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Triskaidekaphobia times two.

There is germaphobia, the fear of germs. Or Germans.  One of the two. Oddly, I do not fear most germs, despite my daily reminders as to how destructive these wee beasties can be.   I recognize their limits and my immunologic strengths and know I have more to fear from cars or unsaturated fats than E. coli or influenza.

There is also a fear of vaccines, the too many too soon that is said to be at the heart, or maybe the left atrial appendage, of one of the imaginary problems with vaccines.  There are, by my counting, 5 live attenuated viruses and 21 different antigens in the vaccine schedule by age 6, for a total of 26 or twice thirteen.  Some fear those antigens and viruses, making it a  triskaidekaphobia times two (1).

From my perspective the paltry quantity of antigens children receive with the vaccine schedule are, when compared to the enormity of antigens in the environment, a rounding error.  We are awash in bacteria, fungi, viruses and an enormous number of environmental organisms.  I think of each of us like Pig-Pen, but instead of dirt, we are in a cloud of micro-organisms.

Our immune systems, contrary to the opinions of the unimaginative who direct scorn and derision at Dr. Offit, can cope.  As discussed, we have a ability to stave off the phenomenal number of organisms that would just as soon use us as the ultimate supersized meal.  Of course, it is not all the immune system that keeps the wee beasties away.  Being warmer than ambient temperature helps.  Understanding disease epidemiology, hygiene and the prn malum q 24 h also keeps the doctor away.Hygiene is an interesting two edged sword, and the rule in medicine is that no good deed goes unpunished. We are cleaner, at least in the urban industrialized wWest, than  most people through most of history.  Exposure to a large assortment of environmental filth and germs, with the exception of my 13 year old’s bedroom, is rare.  Cleanliness has helped to decrease the spread of contagion both in the community and in the hospital, at least for those who believe in good hand hygiene (2) and sterile technique.

However, lack of exposure to the background microbiology has had a potentially interesting downside.  Several epidemiologic studies have demonstrated an association between, to put it crudely, increased cleanliness and an increase in asthma and atopy (3).   The NEJM had a recent article with a similar result,  Exposure to Environmental Microorganisms and Childhood Asthma. From my perspective, this link between cleanliness and allergic disease  is interesting, but not what I want to focus on.  An interesting suggestion of this study is that, while you cannot boost the immune system, evidently the immune system needs a good microbial work out as it develops to ensure proper functioning as an adult.  Not only is the infants immune system able to process and react to a mind boggling number of antigens, apparently it needs to be exposed to these antigens in childhood for optimal function.  The motto ‘Use it or lose it’ applies to B cells as well as biceps.

In the NEJM study they surveyed the bedding and dust for microorganisms in the environment of children who live on farms and those that live in an urban environment.  They did both microbiology counts and molecular methods to evaluate the number of organisms in the environment.

Kids on farms live in a haze of bacteria and fungi at levels far higher than their urban counterparts and to their benefit. Organisms isolated included

“Listeria monocytogenes, Bacillus licheniformis and other bacillus species, corynebacterium species, methylobacterium species, xanthomonas species, enterobacter species, pantoea species, and others. …Staphylococcus sciuri and other staphylococcus species, salinicoccus species, macrococcus species, bacillus species, jeotgalicocus species, and others. …eurotium and penicillium species”

I no longer feel  as bad about the time my son was playing in the dirt, flipped a rock over and, before I could react, ate the slug he found underneath.  He was just exercising his young immune system. The NEJM study only evaluated the microbiology of the inside environment; there was no measurement of the larger outside environmental community.  I would imagine the number of organisms outside the home dwarfed what they could find inside.

As the accompanying editorial notes

“… that newborns begin to be colonized by microbes at birth, coincident with a period of rapid development of the immune system and lungs. These symbiotic organisms can be beneficial (e.g., gut bacteria that synthesize vitamin K) or pathogenic, or they may have no effect on the host (commensals). The authors propose that microbes found on farms adeptly stimulate innate immune receptors in early life and thereby favor the generation of regulatory T cells that promote immunologic tolerance.”

and the results are limited by

” microbial diagnostics provid(ing) only a low-resolution picture of microbial identity and diversity.”

