We reported earlier this summer (see HERE ) on an important new study from Thoughtful House and the University of Pittsburgh describing neuroimaging results that compared a small group of vaccinated monkeys to unvaccinated monkeys during infancy. One interesting footnote in this paper from Acta Neurobiologiae Experimentalis (ANE) made reference to a new publication from the same research group on the delayed development of neonatal reflexes after a birth dose of thimerosal containing hepatitis B vaccine. This published reference to the Canadian journal The Journal of Toxicology and Environmental Health (JTEH) was followed a few weeks later by the publication of the full article. Careful reading of this new article revealed that the August article reported on the same research findings that were first peer-reviewed and published on-line in another journal last year… then abruptly withdrawn after intervention by the publisher, Elsevier, the corporate owner of the journal Neurotoxicology. See HERE for an account of this episode.
Together, the results reported in these two papers represent an important landmark in vaccine safety research. The first published findings from a novel and unprecedented study design, they raise important questions about how United States government regulators have managed the safety profiles of childhood immunizations: not just individual infant vaccines and their ingredients, but, more importantly, the cumulative effect of the intensified program of childhood vaccination that started in 1991. This escalation of intervention (see HERE for an comparison of the U.S. childhood immunization program to those of other countries) in infant immune development—an escalation that included new vaccines administered earlier in life, cumulative exposure to ethyl mercury that exceeded federal guidelines for mercury exposure, and stepped up efforts to ensure on-time compliance with existing mandated vaccines—coincided in time with the dramatic increases in autism rates.
Despite widespread concern over vaccine safety issues, the medical industry has developed an effective public relations campaign over the last decade to defend their products. They have in the process reinforced the federal protection for what has now become the world’s most privileged product line; infant vaccines have received specific exemptions from regulatory standards and liability laws in ways that are truly without precedent. Autism may be a mystery, goes the medical industry line, but the one thing we know for certain is that vaccines have nothing to do with it. Supporting this claim is a cluster of epidemiology studies conducted by public health authorities and vaccine manufacturers and examining populations in Denmark, California and the U.K., all of which claim to find no evidence between autism risk and either thimerosal or the MMR vaccine. Despite the fact that researchers with no affiliation with government authorities and vaccine manufacturers have found the opposite, repeatedly reporting epidemiological support for vaccine safety concerns, the public relations messengers of what some have called “the medical industrial complex” have effectively spread their message: “no credible evidence supports a link between vaccines and autism”; all relevant safety questions have been “asked and answered.”
In evaluating the state of the science that supports these sweeping conclusions, skeptical observers have consistently posed a very simple question. Have any of these supposedly credible studies compared total health outcomes in vaccinated vs. unvaccinated children? The answer to the question, of course, is no. According to the official line, it would be too hard to collect a reliable sample of previously unvaccinated children (making such study designs retrospectively impossible) and medically improper to deprive children of the benefits of vaccination in a properly controlled study (making such designs prospectively unethical). Elsewhere (see HERE ), one of us has called that position “an epistemological obscenity.”
But aside from the controversial aspects of such studies, there are other problems with what most call “vax/unvax” studies in human populations. In a nutshell, if there are subtle forms of developmental injury in human infants from intensive vaccination, there’s no way to carry out the controlled biological investigations to figure out what might be going wrong in the developing human brain.
But if researchers face constraints, both real and perceived, in performing rigorous vax/unvax studies in human children, there’s another alternative: studying the effects of intensive vaccination in infant animals. Starting with the work done at Columbia University nearly ten years ago, a growing number of scientists have reported findings relevant to vaccine safety (and especially on thimerosal exposure) in several animal models, including mice, hamsters (see HERE ) and rats (see HERE and HERE ). The evidence from these rodent studies has been nearly uniform and their conclusions overwhelmingly similar: Thimerosal at the doses involved in the childhood immunization program of the 1990s clearly causes developmental damage in infant rodents.
