Professor Stephen Bustin schools Andrew Wakefield, and I enjoy

I suppose that while I'm on another roll writing about the antivaccine movement I should just embrace it. I was going to start this post out again with one of my periodic laments about how blogging about the antivaccine movement has taken over and crowded out other topics that I like to write about. I realize it's become one of my go-to cliche beginnings, to the point where I sometimes feel lazy when I use it. It is, however, an honest sentiment, and I hide nothing with respect to my opinion of the antivaccine movement and how it endangers public health through the promotion of pseudoscience and quackery. However, I can't resist the topic of this post because it combines a discussion of a key figure in the antivaccine movement with a topic that I'm deeply familiar with. It also involves something that I first discussed way back in 2007, and, really, how often does a blogger get to "close the loop," so to speak, on a topic he first wrote about six years ago?

I'm talking about the hero of the antivaccine movement, particularly in the U.K., namely Andrew Wakefield. Of course, I didn't first write about Wakefield in 2007. My interest in his pseudoscience dates back to before that. However, it was in 2007 that I first read the masterful deconstruction of some of Andrew Wakefield's work by a world expert whose work I referenced frequently and impressed me greatly. It was done in the context of the Autism Omnibus, a huge court proceeding in which the Vaccine Court tried to deal with the claims of so many parents who claimed their children's autism was caused by vaccines by examining a few test cases, meant to be the best cases the plaintiffs could come up with, to see if they would fly. They didn't, and in one of the cases, Stephen Bustin was the reason why. Professor Bustin is a world expert in the technique known as the polymerase chain reaction (PCR). PCR is a technique whereby small sequences of DNA can be specifically amplified, so that very tiny amounts of DNA can be detected. Done properly, PCR is very, very sensitive and can be very, very specific. As you might expect, Andrew Wakefield did not do it correctly. Indeed, PCR seems to be a crank magnet. Indeed, just in January, Sin Han Lee was at it again abusing PCR to claim that the dreaded HPV DNA from Gardasil is killing young girls.

But back to Andrew Wakefield's use and abuse of PCR.

As Matt Carey points out, although Wakefield's infamous 1998 case series in The Lancet that was ultimately retracted due to his scientific misconduct is his most famous publication, it was actually a later publication that seemed to produce the most convincing evidence that there was a link between the MMR vaccine and autism, finding vaccine-derived measles in the intestinal mucosa of autistic children. The PCR tests to detect the measles virus DNA sequences were performed by John O’Leary in his laboratory in Dublin. As part of litigation over MMR in the U.K., Stephen Bustin was hired by vaccine manufacturers to review the methods in the O'Leary lab. Although these results were not initially revealed, Dr. Bustin testified about them in the Autism Omnibus proceedings, which I covered extensively in 2007, using Professor Bustin's testimony to limn the difference between real scientists and crank scientists. Now, he's followed up that testimony with a publication in which he describes exactly why there is no link between measles virus and autism. The entire paper is worth reading in its entirety, but I will, as is my wont, discuss key sections, but first let's summarize what Bustin found wrong with Wekefield's paper:

Absence of transparency: the key publication shows no data; hence an expert reader cannot evaluate the reliability of its conclusions

Unreliable techniques and protocols: analysis of the qPCR data was incorrect

Disregard for controls: obvious evidence of extensive contamination was disregarded

Lack of reproducibility: the data could not be duplicated by several independent investigators

His conclusion was:

The only conclusion possible is that the assays were detecting contaminating DNA. Since MeV is an RNA-only virus and never exists in DNA form, these data must be ignored and it it is my opinion that the authors should withdraw this publication from the peer-reviewed literature.

Let's take a look at Professor Bustin's analysis of the "fruit" of Wakefield and O'Leary's labor, a 2002 paper published in Molecular Pathology entitled Potential viral pathogenic mechanism for new variant inflammatory bowel disease. This is a paper that looked at biopsies of the terminal ileum of children with gut pathology and controls without such pathology, reporting that 75/91 children with histologically confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis were positive for measles virus in their intestinal tissue compared with five of 70 control patients. They even estimated the number of copies of measles virus to be between 1 and 300,000 copies per ng, concluding that "the data confirm an association between the presence of measles virus and gut pathology in children with developmental disorder."

There were, Bustin reports, many problems. First of all, are problems with the samples. For instance:

RNA was extracted from fresh frozen samples as well as formalin fixed, paraffin-embedded tissue (FFPE). However, there is no information on how the fresh samples were frozen, how long they had been stored,what percentage of patient and control samples were fresh frozen or FFPE and whether the same percentage was in each category. This is essential, since it is well established that FFPE treatment modifies and destroys RNA, or in Prof O’Leary’s own words “wax and fixation by itself breaks down RNA” [5]. Hence it was well known at that time that RNA-derived data obtained from FFPE samples must be analysed and interpreted with caution [12-14].

This is an obvious issue. If you are trying to use quantitative reverse transcriptase PCR (QRT-PCR) to quantify RNA transcripts, it can make a huge difference where the tissue came from and how it was handled. Fresh, flash-frozen tissue is best, and that's what I've always tried to use in my laboratory whenever possible. It's well known that RNA in tissue is pretty unstable and starts to degrade almost immediately as soon as it's removed from its blood supply. When harvesting tumors from animals, for instance, I routinely drop them in liquid nitrogen as fast as possible in order to minimize variability. For human tissue, it's usually not possible to do get the tissue frozen that fast, but it's still doable. It is possible to detect RNA transcripts from FFPE tissue. It's even possible to do cDNA microarray experiments using such specimens ("gene chip" experiments that measure thousands of genes at once) or even next generation sequencing (techniques I've mentioned before that allow the sequencing of every RNA, coding and noncoding) in the but the RNA will inevitably be degraded, and special techniques are needed to control for that. There's no evidence that O'Leary did any of that, and, of course, next generation sequencing techniques didn't exist in 2001, and cDNA microarray technology was in its infancy. So, while it's true that these days we have found that RNA can be a bit more robust that doesn't exonerate O'Leary in any way, particularly given the RNA technology that existed at the time.

Perhaps the most glaring issue I see, however, is this:

b. No information is provided with respect to quantification or quality assessment of the
extracted RNA; indeed there is no mention of RNA quality. This is vital information
needed to assess the validity of any quantitative or negative result [15].

"Vital" is putting it mildly. In any paper involving QRT-PCR, it's absolutely essential to verify the quality of the RNA. It makes me wonder how this paper was ever accepted (much like nearly all Wakefield MMR papers, actually). Whenever I review a paper involving PCR, I always look carefully at measures of the quality of the RNA. Heck, if you want to go old school, you could even insist on an old-fashioned formaldehyde-agarose gel showing that the 28S and 18S ribosomal bands are intact! (Yes, to the scientists out there, I know that this is incredibly old-fashioned.) Not to do anything, be it old-fashioned or using newer technologies, to assess the quality of the RNA is completely unacceptable. This is particularly true, given that Bustin points out how QRT-PCR results are summarized without any actual data as either "positive" or "negative."

Also damning is the observation by Bustin about the control transcripts examined. In most QRT-PCR, the level of the gene of interest, the gene that is expected to vary, is normalized to the level of a "housekeeping gene" (or, increasingly, multiple housekeeping genes) whose level does not vary much (preferably not at all) under the experimenta conditions being studied. Often a gene known as GAPDH is used. Sometimes β-actin is used. In this case, Bustin noted that the levels of GAPDH were much lower as detected in FFPE than in fresh frozen tissue, which as expected. However, levels of the measles F gene were identical.

Bustin writes:

Since any RNA present during formalin fixation would have been affected in an identical manner, the obvious implication of these results is that whilst the control RNA was indeed present prior to formalin fixation and so was degraded, the MeV target was not degraded and entered the sample after formalin fixation. Consequently, no MeV RNA can have been present in the tissue and the positive result must have been caused by a contaminant.

This also comes into play if there were large differences between the proportions of FFPE samples and fresh frozen specimens used in the control group versus the experimental group. of course, none of that matters if what is being detected is a contaminant. Supporting that what O'Leary detected was nothing more than contaminants, is another observation. In QRT-PCR, as I explained before, the RNA first has to be turned into DNA before amplification. This is the reverse transcriptase (RT) step, named after the enzyme used to do the step. In fact, we frequently use what we call "no RT controls" in which we do a PCR reaction on the sample without its having been subjected to reverse transcription because amplification of a signal under such conditions means that DNA is being amplified, not RNA.

Guess what happened when Professor Bustin looked at just that question:

Two tests accidentally omitted including the RT step before the PCR test. In the case of the control, the results are as expected: the assay works significantly less well (Figure 5A). This is because Taq polymerase is very inefficient at making DNA from RNA. In contrast, the four MeV samples tested give the same result, regardless, indicating that the test is detecting DNA (Figure 5B). Since MeV does not exist as DNA, the test is not detecting MeV but a DNA contaminant.

