Blockbuster Primate Study Shows Significant Harm from One Birth Dose of a Mercury-Containing Vaccine

http://www.ageofautism.com/2009/09/b...g-vaccine.html
September 30, 2009
Blockbuster Primate Study Shows Significant Harm from One Birth Dose of a
Mercury-Containing Vaccine



[Editor's update: The article is now available for purchase at Science
Direct. See link below.]


By Mark Blaxill


A research team led by scientists from the University of Pittsburgh and
Thoughtful House reported today that exposure to a birth dose of a
hepatitis B vaccine that included an ethyl mercury preservative caused
significant delays in the development of several survival reflexes in male
rhesus macaque monkeys. The findings were published on line today in the
journal Neurotoxicology. [See the abstract below and the link to a site
where you can purchase the article on Science Direct HERE]

In the first safety study of its kind of the hepatitis vaccine birth dose,
the researchers showed that male macaques vaccinated at birth with a
hepatitis B vaccine (HBV) took more than twice as long as unexposed macaques
to acquire three standardized skills typically used to measure infant brain
development. The thirteen vaccinated monkeys each received a dose of Merck's
Recombivax® hepatitis B vaccine to which a weight-adjusted amount of the
ethyl mercury-containing vaccine preservative thimerosal had been added
(each dose included 2 micrograms of ethyl mercury as opposed to the human
infant dose of 12.5 micrograms). Seven unexposed monkeys received either a
saline placebo injection or no shot at all.

Over a two week period following birth, the researchers examined the infant
macaques daily for their ability to perform nine basic reflexes (four
reflexes were tested in two ways, so the paper reports thirteen performance
results). Three of nine reflexes showed significant delays in vaccinated
macaques while two other reflexes were delayed and "approached
significance." As for the three significant reflexes, vaccinated macaques
learned more slowly to: 1) turn their head in response to a brush on the
cheek (the root reflex); 2) open their mouth in response to a brush on the
forehead (the snout reflex); and 3) suck on a nipple placed in their mouth
(the suck reflex).

Although the paper is carefully worded and the results reported modestly,
these findings are certain to receive intense scrutiny. For while hepatitis
B vaccines currently produced in the United States no longer contain
thimerosal, the vast majority of American infants born during the 1990s
received a vaccine formulation similar to the one the thirteen vaccinated
macaques received. In addition, thimerosal-containing HBVs are still
routinely administered to newborn infants in developing countries such as
Brazil. Consequently, the finding that early exposure to potentially toxic
vaccine formulations can cause significant neuro-developmental delays in
primates has explosive implications for vaccine safety management. These
implications go far beyond the domestic HBV program and raise concerns about
HBV formulations sold abroad as well as the domestic influenza vaccine
program. Most influenza vaccines, including the vaccines in the upcoming
swine flu program, contain thimerosal and are routinely administered to
pregnant women and infants.













According to Dr. Andrew Wakefield, Executive Director of Thoughtful House
and a co-investigator of the project, "What is particularly concerning is
that in spite of the recommendation to remove thimerosal from vaccines a
decade ago, millions of people, many of them children and pregnant mothers,
are about to get mercury in their shots. Thimerosal is still routinely used
in Hepatitis B and numerous other vaccines world-wide. "

The authors are careful to point out several limitations of their analysis.
According to the paper, "our study design does not enable us to determine
whether it is the vaccine per se, the exposure to [thimerosal], or a
combination of both that is causing the observed effects. " In addition, the
effects appear in some reflexes to be mediated by other risk factors such as
birth weight and gestational age, suggesting that vaccinating premature
and/or low birth weight infants may create especially high risk. "Infants of
lower birth weight and gestational age were at greater risk" explained Dr.
Laura Hewitson of the University of Pittsburgh, one of the principal
investigators of the study. "The reflexes affected in this study are
controlled by the brainstem, which regulates functions like heart rate,
breathing, and intestinal activity, so these findings give us cause for
concern, especially for low birth weight and pre-term infants who might be
more susceptible to functional brain injury from this vaccine".

