MMR

The MMR jab is a combined vaccine for measles, mumps and rubella. One version of the vaccine available in 2010 in the UK is made by Merck. Another version is made by GlaxoSmithKline (GSK) and is marketed under the name Priorix.

The MMR vaccine became controversial in February 1998, when a research team headed by Dr Andrew Wakefield suggested that it might be linked to an increased risk of autism and bowel disorders. It was GSK's version of the MMR vaccine that was at the heart of the Wakefield case.

Dr Wakefield claimed:

• ‘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.’

• The combination of the three virus strains in the vaccine may overwork the body's immune system and cause the bowel disorder to develop.

Adverse reactions to the vaccine, according to manufacturers

Adverse reactions following administration of the combined vaccine or one or more of its component vaccines, according to Merck's MMR vaccine package information leaflet, include, but are not restricted to:

atypical measles; pancreatitis; diarrhea; vomiting; parotitis; nausea; diabetes mellitus; anaphylaxis; arthritis; arthralgia; myalgia; encephalitis; encephalopathy; Guillain-Barré Syndrome (GBS); febrile convulsions; afebrile convulsions or seizures; ataxia; polyneuritis; polyneuropathy; ocular palsies; paresthesia; aseptic meningitis; and death.

GSK's Priorix information leaflet lists adverse reactions including bronchitis, diarrhoea, vomiting, colitis, gastroenteritis, herpes zoster (varicella), herpes simplex, viral infection, lymphadenopathy, arthritis, thrombocytopenia, thrombocytopenic purpura, and meningitis.

Doubts about MMR safety

Among those who went on record as doubting the safety of MMR is Dr Peter Fletcher, former chief scientific officer at the UK's department of health. A 2006 article in the Daily Mail reports:

after agreeing to be an expert witness on drug-safety trials for parents' lawyers, he [Fletcher] had received and studied thousands of documents relating to the case which he believed the public had a right to see.

He said he has seen a "steady accumulation of evidence" from scientists worldwide that the measles, mumps and rubella jab is causing brain damage in certain children.

But he added: "There are very powerful people in positions of great authority in Britain and elsewhere who have staked their reputations and careers on the safety of MMR and they are willing to do almost anything to protect themselves."

MMR studies

In March 1998, the Medical Research Council set up a panel of experts, headed by the GP, Dr Michael Fitzpatrick, to examine the claims. They concluded there was ‘no evidence to indicate any link’ between MMR jab and bowel disease or autism in children.

A 14-year study by Finnish scientists concluded in April 1998, claiming to find no danger associated with the MMR vaccine.

In April 2000, ‘Dr Wakefield and Professor John O'Leary, director of pathology at Coombe Women's Hospital in Dublin, presented research to the US Congress showing what they said was ‘compelling evidence’ of a link between autism and MMR. However, it did not ‘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 claims were ‘unverifiable by usual scientific means.’

In January 2001, Dr Wakefield announced that the vaccine had never undergone proper safety tests. In a study published in the journal Adverse Drug Reactions and Toxicology Review, Dr Wakefield said original safety checks on the vaccine were poorly conducted and only lasted for four weeks. The Department of Health rejected the claim again.

In February 2001, the British Medical Journal published a major statistical analysis concluding the soaring rate of autism in recent years was almost certainly not due to the MMR injection. However, the study was conducted by James A Kaye, Maria del Mar Melero-Montes, and Hershel Jick, associate professor of medicine, at Boston Collaborative Drug Surveillance Program, Boston University School of Medicine. In 2003, a footnote of another paper published in the BMJ by Kaye and Jick stated, "The Boston Collaborative Drug Surveillance Program is supported by grants from Abbott Laboratories, Berlex Laboratories, GlaxoSmithKline [a MMR manufacturer], Hoffmann-La Roche, Ingenix Pharmaceutical Services, Johnson & Johnson Pharmaceutical Research and Development, Pharmacia Corporation, and Novartis Farmacéutica."

In September 2001, researchers from St George's Hospital in London and the Institute for Child Health gave 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.

In December 2001, the Medical Research Council announced the results of its research which was commissioned by the Department of Health. They found no link between the vaccine and autism.