Here's a general hint about PCR: If you get the same results no matter what, chances are, you're dealing with a contamination problem. There are also many other reasons to suspect that what O'Leary was measuring was contamination, reasons that Bustin enumerated and I discussed in that post six years ago. For these reasons, Bustin correctly concludes that the results of Wakefield's 2002 paper should be completely discounted. It's true that Bustin's new analysis doesn't change anything in that Wakefield's results have been completely discredited for several years now.

Amusingly, Wakefield is in a pugnacious mood and has shown up on the antivaccine crank blog Age of Autism. It turns out that Bustin's criticism isn't the only flak he's been taking. A recent episode BBC's Newsnight looked at the current outbreak of measles in the U.K. due to low vaccine uptake rates. Wakefield was, of course, given considerable blame. Now Bustin piles on. And how does Wakefield respond? He blames the government for the measles outbreaks because it didn't believe his claims that vaccines can cause autism and wouldn't allow parents to use the single dose measles vaccine. The chutzpah boggles the mind!

But Wakefield's just getting warmed up. After working himself into a fine lather, he builds up to a climax worthy of his level of crankitude. Basically, like any good crank, he challenges his enemies to...a live public debate:

The more light that shone on this subject by way of informed, balanced debate, the better. I am offering to debate any serious challenger on MMR vaccine safety and the role of MMR in autism, live, in public, and televised.

What is it with cranks and live public debates? Of course, I know. Live public debates allow cranks to do the Gish gallop to their heart's content, flitting hither and thither and yon among cherry picked and/or bogus studies to their heart's contant, like a demented bee pollinating a field of pseudoscience.

Somehow, I bet that if Professor Bustin were to take Wakefield up on his offer, Wakefield would find a way to politely decline.

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Don't say looking at the 18S and 28S rRNA bands on a gel are old-school, we still reguarly do that in our lab! Actually, now that I think about it, most of what we do in our lab is pretty old-fahsioned...

By The Lab Mix (not verified) on 11 Apr 2013 #permalink

I love that second to last paragraph, That description of the Gish gallop should see wider use.

Somehow, I bet that if Professor Bustin were to take Wakefield up on his offer, Wakefield will find a way to politely decline.

Wakefield postured about debating Dr. Offit but couldn't get a response. He doesn't seem to realise that legitimate scientists (or journalists) aren't going to give cranks like him any credibility by debating. If anyone did actually take him up on a debate, I could only imagine the strings Wakefield would attach.

Does anyone know how the lawsuit is going? Weren't there deadlines of some sort last month?

By Science Mom (not verified) on 12 Apr 2013 #permalink

I've done plenty of formaldehyde/agarose gels, and am "old school" as much as anyone, but the Agilent Bioanalyzer does give the same QC data, with much less sample. If you have access to one, that is.

But if he gets product from no RT controls is sounds like like carry-over contamination.

By Nick Theodorakis (not verified) on 12 Apr 2013 #permalink

Andrew Wakefield needs to acknowledge that he's been debated in the proper venue: the scientific literature. He lost. Resoundly.

Prof. Bust in says that the Uhlmann paper should be retracted. I agree. I suspect it will be once the litigation against the BMJ is over. Note that the journal is published by BMJ.

"Of course, I know. Live public debates allow cranks to do the Gish gallop to their heart’s content,"

As in 100 power point slides including a "China plume" of mercury vapor and cremations to explain the reason why autism rates in California failed to decline after the phase down of thimerosal? Orac will recall the reference, but this is a comment about another piece of history: the debate between David Kirby and Arthur Allen. Mr. Kirby tried to argue that emissions from China coal plants were the reason why the prevalence want falling. That was 2007 as well. Even then they knew the primary pillar of the mercury hypothesis was failing.

By Matt Carey (not verified) on 12 Apr 2013 #permalink

Should read "prevalence wasn't falling", not want falling,

By Matt Carey (not verified) on 12 Apr 2013 #permalink

When I read Wakefield's whinging about the Wales measles epidemic and trying to shift blame to the UK government, I facepalmed so hard the neighbors thought there was an earthquake. Was going to include a little bit about it in my post today, but I got a bit too into the chickenpox story out of New York and didn't have time/space for it.

About debates: Barry Bickmore, a Utah geoscientist, has offered to debate "Lord" Monckton, a silver-tongued English climate-change denier; but the ground rules offered were (1) the debate takes place in the form of written communications on the internet; and (2) neutral fact-checking has to be in place.

Needless to say, "Lord" Monckton declined, because if he can't BS, he has no case whatsoever.

Bickmore is a political conservative, by the way.

By palindrom (not verified) on 12 Apr 2013 #permalink

The rain falls unceasingly here on the cliffs, all- even the dark waters swirling far below- is enshrouded in a misty pall. Surfaces of buildings, vehicles and roadways shine barely, liquidly reflecting the meager light, seeming to merge with each other into a softly gleaming wholeness which I might even consider beautiful if I were not feeling so morose... we will ourselves, also fade away into the mists, precisely like ...

Oh, sorry about that... it happens whenever I consider what alt med has wrought and it's raining.

Andy has an audience that will never listen to Prof Bustin or other reasonable critics: they are under his spell.
He constructed a hypothesis based upon the fears of parents and knows precisely what they believe and how it is necessary emotionally to them.

It isn't about logic or evidence: it is purely emotional. How can you argue with an article of faith- which depends upon what is unseen, as the Christians say, and un-proven? And based upon need?

Surveying woo-meisters and anti-vaxxers, I notice that their message depends upon frequent re-iteration and usually, an emotional delivery: what I hear often sounds like a minister proclaiming gospel, not scientific observations about the world. It is a foray into unreality where rules of practical life hold no sway. You can't talk sense to these people because they do not use it to guide their beliefs.

What I surmise, reading and listening, is that alt media is slowly creating an alternate reality:
the material that we rely upon- for news, information and evidence- is automatically dismissed as being compromised or reflecting vested interests of corporations and governments but these criticisms are never levied against their own. There seems to be no common ground.

We are talking about evidence that exists independently of ourselves and our needs- they are only interested in evidence that answers their needs. Alt med answers wishes and prayers. Its peddlars understand what those wishes and prayers are.

The only believers we can address are those who can, after self-examination, accept that they are followers because it serves as emotional insulation from the harshness of reality. I suspect that those few are not the well-known voices but the quieter lurkers on alt med sites and internet media who are not yet entirely convinced.

By Denice Walter (not verified) on 12 Apr 2013 #permalink

I'm with you Lab Mix. 18S and 28S rRNA bands on a gel are old-school, but that doesn't mean it's bad. If it worked then it works now.

@Dangerous Bacon - as God is my witness, I swear I thought turkey vultures could fly!

By Mephistopheles… (not verified) on 12 Apr 2013 #permalink

Does anyone know how the lawsuit is going? Weren’t there deadlines of some sort last month?

Three copies of all briefs filed to date have to be resubmitted by Monday.

I have worked and published with RNA from FFPE tissue starting in 2005. We made many probes to get the technique optimized. We used four genes to normalize RNA quantity. Anything that would have appeared equally between the samples would have been a major crisis ( fortunately nothing did, and we published the paper). Science has evolved and got better and easier but qRT-PCR still has the same principles. The Wakefield paper has extremely clumsy methods. what they see is a contamination and I am appalled that they got to publish it in the first place.

By the way, I still believe in ribosome subunits. They would have been so nice to have back then... They are a well tested and trusted method.

By Montserrat Blanco (not verified) on 12 Apr 2013 #permalink

Thanks Narad, I'd hoped you would know.

By Science Mom (not verified) on 12 Apr 2013 #permalink

I realize that this isn't a biochemistry methods discussion site, but yeah, I will occasionally do a formaldehyde agarose gel just as a quick and dirty screen before sending samples for DNA microarray analysis, which always includes the Agilent Bioanalyzer as a quality control step. The Bioanalyzer isn't doing anything all that different conceptually, but it does the runs and analyzes the results rapidly. What's important is that the RNA be strongly denatured, because otherwise its natural inclination to form double strand hairpins and tertiary structure fuzzes the results. Of course if you are working on mitochondrial RNA, you are looking for 16S and 12S rRNAs, and the 18S would be an indication of cytoplasmic rRNA contamination. By the way, Ambion (or whoever owns them now) made a very nice RNA loading dye containing formaldehyde, and a few tubes of it last a long time.

Slightly obscure, but distantly related to some of this discussion -- Methylmercuric hydroxide is the best RNA denaturing agent I have used, and works with an agarose slab gel. I doubt whether any manufacturer supplies it at biological grade nowadays, but it gave beautiful separation and distinct bands when we used it. We were always very careful with it due to its ability to cause the Minamata syndrome if ingested at high quantities.

And yes, the need to get RNA purified away from the enzymes that degrade it is always an issue. Going from living tissue to completely denatured samples (where the major target of denaturation is the enzyme population) within a few seconds is always the best approach. Flash freezing allows you to accomplish this if you are careful in the subsequent steps. We've had some success using the by-now accepted use of RNA-Later, but for tissue culture cells, there's nothing quite as good as dissolving the whole thing in RNA extraction buffer immediately.

