Last June Autism Speaks suddenly announced that their president, Mark Roithmayr, was leaving and being replaced by Liz Feld. (Mr. Roithmayr is now Chief Development Officer at the Leukemia & Lymphoma Society) There was little information about why Mr. Roithmayr left. The suddenness and the lack of information given out for the departure of an executive pointed to there being much more going on behind the scenes. Things going on which Autism Speaks would prefer did not become public.
In reading up on the group Focus Autism, I found a past webpage of emails from the founder, Barry Segal. One of those is copied below:
Barry Segal’s email to Bob Wright June 21, 2012
Bob,
Good work on Mark. On June 1st, I sent an email to you as well as Peter Bell that stated, “I feel Mark Roithmayr is not an asset to Autism Speaks.” In three weeks he was gone. You acted faster than Warren Buffet. When I wrote him that his top three men at JM knew nothing about roofing, it took him 90 days to replace them.
Here’s the problem. The gist of it is that the government was not going to do the necessary environmental and vaccine research due to political restrictions of public money, but that did not mean that private sector organizations, like Autism Speaks, had to follow those restrictions, per Kevin Barry.
It doesn’t matter whether you have Liz Feld, Donald Trump or Alex Rodriguez on the board. Unless Bernie relents and lets Autism Speaks go after the vaccine involvement, nothing will be gained.
Barry
It appears clear to me from this email that Mr. Roithmayr was pushed out. If we take the email above at face value, Barry Segal (a large donor to Autism Speaks) wrote to Bob Wright (Founder of Autism Speaks) and Peter Bell (executive vice president for Autism Speaks), pushing for Mr. Roitmayr’s ouster. Mr. Segal has elsewhere indicated that both Bob Wright and Peter Bell want more work done on vaccines and autism.
Given the next two paragraphs of the email, it appears that Mr. Segal’s complaint about Mr. Roithmayr was, indeed, his stance on vaccines:
It doesn’t matter whether you have Liz Feld, Donald Trump or Alex Rodriguez on the board. Unless Bernie relents and lets Autism Speaks go after the vaccine involvement, nothing will be gained.
I read this to say that while pushing Mr. Roithmayr out was a step forward (in Mr. Segal’s view), that Bernie (I assume Marcus, of the Marcus Autism Center and Autism Speaks) is still in the way of the wish to push Autism Speaks further into pursuing vaccines.
Kevin Barry, on the other hand, is a former president of Generation Rescue (an organization which especially then was very vocal about vaccine causation) who went to work as a consultant for Autism Speaks in 2006. While at Autism Speaks, Mr. Barry was apparently using others to post his messages to discussion boards. In this case, a call was sent out on the “Evidence of Harm” board for people to give input to Autism Speaks on the “epimdemic ‘debate’ “:
Hi Heidi, Confidential. I am not allowed to comment on the Boards. Would you post this to the EOH board as if you can upon it yourself? It is a page where people can comment on the epidemic “debate”. It would not hurt if Autism Speaks heard more feedback from EOH parents. Thanks, Kevin
In 2009 Autism Speaks lost Eric London (founder of NAAR and member of the Autism Speaks Scientific Affairs Committee) largely due to difference over vaccines. Earlier in 2009, Autism Speaks’ executive vice president of communications and awareness, Alison Tepper Singer, resigned prior to an IACC meeting in which a vote was to take place on vaccine related research. “Knowing she might cast a vote with which Autism Speaks might disagree, she resigned from Autism Speaks prior to the meeting.” In the press release following her departure, Ms. Singer wrote:
“However, for some time I have had concerns about Autism Speaks’ policy on vaccine research. Dozens of credible scientific studies have exonerated vaccines as a cause of autism. I believe we must devote limited funding to more promising areas of autism research.”
The same day, Autism Speaks published a press release, Autism Speaks Withdraws Support for Strategic Plan for Autism Research, Decries Unexpected Change in Final Approval Process. Yes, Autism Speaks pulled it’s support for the Strategic Plan because it didn’t include vaccines. The press release included this statement from Bob Wright:
“We are angered and disappointed by this last-minute deviation in the painstaking process of approving the Strategic Plan. Members of the autism community have worked tirelessly during the last two years to develop a plan that would set the stage for significant progress and discoveries for autism research over the next five years,” said Bob Wright, co-founder of Autism Speaks. “In a matter of minutes, the Federal Members of the IACC destroyed much of the good will that had been established during the course of this process. Because of this surprise tactic, we now have a plan that is tainted and cannot be supported by the autism community.”
It appears that even though Autism Speaks has not made such strong statements about vaccine causation in the past few years, the sentiments remain strong within the organization. Strong enough apparently to push the president out.
If it is true that Mr. Roithmayr was pushed out over vaccines, this would mean that the fears of many are validated: that Autism Speaks has a public face adhering to the science of today, while inside they still have a strong faction, including the founders and executives, pushing for a focus on vaccines. And that there is no room for someone with an opposing view.
—
By Matt Carey
Left Brain Right Brain 
Oh, this is deeply depressing if true. They are an imperfect organisation but they are doing so much good work.
They aren’t. They’re a hate group.
There is no getting around it, anymore. Autism Speaks, in spite of its public face, is still clinging to the possibility that somehow, some way, vaccines are implicated in the onset of autism. When push came to shove with the pugnacious Mr. Segal, Bob Wright caved and booted the president of Autism Speaks out the door.
When you allow powerful donors from outside your organization to dictate policy and the direction of an agency, you’ve forgotten your mission and your pledge to be a uniting force for research and for the promotion of good will toward autistic people. Shameful.
I would temper this somewhat. Barry Segal does not represent Autism Speaks and the comments can be seen as a bit self-promoting.
He commented on Facebook:
and
He seems confused. As I recall, he previously wrote that Bernie Marcus had a coworker with an autistic kid and that’s what got him into autism. Now he’s claiming Marcus himself has an autistic kid?
He’s always calling out sources by name, which is unprofessional and, I think, a bit suspect.
With that and his delusions of grandeur, I highly doubt he is endearing himself to anyone he is at odds with. What a weird, self-serving, incestuous mess they all are.
If Bob Wright wants access to his grandson, then he will do what he is told.
I really hate fear-mongering, irrationality, and the conglomerate nature of Autism Speaks. Their behaviors have long disturbed me, having been part of the online autistic community since 2004, mainly through WP, smaller fora such as my own, chats, etc. However, as a scientist I find it genuinely concerning that vaccine research has been mainly epidemiological in origin. This is not the equivalent of solid wetlab-based in vitro and in vivo work. I am neither in support of a link between vaccines and health risks nor against it. But as the research stands, I truly don’t feel we can draw solid conclusions from it. Epidemiology can completely cover small yet important case-by-case details, which is why population health risks are not solely investigated at this level. Yet that is the bulk of the research to date. Frankly, I don’t feel capable of supporting either faction because, to me, the evidence just isn’t in. To perform a few developmental studies using animal models complemented with in vitro work would not be inordinately expensive, ones which do more than simply measure the weight and the animal’s capacity to thrive but actually look at brain development and the development of other organ systems in detail. But no governmental body wishes to fund it, and private organizations seem to attract quacks for scientists who seem only capable of constructing poorly designed experiments which are of no more use than no research at all. Society has a question, and I have no issue with people attempting to answer it. But attempts should be realistic, not slapdash as they have been. Otherwise it amounts to making up one’s mind a priori and then finding the study that’ll give you the answer you want. And both sides are emotionally invested and exceptionally biased. I’ve known parents who seem as though they’re about to hack your head off with an ax if you suggest vaccines may not cause autism, and I’ve known plenty of high-functioning autistics who’ll engage in profane shouting matches to the point they’re cursing that you were ever born should you suggest vaccines may provide some health risk. Everybody’s just way too emotionally invested in this, which doesn’t generally make them good skeptics.
I believe that Matt Carey and other science bloggers have done an excellent job of analyzing the many research articles that have been published. I follow the research as it is published and I read how the safety of vaccines is monitored for any and all reports of untoward reactions:
http://www.cdc.gov/vaccinesafety/Vaccine_Monitoring/Index.html
Many of us who post on blogs do have children with developmental disabilities, including autism and our interest is not based on “emotions”.
Getting back on topic, thank you Mr. Carey for revealing has impacted the work of Autism Speaks. I am quite amazed that Mr. Segal has publicly revealed how he has worked behind the scenes to set the agenda and the direction for Autism Speaks.
Hi Emily Williams –
Very nicely stated and I, for one, agree with you wholeheartedly. Around here, that might not stand for much, but looking at your history of publications, I am inclined to stick with someone who appears to be actively publishing regarding autism.
Seeing by your CV on your site, you’ve published quite extensively on autism, and look to be part of Cassanova’s lab, or otherwise work quite closely with him. I would state for the record that I found Above genetics: lessons from cerebral development in autism to be particularly good.
