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Respectful Insolence

"A statement of fact cannot be insolent." The miscellaneous ramblings of a surgeon/scientist on medicine,
quackery, science, pseudoscience, history, and pseudohistory (and anything else that interests him)

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orac.jpg Orac is the nom de blog of a (not so) humble pseudonymous surgeon/scientist with an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his miscellaneous verbal meanderings, but just barely small enough to admit to himself that few will. (Continued here, along with a DISCLAIMER that you should read before reading any medical discussions here.)

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

Category: Alternative medicineAntivaccination lunacyAutismMedicineQuackery
Posted on: September 4, 2008 3:00 AM, by Orac

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"

Comments

One of the complaints is that the study didn't find what they "should" because they were looking at the wrong group.

They were attempting to recreate these results:

http://www.ncbi.nlm.nih.gov/pubmed/11950955

Which showed something like 77% positives for measles RNA. It wasn't replicated.

Posted by: Sullivan | September 4, 2008 3:56 AM

Sooner or later the antivax crowd will have moved the goalposts clear out of the stadium.

Posted by: DLC | September 4, 2008 4:52 AM

Like you say, they will do and say absolutely anything to blame those nasty vaccines, no matter what. They are just pure eevil. Hence the rationalisation from Fournier: (now why do I think of gangrenous genitals each time I read her name?)

"The controls all received the MMR vaccine, so it is possible that the GI pathology in controls, but not the autism, was caused by vaccine measles."

Yup, MMR doesn't cause autism, so it just causes gut problems, OK?

Posted by: DT | September 4, 2008 5:39 AM

While it is reasonable to take pleasure in the discomfiture of the anti-vaccinationists there are important consequences to this study.

Firstly, new parents should be assured that MMR is safe and has no connection to autism.
Secondly, if the MMR causation theory fails in the Omnibus proceedings before the special masters it will make it difficult totake it to open court. Imagine a decent attorney interviewig O'Leary about the disparity between his lab's old results and his new results.
Finally and probably most importantly for the autism community, there is a subset of autistic children with apparently intractable GI disorders that cause them immense distress. While it is not clear whether or not GI disorders are more prevalent with regard to regressive autism than they are in the mainstream, there sems to be a disproportionate amount of suffering involved. Now mainstream researchers can investigate this without risking the taint of association with the anti-vaxers, it may provide relief for these sufferers and their families.

Posted by: mike stanton | September 4, 2008 6:22 AM

Doctors can't just go around doing colonoscopies and gut biopsies on "control" children.
Surely the CDC can afford a short jaunt to Area 51 where they can compare notes with UFOs that fly around doing thousands of colonoscopies each day?

Posted by: llewelly | September 4, 2008 8:22 AM

I like this blog, but statements like this
"either that, or she figured out that flirting with the band of pseudoscientists and ideologues making up the antivaccine movement was the surest way to kill her scientific career deader than dead"

just provides fodder for the conspiracy mill. Expelled: The Vaccine edition will be built quotes like this.

Posted by: I am so wise | September 4, 2008 8:53 AM

You're not going to get me to apologize for pointing out that becoming a pseudoscientist is one of the surest ways to kill a scientific career. It is and should be.

Posted by: Orac | September 4, 2008 9:06 AM

Because, you know, it's absolutely, postively, got to be something in the vaccines.

It's the dihydrogen monoxide.

Posted by: D. C. Sessions | September 4, 2008 9:24 AM

"...bcoming a pseudoscientist is one of the surest ways to kill a scientific career."

Hey, it hasn't bothered Boyd Haley (University of Kentucky chemistry professor and hero to the antifluoridation and antivax movements).

Maybe the key is to maintain a base of respectability (preferably tenure) in one's field while embracing looniness as a sideline.
That way one can garner lots of attention (and potentially, outside speaking fees) while protecting one's regular paycheck.

Posted by: Dangerous Bacon | September 4, 2008 9:30 AM

Cue Dawn and Undergraduate Girl in 3...2...1...

