Yet another really bad day for antivaccinationists: No link between MMR and autism–again

ResearchBlogging.orgThis is getting to be monotonous, but it’s a monotony that I like, as should anyone who supports scientific medicine and hates the resurgence of infectious diseases that antivaccinationists have been causing of late with their fearmongering about vaccines that frightens parents into refusing to vaccinate their children. It’s the drumbeat of studies, seemingly coming out every few months, that fail to find even a whiff of a link or correlation between vaccines, thimerosal-containing or otherwise, and autism. You’d think that the pseudoscientists who are so utterly convinced that it absolutely, positively has to be the vaccines causing autism and that if it isn’t vaccines must be causing some horrible chronic health problem or other would have gotten the message by now. It doesn’t matter that the pace of these studies has been accelerating, with one last fall that showed no link between vaccines and non-autism neurodevelopmental disorders, followed by another study that showed no link between thimerosal-containing vaccines and autism, followed in even more rapid succession by yet another study that failed to find a link between the MMR vaccine and autism. That list doesn’t even take into account studies from the year before that that trashed the concept of the “autism epidemic” and failed to find any correlation between vaccines and autism.

Yesterday evening, yet another study failing to find a link between MMR and autism, this time out of Columbia University, was released. Even better, the first author on the study is Mady Hornig, who became a hero of the mercury militia a three years ago with her infamous “rain mouse” study, in which she performed experiments of dubious ethics on some very unlucky lab mice and claimed it was “evidence” that thimerosal caused autism. She was even a common speaker at mercury militia–excuse me, I mean National Autism Association (NAA) –events, along with hard core members Boyd Haley, Richard Deth, Mark Blaxill, Jeff Bradstreet, and others, as well a speaker for FAIR Autism Media, along with Mark and David Geier, Thomas Burbacher, Boyd Haley (again), Andrew Wakefield himself, and many others. The paper reporting her study is even hosted on the NAA website, as well as that of SAFEMINDS.Unfortunately, her experiments were anything but evidence supporting a link between thimerosal and autism, just as these endorsements imply.

This latest study makes me think that perhaps Dr. Hornig, contemplating her descent into antivaccine pseudoscience, may have had a “come to Jesus” moment and is trying to regain her scientific mojo (although I’ll only really believe that when I see her give up trying to show that thimerosal causes autism using her mouse model). Either that, or she figured out that flirting with the band of pseudoscientists and ideologues making up the antivaccine movement is the surest way to kill her scientific career deader than dead and thereby end up working in the basement of her house like Geier, père et fils. In other words, perhaps she decided that tenure and a continued scientific career meant more to her than the momentary notoriety and adulation that come from being the darling of the mercury militia.

Whatever the case, Dr. Hornig has done a study with W. Ian Lipkin as the senior author published in PLoS ONE entitled, Lack of Association Between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study. Before I get to the study itself, let’s look at the news report:

CHICAGO (Reuters) – Scientists who tried to replicate a study that once tied a measles vaccine with autism said Wednesday they could not find any link and hope their study will encourage parents to vaccinate their children to combat a rash of measles outbreaks.

Parents’ refusals to have their children vaccinated against measles have contributed to the highest numbers of cases seen in in the United States and parts of Europe in many years.

Measles kills about 250,000 people a year globally, mostly children in poor nations.

Yes! I love it when a mainstream news article lays out the price of antivaccination idiocy right there near the beginning. The beauty of this study is that it tried to replicate the original study done by Andrew Wakefield (you know, the one that was bought and paid for by trial lawyers). As you may recall, ten years ago, Wakefield published a paper in The Lancet describing a series of children with regressive autism and gastrointestinal complaints. He described intestinal abnormalities, including reactive lymphoid hyperplasia in the ileum, and the parents of several of these children reported the onset of symptoms temporally related to the MMR. This led to the hypothesis that the MMR was associated with autism and GI complaints, and what later followed were additional papers that purported to find measles RNA in the gut of autistic children.

Thus was born the MMR scare in the U.K., a scare that, a decade later, has resulted in the resurgence of the measles in there to the point that it has become endemic again a mere 14 years after having been declared under control. Sadly, he had lots of help from the press, which published credulous inanities about this link, regardless of how shoddy the science was (and shoddy it was indeed).