Did you write a piece @ LBRB answering questions re: TMS a few years ago? I can’t find it anymore, but I thought it was someone from that lab.
– pD
So by your own argument, you should refrain from writing on the internet your opinions on science until you start publishing on autism?
Otherwise you have a very strange debate tactic here: everyone else’s opinion is discounted because they aren’t “actively publishing on autism” (sorry that I didn’t publish my imfar study, and my publication last year was only a response, by the way), but your opinion is valid.
So am I. That’s how I came to understand the current science.
I recently had a long discussion with one of the most respected people looking at environmental risk factors. I was asked “are there still groups who believe vaccines cause autism” after hearing that yes, indeed, there are, I was asked, “after all we’ve done?”
Too the vast majority of people publishing on autism, the vaccine hypothesis is failed. so if you prefer to listen to those who actively publish, you are welcome to do so.
Hi Sullivan –
Nested commenting problems, but I’ll try.
Otherwise you have a very strange debate tactic here: everyone else’s opinion is discounted because they aren’t “actively publishing on autism” (sorry that I didn’t publish my imfar study, and my publication last year was only a response, by the way), but your opinion is valid.
The person who had insults of ‘vapid’ and ‘clueless’ is an actual researcher who has a lot of non junk studies with her name on them, including some as PI.
Science Mom may publish under her real name, she seems clever enough but for now, all I saw was a bunch of insults being thrown at someone who actively participates in autism research; which we very rarely see in this forum. Instead of reasoned questioning, she was attacked and compared to an AOA scientist. To be frank, as something of an owner of this site, I was a bit surprised you didn’t find the way she was treated embarrassing.
In any case, it wasn’t a ‘debate tactic’, just me saying that I agreed with her.
I was asked “are there still groups who believe vaccines cause autism” after hearing that yes, indeed, there are, I was asked, “after all we’ve done?”
I think you mean, ‘the thimerosal’ and MMR cause autism. In all of your responses to me, I notice a distinct lack of actual analysis on our vaccine schedule and autism; instead just a bunch of incredulity that I don’t accept the equivalency of studying one shot at eighteen months with all of the shots during infancy, or one ingredient versus all ingredients. You know as well as I do how weak our analysis has been in this regard.
– pD
I will continue to dig through the literature, but thus far the dearth of animal studies– a gold standard for risk assessment– are not forthcoming. Which concerns me. I have no issue with the concept that there may be no connection. But I’m a scientific stickler and I haven’t seen the work that truly answers the question. Epidemiology has severe limitations when concerning disease-exposure relationships and that’s the bulk of the science performed. I commend the epidemiologists for getting on the ball, but lab-based science does not appear to have adequately taken up the mantle and put this question to rest (perhaps for reasons of unpopularity and difficulty getting funded). Again, I reiterate that I have no preference for either of the pro/con factions be correct/wrong; I simply want the science to be conclusive. I would hope that that is something both sides could agree on. Ultimately, certainty is more important than being right, isn’t it?
@Emily – the anti-vaccine groups believe, without a doubt, that vaccines are the cause of not only autism, but a host of other chronic health conditions as well (including obesity, if you can believe it). They don’t need evidence, because they BELIEVE with their entire psyche that this is true & no amount of evidence will persuade them that they are, in fact, wrong.
The only piece of evidence that they even begin to support is the creation of a true Double-Blind, Placebo controlled vaccine vs. no vaccine study – which, for a variety of ethical reasons (not to mention the logistical problems with selecting a few thousand or a few tens of thousands of babies for the study) this is not possible – oh, it could be done, but in conducting such a study, the researchers would be committing an ethical lapse not seen in medical science since the Tuskegee Study of the 1940’s.
What they are asking for is shear human experimentation, built around a premise that has been refuted by established science for well over two decades.
That’s the problem. They aren’t rational, logical or even very much sane.
Why would a primarily epidemiological nature of vaccine studies be so concerning? We are interested in populations after all. But what of the clinical studies that also fail to find any vaccine implication in autism development? As a scientist you should know that we can’t prove a negative but we can form a very solid consensus with the data available. The studies to date are also much more telling of a vaccine-autism association than “solid wetlab-based in vitro and in vivo work.”, pretentious and vapid. What studies do you propose that either haven’t been done or underway? I know of several that seek to elucidate the relationship of immune modulation and mitochondrial function with ASDs just to name a couple.
You have that completely wrong; epi studies are employed to identify risks at the population level. You are guilty of creating a false balance in the name of scepticism; demanding perfect evidence is not sceptical at all, just cynical.
Ah, what do you propose as an animal model? As for expense and ethics, how would you justify non-human primate research?
More pseudo-scepticism. Why don’t you present a vaccine-causes-autism study that you find compelling enough to question the body of literature which can find no causality? What studies that fail to find vaccines as an autism aetiology are “emotionally-invested and exceptionally biased”?
As an example, one of the key studies on the MMR question was Hornig, et al.. That was biological, not epidemiological.
Hi Science Mom –
I wouldn’t speak for Ms. Williams, but I have some ideas that seem to be related tangentially.
What studies do you propose that either haven’t been done or underway?
Well, I think we’d be better off understanding from a starting point, what does the innate immune response from our vaccine schedule look like? That is, what are the qualities and quantities of the cytokine and chemokine response invoked post vaccination?
The thing that bothers me the most about this discussion is that we don’t seem to have bothered even looking at this rather basic question; especially in the infant population. Maybe I’m wrong, maybe this data is available, and my pubmed foo is insufficiently designed to find it. Have these studies been done? Are they underway? Do you think we should try to investigate this type of thing?
This is a difficult task, the neonatal and infant immune response is unquestionably different than that of adults, and the autism population likely different even from that.
Once we understand what the immune response post vaccination looks like, we can pondering the right way to ask questions toward whether or not vaccination is capable of modifying the immune system in ways other than generation of immunological memory. We haven’t even gotten started.
You have that completely wrong; epi studies are employed to identify risks at the population level.
But we haven’t performed these studies! We have studied the MMR, and thimerosal regading autism. Within the past year, the FDA came out with a new list of warnings on statins, only after a metadata analysis of over 18000 users; I don’t think we have anything close to that regarding the process of vaccination. I may be wrong; could you point me towards any epi studies that studied vaccination as a process that we used to identify risks at a population level?
Ah, what do you propose as an animal model? As for expense and ethics, how would you justify non-human primate research?
The thing that bugged me the most about the Hewitson study wasn’t the results, but the scientifically flacid attacks against it. Sure, they didn’t have enough numbers for their findings; yes they had idiotic groupings of animals. Yes they had conflict of interest. But I would have expected the response to be , ‘here is a study of a few hundred primates that got the vaccine schedule vs placebo. We found no changes in behaviors. We observed no changes in immune profile. We observed no changes in microglial activation status. We observed no changes in the neuroimmune environment.’
We haven’t done that. I’d agree that the ethics are tough on primates; but if we can’t use rats (bad model), can’t use humans (they’re human), we have to use something.
Why don’t you present a vaccine-causes-autism study that you find compelling enough to question the body of literature which can find no causality?
The ‘body of literature’ is the MMR and thimerosal, which is like saying studying smoking one cigarette a day is the same as smoking a pack a day, or smoking tar free cigarettes tell us about smoking any cigarettes.
The neuroimmune findings in the autism realm aren’t going to go away. Similarly, the findings of immune involvement in brain development, in utero, and postnatally, aren’t going to go away either. The microglia are actively sculpting the neural network at the same time we start vaccinating, and as imprecise as our animal models are, they all tell us that when you initiate changes in the periphery, you also get changes in the CNS, including a differential morphology of microglia and an altered neuroimmune environment. Unfortunately, the autism population seems to show both a propensity towards a state of inflammation and evidence of an impairment in regulating the immune response. That isn’t psuedoscience, it is the consensus of dozens of studies.
Unfortunately, all of these findings postdate the expansion of our vaccine schedule by a decade or more. The fact that existing ‘vaccine-cause-autism’ studies are run by hacks is a fact, but a fact that does nothing to disturb the voluminous literature on the interconnected nature of the immune system and the CNS, or the dispassionate reality of developmental programming models that tell us that events during early life can be have life long effects where the same insult later in life results in only a transient change.
– pD
You are not seriously defending Hewitson’s studies? If so, perhaps you could remind yourself of the real complaints about the studies.
Consider first that she claimed one thing in her abstract for imfar and the opposite in her paper. She claims that it is normal for parts of the brains of monkeys to shrink as they age. She gives no error bars to her measurements so we can’t say anything about whether her results are meaningful. Given that more careful researchers than she have observed scatter in the measurements of amygala of these monkeys, I think her entire work on that is nonsense. This is ignoring the fact that out of original pool of monkeys, many were not included in the analysis.