Posted by: BGT | September 4, 2008 9:36 AM

I love this blog. I was at our pediatrician's office last week, getting the 15 month check up for our daughter. Included were an MMR booster, varicella, and something else I can't recall right now. I asked him if there had been any increase in parents questioning or objecting to the vaccines recently. He rolled his eyes and said, "well, there his been a litle bit of an upspike."

He asked if I knew the origins of the problem, assuming I wasn't an objector. I replied, "Yes, the Wakefield study 10 years ago in Lancet that was since withdrawn and discredited." He looked at me, realizing that I knew what I was talking about. Next time I'll mention this study and ask him if other parents are aware of it.

I know that's not really a comment, I just wanted to say thanks. I appreciate having access to the information and analysis you provide.

Posted by: chris | September 4, 2008 9:36 AM

Well, one counter might be that Hornig et al. (2004) was a study with numerous and significant problems, which it clearly was, so why should we think a new study by Hornig is reliable? One thing's for sure, though. The "conflicts of interest" canard does not apply to this study.

Posted by: Joseph | September 4, 2008 9:38 AM

The link between GI issues and autism makes a lot of sense scientifically. As the number of genetic mutations linked to autism grows it is more than likely than some of these mutations may also result in GI conditions. Gene products can have different functions in different cell types. Therefore, a dysfunctional protein that alters neuronal synapse functions or neuronal cell growth may result in overactivity of, let's say, macrophages. I saw a presentation at a conference a few years back that showed just that. Unfortunately, I can't seem to find my notes to give you the specifics. I think that this is a much more plausible explanation than non-existent viruses and toxins.

Posted by: ozzy | September 4, 2008 9:59 AM

It's posts like these that make me love this blog!!!

Posted by: Orodriguez | September 4, 2008 10:40 AM

I'm interested in your opinions about something. My son, who is severly autistic, has numerous GI issues. We just recently received his allergy tests back and found out that he is allergic to Wheat, Milk and sesame seeds. Does anyone know if this is common among autistic children? Additionally, if it is common, wouldn't a GFCF diet benefit these children? Just curious, and for the sake of debate.

Posted by: Craig Willoughby | September 4, 2008 10:44 AM

Similar to what Chris noted, our pediatrician was very happy when we went in for shots and made clear that we understood the safety and efficacy of vaccines. And I turned her on to scienceblogs as well.

Posted by: Rev Matt | September 4, 2008 10:49 AM

We just recently received his allergy tests back and found out that he is allergic to Wheat, Milk and sesame seeds. Does anyone know if this is common among autistic children? Additionally, if it is common, wouldn't a GFCF diet benefit these children?
Were these skin-prick tests or blood tests? If blood tests, did they test for IgE or IgG levels (some people refer to the latter as delayed allergy or intolerance)?

There is a double-blind trial planned for the GFCF diet for children with behaviour on the autistic spectrum.

Posted by: Mary Parsons | September 4, 2008 11:27 AM

The link between GI issues and autism makes a lot of sense scientifically. As the number of genetic mutations linked to autism grows it is more than likely than some of these mutations may also result in GI conditions.

Especially considering the other close relationships between the GI and CNS. Polio certainly isn't the only pathology that jumps that particular crack in the pavement.

Posted by: D. C. Sessions | September 4, 2008 11:30 AM

Glad to hear that Hornig et al attempted replication of the discredited study, and have learned from past critique(s) how to get their act together to produce a higher quality report/study product.

Not glad to hear the usual suspects keep trying to put their 'it wasn't done right' spin on it.

DB,
Boyd is making his current attempt at an end run around FDA regulations with his OSR 'not a chelator, its a nutritional supplement' product. He may yet end up on the less respectable list, or at least his duck and weave through the rules might get him there. (Already has in the opinion of a few, Kathleen/Neurodiversity.com has blogged a bit about this.)

