The toxic legacy of Andrew Wakefield and the MMR controversy

A mini-resurgence of measles

The BBC news website has just reported (11/3/2016) fears that a new epidemic of measles may be starting in London and the South East of England. Public Health England (PHE) says that 20 cases were reported in this area in February and unusually most of them were in young adults and most needed hospital treatment. The effects of measles are generally more serious in this older age group. This latest warning follows a 2013 epidemic centred on Swansea in South Wales where over 1200 cases and one death were recorded in eight months. The prevalence of measles started to rise a decade ago, for example there were roughly as many cases in the two years 2007-2008 as there were in the previous eleven years.

The most recent epidemics have occurred despite PHE reporting record rates of MMR vaccination in young children; in April 2013, 94% of under 5s had received one dose of MMR (measles, mumps and rubella) and 90% had received the recommended two doses. The problem is that there is a large reservoir of unvaccinated older children and young adults whose parents opted not to take up MMR vaccination because of doubts about the safety of the MMR vaccine caused by publicity surrounding the “Wakefield affair”. Nationally, around 500 cases of measles per quarter were still occurring in 2013 because of this large reservoir of unvaccinated older children and young adults.

The story of the “Wakefield affair”

In 1998, Andrew Wakefield and 12 co-authors published a paper in the Lancet which seemed to suggest the possibility of a link between the MMR vaccine, autism and inflammatory bowel disease. Remarkably this paper was based upon just 12 children i.e. one less than the number of authors of the paper. These 12 children were claimed to be consecutive referrals to the Royal Free Hospital in London for bowel and developmental problems that were symptomatic of regressive autism i.e. autism that seems to develop after previously normal development. Even if all of the claims of this paper were beyond reproach then it could do little more than suggest a coincidence that was perhaps worthy of proper scientific investigation. The impact of the paper was out of all proportion to even its claimed scientific merit and of course we now know that the flaws and false claims in this paper ultimately led to its retraction by the Lancet. This scientifically weak and unremarkable paper has been cited more than 750 times in other scientific papers and has become the most cited retracted paper of all time. The impact of the paper was amplified by Wakefield’s public statements questioning the safety of MMR compared to a single measles vaccine and what amounted to an anti-MMR campaign by elements of the British media who also suggested that parents should be able to opt for the single vaccine. In the 7 years up to 2007 there were over 5300 articles in British national newspapers that mentioned MMR and most of these did not mention the mass of scientific evidence that the vaccine was safe.

 

Public opinion polls suggest that this media exposure led to a dramatic decline in public faith in the safety of MMR and by October 2003 just 50% of those questioned classified the vaccine as safe. This decline in confidence about the vaccine’s safety not surprisingly led to a decline in the take up rates for the MMR vaccine which fell to just under 80% in 2004 compared to 92% a decade earlier. This decline is crucial because of what is known as herd immunity. When a high proportion of the population (90-95% for measles) are vaccinated or otherwise immune then even those who are not vaccinated are largely protected because of the inability of the disease to spread because of the low numbers of unvaccinated people. When vaccination rates are very high then those who choose not to be vaccinated or are unable to be vaccinated get a free ride and are protected because of herd immunity. It was by a concerted campaign to achieve herd immunity levels in populations around the world that smallpox was eradicated. For several years, the Wakefield effect meant that levels of measles immunity fell well below those needed to achieve herd immunity in the UK.

The impact of the Wakefield paper was remarkable not just because of the clear weakness of such a preliminary study but also because of the mass of evidence confirming the safety of the MMR vaccine. In a review published in 2009 it was reported that 20 large studies from different countries and using a variety of methods had found that MMR did not cause autism. These studies were large enough to detect even a rare link between MMR and autism. There is general agreement amongst scientific experts that this evidence is compelling.

The fate of the Lancet article and Andrew Wakefield

Wakefield was dismissed from the Royal Free in 2001 and moved to Austin Texas where he became executive director of a private organisation called Thoughtful House (now the Johnson Center for Health and Development). This institution was devoted to the study and treatment of childhood development disorders like autism. He became a focus of attention and admiration for anti-vaccine groups in the USA.