Then there’s her behavior study. The areas of behavior she claims are different are not related to autism, yet people use her tiny study and meagre results and claim “vaccines cause autism in monkeys!”
As a scientist I was appalled by those studies. They were a waste of animals and money.
You do yourself little service defending such obvious poor science. You show selective memory for what the complaints about the study.
So, do you think that Hewitson failed to check for glial activation?
People wield the term “microglial activation” like some sort of light saber which can cut through any discussion, and yet the people who study it don’t link it to possible vaccine reaction.
But, by promoting the fear we end up with people trying “therapies” which range from obviously useless to potentially harmful. And we don’t know yet if there is a protective nature to the activation. You always leave that crucial point out.
Please, you are better than repeating this nonsense analogy.
The “vaccine research is tobacco science” argument is wonderful as a smear, but it actually says more about the person making the argument than the science.
Hi Sullivan –
You are not seriously defending Hewitson’s studies? If so, perhaps you could remind yourself of the real complaints about the studies.
Of course not, just saying that I am appalled that as far as studies on the schedule go, Hewitson is as good as we have. And it is awful. If my interpretation of the literature is incorrect, why not post a better study?
Try to imagine a corollary in the pharmaceutical landscape; a series of drugs with similar mechanisms of action, given to every infant in the country; and we haven’t even given more than 15 monkeys a series of all of them to see if we might be missing something. I think we should be striving for something a lot more robust than this. Do you? If you do, what are your ideas?
If you want to rip Hewitson more, I won’t argue with you. In fact, I’ll agree to every one of your points. That is because I wasn’t defending Hewitson, just relating how worrisome it was that her study is, apparently, the first to attempt studying the entire schedule.
– pD
Hi Sullivan –
Please, yothu are better than repeating this nonsense analogy.
It wasn’t about tobacco; it is about the false equivalency.
If we studied one group of people who drank four beers at noon, four glasses of wine after work, four shots with dinner, and a pint of moonshine before bed, versus another group who took for beers, four glasses of wine, and four shots, but didn’t get the moonshine, does this tell us about moonshine, or does it tell us about drinking?
If we took the same drinking group, and one group got filtered water in their liquor, does this tell us about water status, or drinking?
Replace with any chemical you would like.
– pD
– pD
Hi Sullivan –
So, do you think that Hewitson failed to check for glial activation?
Good question. I didn’t ever read Hewitson; I read enough criticism to know it wasn’t worth my time. In any case, if they did, what does it matter, their sample sizes were so small any findings would be meaningless. Or do the sample size problems only matter when you want to prove that the study was useless for your own purposes, but somehow they don’t matter if you like some of their findings?
I just downloaded it from that poland journal or whatever. Ctrl-F + “microglial” or “microglia” returns no hits. Maybe you’ve got another version where it states that they looked for this? I downloaded the amygdala paper. (?)
But, by promoting the fear we end up with people trying “therapies” which range from obviously useless to potentially harmful. And we don’t know yet if there is a protective nature to the activation. You always leave that crucial point out.
In the animal models of persistent microglial activation, there is nothing to be protective of; the chronic activation is nothing more than a remnant of an insult during pregnancy. It can be prevented with anti-inflammatory agents. There are many possible ways that microglia can achieve the state we seem to observe in autism; the literature tells us that one way is an immune insult during development. Close examination of those studies reveal that the only thing necessary is an unmitigated inflammatory response. While it is possible that what we observe in autism is a different entity all together, I’ve yet to see someone speculate, even wildly, on what that might be. Why should we throw out working models in favor of ephemeral ones, especially in a landscape where we already know much too little?
In any case, Science Mom wondered what kind of studies should be investigated; why is responding to this question, ‘promoting fear’?
@ Emily L. Williams:
You state in your first post…
“However, as a scientist I find it genuinely concerning that vaccine research has been mainly epidemiological in origin. This is not the equivalent of solid wetlab-based in vitro and in vivo work. I am neither in support of a link between vaccines and health risks nor against it. But as the research stands, I truly don’t feel we can draw solid conclusions from it.”
Really Emily? You seem to be clueless about epidemiology. Your statement about the supposed links between vaccines and autism/”health risks” appears to be what others, whose sole sources of *science* is based on what the *journalists* at Age of Autism, the NVIC, SaneVax and SafeMinds, claim about vaccines. You have the education and the capability to comprehend the many published science articles that disprove any reported links, yet still are a fence-sitter. Why?
Here…another example of your inability (or unwillingness), to “chose a side in the debate”:
“To perform a few developmental studies using animal models complemented with in vitro work would not be inordinately expensive, ones which do more than simply measure the weight and the animal’s capacity to thrive but actually look at brain development and the development of other organ systems in detail.”
Here, from Emily Willingham, a science blogger and a scientist, who posted about the *latest* mouse model study…in a long line of animal studies and autism:
http://www.forbes.com/sites/emilywillingham/2013/01/07/mouse-behavior-from-autism-studies-not-reproducible/
“Using the mouse condition to examine the human condition serves a purpose–we can’t very well, for example, purposely knock out a gene in a large group of humans, breed them, and then examine what they do in behavior testing. But mice also are not humans and not even that closely related to us. In a previous post of mine, in writing about best practices for authoring articles about autism, I noted:”
“If the study in question is about mice, never talk about how the results will lead to a therapy or a cure or write about the mice as though somehow, they are just tiny humans with tails. Mice have misled us before. They are only a way to model what might happen in a mammal sorta kinda related to us. They are not Us, otherwise we’d live in tiny, crowded places, having 10 children at once and ignoring them when they grow fur, and this autism thing wouldn’t be an issue.”
Emily,
“as a scientist I find it genuinely concerning that vaccine research has been mainly epidemiological in origin. This is not the equivalent of solid wetlab-based in vitro and in vivo work.”
The notion that vaccine research as been “mainly epidemiological in origin” is absurd, as is the idea that epidemiology is somehow less “solid” as a scientific discipline than more wet-lab based studies. Decades of vaccine research have involved the very “in vitro and in vivo work” you so desperately crave, resulting in the discovery of mechanisms by which vaccine adjuvants achieve their effect, the process that leads to development of antigen-specific antibodies in response to vaccination, and the key players that dictate how our immune cells generate “memory” after vaccination so that they can jump into action during a real infection. If vaccine safety is what you meant, well, I’d love to know what in vitro assays you had in mind. Seriously, you can dump just about anything into a culture of neuronal cells and they will show signs of stress or die. Does that have any relevance in vivo? No, not at all.
“To perform a few developmental studies using animal models complemented with in vitro work would not be inordinately expensive, ones which do more than simply measure the weight and the animal’s capacity to thrive but actually look at brain development and the development of other organ systems in detail.”
You say you’re a scientist, but from this statement I have to assume that you must not work with animals. I can’t remember of the last time that I (or any of my co-workers) “simply measured the weight and capacity to thrive” as the sole read-out for an in vivo experiment. And please, please point me to one – just one – in vitro or in vivo study published in a peer-reviewed journal that provides a scientific basis for bleach enemas, for lupron treatment to breakup testosterone-mercury complexes, or any of the crank ideas supported but the ‘other side’ (and featured at the AutismOne conference as ‘science’) that you seem to feel is so evenly balanced when it comes to science.
Sully, can you fix the “recent comment” widget? With the present sub-comment configuration it is very hard to see the most recent comments, or if a comment has been made on an article that has scrolled to another page.
If this is accurate, then it is extremely troubling. That Autism Speaks still wants to follow the vaccine causation line long after it has been completely discredited is bad enough. That the President was kicked out for not being willing to follow this line is even worse.
Qwerty is correct. There is a mountain of lab and clinical studies of vaccine safety. It’s surprising that Emily Willingham doesn’t know this. Possibly she is too new to the issue to have had the opportunity to research this.
GG, A little correction, the Emily who commented here and we are addressing isn’t Emily Willingham, it’s Emily Williams. I daresay that Dr. Emily Willingham is well-versed in autism research.
HI GG –
If this ‘mountain’ of ‘vaccine safety’ studies took autism into consideration, why did we perform a battery of retrospective studies on thimerosal and the MMR? Why bother? I mean, all the time we hear bellyaching about ‘wasted resources’ if someone talks about researching vaccines, and yet, people who supposedly (?) do know better, know about the ‘mountain’ of vaccine safety studies, went off and spent a bunch of time and dollars performing retrospective studies when the answers were already there. Why?
If query is correct, maybe he can provide a link to some animal studies that involve the vaccine schedule and measurements that include things like behavioral changes, or immune profiles?
If these studies are available, maybe someone could link to them, here, in this thread?