Doing DNA analysis on paraffin sections has been used successfully, but the whole approach to embedding fixed tissue in paraffin ignores the problems associated with getting good RNA samples. For example, the process by which tissue is removed from a living organism (or autopsy sample) allows for time to pass, and with it, RNA degradation. Then the process of fixation at room temperature allows for more time to pass. Probably equally important is the issue of getting RNA back from the fixed, embedded sample. Finally, remember that formaldehyde fixation by itself results in a chemical denaturation of RNA, and undoing this is another problem. Trying to make cDNA from a formaldehyde-RNA product is questionable at best.

Bickmore is a political conservative, by the way.

Recent evidence to the contrary, political conservative =/= idiot.

I"m married to a conservative. They're kind of like cats; they want things to stay the way that they've always been, but that doesn't mean they're stupid.

Pain from a recent injury has diminished my natural enthusiasm, and with it my propensity for capslock, but M'OB at #12 gets a squeeee :D

I, too, am abjectly stunned that the Lancet fornicated the canine so thoroughly as to publish a paper with such dreadful research methods. How the heck did it ever pass peer review?? I mean... did they give it to geologists instead of medical researchers by mistake? Nothing against geologists, just the first field off the top of my head where the peer reviewers wouldn't know anything about medical research.

By Melissa G (not verified) on 12 Apr 2013 #permalink

Slightly off topic, but related to Wakefield---there's an episode of the English TV series Doc Martin in which the GP (formerly a vascular surgeon who had to give up surgery due to hemophobia) debates a school teacher on the MMR vaccine. Martin Clunes, who plays Doc Martin, rather nails it to the wall, not that it convinces the school teacher. And, most bizarrely, Doc Martin bears a resemblance to Wakefield, which is funny in itself. (http://query.nytimes.com/gst/fullpage.html?res=9C0CE1D91E30F930A35756C0…)

By Chris Hickie (not verified) on 12 Apr 2013 #permalink

I wish to have a public debate with Barack Obama and the Pope. It should be live and televised.

By Passing Thru (not verified) on 12 Apr 2013 #permalink

@Melissa G,

Aw, shucks! I hope not to cause you physical pain.

By Mephistopheles… (not verified) on 12 Apr 2013 #permalink

Haha, not to worry, it was my stupid trampoline accident that caused me pain!

By Melissa G (not verified) on 12 Apr 2013 #permalink

Palindrom: Bickmore is a political conservative, by the way.

Do you mean a political conservative as defined by the English, or an American political conservative? The two are radically different. If he is the latter, he might have some difficulty attending the debate, since fictional people don't travel well.

By Politicalguineapig (not verified) on 12 Apr 2013 #permalink

like a demented bee pollinating a field of pseudoscience

Beautiful.

And the fruits of Flowerf*cker Wankfield's pollination campaign are heavy and rotten, right here, within spitting distance.

While Wales is drawing press alarm with 600 cases in a population of 3 million, here on my doorstep we're up to 30 new cases in the last week.

In the same time period as the 600 Welsh cases we've racked up 200 confirmed and almost 200 suspected, and awaiting confirmation. In 2011 there were 18 cases. The population of the affected area? 200,000. These are grim stats indeed.

There's an airport right in the middle of the region too and, with the Easter holidays only just over, you can bet it was exported too.

Emergency clinics are making a dent by giving out MMR, but schools are back in term now, so the next few weeks are not going to be much fun.

I wish I could staple Andy's facehole shut. I've got enough to worry about without the very real fear of measles, and he's still bloody banging on about how he was set up. Stupid bell-end.

The recent research on autism shows the idea of stagnation in autism numbers has again surged forward with more than one per cent of children suffering this lifelong brain disorder.

Many people claim the mercury vaccines (mercury has delayed effects on brains - delays of months or years) cannot explain this problem fully.

But if you note the 2013 paper it stops looking at children who got their vaccine in 1999 so the numbers of autism sufferers is effectivlel nearly reporting what happened 15 years ago if we take this as the latest science on the subject.

I refer to the DeStefano, Price data on autism versus antigen numbers which arguably shows a more than fourfold link denied in the title by suggesting no link!

By John Fryer (not verified) on 12 Apr 2013 #permalink

@John Fryer - It's my understanding that an overwhelming number studies show there is no causal link between vaccines and autism. Could you please expand on why you believe there is such a link and discuss the evidence?

By Mephistopheles… (not verified) on 13 Apr 2013 #permalink

John Fryer,

I refer to the DeStefano, Price data on autism versus antigen numbers which arguably shows a more than fourfold link denied in the title by suggesting no link!

Please clarify where in that paper (PDF), or in the supplementary technical report (PDF) this link is shown.

If, as I suspect, you are referring to Exhibit 9.4.7 on page 194 of the technical report, it found an 8.73-fold increase in risk of regressive ASD when looking at prenatal exposure to thimerosal independently of post-natal exposure, and a 4.28-fold decrease in risk of regressive autism when looking at post-natal exposure independent of prenatal exposure to thimerosal. You could argue that this demonstrates a protective effect of thimerosal-containing vaccines in the children of women who were not exposed to thimerosal during pregnancy i.e. the vast majority of children. Or you could argue that these results are due to chance, as you would expect when looking at dozens of different combinations of thimerosal exposure and possible outcomes, a conclusion that fits with the scatter of positive and negative effects found in that technical report, 1 in 20 of which you would expect to be statistically significant at p<0.05 by definition.

By Krebiozen (not verified) on 13 Apr 2013 #permalink

But if you note the 2013 paper it stops looking at children who got their vaccine in 1999 so the numbers of autism sufferers is effectivlel nearly reporting what happened 15 years ago if we take this as the latest science on the subject.

Incorrect. The study groups included were born between 1 Jan 1994 and 31 Dec 1999. Vaccination was followed for two years which puts last vaccination at 31 December 2001.

By Science Mom (not verified) on 13 Apr 2013 #permalink

AJW showed up to b!tch and moan on Gary Null's idiotic self-serving** woo-fest yesterday ( see Progressive Radio Network/ shows/ Gary Null show- at about 43 minutes in).
He discusses his vindication because of recent studies ( Krigsman et al) and Walker-Smith's appeal. He is trying to sound as if he is soon to be exonerated.
And widely venerated I suppose.

He's probably making the rounds of woo-ville as a pre-emptive strike of sorts.

** as well as self-servicing

By Denice Walter (not verified) on 13 Apr 2013 #permalink

The fact that AJW is not in jail is a neverending source of misery to me, but perhaps less so than the misery of the victims of his epidemics.

By Melissa G (not verified) on 13 Apr 2013 #permalink

He discusses his vindication because of recent studies ( Krigsman et al) and Walker-Smith’s appeal. He is trying to sound as if he is soon to be exonerated.
And widely venerated I suppose.

When you are left co-opting others' work or accomplishments, you've lost. But hey, his sad rump of disciples buy it.

By Science Mom (not verified) on 13 Apr 2013 #permalink

@Denice Walter: what's even funnier is that Walker-Smith's appeal doesn't in any way exonerate him. If anything, it makes things worse for him.

By Julian Frost (not verified) on 13 Apr 2013 #permalink

[The government] didn’t believe [Wakefield's] claims that vaccines can cause autism and wouldn’t allow parents to use the single dose measles vaccine.

I am reminded of the scene in 1984 at the political rally, where the speaker in full tirade against Eurasia is slipped a note and in mid-sentence, without even breaking the syntax, switches to the new enemy Eastasia.

"Vaccines cause autism, which is why the government should give children vaccinations!"

And The Independent which is supposed to be a quality daily newspaper in the uk disgraces itself by running an article yesterday written by Andy himself. Most of the comments below the article are deeply scathing of both Andy and the paper.

http://www.independent.co.uk/life-style/health-and-families/health-news…

Ben Goldacre excellent on this on both his blog and twitter feed.

By Pixiedemon (not verified) on 13 Apr 2013 #permalink

The Independent [...] disgraces itself by running an article yesterday written by Andy himself

See how the establishment are silencing him!

By herr doktor bimler (not verified) on 13 Apr 2013 #permalink

Pixiedemon: How do you get the comments to show? I'm trying in both mozilla and Explorer, and I've got nothing yet.

By Politicalguineapig (not verified) on 13 Apr 2013 #permalink

If Wakefield's position is that the measles component of MMR infects the bowel, causing 'autistic enterocolitis', how would the single measles vaccine be any different? It's a live attenuated vaccine just like MMR, but with mumps and rubella components too. Even suspending my skepticism about his view of things, I don't see why he would believe this. I suspect he doesn't.

By Krebiozen (not verified) on 13 Apr 2013 #permalink

It is my opinion that the guy is simply a sociopath.

By Melissa G (not verified) on 13 Apr 2013 #permalink

I hit the "+" magnifier twice to allow me to read every word above. I particularly enjoyed Montserrat Blanco
and Bob G's notes. And Bacon's humor.

