16 April 2003 17:00 GMT

by Henry Nicholls

Oxford - Further testing of the hypothesis that the 3-in-1 measles, mumps, and rubella (MMR) vaccine causes autism is impossible, say researchers. Worse, they add, it is unethical.

The putative link between MMR vaccination and autism was first published in 1998 by Andrew Wakefield and colleagues at the Royal Free Hospital in London. The hypothesis emerged on the back of a growing body of parental reports of an apparent association between a steady increase in diagnosed cases of autism and the introduction of the MMR vaccine.

But these are no more than temporal associations, says Elizabeth Miller, epidemiologist and head of the Immunization Division of the UK government's Public Health Laboratory Service

"The hypothesis was perfectly reasonable to generate given the observations," Miller told delegates at the 3rd International meeting of the Edward Jenner Institute for Vaccine Research, here in Oxford. But almost every one of the dozen-or-so studies to test Wakefield's hypothesis has failed to support it, she says. "He rejects these studies on the basis that they're not testing the hypothesis, but that's because the hypothesis keeps on evolving," she said.

For example, following initial studies that did not demonstrate a link, the hypothesis shifted to one that suggested an association would only be detected in the presence of other factors, such as antibiotics and atopy, says Miller.

The latest incarnation of the hypothesis, she says, is that the vaccinated measles virus persists in the gut of those with autism. "It's now evolved into a place where the hypothesis is untestable," said Miller. There is no ethical reason for gastroenterologists to take biopsies from children, she says, which would be necessary to put the hypothesis to the test.

Furthermore, there is strong criticism of the technique, immunogold electron microscopy, with which Wakefield claims to have identified measles virus in the gut. "The reagent they used to demonstrate the presence of the measles ... is wholly non-specific," said John Hermon-Taylor, chairman of the Department of Surgery at St George's Hospital Medical School in London. "The science is flawed," he said.

Miller agrees. "I don't think Wakefield is operating with the conventional scientific method," she told BioMedNet News.

The potentially fatal childhood diseases measles, mumps, and rubella had been virtually absent from the UK since the government introduced the MMR program in 1988. However, Wakefield's evolving hypothesis has led parents to seek alternative immunization through private routes or to shun vaccination altogether, resulting in local outbreaks of these diseases around the country.

The first signs are appearing of an increase in these diseases where vaccination is rejected. "We're now seeing significant outbreaks in these low-coverage communities," said Miller. If coverage of MMR vaccination does not improve, these dangerous viral diseases will become increasingly common within a matter of years, she warns.

In spite of the combined evidence of numerous studies, the British public remains wary of governmental advice on health issues in the absence of an alternative explanation for the rise in autism and, especially, in the wake of government mismanagement of the BSE crisis and foot-and-mouth disease. Some 1500 families have been given legal aid to bring a court case against the main manufacturers of the MMR vaccine. Miller expressed hope that this will lay the controversy to rest once and for all.

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