In 2004 the Lancet paper was partially retracted by ten of the original authors who made it clear that they did not suggest that MMR vaccination was a cause of autism. In May 2010, the General Medical Council (GMC) found that Wakefield was guilty of serious professional misconduct and he was struck of the UK medical register. The Lancet paper was fully retracted in February 2010 because of ethical concerns and because it had become clear that the 12 subjects were not consecutive referrals as had been claimed; had this been known in 1998 the paper would not have been accepted. The GMC report focused particularly on unethical practices and misleading claims made by Wakefield in response to questions at scientific meetings. They were also critical of the research practices of the Wakefield team. Wakefield resigned from Thoughtful House when he was struck off the UK medical register.

There is now no doubt that the work reported in the paper was fundamentally flawed and made no credible link between MMR, autism and inflammatory bowel disease. A journalist, Brian Deer, made a detailed and reasoned case in an article published in the British Medical Journal (BMJ) in 2011 suggesting that the data published in the paper was not only flawed but also fraudulent. An editorial in the BMJ in response to Deer’s article used the headline:

“Wakefield article linking MMR vaccine and autism was fraudulent”

Amongst the claims made by Deer:

  • The patients were not consecutive referrals to the Royal Free as claimed and some had been referred by a lawyer preparing a lawsuit against the vaccine manufacturers
  • Wakefield was not an impartial investigators but had substantial financial interest in MMR – he received large sums from lawyers to investigate the safety of MMR and had also patented an alternative single measles vaccine
  • The figures in the paper bore no resemblance to those derived from patient notes – in the Lancet it was claimed that 11/12 patients had inflammatory bowel disease (colitis), 9/12 showed signs of regressive autism and in 8/12 patients the symptoms were said to have started within two weeks of the MMR vaccination and in 6 patients all three of these conditions applied. The true figures bore no resemblance to these claims and even maximum estimates were much lower and no patients actually met all three conditions. Most children showed no evidence of inflammatory bowel disease even though this claim was part of the paper’s title.

The BMJ editorial concluded that these major discrepancies could not be due to honest error but were the result of an elaborate fraud.

Wakefield has tried to sue his critics in the British and American courts but on both occasions the case has been dismissed with costs against Wakefield and his insurers. In the UK case, the judge accused Wakefield of using litigation as a public relations exercise to influence public opinion and deter his critics and that the lawsuit was:

“A weapon in his attempts to close down discussion and debate over an important public issue”

Vaccine risks in perspective

Vaccination has been one of the modern medicines biggest success stories. It has eradicated smallpox, is close to eradicating polio and has dramatically reduced the toll of many other infections like diphtheria, whooping cough, tetanus, mumps and yellow fever.

Prior to the start of measles vaccination in the UK in 1968 most children had measles at some time and  there were 200-800 thousand notified cases each year with an average of around 100 deaths per year. MMR was introduced in 1988 and within a few years over 90% of children were vaccinated. Between 1992 and 2006 there were no deaths from the acute effects of measles and just a small number of recorded cases each year. Measles not only killed some of the infected children but resulted in thousands of children being hospitalised because of complications like encephalitis, convulsions and pneumonia. Some children suffered permanent hearing impairment or eye damage as a consequence of measles infections. Small numbers of people die from a rare but fatal long term complication of measles, sub-acute sclerosing panencephalitis, which may take decades to manifest. Measles death rates in industrialised countries are around 1 in 5000 cases but deaths and serious complications are much higher in poorly nourished, sick or immunocompromised children. In 2000 there were around 545,000 deaths from measles worldwide but increased vaccination rates had reduced this to 145,000 by 2013 and thus saved millions of lives.

Whilst some vaccines may have rare adverse effects, these risks are minute in comparison to the risks run by unvaccinated populations. If there are only a small number of individuals who chose not to vaccinate their children they may still get a free ride and benefit from herd immunity if most of the population is vaccinated.

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2 thoughts on “The toxic legacy of Andrew Wakefield and the MMR controversy

    • Vaccine policy is public health. There seems to be no justification for re-introducing single vaccines. It is important for herd immunity to get very high coverage for all three vaccines within MMR. Some parents did opt to have single vaccines privately.

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