Respectful Insolence

People who have read my review of FRONTLINE’s The Vaccine War may have noticed that the comments have featured someone who may or may not be a concern troll but is definitely at the very least very naive about the anti-vaccine movement. This commenter thinks that being harsh in my assessment of anti-vaccinationists will never reach anyone and only turn off the undecided. This commenter wrote:

Anti-vacciners’ view is in many cases just as strongly held as yours, and their data is just as compelling to them as yours is to you. Tell me, how many idiots yelling at you that you are stupid for thinking what you think would it take for you to change your mind? Any? Or would you be more likely to change it if someone came along and showed you the flaws in your reasoning/’data’?

Now it seems to me that the constructive way through this, if anyone wants to try it, would be to try to show anti-vacciners where the data they lean on is a) plain false, b) incomplete and c) faulty (misunderstanding of the way statistics works plays a HUGE part here). And I get that that is what lots of people are trying to do, but since they do nothing but focus on the autism “question” (which is actually only one really tiny part of the anti-vaccine concern) they are often completely missing the point.

My response was:

You’re either a concern troll or an incredibly naive newbie.

What makes you think that I and others haven’t tried to show these people the flaws in their data, “science” (I hate to use that word to describe the pseudoscience they use), and “reasoning” (such as it is). I have. Paul Offit has. The CDC and AAP have. Virtually every public health governmental agency and private institution has. Hell, Dr. Jim Shames on the FRONTLINE special itself was portrayed trying to reason with antivax mothers using a very cuddly, quiet, respectful tone. How far did he get? Not very. How far is he getting? Judging from the frustration in his voice during some interviews, not very.

In fact, I’ve written a couple of posts about this very issue. Here’s one where I challenge those who tell us to “make nice” on other scientific issues (like creationism, for example) in order to “persuade” the unpersuadable to come up with a technique to persuade antivaxers.

After that, I pointed out a couple of posts, one in which I challenged the promoters of making nice with pseudoscientists to put up or shut up when it comes to the anti-vaccine movement, and one in which I criticized a friend for a very misguided idea of “building bridges” to the leaders of the anti-vaccine movement. Of course, I was a bit puzzled because, if anything, my review was less “insolent” than my usual broadsides at the anti-vaccine movement, but maybe this is the first time this commenter has ever encountered this blog.

However, one thing I noticed is that J.B. Handley himself in the extended interview provided on the FRONTLINE website has provided me with an excellent example (thanks, J.B.!) of exactly what I’m talking about:

What makes you think you know better than all these scientists?

I just think the scientists who really stand at the front of this debate to contest our community are liars. I think they say things that are lies. I think they stand up there and say that it’s been proven that vaccines don’t cause autism. If they were parsing their words carefully and really being accurate relative to the science that has been done, I would trust them a lot more than I do. The minute something like that comes out of their mouth, I view them as partisan liars who don’t have our kids’ best interest at heart.

The only thing business has given me is the chance to detect lies and to see people clearly for what they are. I understand numbers very well. I’m perfectly capable of reading a scientific study and knowing what questions were asked and how the data was run and how it was analyzed.

There are some scientists — they’re few and far between on the other side — who tell the truth about what has and hasn’t been studied. But most use hyperbole and fear to try and get this issue to go away, and it’s just not going away, because I’m the guy who has to take the phone calls every day from the new parent who just watched their kid regress.

In other words, if scientists say something J.B. doesn’t want to hear about vaccines, something that directly contradicts his religion-like belief that vaccines cause autism, then to him they must be lying. (He’s called me a liar on various occasions as well.) To J.B., only the scientists on “his side” are not lying or corrupt. To J.B., physicians and scientists like Paul Offit, Anthony Fauci, can’t possibly be telling the truth; it can’t be that they honestly believe the studies and the science that have failed to link vaccines to autism. Truly, Handley exudes the arrogance of ignorance here, in essence apparently believing himself so smart, so savvy, that his view must be right and when scientists tell him he’s dead wrong he simply can’t accept it and concludes they must be not just mistaken but lying about the evidence.

Unfortunately, J.B. has demonstrated time and time again that he wouldn’t know a good (or bad) scientific study if it bit him on the proverbial posterior. In fact, so convinced is J.B. by his anecdotal evidence and personal experience that vaccines must cause autism that his definition of a “good” study is apparently any study, no matter how methodologically flawed, that jibes with his fervent belief that vaccines cause autism. Conversely, his definition of a “bad” study is apparently any study that does not, from which it follows (to J.B.) that every study that disagrees with his pseudoscience must be either bad science or corrupt science–or the scientists must be lying about them. Or all three at once. So confident is J.B. in his beliefs that he won’t even consider the possibility that these scientists are just as committed as he is and believe in their good science just as much as J.B. believes in his bad science. Of course, one side is right in this case, and it isn’t J.B., but no amount of scientific, clinical, and epidemiological evidence will ever convince him that he is wrong, and that’s why I can say with confidence that J.B. does not understand science. If you don’t admit the possibility that your hypothesis is wrong and actually look for evidence to show that it is incorrect in order to test it against reality, then you don’t understand science.

J.B. Handley, data and study cherry picker that he is, most definitely does not understand or accept the scientific method.

In contrast, I’ve always been very clear on this. Although quacks, pseudoscientists, and anti-vaccine zealots don’t believe me when I say it, there is evidence that could be produced that would lead me to change my mind on the vaccine-autism question. For example, if scientific and epidemiological studies of high quality were to be done that were to show a clear link between vaccines and autism, I’d start to question my current conclusion that vaccines don’t cause autism. If enough of these studies were published that they started to call into doubt the existing body of evidence refuting the vaccine-autism link, I would go further than questioning. Indeed, if enough such studies were published, I could well be forced to change my mind and, as Tim Minchin put it if he were ever to see evidence that proved homeopathy works, be forced to act:

If you show me
That, say, homeopathy works,
Then I will change my mind
I’ll spin on a fucking dime
I’ll be embarrassed as hell,
But I will run through the streets yelling
It’s a miracle! Take physics and bin it!
Water has memory!
And while it’s memory of a long lost drop of onion juice is Infinite
It somehow forgets all the poo it’s had in it!

You show me that it works and how it works
And when I’ve recovered from the shock
I will take a compass and carve “Fancy That!” on the side of my cock.

On second thought, maybe I’ll pass on taking sharp instruments to my private parts. Running through the streets yelling will suffice quite well, thank you very much.

In any case, show me solid scientific and epidemiological evidence that vaccines cause autism that is of sufficient rigor to call into doubt the large body of evidence that has thus far found no link between the two, and I’ll make like Tim Minchin if homeopathy were ever shown to work (minus the genital mutilation, of course, as amusing as it is in his beat poem). Like Tim, I’d be as embarrassed as hell, but I’d admit my previous view was wrong, change my mind, and admit my change of heart freely because science is what drives me far more than anything else when considering such questions. That’s the difference between J.B. and me. J.B. will never–I repeat, never–admit he is wrong based on science, no matter how much science contradicting his ideas and beliefs piles up in front of him. In the end, although I’d love this discussion to be about science and use science as my weapon to combat the anti-vaccine movement, I am under no illusion whatsoever that I will ever convince people like J.B. Handley, Barbara Loe Fisher, Jenny McCarthy, and their fellow travelers. However, I can do and have done is to have persuaded those on the fence. That’s about the best I can hope to do. And, although ridicule is very appropriate, given the looniness of much of what anti-vaccinationists claim, ridicule is far from the only weapon in my armamentarium, as much as it stands out in this blog. I use many other methods, and have pointed out time and time again that it is not the parents who are confused who are the victims of the occasional Orac-ian screed chock full of insolence. It’s the arrogantly ignorant.

Like J.B. Or Jenny McCarthy. Or Barbara Loe Fisher.

You know, perhaps I should “deconstruct” some of the interviews on the show. There’s a lot of blogging material there. But not here, though. Orac is far too insolent, far too mean, and far too nasty. He even might be accused of hating mothers! Perhaps my other blog would be the place…perhaps on Monday. Maybe J.B. would actually finally show up there, as he never shows up when I criticize him under my own name.

Maybe…

It’s too bad that this weekend is a major grant crunch time. No promises.

Comments

  1. #1 Shay
    April 29, 2010

    The only bridge one should build to an anti-vaxxer is one tall enough from which to push him/her/it.

  2. #2 David N. Brown
    April 29, 2010

    “I think they say things that are lies… The minute something like that comes out of their mouth, I view them as partisan liars who don’t have our kids’ best interest at heart… most use hyperbole and fear to try and get this issue to go away…”

    Gee- that’s exactly what I’ve been thinking about the “Hairy Biped”!

  3. #3 reasonablehank
    April 29, 2010

    There is no other conclusion to draw from the hubris of JB Handley, and his band of acolytes:
    http://en.wikipedia.org/wiki/Dunning%E2%80%93Kruger_effect

  4. #4 =^skeptic cat^=
    April 29, 2010

    “Those people” and the people who say that HIV isn’t the cause of AIDS have this kind of hive mentality which makes them seem a good deal more numerous than they actually are. You’ll never get a single “uncivil” comment from an antivaxxer it is always 3 or more right in a row (usually saying the exact same thing: “shill or stupid”) and then you never hear from them again. Those people who say we didn’t land on the moon can be a less than civil at times but at least they fight fair, coming at you one at a time and sticking around to have a conversation.

  5. #5 Cath the Canberra Cook
    April 29, 2010

    Wait, does a perspex box of blinking lights even HAVE a cock?

  6. #6 Rogue Medic
    April 29, 2010

    When we are willing to call something science only when it agrees with our prejudices, we demonstrate that we do not begin to understand science.

    So it is with the anti-vaccinationists.

    Everything must have a cause that is simple, easy to explain, and does not cause any blame to fall on me – ever, for any reason. These are rules anyone could live comfortably with.

    Just ask any party line anti-vaccinationist.

    This is all subjectivity, but science is about eliminating subjectivity as much as possible – not worshiping subjectivity.

    Science is about objectivity.

    What else can I do to look for flaws?

    Not, How can I cover up these flaws that make me look bad, because if it makes me look bad, it must be wrong!

  7. #7 MD PhD
    April 29, 2010

    In 2006 JB Handley said “Like many parents trying to understand what happened to their child, we re-traced Jamison’s steps back to that fall and Christmas of 2003. The decline seems to have begun sometime in January, soon after the second flu shot. He began to play alone. His words stopped. He started running back and forth along walls and fences. For hours.”

    In 2010 JB Handley said “… My kid got six vaccines in one [day], and he regressed. You don’t have any science that can show me that the regression wasn’t triggered by the six vaccines. There is no real-world study that shows me that those six vaccines didn’t cause my son’s autism.”

    What is your theory?
    In 1965 Dr. Austin Bradford Hill found a link between smoking and lung cancer. In his paper (The Environment and Disease: Association or Causation?) he details a clear and concise way to evaluate possible environmental exposures as cause of disease. Even though the paper is old is is very useful for investigating questions like the vaccine-autism hypothesis. Bottom line… the theory is not plausible.

  8. #8 xtaldave
    April 29, 2010

    Great post.

    I absolutely agree with your final point regarding changing your stance based upon available science. A lot of AltMedders and Woo enthusiasts take great pains to try and point out that science is either dogmatic or closed minded. However, if someone can conclusively demonstrate that and how say, homeopathy works – science will scratch it’s collective head, accept the new paradigm and move on.

    What is interesting if you turn this on them, and ask them what evidence would convince them that “homeopathy doesn’t work”, or “vaccines don’t cause autism.”

    The silence is often deafening.

  9. #9 Rogue Medic
    April 29, 2010

    Of course, maybe Orac just needs to read The Secret, adopt an appropriate mantra (such as Oprah), figure out what variety of crystal he is, and go hug Jenny.

  10. #10 mikee
    April 29, 2010

    As I was watching the Frontline programme I thought at first the anti-vaxers were coming across as quite reasoned and logical but then I started to notice a few more irrational ideas creeping in that indicates their contempt for anyone who disagrees with them (like real scientists). I wonder if some of the more irrational comments from them were not included in the programme, and if in fact this will help them. Also something the interviewer said seemed to me to directly imply a causal relationship between vaccines and autism, but I need to rewatch it as I was dozing off towards the end.

  11. #11 Rogue Medic
    April 29, 2010

    @ mikee,

    I wonder if some of the more irrational comments from them were not included in the programme, and if in fact this will help them.

    The producers/editors apparently eliminated a couple hours of Dr. Jay Gordon and a similar amount of JB Handley. Both are complaining that this makes them look bad. I think their claim only demonstrates a complete lack of self awareness.

    Most people acting foolishly in the public have to pay a publicist to try to repair the damage. Dr. Jay received a significant gift from Frontline. The producers/editors prevented Dr. Jay from looking as stupid as he wanted to look.

    Maybe if Dr. Kevorkian had been producing/editing the show JB Handley and Dr. Jay would have been given more time to self-destruct.

    JB Handley and Dr. Jay think that they would have been able to spew nonsense and not have it followed by clear evidence that each statement is false. That just would have required a much longer show. A broadcast of Oracian length.

    JB Handley was not afforded as much protection as Dr. Jay, but just imagine how idiotic the stuff was that was cut.

    Just think about if they diluted and successed that idiocy 20 or 30 times. That could be used to resuscitate the brain dead. I considered suggesting that they could cure autism, but that would be an obvious violation of the law of similars.

    JB Handley and Dr. Jay act as if similar amounts of interviews with scientists were not also cut. That is the big problem that I have been commenting on – these seem to be people with only the ability to see things from the most selfish perspective. They appear to be completely unaware of (probably uninterested, too) any other way of looking at things.

    These anti-vaccinationists are what I would expect if Veruca Salt and Mike Teevee wed, had children, and began giving parenting advice – if the children survived the shaken baby syndrome.

  12. #12 Gingerbaker
    April 29, 2010

    Can it be demonstrated in lab animals that high levels of vaccine components can cause symptoms of autism?