In February 2002, Dr Wakefield and Professor O'Leary publish a paper in the journal Molecular Pathology. It suggested a possible link between the measles virus and bowel disease in children with developmental disorders.

In February 2002, a team from the Royal Free Hospital published a study on the British Medical Journal website saying there is no link between MMR and autism.

In March 2005, researchers at the Yokohama Rehabilitation Center and the Institute of Psychiatry in Japan said they had 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.

In May 2006, Dr Stephen Walker in America reported that his research team had found measles virus in the guts of autistic children with bowel disease. The study appeared to confirm the findings of Dr Andrew Wakefield. Walker said: "Of the handful of results we have in so far, all are vaccine strain and none are wild measles. This research proves that in the gastrointestinal tract of a number of children who have been diagnosed with regressive autism, there is evidence of measles virus. What it means is that the study done earlier by Dr Wakefield and published in 1998 is correct. That study didn’t draw any conclusions about specifically what it means to find measles virus in the gut, but the implication is it may be coming from the MMR vaccine. If that’s the case, and this live virus is residing in the gastrointestinal tract of some children, and then they have GI inflammation and other problems, it may be related to the MMR." He claimed the finding did not show that the MMR vaccine caused the condition.

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

Comments on the above studies

2005 Japanese study

In Japan, the MMR was replaced by single vaccines. Children given these single vaccines formed the control group in the 2005 Japanese study. These single vaccines contain similar ingredients to the MMR, albeit that they are given separately. For example, the single measles vaccine contains the live measles virus, which has been identified in some studies as a possible causative factor in Crohn's disease. Therefore the Japanese study does not show that MMR is safe. It does show that MMR is no more likely to cause autism than single vaccines. But it does not exclude the possibility that both the MMR and the single vaccines may cause autism.

The rationale behind giving single vaccines is that they are less likely than combined vaccines to overwhelm the child's immune system. But this is an assumption that is not proven. As of 2009, according to Dr David Haslam (chairman of the college of the council of the Royal College of GPs and a supporter of MMR), there is no proof that single vaccines are safer than combined vaccines, and there are fewer studies of single vaccines.

Dr Viera Scheibner, a long-term researcher and critic of vaccinations, issues the following caution about Andrew Wakefield's backing for single vaccines in an article co-authored with Bronwyn Hancock:

researchers ... and parents, particularly in the United Kingdom, are calling for the three vaccines (measles, mumps and rubella) to be administered individually as if this were the solution to the problem. However it is not just the combined vaccines, such as MMR or DPT that cause autism, and therefore the separate administration of the vaccines will NOT resolve the problem. In fact we know of cases of autism occurring after the individual vaccines. Indeed, the risk may, to the contrary, be even increased. Dr Wakefield has not referred to ANY research that has looked into the relative risk of developing autism after the separate vaccines as opposed to the combined MMR (and we are not aware of any), so there is no basis for such a recommendation.

Critics of Scheibner point to her lack of medical training. But what appears to be beyond doubt is that as of May 2010 there is no research on possible links between autism and single vaccines. Thus a study needs to be done on the comparative incidence of autism in populations given the MMR, with two control groups: one given single vaccines, and another unvaccinated.

MMR and freedom of information

In January 2009 the Daily Mail reported on a Freedom of Information ruling on MMR data:

Confidential documents on the introduction of the MMR vaccine should be released by the Department of Health, says the Information Commissioner. Richard Thomas ruled that their release was in the public interest, despite months of foot-dragging by officials.

He said minutes from three committee meetings before the introduction of the Measles Mumps and Rubella jab in 1988 should be published under the Freedom of Information Act.

The article says the information is expected to include data from the pre-licensing studies of MMR before the nationwide immunisation began in 1988. Jackie Fletcher, who runs the vaccine awareness group Jabs, said parents who believed their children were damaged by MMR, want to know the basis on which the vaccine was originally approved.

MMR litigation

Group claim (UK)

In June 2007, a group claim by parents against vaccine manufacturers for damages on behalf of children allegedly damaged by the MMR vaccination collapsed when legal aid was withdrawn. The litigation, which at one time peaked with 2,500 children in the group, had been in progress for several years.