– pD
@pD
“If this ‘mountain’ of ‘vaccine safety’ studies took autism into consideration, why did we perform a battery of retrospective studies on thimerosal and the MMR? Why bother?
Because science is largely supported by government funds, and congress cares (as they should) about what their constituents think, regardless of whether it’s scientifically sound or not. Nevertheless, numerous retrospective studies were conducted and found no link between thimerosal and autism.
“If query is correct, maybe he can provide a link to some animal studies that involve the vaccine schedule and measurements that include things like behavioral changes, or immune profiles?”
This is a frequent request from anti-vaccine folks. As someone whose blog states that they are self-educating in multiple scientific disciplines, you should know by now that when someone makes an extraordinary claim in science (i.e. vaccines/thimerasol/too-many-too-soon/toxins cause autism), the burden of proof is on them. So, I ask you, in the face of negative epi data and no plausible mechanism by which vaccines may cause autism, what is the body of data that supports a causal role for vaccines in autism?
To be brief (for me), I’ve never seen a mouse study that tests the impact of the current pediatric vaccine schedule on neurodevelopment and immune system function. The reasons for this should be apparent: measures of mouse behavior have limited relevance to human autism, mice are fully inbred, and the vaccine schedule for human infants spans the first two years of life which would equivalent to the full lifespan of a mouse. These major issues, among many others, would make extrapolating from mouse to human very difficult in the context of autism. In essence, it all comes down to *exactly* what you’re trying to model, and currently there is not a satisfactory animal model for autism. C. elegans (the worm) has proved to be a fantastic model to understand neurodevelopment, but clearly it poses problems when you want to model complex social behavior.
I’m guessing that most of the data you would like to see is not in primary scientific publications, but rather was addressed as part of pre-clinical and phase I clinical studies. If you want to learn about the vaccine trial and safety testing, perhaps this Coursera class would be of interest (I can’t vouch for it…haven’t taken it):
https://www.coursera.org/course/vacctrials
In a more general sense, I would say that simply taking a college-level course in immunology should reveal that most of the theories that circulate on the anti-vaccine and biomed blogs don’t have a scientific leg to stand on.
Why did you redefine the mountain to not include the retrospective studies?
Have you so discounted them in your mind that they don’t count?
Hi querty –
Because science is largely supported by government funds, and congress cares (as they should) about what their constituents think, regardless of whether it’s scientifically sound or not.
Haha. So if Mark Blaxill keeps on bleating, the government will just keep on pressing out new thimerosal studies? Why not just whip out the Phase I studies from the manufacturers?
So, I ask you, in the face of negative epi data and no plausible mechanism by which vaccines may cause autism, what is the body of data that supports a causal role for vaccines in autism?
But the animal literature tells us again and again that there is a plausible mechanism; an immune challenge in early life.
I’ve been accused of too many links / whatever the insult is, so here are a few you might consider checking out.
Microglia in the developing brain: a potential target with lifetime effects
Enduring consequences of early-life infection on glial and neural cell genesis within cognitive regions of the brain
The first is a review from an NIH researcher; the findings tell us again and again that events in early life can shape the function of microglia, which eventually percolates up to shape behavior, and even neuroanatomy.
Look, if we talk about things that happen in utero this is a completely uncontroversial statement. What you will not find in the literature is anything that tells us that there is some magical portal at the exit of the womb that suddenly confers protection from future insults.
These major issues, among many others, would make extrapolating from mouse to human very difficult in the context of autism.
OK. Animal models are super hard for autism. In the meantime, they are the best thing that we have for prospective studies. I think that the dearth of epidemiological evidence for the process of vaccination presented in this thread speaks for itself regarding how much we have available for humans. So what to do? Throw up our hands and just decide we’ve up and done well enough?
I’m guessing that most of the data you would like to see is not in primary scientific publications, but rather was addressed as part of pre-clinical and phase I clinical studies.
Indeed.
Forget about autism though. What about something as simple as understanding the innate immune response from vaccination, my first, and easiest, recommendation for ‘what we should be studying’. Can you show me that in mice? Or monkeys? Or people? I don’t think you can.
Here is a paper published in 2010.
Ontogeny of Toll-Like Receptor Mediated Cytokine Responses of Human Blood Mononuclear Cells
Our data contradict the notion of a linear progression from an ‘immature’ neonatal to a ‘mature’ adult pattern, but instead indicate the existence of qualitative and quantitative age-specific changes in innate immune reactivity in response to TLR stimulation.
This study was funded, in part, by NIH grants. It used three tiemframes, cord blood, one year, and two year, and found distinct, time dependent difference in innate immune response, in vitro.
Here, we applied the most comprehensive analysis focused on the innate immune response following TLR stimulation over the first 2 years of life in the largest such longitudinal cohort studied to-date (35 subjects).
Thirty five kids, checked in a test tube, at birth, and again after the majority of the vaccine schedule is administered; and it is described as ‘the largest longitudinal cohort to date’.
If we had in vivo measurements of innate immune response following vaccination, wouldn’t our studies dwarf this? Wouldn’t they be of interest to the researchers, or to the NIH, who funded the study? Why on Earth would Corbett spend two years collecting data, if this information was available in ‘pre-clinical’ trials? Why would the NIH fund this study if the data was part of a MERCK trial? (or many trials?) And, a trial of say, innate immune response to DTaP would have much more precise timelines, two, four and six months, instead of a year and two years. Why not incorporate this data into their paper?
Here is a study from 2005.
Effect of influenza vaccine on markers of inflammation and lipid profile
Despite wide use of the influenza vaccine, relatively little is known about its effect on the measurement of inflammatory markers.
This was published in Vaccine. Now ponder this, if this data was available in pre-clinical trials, as you suggest, why would Vaccine peer reviewers and editors accept this opening statement? Why would the researchers waste their time, if this data was already available?
The simplest explanation, to me, is that there is no such data is available; we have a bazillion hits on the ability to generate antibodies; the desired effect of vaccination, but next to nothing on generation of the innate immune response. It has not been until very recently that we have discovered that the innate immune system is interconnected with the CNS. It was always thought to be unimportant.
Perhaps you have another, better explanation. (?)
In a more general sense, I would say that simply taking a college-level course in immunology should reveal that most of the theories that circulate on the anti-vaccine and biomed blogs don’t have a scientific leg to stand on.
I agree with you. I’m not basing my arguments on any of those theories.
– pD
Here we go in the same old circle. “You haven’t made a good argument that microglial activation is related to vaccines” followed by the response “you don’t think microbial activation is important. Here’s a bunch of studies (which we’ve already seen) which say it is”
The work of Pardo’s group is potentially one of the most important findings of the past decade. It is also one of the most misinterpreted.
You do a lot of hand waiving. That’s fine but you present it as far more solid reasoning than it is.
Here’s an example of why people bring up the topic of links. You are using the “he with the most links wins” argument. If you want a bunch of links on vaccination, go read plot kin/offfit. I think they have 20,000 in their, what, 1600 page book.
Have you admitted that neither thimerosal nor MMR increase the risk of autism?
Have you dismissed the follow on study to Thompson (2007) which says that using a delayed and/or lesser vaccine schedule does not increase the risk of autism?
@pD
“Haha. So if Mark Blaxill keeps on bleating, the government will just keep on pressing out new thimerosal studies?”
In a sense, yes. Did you see the recent congressional hearing?
“But the animal literature tells us again and again that there is a plausible mechanism; an immune challenge in early life”
Wrong, and I fail to see how any of your links provide compelling evidence for a causal relationship between vaccines and autism. What some studies have hinted at (including the ones you provide links to!), is that perinatal systemic infections are bad (shocker, I know) and that they might be associated an increased risk of autism (or at least behavioral issues in mice). All the more reason for mothers to be up to date on vaccinations before getting pregnant.
“What about something as simple as understanding the innate immune response from vaccination, my first, and easiest, recommendation for ‘what we should be studying’. Can you show me that in mice? Or monkeys? Or people? I don’t think you can.”
Again, wrong. So wrong that it’s actually painful. There are many studies of innate immunity to vaccines in mice and monkeys and humans (albeit less so for the latter two, for obvious reasons). Indeed there are entire laboratories both in the US and abroad that do nothing but study this exact topic in great detail, down the specific molecular mechanisms. There’s really no need to cite specific papers here, since the field is bigger than any one single paper. For starters, check out the nobel prize in Physiology/Medicine awarded in 2011 to Jules Hoffmann, Ralph Steinman and Bruce Beutler. Read about their work on innate immunity and the hundreds of papers that followed (hell, just read the papers coming out of ONE lab….Shizou Akira), all of which have helped solidify what we now know about innate immunity to infections and vaccinations. We also know some of the the molecular mechanism by which alum, the only vaccine adjuvant approved for use in humans, enhances immunity to vaccine antigen. So, tell me again how there are no studies of innate immunity to vaccines?
