Feb 08 2009
Pity poor Andrew Wakefield.
Actually, on second thought, Wakefield deserves no pity at all. After all, he is the man who almost single-handedly launched the scare over the MMR vaccine in Britain when he published his infamous Lancet paper in 1998 in which he claimed to have linked the MMR vaccine to regressive autism and inflammation of the colon, a study that was followed up four years later with a paper that claimed to have found the strain of attenuated measles virus in the MMR in the colons of autistic children by polymerase chain reaction (PCR). It would be one thing if these studies were sound science. If that were the case, then Wakefield’s work would have been very important and would have correctly cast doubt on the safety of the MMR. Unfortunately, they were not, and, indeed, most of the authors of the 1998 Lancet paper later withdrew their names from it.
Over the next decade, aided and abetted by useful idiots in the media, by British newspapers and other media that sensationalized the story, and the antivaccine movement, which hailed Wakefield as a hero, Wakefield managed to drive MMR vaccination rates in the U.K. below the level of herd immunity, from 93% to 75% (and as low as 50% in some parts of London). As a result Wakefield has been frequently sarcastically “thanked” for his leadership role in bringing the measles back to the U.K. to the point where, fourteen years after measles had been declared under control in the U.K., it was in 2008 declared endemic again.
Worse, this fear was based on the worst science imaginable. First, no scientist not associated with Andrew Wakefield has ever been able to replicate his work. Second, as was exposed by U.K. reporter Brian Deer, not only was Wakefield paid big bucks by trial lawyers seeking to sue vaccine manufacturers for “vaccine injury” to do his studies on autistic children, a conflict of interest he never revealed and that had to be exposed through Deer’s investigations, but months before he published his Lancet paper Wakefield had applied for a patent on a an allegedly safer single measles vaccine that could succeed best if the safety of the MMR were called into doubt. Even after all of this came to light, leading to Wakefield’s correctly being dragged in front of the General Medical Council for charges of scientific misconduct. Even after this, he still enjoys a cult of personality that I can’t figure out, and is often portrayed as being “persecuted” by the British medical establishment. Third, was revealed at the Autism Omnibus proceedings when PCR expert Stephen Bustin testified about the shoddy methods at the laboratory used to do the PCR on the colon biopsies. In brief, the laboratory used was set up such that cross contamination between the plasmids used to maintain the measles virus sequences and the area where the PCR was done. PCR is very sensitive; if there is contaminating plasmid sequence, it is very easy to amplify and detect it even when there is nothing in your samples. Indeed, I’ve experienced this very problem on occasion in my own lab. Unfortunately, in the case of Wakefield’s research, no controls were done to make sure that contamination was detected in the negative controls. Finally, Wakefield’s results were roundly refuted in an attempt to replicate his work that was published last year. As you can see, Wakefield’s work and ethics are about as bad as it gets.
Or so I thought, until readers started sending me this article published in The Times, again by Wakefield’s nemesis Brian Deer. Holy crap. If only a fraction of the allegations in this article are true, not only is Wakefield an unscrupulous and incompetent scientist but he’s a scientific fraud as well:
The doctor who sparked the scare over the safety of the MMR vaccine for children changed and misreported results in his research, creating the appearance of a possible link with autism, a Sunday Times investigation has found.
Confidential medical documents and interviews with witnesses have established that Andrew Wakefield manipulated patients’ data, which triggered fears that the MMR triple vaccine to protect against measles, mumps and rubella was linked to the condition.
The research was published in February 1998 in an article in The Lancet medical journal. It claimed that the families of eight out of 12 children attending a routine clinic at the hospital had blamed MMR for their autism, and said that problems came on within days of the jab. The team also claimed to have discovered a new inflammatory bowel disease underlying the children’s conditions.
However, our investigation, confirmed by evidence presented to the General Medical Council (GMC), reveals that: In most of the 12 cases, the children’s ailments as described in The Lancet were different from their hospital and GP records. Although the research paper claimed that problems came on within days of the jab, in only one case did medical records suggest this was true, and in many of the cases medical concerns had been raised before the children were vaccinated. Hospital pathologists, looking for inflammatory bowel disease, reported in the majority of cases that the gut was normal. This was then reviewed and the Lancet paper showed them as abnormal.
The complete story reveals behavior on the part of Wakefield that leaves me just shaking my head in disbelief. It’s simply unbelievable.