Despite their interest in the brainstem, the authors note that the "the
mechanism of these effects and the requirement for [thimerosal] is not known
and requires further study." At least some of that further study is
underway. According to Wakefield, "This study is part of a larger research
program looking at the safety of the vaccine schedule from birth to age four
years."

In fact, some findings from the group's own further study may already be at
hand. Close reading of the published paper reveals that these macaques were
followed for only fourteen days from birth for adverse responses to HBV
because "infants received further interventions on Day 14 which would have
confounded the independent effects of the HB vaccine." These further
interventions were most likely additional vaccinations. Over a year ago,
Age of Autism reported on a series of abstracts presented at an autism
conference by many of the same authors (see HERE). These abstracts describe
a study design in which multiple vaccines were administered, in addition to
HBV. The current study design appears similar to the earlier reports, but
differs from the previous abstracts in the number of vaccine exposures (one
vs. multiple, including MMR) and the number of unexposed macaques (three vs.
seven).

Careful methods, conservative findings

Basic reporting aside, it's worth digging a bit deeper into some of the
details of the study design, which will almost certainly attract further
attention. There are numerous elements that go into a primate study like
this, elements that can and should influence the scientific acceptance of
the results. These include: the quality of the primate lab and research
group, the quality of the study design and testing methods, the size of the
sample, the authors' statistical interpretations and potential biases.

Primate research expertise. The macaques were bred and housed at the primate
nursery of the Pittsburgh Development Center (PDC) at the University of
Pittsburgh, where the research team's principal investigator, Dr. Laura
Hewitson, is a member of the faculty. The PDC is a part of the Magee Women's
Research Institute of the University of Pittsburgh's School of Medicine. PDC's
research mission includes stem cell development and infertility in addition
to an infant development research program of which the Infant Primate
Laboratory headed by Dr. Hewitson is the driving force.

The PDC was founded in 2001 and its primate program is relatively new. But
the director of the PDC, Gerald Schatten, came to Pittsburgh from Oregon
National Primate Center, one of nine National Primate Research Centers
(NPRCs) sponsored by the National Institutes of Health (NIH). In addition,
the vaccine study's PDC team has benefited from the direct involvement of
two of the most prominent primate researchers in the nation. The late Gerald
Ruppenthal was an active collaborator of the PDC and in that capacity also
"assisted in the [vaccine] study design, training and implementation of the
infant primate developmental measures prior to his death in 2004."

Perhaps most importantly, one of the vaccine study co-authors is Dr. Gene
Sackett, who was once director of the University of Washington's Infant
Primate Research Laboratory, another one of the nine NIH primate centers
(now headed by Dr. Thomas Burbacher). He is now Professor Emeritus at the
University of Washington. Along with Ruppenthal, Dr. Sackett was co-editor
of one of the most widely used texts for primate research, Research Protocol
and Technician's Manual, published in 1992.

In short, while the PDC is a relatively new primate facility, both the PDC
primate facility and the vaccine study team have benefited from the active
support and participation of the country's leading primate experts.

Study design and testing methods. The study was carefully designed and
tightly controlled to prevent bias from entering into any of the
assessments. Crucially, the exposure status of the macaques was not known to
the team. "Neonatal assessments were performed by [Lisa A. Houser] who was
unaware of the study group assignment of each animal, the number of animals
in each study group and the number of study groups." Adding rigor to the
implementation of the testing, Houser "underwent extensive training" in
making these assessments by the leading experts in the field, Gerald
Ruppenthal, before his death.

In addition to Ruppenthal's involvement as a trainer, Dr. Sackett's
involvement as co-author and data analyst ensured that Houser's data
collection was sound. Dr. Wakefield and Dr Hewitson designed the study, but
neither was involved in data collection or statistical analysis. Dr.
Wakefield's role in the ongoing autism-vaccine controversy may make the
design subject to added criticism; at the same time, it provided added
incentive to make the design impervious to superficial criticism.

