With antivaxers, it’s always, first and foremost, all about the vaccines, which in their belief system cause autism, developmental delay, autoimmune diseases, diabetes, sudden infant death syndrome (SIDS), and all manner of other health issues and diseases. In supporting this belief, antivaxers are like the proverbial drunk walking down the street at night, using the lamppost of science not for illumination, but rather for support of his beliefs. Yes, antivaxers are experts at cherry picking and misinterpreting scientific studies. They’re also very good at co-opting any scientific finding that they can spin to give their beliefs even the patina of plausibility. Towards the end of last week, I witnessed that very thing based on the publication of a recent study of autistic brains published last week in the Proceedings of the National Academy of Sciences (PNAS). This led Kate Raines over at The Vaccine Reaction to comment, as well as a fair number of Twitter antivaxers, for example, to start waxing all “science-y” about a couple of cytokines, IL-18 and IL-37 and a study by Theoharis Theoharides and Susan Leeman at Tufts University and Irene Tsilioni, their collaborator at the University of Chieti in Pescara, Italy:
Let’s look at the study. Before I get to meat of the study itself, though, I couldn’t help but note that that one name sounded vaguely familiar to me when I first looked at the paper. So I did what I always do when I see a name that sounds familiar to me. I searched my blogs to see if I had ever written about him before. Guess what? I had! And guess what else? Theoharis Theoharides received a bit of my not-so-Respectful Insolence back in 2013 for peddling an “anti-inflammatory” supplement to treat autism. He was associated with something called AutismFreeBrain (whose website now features cannabis “research” but whose original can still be found at Archive.org, thanks to the almighty Wayback Machine). Let’s quote a blast from the past, straight from what used to be the AutismFreeBrain website:
Putting an End to Autism by Fighting Brain Immunity Storms™
AutismFreeBrain, Inc. was created to fund innovative research to develop a cure for Autism Spectrum Disorders (ASD). Our studies have identified inflammatory processes in the brain, we called Brain Immunity Storms, that are much like an allergic reaction, releasing surges of molecules that disrupt areas of the brain responsible for emotion and language.
“Fighting brain immunity storms”? As I noted at the time, whenever you see a website like this asserting that neuroinflammation is, in essence, the be-all and end-all of the pathogenesis of autism, you know that there’s likely to be some serious woo involved. It was true six years ago and is still true now that there have been a number studies suggesting an association of markers of inflammation with autism, but the significance of these observations hadn’t been worked out then and still haven’t been worked out. Not that any of this deters antivaccinationists from glomming onto studies like the one I’m about to discuss. The term “inflammation” is a term much beloved and abused by quacks of all stripes, and autism biomeddlers are no exception. This tendency to view autism as an inflammatory condition probably has a lot to do with the general antivaccine leanings of most such practitioners. Basically, inflammation is a convenient means for them to link their two greatest hatreds: vaccines and autism.
This wasn’t Theoharides’ only foray into dubious treatments for autism. He also hawked a supplement called Neuroprotek. It wasn’t even Theoarides’ only foray into cure-all supplements, as he also hawked a supplement he called CystoProtek (to treat interstitial cystitis) and another called Prostaprotek, to treat us old dudes at risk for prostatic hyptertrophy. Indeed, Algonot, Theoharides’ company, was even hit by an FDA warning letter in 2011 for marketing those supplements to treat disease. In any event, as I noted at the time, Theoharides has a very good publication record, nearly 400 publications on a PubMed search that I did yesterday, and many of those publications appear to be respectable. He’s also still the director of the Molecular Immunopharmacology and Drug Discovery Laboratory at Tufts. Unfortunately, he’s lent his name to some dubious supplements and antioxidant concoctions to use to treat autism based on his apparent belief that autism pathogenesis involves neonatal mast cell activation.
So with that background, it is perhaps not so odd to find Theoarides publishing a paper like this in PNAS. I also note that this paper was communicated by his coauthor, Susan E. Leeman. Back in the day, members of the NAS could basically publish anything they wanted to in PNAS by simply communicating it and then picking their peer reviewers, and early in my scientific training PNAS had a reputation as a bit of a dumping ground for NAS members and their friends, for whom they could communicate up to two papers a year. These days, PNAS is much more of a standard peer-reviewed journal, but, even so, I always have a bit of suspicion regarding papers communicated by NAS members for their friends or co-authors.
The paper itself utilized human brain tissue from the NIH NeuroBioBank at the University of Maryland from deceased Caucasian boys aged 3-14 years old, eight with an autism spectrum disorder (ASD) diagnosis and eight neurotypical children. Perusing the methods section, I already saw one big problem:
The only inclusion criteria used were males, 1 to 12 y of age, who had died in car accidents. Unfortunately, there is no available information of how diagnosis of ASD was reached, what the level of cognitive or functional level was before death, or the presence of any comorbidities. Controls were selected without any known brain disease or trauma and were matched to the subjects with ASD to the extent possible as shown in SI Appendix, Table S1.
So right away, we see that this is a very small study and that there’s basically no clinical information about the patients with ASD to tell how severely they were affected, whether they had other comorbidities, such as other developmental delay, seizure disorders, etc. In any event, Theoharides and his investigators did Western blot and isolated RNA for quantitative reverse transcriptase PCR to measure protein and RNA levels, respectively. The authors decided to investigate the levels of two cytokines in particular, interleukin-18 and -37 (IL-18 and IL-37), and they decided to concentrate on the amygdala and prefrontal cortex because of evidence in human and animals connecting the amygdala to social behavior. As for the cytokines studies:
Interleukin-37 (IL-37, previously known as IL-1F7) belongs to the IL-1 family of cytokines (29) and is a natural suppressor of inflammation (30–32). Five isoforms (a–e) have so far been identified with the “b” isoform being the most well studied (33). IL-37 is produced mainly by activated macrophages in response to Toll-like receptor (TLR) activation. An IL-37 precursor (pro– IL-37) is cleaved by caspase-1 into mature IL-37, some of which (∼20%) enters the nucleus and the rest is released along with the pro–IL-37 outside the cells (34) where both are biologically active. Extracellular proteases can then process pro–IL-37 into a much more biologically active form as shown for the recombinant IL-37b with the N terminus Val46 (V46-218) (35).
