Totally False in at Least Two Dimensions "New Study: Baby monkeys develop autism after routine CDC vaccinations"

 I have no idea why the Hewitson macaque-vaccine "study" is being presented as news, or as meaningful.  Hewitson's team's research (and ethics) were severely criticized from 2008 to 2010 by research scientists.  Also, I don't think either the amygdala growth study or the HepB study have been replicated.

First it's Catherine J. Frompovich at VacTruth on April 29, 2012:

Monkeys Get Autism-like Reactions to MMR & Other Vaccines In University of Pittsburgh Vaccine Study

Then Ethan A. Huff at Natural News picks up the beat  on May 6, 2012:

Vaccine bombshell: Baby monkeys given standard doses of popular vaccines develop autism symptoms

Both stories go on to represent the Hewitson monkey studies as (a) fact (b) news.  They are neither.

No, the macaques in the study did not develop "autism like reactions".  No, you can't draw any conclusions from the studies.   All you can really tell is that twenty infant macaques (and maybe fewer) were subjected to invasive procedures and death -- for no benefit.

The Hewitson studies are confusing because of their history and the fact that the same monkeys are used to make different points.  

Here is a listing of the publications that used infant macaques injected with vaccines and that listed Hewitson as an author.

1. 2008: Poster presentation at the International Meeting For Autism Research (IMFAR) poster 3024:    Pediatric Vaccines Influence Primate Behavior, and Amygdala Growth and Opioid Ligand Binding: authors L. Hewitson, B. Lopresti, C. Stott, J. Tomko, L. Houser, E. Klein, C. Castro, G. Sackett, S. Gupta, D. Atwood, L. Blue, E. R. White, and A. Wakefield. "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)". (Exposed to thimerosal,N=13 ; unexposed; N=3). (The "significant changes in bhavior after MMR" study) 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.
2. 2008: Poster presentation at IMFAR poster 3028 Pediatric Vaccines Influence Primate Behavior, and Brain Stem Volume and Opioid Ligand Binding authors A. Wakefield C. Stott, B. Lopresti, J. Tomko, L. Houser, G. Sackett, and L. Hewitson. "The objective of this study was to compare brain stem volume and opioid binding in rhesus infants receiving the recommended infant vaccine regimen." (Exposed to thimerosal,N=13 ; unexposed; N=3). (The "delayed reflexes study") Conclusions: This animal model examines the neurological consequences of the childhood vaccine regimen. Functional and neuromorphometric brainstem anomalies were evident in vaccinated animals that may be relevant to some aspects of autism.
3. 2008:  Poster presentation at IMFAR poster 3033 Microarray Analysis of GI Tissue in a Macaque Model of the Effects of Infant Vaccination  authors S. J. Walker, E. K. Lobenhofer, E. Klein, A. Wakefield, and L. Hewitson.  Objectives:   This study was designed to evaluate potential alterations in normal growth and development resulting from the vaccine regimen that was in use from 1994-1999.  Specifically, this portion of the study was to compare the gene expression profiles obtained from gastrointestinal tissue from vaccinated and unvaccinated infants.  (Vaccinated, N=7;  Unvaccinated, N=2)  Conclusions:   We have found many significant differences in the GI tissue gene expression profiles between vaccinated and unvaccinated animals.  These differences will be presented and discussed.   
4. 2009 (October) Paper in NeuroToxicology; withdrawn February 2010: Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing Hepatitis B vaccine: Influence of gestational age and birth weight L. Hewitson, L. Houser, C. Stott, G. Sackett,  J. Tomko,  D. Atwood, L. Blue, E. R. White, and A. Wakefield.
5. 2010 Paper in Acta Neurobiol Exp (Wars). 2010;70(2):147-64. Influence of pediatric vaccines on amygdala growth and opioid ligand binding in rhesus macaque infants: A pilot study. L. Hewitson, B. Lopresti, C. Stott,  NS Mason and  J. Tomko.  (This appears to be the same study as the poster presentation 3024, minus some authors. & adding NS Mason.)
6. 2010 Paper in Toxicol Environ Health A Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing hepatitis B vaccine: influence of gestational age and birth weight. Hewitson L, Houser LA, Stott C, Sackett G, Tomko JL, Atwood D, Blue L, White ER.J Toxicol Environ Health A. 2010;73(19):1298-313.PMID: 20711932 (this appears to be the same paper as the withdrawn NeuroToxicology paper with the subtraction of  Wakefield as a co-author).