None of these studies, however, involved infant primates and none of them were addressed to the larger questions of vaccine safety beyond thimerosal, especially to the safety concerns regarding the controversial measles-mumps-rubella (MMR) vaccine. In this light, the scientific importance of the Thoughtful House project becomes clear: it is the first study ever designed to do a comprehensive and rigorous look at the cumulative biological effects of the most controversial elements of the childhood immunization program launched in America in 1991.
As we welcome the publication this week of our own book, The Age of Autism, we think it’s worth taking stock of the lessons so far from this primate project, the most authoritative investigation to date of the question: how does brain development in vaccinated infants compare to unvaccinated infants? To date, we now have preliminary results from this project on three aspects of the childhood immunization program human infants began experiencing starting in 1991
1. Delayed development of neonatal survival reflexes
The publication of the neonatal reflex study in JTEH reminds us once again (and restores to the official record) of crucial evidence on the risks of the birth dose of the hep B vaccine. Of all the questionable practices surrounding childhood vaccines, the hep B birth dose probably raises the most questions. The CDC’s policy with respect to hep B vaccines—the introduction of a mandate that government intervention was required to protect all infants from their mothers (the primary source of potential neonatal hepatitis B infection)—effectively removed from parents’ hands the determination of whether or not their own behavior put their children at risk. Since infant risk of hepatitis B infection comes almost entirely from the mother (largely during the exchange of bodily fluids during birth), and since mothers contract the hepatitis B virus largely through unprotected sex and hypodermic needles, if a mother wants to protect her newborn baby from hepatitis B virus, there are many other options besides perinatal vaccination. But instead of giving women the option of informed choice, CDC simply mandated the vaccine for all infants at birth (and we’ve even heard numerous reports of infants receiving the vaccine without parental consent). In the process, their aggressive policy intervention exposed newborn infants to both a dangerous mercury compound and an unprecedented immune stimulation at the earliest possible moment of life.
What was the infant primates’ developmental response to the exposure? As the JTEH study showed, the vaccinated infants experienced pronounced delays in several developmental reflexes. These reflexes—technically known as the root, snout and suck reflexes—are all critical survival reflexes that allow a newborn infant to locate and latch into the mother’s breast. Without these reflexes, infants lose their ability to nourish themselves in the most precarious period of their lives.
Primates aside, surprising support for a connection between this reaction in primates and the delayed development of similar reflexes in autistic infants comes from the original case histories of the eleven children described by Leo Kanner in his 1943 paper, Autistic Disturbances of Affective Contact. In our book, we have uncovered the identity of seven of these children and their parents. The parents often reported in some detail on their children’s success in breast feeding, and of the eleven children, three experienced difficulties in feeding. The descriptions sound eerily similar to the JTEH findings.
Wendell Muncie, the father of Case #5 and a colleague of Kanner at Johns Hopkins (whose wife was also a Hopkins nurse), told doctors that his daughter Bridget “nursed very poorly and was put on bottle after about a week. She quit taking any kind of nourishment at 3 months. She was tube-fed five times daily up to 1 year of age. She began to eat then, though there was much difficulty until she was about 18 months old.”
When we first reported on the neonatal reflex findings (see HERE ) several of our readers commented that they observed similar reactions after their child received the birth dose of hep b vaccine. A comment from “jenb” was particularly striking. She wrote,
I was floored when I read this because I think this is exactly what happened to my son….I held him to my breast within minutes of being born, he latched on immediately and was a very strong nurser. He had a strong rooting, sucking reflex. At some point during my stay the nurse came to get him his heel prick test. The reason I remember this so clearly is because I was so furious at what they did next.… What i remember is the nurse bringing him back and saying “He'll probably want to nurse because he was just circumcised” I was like WHAT! Of course she panicked and got upset because she didn't get our consent…The reason this is important is because I noticed he was not crying. I thought that was really strange after going through such a painful procedure and he was very listless, when I put him to my breast he did nothing. His lips were very floppy, it was like he had lost his sucking and rooting reflex….I have always stated that I think they gave him the Hep B while he was getting his [circumcision] and that was probably his first vaccine injury.
