in the unvaccinated monkey, whereas in the vaccinated monkey it seemed to become more focused in the amygdala. But more importantly, I noticed that in the vaccinated monkey, the PET scans are symmetrical, whereas the in the unvaccinated monkey, the left lobe shows more activity, especially in the back. Of course this may be a matter of right/left differentiation. But look at the MRI scans.

The MRI of the vaccinated monkey is very symmetrical. Not so with the unvaccinated monkey. The back of the right lobe is much smaller than the back of the left lobe. Furthermore, there is a large “hole” on the right side that does not have a match on the left.

I freely admit that I am not qualified to evaluate PET or MRI scans. But it sure seems plausible that at least one of the two controls the used had significant anomalies in brain structure. If true, this would invalidate the results reported.

Add me to the chorus wondering whether the University of Pittsburgh IACUC was drugged when they approved this.

@MI Dawn,

You’re welcome.

I had to rush the last comment a bit so I could hustle to work, but my curiosity was itching, so I had to scratch it when I got home and could do some more research.

Too Much Monkey Business was a popular Chuck Berry song and lots of groups covered it. You can see Elvis and The Beatles do it on YouTube and the Yardbirds did it on their album Five Live Yardbirds.

Both this “paper” and Haley’s response to the FDA (see Orac’s previous post) appear to follow a clear pattern. IMO, the aim of these people is not to gain credibility in the scientific community. It is simply to produce something (anything) that will keep the true believers happy. There must be quite a few users of OSR out there that would be worried by the Tribune stories. So Haley needs something to calm them down. No one believes Wakefield anymore, at least not in the mainstream. But the AoA people need something to keep them going. So, they’ve been given a crumb of “science” that allows them to hang on to their faith-based view that vaccines cause autism. These people will not be swayed anyway. As JB Handley says in the Trib, “We don’t trust the FDA or the CDC. We don’t trust you. We don’t trust most doctors. We only trust each other”.

Fortunately, the true believers are relatively small in numbers. I don’t think that many people would be fooled by these monkeys. They know that even if vaccines did cause autism in some children, they certainly don’t cause autism in all children who receive vaccines. So, why then, does Hewiston see such a huge effect in such a few monkeys?

@Brian

I was the one who posted the question about ‘normal’ amygdala development, in hopes of planting a ‘seed’ of doubt in their readers. I didn’t even see the response post with the Payne et al article before they removed it. So far someone has offered that the ‘control’ group shows us what is normal, and someone has suggested saline offers a protective factor (by shrinking the amygdala). I posted a response playing ‘dumb’ again, and then posted one with the Payne reference…I’m guessing those won’t show up, and my original one will be removed. Time will tell.

@betty watson

Hopefully you kept copies of your comments so that, if they do not appear at AoA (or appear and subsequently get deleted), you can post them over at Silenced by Age of Autism. I’ll have a comment thread up soon for people to copy their posts to.

My vote for the most moronic justification in the paper: “We purposefully assigned a larger number of animals to the exposed group in order to optimize the chances of observing what we anticipated to be an uncommon or idiosyncratic effect.”

If it is an uncommon effect, it could only be attributed to the exposure if you have a LARGE control group to show it does not occur in the unexposed group!

That statement could also be used to justify the following: “statistical significance is for aholes”

Both this “paper” and Haley’s response to the FDA (see Orac’s previous post) appear to follow a clear pattern.

The pattern I see as of late is the implosion of the anti-vax movement.

There might be a story of interest for the curious journalist in the fact that 8 authors from the IMFAR abstract (not counting Wakefield) are not listed in the final version of the paper. Someone should interview those people and find out what went on behind the scenes.

>>Geez, the comments are getting worse:
>>
>> The increased head size is likely caused by heavy metal
>> interference with apoptosis (programmed cell death)..

Those stupid ignorant anti-vaxxers , they don’t know that
low levels of BCL-2 in autistic children actually protects
against oxidative-stress induced apoptosis

1)Dysregulation of Reelin and Bcl-2 proteins in autistic cerebellum.
http://www.ncbi.nlm.nih.gov/pubmed/11814262

2)Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain
http://www.fasebj.org/cgi/content/abstract/fj.10-154484v1

Oh it’s the other way around, never mind ,stupid anti-vaxxers.

Hmmmm. Two of the authors whose names appeared on the IMFAR abstract but not on the final version of the paper — David Atwood and Lisa Y. Blue — are colleagues of Boyd Haley, co-developers of BDETH2/OSR#1, and associated with Merloc LLC. (Merloc is the start-up that’s licensed the same chelating molecule from the University of Kentucky, to be used for toxic waste cleanup purposes, that Haley’s licensed for medical/”nutraceutical” purposes.) I wonder what the contribution of either (or the other University of Kentucky chemist, for that matter) to this paper might have been (how is their expertise relevant to the subject matter of the paper?), and, of course, why their names don’t show on the final version.

