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

 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: mh2092@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