Sample size. At first glance, the number of infant primates involved,
thirteen vaccinated macaques and seven unexposed (the paper avoids using the
word "unvaccinated" to describe the latter group since four were injected
with saline placebo and three received no shot at all) may seem low. Some
might offer the concern that this sample is too small to draw any strong
conclusions, but this would reflect ignorance of how primate research is
typically conducted. Unlike rats and mice, which can be bred in laboratories
in relatively large numbers, primates are expensive to raise. And since the
purpose of study designs involving infant primates is to infer human
exposure risk from the developmental outcomes of our closest animal
relatives, the testing protocols are designed to be sufficiently precise so
that valid conclusions can be drawn from small numbers of animals.

In other words, the sample is sufficiently large for a study of this type,
especially since only two exposure groups were studied. In addition, all 20
macaques described were male, eliminating any confounding effect of gender
and further raising the statistical power of the sample.

It's worth comparing the size and composition of these study groups to that
of two comparable research projects that have been frequently cited and
widely accepted as sound. In the first of these, published in 2005, Dr.
Thomas Burbacher, from University of Washington's NPRC, led a study team
that examined the effects of thimerosal and methyl mercury in infant
primates. In this study, Burbacher's team examined a different species of
macaques in a mixed-gender sample that included seven controls and seventeen
animals in each of the two (thimerosal and methyl mercury) exposure groups.
The total study involved 41 infant male and female macaques. In a second
comparable project, Dr. Burbacher published an influential series of studies
on the effect of subclinical methyl mercury exposure, spanning five papers
published from 1994-96, in adult macaques. His study sample examined
multiple exposure groups with five female macaques in each group and only
four unexposed females. The total study involved 27 adult female macaques.

It's worth noting that the seven unexposed macaques reported in today's
paper represents an increase in unexposed animals relative to the three
animals in the conference abstracts published last year. Last year's control
group was similar in size to the 1994-96 Burbacher control group (three
infant males vs. four adult females) but may have raised concerns over
adequate sample size. The current study's unexposed population is equal in
size to Burbacher's infant (but mixed gender) 2005 control group and larger
in size than the 1994-96 control group of adult females.

When considering both the confounding effects of gender and the number of
animals per exposure group, today's study compares favorably to both of
these prior studies, with more gender specific controls than either of the
Burbacher studies and more animals of a single gender in the main exposure
group than either study as well.

Statistical interpretations. Setting aside the typical standards for primate
work, from a purely statistical perspective the raw numbers involved in this
vaccine study are still not large. That means that for any difference in
developmental outcomes to reach statistical significance, it would have to
be large. And despite the modest sample sizes, the statistical differences
reported by the researchers are quite robust. Across a wide range of
statistical tests the root reflex finding consistently reached significance
with 99% confidence, the suck reflex finding reached significance with 98%
confidence and the snout reflex finding reached 95% confidence in two out of
three analyses and with 94.5% confidence in the third (95% confidence is the
level generally accepted as "statistically significant").

These findings are clearly sufficient to make the findings important, but it's
worth noting that the authors' interpretation of their data analysis is
highly conservative. In addition to significant findings in three of the
nine reflexes, it's quite plausible to make the case that two more of the
reflexes were delayed by HBV exposure as well. The analysis of these
reflexes--the auditory startle reflex and the grasp hand reflex--"approached
significance" in each case. Two different methodological obstacles
contributed to the failure to reach significance.


1. In the case of the auditory startle reflex, the sheer size of the
difference between the two groups was larger than any of the three reflexes
that showed statistically significant differences. The vaccinated macaques
took a full two days longer on average to acquire the auditory startle
reflex than the unexposed group; by contrast, the difference between the
averages of the two groups' time to acquire the root reflex was just 1.2
days. The difference in the auditory startle was also understated, since one
of the vaccinated macaques never acquired the reflex during the entire two
week observation period. Because of the modest sample size, however, the
relatively larger variation in this group made the result significant with
only 89% confidence.