No matter what one's opinion of AW might be, it is The Lancet which truly did "Fornicate the canine" here. (Thank you, Melissa.)

By Jay Gordon, MD, FAAP (not verified) on 13 Apr 2013 #permalink

@Jay Gordon:
How exactly did the Lancet screw the pooch?

By Julian Frost (not verified) on 13 Apr 2013 #permalink

How exactly did the Lancet screw the pooch?
They trusted the author of a manuscript submitted to them not to be lying about his observations.

By herr doktor bimler (not verified) on 13 Apr 2013 #permalink

I don’t see why he would believe this. I suspect he doesn’t.

He's omitting the "transfer factor" part of the story.

I can see where it would be difficult for major media in Britain to avoid interviewing Wakefield now, given that his debunked 1998 study has come up in explanations of why so many older children in Wales never got vaccinated against measles.

What is unpardonable is for the Independent to give Wakefield prominent space for a "full statement", which stands alone on the linked page without refutation by those who know better.

I can't find any Ben Goldacre blog commentary on this matter - anyone got a link?

By Dangerous Bacon (not verified) on 13 Apr 2013 #permalink

Anyone else wondering if Dr Jay has been over to AOA for a discussion yet, WRT his statements* that suggest the vaccine/autism hypothesis is wrong?

Have you Jay? It would be so ethically and morally bankrupt to allow people to continue entertaining the notion, one you helped to propagate, if you know it's not correct.

Only an attention and publicity-seeking, disingenuous, fearmongering arsehole intent on continuing to profit from misery and desperation, wouldn't share such news. Isn't that right Jay?

Lucky you're above all that, and almost certainly crafting just such a statement.

http://scienceblogs.com/insolence/2013/04/09/the-i-told-you-so-fantasy-…

How do you get the comments to show? I’m trying in both mozilla and Explorer, and I’ve got nothing yet.

It appears to be a version of Disqus that is even more broken than usual. I can't see them either. It just keeps trying to load realtime.services.disqus.com/api/2/thread/1208178397?hose_[counter] over and over.

DB, I just googled Ben Goldacre's Twitter feed! He has been talking about it all day in quite an entertaining fashion, and WOW, I don't think I have EVER seen him so angry! Justifiably so!!! While you're at it, have a look at Dara O'Briain's Twitter feed, too! Independent, GET INTO THE SACK!

By Melissa G (not verified) on 13 Apr 2013 #permalink

Way to GO, lilady!!! You are ROCKIN' the comment thread, and outing the AoA affiliates so that innocent comment-readers can see who exactly is defending AJW. I'm thumbing you up!!!! :D

By Melissa G (not verified) on 13 Apr 2013 #permalink

@ Melissa G. I *manage* to do my share of chasing the AoA cranks off blogs. :-)

elburto: You misunderstood. I think that the Lancet gave a small study deserving a "letter to the editor" designation too much space without due diligence. I don't think that AW's article proved a vaccine/autism connection and the article's retraction certainly didn't disprove that connection.

And, by the way, if you're waiting for proof that flame retardant-soaked pajamas or giving six vaccines to a six-week-old increases the incidence of abnormal neurological development in genetically susceptible kids, you're going to see a lot of children harmed.

By Jay Gordon, MD, FAAP (not verified) on 13 Apr 2013 #permalink

you're going to see a lot of children harmed

Oh the fvcking irony of it all, you disgraceful little charlatan.

Last year babies were dying of pertussis in my country. Universities and schools were riddled with cases of mumps. And now? 600 cases of measles in Wales, country with a population of only 3.5 million. 400 cases in my region of England, confined (for now) to an area where only 200,000 people live. The infection rate is currently 30 a week.

I'm already seeing children harmed, you callous and deluded moron. All thanks to the likes of you and your sociopathic little marra, Wankfield. Harmed, maimed, killed, because you'd both rather profit from fear than actually live up to any professional oath you may have taken.

I'm in fear for my life over this measles epidemic. If I get it, then I'm dead. No ifs, no buts. But hey, as a damaged, broken, imperfect waste of DNA why should I be protected by some 'herd', when nature can take me, and people like me, out of the gene pool.

Oh, and your "flame-retardant soaked pyjamas" schtick is hilarious. I know that some of your countrymen have difficulty understanding that America=!The World, but trust me, in case you harbour similar delusions, it's true. Here, in my backward Third World country, children's nightwear has been mandated by law to be flame-retardant for decades. The material must meet flammability standards, whether that's achieved using the manufacturing materials used, or the treatment thereof.

Since 1988 the same is true for the settees and chairs they sit on, and the mattresses they sleep on. Same goes for curtains, wall-coverings, bed bases, pillows, cushions, upholstery, etc.

Labelling is mandatory and must be permanently attached to furniture. Furniture cannot be resold without those labels.

And yet, the rates of ASD detection do not correlate. Oh, and you didn't answer my question Dr Divvy, when do you intend to visit your little friends at AOA and TMR and ask them why they're so "obsessed" about vaccines? When are you going to give the same memo to Andy?

#53 Oh noes! Pajamas soaked in water! THE TOXINZ!!!

@Elburto

Whereabouts are you, and was it particularly effected by the MMR scare?

By Elihphile (not verified) on 14 Apr 2013 #permalink

@Elliphile - the North-East, slap. bang in the Darlington/Stockton/Middlesbrough infection zone. Wifelet works in Darlo, along with 3000 coworkers who are virtually all parents. To says she's stressed is an understatement.

I worked for the local NHS in my pre-cripple days and don't remember much objection to the MMR. In fact, many parents considered it a point of pride to ignore the "bollocks that soft southern dickhead [was] spouting". Not many fans of Andy, because the region's history of poverty meant that previous VPDs had burned some pretty rotten memories into the collective memory of people up here. Hell, my own brother-in-law has visual and motor impairments as a result of measles-encephalitis as a two year old (1968).

There's the airport though, and two more within an hour's drive (one an hour to the North, one an hour South). The current outbreak started at the end of the six weeks' holidays, with October week, Christmas and Easter since then, which sounds fairly insignificant until you realise that universities are a big draw to the region, especially for international and Home Counties students because of the low cost of living and dedication to the weekends!

Since employment up here is mostly in call centres and shops, and almost all have a constantly rotating stream of casual/part time student workers. So it's really easy to see how a disease like measles could roar through here. Both of the recent mumpidemics started at universities (Other Mrs elburto was a student when we met. Mumps was her first big gift to me, how cute!). All of the local institutions offer MMR at the beginning of the first semester each year.

We're socially and geographically very similar to Wales too. Same problems, same social spread, same industrial past and landscape, similar in that those industries have largely been replaced by educational institutional centres at former polys, call centres and retail parks. Maybe that's why both areas have been hit so hard?

I'm slightly surprised by the suggestion of university students as the predominant vector, not because I'm surprised at the concept of students spreading disease- they do- but because the overwhelming majority of those currently in higher education will have been born between the introduction of MMR and the Wakefield scare. I graduated last year and have had at least three, possibly four doses of measles vaccine, over the years: when I was a baby, not long after it was introduced, measles-rubella during the mid-nineties revaccination, when I was six, and another MMR booster during one of the "mumpademics," (amusing term btw) when I was sixteen.

That particular mumpademic was driven by those slightly older than me, who just missed out on the MMR when they were babies, most of whom will have left university by now.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5507a1.htm

By Elihphile (not verified) on 14 Apr 2013 #permalink

Dr Jay, you clearly do not understand the editorial process. That surprises me given the long list of peer reviewed papers pub med brought up for you. Due diligence" as you call it (a business term and we all know you're in the fear mongering business) was given to the 1998 paper. On the balance of the peer reviewers it should not have been published. Sadly, for the 700 Welsh children now infected with measles and a every autistic child subjected to sick purification rituals that your famous client likes to call biomed intervention, Richard Horton, then editor of the Lancet, fancied himself as some kind of maverick journalist and cast those opinions aside. He'd had his fingers burned by Wakefield before. Pity he hadn't learned from that experience.
While we're at it, would you like to elaborate on your Twitter comments that, and let's just get to the nub of it, the greatest danger to newborns is toddlers?

Since Jay Gordon dropped in to suggest that he (unlike so many of his fellow antivaxers) didn't fall for Wakefield's MMR-autism link, it's well to remember that until quite recently, Jay had on his website a fawning tribute to Wakefield (in which he said that seeing the Great One in person removed any lingering doubts Jay had about him (the tribute was quietly deleted after being on Jay's website for a number of years).

As for "flame retardant-soaked pajamas", it's good to see Jay branching out from his previous reminders of concerns we should be addressing but ignore due to our unfortunate focus on immunization:

"I think that the public health benefits to vaccinating are grossly overstated. I think that if we spent as much time telling people to breastfeed or to quit eating cheese and ice cream, we’d save more lives than we save with the polio vaccine."

http://scienceblogs.com/insolence/2008/07/19/dr-jay-gordon-pediatrician…

By Dangerous Bacon (not verified) on 14 Apr 2013 #permalink

My kids had their MMR shots.