Craig,
Some people claim it is common, others state it is totally unrelated. Didn't you get the impression from this article that they studied kids with some pretty nasty GI issues that weren't autistic? I assume you read the main post?

Posted by: Patrick | September 4, 2008 11:38 AM

Lots of kids have GI issues, it is not limited to autistic kids. I've known of kids in my son's special ed. preschool that had GI issues related to the motor control disabilities that landed them in that class (speech disorder caused by neurological motor control problems: often oral motor dyspraxia, some dysarthria and a fraction were autistic).

For my two sons, the disabled kid had very few GI problems, most of my issues were with the younger "normal" child. Which is why I find it amusing that so much stress is put on this issue. Okay, that was anecdote, but most of the "my kid with autism has GI problems" are also anecdotes.

Sometimes I think it is related to stress... the poor kids are stressed out over the parents hovering over them, taking them to multiple doctors, therapies and whatever.

By the way, the above is a wild guess. Though the fact remains that the MMR has been around since 1971, and has never contained thimerosal, and has been proven AGAIN to not be associated with autism.

Posted by: HCN | September 4, 2008 11:39 AM

Mary, it was an IgG. We've since put him on a GFCF diet, and his behaviour has improved remarkably. Makes a lot of sense that it would since his tummy was hurting and he couldn't tell us what was wrong. And thank you very very much for the link....good info there :)

Patrick, I did read the main post, but it didn't really go into great detail as to if these type of GI problems that are associated with food allergies are common in ASD kids. My point of curiousity is if anyone knows if Wheat and Milk allergies are a commonality among children on the spectrum.

Posted by: Craig Willoughby | September 4, 2008 12:22 PM

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.

I haven't yet read this entire post, and this is only tangentially related (if that, even) to the topic, but I have a question/observation. Whenever the issue of violent animal rights activists has been raised recently, people (including you, Orac) have gone out of their way to point out how difficult it has become and how many bureaucratic hoops they have to jump through to get approval for research with animals. But almost every week here I read of another instance of animal research of "dubious ethics" being done at a university - the monkey research funded by Phillip-Morris, the horrible autism research with monkeys at the U. of Pittsburgh, and now this study. This doesn't exactly lead me to believe that solid safeguards are in place to protect animal welfare. I really don't know what to think at this point.

Posted by: SC | September 4, 2008 12:52 PM

There is some anecdotal evidence that GFCF diets do help some autistics. It certainly makes sense that it would in the case of an autistic who has those allergies - as it would for anyone, autistic or not, who does.

As for the possible GI-Autism connection, it seems plausible to me that there could be a feedback cycle. GI issues can be caused by chronic stress, which is common for autistics, after all. In addition, those GI issues would certainly make it that much harder to deal with other issues, such as sensory sensitivities and the like. As for which comes first in those individuals, I can't say. I can say, though, that I think that "autism" will turn out to be a group of conditions, rather than a single condition. Indeed, genetic studies finding different genes associated with autism seems to confirm this notion.

Posted by: Paper Hand | September 4, 2008 12:53 PM

Craid said "My point of curiousity is if anyone knows if Wheat and Milk allergies are a commonality among children on the spectrum."

Again, I have to take issue with milk and gluten intolerance being common with just autistic kids. It is fairly common with other kids. My sister is lactose intolerant, so she had issues with milk from birth (she was two months premature, and has no disabilities other than being an annoying little sister, :p ). The same goes for celiac disease... of which I know a few people (none are disabled, including the young lady who has both celiac and is lactose intolerant, which was discovered through medical testing, oh, and her mom has has celiac, as does her grandfather).

While most have problems in their digestive system, I knew one fellow who got bumps all over his skin when he had gluten. A couple of years ago I went to lecture on Diana Wynne Jones (Howl's Moving Castle), and was told that at one time she became very ill and disabled. It turned out to be either a milk or wheat allergy, and once she stopped using on or the other it she was okay (I looked but I can't easily find an online reference).