Basically, the design of the study was pretty simple, and, better yet, it was an intentional attempt to replicate the research of Andrew Wakefield using rigorous methodology. The design was a case control study in which children with autism and GI problems were compared to children with GI problems and no autism for a number of parameters, including MMR vaccination and the presence of measles virus RNA in the gut of children who underwent endoscopy. The overall approach was to determine whether children with autism and GI symptoms were more likely to have detectable measles virus RNA in the gut. The result?

Zero correlation. Nada. Zip. One out of the 25 autistic children in the study had detectable measles virus RNA present in their biopsies, while one out of the 13 children without autism also had detectable measles virus RNA present. There was not even a hint of a statistically significant difference between the groups, nor was there a correlation between the timing of the MMR vaccination and the onset of autism or GI symptoms. Basically, this study was negative, and very strong evidence against the contention that MMR causes autism or chronic GI problems. So strong was the evidence that even Rick Rollens grudgingly admitted it in a back-handed way:

“No longer can mainstream medicine ignore parents’ claims of clinically significant GI distress,” said Rick Rollens, a parent and autism research advocate.

He commended the researchers for their work but said, “This study by itself does not exonerate the role of all vaccines.”

Sound familiar? It’s just like the thimerosal shuffle. As studies come out exonerating thimerosal as a cause of autism, antivaccinationists invoke other “toxins,” sometimes going to ridiculous contortions to do it. Because, you know, it’s absolutely, postively, got to be something in the vaccines. It’s the same thing here. The MMR has been exonerated as a cause of autism, but Rollens knows that it’s just absolutely, positively got to be some vaccine that causes autism.

One observation that came out of this study is that there is indeed a correlation between GI complaints and regressive autism. Neither are associated with the MMR, but they are associated with each other. This is certainly an observation that should be followed up with further study; what this study contributes is that it frees researchers to stop wasting precious research dollars studying the hypothesis that MMR causes autism. It doesn’t. Between a previous study by Baird et al and the current one, among others, the science is quite clear that there is no link between MMR and autism.

The reaction to this study by the antivaccine contingent is instructive. There are two main reactions, the ridiculous and the even more ridiculous. To understand just the ridiculous, you first need to know that this study had a very interesting design aspect. All the samples were sent to three different laboratories for analysis, completely blinded so that the labs didn’t know which experimental group each patient was in, and tests of concordance were done, to verify that the three labs agreed. Prior to the beginning of the study, the three labs were tested with positive and negative controls. So what? You ask. Let’s go back to a discussion of the Autism Omnibus last year, where polymerase chain reaction (PCR) expert Stephen Bustin examined John O’Leary’s laboratory, where the the reverse transcriptase PCR (RT-PCR) was performed to detect measles RNA. Bustin demolished the methodology of that laboratory demonstrating conclusively that the “postives” detected were all false positives made possible by plasmid contamination, as I discussed here and Kev has also discussed.

The O’Leary laboratory was one of the three labs used in this study.

Let’s put it this way. A little birdie told me that David Kirby himself was in on a teleconference for reporters about this study held yesterday and that he asked a lot of questions about the O’Leary lab. I’ve also heard rumblings from the antivaccination underground that the talking point will be that this study is a “two-edged sword” in that it supposedly the fact that the O’Leary lab performed competently now somehow exonerates its horrible performance several years ago. It doesn’t. Bustin’s deconstruction of the methodology in use at the O’Leary lab at the time was devastating, demonstrating a level of incompetence beyond belief. What is far more likely is that O’Leary was forced to clean up his act and tighten up lab discipline in order to be included as one of the labs in this study. Still, don’t be surprised if David Kirby posts (or has in the interim between when I wrote this and it posted to this blog posted) yet another one of his Huffington Post obfuscations claiming that this new study, because the O’Leary lab did OK this time, somehow rehabilitates Andrew Wakefield and that we should take another look at his original results.. Don’t fall for that line. The same little birdie also told me that Kirby asked questions about the Michelle Cedillo case, which is in essence a non sequitur. However, apparently Cedillo’s biopsy samples were also processed by Dr. O’Leary’s lab, and Kirby seems to think that maybe this study could therefore be used to support her test case in the Autism Omnibus. Again, don’t fall for that line; it’s virtually certain that Dr. O’Leary must have cleaned up his act. Remember, his lab was tested before it was allowed to process real patient samples from this study.