Although no specific receptor for IL-37 has been identified, a number of studies showed that extracellular IL-37 binds to the alpha chain of the IL-18Rα (36, 37), but with much lower binding affinity than that of IL-18 (38). Moreover, IL-37 binds to an IL-18 binding protein (IL-18BP) (39), and to the decoy receptor 8 (ILR8) (40) via which IL-37 inhibits innate inflammation (35, 41, 42) in vitro and in vivo (42).
To boil it all down, IL-37 is anti-inflammatory, blocking the action of IL-18, which is pro-inflammatory. I can also summarize the findings of the study fairly easily. The authors found higher levels of messenger RNA for IL-37, IL-18, tumor necrosis factor (TNF), and the receptor for IL-18 in the amygdalas of autistic brains than in neurotypical brains. However, if you look at the graph, you’ll see that there is a lot of overlap between the groups:
The same is true of the dorsolateral prefrontal cortex:
The authors also found lower NTR3/sortilin protein levels in amygdala and dorsolateral prefrontal cortex of children with ASD than in non-ASD controls. This is a receptor for neurotensin. To be honest, I wasn’t clear on why the authors even bothered with this other than that because neurotensin stimulates microglial cells, which are a specialized population of macrophages that remove damaged neurons; so supposedly a lower level of microglial activation would allow damaged neurons to remain in the areas of autistic brains studied.
Before I go into the significance of Theoharides’ paper (which isn’t much), I also can’t help but point out some rather poor statistics. In the cell culture experiments in which the authors treated cultured microglial cells with IL-37 in the presence and absence of neurotensin, they appear to have used Student’s t-test to compare groups for statistical significance. That’s a big no-no in an experiment with more than two experimental groups. (There were five, counting a positive and negative control in each of this set of experiments.) That’s the second time yesterday I saw that particular error in a manuscript, an error that is a particular pet peeve of mine, because earlier in the day I had reviewed a manuscript sent to me by a journal and it had the same statistical issue. Seeing such a shoddy statistical mistake reminds me just how badly some biomedical researchers are with statistics. Even I know they should have used ANOVA or another. Moreover, I always wonder: Why didn’t the peer reviewers catch such an obvious mistake?
Be that as it may, the cell culture experiments don’t really add anything to the paper anyway; so let’s go to the authors’ interpretation of their results:
Microglia are responsible for innate immunity of the brain (46, 47). Recent evidence indicates that brains of children with ASD have activated microglia (25, 26, 48, 49). The increased gene expression of TNF, IL-18, and IL-18R reported here supports the presence of inflammation in the amygdala and dorsolateral prefrontal cortex of children with ASD. We also show that the gene expression of IL-37 is increased in these same areas, but the reason for this increase is not clear. A speculation why this might occur is that IL-37 gene expression may be increased in an effort to suppress the inflammation in that part of the brain. Increased IL-37 gene expression was reported in the brain of patients after ischemic stroke and protected them from further inflammatory brain injury (50). Other studies also showed elevated serum IL-37 concentration in patients with sepsis (51) and in ankylosing spondylitis (52).
Overall, Theoharides and colleagues propose a model in which increased expression of IL-18 and its receptor indicates inflammation in the amygdala and dorsolateral prefrontal cortex. Neurotensin released in these areas or entering the brain through the blood brain barrier stimulates microglia primarily in the amygdala through activation of the NTR3/sortilin receptor. (Except that the authors’ results show that NTR2/sortilin receptor is lower in the relevant areas of the autistic brains that they examined, and the only reason to mention neurotensin entering through the blood-brain barrier seems to be to invoke a source of neurotensin from the gut, given that since Wakefield gut inflammation is supposed to contribute to autistic symptoms.) According to the authors’ model, microglia then exhibit abnormal synaptic pruning (the process by which synapses are “pruned” to the proper number) and secrete IL-1β and CXCL8, which contribute to focal inflammation resulting in direct damage to neurons and disrupted connectivity between them that contribute to the symptoms of ASD. IL-37 is increased in these brain areas in an effort to inhibit the release of the proinflammatory molecules thus providing a potential treatment option for ASD. So to boil it all down, the idea is that the pro-inflammatory cytokine IL-18 is elevated, supporting the presence of inflammation, but that IL-37 is also elevated, potentially to try to block the inflammation caused by elevated IL-18, but for whatever reason it’s not elevated enough to block the action of IL-18. Why authors seem to prefer IL-37 as a target for treatment, I don’t know. It’s usually easier to block the action of a protein than to augment it. Why not try to block the action of IL-18 instead?
Basically, it’s all a lot of handwaving and speculation on the part of Theoharides and colleagues.
There is, of course, evidence suggesting a role for inflammation in the pathogenesis of autism and ASD, thus leading antivaxers to “reason” thusly: “Aha! There’s evidence of inflammation in the brain in autism. Vaccines can cause inflammation! Therefore this evidence of inflammation must indict vaccines as a cause of autism!” Unfortunately for them, the problem is that we really don’t know whether the inflammation is an epiphenomenon (i.e., a secondary effect or byproduct that arises from but does not causally influence a process) or part of the actual physiologic process that results in ASD. We do know, however, that there is a large genetic component to autism and autism spectrum disorders. We also know, with about as much certainty as it is possible to have in biomedical science, that vaccination is not associated causally with the development of autism. A small paper with unconfirmed findings mixed with a whole lot of speculation won’t change that.
114 replies on “Autism and brain inflammation: A study by Theoharis Theoharides used and abused by antivaxers”
That was the study Greg posted in a comment. Nice to see you do a proper takedown of it.
What ‘takedown’ Julian? It’s the same desperate pattern of attempting to deflect by throwing BS against the wall and hoping it will stick. It goes something like this….