If I were in Elburto's position, I might try to whine less and take more proactive steps to find a secondary antiviral strategy. Like maybe cut down on the carbs, maybe boost my blood vitamin D over 60 ng/ml in winter, make arrangements for IV sodium ascorbate with the U Kansas protocol. Perhaps consider flavonoids, hydroxycobalamin and Zn too.

In fact, I suspect if more of these were practiced in pediatrics, there would be less bitching by the vax uncertain parents about vax injuries.

@#61.

Geez, you're a prat.

@Shay: "Prat" doesn't do justice to prn's comment at 61, but it's a good start. Still, the comment's got plenty of good uses. I can think of three off the top of my head:

1. It's a perfect example of "blame the patient" mentality.

2. It's a great example of the hubris of ignorance. Without knowing any specifics of elburto's condition, prn knows precisely how to treat her ailments. It must be nice being all-knowing!

3. It's a wonderful way to show how jargon can be co-opted. I mean, god forbid we spell out "zinc" or explain what the U Kansas protocol is; such trifling matters might undermine a speaker's authority.

prn:

If I were in Elburto’s position, I might try to whine less and take more proactive steps to find a secondary antiviral strategy

I like to rely on facts, not opinion. Your suggestion assumes there are anti-virals for an RNA disease like measles. Can you please list those medications, and if there have been issues with resistance from the anti-virals.

The building up of resistance is why those with HIV are on triple anti-viral therapy, and the three drugs need to be switched around periodically.

Also, by looking it up, measles is a Group V RNA virus, but HIV is a Group VI RNA retrovirus, so this means that they may require different kinds of anti-virals. I am sure you know all about those, since you are the one giving out unsolicited medical advice.

Ahh prn, ever the chucklef*ck.

Your suggestions were hilarious, thank you. I especially like the suggestions that eliminating carbs, b12, and vit C loading, can override the things that put me at risk. You should be on the stage!

I suppose that next you'll be telling me I should add jogging to the regime too? Do you have a preferred method for the administration of the b12?

So many questions! I do appreciate the fact that the synaptic junkyard between your ears must have worked overtime to produce such a thoroughly sound protocol for someone you've never met. Oh hang on, maybe you're telepathetic in addition to your amazing people skills, and your gift for astonishingly smooth performances of craniorectal inversion.

Sir, I salute you!

@Elliphile - the last few years have seen numerous outbreaks of mumps at tertiary and higher ed. institutions. Even a quick'n'dirty google brings some up: https://www.google.com/search?q=UK%20mumps%20university%20outbreak&clie…

Shouldn't post after two hours of sleep, especially not in the throes of laughter.

Correction:

I especially like the suggestions that eliminating carbs, adding b12, and vit C loading can blah blah blah...

(the tribute was quietly deleted after being on Jay’s website for a number of years)

Not the only thing that he's sent down the memory hole. Tilden's site characterizes the January 7, 2011, interview as follows: "World Renowned Pediatrician, Dr. Jay Gordon, joins the Tilden ranks to further reiterate that there really is no link between autism and vaccinations in children."

That must have chapped some AoA ass after J.B. Handley had been touting Dr. Jay's "searing critique" of Frontline just eight months earlier.

I lost the thread here. What's Jay Gordon saying that's meant to be wrong. The only quote I've seen appears quite anodyne.

If he's changed his mind, isn't that a good thing?

By Passing Thru (not verified) on 14 Apr 2013 #permalink

#66 I was going to make a joke that he was diagnosing you remotely, but unfortunately, some people actually believe in that, so it's not really funny anymore.

Woo-sters spoil people's fun. Unlike Woosters, who are fun incarnate, provided they bring their butlers to Save the Day.

@ Chris

Re: prn opinion

Your suggestion assumes there are anti-virals for an RNA disease like measles.

Actually, prn's post is worse than this. He is suggesting that removing carbs, and loading on Vit C, D, etc are a "secondary antiviral strategy".
Without ever checking first if the patient (and elburto is very patient indeed, considering the fools one could meet on the internet) does have a deficit in said nutriments. Or if the doctors aren't already addressing any existing nutritional deficits.
I won't even go into the scarse evidence of a positive effect on the immune system of force-feeding these nutriments beyond the recommended daily uptakes. Actually, health agencies' recommended daily doses for vitamin D have been cut in half, last year, from 1000 to about 400 units. The need for vitamin D may have been overestimated.
I just know my family's regular doctors do check for deficits and prescribe supplements where apparently needed (iron for my sister's anemia, and so on). So my default position isn't to assume a doctor will miss a lack of vitamin C.

tl;dr: don't ask for, and don't give medical diagnosis over the internet.

By Heliantus (not verified) on 14 Apr 2013 #permalink

@ Jay Gordon

As you continue help "fornicate" infant and child vaccination rates in America, would you care to tell us how many cases of autism you've "prevented" from your new book? I guess you were so busy not vaccinating children you had to hire a ghostwriter to transcribe your notes from the toilet paper upon which you set down your first draft?

That the AAP allows dangerous, profit-seeking charlatans like you in their ranks is pathetic, as is the medical school that claims you as faculty. You truly have no shame, and you continue to remain too lazy to actually get off your duff and do real research instead of spouting the unvalidated nonsense you do.

Chris Hickie, MD, PhD, and proudly NOT FAAP (until the likes of you are expelled)

By Chris Hickie (not verified) on 15 Apr 2013 #permalink

Sorry to come to this discussion late, but I think the main reason the O’Leary/Wakefield/Uhlmann paper has not been retracted is that, for all of us who have the information, there’s not enough hours in the day to prepare the documents and submit them in coherent form. Medical journals don’t have great staffs sitting around just waiting to trawl through old papers, and certainly their publishers are not keen to fund such activities, despite the public importance.

This is now being done.

Indeed, there would be every reason to retract very substantial numbers of Wakefield papers. I could do the preparatory work for about four more, without any further research into them.

In one of my less charitable moments, I did think that I would be stirred into life each time that billious old sow Jenny Allan and her associates pipe up. This would produce a kind of ratchet effect, by which every time the cranks get abusive, another of Wakefield’s papers is retracted. They might learn from this. But perhaps not.

By Brian Deer (not verified) on 15 Apr 2013 #permalink

And, by the way, if you’re waiting for proof that flame retardant-soaked pajamas or giving six vaccines to a six-week-old increases the incidence of abnormal neurological development in genetically susceptible kids, you’re going to see a lot of children harmed.

Tell you what, jay, let's simplify things as much as possible:

What in your opinion is the single strongest, most compelling piece of evidence demonstrating exposure to flame retardant treated pajamas increases a child's risk of developing autism or otherwise harm them?

I mean, there is some actual reason why you believe we should expect to see all these children harmed--right?

Heliantus:

@ Chris

Re: prn opinion

Your suggestion assumes there are anti-virals for an RNA disease like measles.

Actually, prn’s post is worse than this.

One other way it is even worse, it not only is there an issue with anti-viral resistance, but the medications are dreadful on the body. One reason why some HIV positive folks convince themselves they are bad is because the side effects are debilitating.

Yeah, prn, should not being giving unsolicited medical advice to anyone.

@Mewens:

Wanker, then?

Shay a #77
Nail meet hammer

I have 50 quatloos that says prn is an engineer.

By Militant Agnostic (not verified) on 15 Apr 2013 #permalink

Oh now guys, don't insult wankers by calling Doctor prn one!

Tosspiece, bellend, gobsh¡te, numpty, waste of a wankstain, retained placenta, sh¡tehawk, ringpiece, etc. But wanking? That can be so calming. :-D

Hey hey, Dr prn - I need to know how to take the b12 for the best effects, whether you recommend exercise for me and how best to facilitate that, and how I can most efficiently reduce my carbs. Don't wanna catch measles so I NEED your wisdom.

I mean surely you didn't just walk in, spout off some personal ideology, and flounce out, did you? That would displease me, and everyone else who wants your virus-avoidal guidance.

shay@62, elburto@66,79 Mewens@64, Heliantus@71, 77
Medical advice? Really, from me, such a known, prejudged and despised minority here?

I constructively general suggested avenues of investigation for immune function and direct chemical attack on viral infections where someone complained that their life is so endangered that they feel the need to advocate what some call, "gunpoint medicine." I used myself as the reference body.

You four apparently have no inkling what I am talking about from the literature on vitamin D research of the last 15 years, or the observed actions of high dose, IV sodium ascorbate with iron, copper and/or cobalt cations present. I don't think your responses even count as pathological skepticism, more like mere truculent ignorance, superstition and empty rhetoric.

The University of Kansas protocol references an IRB approved administration method that includes very conservative screening for potential contraindications with IV ascorbate.

I also attempted to constructively suggest a way to engage worried but not dogmatic parents on their vaccine injury worries that they might find credible.

