by David Isaacs
The Lancet paper did not make it clear that the children had been selected by Wakefield rather than referred to the clinic for investigation in the normal way. At the time when Wakefield tested the children, many of their parents were already clients of Richard Barr, and Wakefield had found most of them through anti-MMR-vaccine campaign groups. Several parents had lodged compensation claims before the children were referred. None of the families lived in London. Two children were patients of the same doctor 450 kilometres from the Royal Free Hospital, three attended another clinic, and one was flown in from the United States.
Wakefield had declared to The Lancet that he had applied for and received Research Ethics Committee approval for the study, but he had misled the committee by claiming the children had been referred for treatment in the normal way. Arguably, Wakefield had used the 12 autistic children as guinea-pigs to prove a pre-formed theory. The Lancet paper claimed that all 12 children were previously normal, but the GMC found that five already had developmental problems before being given the MMR vaccine. Wakefield claimed that MMR vaccine had caused autism because the children had developed the condition within two weeks of receiving it, but it turned out that he had falsified data. The United States patient flown over specially to see Wakefield was reported in the Lancet paper as first developing symptoms of autism one week after receiving MMR vaccine, but the child’s father insisted he had told Wakefield the symptoms had started two months before the child had been given the vaccine. Another patient was reported as becoming symptomatic two weeks after receiving MMR vaccine, yet the mother remembered it as being somewhere between two and six months afterwards. The facts did not fit with Wakefield’s assertion of a close temporal relationship between vaccination and the onset of autistic symptoms, so Wakefield had simply changed the story to fit his theory.
On review by experts, the children’s gut biopsies were found to be predominantly normal – certainly not nearly as abnormal as reported in the Lancet paper. Wakefield had changed diagnoses and histories to give the impression of a link between MMR, bowel disease and the sudden onset of autism that was not otherwise evident. Every one of the 12 cases had been altered substantially. As Brian Deer baldly stated: ‘Wakefield had been secretly payrolled to create evidence against the [MMR] shot and, while planning extraordinary business schemes meant to profit from the scare, he had concealed, misreported and changed information about the children to rig the results published in the journal.’
This was high-stakes scientific fraud. None of Wakefield’s 12 Royal Free co-authors had been aware of his deception, and all became increasingly alarmed as new revelations emerged. In 2004, as the full enormity of Wakefield’s dubious research practices was starting to be uncovered by Brian Deer, The Lancet asked Wakefield and his co-authors to retract their paper. Ten retracted, including Professor John Walker-Smith and Dr Simon Murch, a junior consultant. Nevertheless, the GMC charged Walker-Smith and Murch, as well as Wakefield, with serious professional misconduct in 2004. Walker-Smith is a renowned Australian gastroenterologist who became Professor of Paediatric Gastroenterology at the University of London. I worked with him there. He had a picture of Queen Elizabeth II on his desk, flanked by miniature flags, a Union Jack and an Australian flag. He was always immaculately dressed, more English than the English, in eye-watering blue shirts with a starched white collar and a hospital tie. His middle initial is A, and his students and junior colleagues always referred to him as JAWS. Although we were at opposite ends of the political spectrum, I always admired John’s intellectual integrity.
In the United States in 2009, the Federal Court heard a test case of petitions from some 5000 families that MMR vaccine had caused their children’s autism. One of the presiding judges, George L Hastings, was highly sceptical of Wakefield’s ‘autistic enterocolitis’, and said: ‘Therefore, it is a noteworthy point that not only has that “autistic enterocolitis” theory not been accepted into gastroenterology textbooks, but that theory, and Dr Wakefield’s role in its development, have been strongly criticized as constituting defective or fraudulent science.’
In 2010, a GMC panel of three doctors and two lay members found Wakefield guilty of dishonesty and of the abuse of developmentally challenged children, labelling him as ‘unethical’ and ‘callous’. His research was found to be fraudulent and performed without valid ethical approval. The GMC struck Andrew Wakefield off the medical register. Wakefield was no longer allowed to be a medical doctor in the United Kingdom. In United States terms, this would be to revoke his licence to practice.