BTW, Journal of Toxicology and Environmental Health, Part A, is edited by a fellow named Sam Kacew in Ottawa. He’s made public statements supporting the mercury-autism hypothesis, and was not a bit happy with me when I shared with him and his Editorial Board my concerns regarding IRB supervision of human subjects research conducted by Mark and David Geier, and David Geier’s claim to have conducted his research under the aegis of The George Washington University, He’s published quite a few articles supportive of vaccine-autism causation hypotheses.

Kathleen,

interesting history on Jounral of Toxicology and Env. Health. I hadn’t thought to search for the name “Geier”.

That said, I think Atwood is mentioned in the acknowledgments, but not Blue. My assumption is that they likely did the mercury concentration testing and, possibly, the actual mercury spiking of the vaccines.

“We purposefully assigned a larger number of animals to the exposed group in order to optimize the chances of observing what we anticipated to be an uncommon or idiosyncratic effect.”

In other words, “We are interested in collecting individual anecdotes that confirm our expectations, not in testing their significance”. I wish I could make such an admission to the reviewer(s) and still get a paper published.

I looked at the Geier’s paper … more attempts to link mercury to autism. And poorly written.

I feel like Dan Ackroyd in Saturday night live, hosting Bad Cinema. only it’s Bad Science.

“My older autistic son had a remarkably large head as a toddler which is now a more normal size as a teenager.”

Don’t tell me they’ve decided to believe in phrenology, too!

Talking of the “disappearing authors”, I imagine they consist of those with some sense of having a reputation to preserve/salvage. One of them, Carlos Castro, is a clinical instructor at U Pittsburgh and the only clinically-qualified Faculty Member at the Pittsburgh Development Center (PDC) where Hewitson used to work. (Hewitson is now listed as an “Adjunct Associate Prof”, so it is a bit opaque what her precise connection is with the PDC these days).

Of the authors of the current excuse for a paper, long-time Wakefield side-kick Carol “Try me shithead” Stott obviously needs no introduction to seasoned Wakefield watchers (see Brian Deer’s link).

A poke about on the PDC website, and the U Pittsburgh one, reveals that Brian Lopresti is the manager of the Radiology Dept microtomography lab, and Neal Mason is a Non-Clinical Asst Prof in Radiology, a chemist / PET guy specialising in the synthesis of labelled compounds for PET. So one might guess that those two are the “tech guys” for the study, with perhaps little sense of the wider autism / mercury controversy. Jaime Tomko seems likely to have been a research assistant of some kind at PDC as she appears in the middle of the author list on a lot of papers from the Center.

I was interested to see that the Head of the PDC is Gerald Schatten, who achieved an, er, unwanted fame via his role in the Hwang Woo Suk scandal.

The whole thing is oddly reminiscent to me of the 1998 Wakefield paper – lots of authors (at least on the initial abstract), all doing bits of stuff, but quite possibly some having a limited sense of the overall pattern of results / interpretation / writing up. (At least, that is what many of the authors of the 1998 Lancet paper later intimated). Anyway, it is hardly in doubt that this is Dr Hewitson’s show, so she is the one whose reputation – if she has any left – is on the line.

PS No links, sorry – bypassing the spam filters.

I’m going to experiment on monkeys brains with my evil vaccines. I have no idea what might happen, but whatever happens I can blame my vaccines…\

I hadn’t noticed it until pointed out by Kevin W., but the MRI and PET scan on the ‘control’ is highly abnormal in appearance. I don’t look at that many, but the gray/white borders seem to be vanishing. In fact, on the control animal, the white matter, especially in the posterior lobes seems completely gone. This seems to correlate with the complete lack of uptake on the PET scan, look at the posterior lobes, at both T1 and T2, no uptake. Plus, I agree with Kevin as well, what’s that area of missing brain in the left parietal lobe? That’s either congenital, or from a craniotomy. Maybe a radiologist in the group, or Dr. Novella can look at it a little more closely, but something looks very wrong with the control’s imaging, and with only 2 controls, it seems very likely that this alone explains the difference in the the 2 groups.

And double-hmmmm. Two recent papers by Hewitson pertain to cognitive development in rhesus macaques — Growth and developmental outcomes of three high-risk infant rhesus macaques (2007) and Neonatal behavior and infant cognitive development in rhesus macaques produced by assisted reproductive technologies (2006). (Several others pertain to the development of primate models for assisted reproduction.) You’d think that someone with that much experience working with macaques would have been familiar with Payne et al — Maturation of the hippocampal formation and amygdala in Macaca mulatta (2009) — which documented that in normal development, the amygdala in macaques normally increases in size. Could this oversight be indicative of simple carelessness, or could it be indicative of deliberate disregard for evidence that shrinkage in the amygdala of the controls in her thimerosal study might indicate pathology, or at the very least, atypical development?

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