The mercury preservative used in some
vaccines can cause behavioral abnormalities in newborn mice
characteristic of autism, but only in mice with a specific
genetic susceptibility, Columbia University researchers report
today.
The findings challenge the results of several large studies
on autism and bolster the fears of parents who have long
believed their children were harmed by the vaccines.
The fact that the preservative, called thimerosal, had an
effect on only one strain of mice could explain why
researchers had found it so difficult to prove or disprove a
link to autism.
"The exciting thing is that this gives us a way forward in
understanding why we have not seen more conclusive findings on
either side of the fence, and how we need to design studies to
pick up gene-environment interactions," said Ellen Silbergeld
of the Johns Hopkins School of Public Health, who was not
involved in the study.
"I believe this has enormous implications for public
health," said Dr. Julio Licinio of UCLA, editor of the journal
Molecular Psychiatry, where the report is appearing.
"Showing that genetic background impacts on the outcome of
thimerosal exposure is a major breakthrough."
He added that the study clearly showed that there was a
link between vaccines and autism "for some groups and not for
others."
An Institute of Medicine report released last month
concluded that there was no evidence to support a link and
suggested that researchers study other possible causes.
Dr. Steven Goodman of the Johns Hopkins School of Medicine,
a member of the commission that prepared the report, said
those on the commission were aware of the research.
"It's a tantalizing little piece of evidence that requires
a lot more work" to overturn the "tremendous amount of human
work that doesn't find a clue of a connection," he said.
The researchers have not yet identified the human analog of
the mouse gene or genes that confer susceptibility to the
effects of thimerosal, so it is not clear what proportion of
children could be at risk from vaccinations containing the
preservative.
What they do know is that the genes are involved in the
immune system and that they make the mice more vulnerable to
autoimmune diseases. Researchers already know that as many as
a third of families with an autistic child have a history of
autoimmune problems.
The researchers do not believe that all cases of autism ?
or even a majority of them ? are caused by vaccines, said Dr.
Mady Hornig of Columbia, the lead author. "Autism is a
constellation of syndromes that almost certainly has many
different causes," she said.
But the link to thimerosal may help explain recent
increases in the incidence of the disorder, she said.
Thimerosal, which contains ethyl mercury, has long been
used as a preservative in vaccines. Critics contend it became
a problem in the 1970s, when the number of vaccines given to
children increased sharply.
Since 1999, it has been removed from most of the vaccines
routinely recommended for infants and children. It is still
used in injectable influenza vaccine, though some
thimerosal-free flu vaccine is expected to be available this
year.
Autism is a severe developmental disorder in which children
seem isolated from the world around them.
There is a broad spectrum of symptoms, but the disorder is
marked by poor language skills and an inability to handle
social relations.
No cure exists, but many problems can be alleviated with
intensive behavioral therapy.
Between 1975 and 1985, studies showed the U.S. rate of
autism to be about four cases per 10,000. Between 1985 and
1995, the numbers tripled to 12 per 10,000. But researchers
now think the actual rate may be much higher, on the order of
20 cases per 10,000.
Several epidemiological studies have failed to find a link
between vaccines and the increase in autism, and laboratory
studies in mice and other animals have also failed to show a
connection.
But researchers may have simply looked at the wrong
animals, said Dr. W. Ian Lipkin, in whose laboratory the new
work was carried out.
Hornig and her colleagues studied four strains of mice,
including one strain ? called SJL/L ? in which mercury had
previously been shown to stimulate autoimmune disorders.
Newborn mice of each strain were injected with either
thimerosal or a thimerosal-vaccine combination at ages
corresponding to those when human infants are typically
immunized.
The doses of mercury were also comparable to those used in
humans.
The three strains of mice with no autoimmune susceptibility
showed no effects from either type of inoculation.
But virtually all of the SJL/L mice developed a variety of
problems, including delayed growth, abnormal response to novel
environments, decreased exploration of their environments,
abnormalities in brain architecture and increased brain size.
All of those are typical of children with autism, Hornig
said.
"This is clearly showing that there is an interaction of
genes with the environment," said Dr. Daniel H. Geschwind of
UCLA, who had been looking for genetic causes of autism and
was not involved with the Columbia study. "The strain
difference is ... quite fascinating. This will clearly rev the
debate [about vaccines] up again."
The researchers are now following up on these findings by
trying to determine what other genes, if any, may be involved
in the mercury susceptibility.
They are also working with researchers at Brigham Young
University to try to find families with a genetic defect
comparable to that observed in the SJL/L mice to determine
whether they have a higher risk of autism.