    I know it won’t convince the Handleys of the world, but a negative result might go some distance for the undecideds.

  13. #13 David N. Brown
    April 29, 2010

    “JB Handley and Dr. Jay think that they would have been able to spew nonsense and not have it followed by clear evidence that each statement is false.”
    Exactly what they will have gotten used to thanks to AoA censorship.

    I think what the complaints show is that antivaxxers will always twist media coverage in their own favor. Therefore, I say they should not be represented at all, except in quotations and clips for purposes of refutation. I also think blogs and news sites should go Old Testament, and make every posted comment by any member of AoA disappear until AoA’s own “moderation” is shut down.
    On the lighter side, on the downsides of accurate representation in the media, one of my all time favorite “Pearls Before Swine” punchlines: “I would now like the opportunity to rebut myself.”

  14. #14 DLC
    April 29, 2010

    But really, Orac . . . don’t you know that Framing is Everything ?
    Oh nevermind.

  15. #15 Neil Craig
    April 29, 2010

    “You’re either a concern troll or an incredibly naive newbie”

    Thats the way to go. Not namby pamby intelligent discussion of the facts just straight in there wiyh gratuitous ad hominum attacks. Cicero would be proud of you.

    Of course scientific truth has nothing to do with it or you would be equally critical of those who will never be convinced (mainly because they refuse to look at the evidence) that the various spurious government supported scare stories useful for imposing fascism (eg passive smoking, salt, catastrophic warming, LNT, nuclear waste etc) are at least equally lacking in evidence.

  16. #16 Rogue Medic
    April 29, 2010

    At least we don’t have to worry about whether Neil Craig is a concern troll or an incredibly naive newbie. He is just a standard issue troll. Nowhere near being on topic, but just watch him go!

    Neil Craig is much too good for any ad hominem attacks. Certainly he would never use any logical fallacies. He is here to correct everything. Maybe he has too much salt in his diet. That might explain it.

  17. #17 a perfect circle
    April 29, 2010

    That troll poo @15 smells of tu quoque.

  18. #18 DrFrank
    April 29, 2010

    Yes, of course nuclear waste is a spurious government supported scare story.

    They just covered it up so that the juggling industry wouldn’t have access to cheap materials for glow-in-the-dark balls.

  19. #19 Voice 0'Reason
    April 29, 2010

    You must admit, there’s no good evidence that salt cause global warming!

  20. #20 Pablo
    April 29, 2010

    I was reading the PBS vaccine forum yesterday, and there was a comment something like, “Who are you going to believe? Anecdotal stories from your friend? Or complete studies of nameless groups by the Government and Big Pharma?”

    Now, I’m not sure if the poster was being sarcastic or serious, but the attitude is pretty fair, I think. How can you believe science when you’ve got JB Handley’s ever-changing anecdote?

  21. #21 Jud
    April 29, 2010

    the various spurious government supported scare stories useful for imposing fascism (eg passive smoking, salt, catastrophic warming, LNT, nuclear waste etc) are at least equally lacking in evidence.

    The crank magnetism is powerful in this one.

    Let no fascist government ever infringe upon his right to smoke, eat salt, and generate nuclear waste! (That last seems a bit out of left field, even in this sweeping collection.)

  22. #22 Seb30
    April 29, 2010

    @Neil 15
    “Not namby pamby intelligent discussion of the facts just straight in there wiyh gratuitous ad hominum attacks”

    Yes, I agree, Orac could have spent a few paragraphs in his answer explaining why he thinks this of the commenter. Heck, Orac could have started a full post just to clarify his opinion, and have an open thread to give a chance to the commenter to counteract it.
    Oh, wait.

  23. #23 Neil Craig
    April 29, 2010

    Could have. Didn’t.

    Nor, I see, does naybody else have any inteligent arguments to bring forward, just a lot of glow-in-the-dark balls.

    Point made.

  24. #24 CurlyJim
    April 29, 2010

    @15: wait, nuclear waste is lacking in evidence?

  25. #25 Jud
    April 29, 2010

    Says Neil Craig:

    Nor, I see, does anybody else have any inteligent arguments to bring forward

    Nope, we’re just lost in admiration. For me, the feeling is akin to watching Johnny Knoxville put the family jewels at risk yet again in an episode of Jackass, like the one where he tests an athletic cup against a tennis ball machine. You just can’t believe anyone would really do this, but it’s kinda funny in a sick way.

  26. #26 speedweasel
    April 29, 2010

    A lot of AltMedders and Woo enthusiasts take great pains to try and point out that science is either dogmatic or closed minded. However, if someone can conclusively demonstrate that and how say, homeopathy works – science will scratch it’s collective head, accept the new paradigm and move on.

    The antivaxer’s position on science can probably be explained by their interaction with science.

    To start with they are just plain wrong, which doesn’t help them get along with the folks who are clearly right. They don’t have compelling evidence to support their claims; hence they are unable to challenge established paradigms which must frustrate them, bolstered as they are with a sense of their own importance. They refuse to engage honestly in the scientific process, proffering poorly manufactured ‘evidence’ and generally humiliating themselves both in scientific circles and more recently, in the media (which is what stings the most for them.) Then, they come off second best in their every interaction with doctors, scientists and rationalists, getting their arses handed to them from one end of the Internet to the other.

    Is it any wonder they decry science?

    Much easier for them to caricaturize and science and misrepresent the motives of scientists than it is for them to summon the intellectual honesty required to honestly asses the evidence and admit they are wrong. In short, they are in denial, propped up in their delusion by the DK effect and soldiering ever onwards in service of their ego. Weak minded, intellectual cowards who would rather risk the lives of your children than admit their own fatuousness.

  27. #27 speedweasel
    April 29, 2010

    Shorter speedweasel: “Science is standing between anti-vaxers and what they desperately want to believe.”

  28. #28 Adam_Y
    April 29, 2010

    that the various spurious government supported scare stories useful for imposing fascism (eg passive smoking, salt, catastrophic warming, LNT, nuclear waste etc) are at least equally lacking in evidence.

    Ummmm… Even the tobacco industry acknowledged that second hand smoke is dangerous.

  29. #29 JohnV
    April 29, 2010

    Neil Craig also appears to be a sarcasm denialist :P

  30. #30 somewhereingreece
    April 29, 2010

    Neil Craig, you obviously posted your comments within two seconds of coming to the blog for the first time.

    Orac, An excellent post yet again. I fail to see why scientists have to be civil to people who accuse them of accepting bribes for the sole purpose of covering up treatments damaging to children (and said scientists immunize their children as well! Oh the humanity!{/sarcasm}). Tim Minchin’s NSFW rebuttals are way too good for them.

    “Storm” was a fantastic song. It is like he took the homeopathy verses of “If open your mind too much your brain will fall out (take my wife!)” and expanded on it.

  31. #31 Joseph
    April 29, 2010
  32. #32 Ross the pediatrician
    April 29, 2010

    Orac, would you expect that the anti-vax noise might die down if we were able to show more tangible progress to understanding the etiology of autism. I am finding it difficult to ride the scientific high horse with parents of affected children while needing to admit that science hasn’t yet produced answers to what’s causing autism.

  33. #33 Seb30
    April 29, 2010

    @23 Neil
    “Nor, I see, does naybody else have any inteligent arguments to bring forward”
    Well, I was not aware there was something to discuss in your post.

    I have a hard time figuring out your list of gov’ scare stories. It looks like a catalog à la Jacques Prévert (you forget the raccoons).
    http://pagesperso-orange.fr/j.ballot/lire/Prevert.html#inventaire

    “eg passive smoking, salt, catastrophic warming, LNT, nuclear waste etc”
    OK, I suppose you deny that all of these things exist or are bad things. If you don’t, please clarify, but don’t blame us for not understanding a post empty of, how do you say, ah yes intelligent arguments.
    The way you say it, you seem to imply there are no nuclear waste. My dad was working on MOX fuel. He would be very surprised to learn that plutonium does not exist. Or that it’s inert.

    Actually, this may not be the best place to talk about any of your pet stories. You have plenty of blogs to discuss passive smoking, global warming, and so forth. JREF comes to mind, even if I found their posting system to be nightmarish.
    The current thread is about the antivaccination activists, I believe. You may elicit better responses if you were to stick to the matter at hand.

  34. #34 somewhereingreece
    April 29, 2010

    @Ross the paediatrician (#31)

    It is very well proven that vaccines are not the cause of autism. Trying to resuscitate that dead ancestor of equines is diverting time, effort and funds from trying to find the real causes

  35. #35 MartinM
    April 29, 2010

    On behalf of Scotland, I’d like to apologise for Neil Craig.

  36. #36 Liz
    April 29, 2010

    I am a mom and this is what we moms “know”: we can pick up very subtle clues that our children aren’t well, we can spot a fever, we know when to let them rest it off or when it’s time to get to the doctor. We “know” when our kid is being a drama queen (or king) versus being really ill.

    (Not all moms, mind you – some of them rush their kids to the ER for every fever over 101. I am speaking in broad generality, of course.)

    This is what we don’t “know”: If that rash is just a nasty diaper rash or serious strep infection, what exact virus is causing our child’s 104 fever (unless it shows telltale signs, which they rarely do), what is regular tantrum-like behavior and what is the true first signs of Autism, etc. Anecdote alert: I had a cousin who would beat her head against a wall and go mental about EVERYTHING in a weird way for years. But this was before anyone gave a crap, so my aunt had no one to turn to. My cousin is 38 years old now – perfectly normal, friendly, smart & successful human being. If she were 4 years old today, I shudder to think what kind of “therapies” she’d have to endure.

    Moms are great. Moms know how to take care of their kids. But can we stop acting like moms know everything? Because THEY DON’T. I DON’T. When I mentioned the other day that my kids accidentally might have eaten moldy bread, another mother at the park piped up, “Honey, mold is penicillin. They will be just fine. Case closed (dramatic arm gesture).” And she walked away.

    Case closed, indeed.

  37. #37 Rene Najera
    April 29, 2010

    *Yawn* What did I miss?
    DISCLAIMER: The opinion in this comment is my own and in no way represents the opinion of my employers, past, present, and/or future, and anyone who comes that unreasonable conclusion is, well, unreasonable.

  38. #38 mikerattlesnake
    April 29, 2010

    “Nor, I see, does naybody else have any inteligent arguments to bring forward”

    Your initial post deserved nothing of the sort, only mockery.

    @31

    While we may not have a definitive answer, we have more plausible answers than vaccines. None of the antivax ‘theories’ hold up under any sort of analysis of the data. Expanding diagnosis, increased awareness, and increased maternal age do (at least to some extent), though they have not been definitively proven. There are probably genetic factors and possibly environmental factors, but it seems that it’s going to be hard to nail down. Defering to wingnuts because science takes time is an untenable position.

  39. #39 passionlessDrone
    April 29, 2010

    Hi Orac –

    Show me solid scientific and epidemiological evidence that vaccines cause autism that is of sufficient rigor to call into doubt the large body of evidence that has thus far found no link between the two, and I’ll make like Tim Minchin and do what he would do if homeopathy were ever shown to work. I’d be as embarrassed as hell, but I’d do it because the science is what drives me.

    Hm. Well, I can’t do that; but I am curious why so many people that should be able to understand the difference between studying thimerosal and the MMR versus studying vaccination seem so willing to confuse the two things; i.e., ‘vaccines in general’. I’m not sure if this is lying or not, but the idea that we’ve studied vaccination is, at best, intellectually dishonest.

    The fact that we haven’t studied vaccination wouldn’t necessarily be a problem if we didn’t have a lot of evidence that children with autism generate different, frequently more robust innate immne responses than children without autism. The mechanisms of this aren’t clear, but several studies have shown that when challenged in vitro with a variety of TLR agonists, the autism population creates more pro-inflammatory cytokines than their non diagnosed peers (1,2,3). Furthermore we have several studies indicating that as indirect measurements of a more intense innate immune response are increased, so too, is the severity of autistic behaviors (4,5).

    The assumption has always been that a robust innate immune response without the associated virulence of the pathogen was harmless. I believe this underlies the reason that we have plenty of research on the adaptive immune response in a pediatric population, but absolutely no research on the innate immune response to vaccination in this age group. Unfortunately there is a growing body of literature that tells us that there may be time dependent effects of immune challenges that can produce difficult to predict outcomes in immune functioning and behaviors.

    A good example of this might be the recent study, “Postnatal programming of the innate immune response” wherein the researchers report:

    The postnatal period represents a malleable phase in which the long-term behavior and physiology of the developing organism, including its immune responses, can be influenced. Postnatal challenge of the immune system by introduction of live replicating infections, or administration of bacterial and viral mimetics, can result in a multidomain alteration to the defenses of the adult host. Findings from our laboratory and others’ indicate that the postnatal administration of lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (PolyI:C), which mimic bacterial and viral infections respectively, can influence the neuroimmune response (generation of fever and production of cytokines) to a second challenge to the immune system in adulthood. This long-lasting alteration in the innate immune response is associated with myriad other effects on the animal’s physiology and appears to be primarily mediated by a sensitized hypothalamic-pituitary-adrenal axis.

    These animals weren’t getting sick, they were just had bacterial or viral mimics administered. Some of the same authors have papers utilizing cytokine antibodies, or straight cytokine administration to demonstrate that, indeed, it is the innate immune response that can cause persistent changes into adulthood [6,7,8,9].

    There are over a dozen studies involving early life immune challenges in animal models with rather unexpected changes.

    So, I cannot prove that vaccines cause autism, I believe a strong case can be made that our population of interest may constitue a succeptible subgroup; a set of infants who react more vigorously to vaccines, and further, that without quality analysis, our ability to have certainty that vaccines are not impacting our children in unexpected ways is greatly hindered. In the meantime, we have drastically increased the number and robustness of the immune insults to our infants at their earliest pediatric appointments; the underlying function of which, generation of an immune response, is completely unstudied in terms of autism. It is possible to believe all of this without questioning the efficacy of vaccines at their desired goal, and indeed, be very scared of a return of deadly diseases of the past, but as someone who considers himself a skeptic, the claims by those like Hviid, that ‘the question has been answered’ are mind bogglingly naive and depend on large leaps of faith. This is a forum where statements long on faith and short on data is supposed to get eviscerated, and instead, it is being triumphantly embraced.