“Now ponder this, if this data was available in pre-clinical trials, as you suggest, why would Vaccine peer reviewers and editors accept this opening statement? Why would the researchers waste their time, if this data was already available?
Because it’s common to open the intro of a paper or grant with a broad and vague statement like that. Reviewers will rarely ask you to temper these statements, in part because one can argue about what it means to say we “know relatively little” about something. Relative to what?
“If we had in vivo measurements of innate immune response following vaccination….”.
I think what you’re getting at here is your desire to see a day when a whole panel of immune ‘markers’ are routinely used in clinical settings to monitor the health of an individual’s immune system. Yep, that would be nice. Outside of a crude CBC panel, nothing like this exists yet, although there are people actively pursing biomarkers of disease or more complex ‘systems biology’ approaches to integrating and understanding how many immune factors work together during disease. In mice, this sort of comprehensive analysis is easier, only because we can dismantle the entire mouse organ by organ, tissue by tissue, cell by cell and analyze hundreds of parameters (actually, as I sit here typing this comment, I’m analyzing immune responses in cells I recovered from the brains of infected mice….one cell at a time, for millions of cells). We just can’t put the mouse back together afterwards.
Hi qwerty –
Did you see the recent congressional hearing?
I predict a grand total of zero vaccine studies will become of the latest hearing.
What some studies have hinted at (including the ones you provide links to!), is that perinatal systemic infections are bad (shocker, I know) and that they might be associated an increased risk of autism (or at least behavioral issues in mice).
The study I referenced used a postnatal day 5 e-coli challenge, but others have observed effects up to postnatal day 14. It isn’t that ‘perinatal systemic infections are bad’, it is that during critical developmental timeframes, their effect can be persistent in the brain.. The kicker is that the physiological effect observed, chronic activation of microglia in treatment animals, bears strong similarity to observations of the microglia in the autism population. It isn’t all about how many friends a rat tries to make; it is also about the neuroimmune environment, which can be persistently altered through early life immune challenges.
Indeed there are entire laboratories both in the US and abroad that do nothing but study this exact topic in great detail, down the specific molecular mechanisms.
Great, then show me something similar to the influenza paper I showed you with infants. The population we are vaccinating are infants. They don’t get one vaccine at a time, or one specific TLR agonist at a time. They get several, all at once, and as you reference, including alum.
For starters, check out the nobel prize in Physiology/Medicine awarded in 2011 to Jules Hoffmann, Ralph Steinman and Bruce Beutler.
If I remember correctly, there was something of a minor dustup regarding who, exactly ‘deserved’ the Nobel, with Ransohoff thinking maybe he got to the TLR discovery first.
But those are about the nuts and bolts; sure we know that LPS triggers TLR4 and MyD88 is involved. Great. Sure we know that POLY:IC triggers TLR3. Wonderful. Yes, we know that *somehow* alum interacts with the inflammasomme, and that *somehow* this participates in the generation of an innate immune response with corresponding, eventual, generation of immunological memory. My cconcerns are not exclusionary of that data set, but rather, depend on them, and indeed, the nascent nature of the interactions between the innate immune system and several cognitive disorders.
Unfortunately, understanding all of the individual pieces (and more) does not necessarily tell us about what happens when we do all of those things, all at once, in an infant population.
For example, triggering multiple TLRs simultaneously can result in a non-linear increase in cytokine production; (i.e., TLR ligands induce synergistic interferon-ß and interferon-?1 gene expression in human monocyte-derived dendritic cells, or Synergy Between Viral and Bacterial Toll-Like Receptors Leads to Amplification of Inflammatory Responses and Preterm Labor in the Mouse. (or many others)
Similarly, as Corbett observed, the infant immune response is qualitatively different than that of adults. Or, we could look to
Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors
Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR) responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production.
While, again, we suffer from usage of the test tube and straight TLR4 agonists, the effect of time dependency is noted. [Does it strike you as odd that the crucible of evolution has given us an immune system that attempts to belay an inflammatory response at the earliest stages of life, when we are our most vulnerable? Maybe this is actually a feature, as opposed to a flaw, but I digress. . . ]
LPS elicits a much larger and broader inflammatory response than Escherichia coli infection within the hippocampus of neonatal rats
was published around two years ago; what they found was a different neuroimmune profile depending on insulting agent. I’m not arguing one is equal to vaccination, but rather, that if our question set entails, ‘what does the resultant immue (or neuroimmune) change look like following challenge?’, we cannot substitute one trigger with another without corrupting our findings. Basic understanding of TLRs don’t really help either.
So while knowing that alum interacts with the inflammasome is nice, and knowing that TLR4 interacts with LPS is nice, those individual pieces of knowledge do not necessarily give us quality insight into what the innate immune response post vaccination looks like in our target population. There are too many moving parts to make assumptions about; we need to actually attempt the observation. I am asserting that we have not made those observations. As noted earlier, science cannot prove a negative, but you can easily disprove this statement, if you have the data. Just saying that plenty of labs are working on understanding the immune system, while a true statement, is no replacement for actual observations after vaccination. And then, of course, figuring out what a child predisposed to impairments in regulating the immune response looks like, is even more challenging (and interesting).
Reviewers will rarely ask you to temper these statements, in part because one can argue about what it means to say we “know relatively little” about something.
OK. What about Corbett? Why stick a bunch of kids at a year and two years, then spike their blood with TLR agonists to try to characterize the immune response? Why not just use the data from vaccine trials, or Hoffman data, or Ransohoff data? Why fund this study?
I think what you’re getting at here is your desire to see a day when a whole panel of immune ‘markers’ are routinely used in clinical settings to monitor the health of an individual’s immune system.
Close, What I’m getting at is a characterization the innate immune response post vacccination in our target population; infants, evaluating what we give them, innoculations for several diseases, simultaneously. Unfortunately, the time dependent changes in infant immune response means we cannot extrapolate out from adults, and similarly, the fact that the reality involves toggling a lot of diffferent TLRS, and whichever mysterious mechanisms of alum, means spiked blood from a single TLR agonist, sans alum, does little to illuminate what is actually happening.
Yep, that would be nice.
Well, at least we seem to agree on something!
Outside of a crude CBC panel, nothing like this exists yet, although there are people actively pursing biomarkers of disease or more complex ‘systems biology’ approaches to integrating and understanding how many immune factors work together during disease.
[Love the system biology approaches, even though the complexity problem is very real.]
Why not just try to measure some of the big boys in the inflammatory and chemokine matrix to start? CRP/IL-6/TNF-alpha/IL-B1/CCL#/IL-12/IL-10 would be nice, and it seems like we’ve got the ability to detect for those, in vivo post vaccination. Unforutnately, when I’ve seen them referenced, they are for adults and following single vaccination.
I’m analyzing immune responses in cells I recovered from the brains of infected mice
Good job! Keep it up!
– pD
Hi qwerty –
Did you see the recent congressional hearing?
I predict a grand total of zero vaccine studies will become of the latest hearing.
What some studies have hinted at (including the ones you provide links to!), is that perinatal systemic infections are bad (shocker, I know) and that they might be associated an increased risk of autism (or at least behavioral issues in mice).
The study I referenced used a postnatal day 5 e-coli challenge, but others have observed effects up to postnatal day 14. It isn’t that ‘perinatal systemic infections are bad’, it is that during critical developmental timeframes, their effect can be persistent in the brain.. The kicker is that the physiological effect observed, chronic activation of microglia in treatment animals, bears strong similarity to observations of the microglia in the autism population. It isn’t all about how many friends a rat tries to make; it is also about the neuroimmune environment, which can be persistently altered through early life immune challenges.
Indeed there are entire laboratories both in the US and abroad that do nothing but study this exact topic in great detail, down the specific molecular mechanisms.
Great, then show me something similar to the influenza paper I showed you with infants. They don’t get one vaccine at a time, or one specific TLR agonist at a time. They get several, all at once, and as you reference, including alum.
For starters, check out the nobel prize in Physiology/Medicine awarded in 2011 to Jules Hoffmann, Ralph Steinman and Bruce Beutler.
If I remember correctly, there was something of a minor dustup regarding who, exactly ‘deserved’ the Nobel, with Ransohoff thinking maybe he got to the TLR discovery first.
But those are about the nuts and bolts; sure we know that LPS triggers TLR4 and MyD88 is involved. Great. Sure we know that POLY:IC triggers TLR3. Wonderful. Yes, we know that *somehow* alum interacts with the inflammasomme, and that *somehow* this participates in the generation of an innate immune response with corresponding, eventual, generation of immunological memory. My concerns are not exclusionary of that data set, but rather, depend on them, and indeed, the nascent nature of the interactions between the innate immune system and several cognitive disorders.