Exley et al found excessive amount of aluminium in dead autistic brains and even exceeding previous finding for ALS and Orac and Choir responds….
https://www.sciencedirect.com/science/article/pii/S0946672X17308763
This paper found excessive inflammatory cytokines in dead autistic brains and Orac and Choir responds….
Anderson et al, 2019 also finds evidence of inflammatory ‘cuffing’ and also evidence of actual brain cells getting destroyed, and one of Orac’s Choir member, Athaic, responds…..
https://eurekalert.org/pub_releases/2019-10/bidm-sfe101719.php
Sing along now everyone! ‘Let’s go shilling! Everybody goes shilling! Shilling in the U-S-A!’
In other words, you don’t understand what this study is about ergo, don’t understand Orac’s reasoned explanation for why it shouldn’t be weaponised by anti-vaxxers.
Except he didn’t. You can’t claim “excessive” when there was no comparison. Additionally, his methods were so shoddy, it’s not taken seriously by other scientists. Not that you can understand that either and just wave it off as conspiracy or shilling. How lazy and pathetic.
I should have know you will be dishonest and distort what I wrote.
Actually, no. I knew it. I just don’t care.
I smell sour grapes. Did the articles you put in failed to have the expected bombshell effect?
Aarno Syvänen downthread just put a reference going this way.
The articles you referenced say nothing implicating vaccines specifically.
Our position is logical. Yours isn’t.
There are a possibility genetic cytokine levels are high. Read my comment below. This would explain why epidemiological studies would find no connections.
As for Anderson paper, it is not published yet, so it cannot be evaluated.
@ Aarno
The Anderson article I’m talking about is definitively available. Well, it’s behind a paywall.
https://doi.org/10.1002/ana.25610
Funny you should mention that paper. I’ve already read it. I was going to discuss it too in this post, but the post was getting too long and it was getting late last night…
Indeed.
That won’t stop those who hear what they want to hear and disregard the rest.
…hear what they want to hear and disregard the rest… : )
There’s music to go with that lyric! (The Boxer)
Thanks for noticing that wonderful connection – it’s brought a smile to my hairy face!
In addition, what is neonatal cytokine profile of autistic people ? Google Scholar search “neonatal cytokine autism” gives some answers.
For instance,
Paula Krakowiak, Paula E Goines, Daniel J Tancredi, Paul Ashwood, Robin L Hansen, Irva Hertz-Picciotto, Judy van de Water
Neonatal Cytokine Profiles Associated With Autism
Biological Psychiatry, Volume 81, Issue 5, 2017, pages 442-451
One known cause of autism is interleukin gene mutations.
I agree. At my semi-amateur level, I was coming to that, after quickly reading the two papers Greg linked to in the other thread
I know the second paper (Anderson) indicated the reported cause of death, but not much more about medical history, including vaccination status, so it’s a bit weak to draw conclusions. We go quickly into speculation territory.
AFAIK, the markers the authors of these papers are discussing are markers of a ‘normal’ immune reaction following an infection, it’s not vaccine-specific. Remove vaccines from the equation, it’s not a given that these symptoms will go away. There are plenty of wild germs which are all too happy to provide a cause for immune-related inflammation. A number of them famous for being the cause of childhood diseases.
Further, in that other paper, this inflammation was shown in only roughly 60% of the autistic tissues. At best implying that for 1/3 of the sampled people, the cause for autism was ‘other than brain inflammation’ (or for some reason, the symptoms were not apparent), at worst a strong indicator that brain inflammation is indeed an epiphenomenon. An effect or co-effect, but not a cause.
You still haven’t responded by telling me the percentage of controls that experienced inflammatory ‘cuffing’, brain cells getting gobbled, in the Anderson paper.
(sigh)
Zero. So what? In all my posts about the Anderson paper, I didn’t deny it. Assuming the relevance of the comparison control vs autistic tissues is actually inherent to my discussion of these papers’ results.
Of all the points to discuss about from this paper, you have an odd obsession over the control samples.
Lowly science writer and biomedical editor here. What strikes me about all of these assumptions and unjustified conclusions is that the really relevant, detailed history of these kids was fuzzy to begin with, so why on earth are they cooking up so many detailed conclusions? Whatever happened to “garbage in, garbage out”?
This typifies much anti-vax crowing about autism “research”: there is often, like the paper ATL here, no evidence that anyone actually was autistic nor how any diagnosis was reached; “assessments” for possible autism use tools which no-one in the biz actually uses, either because they generate false positives or are nowhere near the quality of what our NICE calls gold standard, like the Geiers and some of their disciples; don’t actually formally assess for possible autism, but use short-scale ticky box questionnaires; use unsubstantiated, net-based, self-report from parents linked to anti-vax organisations…
Personally I need to know how any assessment for autism was carried out and a diagnosis reached before I will give credence to any paper on the subject from anyone.
Student’s t-test to compare groups for statistical significance. That’s a big no-no in an experiment with more than two experimental groups.
I believe I learned that as an undergrad a few centuries ago.
And if I read those figures correctly we have an N = 16 (8 & 8)?
Why would a journal editor not reject such a joke paper automatically?
Brain tissue from dead children, with or without ASD, is not a readily available resource for researchers to conduct large scale studies. Small sample sizes like this are worth publishing just to illuminate what knowledge has been gained. These authors identified some interesting differences between the brains of children with ASD and those without, as well as identifying some areas where no differences were found. The results should not be used to justify any strong conclusions, but they are useful to focus future studies on the areas where differences were found.
But there is little evidence that the brains in question were actually affected by any standard definition–so it’s really quite useles from the get-go–and a waste of precious study material.
That is no excuse for not using the appropriate statistical tests.
As there is no information about the accuracy of the clinical diagnosis and whether the diagnoses were the same or different across the autism set, it has all turned out to be a colossal waste of time.
They also conducted at least 22 different t tests on the brain tissues, which gives them a 68% probability of getting at least one false positive.