A high court judge, Justice Keith, ruled that all but two claims against various pharmaceutical companies must be discontinued, under threat of being struck out, because the withdrawal of legal aid by the Legal Services Commission had made their pursuit impossible. But the judge said his ruling did not amount to a rejection of any of the claims that MMR had seriously damaged the children concerned.

The collapse of all the other cases because they had no public funding came a month after the FOIA Centre revealed that another high court judge who had blocked legal aid in 2004 had a brother who sits on the board of a drugs company embroiled in the litigation. The ruling by Sir Nigel Davis – whose brother, Sir Crispin Davis, is a non-executive director of GlaxoSmithKline – to dismiss the attempt to restore legal aid left many families without lawyers to represent them.

Some of the parents involved in the litigation complained to the Office for Judicial Complaints (OJC) about the conflict of interest. Private Eye reported on the verdict of the OJC on the complaint:

MMR LEGAL AID: Mr Justice Davis has been cleared of any wrongdoing for not disclosing that his brother was a director of Glaxo SmithKline when he sanctioned the withdrawal of legal aid from families who claim their children were damaged by the drug company's MMR vaccine.

The Office for Judicial Complaints (OJC) has advised more than 100 parents who complained of the conflict of interest that the high court judge states categorically that he was not aware at the time that his brother, Sir Crispin davis, was a non-executive director of GSK, one of three defendant drug companies in the MMR controversy.

But when the Eye and others asked his office about a potential conflict five months ago, a statement was issued on his behalf which said: "In 2003, Mr Justice Davis's brother was appointed as a non-executive director of GSK. At the date of the hearing before Mr Justice (February 2004), the possibility of any conflict of interest arising from his brother's position was not raised with him and did not occur to him. If he was wrong, any possible remedy must be sought in the court of appeal."

This is not quite the same as saying he knew nothing about it. The parents are now asking Sir John Brigstocke, the judicial ombudsman, to investigate this apparent inconsistency. They are also asking whether the OJC were right to dismiss a second complaint of a possible conflict. Sir Crispin is also Chief Executive of Reed Elsevier, publishers of The Lancet. Although the magazine published the original controversial research by Dr Andrew Wakefield and others at the Royal Free Hospital, its editor Richard Horton had been widely quoted just before the legal aid hearing saying the study was flawed because of an alleged conflict of interest.

In the High Court case before Mr Justice Keith, Mrs Wickens, a mother of an alleged MMR-damaged child who was suing for damages in the litigation, testified that she had called the Legal Services Commission and asked why the legal aid for the case had been dropped. Mrs Wickens said:

Somebody very senior from the Legal Services Commission phoned me back and in the course of the conversation, he said that the decision to stop the Legal Aid came from above. Now I said to him, what do you mean by above. He said (inaudible) that the decision to stop Legal Aid came from the Government.

US litigation

In early 2008 the US government awarded compensation under its vaccine damage programme to a child diagnosed with symptoms of autism after she had a series of vaccinations, including MMR. The decision was hailed as "unprecedented" by vaccine damage campaigners. The claim was one of nearly 5000 cases pending in the American vaccine "court", which allege that mercury-containing vaccines resulted in autism.

Washington-based attorney Jim Moody, one of the lawyers involved in the cases, said the case was scheduled to go to trial in May, but "to everyone's surprise" the government conceded liability.

"It is also significant they conceded it was causing autism, they could have just said vaccines caused injury or been vague," he said. "Never before has our government linked vaccines to autism."

GMC hearing

In January 2010, the results of a three-year investigation by the General Medical Council into the fitness to practise of Wakefield and two other doctors from the MMR research team, Professor Simon Murch and Professor John Walker-Smith, were announced: Wakefield and Walker-Smith had been found guilty of professional misconduct and were struck off the doctors' list. Murch was found not guilty.

The Lancet, the journal that published Wakefield and colleagues' paper, retracted it on 2 February 2010.