Let’s step back a minute. The original Lancet paper examined the cases of twelve children with autism and other neurodevelopmental disorders. In the paper, it was reported that in 8 of the 12 children with regressive autism the onset of developmental changes closely followed MMR vaccination and in one of the 12 it followed measles infection. Moreover, colonoscopy showed colon abnormalities “ranging from lymphoid nodular hyperplasia to aphthoid ulceration.” In 11 children, biopsy histology showed patchy chronic inflammation in the colon. The conclusion was that there was an apparent association between MMR vaccination and a syndrome of regressive autism and inflammatory bowel changes. Even though the paper’s tone was more tentative than one would have thought given the furor it launched and even though it stated that the authors “did not prove an association between measles, mumps, and rubella vaccine and the syndrome described,” Wakefield promoted his results to the media as though he had definitely found a link between the MMR vaccine and a syndrome consisting of regressive autism and inflammatory bowel disease. Thus was launched the scare that caused a thousand cases of measles (in 2008) that could have been avoided and caused many autistic children to be subjected to invasive procedures they didn’t need, sometimes at the cost of serious complications.
If the latest information is true, however, Wakefield is guilty of more than shoddy science and unreported conflicts of interest. He is guilty of scientific fraud and falsifying the medical reports of these children. For example, take Child 11, whose father requested a second set of testing on his child’s biopsy specimens:
MR ELEVEN’S taxi dash was a small ride in his desperate quest to find an answer for his son’s condition. Today, Child Eleven is much improved: at 17, he is a terrific scholar, although too nervous to drive.
The extra tests on his biopsies produced striking results. His father asked the cancer institute to look for the measles virus, which lay at the heart of Wakefield’s concerns over the vaccine. According to a theory that underpinned the project, this virus in MMR was the cause of bowel disease, which then did damage to children’s brains.
“It took a big fight to get the information,” said Mr Eleven. “They told me there was no measles virus. I had the tests repeated three times at different labs in the US, and they all came back negative.”
This struck a different note from what Wakefield suggested when describing his research to the world.
“We would not have presented this paper to The Lancet had we not undertaken extensive virological studies already,” he told the 1998 press conference.
Of course, this anomaly could simply have been due to the aforementioned incompetence of the lab that Wakefield used to test his specimens for MMR strain measles virus, with its procedures guaranteed to produce false positives. Unfortunately, there’s more. A lot more. Take Child One:
In the paper this claim would be adopted, with Wakefield and his team reporting that Child One’s parents said “behavioural symptoms” started “one week” after he received the MMR.
The boy’s medical records reveal a subtly different story, one familiar to mothers and fathers of autistic children. At the age of 9½ months, 10 weeks before his jab, his mother had become worried that he did not hear properly: the classic first symptom presented by sufferers of autism.
This is an incredibly common story among parents who believe that vaccines caused their child’s autism. Many vaccines are scheduled to be given during the same time that children often show the first behavioral alterations associated with autism, and it is not uncommon either for such changes to occur within a few weeks of a vaccination by random chance alone, nor is it uncommon for parents to remember incorrectly that the child’s symptoms started soon after a vaccine when they did not. Indeed, it is not uncommon at all for experts to be able to detect the subtler signs of autism on videotapes of babies before the parents noticed and before the child received the vaccinations for which parents blame the condition. Unfortunately, human memory is fallable, and it easily relates events that are not closely related, particularly in response to other information or preexisting beliefs. This happens all the time with vaccines and autism, where numerous epidemiological studies have failed to find an association between either mercury in thimerosal-containing vaccines and autism, between MMR and autism, and between vaccines in general and autism.
And Child Two:
This was Child Two, an eight-year-old boy from Peter-borough, Cambridgeshire, diagnosed with regressive autism, which, according to the Lancet paper, started “two weeks” after his jab.
However, this child’s medical records, backed by numerous specialist assessments, said his problems began three to five months later.
And the list goes on:
Only one was a girl, Child Eight, aged 3, from Whitley Bay, Tyne & Wear. She was reported in the journal as having suffered a brain injury “two weeks” after MMR.
Her medical records did not support this. Before she was admitted, she had been seen by local specialists, and her GP told the Royal Free of “significant concerns about her development some months before she had her MMR”.