    – pD

    References

    1. Differential monocyte responses to TLR ligands in children with autism spectrum disorders [Enstrom, 2010]

    2. Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders [Ashwood, 2009]

    3. Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression [Jyomouchi, 2001]

    4. Macrophage Migration Inhibitory Factor and Autism Spectrum Disorders [Grigorenko, 2008]

    5. Increased serum levels of high mobility group box 1 protein in patients with autistic disorder. [Enzo, 2010]

    6. Postnatal programming of the innate immune response [Galic, 2009]

    7. Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats [Galic, 2008]

    8. Early-life immune challenge: defining a critical window for effects on adult responses to immune challenge [Spenser, 2006]

    9. Long term alterations in neuroimmune responses of female rats after neonatal exposure to lipopolysaccharide [Spenser, 2005]

  40. #40 dNorrisM
    April 29, 2010

    “Honey, mold is lysergic acid.”

  41. #41 cynic
    April 29, 2010

    pD,

    Thank you for your post.

  42. #42 Joseph
    April 29, 2010

    Well, I can’t do that; but I am curious why so many people that should be able to understand the difference between studying thimerosal and the MMR versus studying vaccination seem so willing to confuse the two things; i.e., ‘vaccines in general’. I’m not sure if this is lying or not, but the idea that we’ve studied vaccination is, at best, intellectually dishonest.

    I don’t think anyone is confused about that, pD. It’s a question of what sorts of hypotheses can be taken seriously at this point. The vaccine rejectors already proposed 2 mechanisms. Both hypotheses have failed completely. Why should any additional hypotheses be taken seriously, any more than an arbitrary made-up hypothesis (e.g. french fries cause autism) ? The track record of vaccine rejectors is dismal, and the likelihood that they are right is rapidly approaching zero.

    Additionally, and I’ve pointed this out previously, individual-level dose-response studies of thimerosal are, essentially, dose-response studies of vaccines in general, because the thimerosal dose a child got in the 1990s is probably a good proxy of vaccination load.

    There’s no question vaccination has been studied. It’s nonsense to say that’s a dishonest claim.

  43. #43 BlueMaxx
    April 29, 2010

    DR ROSS at (around) entry #32

    …but you SHOULD be able to get on the horse for Immunizations, given that while we don’t know what causes/triggers autism… we DO know there is no
    causation from vaccines. And we also do know that
    vaccines do actually prevent morbidity and mortality.

    RIGHT?

  44. #44 jaranath
    April 29, 2010

    Ross: I think somewhereingreece misinterpreted your question. I believe you’re saying “yeah, it’s great we know vaccines aren’t the problem, but it’s hard for me to convince parents we’re sure of that when we don’t know what the real cause is. Will finding that out shut up the antivaxxers?” My answer would be: Yes and no.

    I think a clear understanding of the real causes might help with the fence-sitters who are currently influenced by the antivaxxers. But while I think it will, it may not. Consider the success of homeopathy and other CAM woo despite vague or absurd models of action vs the clear models of so much of real medicine. We know what cancer is, how it’s caused, and how to treat it (with varying degrees of success), but that doesn’t stop a ton of people from buying into the BS of Trudeau and his ilk, sometimes to their death. If the scientific explanation for autism turns out to be sufficiently complicated and technical, and hard or impossible to prevent, people may still go for the easy answer.

    But for the core groups of antivaxxers…no. It will change nothing. They may lose some money, an people may pay less attention to them, but they will not back off. Because for the hardcore, this is not about autism, or mercury, or ether, or antifreeze, or pig viruses, or fetal tissue. It is about vaccines themselves, as a basic concept. Not necessarily the idea of preventing diseases, but the idea of injecting you with a needle containing disease-derived substances. There is a deep instinctual revulsion happening, an anti-contamination disgust reaction. You might peel away some of the core if they’re truly in this just for the autism, but antivaxxers have been around long before autism was associated with vaccines and will be around long after.

  45. #45 passionlessdrone
    April 29, 2010

    Hi Joseph –

    The french fry argument doesn’t apply because we have no evidence that autistics respond different to french fries, but we do have evidence that they do respond differently to an immune challenge. Do you understand the effect this has on the foundation of your argument? Have you read Enstron, Ashwood, or Jyonouchi?

    Have you read Griogrenko, who states:

    Thus, the central hypothesis underlying this research was that a genetic predisposition to a particular level of MIF production may lead to a proinflammatory profile of cell activation that, if present during a neurodevelopmentally sensitive period, might contribute to the etiopathogenesis of autism.

    This study was funded in part by the NIH and involved the genotyping, blood draws, and behavioral analysis of hundreds of individuals across two continents. Do you think someone would consider doing this immunological study if the likelyhood of significant findings was in the French Fry range?

    Have you read Garbett, who states:

    The most prominent expression changes in our dataset are clearly related to neuroimmune disturbances in the cortical tissue of autistic subjects. The idea of brain inflammatory changes in autism is not novel; epidemiological, (DeLong et al., 1981; Yamashita et al., 2003; Libbey et al., 2005) serological studies (Vargas et al., 2005; Ashwood et al., 2006) and postmortem studies (Pardo et al., 2005; Vargas et al., 2005; Korkmaz et al., 2006) over the last 10 years have provided compelling evidence that immune system response is an essential contributor to the pathophysiology of this disorder (Ashwood et al. 2006). Finally, converging post-mortem assessments and measurements of cytokines in the CSF of autistic children (Vargas et al., 2005), may indicating an ongoing immunological process involving multiple brain regions.

    I could go on and on, but the point is already clear. There is a vein of similarity, accumulating evidence of immune mediated pathology in autism. French fries, bigfoot, ufos, and pirate frequency analogies have no mechanism by which the immune system can be modified, but it is absolutely at the heart of vaccination. You don’t get vaccination without it. You can keep on pretending that we don’t have abundant evidence of immune contributions to the pathology of autism if you’d like, but that does nothing to reduce these findings, however, it does have an impact on your credibility.

    Regarding proxies, I suppose I wouldn’t have as much problem had Hviid said:

    Additionally, and I’ve pointed this out previously, individual-level dose-response studies of thimerosal are, essentially, dose-response studies of vaccines in general, because the thimerosal dose a child got in the 1990s is probably a good proxy of vaccination load.

    We’ve gone from ‘the question has been answered’ to ‘we essentially, probably, have good proxies’. That isn’t the narrative being sold.

    – pD

    References:

    1. Macrophage Migration Inhibitory Factor and Autism Spectrum Disorders [Grigorenko, 2008]

    2. Immune transcriptome alterations in the temporal cortex of subjects with autism [Garbett, 2008]

  46. #46 CurlyJim
    April 29, 2010

    Just came across a modelling paper on winning arguments on unsettled subjects on arXiv, which would seem tangentally related to Orac’s actual post: Public debates driven by incomplete scientific data: the cases of evolution theory, global warming and H1N1 pandemic influenza
    Basically says that, assuming their model is correct, the determining factor in debates is not convincing the open minded, but the generation of “inflexible actors” inside one’s own camp. Possibly this explains why science often seems to be on the losing side of such arguments.
    pd: Am I crazy, or does your above remarks mean that autists could be more likely to exhibit adverse vaccine responses, which combined with the onset of autistic symptoms at that age, would provide fine, fine confounding factors for people to confuse vaccine response and autism?

  47. #47 Joseph
    April 29, 2010

    The french fry argument doesn’t apply because we have no evidence that autistics respond different to french fries

    @pD: One could easily scan PubMed and find indications of something that could remotely be related to french fries, just like you do with vaccines. Try, for example, “unsaturated fat autism.”

    Have you read Griogrenko, who states:

    No, but I’m well aware of various findings suggesting a difference in the immune system of autistics. However, the leap you make is basically like saying that because children with Down Syndrome have immune system differences, then it’s prudent to study the association between vaccines and Down Syndrome. It’s a stretch to say the least.

  48. #48 MikeMa
    April 29, 2010

    Rene,
    Is that disclaimer the end of your pain I hope?

  49. #49 Kit
    April 29, 2010

    Are we all agreed that vaccines may cause encepgalitis?

  50. #50 cervantes
    April 29, 2010

    I don’t know anything about whether the immune systems of people diagnosed with autism tend to be abnormal in some way, but I do know that whether or not they are vaccinated, they will be exposed to innumerable antigens, including actual viruses that multiply in their bodies and assault their immune systems with billions of copies. If some sort of hyperactive immune response has a causal association with autism, then vaccination would most likely be protective. At worst it wouldn’t matter. I’d be much more worried about a kid actually getting measles, mumps and or rubella than a vaccine if this assertion is correct.

  51. #51 Cuttlefish
    April 29, 2010

    Notes and quotes and anecdotes
    And third- or fourth-hand stories
    A cheesy website, which promotes
    Colloidal silver’s glories
    A drop of homeopathy,
    A touch of chiropractic,
    Let’s claim it’s enteropathy,
    Or try another tactic—
    It doesn’t matter much at all
    Which quack earns our reliance,
    So long as children never fall
    Into the hands of science!

    Tales of sales and such details
    Show evil in Big Pharma
    When alt-med leaves such paper trails
    We’ll claim it’s just bad karma.
    Vaccines are money-grubbing schemes—
    Each virus or bacillus
    Is part of nature’s plan—it seems
    That doctors want to kill us.
    We’ll separate the false from true
    By confirmation bias—
    There are no data we can’t skew;
    Just go ahead and try us!

    We agree, the CDC
    Has no concern for health
    It’s all a great conspiracy
    Protecting doctors’ wealth
    You can’t trust doctors any more
    It isn’t even funny—
    This is important! This is war!
    We trust the former Bunny!
    Vaccines are tools of mind control
    That’s really why they’re made
    But they’ll have no effect on us—
    The tinfoil hat brigade!

    http://digitalcuttlefish.blogspot.com/2010/04/dispatches-from-vaccine-wars.html

  52. #52 JMG
    April 29, 2010

    I’m not sure if this is lying or not, but the idea that we’ve studied vaccination is, at best, intellectually dishonest.

    As soon as I read this line, I stopped. You fail.

  53. #53 Orange Lantern
    April 29, 2010

    Fantastic work, Cuttlefish! You have great talent.

  54. #54 Sid Offit
    April 29, 2010

    @Joeseph

    Should we not have adopted the heliocentric model of the solar system because it involved “shifting the goalposts” away from the Ptolemaic model. And should we continue to believe Pfeiffer’s bacillus is the cause of influenza because to think otherwise would entail “shifting the goalposts”?

  55. #55 Rene Najera
    April 29, 2010

    @MikeMa
    No, it’s only the beginning.
    DISCLAIMER: The opinion expressed above is my own and does not represent the opinion of anyone else. I mean, really, think about it. I’m a guppy compared to the big tuna (of which one can would have more mercury than you could possibly imagine).

  56. #56 Peapoh
    April 29, 2010

    Go Cuttlefish! XD

  57. #57 Dan Weber
    April 29, 2010

    I think the poster that Orac is harshing on was a naive newbie. But weren’t we all that at one point?

    I remember asking “why can’t we just do a study to see what happens if we delay vaccines a few months?” when I first came around this blog. I understand now what is wrong with that proposition, but that’s because I stuck around to find out. I could have easily found myself scared off.

    Someone unfamiliar with the anti-vaxxers disgusting tactics could be understood for saying that we should try being kinder to them.

  58. #58 passionlessdrone
    April 29, 2010

    Hi CurlyJim –

    Am I crazy, or does your above remarks mean that autists could be more likely to exhibit adverse vaccine responses, which combined with the onset of autistic symptoms at that age, would provide fine, fine confounding factors for people to confuse vaccine response and autism?

    I suppose you could take them that way; for example, several of the pro-inflammatory cytokines such as tnf-alpha, il-6 or il1-b are pyrogenic, and thus, a person with the same immunological profile might generate more of these, and thus, might have a fever more frequently than someone without in response to a vaccine.

    But that isn’t what I really meant. My point is that we have several different bodies of evidence (or lack thereoff):

    1) There is immune dysfunction within the autism population, and given the sufficient unknowns in the autism realm, participatory influences of the immune system in autism patholgoy are biologically feasible. The quotes from Grigorenko or Garbett I posted above speak towards this being a view held by people other than JB Handley. A number of the observed immune differences involve a tendency towards a pro-inflammatory state.

    2) Modifications to the immune system during development are not always harmless, even in situations where there is no associated virulence from microbial agents. The Galic 2008 reference above is a great example, a single, mild transient inflammatory event was sufficient to cause permenant brain excitability differences. The specific cytokine responsible, tnf-alpha, has been shown to be created an exaggerated levels in vitro in the autism population. The effects observed were time dependent.

    3) A complete lack of the analysis of the act of vaccination itself, as opposed to thimerosal or the MMR, regarding autism.

    Given that, proclamations that ‘the question have been answered’ seem a bit premature.

    – pD

  59. #59 passionlessdrone
    April 29, 2010

    Hi Joseph –

    One could easily scan PubMed and find indications of something that could remotely be related to french fries, just like you do with vaccines. Try, for example, “unsaturated fat autism.”

    Unfortunately for your analogy, vaccines are not ‘remotely related’ to an immune response; they are all about an immune response.

    Regarding french fries, however, you might be interested in this paper then: “Enduring consequences of maternal obesity for brain inflammation and behavior of offspring” It’s pretty crazy stuff! [seriously!]

    No, but I’m well aware of various findings suggesting a difference in the immune system of autistics. However, the leap you make is basically like saying that because children with Down Syndrome have immune system differences, then it’s prudent to study the association between vaccines and Down Syndrome. It’s a stretch to say the least.

    We know what causes Down Sydrome! If a woman wants to know how to drastically, drastically reduce her chances of having a child with DS, we can tell her exactly how to do this. We are also not observing explosive growth in the number of children with down syndrome. This is nothing like autism.