The GMC report on the hearing (GMC, Fitness to Practise Panel Hearing, 28 January 2010) can be read here. The following factors emerge from the report:

• The GMC Panel state in their introduction to the report that they "wish to make it clear that this case is not concerned with whether there is or might be any link between the MMR vaccination and autism."
• Serious symptoms of bowel dysfunction and autism were suffered by children that featured in Wakefield et al's case review, and these were linked by parents and in some cases by GPs and consultants (ie not just Wakefield and the other two doctors on trial) to the MMR vaccine
• A whole team of doctors and consultants - not just Wakefield and the other two doctors on trial - were caring for and deciding on the investigations to be performed on the children and on their treatment. These experts are all named in the report.
• The invasive procedures (colonosocopy and lumbar punctures) that Wakefield was accused of causing to be done on the children were standard investigations performed at the hospital on children suffering serious bowel symptoms and/or suspected meningitis. It also becomes clear that Wakefield was not in charge of deciding on or carrying out these procedures, which were done by consultants whose speciality they were. However, the GMC panel decided that in the case of a lumbar puncture on a child, "by signing the forms you [Wakefield] ordered the investigations".

Wakefield was accused of not obtaining proper ethics committee approval for the tests he allowed to be performed on the children. But according to journalist Brian Deer, Wakefield said in 2005 that the Lancet study was a case review of patients referred to and treated at the Royal Free rather than a clinical research study and therefore no ethics committee approval was required. Wakefield said: "In contrast to a clinical research study requiring ethical approval, the Early Report [the initial paper published by Wakefield et al in The Lancet] was a report of clinical findings of tests which had been performed solely on the basis of clinical need".

The Royal Free told the Lancet in 2004 that it saw "no ethical wrongdoing" in the study.

It is not possible for any member of the public to read both sides of the story in the GMC report. This is because while all the allegations against the doctors are published fully, with the GMC verdict on each allegation (e.g. "proven" or "not proven"), the doctors' defences do not appear. Nor have the doctors' defences been quoted in media coverage, reportedly because no media persons attended the hearing but only turned up for the verdict. As of June 2010, the only coverage of the doctor's defences is in the account of the health writer Martin Walker, who did attend the hearing and in the account of Jim Moody, attorney for the National Autism Association (NAA) in the US, who said that "false and misleading testimony" was given against the doctors at the hearing. Moody submitted an official complaint to the GMC against some of those who testified against Wakefield and colleagues (Dr Richard Horton, Dr David Salisbury, Dr Arie Zuckerman, Dr Michael Pegg, and Dr Michael Rutter), for what Moody alleged was "Breach of duty of honesty and candor; False Testimony; Misuse of Professional Position, Failure to Disclose Conflicting Interest, False Expert Testimony".

Conflicts of interest: GMC

• Professor Denis McDevitt, who was originally proposed by the GMC as chair of its fitness to practice investigation into Wakefield and colleagues, was himself a member of a 1988 government safety panel which approved Pluserix MMR vaccine as safe for vaccine manufacturer Smith Kline & French Laboratories (later GlaxoSmithKline). This was revealed in previously secret government minutes that were disclosed by the MMR litigation brought by parents of alleged MMR-damaged children. Also, at the time that the panel approved the vaccine, McDevitt was being paid as a research fellow by MMR vaccine manufacturer, Smith Kline & French Laboratories.

The government minutes that reveal these facts are also interesting from the point of view of the adverse reactions reported to the early version of the MMR vaccine, using the subsequently discontinued Urabe strain of mumps virus. The reactions included convulsions, neurological complications, meningitis, and encephalitis. One member of the panel raised concerns about "the potential infectivity of the mumps component of MMR to susceptible contacts", though he was "assured" that it was "not transmissible".

According to an article by Martin Walker on the Age of Autism vaccine damage information site, McDevitt was dropped as proposed chair of the GMC fitness to practice hearing into the three doctors when campaigners revealed these conflicts of interest. The chair subsequently chosen by the GMC was Dr Surendra Kumar.