This does not mean that I believe everyone has problems with gluten and milk. I am fine with both, as are my children (I just have to restrict fats due to a genetic tendency to high cholesterol).

Both have a strong genetic component, especially since there are who bunches of people on this planet who just cannot digest milk, and the same goes for wheat (specifically gluten, which is in lots of other grains). I did a check on PubMed for "gluten disability" and found very few papers. It does not seem to be a big issue.

Posted by: HCN | September 4, 2008 1:03 PM

Oops, I am sorry but I mistyped Craig's name.

Posted by: HCN | September 4, 2008 1:09 PM

" My point of curiosity is if anyone knows if Wheat and Milk allergies are a commonality among children on the spectrum."

Craig,

Ozzy was right on in his 9:59 post. Copy number variations (genes) that lead to autism (synaptic growth/functions in neurons) could have marked effects in other tissue-types as well (such as the intestinal epithelia and/or any number of those involved in the immune system). You can see these types of tissue-specific effects in individuals with other diseases, such as Downs syndrome or myelodysplastic syndromes, schizophrenia, as well as several others.

Posted by: RJ | September 4, 2008 1:19 PM

@Joseph: If you read both papers without knowing the author list, you would still conclude that Hornig et al. 2008 is a better study that is much more methodologically sound than Hornig et al. 2004.

Posted by: synapse | September 4, 2008 1:23 PM

Nice analysis on the study and antivax idiocy. Anyways, that correlation with GI problem and autism seems interesting, though kids do have GI problems once in a while, so... I also agree that being a pseudoscientist should endanger the scientific career.

Posted by: IBY | September 4, 2008 2:49 PM

Well, thanks to everyone that answered my posts. I do, however, have a final thought. Now, this is not to argue or anything, but doesn't this study only discredit the Autistic GI/MMR connection? It doesn't even discuss the MMR/Encepalopathy connection, which is a common anecdote among parents pointing to vaccines and autism.

Posted by: Craig Willoughby | September 4, 2008 3:05 PM

HCN,
I took no offense at the Typo. I knew who you meant :)

Posted by: Craig Willoughby | September 4, 2008 3:08 PM

Orac, you don't get enough props for your writing. You take what could be boring or confusing and make it downright punchy. Good content and good style! I love it!

Posted by: isles | September 4, 2008 3:50 PM

Now, this is not to argue or anything, but doesn't this study only discredit the Autistic GI/MMR connection? It doesn't even discuss the MMR/Encepalopathy connection, which is a common anecdote among parents pointing to vaccines and autism.

The problem is that speculations are easy -- I could come up with a dozen before my soup gets cold. Every time an antivaccinationist comes up with some screwball idea (histidine, anyone?) it can take years of hard work to bleach its bones.

Meanwhile, the University of Google is cranking out more cranks with more notions, each of which requires still more effort to specifically nail down.

Wouldn't it make more sense to simply compare rates among vaccinated and unvaccinated populations? That's a test that has enough power to put a pretty hard upper limit on any risk.

Posted by: D. C. Sessions | September 4, 2008 4:13 PM

"Wouldn't it make more sense to simply compare rates among vaccinated and unvaccinated populations? That's a test that has enough power to put a pretty hard upper limit on any risk."

Absolutely! I agree with you 100%. And honestly, it would put much of this debate to rest.

Posted by: Craig Willoughby | September 4, 2008 4:30 PM

"It doesn't even discuss the MMR/Encepalopathy connection, which is a common anecdote among parents pointing to vaccines and autism."

No, it doesn't. Studies are very specific as to what they examine, and the subsequent conclusions need to be directly related to the research conducted. No, encephalopathy was not examined, therefore, it would be merely speculation to comment on it (this is a fundamental error your friends at AoA do all the time...derive conclusions that were not based in the actual results of the research, rather try to relate x, y, and z with study variables a, b, and c). The Burbacher study is my favorite. Somehow, it was determined that vaccine-based mercury was in the primate brain...the study was never designed to make that conclusion, nor did the authors make the claim. In this study, the authors tell you exactly what was examined...and that's what you take from it...that it! No more. The discussion may involve conjecture, but that is to 1) help the scientific community to put the results in context and 2) to help create new hypothesis for more studies. They are not conclusions.