There are far more wee beasties in and on us that we can currently identify. Farms, I would wager, are filled with far fewer bacteria than the environment in which pre-industrialized humans evolved.  Too many too soon runs counter, as does much of what is understood by antivaxers, to reality. When you are young, you can’t get enough.  The early immune system is the Johnny Rocco of the body (4).

The world is a crowded place at the level of the microorganism and we have evolved to respond to that crowding from birth.  Not just respond, but we need to be exposed to these antigens.

“Nothing is unnatural – just untried.” ~Rita Mae Brown

It may be argued that vaccines are not natural, whatever natural is.  I am the result of natural selection, so is not everything I do natural?  Infection with a needle is not how bacteria, fungi and virus get into the body.  I suppose this is a group of people who never had a percutaneous injury with a splinter or a cut from a thorn or a child who did not skin their knee on the dirt.  Percutaneous inoculation is a common way to be exposed to environmental antigens, just not as safe a way when sterile technique is avoided.

One would wonder if vaccines, in our ever so clean modern environment, could not only protect against the plagues of the past, but be a surrogate for our former environmental exposure to microbial squalor?

“adolescents having been vaccinated (n = 694) had a significant lower risk to suffer from asthma or atopic diseases than non-vaccinated adolescents did (n = 24) [odds ratio (OR) = 0.30; 95% CI: 0.10, 0.92]. The relationship did not depend on the disease against which the vaccine was used as prophylaxis, the observance of the vaccination schedule or the number of inoculations. A higher protection was observed in the case of live attenuated vaccines (oral poliomyelitis and bacilli Camille-Guerin; OR = 0.26; 95% CI: 0.08, 0.83). These results, in agreement with previous ecological data, support the hypothesis that early vaccines could promote Th1 proliferation in response to the infectious agent contained in it, which inhibits the enhancement of atopic manifestations. Further studies are needed to confirm the phenomenon.”

None of the above is  rock solid information when applied to vaccines, but an intriguing curiosity and, perhaps, hints about into disease etiology, but interesting when considering the potential responses of children to vaccines.  Too many too soon?  Doubt it.  Just enough, just in time?  Maybe.  Consider that receipt of MMR on schedule has been associated with decrease in autism.  I, of course, do not know what causes autism.  I had thought that the MMR results could be explained by lack of protection to neurotropic virus in the unvaccinated, but now I wonder.  There are articles on autoimmunty as a factor in autism, way beyond my current knowledge base . I will defer to others on the validity of these studies, I note them with interest but no deep understanding.

I think all human disease has, at its core, an association with infections. Most of the microbial studies on autism have concerned the use of antibiotics to treat the disease.  Autism rates have increased along with the expanded vaccine schedule, increasing cleanliness, global warming and the decline in pirates. The Amish do not get autism and they don’t live in a (relatively) sterile urban environments, and use a horse and buggy for transportation.    There must be a association in there somewhere that is actually causal. I know, probably not, but play along at home.

Let us  speculate: It would be ironic if  someday it was determined that part of the etiology of autism is, like asthma,  partly due to our microbial free environment and subsequent immune dysregulation and that vaccines, by supplying a surrogate immune stimulation, are protective.  Those who fought vaccines as a cause of autism turn out to be partly responsible for autism’s spread.  Truly worthy of  Medical Hypothesis, I admit, but it is amusing to speculate.  Someday science will sort it out.

It is fun to think about possible ramifications of the current literature.  I would certainly not use the speculation as a basis for my practice or to develop a therapeutic or preventative intervention with an exclamation mark. Hmm.  Or should I? I need to patent  a neonatal and infant probiotic  autism prevention supplement (NIPAPS!) containing the correct proportion of live and killed naturally occurring environmental bacteria and fungi.   There is a fortune to be made if I can just get rid of my ethics and morals.

Rationalization.

(1)  Not certain what ancient Greek for ’26′ would be.

(2)  Stay away from the Atlanta VA ICU. http://www.medscape.com/viewarticle/737884

(3)  Sorry.  Just epidemiology.  No gold standard, randomized, placebo controlled, blind trials utilizing the hypothetical/deductive technique, so ignore everything that follows. I am a snot.