Five days later, The Lancet completely retracted the Wakefield paper from the scientific literature, declaring it was ‘utterly false’. It had been extraordinarily foolish, even negligent, of The Lancet to have published such poor science, and for the journal editors to have failed to recognise the damaging effect it might have. It had taken The Lancet 12 years to do the right thing.
In 2010, when the GMC found Andrew Wakefield guilty of research misconduct, it found John Walker-Smith guilty of the same charge and struck them both off the medical register. Simon Murch was exonerated. Professor Walker-Smith had retired nine years earlier. The GMC ruling seemed excessively punitive, since he was not party to Wakefield’s fraud. In 2012, the High Court ruled that the GMC panel’s decision about Professor Walker-Smith was flawed by ‘inadequate and superficial reasoning’ and overturned it. Andrew Wakefield argued that the High Court’s decision vindicated him too, but his own application to the High Court to appeal the GMC ruling was turned down.
In 2011, the BMJ published damning papers by Brian Deer analysing the extent of Wakefield’s research misdemeanours. Fiona Godlee, the BMJ’s editor-in-chief, wrote an accompanying editorial entitled ‘Wakefield’s Article Linking MMR Vaccine and Autism Was Fraudulent’. The same year, Brian Deer was awarded the British Press Award and the HealthWatch Award for his persistent and courageous investigation.
Wakefield denied everything, cried conspiracy and accused Deer and the BMJ of conducting a vendetta against him. Many United Kingdom doctors belong to a medical defence organisation, a form of doctor’s insurance agency, which defends them if they are sued by a patient; Wakefield persuaded this organisation to embark on a lawsuit costing $2 million, which he abandoned after two years. His supporters still write on social media protesting his innocence.
The Royal Free Hospital offered Wakefield the opportunity to repeat his research, using a larger sample of 150 patients and with controls. The research never happened. Wakefield characteristically said his failure to take up the offer was the fault of others, rather than accepting that his bluff had been called and admitting he could not conduct the study, whose results he knew would be negative.
As a result of the controversy, measles immunisation rates fell markedly in the United Kingdom, from between 90 and 92% before the scandal to 80% in 2003 and as low as 30% in some areas. National rates did not reach 90% again until 2011. In the four years from 1998 to 2001, 10,794 cases of measles were reported nationally; between 2006 and 2009, that number rose to 17,654. We know that infectious diseases are under-reported, so the true impact of the Wakefield scandal on measles infection may have been much greater. About 1 in every 1000 children who catches measles will develop measles encephalitis; of every 10 children who develop measles encephalitis one will die, as Roald Dahl’s daughter Olivia did, and two or three will have permanent brain damage. It is highly likely that the Wakefield scandal condemned many children to brain damage and left many others dead. For example, a small Dublin hospital admitted 11 children to hospital with measles in just seven months in the year 2000, and three of them died.
The controversy prompted a number of large scientific studies, all of which found no evidence whatsoever that MMR vaccine is a cause of autism. Ironically, the fall in MMR vaccine uptake in the United Kingdom provided a natural experiment: if Wakefield’s claims were correct, rates of autism should have fallen too, but no such fall occurred.
The Wakefield MMR
–autism saga is a sorry one for the medical profession and for the world, and the repercussions persist. Though MMR uptake in the United Kingdom has recovered to previously high levels, as we shall see in the next chapter, the MMR–autism debate has continued to resonate in Europe and the United States.
Vaccine surveillance and rotavirus
The many vaccine tragedies have not gone unheeded. Any new vaccine is extensively tested for efficacy and safety in clinical trials before it is introduced into the immunisation schedule. After it is introduced, intense post-marketing surveillance for adverse effects is conducted regionally and nationally in all industrialised and many developing countries. The aim of the surveillance is to detect extremely rare adverse effects, such as a one-in-a-million complication that could not be detected in clinical trials, even trials involving many thousands of subjects.