Posted by: RJ | September 4, 2008 4:38 PM

I think that one of the factors that made this study better than the Hornig (2004) study was the presence of more "adult supervision". I sincerely hope that Dr. Hornig will seize this opportunity to rehabilitate her scientific career.

Dr. Hornig's video of the mouse "grooming" through its cagemate's scalp (which was screened at several DAN! and DAN!-esque "conferences") should have been the end of her scientific career - not for pseudoscience but for neglect/abuse of experimental animals! That breed of mice is known for agressive behavior between adult males; they should never have been in the same cage together.

The fact that she or her lab staff filmed one mouse injuring another rather than immediately intervening is proof positive that there was a serious problem in her lab. She was extremely lucky that she managed to dodge and weave (and perhaps lie?) her way out of that without the investigators coming across the videotape she was showing to parents across the country.

I'd also like to draw a distinction between experiments that are abusive, cruel or neglectful (by design or by carelessness) - which are a violation of university, state and federal regulations - and experiments where the animals are treated properly, but their sacrifice is wasted by poor study design and/or poor interpretation of the data.

While it may not be a violation of regulations to experiment on animals in a way that produces no useful data (the Pittsburgh monkey experiment comes to mind - as does Dr. Hornig's original "Rain Mouse" experiment), it is an ethical lapse.

Experimental animals should be used in a way that minimizes their suffering and maximizes the information obtained. Repeatedly trying to "prove" that thimerosal causes autism is an unethical use of experimental animals, especially since there is no animal model of autism and no way to unambiguously determine that an animal is "autistic".

Finally, the idea that the acceptable performance of the O'Leary lab on this study somehow expunges their excremental performance in the past is laughable. If I have a student who fails nine examinations but scores a "C" on the tenth, should I go back and change the nine "F"'s to "C"'s?

I think that it's nice that the O'Leary lab has regained a satisfactory level of competence, but that does not change the fact that their previous work is known to be extremely substandard. David Kirby should give up hoping for a better past and concentrate on the present.

Posted by: Prometheus | September 4, 2008 4:57 PM

First of all, as for autism and gut problems. The famous "gut problems" of autism are mainly constipation, not diarrhea (that ruins the lives and the oriental carpets of rich, spoiled parents according to David Kirby). This same problem of constipation is found in other developmentally disabled kids. From what I understand, part of the problem is simple and doesn't require an exotic explanation of a genetic disorder involving the construction or chemistry of the guts of autistic kids. It's that it takes a certain amount of awareness, intelligence and communication skill to know when to go to the bathroom. If the kid isn't communicating or understanding normally he may end up constipated. Then there's the issue of the odd diets of autistic kids (including possible pica).

But on top of that the gut is very sensitive to stress and autistic kids have been shown to have more stress induced cortisol in their saliva, and they stay stressed longer than typical kids having had the same stressor.

People aren't researching the effect of stress on the guts of autistic children even though this is the obvious place to start (could explain constipation AND diarrhea, AND other health problems). They seem to want to go after the exotic stuff first, "Oh it's probably the 6GZP2 gene and the RCMP1 allele...." and "Oh, it's probably some heinous xenobiotic!!! I bet we can sue someone!!!"

As for Mady Hornig, if you knew what she and Ian Lipkin and whoever else was involved from their lab did. It would curl your hair. She was investigated by the NIH OLAW (office of laboratory animal welfare) because the abuse she and Lipkin carried out on the mice was something she shared at the IOM, to the director of the CDC and to many attendees at various mercury mom conferences. Then when they pinned her on what she did, she denied that what she had been saying to the IOM, CDC, etc was true.

