Jun 11, 2004
NEW YORK, USA: Scientists in the United States have raised fears that a mercury-based preservative used in vaccines may cause symptoms of autism.
Researchers at Columbia University in New York found autism-like damage in the brains of mice exposed to the preservative, thimerosal.
In the United Kingdom, it is used in the DTP jab for diphtheria, tetanus and whooping cough and in some flu jabs.
The study, published in the latest edition of the journal, Molecular Psychiatry, has been challenged by various expert groups, who say there is no evidence that the preservative poses any risk.
A major review carried out by the US Institute of Medicine published last month found no evidence that thimerosal was linked to autism.
Similarly, investigations by the UK Committee on Safety of Medicine, Europe's Agency for the Evaluation of Medicinal Products and the World Health Organization concluded that the preservative was safe.
However, the Columbia team said they had found that mice exposed to thimerosal showed signs of changed behaviour and brain abnormalities. The animals had been bred to be vulnerable to developing disorders of the immune system. They researchers argued that it was possible that children with similarly compromised immunity may also be at risk.
The lead researcher, Dr Mady Hornig, said the Institute of Medicine may have jumped to premature conclusions.
She said: "We feel very strongly that any future immunisation programme is well built on careful analysis that doesn't stall areas of research before they have been thoroughly researched."
A British Department of Health spokesman said: "Vaccine safety is of paramount importance and all vaccines used in the UK are tested for their safety and efficacy."
The Columbia University researchers reported that thimerodal used in some vaccines could cause behavioural abnormalities in new-born mice characteristic of autism, but only in mice with a specific genetic susceptibility,
The fact that 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 Dr Ellen Silbergeld. of the Johns Hopkins School of Public Health, in Baltimore, 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."
The 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 analogue 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 of the latest study. "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, Dr Hornig added.
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 in the US this year.
Autism is a severe developmental disorder in which children seem isolated from the world around them. Several epidemiological studies have failed to find a link between vaccines and the apparent 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.
Dr 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. New-born mice of each strain were injected with either thimerosal or a thimerosal-vaccine combination at ages corresponding to those when human infants are typically immunised. 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 were typical of children with autism, Dr 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.
Sources: Molecular Psychiatry, BBC News Online, Los Angeles Times, June 8, 2004