• Dr Surendra Kumar chaired the GMC fitness to practice hearing into the three Royal Free doctors. He read out the verdict of the General Medical Council (GMC) panel, which condemned the doctors as “dishonest”, “irresponsible”, and as acting “contrary to the clinical interests of this child”. In 2003 Kumar disclosed a shareholding in GlaxoSmithKline. He still had shares in GSK in 2004. GSK was a defendant in litigation brought by parents of alleged MMR-damaged children under the legal aid scheme, litigation in which the parents employed Wakefield as an expert witness.

Conflicts of interest: Andrew Wakefield

Dr Andrew Wakefield was accused of a conflict of interest in that he was employed by the group of parents who sued vaccine manufacturers for alleged vaccine damage of their children. Dr Richard Horton, then editor of The Lancet, told the GMC that he had been unaware of this alleged conflict of interest on the part of Wakefield at the time he published Wakefield's MMR paper in The Lancet, though Wakefield told the GMC he had declared it. A discussion of this incident by John Stone, a supporter of the vaccine-damage advocacy group JABS, based on contributions to the BMJ Rapid Responses forum, is here.

The argument that Andrew Wakefield was legally correct in stating that there was no conflict of interest in this respect was made, ironically, by those making the case for MMR. In defending herself against a parallel allegation of conflict of interest made in Private Eye (19 March 2004), Professor Elizabeth Miller, head of the Health Protection Agency's Immunisation Department and expert witness for the vaccine producers - presumably with the best legal advice - wrote:

there can be no conflict of interest when acting as an expert for the courts, because the duty to the courts overrides any other obligation, including to the person from whom the expert receives the instruction or by whom they are paid.

This legal view was also given by barrister Robert Hantusch in a letter to the Times of 24 February 2004:

But the courts do not consider that the engagement of someone to act as an expert witness in litigation has the effect that that person is then biased. Indeed, if this were the legal position, no paid professional could ever at any time give evidence to a court.

Wakefield was also accused by Brian Deer in the Sunday Times and Channel 4 television's Dispatches of a conflict of interest in that he had filed a patent in 1997 as a co-inventor of an alternative vaccine against MMR, and a pharmaceutical composition for treating inflammatory bowel disease.

Deer's evidence for his allegation that Wakefield applied for a patent on a rival vaccine is here:

Revealed: the first Wakefield MMR patent claim describes "safer measles vaccine", briandeer.com, acc 3 Jun 2010.

But the patent application does not mention Wakefield. The applicants are named as the Royal Free Hospital and Neuroimmuno Therapeutics Research Foundation, an organisation that does not appear to be connected to Wakefield or his research colleagues for the Lancet paper.

Wakefield responded to Deer's and the Dispatches allegations in a statement saying:

Since many of the claims by journalist Brian Deer have been demonstrably false and there in no objectivity in the manner of their intended portrayal, I declined to participate in any way in the making of the Dispatches programme... I was not invited to comment on the Sunday Times article prior to its publication.

The claim appears to be that, whilst at the Royal Free Hospital, I was developing a new vaccine to compete with MMR and that I conspired to undermine confidence in MMR vaccine in order to promote this new vaccine, and that this represented a conflict of interest. This is untrue. The facts are that:

• no vaccine or anything resembling a vaccine was ever designed, developed or tested by me or by any of my colleagues at the Royal Free Hospital;

• it has never been my aim or intention to design, produce or promote a vaccine to compete with MMR;

• my genuine concerns about the safety of MMR are wholly unrelated to any desire or opportunity to develop a competing vaccine;

• there was no conspiracy as insinuated by the Sunday Times article;

• there was no conflict or interest, actual or perceived.

In contrast, it was our intention, at one stage, to conduct a formal therapeutic clinical trial of a compound that might have the ability to promote the body’s immune response to measles in order to assess the effects of this therapy upon the disease in children with regressive autism and bowel disease. This compound is known as Transfer Factor and whilst there is a large scientific literature on this subject, the nature and mechanism of action of Transfer Factors are largely unknown.

The Transfer Factor that was intended for use in the trial was to be against measles virus. I have urged and continue to urge parents to have their children vaccinated against measles using the current vaccines. This would be in direct conflict with the intentions that are part of the claim that I was developing a new vaccine to bring onto the market. Whether a Transfer Factor could ever protect children against measles is entirely speculative and is something that was never studied or pursued by me or any of my colleagues.