The special risk of the birth dose of the hep B vaccine has also been supported by independent epidemiological analyses. Based on two separate data sources--the National Health and Nutrition Examination Survey (NHANES) and the National Health Interview Survey--Carolyn Gallagher and Melody Goodman have produced findings that dovetail almost perfectly with the neonatal primate report. According to Gallagher and Goodman’s research, in male infants vaccinated at birth with a thimerosal-containing hep B vaccine, the need for early intervention services (NHANES) and the odds of receiving an autism diagnosis (NHIS) was increased anywhere from three- to nine-fold
And then, of course, there was the original CDC analysis on thimerosal using data from the Vaccine Safety Datalink (VSD). The very first VSD analysis performed in late 1999 also found an elevated risk of autism in infants who had been treated aggressively for hepatitis B risk, both with thimerosal-containing vaccines and immune globulins. The risk of autism was anywhere from eight to eleven times higher in the highest exposure group as compared to children receiving zero exposure at one month of age (the high exposure group received over 25 micrograms of ethyl mercury, meaning there had to be an additional source besides the hep B vaccine, almost certainly hep B immune globulin). In the next round, however, the children with these high exposures were removed from the analysis because “children that received hepatitis B immunoglobulin, as these were more likely to have high exposure and outcome levels.”
It’s important to keep these analytical tricks in mind as we consider the latest study from CDC on thimerosal and autism (the one that suggests that thimerosal is good for infants and protects them against autism), but let’s leave that discussion for another day.
2. More rapid brain growth
Unlike the JTEH paper, which focused on observable reflexes during a short period after the birth dose of hep B vaccine, the ANE paper (available free HERE ) covered a longer period, relied on brain neuroimaging data and homed in on regional development in the primate brains before and after administration of the MMR vaccine. Much of the ANE paper centered on an analysis of changes between two developmental milestones: “T1” (before receipt of the MMR vaccine as well as the fourth doses of the Hib and DtaP vaccines) and “T2” (after receipt of the MMR and fourth doses of Hib and DTaP). But one little-noticed finding permits us to fill in an earlier gap: the period between the birth dose of the hep B vaccine and the receipt of MMR vaccine at 12-18 months: a period during which 187.5 micrograms (mcg) of mercury was administered in the series of thimerosal containing hep B, DTaP and Hib vaccines administered to human infants throughout the first year of life.
But before reviewing the ANE paper’s findings, let’s start with a few observations on the study design and primate sample described therein. Although the neuroimaging work was mostly designed to pinpoint brain changes before and after MMR, the research team made their observations using an experimental design that paralleled real world effects on human infants. So not only did the monkeys receive MMR, they also received multiple doses of thimerosal-containing vaccines, including one dose of Hib and DTaP vaccines that occurred at the same time as the MMR. In addition, the infant monkeys were placed on a dietary regimen that included gluten-based foods and casein containing fluids.
Although the study design was innovative and carefully crafted, it’s important to emphasize that it’s a “pilot study”, which basically means that the sample size is small and designed to prove out the design for larger scale experiments. The ANE sample, with a primate cohort of 13 vaccinated and 3 unvaccinated infants, overlapped in large part with the cohort described in the neonatal hep B paper, except for the fact that the unexposed JTEH group included four additional primates. Only a subset of the ANE sample yielded usable neuroimaging results, which meant that the study findings were based on an even smaller sample of 9 vaccinated and 2 unvaccinated monkeys. The authors were careful to note this limitation, and commented “the size of the study group limits the strength of the conclusions that can be drawn.” To deal with the problem of small sample size in the pilot study, the authors analyzed their data intensively, arguing that “the use of statistical modeling and repeated measures contributed to the study’s power and increased the accuracy of the estimates.”
They weren’t kidding. The statistical analysis in the paper includes a complex set of tables reporting on a blizzard of different numbers: mean volumes, differences of means, main effects, interaction effects, within group and between group comparisons, etc.