Isn’t another problem here the assumption that inflammation=vaccines? Aren’t there a lot of other potential sources, including a few vaccines prevent?
(Said above better by Athaic).
@ Dorit Reiss:
Exactly.
But anti-vaxxers will use whatever they find to justify their unrealistic fear of vaccines even if it doesn’t fit.. The Krakowiak et al study even suggests that cytokine profiles may be a way to identify ASDs early.
As I’ve mentioned more times than I care to admit:
whilst anti-vax supporters discuss kids’ skills/ problems as they appear post vaccination ( usually age 1-2) claiming that their kids were “normal” before vaccines, researchers have been investigating much earlier indicators like brain waves, patterns of gaze or movements seen in videos . Kim Rossi and Katie Wright ( twitter) scoff at the money “wasted” on studies of gaze or genetics because they illustrate just how inadequately the vaccine causation hypothesis explains ASDs. In fact, a recent study** shows how unvaccinated younger siblings of kids with ASDs have the SAME rate of ASDs as vaccinated ones**
** I won’t provide the title because Orac’s regulars already know it by heart and anti-vaxxers are immune to learning from research like this
it’s Anjali Jain et al, JAMA, April 2015.
And here are my questions: is this what inflammation of the brain really looks like? Are these the expected levels of IL-37 and IL-18? Or, if there were an infection would you expect them to be much higher? How well do these cytokines persist in the brain after death? Are cytokines released during death?
And they say that IL-37 is released due to TLR activation. Which TLR? There are many and they have very different activating factors themselves.
Also, student’s T on 5 groups? What statistical software were they using, Excel? I mean, come on. You’re professors at universities. You should know this, and if you don’t you should be able to wander down the hall and ask the biostatistics department.
Not seen in my previous comments, but yeah, these questions came to my mind. Well, more generally, are these cytokines remnants from the development of ASD, or are they due to later events? The donors didn’t get killed and harvested after they ‘become’ autistic, but later in their life.
Not being a specialist myself…
In theory, that’s what the control tissues are for, to provide a baseline. But given the traumatic aspect of some of the donors’ deaths, I would welcome some reassurance that control and autistic tissues are indeed comparable.
Indeed.
What else is there to say?
To anti-vaxxers it is always the vaccines, never anything else. The fact that children suffer numerous infections in the first couple of years of life counts for nothing.
@ Chris Preston,
Oh sure, that’s why the worldwide autism rate of of 1 in every 45 children, that had persisted for 200,000 years; finally started to plummet dramatically; after those infection reducing vaccines were introduced.
Especially note how the rates went into a free-fall after each addition & increase to the immunization schedule! Profound!
Obviously; decreasing infectious disease with vaccines has been an answer to our prayers as autism appears to be becoming a thing of the past; as autism has obviously been caused by childhood infections all along.
(sarcasm)
Jesus freak man can you hear yourself?
And speaking of brain and body on fire, but it’s actually the ‘gift’ of autism, I am sure everybody remembers, Carly Flieschmann. She was that non-verbal autistic girl in that ABC interview that could type her complex ideas and thoughts. Interestingly, the first words Carly typed wasn’t ‘hi mom’, or ‘want food’ or ‘look’. Those words were ‘hurt’ and ‘help’.
Hearing that gave me chills. There was something eerie to it, as a scene out of an horror movie. Autism the demon, torturing that poor child.
Leave it to you to reduce her life and contributions to self-serving shrill and hysterical detritus. She’s contributed more in a single blogpost than you ever will with all your trolling.
Here we go, when gergle’s smelly brain dump doesn’t pass muster, gergle change the subject and fail…
… No. Just… no.
If you were more interested about autism beyond vaccines, you would know that there are several explanations other than inflammation for these words.
We provide autistic people with means of communication in part so that they get help for the tasks they can’t do alone (instead of letting their needs be ignored).
One of the major things I learned in past years is that one of these needs are quite often basic health care ; and that untreated pain is often one of the major cause of behavioral problems (like suffering from cavities and being incapable of getting help).
Carly Fleishman uses facilitated communication. She has never been independently observed typing coherent communication.
Not that this is really relevant to vaccination. Vaccines didn’t cause her autism.
Damn, that’s right. I dropped the ball on that one. Thanks for inadvertently reminding me.
The very story you posted states she typed those words in response to being sick, not being autistic. Why hold a view so weak you have to lie to support it?
Can’t believe that I have been banned so many times here and accused of being a troll. Aren’t my inputs not serving as inspirations for Orac’s blogs?! To think I participate and I am the only one here not getting paid. No end in sight for the discrimination and persecution ‘antivaxxers’ face.
EOSTFU!
If someone is paying me for commenting here, can you get on to their payroll department, being as you seem to know so much about it, and get them to send my money on? I’m retired, so I need it.
There’s a good chap!
Same here…where’s the line for those pay offs? My Goddess, does he really think that?
I’m in the UK. Can I get my cheque in dollars till the whole Brexit thing stabilises?
Mind you, technically Greg is correct. I am getting paid, just not for this sort of thing. That’s the benefit of having a job. No wonder Greg is bitter. He’s unemployed.
Notably, I don’t see that Theo-Theo correlated actual histologic evidence of inflammation in the brains of the auto accident victims with elevated cytokine levels. And what would lead to the conclusion that IL-37 increases are insufficient to completely damp down the elevated IL-18? Could be that homeostasis is occurring with no actual increase in inflammation.
Looking at the Beth Israel press release (in relation to the Anderson paper) I was struck by this passage:
”With no apparent evidence of viruses known to infect the brain, the presence of these tissue-attacking immune cells throughout the autistic brains suggested one of two scenarios, explained Anderson. Either the T-cells are reacting normally to a pathogen such as a virus, or they are reacting abnormally to normal tissue – the definition of an autoimmune disorder.”
I see a third possibility – that the T-cells are reacting normally to abnormal brain tissue – astrocytes that are malfunctioning due to a genetic abnormality or acquired condition.
