http://www.flu.org.cn/news/2004986362.htm
Thimerosal, New study reopens debate on vaccinations
Published: Sep ,8,2004 16:21 PM
Special to The Wall Street Journal & Medicalnewstoday

By Tara Parker-Pope
The Wall Street Journal

Just a few months after the nation's top medical adviser rejected a
link between vaccines and autism, a mouse study has reignited the
debate and raised new fears among parents considering vaccinations and
flu shots for their kids.

For years, a cadre of parents and physicians have contended that
thimerosal, an ethyl-mercury compound that has been one of the most
widely used vaccine preservatives, is partly responsible for an
apparent rise in autism in recent decades. But broad population studies
haven't supported the claim. In May, a major report from the Institute
of Medicine's Immunization Safety Review Committee rejected a link
between autism and vaccines.

But today, a congressional committee will review a June study from
Columbia University, which found that a preservative used in vaccines
can cause autism-like symptoms in a specific strain of mice. The
research raises questions about whether some people might be
genetically vulnerable to the effects of thimerosal.

The study also raises questions about a new push by the Centers for
Disease Control and Prevention to add flu shots to the immunization
schedule for school-age kids. The vast majority of flu shots given
still contain the preservative.

In the study, researchers administered thimerosal to four strains of
young mice. Three of the mice strains were unaffected by thimerosal,
but the fourth developed problems consistent with autism such as
delayed growth, social withdrawal and brain abnormalities. The mice
were known to have a genetic susceptibility to mercury.

Thimerosal, found in childhood vaccines, can increase the risk of
autism-like damage in mice

A new study indicates that postnatal exposure to thimerosal, a mercury
preservative commonly used in a number of childhood vaccines, can lead
to the development of autism-like damage in autoimmune disease
susceptible mice. This animal model, the first to show that the
administration of low-dose ethylmercury can lead to behavioral and
neurological changes in the developing brain, reinforces previous
studies showing that a genetic
predisposition affects risk in combination with certain environmental
triggers. The study was conducted by researchers at the Jerome L. and
Dawn Greene Infectious Disease Laboratory at the Mailman School of
Public Health, Columbia University. Over the past 20 years, there has
been a striking increase--at least ten-fold since 1985--in the number
of children diagnosed with autism spectrum disorders. Genetic factors
alone cannot account for this rise in prevalence. Researchers at the
Mailman School, led by Dr. Mady Hornig, created an animal model to
explore the relationship between thimerosal (ethylmercury) and autism,
hypothesizing that the combination of genetic susceptibility and
environmental exposure to mercury in childhood vaccines may cause
neurotoxicity.

Cumulative mercury burden through other sources, including in utero
exposures to mercury in fish or vaccines, may also lead to damage in
susceptible hosts. Timing and quantity of thimerosal dosing for the
mouse model were developed using the U.S. immunization schedule for
children, with doses calculated for mice based on 10th percentile
weight of U.S. boys at age two, four, six, and twelve months.

The researchers found the subset of autoimmune disease susceptible mice
with thimerosal exposure to express many important aspects of the
behavioral and neuropathologic features of autism spectrum disorders,
including:  Abnormal response to novel environments; Behavioral
impoverishment (limited range of behaviors and decreased exploration of
environment); Significant abnormalities in brain architecture,
affecting areas subserving emotion and cognition; Increased brain size.

These findings have relevance for identification of autism cases
relating to environmental factors; design of treatment strategies; and
development of rational immunization programs. The use of thimerosal in
vaccines has been reduced over the past few years, although it is still
present in some influenza vaccines. Identifying the connection between
genetic susceptibility and an environmental trigger for autism--in this
case thimerosal exposure--is important because it may promote discovery
of effective interventions for and limit exposure in a specific
population, stated the lead author Dr. Mady Hornig. Because the
developing brain can be exposed to toxins that are long gone by the
time symptoms appear, clues gathered in these animal models can then be
evaluated through prospective human birth cohorts--providing a powerful
to tool to dissect the interaction between genes and the environment
over time.

Citation source: Molecular Psychiatry 2004 Volume 9, advance on line
publication doi:10.1038/sj.mp.4001529

For further information on this work, please contact Mady Hornig, MD,
Columbia University, Mailman School of Public Health, Greene Infectious
Disease Laboratory, 722 W 168th St, New York, New York 10032, United
States of America, phone: 212-342-9036; FAX: 949-824-1229; e-mail:
mh2...@columbia.edu

ARTICLE: "Neurotoxic effects of postnatal thimerosal are mouse
strain-dependent"

M Hornig, D Chian, W. I. Lipkin

Greene Infectious Disease Laboratory, Mailman School of Public Health,
Columbia University, 722 W 168th St, New York, New York 10032

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