    But there is a reason it isn’t such a stretch, all of the animal studies I posted above as references 6,7,8,9! [there are plenty of others] All of them showed that an surge in the innate immune system during critical developmental timeframes had persistent, difficult to predict outcomes in the adult animals. These same innate immune system messengers, tnf-alpha, il-6, il1-b have been shown to be created by children with autism at exaggerated levels.

    – pD

  60. #60 passionlessdrone
    April 29, 2010

    Hi JMG –

    As soon as I read this line, I stopped. You fail.

    That is unfortunate. Can you show me any studies on autism and vaccination that don’t involve thimerosal and / or the MMR? This should be a simple task if your conviction is backed by data. If you can’t, then you fail.

    – pD

  61. #61 Zoe
    April 29, 2010

    “I think the poster that Orac is harshing on was a naive newbie. But weren’t we all that at one point?”

    Yes, I suppose I”m hopelessly naive as well, but I do think I speak for a lot of people who are sick to death of the namecalling and never getting anywhere. It’s almost as bad as Congress! Of course, the guy who yelled “liar” at Obama during the State of the Union got tons of money, so maybe the screamers are onto something. I guess I like the alternate personality a bit better, but he probably doesn’t get as many readers. ;-)

  62. #62 Jud
    April 29, 2010

    but we do have evidence that they do respond differently to an immune challenge.

    …and since the immune system was never challenged before vaccines (people never got diseases caused by infectious agents?), that’s why we see a difference in the level of reported autism? C’mon, can we get an admission that this makes no sense at all?

    On the other hand (and also in response to the pediatrician), there is statistically significant evidence of a linkage between both maternal and paternal age and the incidence of autism. Are people these days tending to have kids when they’re a bit older, at the same time we see an increasing incidence of autism (assuming for the moment that increased reporting isn’t entirely responsible)? Yep. And there is a quite definite linkage between parental (I believe it’s mostly or exclusively paternal) age and the incidence of another neurological disorder, schizophrenia.

    So why are you (why is anyone?) still barking up the vaccine “tree”?

  63. #63 Rorschach
    April 29, 2010

    Sid, are you honestly as stupid as you appear to be, or is it a playful act?

    Shifting the goalposts refers to the tendency to maintain the ultimate product of one’s beliefs while the underlying supports are changed. Antivaxers always claim it’s the vaccines: if not a specific vaccine, then maybe an ingredient in them, or if not an ingredient, then ‘too many, too soon.’ But it’s always the vaccines.

    You’ll note that in a away, shifting goalposts is exactly what defenders of the geocentric universe did. As astronomical observations became more informative, the epicycles that the Ptolemaens had to invent to preserve their world view became increasingly ridiculous. Eventually, though, the truth won out.

    Nitwit.

  64. #64 Smarter Than You
    April 29, 2010

    Well then Mr. Aflac, I mean ORAC…you will be very embarrassed very soon. I’m guessing somewhere around November / December timeframe. This is your year buddy!!!

  65. #65 Rob
    April 29, 2010

    @passionlessdrone

    If the immune response to vaccination in children who are hypersensitive to immune system triggers is potentially related to autism, then why was autism not far more prevalent when children used to actually get measles and mumps? Having the disease is vastly more taxing on the immune system than a vaccination. By this line of reasoning, children whose immune system has to deal with a large number of highly infectious agents should exhibit higher rates of autism.

    On the contrary, the incidence of autism has increased while the incidence of the diseases that vaccinations prevent has decreased.

  66. #66 mikee
    April 29, 2010

    “I do think I speak for a lot of people who are sick to death of the namecalling and never getting anywhere.” Zoe

    Hey Zoe, I couldn’t agree more. Perhaps arguing the facts with hard line vaxxers will never change their minds but neither will contempt, smugness or name calling. I think when such techniques are used it not only hardens the view of the hard liners but also pushes those who are unsure in the wrong direction.
    I remember reading a piece of advice on what to do when you have given a scientific presentation and you get someone who asks aggressive questions during question time. If you remain polite and rational the audience will be on your side. If you become aggressive back, the audience will start to support the questioner.
    A fellow skeptic also once told me “Attack the woo, respect the person”
    Right, time to put my flak jacket on and raise the shields :-)

  67. #67 Sid Offit
    April 29, 2010

    @Rorschach

    I thought you were killed at the end of Watchmen

  68. #68 passionlessDrone
    April 29, 2010

    Hi Jud & Rob –

    …and since the immune system was never challenged before vaccines (people never got diseases caused by infectious agents?), that’s why we see a difference in the level of reported autism? C’mon, can we get an admission that this makes no sense at all?

    If the immune response to vaccination in children who are hypersensitive to immune system triggers is potentially related to autism, then why was autism not far more prevalent when children used to actually get measles and mumps?

    Your analysis makes no allowance for a time dependent effect, one that was observed in several of the animal studies I posted; i.,e observed effects if the animal was challenged at postnatal day 14, but not on postnatal day 21. Throughout history an infant got exposed to plenty of stuff, but exposure over time was a curve throughout the population. The chance that an infant would get diptheria, typhoid, tetanus, hepatitis, polio and pncuemococcal by sixty days from the womb was very, very low. We’ve skewed this quite a bit, now our immune challenge exposure looks like a straight line, and we’ve done most of the addition to the schedule at the earliest time frames, two, four, and six months.

    Why is that in a system as complicated as the developing immune system we only seem to want to acknowledge time dependent effects when convenient to a strawman argument?

    On the other hand (and also in response to the pediatrician), there is statistically significant evidence of a linkage between both maternal and paternal age and the incidence of autism. Are people these days tending to have kids when they’re a bit older, at the same time we see an increasing incidence of autism (assuming for the moment that increased reporting isn’t entirely responsible)? Yep. And there is a quite definite linkage between parental (I believe it’s mostly or exclusively paternal) age and the incidence of another neurological disorder, schizophrenia

    I have absolutely no problem with the idea that older parents lead to more autism diagnosis, or other neurological problems. I happen to think that the potential problem of a true increase is too important to rest on the laurels of this God of the Gaps style argument.

    – pD

  69. #69 Todd W.
    April 29, 2010

    @mikee

    I tried the respectful approach over at Age of Autism. They banned me, after allowing some of their sycophants to sling away at me. So, I created the Silenced by Age of Autism blog to allow people to post comments that otherwise get censored or banned at AoA. Even at Silenced, I maintain a generally respectful, if occasionally blunt, tone.

    The hardliners will not be swayed by a respectful approach, from my experience. And I’d even say that regardless of the approach, the more a hardliner is questioned, the more entrenched they will become. Now, juxtaposing a respectful tone against such hardliner opinions is a good tactic when trying to convince observers.

  70. #70 bluemaxx
    April 29, 2010

    ATTENTION “smarter than you”… you ego needs tuning!

    and your post is arrogant and of course, seemingly out of context with the thread. Sort of how SID Off-it usually posts.

    if you have some sort of smugness borne out of factual knowledge, please share. If you just want to post weird threats about the upcoming fall season… please spare the group your noise.

  71. #71 gevesson
    April 29, 2010

    @54: If you want to shift the goal posts, you need to be *right*.

  72. #72 Basiorana
    April 29, 2010

    @Ross the pediatrician: I’ve repeatedly shown anti-vaccinationists the studies linking autism to older parents, and parents who have autism, that clearly show that there is a genetic component (even if we have no idea of the mechanism or the genes involved yet) and that vaccination is irrelevant. Now, current studies may not justify a complete turnaround, but the answer I’ve gotten is never “that’s not enough evidence,” it’s “you’re blaming the PARENTS, you’re a horrible PERSON, it’s not OUR fault!” with a side of “I KNOW IT’S VACCINES!”

    So in short, if the link was cleared up and understood better, then the current crop of anti-vaxxers wouldn’t change; their children would eventually come to accept it, and in a few generations it would be universally accepted that autism was caused by ______ genetic factors.

    That said, your job (convincing parents to vaccinate) will NOT get easier; antivaxxers are constantly coming up with new problems for vaccines to cause and have been since the precursor to vaccinia, variolation, was introduced to the West. If it doesn’t cause autism or asthma or allergies, they’ll pick something else for it to cause, some other unexplained thing, like fibromyalgia. There is always something vaccines cause, however implausible the hypothesis is.

    @passionlessdrone: Actually, if it were not for a combination of abortion and the fact that Down Syndrome children are usually infertile, the Down’s rates WOULD be rising. Women are having children later and later each year. They also get tested for Down’s– and over 95% will abort if the fetus shows signs of it. With autism, you can’t test for it in the womb, so no abortion; and mildly autistic people will then have children of their own, which further drives up the rates. Plus, every year diagnosis improves.

  73. #73 shannon
    April 29, 2010

    something that really bothers me about this Dr.Gordon quote:

    “‘Distraught, confused moms against important, well-spoken, calm doctors’ was your narrative with a deep sure voice to, literally, narrate the entire artifice.””

    he is trying to frame this as a feminist or gender issue, one that he is, naturally, on the right side of. ie, the womens’ opinion doesn’t matter, andn they are being portrayed as hysterical, against the kind and wise Patriarch, and how wrong is that.

    the problem is that antivaxers don’t get to have a corner on feminism, in order to pursue their agenda, or otherwise. Feminism has always relied on statistical evidence to further its views, and if it’s not, then it’s not doing its job and, it’s probably not feminism.

    as a pro science feminist, science is our ally. evidence is our ally. always. I’m not stupid enough to let them use this angle to frame their debate. it’s offensive, and it’s also completely mis-representative.

  74. #74 Jud
    April 29, 2010

    passionlessDrone writes:

    Your analysis makes no allowance for a time dependent effect

    I have absolutely no problem with the idea that older parents lead to more autism diagnosis, or other neurological problems. I happen to think that the potential problem of a true increase is too important to rest on the laurels of this God of the Gaps style argument.

    I don’t say this with any personal disrespect, but your arguments show significant problems with comprehension and logic.

    Taking the second quote first: It appears from this that you do not comprehend what a “God of the Gaps style argument” actually is. This is when one has no evidence of the existence of something (e.g., God), so one seeks to find the gaps where explanations do not exist and point to them, saying “Aha! Goddidit!” There is good evidence, in the form of statistically significant results of scientifically valid studies, that increased parental age is positively related to incidence of autism in offspring. No “gaps” – evidence! Whereas your insistence on some sort of vaccine-related explanation is a classic “God of the Gaps style argument,” since there is at present no scientifically valid evidence whatever for it, and the more actual evidence of other causes is found, the less anyone should be able to run around screaming “Aha! MMR/thimerosal/TooManytooSoondidit!”

    Now, re the first quote, two very large logical problems. Taking the less important first, as already mentioned by another poster, our immune systems are ‘challenged’ every single second of every day. There are quite significant immune challenges that occur even before birth. We do a somewhat remarkable continuous immune-system balancing act (not always successful in all of us) to avoid being sickened by our own quite viable intestinal flora. The ‘challenge’ presented even by multiple vaccines in infancy using weakened, killed, or partial antagonists is background noise in comparison.

    Now, regarding the second problem with your first quote (and with the entire argument you’ve been making in regard to studies of immune system reactions), there is an elementary logical flaw. The immune system reaction studies would be useful to establish the mechanism of action of one link in a causative chain between vaccines and autism if and only if there were such a chain. But there have been multiple excellent studies refuting to a scientific near-certainty (“God of the Gaps-style arguments,” anyone?) the proposition that there is any such causative chain whatever.

    To put it more simply: Proposition One = Vaccinated kids have no greater incidence of autism than unvaccinated kids. Proposition Two = Autistic kids’ immune systems react differently to ‘challenges’ than those of non-autistic kids. Since Proposition One is scientifically valid, the only appropriate response to Proposition Two is “OK, and if you’re right, so what?”

  75. #75 Shannon
    April 29, 2010

    additionally, the woman interviewed on the “vaccine war” show is also a pro-“natural birth” mom who gave birth at home with no medical assistance.

    don’t these women realize their “success” in these shenanigans is …..pure luck? Obviously not.

    sheesh, it’s almost like she’s trying to get her child killed. sorry, but…. good grief.

    http://www.msnbc.msn.com/id/34225823/ns/health-pregnancy/

  76. #76 passionlessdrone
    April 29, 2010

    Hi Basiorana –

    You might be surprised to learn that there is actually slight increase in Down Syndrome, even with more terminations. Joseph pointed it out to me here a few months ago. I had to admit I was more than a bit surprised.

    [Prevalence of Down syndrome among children and adolescents in 10 regions of the United States - Shin 2009]

    The rate of increase in DS is microscopic when compared to the rate of increase in the autism realm. As far as improved diagnostics, I won’t argue against a diagnostic component to what we are observing, but again, the ramifications of a real increase are too worrisome to me to accept the ever expanding estimates provided by soft scientists.

    – pD

  77. #77 Scott
    April 29, 2010

    As far as improved diagnostics, I won’t argue against a diagnostic component to what we are observing, but again, the ramifications of a real increase are too worrisome to me to accept the ever expanding estimates provided by soft scientists.

    It would be bad if it were true, therefore it must be true despite mountains of evidence to the contrary and not a single iota to support it? That makes less than no sense.

  78. #78 Sid Offit
    April 29, 2010

    @Jud
    The ‘challenge’ presented even by multiple vaccines in infancy using weakened, killed, or partial antagonists is background noise in comparison.

    Vaccination alters the way in which the immune system responds. Therefore the power of the challenge is immaterial. You’re argument is akin to arguing that white flour is healthier than whole wheat because it’s easier to digest

  79. #79 passionlessDrone
    April 29, 2010

    Hi Judd –

    I don’t say this with any personal disrespect, but your arguments show significant problems with comprehension and logic.

    Of all the times I’ve been called stupid here, this ranks among the most respectful. Thanks.