The Channel 4 programme implies commercial aspirations for personal gain. In fact, the aim of the patent was to generate funding for the research programme and a new Centre for Gastroenterology at the Royal Free Hospital. This can be substantiated by contemporaneous documentation.

The patent application was motivated by two main factors. First, it was felt that there may be difficulty in raising traditional grant funding for cutting edge, controversial work that was vulnerable by virtue of the fact that it might conflict with perceived wisdom and the commercial interests of others. Secondly, there was, and is, a government-led emphasis on commercial exploitation of discoveries within the medical school.

Resources

See also:

• Crispin Davis
• Nigel Davis
• Andrew Wakefield

Lancet retracts Wakefield study

The Lancet, the journal that published Wakefield and colleagues' paper, retracted it on 2 February 2010. The Lancet issued the following statement, which did not comment on the findings of the study but only on how the children were referred to the researchers and whether the approval of the ethics committee had been obtained at the time of publication:

Following the judgment of the UK General Medical Council’s Fitness to Practise Panel on Jan 28, 2010, it has become clear that several elements of the 1998 paper by Wakefield et al are incorrect, contrary to the findings of an earlier investigation.

In particular, the claims in the original paper that children were ‘consecutively referred’ and that investigations were ‘approved’ by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published record."

The ethics committee approval question about the Wakefield paper was pursued by Evan Harris and the journalist Brian Deer. Back in 2004, after Harris raised the question in Parliament, Humphrey Hodgson, Vice-Dean of Royal Free and University College Medical School, replied:

We are entirely satisfied that the investigations performed on the children reported in the Lancet paper had been subjected to appropriate and rigorous ethical scrutiny.

Also in 2004, an investigation by The Lancet found that the evidence did not support the allegation that proper ethical approval was not received. The Lancet said:

The evidence we have seen indicates that ethics committee approval was given for data collection from clinically indicated investigations in the children with an initially undiagnosed illness and who were described in the 1998 Lancet paper.

According to Brian Deer, Wakefield said in 2005: "In contrast to a clinical research study requiring ethical approval, the Early Report [the initial paper published in The Lancet] was a report of clinical findings of tests which had been performed solely on the basis of clinical need".

BBC drama featuring criticism of MMR banned

In 2006, two episodes ("One Angry Man" and "Heart of Darkness", series 5) of the BBC legal drama series, Judge John Deed, contained a storyline critical of MMR. Just one viewer complained, whereupon the BBC banned the re-broadcast or distribution on DVD of the two episodes in their original form.

The following information regarding these episodes of Judge John Deed has been placed in the public domain by the BBC:

Judge John Deed, BBC1, 10 February 2006

Complaint

A viewer complained that various aspects of the storyline combined to convey the message that the MMR vaccine was harmful to children’s health.

Ruling

We agreed that the episode conveyed the message complained of, and was therefore in conflict with the obligation of due impartiality on matters of public controversy. Steps were already being taken by Drama and Editorial Policy to ensure that future episodes would observe the requirements of impartiality insofar as they apply to drama of this kind, and it was agreed that the episode in question would not be re-broadcast, except in a context in which the requirements of impartiality were met. On that basis, we considered the complaint to be resolved.

A Freedom of Information request to the BBC requesting disclosure of the correspondence on this subject between the complainant and the BBC was refused by the BBC on the grounds that "The BBC’s independence and impartiality would be at risk through disclosure of further information on editorial complaints".

Resources

• Michael Fitzpatrick, MMR and Autism: What Parents Need to Know, Routledge; 1st edition (24 Jun 2004). Defends the safety of MMR.
• Richard Horton, MMR: Science and Fiction - Exploring a Vaccine Crisis, Granta Books (30 Sep 2004). Horton is an advocate of MMR but analyses the malign influence of financial conflicts of interest in medical research today.
• Silenced Witnesses, Volumes 1 (2008) and 2 (2009). Written by the parents of the MMR class action lawsuit. Ed. Martin Walker. Slingshot Publications.