I saw this Theoharides paper making the rounds in anti-vax forums, but all I could see was the abstract as it’s paywalled. Even this first part you cite (which I hadn’t seen before) makes me shake my head:
So the autism group died in car accidents and the control group did not? I will assume Theoharides et al had the minimal courtesy not to use children whose cause of death from the car accident was head trauma. However, dying from any trauma causes all sorts of inflammatory responses and if they don’t know whether the child died immediately or not–because if not immediately then messenger RNA changes in could easily have occurred due to trauma alone. This whole thing seems pointless, especially if the controls did not die of trauma.
I don’t know about the head trauma issue, but my reading of the paper is that all the children, both with and without ASD diagnoses, had died in car accidents.
Well it says “Controls were selected without any known brain disease or trauma and were matched to the subjects with ASD to the extent possible as shown in SI Appendix, Table S1.”.
Without any trauma to me implies controls didn’t die in a car accident (which is trauma, which honestly is a bizarre inclusion criteria to begin with unless it was the most common cause of death for the tissue bank for this age group was car accidents), but maybe they meant the controls died in a car accident but had no history of head trauma or trauma prior to the car accident…but if you died in a car accident, you suffered severe trauma.
The wording of that whole paragraph is awful. Lousy peer review IMHO.
@ Christopher HIckie
I read “The only inclusion criteria used were males, 1 to 12 y of age, who had died in car accidents.” as applying to all 16 individuals included irrespective of ASD diagnosis. I did interpret it as no trauma prior to the accident that killed them, but it could be certainly be clearer.
Wow! That was my first thought (car accidents=trauma=inflammation), but I didn’t post the question because not being a doctor or medial person of any kind, I thought maybe I was just making shit up.
mediCal person What’s a “medial person”, eh?
‘What’s a “medial person”, eh?’ – Just an average Jo….
For Greg:
Former Anti-Vaxxers Explain What Changed Their Perspective
C’mon Julian! — changing minds?! Haven’t you heard of the Vaxxed Bus? Antivaxxers becoming provaxxers, or provaxxers becoming antivaxxers? If you want to fight the war of who is actually changing minds, it’s your bow-and-arrow versus our hydrogen bomb.
More like a methane gasbag.
You already tried yesterday to drop a bomb, it was more of a pétard mouillé. Really ready for a re-match?
BTW, fragging your own team, as you Antivaxers are wont to do, doesn’t count.
Julian, here in Ontario they have you attend a propaganda video session if you’re seeking exemptions for your kids. Do you know how many ‘antivaxx’ parents the Ministry concedes changed their minds. Zero!
Funny, last year they accepted my affidavits without asking me to attend. Had they requested, I’d probably pass the time having one of these civil discussions with you guys.
Yah, death is a fantastic marketing tactic.
said gergle….
While you’re having fun with the rest of the peoples here, here I am taking excellent care of your wife who asked me out because she was seriously lonely.
Now, could you please vaccinate my child? Pretty please? Your wife is okay with that.
Alain
Pointless Memes & Tweets To Help You Press Pause
11 and 13.
Sigh. Okay, here’s my persnickity complaint. I’ll have a more general one in a moment.
“The immortalized human microglia-SV40 cell line derived from primary human microglia was purchased from Applied Biological Materials Inc. (ABM Inc.; Richmond, BC, Canada) and cultured in Prigrow III medium supplemented with 10% fetal bovine serum (FBS)”
I know this is an uphill battle, because the companies that sell the immortalized lines tell you to, but do not culture microglia in 10% serum. There are many serum factors that have been shown to activate microglia; some of them are implicated in additional neuronal death in the post-stroke ischemic penumbra. If microglia are seeing 10% serum in vivo, there’s something very, very wrong (like, well, a stroke).
If you’re doing work on a cell line, transition it to SFM first. If you’re doing primary microglia work, start them off on SFM, they’re used to that.
And don’t say you did experiments on ‘microglia’ if you used an immortalized cell line. Get primary human microglia to confirm any cell-line findings.
(Not to mention that when you plate adherent monocyte-lineage cells, they release a burst of cytokines when they adhere to the plastic, including inflammatory cytokines like TNFa, so you want to let them settle and then change the media before doing any experiments.)
Ooh, good to know! I’m always amazed at the things your sources fail to tell you, like, oh, these MyD88 knockout mice need to be on antibiotics. (Could have told me that before the first batch died, thanks!)
I know when it comes to cellular human treatments everyone’s trying to move away from any kind of serum; it’s just too high-risk to have in your supply chain.
I’m so glad I don’t work with adherent cells.
@Chris:
“Without any trauma to me implies controls didn’t die in a car accident (which is trauma, which honestly is a bizarre inclusion criteria to begin with unless it was the most common cause of death for the tissue bank for this age group was car accidents)”
“Unintentional injury”
https://www.cdc.gov/injury/wisqars/pdf/leading_causes_of_death_by_age_group_2017-508.pdf
Probably includes auto accidents, but also falls and drowning? I’d think drowning would be more reasonable to use than auto accidents.
Looking at the Table in the supplement, it doesn’t say what the cause of death was. It also doesn’t say whether the kid had started puberty or not, which involves a LOT of changes to the body and the brain. That’s a substantial source of potential group imbalance. The ASD group had only two members under the age of 12, the non-ASD group had 5. The post-mortem intervals were also more consistent in the ASD group – 11-20, while it was 3-27 in non-ASD. The mean comes out to be similar, but the range isn’t the same at all, IMO.
Yes, and if you died from a car accident, even if it wasn’t head trauma, it’s quite possible you still had hypoxic ischemia to your brain in the time interval from when the accident occurred to when you died. And if that time was long enough to be in the hospital, then that hypoxic ischemia will trigger all sorts of interleukins in the brain. There is way too much uncontrolled for here in this study IMHO.
Athaic, it was reported that the ‘cuffing’ occurred in more than 2/3rd and closer to 70%
I’d wager that the other 30% were the high functioning ones.