(4) Johnny Rocco: Well, I want uh …
Frank McCloud: He wants more antigens, don’t you, Rocco?
Johnny Rocco: Yeah. That’s it. More. That’s right! I want more antigens!
James Temple: Will you ever get enough?
Frank McCloud: Will you, Rocco?
Johnny Rocco: Well, I never have. No, I guess I won’t.
~ Key Largo

Posted in: Science and Medicine, Vaccines

Leave a Comment (94) ↓

94 thoughts on “Triskaidekaphobia times two.

  1. nybgrus says:

    just to get the pedantic out of the way (and PLEASE NOBODY COMMENT ON THIS AT ALL) – I believe you probably meant “saturated fats” instead of “unsaturated” in the first paragraph.

    There. Now no one needs to question the whole friggin article because of a typo.

    Moving on…

    There is much work on that theory here in Australia. There have been some good studies (sorry – having a gin and tonic and relaxing in the evening so I won’t be bothered to find them at the moment) here showing that autoreactive inflammatory diseases like Crohn’s or even IBS have been alleviated by infecting the patient with hookworm. The theory being that the increased immune stimulation takes the focus away from the self and redirects it.

    It seems to make sense and there are a number of small (and even some larger) studies which seem to consistently push in that sort of direction. It is too soon to start saying we should all huck our children in a pool of raw sewage, but I think it gives us insight into the immune system and potentially some new tools to combat diseases we could do nothing about before.

    Thanks for the article Dr. Crislip. I find ID and micro to be a bit daunting but quite interesting at the same time.

  2. hat_eater says:

    Dr Crislip’s Famous Mudcakes(TM) – Just As Mother Nature Prescribed.

    On a more serious note, my anecdotal evidence seems to confirm the link posited by the NEJM article. In my extended family, there’s only one mother obsessed with cleanliness, and the only children who ever had any prolonged allergic reactions are hers.

  3. windriven says:

    I love starting my day with a blogget o’ pus; a perfect blend of humor and solid medicine.

    It amazes me that, as well understood as is the germ theory of medicine, regular, careful hand-washing is still not ritualistically practiced by all the staff in all hospitals. A miasma of genetic jetsam may be just what the doctor ordered for the kiddies, but not so much for the immunocompromised.

  4. MC “There are far more wee beasties in and on us that we can currently identify.”

    Stream of consciousness comment. A while back on Science Friday they were talking bacterial fingerprints… oh wait here’s the link
    http://www.sciencefriday.com/program/archives/201003193

    Nice article. I’m a big fan of the Hygiene Hypothesis, mostly because it helps me balance my husband’s don’t let the kids touch the floor in public o phobia

  5. Adaptogen says:

    In regards to evolutionary thinking, environmental stressors have the ability to both enhance and impair the immune system. Much like exercise is an imposed stress that results in healing, antigen presentation is a stress that results in immunity. Though my presentation is simplified, this is still a fascinating topic.

    A further topic of interest in regards to this concept is hormesis (a biologically favored response to low exposure of stressor).

    http://en.wikipedia.org/wiki/Hormesis

  6. daedalus2u says:

    There was a recent PNAS paper showing that in mice, exposure to bacteria does affect neurodevelopment. Germ-free mice were more anxious. They attribute the changes to gut bacteria but don’t show how they determined it was actually bacteria in the gut and not bacteria on the skin (as for example my favorite bacteria).

    There is a good blog post on the paper here.

    http://schaechter.asmblog.org/schaechter/2011/03/gut-microbes-and-the-infant-brain-a-surprising-symbiosis.html

    There could be some positive feedback in humans. Reduced exposure to bacteria produces a more anxious phenotype which is more afraid of exposure to bacteria.

  7. David Gorski says:

    just to get the pedantic out of the way (and PLEASE NOBODY COMMENT ON THIS AT ALL) – I believe you probably meant “saturated fats” instead of “unsaturated” in the first paragraph.

    Request denied. I detest pedantry.

  8. David Gorski says:

    There is a fortune to be made if I can just get rid of my ethics and morals.

    Indeed. I’ve said the same thing myself many times. Damn those morals and ethics! :-)

  9. Jan Willem Nienhuys says:

    Not certain what ancient Greek for ’26′ would be.

    icosihexaphobia.

  10. FYI: The link for “Being warmer than ambient temperature helps” to http://www.ncbi.nlm.nih.gov/pubmed/19827944. has a period at the end that breaks the link. Just remove the period at the end to access the link.