    Taking the second quote first: It appears from this that you do not comprehend what a “God of the Gaps style argument” actually is. This is when one has no evidence of the existence of something (e.g., God), so one seeks to find the gaps where explanations do not exist and point to them, saying “Aha! Goddidit!” There is good evidence, in the form of statistically significant results of scientifically valid studies, that increased parental age is positively related to incidence of autism in offspring. No “gaps” – evidence!

    It ooks like you misunderstood me, I’m OK with parental age as a factor; I’m not OK with the notion that we can have certainty that everything else, which is a lot, is diagnostic noise. I’ll try to be more clear.

    The gaps are the ever widening increses in children with autism. As rates rise there is no feasible mechanism by which anyone can disprove that ‘greater awareness’ isn’t responsible for it. Your argument, that advanced parental age constitutes all of the true increase absolutely mandates that the rest is the result of diagnostic changes. So, for example, if autism rates double again in the next year, there is nothing to keep the ‘greater awareness’ arguments from being used; it just sucks up the entire increase.

    Now, re the first quote, two very large logical problems. Taking the less important first, as already mentioned by another poster, our immune systems are ‘challenged’ every single second of every day. There are quite significant immune challenges that occur even before birth.

    Hm. Do you have any idea why, then, for example, one in four chidren get a fever in the days after getting the DTAP, but on any given day, nowhere close to one in four children get a fever? [1]. If our daily exposure to antigens “every second of the day” is so meaningful compared to a vaccination, why should this be the case? What do you attribute this side effect to, if not the immune response generated by the vaccine?

    How about this for a bet: We take one hundred children and have them vaccinated at two, four, and six months of age. Each of us gets to pick three days during their first year of life to guess which day they’ll get a fever. I’ll pick the day after their well visits. Every time one of us is correct, the other gives them one hundred dollars. If all things are equal between the day of a vaccination and days where all those seconds pile up, this should be an even bet. To sweeten the deal, I’ll give you $105 to your $100. Which days do you want?

    The ‘challenge’ presented even by multiple vaccines in infancy using weakened, killed, or partial antagonists is background noise in comparison.

    Can you validate this statement with evidence? Seriously.
    Your assertion that there is not an increase in the innate immune response in response to vaccination is unsupported by evidence. Do you have any studies you could show me involving a pediatric population that shows no increase in inflammatory cytokines following vaccination? If such studies exist, the should be simple to post.

    By way of example of the opposite, we could look to: “Effect of influenza vaccine on markers of inflammation and lipid profile” (2)

    Despite wide use of the influenza vaccine, relatively little is known about its effect on the measurement of inflammatory markers. Because inflammatory markers such as C-reactive protein (CRP) are increasingly being used in conjunction with lipids for the clinical assessment of cardiovascular disease and in epidemiologic studies, we evaluated the effect of influenza vaccination on markers of inflammation and plasma lipid concentrations. We drew blood from 22 healthy individuals 1 to 6 hours before they were given an influenza vaccination and 1, 3, and 7 days after the vaccination. Plasma CRP, interleukin (IL)-6, monocyte chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble receptor alpha, and serum amyloid A were measured, and differences in mean concentrations of absolute and normalized values on days 1, 3, and 7 were compared with mean baseline values. There was a significant increase in mean IL-6 (P < .01 absolute values, P < .001 normalized values) on day 1 after receiving the influenza vaccine. The mean increases in normalized high sensitivity CRP values were significant on day 1 (P < .01) and day 3 (P = .05), whereas the mean increase in normalized serum amyloid A was significant only on day 1 (P < .05). No significant changes were seen in mean concentrations of IL-2 soluble receptor alpha, monocyte chemotactic protein-1, or tumor necrosis factor-alpha. Of the lipids, significant decreases in mean concentrations of normalized triglyceride values were seen on days 1 (P < .05), 3 (P < .001), and 7 (P < .05) after vaccination. Our findings show that the influenza vaccination causes transient changes in select markers of inflammation and lipids. Consequently, clinical and epidemiologic interpretation of the biomarkers affected should take into account the possible effects of influenza vaccination

    What should we make of this study when compared to your hypothesis? The adults in question were surely challenged in the intervening seconds between vaccination and blood draw by everyday exposure, and yet, the researchers observed increases in IL-6. How is this possible?

    I’ve seen this argument made dozens of times, and substantiated with evidence exactly zero times. Why not just show me a study involving innate immune system markers and vaccination in a pediatric population?

    But there have been multiple excellent studies refuting to a scientific near-certainty (“God of the Gaps-style arguments,” anyone?) the proposition that there is any such causative chain whatever.

    Excepting the MMR, none of these studies involved vaccination, they involved thimerosal. Show me a study on vaccines and autism that isn’t about the MMR or thimerosal. Just one.

    To put it more simply: Proposition One = Vaccinated kids have no greater incidence of autism than unvaccinated kids. Proposition Two = Autistic kids’ immune systems react differently to ‘challenges’ than those of non-autistic kids. Since Proposition One is scientifically valid, the only appropriate response to Proposition Two is “OK, and if you’re right, so what?”

    The problem is that you did, indeed, “put it more simply”. Too simply. You have assumed that studying the MMR is the equivalent to studying all vaccinations. It isn’t. (If time isn’t an important factor, why not give the MMR, and every other vaccine the day a baby is born?) You may have assumed that studying thimerosal is equivalent to studying vaccination. It isn’t. You have assumed that antigens that encounter our skin, gastric acid, and mucous are equivalent to those that bypass these defenses and come alongside ingredients ‘designed’ to insure that there is a robust immune response. They aren’t.

    As someone who so gleefully throws out charges of a lack of comprehension, these points ought to be salient to you.

    – pD

    References

    1. Possible Side-effects from Vaccines [CDC - online - skipping link to avoid moderation]

    2. Effect of influenza vaccine on markers of inflammation and lipid profile [Tsai, 2005]

  80. #80 Prometheus
    April 29, 2010

    “Sid” asserts:

    “Vaccination alters the way in which the immune system responds.”

    Please elaborate with citations to peer-reviewed research that supports your claim.

    Prometheus

  81. #81 Sid Offit
    April 29, 2010

    Dev Biol Stand. 1997;89:297-305.
    Bordetella pertussis-specific Th1/Th2 cells generated following respiratory infection or immunization with an acellular vaccine: comparison of the T cell cytokine profiles in infants and mice.

    These findings highlight significant differences in the immune responses generated by vaccination and natural infection with B. pertussis
    ———————-

    Immunology 1996 87 372-380
    Thl/Th2 cell dichotomy in acquired immunity to Bordetellapertussis: variables
    in the in vivo priming and in vitro cytokine detection techniques affect the
    classification of T-cell subsets as Thl, Th2 or ThO
    It has now been firmly established that Thl cells play an
    important role in protection against intracellular pathogens.
    Natural infection with viruses and intracellular bacteria
    appears to preferentially activate Thl cells.2’4 However,
    attempts to induce Thl cells by immunization, especially with
    subunit or purified recombinant antigens, have proved more
    difficult.2′ In
    ————————————–

    Gynecol Oncol. 2008 Sep;110(3 Suppl 1):S1-10. Epub 2008 Jul 24.
    Immune response to human papillomavirus after prophylactic vaccination with AS04-adjuvanted HPV-16/18 vaccine: improving upon nature.

    The immune responses induced by HPV vaccination are different to those after natural infection.

  82. #82 dedicated lurker
    April 29, 2010

    Okay Sid, did any of those say those different responses are a) bad, or B) insufficient to provide immunity?

  83. #83 Chris
    April 29, 2010

    The immune responses induced by HPV vaccination are different to those after natural infection.

    Well I hope it is different! The natural infection increases the risk of cancer.

  84. #84 Archangl508
    April 29, 2010

    “These findings highlight significant differences in the immune responses generated by vaccination and natural infection with B. pertussis”

    “The immune responses induced by HPV vaccination are different to those after natural infection. ”

    Yes, but that is not what your original claim was. These findings highlight that the immune response between the acellular vaccine and natural infection are different, but that is not the same as suggesting that “vaccination alters the immune system”.

    Different antigens elicit different responses even within a similar type of response. Viruses induce different responses from bacteria, parasites, or allergens. Even with the category of viruses an influenza virus elicts a different response from polio virus or ebola virus.

    But the immune system is still functioning in the same way. Antigen is still presented to T cells driving activation, release of cytokines, etc. Where is the “altered immune system”?

  85. #85 Azkyroth
    April 29, 2010

    Orac: I assume you’ve seen this and PZ’s excellent summary but this timely vindication must be nice. :D

  86. #86 Sean O'Doherty
    April 29, 2010

    shittier than you wrote:
    “Yarble!”

    Yeah, makes as much sense as a dead rat in a water tank.

  87. #87 Joseph
    April 29, 2010

    The rate of increase in DS is microscopic when compared to the rate of increase in the autism realm.

    @pD: Once you consider that Down Syndrome is one mutation, whereas autism could very well be dozens of mutations, it doesn’t seem too microscopic, does it?

    I’ve actually run some back of the envelope calculations on this. US Census has historical data on maternal age. Additionally, I used the paternal age vs. autism model from the large-scale Israeli study, and fitted their figures to an exponential function (assuming some correspondence between maternal and paternal age.) Long story short, I estimated that the DSM-III identified autism prevalence in Israel (assuming the level of ascertainment remained constant) would go from 7.57:10,000 in 1980 to 9.11:10,000 in 2007.

    It doesn’t sound like much, but what if you’re looking at DSM-IV autism, with perfect case-finding?

    So I think some real rise is completely plausible, and you can quote me on that. But you already know what I attribute most of the passive-database rise to: information diffusion. The active rise (i.e. from prevalence studies) is mostly due to changes in criteria and changes in case-finding, with awareness plausibly playing some role, depending on the methodology.

  88. #88 Joseph
    April 29, 2010

    Correction to my comment @87: It was ICD-10 criteria, not DSM-III. However, it was basically passive ascertainment, as the authors explain: “these individuals were originally diagnosed and followed up during the 1980s and early 1990s, when the diagnosis of autism was narrow and uncommon, and diagnoses of ASD such as Asperger syndrome were rare (Asperger syndrome was assigned a unique ICD-10 diagnostic classification code only in 1992). The ISAC records of individuals registered during the childhood years of the cohort almost exclusively indicate a diagnosis of autism.

  89. #89 mikee
    April 29, 2010

    @Todd W.

    I think we are on the same page becuase while I think it is important to be respectful there is certainly a place for being blunt.
    Just checked out Age of Autism, you should be proud to have been banned, the arguments are frightenly antiscientific and irrational. By the way “Silenced by the Age of Autism” looks much more professional as well as containing rational arguments. I think it is a great example of how to deal with antivaxxers in a construct

  90. #90 christophe-thill.myopenid.com
    April 30, 2010

    I just think the scientists who really stand at the front of this debate to contest our community are liars. I think they say things that are lies.

    This is libel. Scientists working in health reserach should be represented by, for instance, the NIH, which should go to court on their account about this.

  91. #91 irenedelse
    April 30, 2010

    @ Azkyroth #84: My thoughts exactly! Not only the hard-core anti-vaccinationists will never be convinced by logical arguments, gentle or otherwise (because it’s a matter of faith for them), but the undecided part of the audience is more likely to follow the lead of the more inflexible debaters! Trying to treat illogical and evidence-free anti-vax propaganda as if it was a valid point of view only confuses the issue.

  92. #92 Coryat
    April 30, 2010

    He may be ‘smarter than you’, but luckily I’m me, and not this ‘you’ character, so I don’t feel intellectually surpassed; this gives me the confidence to say that ‘smarter than you’ is dumber than a ewe.

  93. #93 Jud
    April 30, 2010

    passionlessDrone writes:

    Of all the times I’ve been called stupid here, this ranks among the most respectful.

    Not at all what I meant to say, and sorry if it was taken as implied. Stupid, quite evidently not. Mildly obsessed to the point of ignoring some facts and logic, possibly. ;-)

    I’m OK with parental age as a factor [in causing autism]; I’m not OK with the notion that we can have certainty that everything else, which is a lot, is diagnostic noise.

    I completely agree. All I am saying is that parental age appears to be related, so I am claiming no more than what the evidence shows. Where we part ways is that from all I’ve been able to learn, it appears to be approaching scientific certainty that “everything else” does not include vaccines.

    one in four chidren get a fever in the days after getting the DTAP

    First, a nitpick: The actual quotes from the CDC are that “up to about 1 child in 4″ may experience a low-grade fever, “more often after the 4th and 5th doses.” But regarding the entire section of your post that you devote to showing vaccines cause immune system responses: Yes, vaccines, which are designed to cause immune system responses, do what they are designed to do. Color me unsurprised. I don’t know where you got the impression I was trying to say anything to the contrary.

    This doesn’t in the least change the fact that immune system responses to vaccines are no more than background noise, except in vanishingly rare cases. Show me the parent whose child’s worst illness was a low-grade fever in response to a vaccine, and I’ll show you a happy parent. I can certainly say that in my own childhood, I remember one low-grade fever in response to a vaccine, but many far more uncomfortable episodes of illness from “wild” pathogens (a very high fever from measles and bouts of upchucking from several cases of the flu are particularly memorable). I would suppose, though I admit I haven’t studied this, that my experience is still more or less typical, i.e., vaccine reactions will make up a very small part of all illnesses observed in young children. (This in spite of the tendency to report immune system reactions associated with a specific event, such as a vaccine, that might ordinarily go unreported to a doctor – e.g., transient redness, sensitivity, or low-grade fever. How many parents do you know who call a doctor for every single episode of illness in a child, no matter how low-grade or brief? But how many call the doctor if this occurs after a visit in which the child has been vaccinated?) So the notion that vaccines present some sort of unfamiliar or unique “load” to the immune system, vs. the billions of live potential pathogens the body encounters every day, is just plain unsupportable.

    Excepting the MMR, none of these studies involved vaccination

    “Other than that, how did you enjoy the play, Mrs. Lincoln?” The MMR study is clear and compelling evidence that a vaccine for 3 different diseases given in early childhood has absolutely no causative relationship with autism. That can’t be discounted by the simple expedient of beginning a sentence with the phrase “Excepting the MMR….”