Must say I am a big fan of Vaccine Papers, but he did say the cytokines IL-6 and IL- 17 are the culprits in autism inflammation. This study is saying it’s IL-18. If he is lurking I am hoping he will account. Maybe I will take a walk over to his site. Anyone here wants to join me?
And for what it’s worth…..
Theoharides only measured IL-37 and IL-18? Could it be that other inflammatory citokines are also increased with autism proving to be an inflammatory condition?
I happened to cite quite a few of Theoharides papers in my PhD thesis (related to my mast cell work, where he’s a major name on the cytokine side). I never noticed his woo side, but he’s a big name in the field and likely did not need much help to publish in PNAS. It’s likely his name sufficed: even though he used child brain slides for his research (likely the major reason for a PNAS inclusion), it’s quite a light paper in results (which does make it frustrating: a PNAS paper does help start a career).
The stats are wrong (though it’s nice they checked for normal distribution). The way to do his stats like he wants analyze the results is a one-way ANOVA with Dunn’s post-test (which compares each condition to control, as each condition are basically a concentration-response curve). It’s also interesting to see the absence of such a concentration-response relationship in Figure 4. And the results are pretty mild when they look at IL-37 gene expression, an ANOVA with post-test would wipe much of the statistical significance away. It’s also weird that even though there is an effect on IL-37 gene expression, no protein is detected. If the ELISA doesn’t work, they could do a Western blot.
It’s a shame the paper is behind a paywall (PNAS was always open-access to my knowledge, but they do seem to have introduced a relatively cheap 1-year embargo now (cheap, as 10$ is way lower than usual 1-article access charge)).
If autism is due to vaccines creating inflammation/ cytokine storms/ autoimmunity/ microglial activation ( choose one or more)
why does it occur at all in the unvaccinated younger siblings of kids with autism? ( Jain et al). Same rate as vaccinated kids.
This study does not have 12 or 16 Ss -btw- more like 80K+.
Interesting how anti-vaxxers never cite studies involving the aforementioned early indicators or autism sans vaccines.
Why is that?
@ Roadsterguy, Athaic, Murmur, DB, r Chris, Chris P etc: Thanks.
Denice, if the hypothesis put forward based on this paper is correct, then any inflammation, not just those caused by vaccines, such as those caused by vaccine preventable infections and other infections, would cause autism. If this hypothesis were true, autism should have been endemic back in the days before there were vaccines.
It makes no sense when put together with all the other information we know about autism, such as its strong genetic component, it being present well before most vaccines, it being at the same frequency in vaccinated and unvaccinated populations, and so on.
Exactly. That’s why I list studies like Jain’s, early indicators of ASDs or genetics.
A thought experiment for anti-vax believers:
Two researchers in Canada** believe that GMO foods cause problems with children’s growth resulting in shorter stature. They create an elaborate hypothesis about how these products interfere with mechanisms that utilise calcium in bone growth. They measure many of the imagined biomarkers of this hypothesised process in groups of children of different ages. They do complex evaluations of bone growth in infants and toddlers living around industrial farms. Further long term research monitoring infants is planned.
HOWEVER other researchers a decade ago have shown in a large study that kids fed exclusively non-GMO foods and those who ate mostly GMO foods are the same height as adults.
** just joking. Most Canadians are smart.
@ Denice,
why does it occur at all in the unvaccinated younger siblings of kids with autism
Because they only studied kids who didn’t get the MMR vaccine. It’s not the MMR vaccine that is causing autism.
Autism is occurring in the kids who receive the 4th Tdap/DTP concurrently with the first MMR.
The amount of truly unvaccinated kids in those studies was almost nill.
If you’re now claiming autism is caused by concurrent MMR and DTaP (DTP is not used within the US currently), then why would it show up in children you claim didn’t get the MMR?
I’d like to take a moment here to thank and respect the parents of all the children who’s brains were part of this study. It is a truly selfless act to offer up your child’s body not just to organ donation but to this kind of basic science research.
Thank you for this incredibly generous act, and I’m sorry the researchers couldn’t respect your child more by using the correct statistics.
Reflect on that argument for a moment, and consider the full implication of it. Orac is actually suggesting that two separate inflammations may occur within the child. A ‘good’ inflammation from vaccination that is limited to just making vaccines effective, and a bad genetic one that may cause autism. At this point, one may ponder how the two would get along. Personally, I think the relationship would be acrimonious and I can see fights like this…
Good Inflammation: Bad Inflammation, I had enough! Because of you, people are accusing me of giving kids autism! We all know I just
protect kids from diseases! I want you to pack your stuff and get out!
Bad Inflammation: Mr Goodie Inflammation, why don’t you get off your high horse! So what if I give kids autism? What is so bad about that?
Ask the folks at RI — they will tell you there is nothing wrong with autism! It’s just a difference and can also be a ‘gift’!
Unreal!
Again distorting our words?
Nope.
Two points here.
Orac (and a number of us) are reminding the readers that inflammation also occurs in non-vaccinated children. Remove the vaccines, you still inflammation following ‘normal’ immune reactions. If children are predisposed to suffer from an inflammation following vaccination, odds are very good they will also suffer from any other type of inflammation. Maybe even more so.
We also suggest that the inflammation being seen in these post-mortem tissues may have occurred after the children become autistic.
Really, read again our comments.
Actually, you are projecting. You antivaxers are the ones going with the dichotomy that immune reaction to vaccine = bad, immune reaction to wild pathogen = good.
Nope. We are not saying that either.
No Athaic, you are arguing that, not Orac. Orac instead suggested that the inflammation may be due from the genetics of autism, with it either being a byproduct of the autism or the active agent causing the disorder. You are now proposing that the inflammation may be due from a wild source. So, I guess we now have three candidates, with vaccines causing the inflammation and leading to autism being the third., Anyway, I am still sensing a desperate effort to divert by flinging whatever at the wall.
Nope. Well, yes and no.
I was responding to your “Orac suggesting that two separate inflammations,” one good and one bad. Which he didn’t.