  11. Regarding dropping the morals and ethics. Since I try to avoid morals whenever possible and watched Drugstore Cowboy a few times back in the 80(?), I’ve thought on this.

    Upon becoming immoral and unethical, I would suspect that you would find yourself in a very competitive field. It’s not like Oprah starts knocking on your door once you’ve made the decision. There’s a product line to develop, books to write, testimonials to gather, press releases. You’ve got to put in a lot of effort to top some very immoral and unethical people.

    And not just anyone can sell water (omega 3, breathing, caribou milk) as a cure-all. That’s why they call them con artists. It takes talent, creativity and determination.

    Just seems like alot of work to me. I guess some people are good, some people are just lazy. ;)

  12. passionlessDrone says:

    Hello friends –

    So many over simplifications and contradictions here.

    From my perspective the paltry quantity of antigens children receive with the vaccine schedule are, when compared to the enormity of antigens in the environment, a rounding error.

    Too many too soon? Doubt it. Just enough, just in time? Maybe.

    Aren’t these two thoughts rather contradictory? What possible mechanism would you ‘maybe’ assign to this relationship within the context of vaccine exposure being a rounding error?

    I suppose this is a group of people who never had a percutaneous injury with a splinter or a cut from a thorn or a child who did not skin their knee on the dirt

    The more salient question ought to be, how many two month old infants skin their knee in the dirt? I advocate this number is vanishingly small. Seriously, is the skeptical community rife with two month olds that have gotten skinned knees? The distinction between childhood and infancy is so easy to grasp, and yet, is consistently missed in this discussion by people otherwise smart enough to understand the difference.

    If someone were to recommend starting the vaccine schedule at the age at which children started getting skinned knees, there would be howls of protest that infants are the ones more susceptible to diseases (true), but when someone wants to turn around and equate those two timeframes to make a joke, nobody seems to care. It isn’t funny; it is intentional conflation of two very different developmental timeframes. It is sloppy narrative in a forum supposedly dedicated towards rational and dispassionate evaluation of facts.

    It may be argued that vaccines are not natural, whatever natural is. I am the result of natural selection, so is not everything I do natural?

    Adjuvants are definitely not natural, and we really don’t quite understand just how they manage to invoke an immune response. That being said, there is some evidence that danger signals from endogenous sources is qualitatively different than exogenous sources.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913853/?tool=pubmed

    It is thought that part of the mechanism by which adjuvants achieve their effect is by frustruated phagocytosis and the resultant cellular debris is reacted read as a danger signal.

    I will defer to others on the validity of these studies, I note them with interest but no deep understanding.

    If you had a deeper understanding of them, you’d know that there are no less than five studies that show corerlations between autism severity and measurements of inflammation. You’d know that childen with genetic associations to MIF, a known immune promoter, are more likely to have autism. You’d know that there are no less than five studies that have evidence of an ongoing immune response in the CNS of people with autism. You’d know that proteins that participate in the suppression of inflammation are decreased in the CNS in autism. You would know that there are several studies that show that when stimulated with agonists, macrophages and T-cells from people with autism respond with increased inflammatory cytokines compared to people without autism, in vitro. How this would compare with the rounding analysis, I don’t know.

    The field of early life exposure to the dirty world and our relatively nascent understanding of the effects of these interactions is exciting stuff; but it really highlights just how little we know about the developing immune system. Within that framework, why is it that we are only allowed to acknowledge our relative ignorance of the immune system in areas other than vaccination?

    - pD

  13. geack says:

    The “oversimplifications and contradictions” appear to derive from your either deliberately misreading the article, or assigning more weight to certain statements than the author clearly intended.

    —”Too many too soon? Doubt it. Just enough, just in time? Maybe. ” — “Aren’t these two thoughts rather contradictory? What possible mechanism would you ‘maybe’ assign to this relationship within the context of vaccine exposure being a rounding error?”—

    The first part is a reference to the so-far unsupported assertion that early vaccines “overload” the immune system; the second part refers to the fact that childhood vaccines as currently administered are known to provide significant protection from infectious diseases.

