The Origin of the False Claim That Vaccines Cause Autism Is Worse Than You Think

Did the editors of The Lancet in 1998 not understand how science works?

Unfortunately Robert F. Kennedy Jr. is now a regular presence in the national news, and it means that we are going to suffer through yet another cycle of public debate over the false claims that autism has been linked to vaccines. Responsible journalists, medical institutions, and public figures will yet again need to remind everyone that a there is no link between the MMR vaccine and autism, that the issue has been thoroughly investigated in large studies and meta-analyses, whose results are publicly available. It is good to cite this science, but it can lead people who are inclined to be skeptical of vaccines to feel like this is a complex debate with large datasets and difficult statistics that once could parse in different ways.

I want to try something different here. In this post, we’ll go back to the original source of the claim that the MMR vaccine might cause autism, the notorious, now-retracted 1998 paper published by Wakefield, et al. in The Lancet. What people typically know about this paper, if they are aware of it, is that it was retracted and Wakefield and his colleagues were accused of fraud and ethics violations. (They had undisclosed financial interests, they didn’t get the necessary consent for conducting invasive examinations of their child subjects, and they lied about how they assembled their study population. See this summary.)

But you don’t need to know any of that to see that the paper, taken at face value, is obviously terrible. It’s study design (and I’m being generous using the word “design”) has problems can be easily understood by anyone who has even a vague recollection of high school science. When you read this paper, you can understand why a whole movement for “evidence-based medicine” had to be a thing, because the 1990’s Lancet editors clearly didn’t understand how medical evidence works.

Problem 1: There is no statistical power in 12 kids who happen to show up at your clinic

The 1998 Wakefield paper is an “early report” that describes an assessment of twelve children who visited a UK gastroenterology clinic. Their ages ranged from 3-11, and, according to the paper, they had “a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain.” You don’t need any more information than this to understand that a study like this has zero power to find any association between autism and the MMR vaccine. Twelve kids who show up at your clinic, among a population of tens of millions of children who had received the MMR vaccine, will tell you nothing about MMR and autism.

Problem 2: The association of autism with vaccination was a parent report and not a statistical finding

Nine of the twelve children in the study were diagnosed with autism, though the paper does not describe how the diagnosis was made. Three others were ambiguous cases. The main evidence used to claim a link with vaccination, I kid you not, is this:

In eight children, the onset of behavioural problems had been linked, either by the parents or by the child's physician, with measles, mumps, and rubella vaccination.

That is literally the entire basis for suggesting a link between vaccines and autism in this paper - the parents or the child’s physician thought the vaccine caused their child’s condition. There is no statistical analysis, no clear histological or other unambiguous evidence of vaccine effects. The children were all given colonoscopies, and the study reports a miscellany of findings, each of which only occurred in some of the children. Wakefield had earlier explored the idea that measles and the MMR vaccine might be associated with the development of irritable bowel disease (IBD). This idea morphed into his belief that vaccines predispose children to autism via gut pathology. Hence the colonoscopies for his patients.

There is a table in the paper titled “Neuropsychiatric diagnosis” whose columns show the behavioral diagnosis for each subject, the “exposure identified by parents or doctor”, the interval from exposure to first symptoms (usually a few days to a week), etc. This table does not present evidence for anything. It merely lists a small number children who happened to show up at a GI clinic, who have autism and who supposedly received the MMR vaccine within a week of the first symptoms (according to the parents, with no other documentation).

Problem 3: No controls

When you want to find an association between some cause and a disease, you need to include disease cases and healthy controls. If, for example, you wanted to claim that green jelly beans are associated with a risk of cancer, your analysis would need to include control subjects who didn’t get cancer, so that you could check whether the rate of green jelly bean consumption differed among the groups. Alternatively, you could follow two groups, one that ate green jelly beans and one that did not, and ask whether there was a difference in cancer incidence between the groups. The Wakefield study has no real controls. There is no work-up of healthy children presented or an analysis of children who were not vaccinated.

Figure 1 does show a plot of urinary methylmalonic-acid in 8 of the 12 patients versus 14 “age-matched controls.” There is no description of where these control patients came from or anything else about them. There is a p value (p = 0.003), but how it was calculated is not described. And methylmalonic-acid says nothing about autism or vaccines; it is a potential indicator of vitamin B-12 deficiency.

How could anyone consider this science?

There are many other problems in this short paper we could discuss, but by now it should be clear: this work, taken at face value, ignoring the later evidence of fraud, couldn’t possibly say anything about a link between vaccines and autism. It’s a description of twelve children who were vaccinated (like millions of other children the same age), who had autism, and whose parents thought the vaccine caused their autism. This is not science.

It’s true that the authors write that “We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described.” But this leaves out the fact that they didn’t even investigate an association between the MMR vaccine and autism. And yet, in the very next paragraph, the authors write that “If there is a causal link between measles, mumps, and rubella vaccine and this syndrome, a rising incidence might be anticipated after the introduction of this vaccine in the UK in 1988.” It was this idea that caught fire in the media and, nearly three decades later, has left us us with a nominee to lead the U.S. Department of Health and Human Services who goes on television to tell people that vaccines cause autism.

The most perplexing question is how any serious person at The Lancet thought a manuscript like this met the standards for publication in their journal. Medical science, like all science, is an astonishingly effective generator of reliable knowledge when it is based on reliable methods. This paper flagrantly ignores those methods. It is worth noting that in the year after the Wakefield paper The Lancet published a real investigation with nearly 500 subjects and found no association between the MMR vaccine and autism, no evidence of a distinct increase in incidence after the MMR vaccine was introduced, and no relationship between the timing of vaccination and the age of autism diagnosis. But the damage had been done.

A quick read of the Wakefield paper is enough for almost anyone to understand that false claims about vaccines and autism did not arise from some suggestive or worrying early study that was later clarified. The tragedy is that there was never any basis whatsoever for believing the claim.