'It is not about the science. It's about belief'

Andrew Wakefield - the doctor who first linked MMR and autism - has resigned. But does that mean he was wrong about the vaccine? Linda Steele reports

Wednesday December 5, 2001
The Guardian

What is perhaps most surprising about Andrew Wakefield is his apparent lack of bitterness. Wakefield resigned last week from his post as consultant gastroenterologist at the Royal Free and University College Medical School, claiming that he had been forced out for research unpalatable to the medical school hierarchy. "It was inevitable," he says calmly. "The issue is not about science. One is dealing with people's belief systems. And that takes a great deal to change."

The contending beliefs in question belong to two factions: on the one hand, to a medical establishment united in defence of combined measles, mumps and rubella (MMR) immunisation on the grounds of public health; on the other hand, to a small but significant number of scientists, including Wakefield, together with a larger number of parents who have raised concerns about the jab's safety.

Wakefield sparked the controversy when he and colleagues published a paper in the Lancet in 1998, raising the possibility of a link between MMR and regressive autism in a handful of children they had seen with a chronic, possibly new form of bowel disease. Most had been developing normally, reaching childhood milestones, but then began to lose skills, such as speech, play and the ability to interact with others. Parents, or their doctors, blamed MMR.

Probably the move that most angered the scientific establishment, including government public health advisers, was Wakefield's suggestion that, instead of immunising children between 12 and 15 months with the MMR, the three vaccines should be given separately. It was on this point that Wakefield decisively broke ranks with colleagues at the Royal Free; it was not a conclusion that had been drawn - nor could be drawn, say critics - from the research published in the Lancet. The argument, rehearsed by proponents of single jabs, is that children should have a measles vaccine first, thus protecting them against what is the most potentially lethal childhood disease of the three. Later vaccinations can immunise against mumps and rubella.

Innocuous that may seem, but it flies in the face of the government's mass immunisation programme, of which MMR is a key part. The official line is simple: over 500m doses of MMR have been used in 90 countries; the vaccine is backed by the World Health Organisation as the safest way that parents can protect their children against these serious diseases. Wakefield's critics, most notably at the Department of Health (DoH) and the Public Health Laboratory Service (PHLS), have argued that no one else has replicated his results, despite attempts, and that his critique of the triple-jab is based more on hunch than science.

Yet a small but growing number of scientists has begun to question the wisdom of enforcing the triple-jab programme. The current hypothesis - by no means wholly attributable to Wakefield - is that the measles element of MMR in some way damages the digestive function and bowel, allowing substances derived from the incomplete breakdown of foods such as barley, rye, oats and dairy products to pass through a leaky gut wall into the bloodstream. These pass into the brain, disrupting normal brain development and causing autism.

Nonsense, say critics. Assuming that an immune response to MMR could cause leakage, the liver would filter out harmful molecules before they reached the brain. Even if it didn't, toxins would not pass the protective blood-brain barrier. Against this, supporters of the theory argue that other substances, such as alcohol, do make it from gut to brain. And HIV, they point out, is found in both the gut and the brain.

One of Wakefield's significant related claims was finding the measles virus where it shouldn't be - in the gut of the autistic children he was treating. The reason why MMR is risky, the theory runs, is that it overloads developing immune systems with three live viruses at once. The presence of the virus in gut biopsies is what lends weight to the hypothesis that it is the measles component of MMR that does the bowel damage when an overburdened immune system is unable to cope.

Critics slated Wakefield's methods and the DoH dismissed his work as "bad science". A senior official says: "Babies are exposed to millions of immune challenges, through breathing germs in and playing on the floor. Dr Wakefield has a real problem explaining his theory about immunological overload given that the viruses in the vaccine don't have an effect at the same time. The measles virus kicks in at five to 10 days, rubella in 11 to 14 days and mumps in 16 to 21 days." PHLS head of immunisation Elizabeth Miller says that Wakefield was "naïve" and has made "basic errors" in his research methods.

Dr Peter Mansfield, the GP who was reported to the General Medical Council for giving children single vaccines but who was recently cleared to carry on the practice, says that MMR "defies a principle of nature. These viruses are systemic: when they work in the body, they occupy the whole of it, so you're setting up a hurdle for the child." Children almost never encounter the three or even two of the viruses simultaneously in nature and, when they do, they don't have them injected into their bloodstream. Furthermore, research has shown that measles can suppress the immune system and that viruses can interfere with each other to produce adverse effects. Vaccine manufacturers have admitted the difficulty of creating combined jabs "due to the unpredicted immune interference and incompatibilities on mixing of different components."

Faced with a barrage of criticism, however, including slights about the accuracy of his tests, Wakefield sent samples of gut tissue to John O'Leary, chair of pathology at Trinity College, Dublin. Using his own tests, O'Leary has found the virus in significantly more autistic children than covered in Wakefield's first paper. The Department of Health has brushed aside the implications, saying that the work cannot be judged until it appears in a peer-reviewed journal. (Wakefield and O'Learyplan to publish soon.)