So she either lied to the IOM, and the rest or she lied to the NIH OLAW investigators. When this fact was taken to the folks who oversee academic research misconduct, the question was first taken up with interest, then suddenly dropped.

It appeared (to me) that what had happened was that the national security folks with whom Ian Lipkin works didn't want anyone picking on dear Ian Lipkin so they told the academic misconduct people to drop it.

Ian Lipkin might have faced a paddling by the national security folks for working to undermine public trust in vaccines, when he, Lipkin, may be working on stuff like vaccines to fight against bioterrorism.... catch the irony there? I think Lipkin and Hornig's strong statements on behalf of vaccines are related to all of that.

What remains is that Lipkin and Hornig were tightly involved with some very gross animal abuse that was used to undermine public confidence in vaccines. And they have NOT owned up to this and they are still guilty of lying to the IOM (Lipkin, too because he didn't correct Hornig's public statements, AND he's her main-squeeze or love interest, they live together) OR they are guilty of lying to the NIH OLAW investigators.

Burns me up. And Columbia U had just been involved in a big ugly public stink over very blatant the abuse of primates right before Mady Hornig and Ian Lipkin were doing their violent, bloody mousey abuse.

Posted by: Ms. Clark | September 4, 2008 5:28 PM

"...becoming a pseudoscientist is one of the surest ways to kill a scientific career."


Hey, it hasn't bothered Boyd Haley (University of Kentucky chemistry professor and hero to the antifluoridation and antivax movements).

Note to self: make sure I have full Professorship and full tenure before coming out as a certified wingnut. That way I will be secure in my job, though utterly unfundable (see Peter Duesberg).

Of course, they can still can me for "gross moral turpitude", so have to be careful with those undergrads...

Posted by: Dr Aust | September 4, 2008 5:37 PM

Hi Craig, a vax vs. unvax study would be helpful if and only if you could get two populations that were comparable -- ceteris paribus -- only differing in vaccination status.

The problem is that people who do not vaccinate are often not comparable to vaccinating populations, therefore you can't generalize the outcomes very well. For example, if you have a religious colony who refuses to vaccinate, there is a strong chance that they do not match up with the general US population in other ways such as nutrition (might be vegan). Some non-vaccinators are self-selecting, and their demographics may skew upward in socioeconomic status (as was the case of the families involved in the San Diego/La Jolla measles outbreak), so they again cannot be generalized to the rest of the US population. And others who don't vaccinate may also bias their autism diagnoses because their cultures stigmatize mental/neurological disorders like autism, leading to underreporting of autism.

Posted by: Rogue Epidemiologist | September 4, 2008 5:58 PM

"Wouldn't it make more sense to simply compare rates among vaccinated and unvaccinated populations? That's a test that has enough power to put a pretty hard upper limit on any risk."

Absolutely! Except....the most recent study of vaccination uptake in the US indicates that only 0.3% of children are "completely unvaccinated". Even though there are about 82 million "children" (age 19 and under - you folks who are 19 and don't see yourselves as "children" can blame the Census Bureau) in the US, that works out to only 247,000 unvaccinated "children".

If you want to look specifically at the younger children - 9 and under - then you only have a total population of about 41 million and only 122,000 "unvaccinated".

If there is no difference between the prevalence of autism in the unvaccinated children, we could expect about 1 in 150 of them to have autism, which works out to 811.

To make a statistically meaningful study, we would have to have a large enough group of "unvaccinated" kids to ensure that any difference between them and the vaccinated kids would be real and not due to random chance. This means that we'd need to have at least 2,000 - 5,000 kids in each group (vaccinated and unvaccinated) to really settle the issue.

[Note: 2,000 subjects in each group works out to only about 15 - 16 "expected" autistic children in each group. This is about the lower end of getting any reliable data out of the study]

And to really settle the issue, each of these kids would have to be evaluated by someone trained in evaluating for autism and using the same tests and criteria.