2. In the case of the grasp hand reflex, a result that was significant
with 93.5% confidence, both vaccinated and unexposed macaques acquired this
reflex relatively quickly. But since every one of the unexposed macaques
acquired the reflex at the first examination, the average time to acquire it
was "left-censored", meaning that it was assigned the minimum possible value
of 0.5 days, and almost certainly overestimated the development time of the
unexposed sample. If the unexposed group had been measured without any need
for "left censoring", then only a modest reduction (under 10%) in the mean
time to acquire the grasp hand reflex would have been enough to bring this
result into the significant range.

To make the point more simply, it would have taken only modest differences
in the management of the data analysis to make over half of the measured
reflexes show significant delays instead of a third of them. Pointing this
out is not intended as a criticism of the study, however, but rather a
demonstration of how conservative the authors were in their interpretation
of the results.

Finally, for the three reflexes that were initially found significant, the
authors dug deeper and conducted two different kinds of regression analysis
to ensure that the differences were not affected by other factors such as
premature birth or low birth weight (the study's tables provide a
painstakingly intricate array of these regression model outputs). The first
of these showed a consistently strong developmental benefit of not being
vaccinated, with unexposed macaques having a "risk" of developing the three
reflexes (where the risk was actually a benefit) that was 3-5 times the
"risk" of the vaccinated group (although the snout reflex risk level only
reached 94% confidence). The second set of regressions attempted to
distinguish whether the effect of vaccination was a main effect or the
result of interaction with the effects of premature birth or low birth
weight. In all models that compared main and interaction effects, the
exposure effect was significant in way or the other: the root and snout
reflexes were best explained as main effects (although the root reflect was
significant as an interaction effect also), while the suck reflex appeared
to be best explained as an exposure risk for low birth weight and/or
premature infants.

It's likely that most readers will skim through the results of these
regression models, just confirming the fact that the results were
significant. But it's important to recognize how carefully the analysts have
investigated if other factors besides exposure could explain the
developmental delays of the vaccinated macaques. In all cases, the delayed
development of these reflexes was clearly traced to vaccination.

Potential biases. One likely tactic of critics of the study will include
attempts to nullify the evidence based on the alleged bias of those
involved. For one, the study is privately funded and acknowledges some well
known autism advocates as financial contributors. These include the Johnson
family (Jane Johnson is co-author of Changing the Course of Autism, a member
of the Board of Directors of Thoughtful House and Director of Defeat Autism
Now!), SafeMinds, the Autism Research Institute and Elizabeth Birt. Although
all of these groups make clear their research interest is vaccine safety,
they are frequently attacked for being "anti-vaccine", an epithet that will
almost certainly be hurled again here.

The most aggressive attacks, however, will likely be reserved for the study
authors. The basis of these attacks is best anticipated by the following
conflict of interest disclosure in the published paper. "Prior to 2005,
[Carol Stott] and [Andrew Wakefield] acted as paid experts in MMR-related
litigation on behalf of the plaintiff. [Laura Hewitson] has a child who is a
petitioner in the National Vaccine Injury Compensation Program. For this
reason, [Hewitson] was not involved in any data collection or statistical
analyses to preclude the possibility of a perceived conflict of interest."

Related evidence on the hepatitis B vaccine

In spite of the active involvement of autism-related organizations and
parents in the study's design and funding, this narrow investigation of HBV
exposures doesn't bear directly on the question of whether HBVs with (or
without) thimerosal contribute to causing autism. The only harm described in
these vaccinated macaques is in a tightly defined set of "survival reflexes"
during a brief window after birth and exposure. We will have to wait for
future reports from the research team to gauge both the nature and the
persistence of the development delays in the vaccinated group.