Finally, predictably, the Wendy Fournier of the National Autism Society was first off the mark with her criticism, and a truly laughable bunch of nonsense it is. Amusingly, she starts out by calling this a “CDC study.” Actually, it’s a study out of Columbia University, Massachusetts General Hospital and Harvard University, Trinity College in Dublin, and the Measles, Mumps, Rubella, and Herpesvirus Laboratory and the Branch National Center for Immunization and Respiratory Diseases at the Centers for Disease Control., and its funding came from CDC grant U50 CCU522351 to AAP and by National Institutes of Health awards AI57158 (Northeast Biodefense Center-Lipkin), HL083850, and NS47537. Predictably, Fournier wants to make this sound like a conspiracy of some sort or imply conflict of interest. Of course, she neglects the fact that investigators Mady Hornig and John O’Leary, among others, were until this study heroes of the antivaccine movement. Some conspiracy.

Fournier’s “complaints” are lame in the extreme:

The CDC study was designed to detect persistent measles virus in autistic children with GI problems. The assumption being if there is no measles virus at the long delayed time of biopsy, there is no link between autism and MMR. But NAA says this underlying assumption is wrong. The questions should have been: Do normally developing children meeting all milestones have an MMR shot, develop GI problems and then regress into autism? Do they have evidence of measles and disease in their colons compared to non-vaccinated age and sex matched controls

Point one: The study didn’t just look at the presence of measles virus in the gut. It also looked at the timing of MMR vaccination compared to a number of health parameters. Indeed, the authors analyzed not just whether MMR preceded symptoms but did statistical modeling of how long the interval between vaccination and symptoms was. The answer was that there was no correlation. Of course, Fournier’s whine is nothing more than an example of the old crank adage: “If you don’t like the answer, change the question.”

Point two: Does Fournier know how stupid her demand for checking non-vaccinated age- and sex-matched controls is? She clearly knows nothing about clinical research or medical ethics. Colonoscopy is an invasive procedure. Not only does it require general anaesthesia in small children, but there is a small but real risk of serious complications. It’s not a procedure to be done without a firm indication, which is what the investigators did. They selected children for whom colonoscopy was indicated based on their clinical presentation and symptoms. Doctors can’t just go around doing colonoscopies and gut biopsies on “control” children. In addition, even if she meant that the controls with GI problems should have been free of exposure to the MMR, that is a methodological obstacle that would be very difficult to overcome, given how few children of that age have not received the MMR, and if ths hypothesis being studied is that MMR is causative for autism, autistic enterocolitis, or enterocolitis itself, looking for correlation between receiving MMR before the onset of symptoms is a valid methodology to pursue to test that hypothesis. Of course, an understanding of medical ethics was never the strong suit of antivaccinationists.

Neither are statistics, as Fournier demonstrates:

In the current CDC study, only a small subgroup of children was the correct phenotype to study. From page 7, “Only 5 of 25 subjects (20%) had received MMR before the onset of GI complaints and had also had onset of GI episodes before the onset of AUT (P=0.03).” The other 20 autistic children in the study had GI problems but the pathology developed before the MMR vaccine. Additionally, the controls all received the MMR vaccine and had gastrointestinal symptoms. The controls should have been free of exposure to vaccine measles in order to make a comparison relevant for purposes of causation.

This analysis was the one of the major points of the study, the point being that there was no difference, statistically speaking, between the number of children in the autism + GI complaints and the GI complaints alone group, indicating that there was no association between having the MMR vaccination before the onset of symptoms and the development of symptoms. As for her complaint that all the controls received MMR and had GI symptoms, see my previous response. It applies here, too. The only grain of truth is that, yes, this study wasn’t all that large. It did, however, study four times the number of patients that Wakefield’s original study did, and it was far, far more rigorous in design and execution, including excellent blinding. Also, for reasons mentioned before, no study of this type is ever likely to achieve high numbers because it requires an invasive procedure. In any case, the study had more than adequate power for the questions answered and accrued enough patients to have highly statistically significant results.