But while the paper’s tables provide large amounts of data, they only contain a portion of the results; the text fills in several gaps, but because of the density of the analysis and the scattering of key statistics between the tables and the text, it takes close reading to sort out which numbers are where, how each of them compares to the others and what the numbers really say about the exposures. This is especially difficult considering that the authors report seven different ways to measure effects of the exposure and the passage of time, both for overall brain size and for two specific brain regions. These seven measures were1. The difference between vaccinated and unvaccinated monkeys at T1
In Figure 1 (click to enlarge), we’ve summarized the results for total brain volume (in terms of P values, a key measure of statistical significance) in a different way than the paper for all seven of these measurements. Only one of the seven, the main effect of exposure, was statistically significant. This meant the differences between vaccinated and unvaccinated groups had little to do with the MMR exposure and more to do with the trio of thimerosal-containing vaccines they received in the period before MMR administration. The authors note that “these results raise the possibility that multiple vaccine exposures during the previous 3-4 months may have had a significant impact” on the infant monkeys.
More specifically they were about 10% larger (see Table IIb). That’s a “main effect” that looks a lot like autism. According to Harvard neurologist Martha Herbert, “The most replicated finding in autism, and one that has been found in multiple reliably characterized cohorts and artifact-free samples, has been that the brains are on average unusually large.” On average, about 10%.
3. Abnormal maturation of the amygdala.
The most prominent finding in the ANE paper focused on a single brain region, the amygdala. Here the findings showed that the amygdala development patterns of the vaccinated monkeys were different from those of the unvaccinated (the amygdala regulates emotions and social connection and has been implicated in autism, with both increased size and differences in function). Although the amygdala represents only a tiny fraction of overall brain volume, here the developmental changes observed in the neuroimaging analysis did appear to be related to the MMR exposure. In others words, the seventh measure on the list above, the interaction effect, was significant, or in the authors words, “An interaction effect between time and exposure, manifested by a significant time by exposure interaction term, would indicate that the effect of time is either mitigated or enhanced by exposure. In other words it would indicate that the trajectory of maturational change differs between exposed and unexposed animals.”
When the ANE paper first came out, a bit of chatter in the wackosphere jumped on what appeared to be an unusual finding in the small sample of controls, namely that the amygdala volume of the unvaccinated monkeys actually declined. Was this normal, or just a glitch in a small sample? It’s a reasonable question, and provided a window for critics to argue that there was something wrong with the study. After all, shouldn’t normal amygdalae grow during infancy?
But if we want to be precise, what we’re really asking here is this: what is the normal pattern of maturation of the amygdala in macaques raised under similar conditions during the period in development from 4-6 months of age? And the first step here is to look at the scientific record to see if there are any direct comparables. In fact, there is one, and only one, published study on this topic. In a 2009 study in the journal Hippocampus, Payne et al investigated the “maturation of the hippocampal formation and amygdala in macaca mulatta.” They measured amygdala volume at varying points over the first 28 months of life in 10 macaques, but only obtained measurements in 4 male monkeys for the relevant period spanning 4-6 months of age. Of these, only three of these had multiple scans that took place at times comparable to the before and after scans in the ANE study.
How did the amygdalae in these monkeys develop during this period? Of the three monkeys that had comparable scans, all three showed a period of declining amygdala volume, two of which were quite sharp. This evidence supports the finding of the ANE paper that a period of maturational decline in the amygdalae of infant monkeys is normal, and that vaccine exposures that include MMR interrupt that maturational process in infants.
The neuroimaging report in the ANE paper also included assessments of the activity of opioid receptors across all brain regions. And these assessments showed a marked difference in the development of opioid receptors as the amygdala matured. Opioid activity was measured statistically by region (using the same seven measures), but also in a vivid “heat map” that shows the special affinity of opioid receptors for the amygdala. This heat map is shown below, with a representative unvaccinated monkey on top at T1 and T2 and a vaccinated monkey below.
Dan Olmsted is Editor and Mark Blaxill is Editor at Large of Age of Autism