    (If time isn’t an important factor, why not give the MMR, and every other vaccine the day a baby is born?)

    I’ll let Philadelphia Children’s Hospital answer this one:

    [A]lthough the number of vaccines has increased
    dramatically during the past century, the number of
    immunological components in vaccines has actually
    decreased. One hundred years ago, children received just
    one vaccine, for smallpox. The smallpox vaccine contained
    about 200 immunological components. Today, with advances
    in protein purification and recombinant DNA technology,
    the 14 vaccines given to young children contain only about
    150 immunological components.

    * * *

    [W]hen babies leave the womb and enter the world,
    they are immediately colonized by trillions of bacteria that
    live on the linings of their nose, throat, skin and intestines. Each bacterium contains between 2,000 and 6,000 immunological components. And babies often make an
    immune response to these bacteria to prevent them from
    entering the bloodstream and causing harm. The challenge
    that vaccines present is tiny in comparison to that from the
    environment.

    * * *

    Susumu Tonegawa, a molecular biologist who won a Nobel Prize for his work, showed that people have the capacity to make between 1 billion and 100 billion different types of antibodies. Given the number of immunological components contained in modern vaccines, a conservative estimate would be that babies have the
    capacity to respond to about 100,000 different vaccines at
    once. Although this sounds like a huge number, when you
    consider the number of challenges that babies face from
    bacteria in their environment, it’s not.

    As someone who so gleefully throws out charges of a lack of comprehension

    You mistake me. I hope I’m able to make my points in an interesting way, but I would characterize my feelings as frustration rather than glee. You’re quite obviously intelligent, but you continue to fasten onto “Teh vaccines!” in spite of a lack of any supporting evidence. The fact that vaccines do what they are designed for, provoking an immune reaction, is not supporting evidence. I’m going to try to make the point one last time using a different analogy (and then mercifully leave everyone alone).

    It is a scientific fact that there are bacteria which can metabolize metals. (It is a scientific fact that vaccines provoke an immune reaction.) There are metal structures that fail. (There are children who have autism.) This in no way shows that when, e.g., bridges fall, metal munching bacteria are the cause. (This in no way shows that when children are diagnosed as autistic, vaccines were the cause.)

    You see, an isolated fact (metal eating bacteria; vaccines that provoke immune reactions) that could be probative, in the context of a well supported hypothesis (if metal eating bacteria were, based on good evidence, a contender for causing, e.g., the Bay Bridge failure; if vaccines were, based on good evidence, a contender for causing autism) is, without that well supported hypothesis, just an isolated fact.

  94. #94 passionlessDrone
    April 30, 2010

    Hi Jud –

    Not at all what I meant to say, and sorry if it was taken as implied. Stupid, quite evidently not. Mildly obsessed to the point of ignoring some facts and logic, possibly.

    Fair enough.

    Where we part ways is that from all I’ve been able to learn, it appears to be approaching scientific certainty that “everything else” does not include vaccines.

    Fair enough again. I’d say that a more detailed approach might be that my from my perspective, all I’ve been able to learn includes a big blind spot, and that bothers me a lot.

    This doesn’t in the least change the fact that immune system responses to vaccines are no more than background noise, except in vanishingly rare cases.

    But you are claiming something as fact without substantiating it with clinical evidence. I believe you cannot substantiate with clinical evidence, because it does not exist, is what drives me crazy about this kind of discussion.

    It is insanely simple to find scads of studies about the adaptive immune response regarding vaccines in a pediatric population; but you cannot find anything about the innate immune response. You just can’t. You are assuming that it is background noise without providing any evidence of such.

    So the notion that vaccines present some sort of unfamiliar or unique “load” to the immune system, vs. the billions of live potential pathogens the body encounters every day, is just plain unsupportable.

    What about the influenza vaccine I posted above, where clearly, very clearly the researchers observed an increase in IL-6 post vaccination? Doesn’t this fly in the face of the idea that a vaccine should be background noise? How do you reconcile these findings with what you are asserting?

    Or, how about this study: “HPV-16 L1 VLP vaccine elicits a broad-spectrum of cytokine responses in whole blood.” (1)

    Here, we evaluated innate and adaptive immune system cytokine responses induced by HPV-16 L1 VLP in whole blood (WB) cultures from individuals receiving the vaccine (n=20) or placebo (n=4) before and after vaccination. 11 cytokines were measured: IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-gamma, TNF-alpha, and GM-CSF using multiplex bead arrays. Cytokine profiles from WB samples clearly discriminated between vaccine and placebo recipients and between pre and post-vaccination responses. Significant increases in Th1, Th2 and inflammatory cytokines were observed in WB assays following vaccination. Results from WB assays were compared against parallel PBMC-based assays in a subset of patients. Differences between whole blood assay and PBMC were observed, with the highest levels of induction found for WB for several cytokines. Our results indicate that multiplex assays for cytokine profiling in WB are an efficient tool for assessing broad spectrum, innate and adaptive immune responses to vaccines and identifying immunologic correlates of protection in efficacy studies.

    According to your theory, if I understand it correctly, we should not be able to determine which group got the placebo, and which group got the vaccine, right? Shouldn’t the vaccine just be “background noise” in a sea of other immune responses? In fact, however, what was observed, was exactly the opposite:

    Cytokine profiles from WB samples clearly discriminated between vaccine and placebo recipients and between pre and post-vaccination responses. Significant increases in Th1, Th2 and inflammatory cytokines were observed in WB assays following vaccination.

    How do you reconcile this finding with what you posted:

    So the notion that vaccines present some sort of unfamiliar or unique “load” to the immune system, vs. the billions of live potential pathogens the body encounters every day, is just plain unsupportable.

    Both groups were exposed to billions of live pathogens, but we could still tell by cytokine values which group got the vaccine.. Why are we able to detect “significant increases in TH1, TH2 and inflammatory cytokines” in the vaccine group? Aren’t these findings incompatible with your assertion? This is absolutely a genuine question.

    Go ahead and try to find a study like this involving the shots our infants get. They aren’t there. Instead of posting quotes, why not just post the studies?

    The MMR study is clear and compelling evidence that a vaccine for 3 different diseases given in early childhood has absolutely no causative relationship with autism. That can’t be discounted by the simple expedient of beginning a sentence with the phrase “Excepting the MMR….”

    Yes it can, and the reason it can is because of time dependent effects. This is important. The MMR doesn’t happen until 12 months, or sometimes as late as 18 months. You are making a big over simplification by saying “early childhood”. But before that, at two months, four months, and six months our infants are getting a lot of shots, including most of the new shots added to the schedule.

    Do you have any compelling reason that there aren’t time dependent effects to be taken into consideration? For example, if I were to argue that we should give the MMR on the day a child is born, you’d probably tell me that the guidelines regarding time are there for a reason (have you read about why this is the case?); but that logic has to work both ways. So far, I haven’t had anyone tell me a good reason that two months is the same as a year. Maybe you will be the first.

    Here is why this might be important, the animal studies I posted above, a great one is: “Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats” (2)

    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 TNF with an intracerebroventricular TNF antibody blocked the long-term changes to seizure susceptibility induced by LPS, whereas intracerebroventricular administration of rrTNF 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 TNF-dependant mechanism, making it more susceptible to generate seizures in adulthood.

    Check out what is happening here; the immune response, the pro inflammatory cytokine tnf alpha alone is capable of permenantly altering the brains succeptibility to seizures in a time dependent fashion! You might also check out “Early-Life Immune Challenge: Defining a Critical Window for Effects on Adult Responses to Immune Challenge” (3), which found similar time dependent effects of immune challenges. You have seemingly (?) arbitrarily decided that a vaccine at 12 months is just like five vaccines at two months. The developmeing immune system is a very complicated entity, and as such, we should have good reasons for making broad assumptions. I am genuinely interested in understanding what has guided you to this conclusion.

    And here is where the problem really starts; our population of interest, autism creates tnf-alpha at exaggerated levels than their non diagnosed peers!. See the references I posted above in 39 for this.

    As far as your quotes, they are missing my point, perhaps because I failed to make it concisely.

    Regarding the number of antigens, this is a strawman. By way of example, the Varicella vaccine has more antigens in it than the entire rest of the vaccine schedule! Is this meaningful? Does this mean it has fourteen times the immune effect than the DTAP, which has 5 antigens? Why do you suppose that incidence of fever, for example, is so much higher in DTAP than Varicella if antigen counting is a useful metric?

    Regarding quote two, I believe I provided evidence from the studies that there is a signficant difference in immune response from vaccination compared to everyday exposure.

    Regarding quote three, there is a significant difference between adaptive capacities; i.e., memory, and innate responses; i.e., pro-inflammatory cytokine generation; i.e., tnf-alpha, IL-6, ect.

    I appreciate your cordial tone. I will officially set my sarcasm meter to zero for all future posts.

    – pD

    References:

    1. HPV-16 L1 VLP vaccine elicits a broad-spectrum of cytokine responses in whole blood. [Pinto, 2005]

    2. Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats [Galic, 2008]

    3. Early-Life Immune Challenge: Defining a Critical Window for Effects on Adult Responses to Immune Challenge [Spenser 2006]

  95. #95 D. C. Sessions
    April 30, 2010

    To J.B., they must be lying or corrupt. It’s classic conspiracy theory thinking.

    More like Holy Warrior thinking. I’ve been using the “ignorant, incompetent, or evil” description for 14 years this week.

  96. #96 D. C. Sessions
    April 30, 2010

    Wait, does a perspex box of blinking lights even HAVE a cock?

    Of course, silly. Where do you think fireflies come from?

  97. #97 D. C. Sessions
    April 30, 2010

    You must admit, there’s no good evidence that salt cause global warming!

    On the contrary: back when there was practically no salt on the surface of the Earth, it was extremely cold even at the equator — the so-called “snowball Earth” periods.

  98. #98 Antaeus Feldspar
    April 30, 2010

    Sid, are you honestly as stupid as you appear to be, or is it a playful act?

    Actually, I came to the conclusion long ago that Sid is a “pure troll”; meaning that if new scientific evidence surfaced which caused all of us to conclude that vaccines are horrifically harmful and must be discontinued immediately, Sid would suddenly transform into a defender of vaccination.

    Shifting the goalposts refers to the tendency to maintain the ultimate product of one’s beliefs while the underlying supports are changed.

    mmmmmm, that’s close but it’s also a little off. “Shifting the goalposts” means trying to retroactively change the standard of evidence being demanded, after the original demand has been met. For instance, some antivaxxers who used to insist that every single case of autism was due to thimerosal, and they challenged “the medical establishment” to disprove their dogma. Of course, when thimerosal was removed from vaccines and the dramatic drop in autism rates that would have occurred if thimerosal was the ‘sole cause’ did not occur, did those antivaxxers publicly acknowledge “our hypothesis that thimerosal is the sole cause of autism has been disproven”? Not a single one. Many of them, however, shifted gears and started challenging “the medical establishment” to prove that no single case of autism had ever been caused by thimerosal.

    Of course, when antivaxxers exhibit the behavior you describe, it does amount to shifting the goalposts; they are essentially saying “Prove that vaccines don’t harm our children through this mechanism! Now prove that they don’t harm our children through this mechanism, either! And if you prove that, prove that no child has ever been harmed through this third mechanism!” The goalposts are effectively being shifted away with every new theoretical mechanism that gets added.

    Of course, Sid predictably gets it 100% bass-ackwards, getting ‘change to the dominant scientific model’ confused with “shifting the goalposts.” In the extremely unlikely event that Sid is not a pure troll, he is revealed instead as what might be called a cargo-cult logician: he does not actually know how logical argumentation is done, but he thinks if he assembles structures that bear some outward resemblance to it, it won’t matter what the insides are like! “‘Shifting the goalposts’? I don’t know what that refers to but it has something to do with ideas and something to do with changing; I guess I’ll toss the accusation towards any instances I can think of in history of ‘their’ ideas changing and wait to see the acclaim for my brilliance roll in!”

  99. #99 D. C. Sessions
    April 30, 2010

    The immune responses induced by HPV vaccination are different to those after natural infection.

    Among other things, the vaccination causes lasting immunity.

  100. #100 trrll
    April 30, 2010

    How about this for a bet: We take one hundred children and have them vaccinated at two, four, and six months of age. Each of us gets to pick three days during their first year of life to guess which day they’ll get a fever.

    It is difficult for me to understand why you think that knowing which days a child is exposed to an antigen that provokes the immune system enough to generate a fever is meaningful. Obviously, vaccinations are intended to provoke the immune system, and a fever is a typical manifestation of that. But children are exposed to a lot of antigens. Merely chewing food or brushing teeth introduces potentially pathogenic bacteria into the bloodstream. This is probably why all children are frequently exposed to immune-provoking antigens in the environment. Kids have lots of fevers, only a small fraction of which are related to vaccination. So if you want to look for an immune related “trigger” for autism, based upon the rather weak evidence that autism, like many other medical conditions, may be associated with changes in immune system markers, it seems like a more reasonable hypothesis would be an abnormal response to environmental antigens, which are far more numerous than the antigens in vaccines.

  101. #101 gaiainc
    May 1, 2010

    My interpretation of the cited study, pD, is that comparison group was not a group that had just been exposed to the pathogen. One group got the vaccine designed to make the immune system respond and hey, it responded. Shocking. The other group didn’t get anything to make the immune system respond. Those four patients got placebo, so I wouldn’t have expected any change in cytokines or other immune markers. So the fact that in 24 subjects, the researchers found a difference seems like a very “well, duh” moment. The study shows me that the vaccine provokes the immune system. I expect that. I see nothing there that leads me down the path of improper immune provocation at the wrong time leads to autism.