On to the criticisms:

1. May 16, 2008 Kev at LeftBrain/RightBrain Monkeying Around This post introduces what posters are, in a scientific context.
2. May 17, 2008 Orac at Respectful Insolence Some monkey business in autism research (or why it is not a good idea to provoke Orac 
   1. In the biomedical field, poster presentations are the lowest form of "publication" of one's data. 
   2. The poster presentation only sketches out the methodology, and important 
   3. It's evident that this is really one study divided into MPUs (minimal publishable units) of 3.
   4. Why is the control group so small (3 monkeys) and the effect group so large?  How were individual monkeys assigned to control vs. condition groups? 
3. May 18, 2008 Kev at LeftBrain/RightBrain Laura Hewitson's Stinker, on all 3 IMFAR poster presentations:  Hewitson has severe and significant conflicts of interests (COI) that were not revealed, contrary to the IMFAR requirements.
   1. Her partner is a employee of Thoughtful House,
   2. Her co-author, Andrew Wakefield is (at the time of publication) chief researcher at Thoughtful House
   3. Her partner is on the Board of Directors of SafeMinds (the "thimerosal causes autism" organization)
   4. Hewitson's son has autism
   5. Hewitson and her partner are part of the Omnibus Proceeding--in other words, the Hewitson family are suing the government for compensation for their son's alleged vaccine-caused autism.
4. July 16, 2008 Emily Willingham at A Life Less Ordinary Autism: No Rats Will Be Harmed, But Keep An Eye on the Kids. Most of this post is about the ill-fated NIMH chelation for autism study,  but Willingham addressed some significant flaws in the first two poster presentations, namely, the undisclosed conflicts of interest, and sharply questioning the framing of the discussion:
   1. Willingham highlights  the connection between Thoughtful House and the 3 poster presentations, a conflict of interest that is not disclosed.
   2. Posters 3024 and 3028 use the phrase "Childhood vaccines are a possible causal factor in autism".  This is an astonishing assertion:  by 2008, there was  "no peer-reviewed published research confirming this statement--especially the "causal" part--and a substantial amount countering it".
   3. Poster 3024 asserts, and 3028 implies two things: (a) the majority of childhood vaccines contained thimerosal and (b)the thimerosal might be the vaccine component associated with autism.  This is simply silly on both counts: it is not true that "the majority" contained thimerosal; the MMR vaccine never contained thimerosal; and pediatric vaccines became thimerosal-free in 2001.  
5. October 7 2009 Catarina Science Mom at JustTheVax 20 Monkeys, which discusses the withdrawn 2009 Hewitson HepB study in NeuroToxicology.  She finds that there are multiple procedural and study-design flaws that render the study almost worthless:
   1. The three IMFAR posters mentioned above are clearly part of the same set of monkey studies
   2. There was no randomization of the subjects.  A study either is randomized or not. 
   3. Since there was only one interpreter of the monkeys' behavior pre- and post-vaccine administration, no blinding was possible, introducing another layer of potential biase.
   4. It seems that an additional 4 control animals were added after the IMFAR poster presentations.  Rather than strengthening the study, the late addition of subject weakens study as it adds a possibly confounding variable.
   5. The authors failed to publish baseline biochemical data, such as blood mercury levels pre- and post-injection.
   6. The authors collected data on 18 behaviors and published tables on 13 behaviors.  H0wever,  only 3 reached statistical significance.
   7. The significant conflicts of interest of 3 authors (Hewitson, Wakefield, and Stott) are noted, with a particular emphasis on Stott.
   8. The study was funded by a collection of groups and individuals with vested interests in finding vaccines harmful to health and causal in autism.
6. October 7 2009 Orac at Respectful Insolence Some Monkey Business in Autism Research discussing the withdrawn 2009 Hewitson study in NeuroToxicology;
   1. "Even if the study was well designed and executed (which it is not), and even if the study conclusively showed delayed development of survival reflexes (which it does not), it is still a very, very, very long leap to conclude that vaccines and or thimerisol are responsible for increased autism rates in humans. 
   2. These "survival" reflexes (called "primitive reflexes" in humans) are present at birth in human infants and their  absence would be noted by any competent pediatrician.
   3. Absence or delayed appearance of "primitive reflexes" is not a feature of autism.
7. October 24, 2009 Prometheus at Photon in the Darkness A Made for Court Study? (This is another of Prometheus's master class in how to read and analyze scientific papers -- you would do well to study his technique)
   1. "Most fatal for this study – is that there was not an increase in human infants who were late to suck, root, etc. following the introduction of neonatal hepatitis B vaccination in 1991. Given that the “uptake” of this vaccine at birth was close to (and often exceeded) 90%, an effect of this magnitude would have been noted. Nor is there a difference between the US – which has continued hepatitis B vaccination at birth – and the UK – which almost never gives the hepatitis B vaccine at birth – in developmental delay or autism prevalence."
   2. "This current study, as well as the entire macaque research program by Hewitson, is a good example of terrible research. The subject numbers are far too small for any meaningful statistics, and the outcomes being followed are numerous and tricky with a random scatter of results not even consistent between different publications of the same research."
   3. "What we have is far worse than ideological reporting and spinning of the scientific research – apparently we have the ideological conduction of research in the first place. This is similar to the research program of Benveniste on homeopathy."
8. February 12, 2010 Prometheus at Photon in the Darkness Where are the Monkeys? (on the sudden withdrawal of the 2009 HepB paper in NeuroToxicology)
9. February 12, 2010 Orac at Respectful Insolence Wakefield's "Monkey Business" Hep B paper withdrawn? (on the sudden withdrawal of the 2009 HepB paper in NeuroToxicology)
10. July 16, 2010 Steven Novella at Neurologica Blog Terrible Anti-Vaccine Study, Terrible Reporting, on the 2010 paper in Acta Neurobiol Exp (Wars). 2010;70(2):147-64.Influence of pediatric vaccines on amygdala growth and opioid ligand binding in rhesus macaque infants: A pilot study. 
    1. The number of subjects (9) and controls (2) is far far too small to determine anything.
    2. The authors "also makes multiple analyses (another red flag by itself), which means she can compare multiple variables looking for any difference. Then she invokes the sharpshooter fallacy and declares any change she does find to be clinically meaningful."
       