A masterful summary.
Anything in the articles you loaded and lauded which doesn’t fit with this hypothesis?
“Whatever”? Open a freaking book about the immune system.
There are 10 people in the house with the murdered guy, three of them actually have blood on their hands and are known felons, but no, the murderer can only be the butler. A butler who may not even be present, to boot.
I swear, even Inspecteur Gadget has better sleuth skills than you.
There are mild inflammation and serious inflammation. Vaccines cause sometimes the previous one, VPDs the latter. This because weakened or killed pathogens are used. Of course, no inflammation a is good thing.
Google Scholar search “brain trauma IL18” returns interesting papers.
Elevated Intracranial IL-18 in Humans and Mice after Traumatic Brain Injury and Evidence of Neuroprotective Effects of IL-18—Binding Protein after Experimental Closed Head Injury
Ido Yatsiv, Maria C. Morganti-Kossmann, Daniel Perez, Charles A. Dinarello, Daniela Novick, Menachem Rubinstein, Viviane I. Otto, Mario Rancan, Thomas Kossmann, Claudio A. Redaelli, Otmar Trentz, Esther Shohami, Philip F. Stahel
Journal of Cerebral Blood Flow & Metabolism
First Published August 1, 2002
https://doi.org/10.1097/00004647-200208000-00008
Brain injury, of course, causes inflammation.
As an outsider it looks like it’s hard to avoid entering the rabbit hole and finding out just how deep it goes.
I like to remember that every study and hypothesis, suggesting possible reasons why vaccines could cause ASD, are completely irrelevant. If vaccination cannot be statistically linked to autism then searching for potential links is a waste of time. First prove a link. THEN look for a reason.
I like to remember that every study and hypothesis, suggesting possible reasons why vaccines could cause ASD, are completely irrelevant. If vaccination cannot be statistically linked to autism then searching for potential links is a waste of time. First prove a link. THEN look for a reason.
Numb, if flawed epidemiology studies say jumping off a cliff is safe, people will still get suspicious after seeing the dead body of the person who jumped off a cliff.
A complete non-sequitor. Antivaxxers have rejected studies that refute their beliefs simply because they prove them wrong.
Either give examples of flawed studies and how they are flawed, or STFU.
Greg, this is precisely what I’ve been saying to you. You called them flawed but, if you can’t demonstrate why from a statistical or medical experts point of view, then anything else is sour grapes. Point out why a statistical technique should not have been used. Point out actual mathematical errors. Point out something but try to analyse your objections. Are you objecting because the technique removes or disproves a correlation you have faith exists? Or can you point to a statistics text book and say “here is your own reference book saying don’t analyse that sort of data in this way”. If you try to claim that the very structure of medical statistics hides a vaccine/autism correlation then you are unable to apply logic.
Dangerous One, that doctor in the Highwire video is actually thinking your way, but not that it helps you. At the 14:27 mark he contends that it’s likely not just T-cells going rogue and destroying healthy cells, but those cells doing their jobs and destroying abnormal cells damaged by the heavy metals and contaminants of vaccines. Seriously, if Exely is right and there is indeed excessive amounts of aluminum in autistics brains, what do we think it will do to brain cells?!
The Dangerous One’s full quote….
Another unnamed doctor making unsupported assertions that vaccinesdidit. Can’t you people ever come up with anything credible and interesting?
Unnamed doctor? Actually his name is Dr Nuenschwander, MD, Board Certified Integrative Medicine. Watch his Mic drop.speech to the ACIP, imploring them to change course. It’s gooooddd!
Board Certified Integrative Medicine?
Nice self-own, dude.
I watched that speech. It would only be a mic drop for people who want to believe or who don’t know the actual data behind vaccines – neither of which sit on ACIP.
As to the rest, I can understand why a doctor who sells fake autism cures that involves telling parents vaccines causes autism would not like ACIP’s work. I don’t think the problem is with ACIP there.
https://www.bioenergymedicalcenter.com/services/autism
By the way, our host discussed this doctor in the past.
https://www.respectfulinsolence.com/2018/10/18/vaccine-choice-empowerment-symposium/
Integrative medicine? Did you type that with a straight face? I know your standards are low but you shouldn’t keep announcing just how low.
Yeah, the Dr. Nuenschwander’s a real winner of a anti-vax quack. He runs an holistic clinic called the Bio-energy Medical Center where he’s dumb and ignorant enough to practice homeopathy. And he’s stupid enough at his clinic to have been fined by his state medical board
for giving estrogen to a woman who had a history of estrogen receptor positive breast cancer. Yeah, Dr. Alfred E. Neuman-shwander is what he should be called. Some mic drop…more like a turd plop.
Theoharides does have a COI here (I don’t know if it was disclosed in his paper) for Neuroprotek since it is marketed for autism by many of the resellers of Neuroprotek. From the Algonot web site (https://algonot.com/about-us/) it’s noted:
Theoharides also published research on Neuroprotek trialed on children with autism (A case series of a luteolin formulation (NeuroProtek®) in children with autism spectrum disorders.) wherein he states (mentioning brain inflammation, too):
Additionally on the Autism Free Brain Facebook page they’ve been citing his PNAS article for the last few days.
‘…’he contends that it’s likely not just T-cells going rogue and destroying healthy cells, but those cells doing their jobs and destroying abnormal cells damaged by the heavy metals and contaminants of vaccines.”
Of course, Exley would need actual evidence to support such a theory, but (according to you*) he’s diving right in and saying it’s ”likely”.
*Not clicking on that. The potential damage to brain cells from exposure to Del Bigtree’s fetid little enterprise vastly exceeds anything a vaccine ”contaminant” could do.
Not buying this. Likely couldn’t find enough manure to fling against the wall except, ‘So what if there is evidence of inflammatory ‘cuffing’ and brain cells getting destroyed? Doesn’t mean vaccines are doing it.’ Prove me wrong, Orac. ‘Takedown’ Anderson.
Well, if you are so smart, explain to us in your own words why these studies prove that vaccines are doing it.