    —”It may be argued that vaccines are not natural, whatever natural is… ” — “Adjuvants are definitely NOT NATURAL, and”—

    The author is pointing out that “natural” cannot be meaningfully defined and is therefore not a valid point of discussion. Your use of boldface type doesn’t provide a useful definition.

    Can you reference your two sets of five studies? Are they the same five? I can’t pretend to understand the details of immune-system biology but I’m looking to learn. I’m particularly curious about the in-vitro response study – I hadn’t heard before about any such clear immune differences.

    Sorry for the lousy formatting but I’m new here.

  14. nybgrus says:

    dr. gorski – my apologies. I was merely trying to circumvent before anyone had a chance to bring it up.

    PD – the point of “a rounding error” is to imply that the amount of antigens, “toxins,” what-have-you, that are received in the full course of vaccination is so incredibly small when compared to the amount received in the course of living through your first year or two of life that it may as well be rounded to zero. In other words the notion that vaccines overload your immune system is garbage because the antigen load can be comparatively rounded to zero.

    Get it?

    As for the rest – it is perfectly reasonable to anyone who ISNT an anti-vaccine loon.

  15. Jan Willem Nienhuys says:

    the amount received in the course of living through your first year or two of life

    Are there any estimates for this. I am quite willing to believe this, but it would be handy to have a source to point to, where someone had actually measured or counted the number of bacteria and/or virusses to which the immune system had mounted defenses by the age of two.

  16. daedalus2u says:

    PD, adjuvants are not natural? Skin lipids have about 12% squalene.

    Skin has ~ 1.1 mg squalene/cm2.

    The flu vaccine that had squalene as an adjuvant had ~10 mg.

    I suspect that the reason the body concentrates squalene in the skin is so that it does act as an adjuvant and accelerate immune activity from skin injuries.

  17. Anthro says:

    @nybgrus

    Dr. Gorski’s point is that everyone knows that Dr. Crislip meant “saturated”, so why bother writing about it? It’s a “slip-of-the-tongue” with typing, not an error. Even pedants usually stick to actual grammar errors, not typos.

    ——-

    As someone who grew up with lots of time outdoors, in the mud, playing with slugs, and vaccinated, I am really upset that I have so many allergies. I also will feel vindicated (if these theories hold up) for not making my kids “wash up” much, even before dinner. Other Moms were shocked at my casual attitude to dirty little boys, but at least they don’t have allergies (they’re in their 20′s and 30′s now).

  18. Mark Crislip says:

    My fear of unsaturated fats in this context has nothing to do with my diet, but, trust me, you really do not want to know the details.

  19. Lytrigian says:

    Hello there. I’ve been reading here a long time but haven’t replied before, mostly ’cause I couldn’t be arsed to finish off WordPress’ account creation tango.

    I have an autistic son, fairly high-functioning but clearly on the spectrum. I don’t know how relevant it might be to this discussion, but although I grew up in a semi-rural environment with lots of dirt to play/work in, I’m allergic to… um… well, the world, including my own thyroid gland (so to speak), and his mother is both allergic and asthmatic. He has a collection of allergies himself, most notably to peanuts, despite growing up in a far from sanitary environment.

    Coincidence? How should I know? Maybe worth a look, though, if a genetic predisposition to autoimmune disorders might have something to do with it.

  20. nybgrus says:

    @anthro: i’ve seen many a comment about an omitted word that was quite obvious what it should have been. But that is besides the point. I accept the criticism and will refrain in toto from now on.

    @Jan: I do not know of any studies specifically in that regard off the top of my head – I believe Crislip’s point was one of off the cuff estimations. Based upon some of the microbiome stuff that has come out recently with DNA analysis of lung tissue finding literally 100′s of genomes in an environment previously thought to be sterile:

    http://www.springerlink.com/content/v3401434300753k5/ (sorry, it is a pay access link)

    that alone seems to be more antigenic interaction that from vaccines. Throw in the normal gut flora (in a recent paper they found 536,00 unique bacterial genes in the gut) and we are already at a whopping amount of antigen exposure.