11. July 16, 2010 Sullivan at LeftBrain/RightBrain From IMFAR to Poland: How A Monkey Study Can Totally Change  In this post, Sullivan compares the withdrawn 2009 Neurotoxicology paper to the recently-published paper in 
    1.  Of 13 authors on the original abstract, only 4 remain
    2. A new author was added, N.S. Mason.
    3. In the Neurotoxicology paper, the study had data on 13 vaccinated monkeys. Now the number of monkeys is only 9. 
    4. The Neurotoxicology paper had data on 3 controls. Now it is only 2.
    5. In the Neurotoxicology paper, the vaccinated monkeys “showed attenuation of amygdala growth”
    6. In the Acta Neurobiol Exp paper, the vaccinated monkeys have larger amygdalas
    7. A commenter notes that the researchers adminstered  "the vaccines at four times the human rate
12. July 16, 2010 Sullivan at LeftBrain/RightBrain The genie is out of the bottle: Vaccines cause autism This is Sullivan's sarcastic commentary on how enthusiastic the "vaccines cause autism" brigade is over the Hewitson Acta Neurobiol Exp paper, "Influence of pediatric vaccines on amygdala growth and opioid ligand binding in rhesus macaque infants: A pilot study."  Sullivan has the questions listed below, and concludes "Just another 16 monkeys giving their lives for nothing."
    1. Why is there such a large difference between the number of subject animals and the number of control animals?
    2. Why did the number of control subjects go from 4 to 2?  What happened to the other 2?
    3. Why did the "unexposed" monkeys' amygdalas shrink?
13. July 16, 2010 Kev at LeftBrain/RightBrain The genie is out of the bottle: part 2: More genies, more bottles  As it turns out, this issue of Acta Neurobiol Exp is devoted to "issues in autism", a notion proposed by Professor Dorota Majewska, who is a significant supporter of Andrew Wakefield; the editor missed the three questions that Sullivan posed.
14. July 16 2010 Orac at Respectful Insolence Too much vaccine/autism monkey business for me to be involved in--but evidently not Laura Hewitson
    1. Because all vaccines now are   thimerosal-free, Hewitson had to add thimerosal to the vaccines to produce its replication of the vaccine schedule from the 1990s. 
    2. Because Macaque monkeys mature faster than humans, the macqcques received in one year what humans receive in four years.
15. July 16 2010 ToddW at Harpocrates Speaks Newsflash!  Vaccines Cause Autism...If you are Scientifically Illiterate
    1. On the small sample size, ethics of animal experimentation, and institutional review: "If the sample size is going to be so small that no statistically significant or meaningful results can be found, then there is no reasonable justification for subjecting animals to the research"
16. July 26, 2010 Sullivan at LeftBrain/RightBrain Laura Hewitson has left the University of Pennsylvania
17. July 27, 2010 Emily Willingham at A Life Less Ordinary In the Name of Science