At the same time, the narrow focus of the current study invites a similarly
focused comparison to a small set of recent studies, published and
unpublished, that explored the relationship between HBV/thimerosal exposure
and autism or other neuro-developmental delays (NDDs). Three separate
studies--two recently reported by a pair of scientists from Stony Brook
University, the third disclosed via Freedom of Information Act (FOIA) and
performed by researchers from the Centers for Disease Control (CDC)-provided
compelling additional evidence linking the birth dose of a
thimerosal-containing HBV and elevated autism or NDD risk.

In the fall of 2008, Carolyn Gallagher and Melody Goodman, PhD candidate and
Assistant Professor of Preventive Medicine, respectively, at the Stony Brook
University Medical Center, reported on their analysis of a sample of over
1800 children whose families were surveyed as part of the National Health
and Nutrition Examination Survey (NHANES) in 1999-2000. They took advantage
of two questions posed in that survey: 1) "Does your child receive Special
Education or Early Intervention Services"; and 2) "Has the survey
participant ever received the 3-dose series of the hepatitis B vaccine." At
the time of the survey, all HBVs administered to children under 10 years of
age would have contained thimerosal.

When Gallagher and Goodman analyzed the risk of exposure to the 3 dose HBV
series in children (the study didn't query whether this dose included the
birth dose, but the CDC's universal birth dose recommendation was in place
during the entire study period), they got back a surprising result. There
was no apparent risk of HBV exposure in girls (there even appeared to be a
protective effect), but the risk of needing special services in fully
vaccinated boys was over twice as high as less vaccinated boys and the
difference was statistically significant. When they adjusted the odds for
confounding factors, they estimated the increased risk for boys needing
special services after full HBV exposure to be fully 8.6 times higher than
less vaccinated boys.

Subsequent to this publication, Gallagher and Goodman continued their
investigation. Earlier this month, they published an abstract from a poster
presentation that reported findings from a more focused investigation. In
this analysis they looked at only the birth dose of HBV and boys born before
1999 whose parents reported their child had "received a professional
diagnosis of autism." The more precise data for this work was provided by a
different survey, the National Health Information Survey (NHIS) and would
again have included only thimerosal-containing HBV. They found that "U.S.
male neonates vaccinated with hepatitis B vaccine had a 3-fold greater risk
of ASD."

So from two separate data sources, Gallagher and Goodman have produced
findings that dovetail almost perfectly with today's primate report. In male
infants vaccinated at birth with thimerosal-containing HBV, the risk of
immediate developmental delays (macaques), the need for early intervention
services (NHANES) and autism (NHIS) is increased anywhere from three to
eight fold.

If this finding is so clear, the obvious question is why the CDC's vaccine
safety apparatus hasn't found the same thing.

The answer, of course, is that they have. In their very first examination of
the risk of thimerosal exposure in infants, the single most startling
finding was this: infants who received the largest exposure of thimerosal in
the first month of life showed the highest risk of autism and several other
NDDs. Buried deep in a pile of statistical tables that SafeMinds received
under FOIA was a risk analysis conducted by CDC analyst Thomas Verstraeten
showing statistically significant risk multiples for the most exposed
infants. These ranged from 5 times the risk of unexposed infants in the case
of sleep disorders to 11.5 times for autism. I summarized these data tables
in a report written five years ago. You can find it HERE.

What happened to the CDC findings that are now forcing us to rediscover the
risk of thimerosal-containing birth doses of HBV in monkeys? The answer is
simple. The CDC team simply censored the data. Infants with the highest
levels of thimerosal exposure--those who had received both the HBV and
hepatitis B immune globulins--were simply removed from the study sample. In
Verstraeten's words, "the following children were excluded from the
analysis.Children that received hepatitis B immunoglobulin as these were
more likely to have higher exposure and outcome levels."

Why they decided this was a legitimate exclusion is anyone's guess.
Unfortunately, it leads us all back to monkeys.