At the least, this would mean finding 2,000 unvaccinated kids and matching them (sex, age, socio-economic group, race and location) with 2,000 vaccinated kids and doing full-blown autism workups on all 4,000. I'd be willing to do the study - I'll even run it through a real (non-Geier) IRB - but it's going to be very expensive. PayPal accepted.

Prometheus

Posted by: Prometheus | September 4, 2008 5:59 PM

There's a clip of Mady Hornig showing the famous killer mouse video at the UC Davis MIND Institute (after she had shown it to the IOM, Dr. Gerberding and to various conferences). I was there in the audience when she showed it. I saw the video of one mouse with a bloody spot on the top of it's head and another one seeming to bite at the other's head. She refers to them as if they are males and they were adult mice. Male SJL/J mice will attack and kill each other if kept together past a certain age. These mice were past that age and kept together probably because Dr. Hornig realized that the study had not shown any sort of severe problems at all in the mice given thimerosal (since then Berman at UC Davis replicated her study using 10 times as much thimerosal and found no effect). They punted. They cooked up this video of mice killing each other and and "over grooming themselves" and used it to show to the IOM saying that it proved that autism is caused by thimerosal because autistics are mindlessly violent and self-destructive.

The MIND Institute was a co-funder of the abusive research and if you go to the MIND institute website you can see a video of Mady Hornig at the conference I attended and see her introduce her "gory" mouse video. Gory was her word. The woman brought research ethnics to a low I had not seen before. Perhaps others have done worse, but she used this to label autistic people as mindlessly violent AND to undermine the confidence in vaccines that save lives! And so far, she's mostly gotten away with it!

Posted by: Ms. Clark | September 4, 2008 6:00 PM

http://www.youtube.com/watch?v=IyQ8X4BrgDc
I forgot to include the youtube video that shows the clip of Dr. Hornig at the MIND Institute.

Posted by: Ms. Clark | September 4, 2008 6:03 PM

Mady has been trying to develop and market an autistic mouse model for years. First with Borna Virus then with her thimeroSJL Mice. I wonder if there is any money to be made selling autistic mice.

Posted by: notmercury | September 4, 2008 7:35 PM

Concerning GF/CF diets for autistic children; there's already been a study.

http://www.ncbi.nlm.nih.gov/pubmed/16555138

As expected, parents exhibited confirmation bias and thought that their children were getting better however the study itself showed there was no difference between those on diets and not on diets.

Posted by: Orodriguez | September 4, 2008 8:17 PM

LOL. Prometheus, my money is on it's way! It's only a few dollars (all I can afford right now), but hey, if you're willing to do it, I'm gonna help ya out any way I can! ;)

Orodriguez, in the case of my son, a GFCF diet was the logical choice considering his food allergies. And yes, there was a considerable improvement in his behaviour. Again, I'm 100% certain that it was because he was no longer either constantly constipated or constantly with diarrhea. Additionally, before the diet, he had a serious problem with eating rocks (pica). Since the change in his diet, he no longer has that issue.

My post about the GFCF diet and Milk/Wheat allergies was mainly a curiousity on my part. And all of you have been wonderfully accomodating on that issue. Thanks again!

Posted by: Craig Willoughby | September 4, 2008 9:28 PM

What I don't understand is why don't they conduct a study on the brain before/after vaccination by way of MRI scans? Yes, a study between the vaccinated and unvaccinated would help also, but only if they were to consider the complete family history. Were the parents vaccinated? Chemical exposure during the pregancy? Too simple and very conclusive - which is why it has not yet been done. The do not want answers to these questions.

