Page last updated at 17:11 GMT, Monday, 4 February 2008

MMR research timeline

Vaccination rates dropped following Dr Wakefield's paper

The suggestion that the vaccination for measles, mumps and rubella (MMR) might raise a child's risk of bowel disorders and autism has proved to be one of the most controversial in medical science for decades.

The controversy whipped up by the original research saw vaccination rates fall sharply, prompting fears of a measles epidemic, and widespread condemnation from leading scientists.

It has taken the medical establishment years to reassure the public that the claims were completely without foundation, and for vaccination rates to recover.

This is how the scientific debate panned out.

February 1998:

Research led by Dr Andrew Wakefield, then a reader in experimental gastroenterology at London's Royal Free Hospital, is the first to suggest that the MMR vaccine might be linked to an increased risk of autism and bowel disorders.

This is a genuinely new syndrome
Dr Andrew Wakefield

Dr Wakefield says he has evidence that children's behaviour changed drastically shortly after they received the MMR jab.

He says: "This is a genuinely new syndrome and urgent further research is needed to determine whether MMR may give rise to this complication in a small number of people."

Dr Wakefield theorises that the combination of the three virus strains contained in MMR may overload the body's immune system and cause the bowel disorder to develop.

At a press conference, he suggests individual vaccines to protect against the three diseases might be safer.

However, the research was carried out on only 12 children.

March 1998:

A panel of experts set up by the Medical Research Council says there is "no evidence to indicate any link" between MMR jab and bowel disease or autism in children.

Thirty seven scientific experts gather to review all the evidence and conclude there is no reason to change the current MMR vaccination policy for children.

April 1998:

A 14-year study by Finnish scientists finds no danger associated with the MMR vaccine.

Out of the three million children given the MMR jab, those who developed gastrointestinal side-effects lasting 24 hours or more were traced.

In all, 31 youngsters developed gastrointestinal symptoms such as diarrhoea and vomiting within 15 days of the injection. But their symptoms generally lasted no more than a week.

In one case a baby boy suffered diarrhoea for six weeks but recovered and was healthy when checked six years later.

None of the 31 children developed any signs of autism or any similar syndrome.

The researchers concluded that after a decade's effort to detect all severe adverse effects associated with the MMR vaccine they could find "no data supporting the hypothesis that it would cause pervasive developmental disorder or inflammatory bowel disease."

April 2000:

Dr Wakefield and Professor John O'Leary, director of pathology at Coombe Women's Hospital in Dublin, present research to the US Congress showing that tests on 25 children with autism revealed 24 had traces of the measles virus in their gut.

Professor O'Leary said there was now "compelling evidence" of a link between autism and MMR.

This association, however, would not in itself confirm that the virus causes autism, or even that the source of the virus found is the MMR vaccination, which contains "dead" versions of the measles and mumps viruses.

The Department of Health said the research proved nothing and was "unverifiable by usual scientific means".

Other researchers tried to replicate Wakefield and O'Leary's research - but were unable to do so.

January 2001:

Dr Wakefield renews his concerns about MMR, saying the vaccine has never undergone proper safety tests.

In a study published in the journal Adverse Drug Reactions and Toxicology Review, Dr Wakefield says original safety checks on the vaccine were poorly conducted and only lasted for four weeks.

The claim is rejected by the Department of Health.

February 2001:

A major statistical analysis published on the British Medical Journal website concludes the soaring rate of autism in recent years is almost certainly not due to the MMR injection.

The study finds that the number of cases of autism has continued to rise even though MMR coverage has remained roughly the same.

If MMR was the cause of illness, say the experts, the number of autism diagnoses would also have levelled off by now.

September 2001:

Researchers from St George's Hospital, London, UK, and the Institute for Child Health give the vaccine the all-clear after examining all the studies into MMR that have been carried out. The research is published in the journal Archives of Disease in Childhood.

Using separate vaccines is an untried and untested policy
St George's Hospital researchers

The researchers say: "Using separate vaccines is an untried and untested policy and, as far as protecting children from infectious disease is concerned, a backward step."

December 2001:

A new Medical Research Council review of research, commissioned by the Department of Health, finds no link between the vaccine and autism.

The report suggests autism is the result of a range of causes, with the strongest evidence to date is for genes being mostly to blame.

It suggests several genes interact to create susceptibility to the disorder and believes the interplay between genetic and environmental factors are likely to play a key role, although the nature of this is not yet known.

Commenting on MMR, it says: "In relation to the combined MMR vaccine, we conclude from our review that the current epidemiological evidence does not support the proposed link of MMR to autism spectrum disorders."

February 2002:

Dr Wakefield and Professor O'Leary publish a paper in the journal Molecular Pathology which suggests a possible link between the measles virus and bowel disease in children with developmental disorders.

The study set out to investigate whether children with developmental disorders such as autism and a bowel disorder also had the measles virus in their gut.

It found traces of the virus in the guts of 75 children out of 91 with bowel disease, but in only five out of 70 healthy children.

The researchers theorise that the virus may act as a trigger, leading to problems with the immune system.

Dr Wakefield said most of the children in the study had had MMR, though a few had had the single vaccine.

He and his colleague emphasise that it would be wrong to jump to any hasty conclusions about MMR causing either bowel disease or developmental disorders such as autism.

The editors of the journal also stressed that the paper did not set out to investigate the role of MMR in developmental disorders or bowel disease - and no role was suggested for it.

February 2002:

A team from the Royal Free Hospital - where Dr Wakefield carried out his initial research - publishes a study on the British Medical Journal website saying there is no link between MMR and autism.

The team looked at almost 500 children with autism born between 1979 and 1998.

It found the proportion of children with developmental regression (autism) or bowel disorders did not change significantly over that time.

March 2004:

Majority of colleagues of Dr Wakefield who worked on the Lancet paper retract their support for the claims of a possible link between the vaccine and bowel disease or autism.

In a paper published in The Lancet they said: "We wish to make it clear that in this paper no causal link was established between MMR vaccine and autism as the data were insufficient.

"However, the possibility of such a link was raised and consequent events have had major implications for public health.

"In view of this, we consider now is the appropriate time that we should together formally retract the interpretation placed upon these findings in the paper."

September 2004:

A Medical Research Council team looked at the vaccination records of 1,294 children diagnosed with autism or related conditions between 1987 and 2001 in England and Wales.

These children were compared with 4,469 children of the same sex and similar age who were registered with the same GP surgeries but did not have autism.

Overall, 78% of the children with autism had received MMR. But 82% of the other children had also been given MMR.

The researchers say this 4% difference is not significant, and they argue that the sheer size of their study makes their finding very powerful.

March 2005:

Japanese scientists say they have strong evidence that the MMR vaccination is not linked to a rise in autism after they found a rise in the incidence of autism after the withdrawal of the measles, mumps and rubella jab in their country in 1993.

The researchers from the Yokohama Rehabilitation Center and the Institute of Psychiatry looked at the incidence of autism spectrum disorders among 31,426 children up to the age of seven born from 1988 to 1996.

There were between 48 cases per 10,000 children born in 1988.The rate was steadily seen to rise to 117.2 per 10,000 for those born in 1996 - after MMR had been withdrawn.

May 2006:

US scientists report they have found measles virus in the guts of autistic children with bowel disease.

However, Dr Stephen Walker, the scientist behind the work, states that the finding did not show that the MMR vaccine caused the condition.

February 2008

A team led by London's Guy's and St Thomas's Hospital looked at any differences in the immune response from the MMR jab to see if that could have triggered autism.

Researchers looked at 240 children aged 10 to 12.

They found no difference between children with autism and those without, and concluded the study showed there was no link.

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