A good example of how contemporary surveillance works is what has happened with rotavirus vaccines. Immunisation with the first rotavirus vaccine, RotaShield, started in 1998 but was stopped in 1999 because surveillance showed that children given the vaccine had an increased risk of developing intussusception. This is a condition in which one section of the bowel telescopes into the next, which can prevent blood supply to the affected bowel. Intussusception is rare and can usually be corrected with medical or occasionally surgical treatment. Most cases occur in babies 5 to 10 months old, boys more often than girls. Some virus infections are associated with intussusception, presumably by causing damage or inflammation that affects the bowel.
Later rotavirus vaccines were studied on thousands of infants in randomised controlled trials, and the studies did not detect a significantly increased risk of intussusception. However, this did not mean it was certain that the new vaccines did not cause intussusception, only that the studies could not detect it; the increased risk was possibly too low for the studies to detect.
Surveillance studies showed that within three weeks of receiving their first and second doses of rotavirus vaccine babies did in fact have a slightly increased risk of developing intussusception. The risk was approximately six cases for every 100,000 infants vaccinated.
There is no doubt that in resource-poor countries the benefits of rotavirus vaccine far outweigh the relatively small number of extra cases of intussusception. Very few children die from rotavirus in wealthy countries, where the vaccine was introduced to reduce illness and hospitalisation rather than to save lives. In Australia, the vaccine prevents 7000 hospital admissions each year at the cost of 14 extra cases of intussusception. In the United States the equivalent figures are over 20,000 admissions prevented annually at the cost of about 50 extra cases of intussusception.
Thus rotavirus vaccines are not without some risk, but the public is informed of the risk and the health profession considers it acceptable.
Does money ever come into the equation in decisions about vaccine risk? Of course it does.
Health authorities in different countries had to choose whether to stay with OPV, knowing that 1 in every 2.5 million doses would paralyse a baby (about one baby every five years in Australia and eight babies a year in the United States), or to spend considerably more on IPV.
Resource-poor countries could not afford the far more expensive IPV, so their choice was to continue with OPV. (As we heard in Chapter 4, it also had other benefits for these nations.) However, resource-rich countries were faced with a dilemma. The argument for persisting with OPV was that the huge extra sum spent on IPV represented an ‘opportunity cost’; in other words, they lost the opportunity to spend that money on more effective healthcare intervention – perhaps a different vaccine, or a program to reduce smoking – that would prevent more illness and save more lives. This is a utilitarian argument that says society should make the choice that benefits the most people.
The counter-argument, the one in favour of IPV, says that it is unethical to give a vaccine you know will paralyse children, however few, when a safer vaccine is available. This takes into account the Hippocratic principle of ‘First do no harm’ (discussed in Chapter 13).
While sitting on the national immunisation committee, I had a protracted albeit respectful disagreement with a public-health colleague about whether Australia should switch from OPV to the far more expensive but safer IPV. Eventually the problem was settled when the price of IPV fell (and that of OPV rose), and IPV was incorporated into a single-injection, six-in-one vaccine with DTP, hepatitis B and Hib.
In reality, the healthcare budget of many countries is not as fixed as is sometimes suggested, and money can be found when a strong case can be made for spending it. Yet healthcare professionals have been nowhere near as successful as, say, the military in persuading governments to spend more on their needs. (I talk more about this issue of vaccine cost in Chapter 14.)
Ensuring vaccine safety
As I consider the tragedies and frauds described in this chapter, I reflect on how little, apparently, they have dented the population’s faith in immunisation.
In the early days this was clearly because the diseases were so omnipresent in people’s lives. People crippled by polio were everywhere. Parents were prepared to risk the dangers of the early polio vaccines, even after a disaster like the Cutter Incident, because they feared polio even more. In addition, health authorities learned vital lessons from the tragedies, and introduced safeguards that have made it less and less likely that such an error will be made again.