The lamest of all, however, is this:

Inflammatory bowel disease in the absence of MMR RNA does not mean that MMR shot didn’t precipitate the GI disease and didn’t precipitate autism. A similar example would be rheumatic fever where the infection is cleared quickly but damage to the heart and/or brain last a lifetime.

Talk about moving the goalposts! Remember, the hypothesis being tested was Andrew Wakefield’s hypothesis, which was that somehow the persistence of the measles virus in the guts of children vaccinated with the MMR live virus vaccine contributed somehow to autism and “autistic enterocolitis,” not that the MMR contributed to autism or autistic enterocolitis via some sort of rheumatic fever-like mechanism. Now that this study has provided strong evidence falsifying that hypothesis, antivaccinationists like Fournier are moving the goalposts yet again. If it’s not the persistence of the measles virus from vaccines in the gut that causes autism, then it must be some other mechanism, because to the antivaccinationist it absolutely, positively has to be the vaccines. They just know it, and no amount of evidence will ever sway them to think otherwise.

If you don’t believe me, just read the comments after Age of Autism’s reprint of Wendy Fournier’s press release, for example:

How many sites in the intestine were biopsied? One?

If someone doesn’t want to find the vaccine-strain measles lurking in the gastrointestinal tract, it won’t be found.

The stupid, it burns. From the study itself:

Biopsy material was obtained from terminal ileum and cecum under direct supervision of the team gastroenterologist. For analyses of MV RNA, four random samples were taken from superficial mucosae of ileum and cecum. Additional specimens were acquired at sites indicative of inflammatory GI lesions, if present. All samples intended for RNA analysis were frozen immediately in coded tubes in liquid nitrogen and stored at −70°C until shipment to CU on dry ice. Frozen biopsy specimens were stored in a dedicated −70°C freezer until RNA extraction to avoid inadvertent contamination. A portion of each clinical pathology sample also was retained under blind for histopathologic analysis.

Complaint answered. Next:

OMG, this study is an f-ing joke! Do ya think that they didn’t find measles in the intestines because they didn’t really look?

Unfortunately, it looks like th joke is on us.

No, actually the joke is on Andrew Wakefield. On second thought, maybe the joke is on you too, but it wasn’t the CDC, the AAP, or vaccine scientists that played it on you.

It was Andrew Wakefield, and the same despicable joke of claiming that vaccines cause autismis being played on you by Jenny McCarthy, J.B. Handley, Wendy Fournier, Mark and David Geier, and all the other antivaccinationists are playing on autistic children and their parents. It’s a sick joke that needs to end now because it spreadss misinformation that endangers public health by frightening parents out of vaccinating their children. Unfortunately, only the parents who feed into it can end it. Certainly the pseudoscientists and autism cure industry that depend on the myth that vaccines cause autism never will.

REFERENCE:

1. Mady Hornig, Thomas Briese, Timothy Buie, Margaret L. Bauman, Gregory Lauwers, Ulrike Siemetzki, Kimberly Hummel, Paul A. Rota, William J. Bellini, John J. O’Leary, Orla Sheils, Errol Alden, Larry Pickering, W. Ian Lipkin, Mark R. Cookson (2008). Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study PLoS ONE, 3 (9), 1-8 DOI: 10.1371/journal.pone.0003140

ADDITIONAL COMMENTARY:

  1. MMR still doesn’t cause autism
  2. New MMR study makes the NAA angry
  3. The final nail in the coffin of the MMR vaccine-autism hypothesis
  4. MMR and Autism – No connection
  5. U.S. study clears measles vaccine of autism link
  6. Vaccination doesn’t cause autism volume what-are-we-up-to-now?
  7. NOW is it over?
  8. MMR Vaccine Does Not Cause Autism (not that you didn’t know that already)
  9. Antivax: new evidence shows (again) no link to autism
  10. New study finds no vaccine-autism link
  11. Study Says No MMR-Autism Link; NAA Says “Flawed”