http://www.sciencedaily.com/releases/2006/08/060826171847.htm

Posted by: Dawn | September 5, 2008 7:41 AM

Orac,
What exactly is your field??? In my family we have a "history" of autism. My niece,nephew and two little brothers are all autistic.(or to be PC,they are children with autism)Now I can say with 100% certainty,that all 4 of them were "normal" prior to being vaccinated.Now did a vaccine or even a series of vaccines cause their autism,I don't know.But I can tell you this,all of these 4 children,recieved their vaccinations at different ages,one of my brothers seemed to be a typical child,b/c he was born almost 3 months early,he was not vaccinated with the MMR until he was 2.5 years old,and then bye-bye Michael,hello autistic drone.Here is the thing,mercury was taken out of thermometers b/c it is a poisen,so why would anyone turn around and inject their babies with it.(Thermosil is 49% mercury by weight--that is science and can not be denied). And if there is not a link, Why are thermosil-free vaccines available upon request?? As per your attack on Dr. Buttar,he is doing something pro active. Giving ppl something to believe in.And I have met a few kids that work with a DAN! Doctor and the results are amazing. As far as autistic adults go,show me 1 in 153 adults that are autistic,or that even display PDD-NOS like symptoms? You can't b/c this is an epidemic.Frankly,I don't care how much money these doctors are making,no body bitches that their cardiologist is driving a Jag,or that their OB/GYN is driving a Mercedes.No one goes to medical school so they can drive a Hundai.

Posted by: Gisella | September 5, 2008 9:10 AM

Stand back and make sure she doesn't bit her tongue.

Btw, little psycho girl, this is what thimersil is:

http://www.hitechpolymersindia.com/HT%20Sales/millboards.htm

Posted by: Gisella has drunk the kool aid | September 5, 2008 10:08 AM

Now I can say with 100% certainty,that all 4 of them were "normal" prior to being vaccinated.

Isn't that what the Cedillos said?

Regarding the other comment about vaccinated vs. unvaccinated, there are numerous confounds that would make such a study not very informative. It's quite likely unvaccinated children are inequivalent to vaccinated children in their genetics and lifestyle. Additionally, many siblings of autistic children are often unvaccinated, which is probably one of the reasons why Generation Rescue's survey found autism to be more common among unvaccinated children. If the confounds can be properly controlled for, I'm all for such a study. What I wouldn't like to see is conclusions being trumpeted based on a study that didn't have proper controls.

Posted by: Joseph | September 5, 2008 10:11 AM

As far as autistic adults go,show me 1 in 153 adults that are autistic,or that even display PDD-NOS like symptoms? You can't b/c this is an epidemic.

Canned response.

Posted by: Joseph | September 5, 2008 10:15 AM

"No one goes to medical school so they can drive a Hundai."

Well, I drove a Dodge Colt for 9 years. It would have been longer, except that the interior flooded after a bad storm inundated the lot where I'd parked it and it started smelling moldy all the time.

I blame the vaccines.

Posted by: Dangerous Bacon | September 5, 2008 10:52 AM

Gisela ranted ".Here is the thing,mercury was taken out of thermometers b/c it is a poisen,so why would anyone turn around and inject their babies with it.(Thermosil is 49% mercury by weight--that is science and can not be denied). And if there is not a link, Why are thermosil-free vaccines available upon request??"

This study was on the MMR. So why are you going off on thimerosal? The MMR has been around since 1971 and has never contained thimerosal. Not ever.

So make up your mind, is it the MMR or the thimerosal? Because those are two different things.

Oh, and please tell us what real sciences shows that the MMR is worse than rubella, mumps and measles (there is a 1 in 1000 chance of encephalitis with measles, with several of those actually dying).

Posted by: HCN | September 5, 2008 11:29 AM

Hmmm. Gisella says that there are several members of the family with ASD. To me the first thing that indicates might be a, oh, I don't know, genetic issue, rather than a vaccine issue. Y'know, like how they established a strong heredity link with Aspergers?

As to the mecury/poisons, well it hurts to repeat this yet again. ELEMENTAL MERCURY IS NOT THE SAME THING AS A MERCURY COMPOUND. Sodium explodes on contact with water. Chlorine gas can be used as a chemical weapon. Put them together, and you have a necessary component of our nutrition (table salt). And, just to head it off, your own body produces formaldehyde in greater quantites than you would receive i