Chris@65
You might want to read this booklet,Injectable Vitamin C, just so you know the historical background. Levy's book is more complete. Basically, IV vitamin C is dramatic with fast amelioration of most acute viral diseases and oxidative poisons. Many bacterial infections can be resolved with it or in conjunction with light antibiotics. It is not classed as a standalone treatment for established AIDS.
It is not a standalone adjuvant for cancer, but it seems to be an excellent and highly useful adjunct, along with many other things, for stage IVb mCRC.

prn:

I constructively general suggested avenues of investigation for immune ....

You said, and it is a direct quote: " I might try to whine less and take more proactive steps to find a secondary antiviral strategy."

Which I interpreted as actual scientific antiviral medication. Which are not antibiotics, and are actually quite nasty drugs.

As for rest being "antiviral" strategy", there is only one response: citation needed.

Which means you need to provide actual scientific evidence that your unsolicited medical advice actually works to prevent measles, the most contagious virus known.

The University of Kansas "Integrative Medicine" clinic...aka quack medicine. Tells you something when 1)they can't bill for IV infusions of ascorbate and 2)they seem to charge the patient for the treatment, even though it's considered a "research protocol". The protocol belongs under Burzynski....until I see some peer-reviewed articles, prn, I'll call it quack medicine being done. At least they are honest that this is CAM and not covered by insurance and give the prices up front. I don't see anything that says this is research. Just a group of 2 doctors who are using the University as an umbrella for sCAM.

Fresh, flash-frozen tissue is best

Late to the game and hijacking on a minor point, but - if you haven't tried RNA Later, you should give it a go. It works magnificently to preserve RNA, and best of all - well, I've found that the less you ask a clinical site to do, the better they do it, and "plop the biopsy in this stuff (which is stable at room temperature, so you don't need anything on-site, just bring it to where you're doing the sampling), pop it in the refrigerator overnight, then freeze it and send it to us" is very doable by even a very busy site. And it's very resistant to minor breaches of protocol, like leaving the sample to sit on the counter for a while before putting it in the fridge, or letting it sit for a day in the fridge before freezing it. We've done RNA analysis as part of clinical trials with sites worldwide, and have gotten very good results with it.

By Roadstergal (not verified) on 15 Apr 2013 #permalink

Passing Thru: If he’s changed his mind, isn’t that a good thing?
Except that there's no real evidence that he has changed his mind. I think he's just pretending that he has to keep his medical license. Perhaps l'affaire Wakefield has forced him to be more cautious?

By Politicalguineapig (not verified) on 15 Apr 2013 #permalink

Poor despised prn. I have a slow, solitary tear rolling down my cheek. All for you brah.

Pray tell, how do I convince my local PCT to accept the "advice" of the Kansas Quack Shack? Pretty sure that asking for in-home IV vitamin C, because some wazzock on the internet told me to, will get me nothing but belly laughs and being hung up on.

Also, you haven't recommended a preferred administration route for the B12. Don't leave me hanging here. I'm also surprised you haven't made sure my B9 levels are ok. That's important to know before advising B12 supplementation.

Oh wait, my folate and B12 levels are fine, aren't they? The district nurse who visits to administer my prescription IM hydroxocobalamin takes care of that. B12 shots are a fad for the worried well, and only usually necessary for vegans or someone who cannot absorb B12 through the usual channels. Someone like me, with pernicious anaemia, due to having damaged parietal cells. Anyone else is just going to end up with B12-laced p¡ss.

Don't do carbs either, as I've mentioned before I have IBD and bread/pasta/rice/grains, even potatoes, cause flare-ups and GI bleeding that can only be suppressed with a course of prednisolone. Need to avoid that, of course, because my immune system is already medically suppressed in order to stop it causing any more damage.

So yeah, hope you can see how your "advice" provoked hilarity here. It's hard enough for my doctor and specialists to manage my conflicting conditions, so the fact that some jumped-up muppet thinks he has the answers is just amazing, really.

If I could have the MMR then I would, in a second, but I can't. The only loaded guns in the equation are fvcking lunatics like you, who minimise the positive effects of vaccination, and use their Google U degree to play doctor on the internet. You fuel the delusions and fantasies of every wooligan and ~Warrior Mommy~ who believes that they can prevent VPDs ~naturally~.

Colossal, humongous, fantastasising*, MMS-filled doucherocket.

But hey, thanks for the chance to get some much-needed catharsis. You win my 'Star-Spangled Spoogewipe Award'.

* credit goes to the lovely Edith Prickly.

@JGC -

What in your opinion is the single strongest, most compelling piece of evidence demonstrating exposure to flame retardant treated pajamas increases a child’s risk of developing autism or otherwise harm them?

I don't know about Dr. Jay, but pubmed has a lot of data on pdbe exposure and neurodevelopmental outcome. A lot of it involves prenatal exposure, but not all; i.e.,

In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study (Environ Health Perspect. 2013 Feb;121(2):257-62. doi: 10.1289)

Both prenatal and childhood PBDE exposures were associated with poorer attention, fine motor coordination, and cognition in the CHAMACOS cohort of school-age children. This study, the largest to date, contributes to growing evidence suggesting that PBDEs have adverse impacts on child neurobehavioral development.

There are a slew of others, but this is one of the most recent, and the one with the longest follow up time I could find with limited scanning. As for mechanisms, some are known to interfere with thyroid levels, which is a big no no from a neurodevelopmental standpoint. There is also evidence for oxidative stress or neurotoxic capacities.

@elburto -

And yet, the rates of ASD detection do not correlate.

What is the autism rate in your country?

Regarding the rates of exposure in your country, the clinical data tells us that very particular molecular structures are critical in determining toxicity; i.e,.

Para- and ortho-substitutions are key determinants of polybrominated diphenyl ether activity toward ryanodine receptors and neurotoxicity (Environ Health Perspect. 2011 Apr;119(4):519-26. doi: 10.1289/)

PBDEs possessing two ortho-bromine substituents and lacking at least one para-bromine substituent (e.g., BDE-49) activate RyR1 and RyR2 with greater efficacy than corresponding congeners with two para-bromine substitutions (e.g., BDE-47). Addition of a methoxy group in the free para position reduces the activity of parent PBDEs. The hydroxylated BDEs 6-OH-BDE-47 and 4´-OH-BDE-49 are biphasic RyR modulators. Pretreatment of HEK293 cells (derived from human embryonic kidney cells) expressing either RyR1 or RyR2 with BDE-49 (250 nM) sensitized Ca2+ flux triggered by RyR agonists, whereas BDE-47 (250 nM) had negligible activity. The divergent activity of BDE-49, BDE-47, and 6-OH-BDE-47 toward RyRs predicted neurotoxicity in cultures of cortical neurons.

According to the CDC, there are regional 'consumption' habits of specific pdbes; i.e.,

http://www.cdc.gov/exposurereport/pdf/brominated_flame_retardants_1.pdf

The PentaBDE formulation has been used primarily in the U.S. Of the 7,500 metric tonnes of technical PentaBDE produced in 2001, ~95% were consumed in North America (9)

The PBDEs originating from the PentaBDE mixture have been reported at much higher concentrations in residential dust from the U.S. than from Germany, England, and Australia (11) and in serum samples worldwide (12-17).

But I'm sure you already knew all of that.

It is, of course, possible that rates of PentaBDE mixtures are higher in your country. (?) The cdc document I linked to above includes rates from the US, maybe there are measurements for your country, and we could make an actual comparison instead of a back of the cocktail napkin comparison? Several areas have been studied.

While that doesn't prove exposure to flame retardants causes autism, but I'm certainly more comfortable with the idea of 'less' endocrine disruptors as opposed to 'more', but that might just be me. The longitudinal data like the CHAMACOS study above would seem to be salient, but again, that might just be me.

- pD

By passionlessDrone (not verified) on 15 Apr 2013 #permalink

@JGC -

What in your opinion is the single strongest, most compelling piece of evidence demonstrating exposure to flame retardant treated pajamas increases a child’s risk of developing autism or otherwise harm them?

I don't know about Dr. Jay, but pubmed has a lot of data on pdbe exposure and neurodevelopmental outcome. A lot of it involves prenatal exposure, but not all; i.e.,

In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study (Environ Health Perspect. 2013 Feb;121(2):257-62. doi: 10.1289)

Both prenatal and childhood PBDE exposures were associated with poorer attention, fine motor coordination, and cognition in the CHAMACOS cohort of school-age children. This study, the largest to date, contributes to growing evidence suggesting that PBDEs have adverse impacts on child neurobehavioral development.

There are a slew of others, but this is one of the most recent, and the one with the longest follow up time I could find with limited scanning. As for mechanisms, some are known to interfere with thyroid levels, which is a big no no from a neurodevelopmental standpoint. There is also evidence for oxidative stress or neurotoxic capacities.

@elburto -

And yet, the rates of ASD detection do not correlate.

What is the autism rate in your country?

Regarding the rates of exposure in your country, the clinical data tells us that very particular molecular structures are critical in determining toxicity; i.e,.