This is for the silent viewers: Greg can’t and neither can his fellow travellers because they aren’t very smart but more importantly, are resistant to any ideas that conflict with their own biases. They make ridiculous claims and then rely on the actual smart people to “prove them wrong” because Greg doesn’t want to reveal just how ignorant he is (yes I see the irony but I’m referring to his perspective) because he doesn’t have the chops to ever critically-analyse studies hence why he relies on equally-dim Del Bigtree, Dan Steinberg aka Vaccine Papers and the like.
[…] Autism and brain inflammation: A study by Theoharis Theoharides used and abused by antivaxers October 29, 2019 […]
@ Science Mom:
We provide for lurkers and other exotic internet personae. We can’t affect True Believers: only the uncertain or uneducated.
-btw- Orac discusses Anderson today at RI.
I saw that but I am being kind and allowing a Choir member to be the first to comment.
No false modesty. Go ahead and entertain us with your falsetto solo.
And I note that dear Greg has not remotely addressed the point that there is no evidence in the study ATL that any child was genuinely autistic, as no details are provided about assessment and diagnosis. Without that minor detail all further discussion is redundant.
I still can read this paper (and sorry, I got better things to spend $10 on to get access to it) but anti-vaxxers really can’t be jumping all over this paper (or the Anderson one) about brain inflammation from vaccines being a cause of autism unless they know whether the donors of the brains with autism were even vaccinated. If you don’t know that, you can’t even advance to square 1 or your ridiculous speculation that “it’s the vaccines”
So, I see in short order with Science Mom, Carly Fleischmann went from being an inspiration to a fraud. Perhaps this article may assist others in deciding….
http://livetoad.blogspot.com/2008/02/skepticism-gone-septic.html
Greg, I really think there is something way off with you and your reading comprehension is pathetic.
It’s what happens when one’s brain is straitjacketed into a cartoonish view of the world, in which heavily outnumbered anti-vaccine superheroes battle legions of dastardly pro-vaccine Shill-Villains.
Other antivaxers suffer from the same affliction.
https://grrrgraphics.com/the-australian-freedom-force
Oh good grief you weren’t kidding nor exaggerating.
My fellow and sister minions bring up keen observations:
I myself wonder if some of our critics @ RI in the past few months suffer a kind of blindness to evidence they don’t like: there is overwhelming data that suggest that autism is unrelated to vaccination BUT they instead focus upon multiple possible pathways of “brain damage” via autoimmunity, cytokine storms or whatnot and totally disregard that central fact and genetic evidence. Those who study development of the brain have shown that the differences in brains of people with ASDs occur very early in gestation not at age 1 or 2.
I wouldn’t want to call it a ‘symptom’ or ‘learning disorder’ but something is amiss. Can it be only contrarianism? Can someone function as an adult, work and balance accounts and still be anti-vax? I know psychologists used to discuss ‘conflict-free zones’ of experience opposed to conflicted areas functioning at a lower level.
Ideas, anyone? I know that conspiracy beliefs are more likely amongst certain types of people.
I think it’s a kind of arrogance. Unconscious to a certain extent. The mind prioritizes immediate direct input over indirect input. So you see something spooky and get scared of the paranormal despite there being no genuine evidence that ghosts and spooky stuff exist. Certain people put so much weight on their personal experiences that they cannot conceive a possibility that their interpretation of events is wrong. They know what they saw or heard and anyone who says different is wrong.
I imagine there are shades to this. A higher weight on other peoples experiences too vs science that seems to contradict the experience. All you need are a few other ghost believers to bolster the certainty that you are right and the arrogant eggheads ( “what they need is some simple common sense and to realise that there are more things in heaven and earth etc etc by god”) are wrong. With this attitude you can then use any big Pharma malfeasance or scientific ambiguity as more evidence to back up your claims.
Antivax science is like tossing a coin twice. If both tosses turn up heads then its proof that vaccines cause ASD. Real science is like tossing five or six coins and then tossing or not tossing other coins depending on the results of the first toss. Or, as a scientist could say to an antivaxxer, “there are more things in heaven and earth than are dreamt of in your philiosophy”.
@ Terrie
If you’re now claiming autism is caused by concurrent MMR and DTaP (DTP is not used within the US currently), then why would it show up in children you claim didn’t get the MMR
I should have been more clear. I believe any vaccine could cause autism in a child with the suspected genetic variants; especially the Interleukin coding genes.
I believe the MMR concurrent with any variation of the DTP (Tdap, DTaP) implies an increased risk for ASD.
I was replying to Denice who invoked the vaxxed vs unvaxxed study where the ‘unvaxxed’ group was only unvaxxed for the MMR. That is not a ‘vaxxed vs unvaxxed’ study. That is a MMR vaxxed vs MMR unvaxxed study.
The younger, unvaxxed siblings who supposedly developed ASD were vaxxed as well.
If what you’re claiming was true, removing the MMR would reduce the risk and we’d still see a difference in large scale studies. (The same way studies show seat belts are better than nothing, but not as good as proper car seats) But there is no difference. This is just another case of your distorted thinking and lack of understanding of how science works.
@ Terrie,
No ma’am. Remove the DTP & see what happens.
Remove DTP and what happens is that 10% of children who contract diphtheria die. That’s not count the deaths from tetanus and whooping cough. Take your murder agenda elsewhere.
DTP was removed. That is why we have the DTaP and Tdap vaccines.
Why do you think this should happen to a child: https://elpais.com/elpais/2015/06/29/inenglish/1435559306_461811.html
Chris, and in an ironic bit of timing, two cases of diptheria have turned up in Scotland. Thankfully, due to vaccination, the risk to the general public is small, but it’s a reminder of how precarious public health is.
Yikes! It truly shows how dangerous Ms. Kincaid and her kind really are.
The first Madsen study is ambiguous about that, but the newer studies explicitly discuss completely unvaccinated groups. They have a slightly higher ASD rate, but not enough to be statistically significant.