Meanwhile, a critical paper by David Elliman, a consultant in the department of child health at St Georges hospital in London, and Helen Bedford, of the Institute of Child Health, earlier this year claimed that the results were "inconsistent" and would have to be "confirmed independently". To outsiders, it may all seem like arcane wrangling, but the scientific evidence may eventually come to be examined in court. There are around 1,000 children in the UK employing legal aid to pursue a joint action in the courts alleging damage by MMR against the three manufacturers of MMR - Merck, SmithKline Beecham and Aventis Pasteur, out of around 3,000 whose parents have contacted lawyers. Proceedings have started in the case of about 350.

These parents' persistent question is why the DoH has not bothered to examine their children or their medical records. They are angry that the government has spent £3m on a campaign to persuade parents and health professionals that MMR is safe. "It should be spent on helping our children and further research," says Marion Wickens, who believes that her 10-year-old daughter Melissa's regressive autism and bowel disorder were caused by the triple vaccine.

"Before the MMR, she had a cheeky glint in her eyes. She could speak a few words, she played happily. I watched her lose her eye contact, stop speaking, stop pointing. She was like an empty doll," she says. "Now, she screams night and day, bites herself and tears at her hands. She's in agony because of the inflammatory bowel disease. She attacks young children. I feel so angry. She'll never have an independent life."

Despite parents' claims, Elliman and Bedford argue that research still shows that "the evidence of the safety and efficacy of MMR vaccine is so overwhelmingly conclusive that health professionals should have no hesitation in recommending its use." But Richard Halvorsen, a London GP who offers single jabs, says that he began to worry precisely when he started to read the very scientific papers cited as proof of safety.

"Most, but not all of the published evidence used by those proclaiming that MMR is safe doesn't add to the debate," he says. One study that took place in Finland over 14 years relied on doctors informing the authorities when they thought a child had had a serious, adverse reaction to MMR. The research concluded that serious side-effects of MMR were rare and greatly outweighed by the risks of the natural diseases.

However, the use of "passive surveillance", akin to the GPs' yellow card scheme in Britain, has been criticised for leading to under-reporting and for potentially missing significant reactions. Moreover, the study simply wasn't designed to look for autism. If medical staff weren't asked to look for autism as a possible side-effect, then there was no reason for them to re port it as a reaction to MMR. Given that other research suggests that autism cases quadrupled in Finland over this period, says consultant neuropsychologist Ken Aitken, "had they acknowledged autism as a possible reaction [to MMR], they should have picked up some cases because it had increased considerably in this population."

Aitken, with eminent Canadian epidemiologist Walter Spitzer, has looked at the medical records of 369 autistic children alleged by their parents to be MMR-damaged. Despite media stories of dramatic, instant reactions to MMR, the reality is that most children with regressive autism and bowel disorder suffer a slow degeneration into the condition, he says. The average delay between vaccination and diagnosis of autism was two and a half years. In these circumstances, few of the safety trials went on for long enough to be valid, the two scientists conclude.

Aitken is now convinced that "in a significant number of the children we see, there is a link between their problems and MMR," but that more research is needed into the causes and level of incidence: "Clinically, we're being swamped but there is no central database on autism and the rise in new cases." He and other experts are hoping that reports from the Medical Research Council, due next week, and from the Scottish Parliament expert advisory group, due next February, will call for a large-scale, long-term research project and a national database.

For now, a question mark still hangs over the safety of MMR. Faced with a choice between MMR or nothing, some parents are choosing nothing. Vaccination rates have fallen to 87% (79% in London) - well below the 95% coverage needed to maintain immunity and eliminate infection in the general population. A recent editorial in the journal of the Royal College of General Practitioners reiterated the view that MMR is safe but suggested that parents should be given an option, arguing that: "The DoH, as one arm of government... cannot encourage choice in some areas of public policy and discourage it in others."

The Department of Health argues against such a move, saying that public confidence in vaccines would collapse. The DoH can point to the success of MMR - no child has died of measles in the UK since the vaccine's introduction in 1988 - but the fact is that confidence is already shaken. The question for parents is whether the uncertainty surrounding the MMR vaccine is, in fact, larger than the worry that children might begin to die of natural disease because of the low rate of immunisation.

Disputed facts: conflicting research on MMR

Arguments rage over whether MMR-related research proves the triple jab's safety. Some of key studies are:

· "Peltola twins", in which one Finnish twin in each pair of 581 was vaccinated with MMR and the other with a placebo. Three weeks later, the MMR-vaccinated twins were given the placebo and vice versa. Critics say that three weeks simply wasn't long enough.

· Pre-licensing trials: criticised by Wakefield and a colleague for lasting no longer than 28 days.

· London doctor Brent Taylor and the PHLS looked at 498 cases of autism in the North Thames area. The authors found that, while cases rose, there was no sudden increase when MMR was introduced. Critics have questioned the original records and the likelihood of finding the one child or fewer in 1,000 allegedly damaged by MMR in a relatively small population. They also point to the fact that there was a catch-up campaign when MMR was introduced in 1988 which swept up most pre-school children. This, they argue, muddies the figures, which are organised by year of birth.

· In the US, the Oak Springs symposium reviewed evidence and came down in favour of MMR, but called for further research.
LS

Printable version | Send it to a friend | Read it later | See saved stories

ALL INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR LEGAL ADVICE.  THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH YOUR HEALTH CARE PROVIDER.