Para- and ortho-substitutions are key determinants of polybrominated diphenyl ether activity toward ryanodine receptors and neurotoxicity (Environ Health Perspect. 2011 Apr;119(4):519-26. doi: 10.1289/)

PBDEs possessing two ortho-bromine substituents and lacking at least one para-bromine substituent (e.g., BDE-49) activate RyR1 and RyR2 with greater efficacy than corresponding congeners with two para-bromine substitutions (e.g., BDE-47). Addition of a methoxy group in the free para position reduces the activity of parent PBDEs. The hydroxylated BDEs 6-OH-BDE-47 and 4´-OH-BDE-49 are biphasic RyR modulators. Pretreatment of HEK293 cells (derived from human embryonic kidney cells) expressing either RyR1 or RyR2 with BDE-49 (250 nM) sensitized Ca2+ flux triggered by RyR agonists, whereas BDE-47 (250 nM) had negligible activity. The divergent activity of BDE-49, BDE-47, and 6-OH-BDE-47 toward RyRs predicted neurotoxicity in cultures of cortical neurons.

According to the CDC, there are regional 'consumption' habits of specific pdbes; i.e.,

http://www.cdc.gov/exposurereport/pdf/brominated_flame_retardants_1.pdf

The PentaBDE formulation has been used primarily in the U.S. Of the 7,500 metric tonnes of technical PentaBDE produced in 2001, ~95% were consumed in North America (9)

The PBDEs originating from the PentaBDE mixture have been reported at much higher concentrations in residential dust from the U.S. than from Germany, England, and Australia (11) and in serum samples worldwide (12-17).

But I'm sure you already knew all of that.

It is, of course, possible that rates of PentaBDE mixtures are higher in your country. (?) The cdc document I linked to above includes rates from the US, maybe there are measurements for your country, and we could make an actual comparison instead of a back of the cocktail napkin comparison? Several areas have been studied.

While that doesn't prove exposure to flame retardants causes autism, but I'm certainly more comfortable with the idea of 'less' endocrine disruptors as opposed to 'more', but that might just be me. The longitudinal data like the CHAMACOS study above would seem to be salient, but again, that might just be me.

- pD

By passionlessDrone (not verified) on 15 Apr 2013 #permalink

#61: prn: "If I were in Elburto’s position, I might try to whine less..."

Wow.

That's plumbing new depths of obnoxiousness there.

LW, that is what prn will probably say to some of those injured in Boston today. "So what if you are missing a leg. Stop whining!"

#89 A lot of people are using it as an occasion to say "See, guns aren't a problem!" or that they are. Rather despicable either way.

Khani, I doubt elburto's disability has anything to do with guns.

In explanation, prn was being obnoxious to elburto by telling her to stop whining just because she needs herd immunity to protect herself from measles, yet there is a large outbreak near where she lives. And then prn piles on by suggesting all sorts of solutions without knowing anything about elburto's medical issues.

@prn

Playing the expert doesn't fly in real science. You've got to cite quality sources or show how you came to a conclusion, or it gets called out as nonsense. (At least you made an effort to provide a link in your second post; it's a shame it was just a collection of vanity-journal-published conspiracy theories. Truculent ignorance and superstition, indeed!) I get that some people make a living peddling their seeming expertise, but this blog's basically about eviscerating such nonsense.

Padding your nonsense with science-sounding words and condescending remarks – perhaps because your citations are either nonexistent or not up to the task of proving your assertions – only serves to underline that you a) aren't actually interested in helping others or discovering "the truth," and b) you have a vested interest in being the smartest guy in the room.

tl;dr: You can't make wild claims to skeptics and expect them to blindly worship your expertise.

Erm, forgot one thing: Also, don't be a douchebag. I think that about covers it.

Maybe a touch off the main topic here, but I can't help but think brominated flame retardants in, say, foam furniture stuffing are a touch unwise.

The stuff was never shown to be safe, but is suspected of being an endocrine disruptor. Causes autism? Probably not; whatever a bunch of child abusers latch onto as a cause for their kid's difficulties is the last place one should look. Causes anything? I'd rather not wait a few decades to find out.

PBDE sounds like something that should have limited application, rather than being used to make something fundamentally hazardous (the fast burning plastic/air/fabric contrivance aka foam filled furniture) become commonly accepted.

By Spectator (not verified) on 15 Apr 2013 #permalink

elburto

So yeah, hope you can see how your “advice” provoked hilarity here. It’s hard enough for my doctor and specialists to manage my conflicting conditions, so the fact that some jumped-up muppet thinks he has the answers is just amazing, really.

But your doctors are not reading the Journal of Small Preliminary Studies. The kind of studies that John Ioannidis has shown to be usually wrong.

Also, you haven’t recommended a preferred administration route for the B12.

In prn's case I would recommend a suppository inserted with a Bosch Demolition Hammer.

Colossal, humongous, fantastasising*, MMS-filled doucherocket.

Never get involved in land war in Asia and never get into an internet slagging match with a Brit :)

Chris

LW, that is what prn will probably say to some of those injured in Boston today. “So what if you are missing a leg. Stop whining!”

If they were missing both legs, prn would recommend shoe orthotics.

By Militant Agnostic (not verified) on 15 Apr 2013 #permalink

#91 Pshaw, Elburto has no disability beyond that of pure awesomeness too intense for peons like prn to understand.

And if you disagree she will set you on fire or possibly launch a box of crazed half-starved weasels at you. (You are planning a weasel-launcher for your doombuggy, right Elburto? They are all the rage this season, I'm told!)

Militant Agnostic:

In prn’s case I would recommend a suppository inserted with a Bosch Demolition Hammer.

:-)

Also, thank you for getting my analogy.

The unsolicited medical advice from prn was right up there with some dude suggesting that my son might become autistic with future vaccines after being told the same kid had seizures from a disease before the vaccine was available... as if the vaccine would do it if the disease had already not created issues 23 years ago!

#93 Hear, hear.

He picked the wrong person to try to bully, dammit.

Khani,

Yes! Hear! Hear!

The unsolicited medical advice from prn was right up there with some dude

Greg over in the other thread is trolling, i.e. he is a mendacious little sh1tweasel for the LOLs (and to see how long he can string people along with promises to start answering their questions Real Soon Now). Prn doesn't have that excuse.

By herr doktor bimler (not verified) on 15 Apr 2013 #permalink

Oooh, powertools and weasels could be combined to take down those who inspire my considerable wrath.

Hammerweasels.

Ferretsaws.

Motorstoats!

My ride is going to make the Batmobile look like a Citroen C5

Thanks@Militant Agnostic, LW, Mewens, Khani and Chris. I'm not the best target, primarily because I have the unfair advantage of a 25/8 schedule of continuous retort-fashioning. It's my primary export.

Perhaps I should attach a banner to the elburtobuggy for my inaugural wall of death drive. It'll read "FOR SCIENCE!" and have a bit.ly link to RI and a list of RIers along the bottom edge.

Going at 4mph in the park next door to my house, which is on top of a hill, should make said banner flutter quite nicely.

I don't often comment, prefering to lurk it seems. But Elburto - you absolutely rock. Militant Agnostic is right - don't get into an internet slagging war with a Brit , especially one thinking about Mustelidae-loaded vehicular weaponry ;)

There is some very, very funny stuff here. Elburto, never ever stop posting. You are why Brits are awesome in discussions like this; you know how to respond with *style*.

Regarding Jay's random comment about flame retardants (which he dropped into the thread and then abandoned for us to deal with it as if it were a flaming bag of poo)....

More research would great. More research is very rarely a bad thing, after all. But to draw a parallel with the vaccine-autism thing, removing the flame retardants isn't without risk. Those weren't put in there for no good reason, after all. They were put in there because kids were getting horrifically burned or even killed -- and dying of burns is quite possibly one of the absolute worst ways to go because of the excruciating and unrelenting pain until the person finally succumbs. And when it comes to furniture, it's worth remembering that upholstery is very often a factor in how quickly a house fire proliferates. House fires can be so overwhelming that no flame retardant would solve the problem, but even delaying the full conflagration for a minute could be the difference between life and death for the occupants of the house.

So which do we worry about more? The immediate and well known risk of death and horrific injury by fire, or a possible long-term risk of neurological injury from long-term exposure to products treated with these chemicals? Hard to say. An easy answer might be just to use wool whenever possible, since it's inherently flame resistant (more so than a lot of the synthetic flame retardants, actually), but it's also expensive and some people are allergic to it, so it can't be a universal solution.

Yes, it's worth studying the long-term safety of these materials. But it's not that clearcut whether to discontinue use of them in the meantime, since they have pretty compelling known benefits.

By Calli Arcale (not verified) on 16 Apr 2013 #permalink

Passionless drone, I can't seem to find the section in >i>In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study where they linked the serum PBDE levels they measured to flame-retardant treated pajama's the subjects were exposed to. Any idea where that might be?

That was the question I asked, after all--what evidence indicates exposure to flame retardant treated pajamas increases a child’s risk of developing autism or otherwise harm them.