Unfortunately, understanding all of the individual pieces (and more) does not necessarily tell us about what happens when we do all of those things, all at once, in an infant population.
For example, triggering multiple TLRs simultaneously can result in a non-linear increase in cytokine production; (i.e., TLR ligands induce synergistic interferon-ß and interferon-?1 gene expression in human monocyte-derived dendritic cells, or Synergy Between Viral and Bacterial Toll-Like Receptors Leads to Amplification of Inflammatory Responses and Preterm Labor in the Mouse.
Similarly, as Corbett observed, the infant immune response is qualitatively different than that of adults. Or, we could look to
Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors
Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR) responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production.
While, again, we suffer from usage of the test tube and straight TLR4 agonists, the effect of time dependency is noted. [Does it strike you as odd that the crucible of evolution has given us an immune system that attempts to belay an inflammatory response at the earliest stages of life, when we are our most vulnerable? Maybe this is actually a feature, as opposed to a flaw, but I digress. . . ]
LPS elicits a much larger and broader inflammatory response than Escherichia coli infection within the hippocampus of neonatal rats
was published around two years ago; what they found was a different neuroimmune profile depending on insulting agent. I’m not arguing one is equal to vaccination, but rather, that if our question set entails, ‘what does the resultant immue (neuroimmune) change look like following challenge?’, we cannot substitute one trigger with another without corrupting our findings.
So knowing that alum interacts with the inflammasome is nice, and knowing that TLR4 interacts with LPS is nice, those individual pieces of knowledge do not necessarily give us quality insight into what the innate immune response post vaccination looks like in our target population. There are too many moving parts to make assumptions about; we need to actually attempt the observation. I am asserting that we have not made those observations. As noted earlier, science cannot prove a negative, but you can easily disprove this statement, if you have the data.
Just saying that plenty of labs are working on understanding the immune system, while a true statement, is no replacement for actual observations after vaccination. And then, of course, figuring out what a child predisposed to impairments in regulating the immune response looks like, is even more challenging (and interesting).
Reviewers will rarely ask you to temper these statements, in part because one can argue about what it means to say we “know relatively little” about something.
OK. What about Corbett? Why stick a bunch of kids at a year and two years, then spike their blood with TLR agonists to try to characterize the immune response? Why not just use the data from vaccine trials, or Hoffman data, or Ransohoff data?
I think what you’re getting at here is your desire to see a day when a whole panel of immune ‘markers’ are routinely used in clinical settings to monitor the health of an individual’s immune system.
Close, What I’m getting at is a characterization the innate immune response post vacccination in our target population; infants, evaluating what we give them, innoculations for several diseases, simultaneously. Unfortunately, the time dependent changes in infant immune response means we cannot extrapolate out from adults, and similarly, the fact that the reality involves toggling a lot of diffferent TLRS, and whichever mysterious mechanisms of alum, means spiked blood from a single TLR agonist, sans alum, does little to illuminate what is actually happening.
Yep, that would be nice.
Well, at least we seem to agree on something!
Outside of a crude CBC panel, nothing like this exists yet, although there are people actively pursing biomarkers of disease or more complex ‘systems biology’ approaches to integrating and understanding how many immune factors work together during disease.
[Love the system biology approaches, even though the complexity problem is very real.]
Why not just try to measure some of the big boys in the inflammatory and chemokine matrix to start? CRP/IL-6/TNF-alpha/IL-B1/CCL#/IL-12/IL-10 would be nice, and it seems like we’ve got the ability to detect for those, in vivo post vaccination. Unforutnately, when I’ve seen them referenced, they are for adults and following single vaccination.
I’m analyzing immune responses in cells I recovered from the brains of infected mice
Good job! Keep it up!
– pD
@Sullivan – if this double posts, feel free to delete one / sorry.
@pD
Again, I’ll reiterate, the more straightforward interpretation of the collective studies you cite is that vaccination is an important barrier that helps prevent early life infections from having a lifelong detrimental effect on individuals. Yet, where you perceive a lack of data, you are happy to insert the suggestion that the current vaccine schedule might be adversely affecting brain development. Your plausibility bar is set pretty low. This hypothesis finds good company on whale.to, mercola and other places where even the laws of physics and chemistry aren’t welcome, much less plausible (or even sane) hypotheses regarding vaccines.
As for your specific request: I’m not sure if anyone has looked at markers of innate immune activation in the serum during influenza vaccination of infants/toddlers over time. One likely reason for this is the fact that it’s not clear how these markers correlate with vaccine efficacy or safety (as opposed to serum antibody titers, which are an important factor in assessing influenza vaccines). Indeed, one expects vaccination to elicit elevated levels of markers of innate immunity — if it didn’t, the vaccine wouldn’t work. So if such a study were carried out, and elevations of specific inflammatory cytokines were observed, you would likely have your ‘ah ha!’ moment. But the scientific community would look at this and say ‘uh duh!’.
Regarding the nobel prize. As far as I know, Ransohoff was never in consideration for a Nobel. The controversy that I think you’re referring to involved other folks (Charlie Janeway and Ruslan Medzhitov).
Hi qwerty –
Yet, where you perceive a lack of data, you are happy to insert the suggestion that the current vaccine schedule might be adversely affecting brain development. Your plausibility bar is set pretty low.
As you note, it is not a perception of lack of data, but an actual lack of data. There is a big difference.
I do appreciate that you include the *might* qualifier, which I am certainly applying. Within the context of all nearly all risk factors assigned to autism, they seem to be have a low penetrance, *if* the vaccine schedule can adjust risk, I see no reason it wouldn’t follow a similar pattern.
This hypothesis finds good company on whale.to, mercola and other places where even the laws of physics and chemistry aren’t welcome, much less plausible (or even sane) hypotheses regarding vacci<ones.
Indeed. Unfortnately, the animal literature has abundand examples of lifelong, persistent neuroimmune effects that are tired to innate immune activation, sans pathogen.
For example, Early Life Activation of Toll-Like Receptor 4 Reprograms Neural Anti-Inflammatory Pathways
Thus, postnatal LPS reprograms the neuroimmune axis by priming peripheral tissues to create a novel, prostaglandin-mediated activation of the HPA axis brought about by increased constitutive expression of TLR4 and COX-2.
These animals weren’t challenged with e-coli or any other actual pathogen, just LPS; which tells us that the only thing that *could* be affecting this change is the innate immune response. If my concerns are outside the laws of physics or chemistry, are these findings bogus?
Similarly, Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats found altered seizure susceptibility in LPS treatment animals, which was ablated with concerrent administration of tnf-alpha blockers. It didn’t matter if there was a pathogen or not; it only mattered if there was an unmitigated innate immune response or not.
The most exciting finding of the present study is that a mild inflammatory response evoked by LPS during a critical period of development causes a long-lasting increase in hippocampal excitability in vitro, and enhanced seizure susceptibility to the convulsants LI-PILO, KA, and PTZ in vivo. The latter effect was observed over a range of mildly inflammatory doses of LPS and was only evident if administered during the second postnatal week (P7 and P14), and not before (P1) or after (P20) this time. Importantly, inactivation of the proinflammatory cytokine TNFa with an intracerebroventricular TNFa antibody blocked the long-term changes to seizure susceptibility induced by LPS, whereas intracerebroventricular administration of rrTNFa alone mimicked the effect of LPS on seizure susceptibility. These novel results indicate that a single transient inflammatory episode during development can modify the brain through a TNFa-dependant mechanism, making it more susceptible to generate seizures in adulthood.
Why on Earth would the researchers write this statement, the editors OK this statement, and the peer reviewers pass this statement through if the findings were in violation of known laws of physics? Should these papers be retracted based on violation of fundamental chemistry principles?
If not, this data tells us that there are timeframes during which the brain is maleable to immune challenge in ways that were completely unconsidered just a few years ago.
It would be one thing if you wanted to argue that all of these papers (and many, many more) got it wrong, in the same way, and were willing to present some alternative evidence of your own, but you don’t do that. Instead, you claim the support of authority (your own), the problems of relative ignorance (mine), but offer nothing in terms of the currency of scientific debate, literature to evaluate.
As for your specific request: I’m not sure if anyone has looked at markers of innate immune activation in the serum during influenza vaccination of infants/toddlers over time.
So much for those phase 1 trials. Oh well.
One likely reason for this is the fact that it’s not clear how these markers correlate with vaccine efficacy or safety (as opposed to serum antibody titers, which are an important factor in assessing influenza vaccines).
(Why would titers be indicative of safety, other than just efficacy?)
You see what you’ve done there? You have assumed that there is no correlation between inflammatory markers and developmental outcome. You may be correct, it appears that you have good company, I just worry about a program that interacts with four million infants a year being run on this type of assumption. The findings from Mouihate and Galic above, and their many similar publications are subtle, but barring a massive wave of retractions, real. This is why we might consider rethinking the assumption of no harm. *If* there are similar things occurring as a result of vaccination, our existing research set is completely blind to them, as you note yourself, we haven’t even bothered to evaluate the clinical markers of innate immune activation, much less attempt the fine grained analysis necessary to look for associations.