 

Comments

[Michael Simpson]

OK, let me try this again.

I hate to cast aspersions on the anti-vaccine crowd (but I do it anyways), part of why they're bringing out 2-3 year old studies is probably because there's just no data supporting their beliefs, so retreading old ones like they are Nobel Prize-winning research is the best they can do.
I get annoyed by what I call "research-mining" a corollary to "quote-mining". Using logically fallacious confirmation bias, they mine for the research that supports their point-of-view rather than the broad scientific consensus. I wrote an article that describes how pseudoscience uses research to make their cases. Basically, they rely upon weak or poor research while ignoring all other research.
Published research has an order of quality from best to worst:
1. Secondary research, usually meta-reviews or research that confirms a hypothesis, published in peer-reviewed, high impact journals. These include Nature, Science, PNAS, Lancet (well, save for one piece of fraud), JAMA, NEJM, and many others. High impact means that they are extremely well reviewed, and they're cited in other journals more frequently.
2. Primary research, published in the same journals. The problem with primary research is that, although well-done, has not established a scientific consensus. It hasn't been repeated. And it hasn't been reviewed. But it does have a value, though it should be looked at somewhat skeptically until the body of evidence develops around it.
3. Primary or secondary research in medium-impact journals, which are usually journals that concentrate in a particular area. Whereas PNAS has a broad readership in the sciences, the Journal of Neurology has a highly focused audience. It doesn't mean that it is bad data, it's just that it usually doesn't describe a new theory…yet.
4. Primary or secondary research in low-impact, biased journals. Alternative medicine does this a lot, since the research is usually rejected by the better journals, so they go to one that supports their bias. These are peer-reviewed, but they are strict about who constitutes a peer. Say a homeopathy article will be reviewed by homeopaths not by a broad spectrum of physicians or scientists.
5. Conference abstracts are near the bottom. Even Wikipedia, which can be useful, rejects conference abstracts, "Conference abstracts present incomplete and unpublished data and undergo varying levels of review; they are often unreviewed self-published sources and these initial conclusions may have changed dramatically if and when the data are finally ready for publication. Consequently, they are usually poor sources and should always be used with caution, never used to support surprising claims, and carefully identified in the text as preliminary work."
6. Popular press (newspapers, magazines), unless they link to the research. Then you should just use the research.
7. Blogs, biased press (Natural News is a favorite).
I don't think I've seen a single article in the Vaccines Cause Autism hypothesis that meets #1 or #2.
Anyways, great article, and one I will link to. You looked up a lot of research there, but maybe it's just me, but I simply reject their research because of its quality.

[David N. Brown]

Wow, I'm surprised even anti-vaxxers are still talking about this paper. Here's my take on it:
http://evilpossum.weebly.com/uploads/2/6/2/2/2622709/11monkeys.pdf

I find your own title interesting and perhaps more apt than intended, because, in my opinion, the study's conclusions may have been shaped in no small part by overuse of "2-D" cross sectioning to describe the three-dimensional brain.