Ok, I'll see if a Cremora-powered flamethrower can somehow be modified to accomodate weasels.

I can see the face on the Lowe's sales rep's face now. "You need six feet of PVC pipe for a WHAT?"

@JGC -

Aha So, if Dr. Jay had instead asked, more globally, if exposing our fetuses and infants to endocrine disruptors through a variety of exposure routes might be a factor in altered neurodevelopment, then you wouldn't have had a problem with it? How stupid is Dr. Jay, what with having only one concern regarding endocrine disruptors, exposure routes through infant clothing. Thank goodness you were clever enough to point out that our existing studies do not discriminate between pajama based exposure or other types of exposures, thus showing everyone how ridiculous Dr. Jay's concerns are. My assumption was that the study I linked to, like most in the area, included if exposure was from pajama tops, pajama bottoms, socks, or underoos, so thank you for pointing out to me that pajama level discrimination wasn't part of this study. What lazy researchers! Your earnestness in reiterating your hard hitting question with emphasis on pajamas goes a long way in demonstrating your critical thinking skills and interest in discussion as opposed to scoring Internet points over the hapless Dr. Jay.

@Calli Arcale -

http://seattletimes.com/html/nationworld/2018162658_flameretardant08.ht…

Food for thought.

- pD

By passionlessDrone (not verified) on 16 Apr 2013 #permalink

@ pD,

Once you explain to me how endocrine disruptors are responsible for a lower minicolumns size in the brain (source: https://www.ncbi.nlm.nih.gov/pubmed/16819561) with no other pathologies (in other words, no brain injured autism like Greg often tell us), I'll start believing that you have critical thinking skills, that JGC is out to score internet point and that Dr. Jay is hapless.

Alain

Obviously we need to Green Our Pajamas.

And we must praise pD for recognizing that preliminary research raising questions about neurotoxicity of flame retardant additives is _exactly_ like the flawed, unethical and debunked vaccine research performed by Wakefield and similar-minded cohorts. How foolish we were not to connect the dots!

pD may not realize this, but one cannot engage in "discussion" with Dr. Jay in this forum, seeing that his only interest in posting here is to try to score a quick point and then run away before the laughter hurts his feelings.

By Dangerous Bacon (not verified) on 16 Apr 2013 #permalink

Meanwhile, back at the ranch....

Andy shows up via video @ AoA as he has been banned on television. Freshly botox-ed with newly tinted brown hair, he explains how he is not the cause of the current measles outbreak. Debate anyone? For 16 minutes or so...

Isabella Thomas shows up in the comments, pointing to her own blog entry (linked), explaining the cause of all her woes,

Then Brian Deer shows up ( there) and cleans up.

Brother and sister sceptics,
although I may feel immune to the effects of alt med nonsense, I actually listened to AJW for 16+ minutes and it was not without pain I can assure you.
I honestly believe that I deserve thanks- or at least a free drink- for my efforts.

By Denice Walter (not verified) on 16 Apr 2013 #permalink

How stupid is Dr. Jay, what with having only one concern regarding endocrine disruptors, exposure routes through infant clothing trying to pick up a new shtick after that antivax stuff started looking green around the gills.

FTFY. (I've yet to figure out this list of recommended reading.)

A "pox on you" Denice for posting about Andy's new video :-)

http://www.ageofautism.com/2013/04/andrew-wakefield-responds-on-camera-…

Poor Andy; he looks like he has been defeated (he looks like ten bags of sh!t).

Scroll down to see the link to Isabella Thomas. She and Jackie Fletcher both show up on The Statesman blog and *someone* whupped their butts.

http://www.newstatesman.com/broadcast/2013/01/savile-denialism-and-groo…

Isabella Thomas shows up in the comments, pointing to her own blog entry (linked)

That, BTW, is one of the most crufted-up sites I've seen in a long while. I thought I was going to have to reboot the machine.

Dr. Jay, what with trying to pick up a new shtick after that antivax stuff started looking green around the gills.

A quick Google indicates that the Huffington Post crowd have been increasingly on the case of flame-retardant clothes for the last year, so you can't blame Dr Jay for trying to jump bandwagons.

By herr doktor bimler (not verified) on 16 Apr 2013 #permalink

#101 Will there be room for passengers? I sling a mean stoat.

#103 My snarking about water aside, half the time when I read stuff about "flame retardant" it's like reading the word "toxin."

It's totally undefined and there's a huge list of compounds and substances that they might, maybe, be talking about, or not, and it's utterly impossible to say anything meaningful or definite about them for that reason.

@ Narad: Here's one of the documents, that I linked to when I posted on the "New Statesman" blog:

SUPPLEMENT TO THE AMENDED DECLARATION
OF BRIAN DEER, REPLYING TO PLAINTIFF’S RESPONSE
TO DEFENDANTS’ ANTI-SLAPP MOTION TO DISMISS

Isabella Thomas' two children (child # 6 and Child # 7), were part of the Wakefield study. Thomas *claims* they were denied justice, because the case against the MMR manufacturer did not go forward.

http://briandeer.com/solved/slapp-declaration-supplement.pdf

Is it any wonder then, why Isabella Thomas and other parents whose children were part of Wakefield's study, did not testify on behalf of Wakefield during the GMC hearing?

IANAL...but I *suspect* that Wakefield and the parents did not want to leave themselves open to charges of perjury.

Why piss around with Western European mustelids when you could be firing wolverines?

By Militant Agnostic (not verified) on 16 Apr 2013 #permalink

I'm way behind on this thread, but I am picturing elburto with chainweasels for arms and Militant Agnostic with a wolverine-gun, and it makes me happy.

By Melissa G (not verified) on 16 Apr 2013 #permalink

HOW WOULD YOU LOAD The wolverine-gun???? Do you have a wolverine magazine, and do you carry extra ammo? Does the gun come with a vacuum attachment so you can load random wolverines you encounter in the wild and fire them at people??? Someone C.A.D. this!!!! :D :D :D

By Melissa G (not verified) on 16 Apr 2013 #permalink

HOW WOULD YOU LOAD The wolverine-gun????

Very carefully.

By Krebiozen (not verified) on 16 Apr 2013 #permalink

The wolverine gun has a teleportation-based self-loading mechanism. You pull the trigger, and it teleports a fresh wolverine in from Canada.

I'm sorry, but I think there are also wolverines in Norway, which is a bit closer to Great Britain. I'm not sure it has any effect on teleporting them, but perhaps they might be less sleepy, due to the smaller time-difference.

chainweasels for arms and Militant Agnostic with a wolverine-gun

...and a Polecatapult.

By herr doktor bimler (not verified) on 17 Apr 2013 #permalink

Why piss around with Western European mustelids when you could be firing wolverines?

Ahem.

@Narad

I was torn between images of firing a grumpy X-man (a dangerous proposition) and lobbing rebellious teens. Thank you for that pic.

Andy shows up via video @ AoA as he has been banned on television. Freshly botox-ed with newly tinted brown hair, he explains how he is not the cause of the current measles outbreak. Debate anyone? For 16 minutes or so…

Strike up an orchestra of the world's smallest violins for poor persecuted Andy. I have been thinking lately that we should start calling measles "Wakefield's Disease" in recognition of Andy's contributions to public health.

By Edith Prickly (not verified) on 17 Apr 2013 #permalink

@ Rebecca Fisher: Thanks for the correction (I was awake until the wee hours this morning trying to find a TV station that was broadcasting Margaret Thatcher's funeral). The Brits really know how to do up those ceremonies. "Wanking for coins"...just for you, Becky. :-)

@ Edith Prickly: "Wakefield Disease"...I'll vote for that!

Aha So, if Dr. Jay had instead asked, more globally, if exposing our fetuses and infants to endocrine disruptors through a variety of exposure routes might be a factor in altered neurodevelopment, then you wouldn’t have had a problem with it?

That would be a very different question, wouldn't it, which admitted the problem wasn't with pajamas but with overall PBDE exposure.

Just like asking more globally if exposure to formaldehyde from a variety of sources might be harmful to children rather than aserting "If we have to wait for proof that the formaldehyde children are exposed to due to routine vaccination is harmful you're going to see a lot of children harmed".

Since the approriate response to the latter is "Can exposure to formaldehyde be harmful? Sure, but if you're claiming the exposure a child receives as a result of routine immunization is harmful you'll need to provide evidence that's the case.." I don't see why that isn't an appropriate response to claims that flame-retardant treated pajama's, rather than overall PBDE exposure, are harmful.

elburto, I know you have a partner and all, but I have such an author-function crush on you now, after this thread... Thanks for the amusement.

By Interrobang (not verified) on 17 Apr 2013 #permalink

Thank you for that pic.

Red Dawn of course gave us the brilliant addition to "John has a long mustache" (from The Longest Day) of "the chair is against the wall."

@Lilady

In future, all funerals will be gauged on the "Thatcher" test.

"If you require members of the armed forces to protect your corpse from the general public, you don't deserve a state funeral."

By Rebecca Fisher (not verified) on 17 Apr 2013 #permalink