Future research

The report makes clear that future research is both needed and forthcoming.
The immediate direction of that research is obvious. There is a clear,
indeed urgent, need for further publications that describe what happened to
the vaccinated macaques and their unexposed counterparts as succeeding
vaccines were administered, including the thimerosal-containing DTaP and Hib
vaccines and the MMR vaccine. These publications should include not just how
the two macaque groups' observable development proceeded, but also how their
gastrointestinal tracts were affected by the vaccine exposures and how their
brain development was changed. Judging from last year's conference
abstracts, the study team's research program has included both brain imaging
and gut tissue analysis, so the main obstacle to further dissemination of
the research findings appears to be publication.

Between the May 2008 conference abstracts and today's publication, over a
year has passed and only a small portion of the promised insight from the
original abstracts has been made public. The journal editors at
Neurotoxicology have taken a courageous stand in publishing what is sure to
be unwelcome evidence in some circles. Let's hope we see more from this
project team soon.

Mark Blaxill is Editor-at-Large for Age of Autism and a Director of
Safeminds, one of the organizations that sponsored the study.


Abstract: This study examined whether acquisition of neonatal reflexes and
sensorimotor skills in newborn rhesus macaques (Macaca mulatta) is
influenced by receipt of the single neonatal dose of Hepatitis B (HB)
vaccine containing the preservative thimerosal (Th). HB vaccine containing a
standardized weight-adjusted Th dose was administered to male macaques
within 24 hours of birth (n=13). Unexposed animals received saline placebo
(n=4) or no injection (n=3). Infants were raised identically and tested
daily for acquisition of 9 survival, motor, and sensorimotor reflexes by a
blinded observer. In exposed animals there was a significant delay in the
acquisition of three survival reflexes: root, snout and suck, compared with
unexposed animals. No neonatal responses were significantly delayed in
unexposed animals compared with exposed. Gestational age (GA) and birth
weight were not significantly correlated. Cox regression models were used to
evaluate the main effects and interactions of exposure with birth weight and
GA as independent predictors and time-invariant covariates. Significant main
effects remained for exposure on root and suck when controlling for GA and
birth weight such that exposed animals were relatively delayed in
time-to-criterion. There was a significant effect of GA on visual follow far
when controlling for exposure such that increasing GA was associated with
shorter time-to-criterion. Interaction models indicated that while there
were no main effects of GA or birth weight on root, suck or snout reflexes
there were various interactions between exposure, GA, and birth weight such
that inclusion of the relevant interaction terms significantly improved
model fit. This, in turn, indicated important influences of birth weight
and/or GA on the effect of exposure which, in general, operated in a way
that lower birth weight and/or lower GA exacerbated the detrimental effect
of vaccine exposure. This primate model provides a possible means of
assessing adverse neurodevelopmental outcomes from neonatal Th-containing HB
vaccine exposure, particularly in infants of lower GA or low birth weight.
The mechanism of these effects and therequirements for Th is not known and
requires further study.

"john" wrote in message
...
September 30, 2009
Blockbuster Primate Study Shows Significant Harm from One Birth Dose
of a Mercury-Containing Vaccine


Are we supposed to believe you after the Wakefield fiasco?

I T H I N K N O T!

You can fool some of the people some of the time but not all of the
people all the time.

Give it up.

On Sat, 6 Feb 2010 07:29:45 -0000, "john" wrote:

Blockbuster Primate Study Shows Significant Harm from One Birth Dose of a
Mercury-Containing Vaccine

[Editor's update: The article is now available for purchase at Science
Direct. See link below.]

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W81-4XC57CT-1&_user=10&_coverDate=10%2F02%2F2009&_rdoc=1&_fmt= high&_orig=browse&_srch=doc-info%28%23toc%236641%239999%23999999999%2399999%23 FLA%23display%23Articles%29&_cdi=6641&_sort=d&_doc anchor=&view=c&_ct=61&_acct=C000050221&_version=1& _urlVersion=0&_userid=10&md5=4dfea2dc7075d6dd08741 3b80f4b8f3b

"This article has been withdrawn at the request of the editor. The
Publisher apologizes for any inconvenience this may cause."

Not much of a "blockbuster" it seems.