    What I also have issues with, pD, is that you haven’t presented evidence of the immune response from vaccination being substantially different from the immune response from obtaining the wild type disease (other than in the latter situation you have the disease and that possibility alone makes vaccination more than worthwhile to me). I’m left with if the problem is the immune response period, why should I or my child undergo the higher risk of a poor outcome from the disease than from the vaccination? Autism doesn’t cause death. What my child and I have been vaccinated against do. I’m sticking with vaccination. There’s also the issue that despite the appearance of other vaccines on the US schedule and that other countries have different vaccines and schedules, somehow, autism rates aren’t that different. I don’t have the citation, but there was also the NHS survey in the UK that showed that autism rates in adults were about the same as in kids. So, all this brouhahaing over vaccines just doesn’t make sense to me.

    As to timing of some vaccinations, from what I remember, and I wish I had the actual citations to this-maybe this is from my immunology course in med school, in the process of developing vaccinations in kids, people have found that certain vaccines work better with longer lasting immunity if given later rather than earlier. It’s part of the reason why Hep A, varicella, and MMR are given at or after 12 months.

    About HPV, my lab tests for about 12-15 types that are consider high-risk. If you gain an immunity to one type, you do not gain an immunity to all types, whether the immunity is from vaccine or wild-type. HPV is kind of a pain in the butt that way. Strep pneumoniae presents a similar problem, which is why the adult vaccine has 23 serotypes in it and the pedatric one has 7 (though I’ve heard someone is coming out with a pediatric vaccine that protects against 13 serotypes).

    I think that antigen counting is important. It gives me comfort to know that my child is getting fewer antigens than I did, though he is being protected again more. Go, science! And thanks again to Dr. Offit for helping to develop a vaccine against rotavirus. I do not wish that on anyone. I think that the pertussis bacteria is the problematic component in the DTaP. I don’t know why that the antigens that protect us against pertussis are the same antigens more likely to provoke a more robust response in people. It just seems to be that way. So it goes.

    Just had a thought… wonder if anyone has bothered to go back through autism prevalence/incidence/rates (I’m sorry to all the epidemiologists out there for my complete butchering of these terms) and compared them to the times when there were Prevnar shortages or Hib shortages. Just wondering since these shortages lasted about 1-2 years and during those times, some kids weren’t getting the vaccine or getting a very truncated version with hopes that herd immunity would keep the really healthy ones protected.

  102. #102 passionlessDrone
    May 1, 2010

    Hi trrll –

    Long time, no see.

    It is difficult for me to understand why you think that knowing which days a child is exposed to an antigen that provokes the immune system enough to generate a fever is meaningful.

    The argument was made that those days should be no different than every other day, and in fact, that vaccination is ‘background noise’ in comparison. I do not think that assertion is accurate; the frequency of fever post vaccination is but one piece of evidence I used to make this point. See post 74.

    Obviously, vaccinations are intended to provoke the immune system, and a fever is a typical manifestation of that. But children are exposed to a lot of antigens.

    OK.

    Merely chewing food or brushing teeth introduces potentially pathogenic bacteria into the bloodstream. This is probably why all children are frequently exposed to immune-provoking antigens in the environment.

    I don’t know about the infants you have spent time around, but the ones I know aren’t brushing their teeth or chewing food at two months, four months, or six months of age. (?) Does anyone else out there know of a two month old that gets their teeth brushed?

    Please remember that as pointed out by Mr. Novella, a large percentage of children with autism display signs between six months and a year; long before the events you describe generally take place. Those antigens also don’t come with adjuvants designed to insure a robust immune response.

    Kids have lots of fevers, only a small fraction of which are related to vaccination.

    How many in the first six months of life? Again, our current vaccine schedule, and the area that has gotten the most additions to the schedule is the earliest timeframes, but no evaluations, are at two, four, and six months. How many fevers do most children get in that timeframe? I’d be genuinely curious to know if you could provide a reference on this. How many sets of vaccines do they get?

    And again, I’m only using the fevers as an illustration that equivalencies should not be drawn between the two.

    So if you want to look for an immune related “trigger” for autism, based upon the rather weak evidence that autism, like many other medical conditions, may be associated with changes in immune system markers, it seems like a more reasonable hypothesis would be an abnormal response to environmental antigens, which are far more numerous than the antigens in vaccines.

    My research has, obviously, been quite focused on autism. One thing I have found is that there seems to be some very specific immunological findings that pop up repeatedly; a tendency towards a more robust innate immune response; see for example, references 1 – 5 I posted in post 39. Do you know of any other neurological conditions that manifest in childhood that share a similar immunological profile of exaggerated responses to TLR agonists and/or increased levels of markers known to be associated with inflammatory conditions?

    There seems to be a tendency to want to generalize out to the rather benign sounding, ‘immune system abnormalities’ in this type of discussion. But that isn’t what I am talking about here; I’m more concerned about specific differences, a subgroup of infants who generate more pro-inflammatory cytokines than their peers. The unfortunate fact of the matter is that I cannot seem to find any clinical evidence one way or the other regarding the innate immune response after vaccination in the pediatric population. Do you know of any studies that might help?

    Even without that kind of study available, I might not have such concern if I hadn’t also found a variety of animal studies that indicate that an innate immune response during critical timeframes is not necessarily a harmless event. Thesee challenges need not be catastrophic, nor persistent, in order to have long term effects on the animals, changes that are subtle, and difficult to predict. Again, see my references in 39 and 94 for examples of this.

    Even with those studies in hand, the results of which are problematic to map directly to humans, I might not have concern except for the fact that we haven’t measured the effect of vaccination in our children regarding autism. See my post @94 for reasons why the MMR studies are imperfect models for this, as they fail to take into consideration the possibility of time dependent effects. The fact that people that ought to know better keep on trying to say things like ‘vaccines in general’ when the facts on the ground are we haven’t done any analysis drives me up the wall; it is selective skepticism and embracing hopefull thinking as opposed to dispassionate analysis of data.

    Your thoughts concerning external environmental agents up and above vaccines are rational, and I share them. Unfortunately, measuring ‘the environment’ can be very difficult, though some upcoming studies such as CHARGE and MARBLES are going to give it a shot. Vaccines, on the other hand, at discrete events, and even with all of the confounds associated with crazy parents, offer a binary option as opposed to ‘the environment’.

    I’m not strictly concerned with vaccines by any stretch; have you done much reading regarding endocrine disrupters, and interferrence with thyroid metabolism? I happen to think this is terrifying issue, one likely having a lot of effects on our infants including autism, but no one is getting on TV making the difficult to support claim that ‘the question has been answered’ regarding endocrine disrupters.

    – pD

  103. #103 passionlessdrone
    May 1, 2010

    Hi Gainaic –

    My interpretation of the cited study, pD, is that comparison group was not a group that had just been exposed to the pathogen. One group got the vaccine designed to make the immune system respond and hey, it responded. Shocking. The other group didn’t get anything to make the immune system respond. Those four patients got placebo, so I wouldn’t have expected any change in cytokines or other immune markers. So the fact that in 24 subjects, the researchers found a difference seems like a very “well, duh” moment. The study shows me that the vaccine provokes the immune system. I expect that. I see nothing there that leads me down the path of improper immune provocation at the wrong time leads to autism.

    But what does this study do towards the argument that Jud made in post 74, specifically, that the response from a vaccine is “background noise” compared to everyday exposure? Before we can get to the question of the potential for causation, we have to cut through the chaff first; and the idea that the response from vaccines is not of consequence compared to everyday exposure is the first canard that needed to be struck down. I’m not sure if you are in agreement with me on this point or not?

    Do you think we can safely make comparisons between vaccines and ‘everyday’ exposure to pathogens?

    What I also have issues with, pD, is that you haven’t presented evidence of the immune response from vaccination being substantially different from the immune response from obtaining the wild type disease (other than in the latter situation you have the disease and that possibility alone makes vaccination more than worthwhile to me). I’m left with if the problem is the immune response period, why should I or my child undergo the higher risk of a poor outcome from the disease than from the vaccination?

    You are technically correct; I have not made that argument; we have no evidence on either side of the fence there, just unsubstantiated assertions that one is less robust than the
    other.

    You might also note, I also have not made the argument that vaccination be forgone. I am making the argument that our existing research suite is insufficiently designed to understand if our aggressive vaccination schedule is having unintended consequences for our infants, thats it.

    The problem I see with your analysis, as with many others here, is that it ignores any possibility for a time dependent effects. The effect of an infant getting one of those diseases at two months, no doubt, would be terrible. But that in an of itself is no reason for us not to be curious towards if our vaccination schedule is having impacts up and above disease prevention. What if I were to say that I have much, much less concern over vaccines having subtle but difficult to predict effects when given outside of infancy? I understand quite clearly that infancy is a time of great fragility, I am only making the point that we cannot assume that two months and two years are equal.

    There’s also the issue that despite the appearance of other vaccines on the US schedule and that other countries have different vaccines and schedules, somehow, autism rates aren’t that different. I don’t have the citation, but there was also the NHS survey in the UK that showed that autism rates in adults were about the same as in kids. So, all this brouhahaing over vaccines just doesn’t make sense to me.

    Unfortunately, the types of studies you refer to are notoriously problematic to conduct with accuracy. For example, pick any of the last five studies from the US and they all show drastically fewer children with autism than one that follows. What does that tell you about our ability to meaningfully measure autism rates, if, as the narrative goes, it is primarily mediated through genetics? What has given you confidence that the latest set of studies are accurate, when every previous study has been so inaccurate that it has missed huge swaths of the population with autism?

    I’ve tried to make clear my concerns with assuming that the overwhelming majority of this increase is the result of diagnostic changes; it is possible, but I am of the opinion that the question is too damn important to be left to the social scientists.

    As to timing of some vaccinations, from what I remember, and I wish I had the actual citations to this-maybe this is from my immunology course in med school, in the process of developing vaccinations in kids, people have found that certain vaccines work better with longer lasting immunity if given later rather than earlier. It’s part of the reason why Hep A, varicella, and MMR are given at or after 12 months.

    That is also my understanding. However, you are making my point for me; we have done the research regarding the adaptive immune response in regards to timing. But we have failed to do any research regarding the innate immune response. I’ve asked several times for someone, anyone to show me some research on the innate immune system and our pediatric vaccine schedule. For some reason, no one is willing, or able to do this. Does this strike you as strange, considering the never ending line we are being told, ‘the question has been answered’?

    About HPV, my lab tests for about 12-15 types that are consider high-risk. If you gain an immunity to one type, you do not gain an immunity to all types, whether the immunity is from vaccine or wild-type. HPV is kind of a pain in the butt that way. Strep pneumoniae presents a similar problem, which is why the adult vaccine has 23 serotypes in it and the pedatric one has 7 (though I’ve heard someone is coming out with a pediatric vaccine that protects against 13 serotypes).

    I didn’t want to use HPV as an example, I had to. This is a function of the fact that if you look for studies that measure innate immune system measurements for things like the polio, influenza, dtap, hib, hep-b in the pediatric population, those studies aren’t available.

    I think that antigen counting is important. It gives me comfort to know that my child is getting fewer antigens than I did, though he is being protected again more. Go, science! And thanks again to Dr. Offit for helping to develop a vaccine against rotavirus. I do not wish that on anyone. I think that the pertussis bacteria is the problematic component in the DTaP. I don’t know why that the antigens that protect us against pertussis are the same antigens more likely to provoke a more robust response in people. It just seems to be that way. So it goes.

    You seem to contradict yourself. The fact that the antigens that protect us from pertussis provoke a more robust response is good reason that counting antigens is not meaningful. According to the usefulness of the addition theory, I should be able to take fourteen shots with the same immunological impact as the DTAP to get to the same place I am with a single Varicella vaccine, because DTAP only has five antigens, and Varicella has 69. The immune system is much, much to complicated to be understood efficiently with addition, something Paul Offit probably understands; at least I hope he does.

    Just had a thought… wonder if anyone has bothered to go back through autism prevalence/incidence/rates (I’m sorry to all the epidemiologists out there for my complete butchering of these terms) and compared them to the times when there were Prevnar shortages or Hib shortages. Just wondering since these shortages lasted about 1-2 years and during those times, some kids weren’t getting the vaccine or getting a very truncated version with hopes that herd immunity would keep the really healthy ones protected.

    To my knowledge, this has not been performed. I believe it might be logistically very difficult to do, but I may be wrong.

    – pD

  104. #104 Joseph
    May 1, 2010

    The argument was made that those days should be no different than every other day, and in fact, that vaccination is ‘background noise’ in comparison.

    I think we already discussed this over at LB/RB, didn’t we? Infants gets many fevers in a year. In contrast, they are unlikely to get a fever from vaccination. Overall, the average number of excess fevers is marginal.

  105. #105 passionlessDrone
    May 1, 2010

    Hi Joseph –

    I meant to respond to your earlier posting regarding information diffusion and your notes concerning Isreali prevelance. My poor statistical skills keep me from having much input, unfortunately, though I do tend to trust you in that area. Your thoughts concerning the multitude of genes involved in autism versus a single gene in DS is interesting, and one I’d like to give more thought towards. I appreciate your comments.

    Regarding the number of fevers, we did discuss this at LBRB. I believe that we found that there was some discrepancy between the number of times an infant got sick, four to seven times a year was one value we found, if I remember correctly.

    But again, look at how bunched up the vaccine schedule is, the over whelming majority of which is at the two, four, and six month timeframes. If we were to graph the number of times an infant was sick three times before their six month well visit, do you think it would be in the upper ninety percentile? We have replaced a curve with a straight line and assumed that all things are equal.

    In any case, it is important to note that I am not advocating that a fever, per se, is the meaningful metric other than as a way to disprove the notion that vaccination is equivalent to background noise; i.e., just because you don’t have a fever doesn’t mean you aren’t having an impact.

    By way of example of this, take a look at the HPV study I posted above in post 94; the group had significant increases in inflammatory cytokines, but according to the CDC, the HPV vaccine only causes a fever in one in eight cases. Yet, we were able to see group effects in pro-inflammatory cytokines in the HPV study; the link between cytokines and fever generation are still being investigated, but suffice it to say that the idea that unless you have a fever, there is no effect, is a gross over simplification.