As diseases become rarer, parents who have never seen them depend on their trust of their doctors and nurses. When people become afraid of vaccines and immunisation levels drop, as with whooping cough and measles vaccines in the United Kingdom, the diseases will quickly return and show that parents are correct to trust in vaccines.
In 2011, the WHO introduced a Global Vaccine Safety Initiative to ensure that all countries reach a standard sufficient to ensure vaccine safety. Public health authorities also do surveillance on people receiving long-established vaccines to make sure that if a batch is contaminated, or there has been some unexpected change in the vaccine, it is detected early enough to prevent further damage.
Vaccines have never been safer. Yet as we will discover in the next chapter, that is certainly not everyone’s view.
CHAPTER 12
The modern anti-immunisation movement
No rational argument will have a rational effect on a man who does not want to adopt a rational attitude.
Karl Popper, philosopher (1902–1994)
In his book Autism’s False Prophets, leading paediatric infection specialist Paul Offit describes the infamous 2007 Oprah Winfrey interview with actress Jenny McCarthy on Winfrey’s daytime television show, Oprah. When her son Evan was diagnosed with autism, McCarthy blamed the MMR vaccine. McCarthy said that Evan was given the vaccine, ‘and soon thereafter I noticed a change. The soul was gone from his eyes.’ When Oprah told her that science suggests MMR vaccine does not cause autism, McCarthy said: ‘My science is Evan, and he’s at home. That’s my science.’ The audience cheered.
Words have power, and those are powerful words. Louder Than Words was the title of McCarthy’s book about Evan, and it became a best-seller. At the time McCarthy’s partner was the famous actor Jim Carrey, which arguably increased her profile and the amount of attention she received.
McCarthy said her theory was based not on science but ‘mommy instinct’. She did her ‘research’ at the ‘University of Google’. According to Offit, the day after the Oprah interview, the national Centers for Disease Control (CDC) was flooded with calls about the safety of MMR vaccine and many paediatricians also fielded inquiries.
Ominous though that sounds, there was no perceptible effect on national uptake of MMR vaccine in the United States. Over 90% of all United States children have been immunised every year since 1996. In 1998, the year Andrew Wakefield’s Lancet paper was published, there were only 89 cases of measles reported and no deaths.
Wakefield moved to Austin, Texas, in the early 2000s,
and has made a living continuing to promote his message that MMR causes autism. His most substantial contribution in his new home State appears to be the network of autism-related charities and businesses with which he has been affiliated, and from some of which he has reportedly drawn six-figure salaries. Wakefield was Executive Director of the Thoughtful House Center for Children in Austin from 2005 to 2010 but resigned after he was struck off the United Kingdom medical register. He founded Strategic Autism Initiative in 2010 with Polly Tommey, a British woman with an autistic son. In 2016, Wakefield directed and Tommey produced a film, Vaxxed, which claims there has been a cover-up about vaccine safety at the CDC. Wakefield also founded the Autism Media Channel in Austin, which produces videos that promote a link between autism and MMR vaccine.
Wakefield credits his popularity in part at least to the rise of social media. Conspiratorial anti-vaccination groups are active on Facebook, and researchers fear this could spread the anti-vaccination movement globally. In the 13 years since Wakefield arrived in Texas, the number of unvaccinated children there has increased almost twenty-fold, from roughly 2300 to 45,000.
Nevertheless, most people in the United States continue to immunise their children with MMR vaccine. Why did the Wakefield scandal have so little effect in the United States? The Lancet article, the Deer investigation, the United Kingdom General Medical Council (GMC) inquiry and the other major developments were all local circumstances that resonated more in Britain than overseas. In addition, the American CDC has a strong reputation for expertise regarding infectious diseases and immunisations. The United States also has a strong cohort of paediatric infectious disease experts who were quick to support paediatricians and appear in the mainstream media to debunk myths about MMR vaccine and autism.