Child Six, aged 5, and Child Seven, aged 3, were said to have been diagnosed with regressive autism, with an onset of symptoms “one week” and “24 hours” after the jab respectively.
But medical records show that neither boy was “previously normal”, as the Lancet article described all the children, and that both had already been hospitalised with brain problems before their MMR.
Child Six received his vaccine at the age of 14 months, but had twice previously been admitted with fits.
Child Seven was given his at the age of 20 months but, again, problems already showed.
In other words, one of two things happened, neither of which is flattering to Wakefield. Either he took the history from parents, for whom confirmation bias could easily have led to remembering incorrectly that their child’s behavioral changes were noted shortly after the MMR rather than before it or months later, in which case Wakefield was incompetent for not having examined the medical records. Alternatively, Wakefield did examine the medical records and lied about them in the Lancet paper. Take your pick.
In fact, I might have been willing to give Wakefield somewhat of the benefit of the doubt, viewing the discrepancies between the medical records and what he reported in the Lancet paper as being yet more evidence of his shoddiness and incompetence rather than malice, were it not for the major discrepancies between what Wakefield said about the histology of the biopsy specimens in the paper. The Lancet paper described a uniform pattern of patchy inflammation, but apparently what Wakefield reported does not jibe with what the pathologists saw:
“The uniformity of the intestinal pathological changes and the fact that previous studies have found intestinal dysfunc-tion in children with autistic-spectrum disorders, suggests that the connection is real and reflects a unique disease process, ” the Lancet Paper explained of the “syndrome”.
Yet pathology records of samples taken from the children show apparent problems with this evidence. The hospital’s consultants who took biopsies from the children’s colons concluded that they were not uniform but varied and unexceptional.
For Child Eight, the pathology report said: “No abnormality detected”, while the Lancet paper said: “Nonspecific colitis”. This pattern was repeated for two of the other children, Nine and Ten.
The most striking change of opinion came in the case of Child Three, a six-year-old from Huyton, Merseyside. He was reported in the journal to be suffering from regressive autism and bowel disease: specifically “acute and chronic nonspecific colitis”. The boy’s hospital discharge summary, however, said there was nothing untoward in his biopsy.
Not happy with the readings of the pathologists, apparently Wakefield’s research team met for a “research review” of the biopsy specimens. This in and of itself is not unusual. However, it is unusual that the research team overturned the original readings of so many of the specimens. As Brian Deer put it:
It was not an unusual move for a group of specialists to reconsider the evidence upon which their research was relying. It was nevertheless striking that their conclusion was that 11 of the children’s bowels were in fact diseased when their colleagues had found no abnormalities in at least seven of the cases.
Quite frankly, such conduct beggars the imagination. It’s about as unethical as it gets. But it’s all of a piece with Andrew Wakefield’s behavior. After all, as I pointed out before, he was in the pocket of a lawyer named Richard Barr seeking to sue vaccine manufacturers for “vaccine-induced” autism before he undertook his research. Not only that, but Barr was affiliated with the antivaccine group Jabs, and Wakefield apparently concocted his new “syndrome” after at least some consultation with Barr. But perhaps the most unethical, at least from a human research standpoint, was that the patients recruited to his study were not anything resembling a random or neutral sample. As pointed out by Brian Deer, the parents of these children heard through word of mouth about Wakefield. Add to that the fact that Wakefield subjected these children to unnecessary invasive medical procedures, and then incompetently analyzed the specimens obtained from them for measles virus to produce a virtually preordained result, even if it took scientific fraud to do it, and you see what I mean. Given such a level of ideological blindness that seems to think his cause so just that good science and ethics are optional in pursuit of it, a lack of concern over blatant conflicts of interest, and an appallingly inflated opinion of himself that he is seems to believe that he is actually a persecuted Galileo, is it any surprise that Wakefield may have stooped so far as to falsify research results in his campaign?
Not to me, it isn’t.
Sadly, none of this will matter to antivaccinationists, who view Wakefield as exactly that–a persecuted scientific hero. Although I have yet to see any response from antivaccine blogs like like Age of Autism, I’m sure that they’ll wax ridiculous about what a great doctor and man Wakefield is and how it’s big pharma and its minions who, frightened by the implications of Wakefield’s work, are working hard to demonize him and suppress his “science.” Unfortunately for their reality-challenged world view, sometimes things are as they appear, sometimes there really is no conspiracy, and sometimes a rat is a rat.
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