Indeed, one expects vaccination to elicit elevated levels of markers of innate immunity — if it didn’t, the vaccine wouldn’t work. So if such a study were carried out, and elevations of specific inflammatory cytokines were observed, you would likely have your ‘ah ha!’ moment. But the scientific community would look at this and say ‘uh duh!’.
Well, I’d say we are in agreement once again.
Given that you seem to acknowledge that we have no data on qualification of immune response post vaccination in our target population, that we have not performed even the most rudimentary ‘wetwork’ style analysis on the process of ‘vaccination’ [see: no alterantives to Hewittson], and the animal models tell us that what we once thought could have no clear association to outcome, may, in fact, have biological levers into brain development, you might consider if your bar of plausibility is set inappropriately.
– pD
Hi qwerty –
I’d also point out that this dose is ~10-20x higher than what has been given experimentally to humans to mimic mild symptoms of sepsis, which include changes in respiration, metabolism and inflammatory markers
Please note that Galic observed effects at 25 micrograms/kg.
LPS is a powerful tool for instigating the immune response, but there are rather significant interspecies differences in reactions, with humans being particularly sensitive. For example,
Resilience to bacterial infection: difference between species could be due to proteins in serum
One of the most common assays used to assess novel pathways of inflammation by academic investigators and pharmaceutical companies alike consists of challenging mice with the Gram-negative bacterial cell wall molecule, lipopolysaccharide (LPS), which activates cells through Toll-like receptor 4 (TLR4). Most wild type mice are highly resilient to challenge with LPS. The dose of LPS utilized in most in vivo studies is 1–25 mg/kg, which leads to death in about half of the mice (3–6). This dose is about 1,000,000 times the 2–4 ng/kg dose of LPS utilized in human volunteer studies to induce fever and cytokines (7), and about 1000–10,000 times the dose required to induce severe disease with shock in humans (8;9). It is generally assumed that this marked difference in resilience to pro-inflammatory molecules such as LPS is related to cellular differences between species.
Given that, I’m not sure we should bandy about direct comparison dosages between humans and animal models; there is way too much uncertainty. It is widely used as a model to understand the effects of activating the immune system without pathogenic participation, but beyond that, I’m not sure that we can make anything more than big guesses. I won’t pretend to know what the right equivalency between rat LPS and the two month old vaccine schedule immune activation profile looks like. For whatever reason, LPS is used a lot. I also know of some POLY:IC studies.
Yet, from these studies you assume that since infection, per se, is not required for this effect, and TLR agonists can achieve a similar effect, that pediatric vaccines could do something similar.
Yes. Also, I’d state for the record that I absolutely am not somehow suggesting that an actual infection couldn’t do the same thing; the innate immune response is the innate immune response.
That’s a stretch, but you’re entitled to your opinion, however scientific support is weak for this hypothesis.
Fair enough. I have been accused of an extreme form of the precautionary principle, but when it turns out that we haven’t even bothered to characterize the innate immune response post vacciation, and we are forced to admit that the Hewittson paper was as good as it gets in terms of evaluating the effect of ‘vaccination’, and not ‘one vaccine’, I guess my thoughts are that there is plenty of weakness of scientific data to go around.
A point that you might want to consider is that the autism population has been shown repeatedly to have a propensity for an exaggerated inflammatory response; i.e.,
Elevated serum levels of interleukin-17A in children with autism
Macrophage migration inhibitory factor and autism spectrum disorders
Increased serum levels of high mobility group box 1 protein in patients with autistic disorder
Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome
[Not linking to avoid spam filter/you know what to do.]
Note that all of the above studies, found positive correlations between degree of inflammatory response/predisposition and autistic behavioral severity. There are other studies showing increased production of cytokines that didn’t measure (or report) for behavioral correlations.
Curiously enough, the autism population also has signs of decreased levels of regulatory proteins; i.e.,
Neonatal levels of cytokines and risk of autism spectrum disorders: an exploratory register-based historic birth cohort study utilizing the Danish Newborn Screening Biobank
Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes
So, *if* there is a subgroup of people that *might be* particularly susceptible to the type of insult described in these papers, the autism population just happens to have a risk profile consistent with an exaggerated innate immune response.
I’m assuming you know that human vaccines don’t contain LPS as an adjuvant, right? And for good reason. It’s potent stuff (as illustrated in the papers you cite).
Sure. But, as you stated, vaccines work *because* we induce a robust innate immune activation; it isn’t sepsis, but fever is a very common side effect, and that is being handled centrally, which means we are getting to the CNS. But we do include alum, because without it, our bacterial vaccines don’t generate *enough* of an immune response. You seem think we’ve hit the goldilocks zone. We may have; I hope so.
Yet, in the face of loads of safety data from human vaccine trials, you still feel that it’s a good idea to start looking at serum markers of inflammation in a large pediatric population based on rodent models of mild to severe sepsis. I disagree.
Well, my concern is that the safety trials weren’t designed to test for:
a) subtle differences
b) the effect of the innate immune response, as opposed to the vaccine itself.
For example, here is a link to the prevnar fact sheet from pfizer:
http://labeling.pfizer.com/showlabeling.aspx?id=501
Check out the studies detailing analysis of side effects are described.
The incidence and severity of solicited adverse reactions that occurred within 7 days following each dose of Prevnar 13 or Prevnar administered to US infants and toddlers are shown in Tables 3 and 4.
And
In clinical trials with infants and toddlers, Prevnar 13 was administered concomitantly with the following US licensed vaccines: Pediarix [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined] (DTaP-HBV-IPV) and ActHIB [Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate)] (PRP-T) for the first three doses and with PedvaxHIB [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] (PRP-OMP), M-M-R II [Measles, Mumps, Rubella Virus Vaccine Live] (MMR) and Varivax [Varicella Virus Vaccine Live], or ProQuad [Measles, Mumps, Rubella and Varicella Virus Vaccine Live] (MMRV) and VAQTA [Hepatitis A vaccine, Inactivated] (HepA) for dose 4 [see Clinical Studies (14.2) and Adverse Reactions (6.1)]
While the effect described in Galic may be ‘a stretch’ in so far as pediatric vaccines are concerned, how on Earth would a safety study designed in this fashion be able to detect it?
In the first case, the follow up period was on the order of days. If the type of sublte interactions described by Galic did occur, how would you suggest that follow up times on the order of thirty days be able to detect it? Seriously. How could we possible tell if we had subtly altered neurodevelopment in a two month old by evaluating for adverse reactions for a month?
In the second case, there was no possible way to detect any impact of toggling the immune system at all; there is only a way to detect if infants getting Prevnar13 and the rest of their shots had difference experiences than children getting Prevnar7 and the rest of their shots. Nont only did all children receive many other vaccines, Table 4 defines a control group that got the Prevnar 7 vaccine!
If the mechanism of action we wish to understand is invoking an immune response, as opposed to some quality of the Prevnar vaccine in particular, these safety studies are completely blind to that effect. How could the safety studies, presented here by the manufacturer, detect the possibility I am describing? Please explain to me how this information be teased out from this study.
I would state for the record that our safety studies on vaccines are very good at detecting actue events. I do not, however, think they can detect well for subtle changes, and they are completely incapable of detecting the effect of the process of ‘vaccination’, as opposed to a particular vaccine. If you want evidence to that effect, just look at the data sheet for Prevnar13.
I disagree.
OK.
– pD
@pD
And around and around we go….
It’s not that I think the papers you cite “got it wrong”, nor do I expect a “massive wave of retractions”. They’re fine papers, until you took them out of context. What I’m arguing is that your interpretation of the relevance of these papers to vaccines is very flawed. For example, you first cited a paper that showed a neurodevelopmental change after systemic infection of neonatal rats with E. coli — essentially, sepsis. When I pointed out that this data is a great example of precisely *why* vaccines are important early in life, you responded by citing additional papers that show similar data after injection of 100 micrograms/kg of LPS into neonatal rats — again, a model for inducing mild symptoms of sepsis (including immediate fever). I’d also point out that this dose is ~10-20x higher than what has been given experimentally to humans to mimic mild symptoms of sepsis, which include changes in respiration, metabolism and inflammatory markers. Yet, from these studies you assume that since infection, per se, is not required for this effect, and TLR agonists can achieve a similar effect, that pediatric vaccines could do something similar. That’s a stretch, but you’re entitled to your opinion, however scientific support is weak for this hypothesis.