    We also need to be careful about over simplifying the difference bewteen getting sick and vaccines in regards to the innate immune response. Why? Because we have clinical evidence that if your body believes it is under attack from multiple types of pathogens simulatenously; i.e., different types of bacteria and viruses, it responds synergistically, as opposed to linearly.

    For example, this study: “Multiple signaling pathways contribute to synergistic TLR ligand-dependent cytokine gene expression in human monocyte-derived macrophages and dendritic cells.” was published less than a year ago. (1)

    TLRs are innate immune receptors that recognize pathogen-associated structures. Binding of ligands to different TLRs can induce the production of proinflammatory cytokines in a synergistic manner. We have analyzed the molecular mechanisms of synergy in TLR ligand-stimulated human monocyte-derived macrophages and dendritic cells (moDCs). Stimulation of moDCs with the TLR8 ligand together with the TLR3 or TLR4 ligand led to synergistic IL-6, IL-10, IL-12, and TNF-alpha mRNA expression and cytokine production. DNA-binding assays showed that TLR3 and TLR8 stimulation induced binding of multiple IFN regulatory factor (IRF) and STAT transcription factors to the IL-12p35 gene promoter IFN-stimulated response element in moDCs and macrophages but with different binding profiles and kinetics. We also demonstrate that NF-kappaB, MAPKs and PI-3K pathways have an important role in TLR-induced cytokine gene expression, as pharmacological inhibitors of these signaling pathways inhibited TLR3, TLR4, and TLR8 ligand-induced cytokine mRNA expression and protein production. Especially, synergistic IL-12p70 production was abolished completely in NF-kappaB, MAPK p38, and PI-3K inhibitor-treated moDCs. Our data suggest that TLR-dependent, synergistic cytokine gene expression results from enhanced activation and cooperation among NF-kappaB, IRF, MAPK, PI-3K, and STAT signaling pathways.

    See what is happening here? The inflammatory response is synergistic in intances where multiple toll like receptors are activated simultaneously! You may not be famliar with TLRS, but at a high level, they are a front line pathogen recognition system that is responsible for initiating the innate immune response, and they appear to be tailored to recognize different types of bacteria and pathogens. [For example in the autism realm, check out the Enstrom paper I referenced above, "Differential monocyte responses to TLR ligands in children with autism spectrum disorders"].

    But the study I posted above tells us that the response from responding to one type of pathogen is not necessariliy the same as responding to multiple types of pathogens, and in fact, the idea of using addition to understand the immune response fails us again. Unfortunately, this presents problems with attempting to simply equate getting sick with something (one pathogen), with getting challeged by multiple pathogens all at once. Make no mistake, our two, four, and six month well visits involve triggers for several bacteria (diptheria, hepatitis, typhoid, pneuomococaul, pertussis), and multiple virus (polio, rotavirus, influenza). Given that from a clinical standpoint, we have evidence that there is a qualitative difference in the immune response between a single pathogen, and several, I think we should have a compelling reason to willingly say that getting sick is the same as getting vaccinated for eight pathogens simultaneously. Do you know of any such evidence?

    – pD

  106. #106 Science Mom
    May 1, 2010

    pD, I did not get to read all of your references but I gleaned Garbett et al. and you are over-reaching in your claims. You are intimating that there is a significant number of ASD children that have the same or similar immune phenotype; I would be very careful on that front. They did not find statistical significance for many of the gene expressions they examined and, to their credit, did do validations. You are also not considering what is probably the more likely exposure period, which is first trimester when there is critical neurodevelopment.

    Then there is the ‘chicken and the egg’, which is do children with certain ASD genotypes influence immune system geno and phenotypes or does the immune genotypes influence ASD genotypes and phenotypes? At this juncture, this does not appear to be explanatory for the increase, only suggestive of possible aetiologies.

  107. #107 Sid Offit
    May 1, 2010

    @101

    As to timing of some vaccinations, from what I remember, and I wish I had the actual citations to this-maybe this is from my immunology course in med school, in the process of developing vaccinations in kids, people have found that certain vaccines work better with longer lasting immunity if given later rather than earlier. It’s part of the reason why Hep A, varicella, and MMR are given at or after 12 months

    My understanding is that the presence of maternal antibodies is the main concern

  108. #108 Joseph
    May 1, 2010

    If we were to graph the number of times an infant was sick three times before their six month well visit, do you think it would be in the upper ninety percentile? We have replaced a curve with a straight line and assumed that all things are equal.

    @pD: Why are you assuming it’s a curve? It was difficult enough to find data on the number of times an infant gets sick over a 6 month period.

    Also, when a child gets naturally sick, they are more symptomatic than when they get a fever (usually a mild one) from vaccination. Do you agree with this?

  109. #109 passionlessDrone
    May 1, 2010

    Hi Science Mom –

    I appreciate your comments regarding applying caution, and indeed, it would seem that I should clarify my thoughts. If I led on that it was my belief that all children with autism exhibit an ongoing immunological process in the CNS, I apologize; with a condition with manifestations as heterogenous as autism, there is room for many different avenues to the same endpoint.

    However, lets not forget that Garbet isn’t the only place we seem to have evidence of immune dysfunction in the CNS in autism; we also have Vargas (1), Chez (2), Li (3), and Nguyen(4) to contend with if we want to find a place where immue system in the CNS is a consequence, rather than a participatory member in autism.

    Regarding Garbett, (for those interested, the full paper is availble online and I would recommend it for anyone interested in learning), your point that not all of their findings reached statistical significance is well taken, but even still, take a look at Table 2. The authors specifically state that:

    Note that most of differentially expressed pathways are involved in immune response (shaded).

    They further go on to state:

    The results of our study suggest that 1) in autism, transcript induction events greatly outnumbers transcript repression processes; 2) the neocortical transcriptome of autistic individuals is characterized by a strong immune response; 3) the transcription of genes related to cell communication, differentiation and cell cycle regulation is altered, putatively in an immune system-dependent manner, and 4) transcriptome variability is increased among autistic subjects, as compared to matched controls.

    I’ll admit that in this case, I am unfamiliar with the pathways listed on Table 2 which might allow me to validate this, I am, essentially, taking them at their word.

    We have good reason to believe that their study methodology was sound, however, as they also found overlaps with genes associated with autism in other studies.

    Furthermore, our study also provides additional support for previously reported involvement of MET, GAD1, GFAP, RELN and other genes in the pathophysiology of autism. While the findings were obtained on a limited sample size, the statistical power, together with the previously reported postmortem data by other investigators suggest that the observed gene expression changes are likely to be critically related to the pathophysiology seen in the brain of the majority of ASD patients.

    I’m not sure if you feel the failure of some genetic expression levels failing to meet significance is enough for you to disagree with their statements or not. (?)

    You are also not considering what is probably the more likely exposure period, which is first trimester when there is critical neurodevelopment.

    Once again, I have failed to be clear in my views; even with my long winded posts. My apologies. I have absolutely no problem with the theory of prenatal immune insults as having neurological impacts, up to and including autism. In fact, I am positive that this happens in some instances. From the innate immune system end, I think that the IL-6 work by Patterson is especially significant in this regard. Simlarly, Fatemi has a neat paper on this.

    It is just that I have not becomed convinced that the prenatal period is the only time sensitive period. It may be, but I don’t think we have sufficient understadning to say this with any certainty. Do you?

    Then there is the ‘chicken and the egg’, which is do children with certain ASD genotypes influence immune system geno and phenotypes or does the immune genotypes influence ASD genotypes and phenotypes? At this juncture, this does not appear to be explanatory for the increase, only suggestive of possible aetiologies.

    This is a difficult problem to address. For guidance in this, I am curious what do you think we can learn by evaluating Grigorenko, who performed the MIF study I referenced above? (5) In this case, the authors not only found that MIF promoter alleles were more frequently represented in the autism population, but in fact, that as circulating levels of MIF rose, so did did autism severity. While the authors admit that this is a preliminary finding, it may still have meaning, after all, having autism didn’t give these children the MIF promoter genes.

    There were genetic associations between known functional polymorphisms in the promoter for MIF and autism spectrum disorder–related behaviors. Also, probands
    with autism spectrum disorder exhibited higher circulating MIF levels than did their unaffected siblings, and plasma MIF concentrations correlated with the severity
    of multiple autism spectrum disorder symptoms.

    Similarly, Enzo (6) found that as levels of HMBG1 (another known promoter of the innate immune response affecting TLR2/4) increased, so too did autism severity.

    After allowance for age, BMI, and Raven’s Progressive Matrices scores, we found a positive independent association between HMGB1 levels and the ADI-R Social Scores (HMGB1, the worse the social interaction β=0.39, t=2.81, P < 0.01, Fig. 2); the higher the serum level of HMBG1, the worse the social interaction.

    In this case, we don’t have genotyping available, but the end result, an increase in the innate immune response, is the same. It is possible that these findings are spurious, or that they are consequential to autism, as opposed to causal.

    I appreciate your comments and shall strive to apply a more nuanced approach so as to reduce confusion.

    – pD

    References:

    1. Neuroglial Activation and Neuroinflammation in the Brain of Patients with Autism (Vargas, 2005)

    2. Elevation of Tumor Necrosis Factor-Alpha in Cerebrospinal Fluid of Autistic Children (Chez, 2007)

    3. Elevated immune response in the brain of autistic patients (Li, 2009)

    4. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain (Nguyen, 2010)

    5. Macrophage Migration Inhibitory Factor and Autism Spectrum Disorders (Grigorenko, 2008)

    6. Increased serum levels of high mobility group box 1 protein in patients with autistic disorder [Enzo, 2010]

  110. #110 Sid Offit
    May 1, 2010

    @Feldspar the Logician

    Of course, Sid predictably gets it 100% bass-ackwards, getting ‘change to the dominant scientific model’ confused with “shifting the goalposts

    I didn’t assert that a change in theory is goalpost shifting. I asserted that if the legitimate move from exploring mercury to exploring vaccines in general can be, by vaccine defenders, labeled goalpost shifting, the term goalpost shifting could be used, incorrectly, in the examples I gave.

  111. #111 Antaeus Feldspar
    May 1, 2010

    if the legitimate move from exploring mercury to exploring vaccines in general

    Contrary to Sid’s delusion, the legitimate move would have been to say “Wow, all the evidence that we thought was implicating thimerosal in vaccines as a cause of autism was completely mistaken! We’d better go back and re-examine our data, and let the data point us to a new hypothesis, instead of assuming that a hypothesis the data does not support is nevertheless correct and swapping in a new purely theoretical mechanism for it.”

  112. #112 passionlessDrone
    May 2, 2010

    Hi Science Mom –

    I was thinking a little more about the ‘chicken-egg’ probelm you described above.

    Have you read, “Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain”? It was published a few weeks ago and got a lot of media coverage, possibly because it found epigenetic, and thus, potentially addressable changes in autism. It is a very, very cool paper that I would recommend.

    Anyways, one of the end result of the epigenomic modifications was a decrease in RORA. Where this might help us in this discussion is that RORA plays a part in modulating the neuro-immune response, and has been shown to inhibit tnf-alpha, il-6, and COX-2 in the periphery. (1,2)

    So here, we can find that having less of a component known to help regulate the innate immune response is more common in autism. Further, the researchers observed a dose response, such that the less RORA, the more severe the autism severity.

    For both BCL-2 and RORA, gene expression was significantly higher (P_0.05) in the unaffected control than autistic co-twins (Fig. 4A). Generally, the diagnosed autistic co-twin (_A) had the lowest level of expression of BCL-2 and RORA, while the milder undiagnosed co-twin (_M) exhibited transcript levels between that observed for unaffected sibling controls and autistic co-twins. This suggests a quantitative relationship between phenotype and gene expression of these 2 genes, although additional studies are required to confirm this observation.

    [Note the cautious admission that further study is warranted.]

    Of course, there are other areas where RORA is implicated other than the inflammatory response, most notably Purkinje cell differentation, but we are still left with data that indicates that both ends of an abnormal immune response are capable of affecting autism beahvioral severity.

    What are your thoughts concerning our ability to gain insight into the chicken-egg problem given this? If we would like to find a mechanism by which inflammation is not a participatory component of autism, we need to have reasons that both sides of an immune response are co-incidentally modified as a result of having autism. For example, our MIF studies, which involve an upregulation of the immune response must be coincidental, and our findings of immuno-regulators such as RORA or TGB-Beta1 (3) must also be coincidental. There are, of courses, coincidences occurring every day, but I’m not a fan of invoking them without good reason.

    – pD

    References

    1. The nuclear receptor ROR(alpha) exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes [Journiac, 2009]

    2. The orphan nuclear receptor ROR alpha is a negative regulator of the inflammatory response [Delerive, 2001]

    3. DECREASED TRANSFORMING GROWTH FACTOR BETA1 IN AUTISM: A POTENTIAL LINK BETWEEN IMMUNE DYSREGULATION AND IMPAIRMENT IN CLINICAL BEHAVIORAL OUTCOMES [Ashwood, 2008

  113. #113 Julian Frost
    May 3, 2010

    I usually post comments over at Left Brain Right Brain. However, the commentator Smarter Than You caught my eye.
    STY exemplifies another reason why it is impossible to reason with the anti-vaccinators: they keep saying that new evidence is coming out. STY says November-December this year. “New data” has been arriving “in a few months’ time” for years, and never does. Yet they hope against hope.
    I would like to name this gambit the ‘Billy Bunter Gambit’ in honour of the fictitious character who was eternally and wrongly convinced that a postal order was coming for him.

  114. #114 NJ
    May 3, 2010

    “New data” has been arriving “in a few months’ time” for years, and never does.

    Or, as per Atrios, you could just say they refer to time in Freidman units.

  115. #115 David N. Andrews M. Ed., C. P. S. E.
    June 28, 2010

    @speedweasel:
    “Science is standing between anti-vaxers and what they desperately want to believe.”

    I think that was should refer to this as the speedweasel principle. Because that – as a name for it – sounds pretty good, especially in light of the explanation that came before it!

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