I’m assuming you know that human vaccines don’t contain LPS as an adjuvant, right? And for good reason. It’s potent stuff (as illustrated in the papers you cite). Hardly in the same ballpark as Alum. Yet, in the face of loads of safety data from human vaccine trials, you still feel that it’s a good idea to start looking at serum markers of inflammation in a large pediatric population based on rodent models of mild to severe sepsis. I disagree.
I’m also assuming that you noticed that the authors of the studies you cite don’t jump to the same conclusions as you. In fact they never so much as mention that their data bears any relevance to vaccination or adjuvants….at all.
After checking all of the Segal Family Foundation and Focus Autism 990-PFs (they are avaliable online through the Foundation Center website) Segal only contributed $51,000 in 2011 to Autism Speaks. Interesting how that got him the ear of the Wrights.
There are a lot of walk teams out there who sweat bullets and generate a lot more money every year. Do the Wrights reach out to them???
Not good.
The epidemiology studies on autism are worthless. No one can define autism. Just look at the debate and argument ov the DSM5. Even the editor-in-chief of DSM-IV (1994) said that expanding the definition of mental disorders, which he oversaw, was directly responsible for the false epidemics of autism, attentional disorders and bi-polar disorder.
The one thing the vaccine supporters and the behavioral geneticists agree on is that you can’t have a genetic epidemic.
I didn’t call her clueless pD; I said her call for “solid wetlab-based in vitro and in vivo work.”, pretentious and vapid. Which it is. Ms. Williams is trying to portray herself properly sceptical while the rest of us languish in ignorance and blind acceptance. The preponderance of evidence (which also includes “too many too soon”) does not support a causal relationship between vaccines and autism. If Ms. Williams had stuck to specific paucities in the data regarding say immune dysfunction that is co-morbid with some autisms, then she’d have a valid point. She doesn’t even appear to understand what epi studies are, nor that clinical studies involving subsets of autists have also been conducted and continue to, none of which implicate a vaccine causality to date. Actively involved in autism research does not innoculate one from making mistakes and being immune from criticism particularly when one chooses to present at AutismOne and publish in Medical Hypotheses when one doesn’t (or shouldn’t) need to.
Actually I am the one who stated that Ms. Williams is “clueless about epidemiology”…after she made this comment on epidemiological studies…
“However, as a scientist I find it genuinely concerning that vaccine research has been mainly epidemiological in origin. This is not the equivalent of solid wetlab-based in vitro and in vivo work. I am neither in support of a link between vaccines and health risks nor against it. But as the research stands, I truly don’t feel we can draw solid conclusions from it.”
I then commented that newly developed vaccines undergo clinical trials…and constant monitoring for safety after licensing.
http://www.cdc.gov/vaccines/vpd-vac/rotavirus/vac-rotashield-historical.htm
So what is the history of the first rotavirus vaccine, “Rotashield”? Seven thousand children received the vaccine during clinical trials and there was no indication that the risk of intussusception for vaccinated children exceeded the risk for young children, who did not receive a rotavirus vaccine. Rotashield was licensed August 1998. When did it become apparent that reports of increased risk of intussusception were associated with administration of Rotashield vaccine? The CDC, the FDA and multiple states and local health departments did epidemiological studies of each case and case clusters of intussusception and Rotashield was removed from the marketplace within 14 months of licensure…IMO, a remarkable example of how intensive ongoing passive and active vaccine safety monitoring, really *works* to protect babies, children and adults from serious adverse events…associated with vaccines.
I find it interesting that there is such heated emotion flying my way despite words I truly considered to be calm. I’m curious what the root of this defensiveness is that even the suggestion of performing more thorough science could rattle cages so vehemently. Just curious. This all would actually be an interesting anthropological study in and of itself.
passionlessdrone, sorry of the delay in reply. Yes, Above Genetics was my piece; thank you very much for the compliments. I may’ve done something here on lbrb regarding the rTMS, although memory’s failing me at the moment. Manny Casanova is my partner, and so we do sometimes join our work forces on our common research interests.
@Emily – where do you believe the failings are? A lot of research has already been done & we aren’t seeing a whole lot that would lend any credence whatsoever to the various anti-vaccine positions, so again, what would you recommend?
http://insolemexumbra.wordpress.com/2013/03/03/vaccines-autism-epidemiology-a-call-for-better-science/
^ This would be my best summation as to how I see things. I wrote that following my posting above, because doing so got me to thinking more about it.
Maybe I just haven’t managed to actually find the research that’s been done already– and I’m usually pretty good at rooting around and finding what I’m looking for when it comes to research. The only ones I’ve managed to find are the collection of larger epidemiological studies and then a few poorly designed smaller lab-based studies.
My first concern would be to look at whether vaccine exposure affects brain development. It doesn’t need to LOOK like an animal model of autism, simply to confirm whether there is a biological foundation for such an effect. This, actually, is the kind of study I’d like to see, one which looks at controlled exposure in animals (even mouse would do) and any subsequent aberrations in central nervous system development. A few experiments like this would inform us whether this risk is real or just bollocks. If it’s the former, we can go from there designing more specific studies to get at whether there are potential links in autism etiology. I’d prefer scientists performing this who not only have experience with animal exposure but also are very experienced with central nervous system development and various methods of stereological investigation. It’s this kind of study, well-controlled, in a lab, looking more directly at cause and effect which would ease my mind.
Gene Sacket is working on a replication/follow-on study to Hewitson. U. Washington. I personally would prefer someone not affiliated with the original study, but it is ongoing.
I find it equally interesting that you chose to respond with a passive-aggressive strawman in the face of my calm rebuttal. You stated that in vitro and animal studies were the ‘gold standard’ but they aren’t. In vitro studies are hypothesis-generating for the most part and we don’t have a good animal model for ASD research. Specific pathways may be studied via genetically-modified rodents but hardly a ‘gold standard’.
You also stated that you weren’t satisfied with epi studies but don’t seem to grok what they do and seem remarkably unaware of the clinical studies which have been done. I asked you what studies you found so compelling as to be confused about the current body of knowledge; I have yet to receive a response. Epi studies have been done and no relationship has been found; it’s now time to target research given the heterogeneity of ASDs. To my knowledge, there are many studies in progress and recently published that do address GI issues and immune modulation, aberrant gene expression and pre-natal/peri-natal environmental influences.
May something involving vaccines be elucidated in the course of the many research avenues being explored? Sure but I haven’t seen anything from you that convinces me that precious research budgets should be diverted to massage the fancies of those who have some kind of financial and/or emotional stake in a vaccine-autism causality. And given that you are and have been a presenter at AutismOne, you do have a stake in the hypothesis and those who support it.
My apologies. I was posting passive-aggressively. Thanks for catching me; I reacted to some of the hostilities flying my way and flew some back without thinking.
For some of your points, the link I provided in the post above will probably address a couple of them. Regarding clinical studies, I’d like to hear more if you can post some links. I’m always eager to learn.
Regarding AutismOne, I have been listed as a presenter though I’ve never attended. My partner, Manny Casanova, likes to keep on friendly terms will all factions of debates going on, which means attending conferences like IMFAR as well as conferences like AutismOne. He and I often collaborate, hence the listing of my name. Although I hope you don’t judge me by company kept. I am my own person.
Emily,
I appreciate you returning to comment after a fairly tough response. I left a comment on your blog post. With all due respect, you need to catch up on the research of the past 8 years.
A prime example, you cite the Hornig mouse study, and even state: “What makes this even sadder is the fact that no groups have attempted to replicate this work, leaving a good idea to simply rot on the scientific shelves.”
The attempt to replicate is “Low-Level Neonatal Thimerosal Exposure: Further Evaluation of Altered Neurotoxic Potential in SJL Mice”
The full paper is free online. Here is the final statement from the abstract: “Considered together the present results do not indicate pervasive developmental neurotoxicity following vaccine-level thimerosal injections in SJL mice, and provide little if any support for the hypothesis that thimerosal exposure contributes to the etiology of neurodevelopmental disorders.”
That was published in 2008. And this isn’t the only example of you citing outdated information.
“Regarding AutismOne, I have been listed as a presenter though I’ve never attended. My partner, Manny Casanova, likes to keep on friendly terms will all factions of debates going on, which means attending conferences like IMFAR as well as conferences like AutismOne. He and I often collaborate, hence the listing of my name. Although I hope you don’t judge me by company kept. I am my own person.”
Why don’t you discuss the research that your collaborator/partner Manny Casanova “presented” at the 2010 Autism Conference? Are you now denying that you did not “collaborate” with Manny Casanova and his *theory* about sonograms during pregnancy being a possible factor in the onset of ASDs?
If you need to miss your favourite sports, amusement suites and training acquired immune deficiency syndromes.
Like within the movies, each game is rated for explicit
gamers. Will the Dodgers be able to bounce back from two close losses and turn the
NLCS around in their favor.