    Doing a little napkin-math if you take the average bacterial gene to be 1,346 bp (http://mbe.oxfordjournals.org/content/23/6/1107.full) and the largest prokaryotic genome to be 9.97Mbp and the smallest to be .16Mbp (http://en.wikipedia.org/wiki/Genome#Comparison_of_different_genome_sizes) that gives you an average of 5.1Mbp or 3,800 genes per prokaryote. If there are 536,000 unique genes in that above study, you get 141 completely unique species of bacteria in the gut. These are of course very rough and very conservative and don’t take into account closely related species – this assumes every one is COMPLETELY unique. So if you get just 2 antigenic interactions per species, also completely conservative, that is already 282 plus the lung bacteria we never knew we had makes it pretty reasonable to say that 6-700 unique antigenic interactions is a very reasonable absolute minimum.

    That doesnt take into account the skin, stomach, esophagus, lower urinary tract, female reproductive tract, the upper respiratory system, or the various random pollen, dander, seeds, dirt, and other bugs we would run into.

    According to Crislip, by age 6 you receive 26 antigens via vaccine. Using just the very narrow and extremely conservative estimate of 600 antigens just from bacteria as a part of being alive that gives you 0.041% of your antigenic load coming from vaccines.

    I’d certainly round that off.

    BTW, interesting note – in the article I linked to about the DNA analysis of the fecal samples they not that patients with IBS have a 25% lower bacterial load than normal patients. Seems to further support Crislip’s notion here.

  21. passionlessDrone says:

    @geack -

    I read the article fine.

    the second part refers to the fact that childhood vaccines as currently administered are known to provide significant protection from infectious diseases.

    Mr. Crislip is speculating on the possibility that vaccines are providing protective effects up and above the specific pathogens that they are tailored for, but rather, may be able to emulate the dirty environment we used to live in. He said:

    One would wonder if vaccines, in our ever so clean modern environment, could not only protect against the plagues of the past, but be a surrogate for our former environmental exposure to microbial squalor?

    How could they possibly be a ‘surrogatae for our former environmental exposure to microbial squalor’, if their immunological impact is a rounding error?

    The author is pointing out that “natural” cannot be meaningfully defined and is therefore not a valid point of discussion. Your use of boldface type doesn’t provide a useful definition.

    How about this then, aluminum salts included in vaccines to enable a robust immune response are distinctly different than the types of challenges our ancestors evolved with for millions of years. While aluminum is, technically, a natural substance, within a context of instigating an immune response, the presence of aluminum based salts is distinctly unique within the history of mammals.

    Would you like to argue that alumnimum salts as increasers of the immune response are natural?

    Can you reference your two sets of five studies? Are they the same five? I’m particularly curious about the in-vitro response study – I hadn’t heard before about any such clear immune differences.

    Sure. They are not the same five.

    Regarding an immune response in the CNS:

    Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism [Morgan / 20674603]

    Immune transcriptome alterations in the temporal cortex of subjects with autism [Garbet / 18378158] – full version available online and very cool paper

    Neuroglial activation and neuroinflammation in the brain of patients with autism. [Vargas, 15546155]

    Elevated immune response in the brain of autistic patients [Li / 19157572]

    Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. [Chez / 17560496]

    Regarding associations between autism behavioral severity and propensity towards an exaggerated immune response / inflammatory state, see these papers:

    Macrophage migration inhibitory factor and autism spectrum disorders [Grigorenko/18676531]

    Increased serum levels of high mobility group box 1 protein in patients with autistic disorder [Enzo / 20302902]

    Altered T cell responses in children with autism [Ashwood/20833247

    Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome [Ashwood/20705131] (Note the association of increased inflammatory cytokines and regressive phenotype)

    Alterations of circulating endogenous secretory RAGE and S100A9 levels indicating dysfunction of the AGE-RAGE axis in autism [Boso/17101220]

    Regarding in vitro studies, check out the T-Cell study I listed above, and

    Differential monocyte responses to TLR ligands in children with autism spectrum disorders [Enstrom/19666104] (full version available online)

    Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders [Ashwood / 19211157]

    Also, Jynouchi has several involving differential creation of cytokines in response to a variety of dietary proteins (ie., caesin and gliadin).

    Regarding prenatal models, the Patterson has several very neat studies that have narrowed in on the effect of IL-6 on the developing brain. He had one that came out about two months ago that was very elegant, Activation of the maternal immune system induces endocrine changes in the placenta via IL-6.

    - pD

  22. nybgrus says:

    sorry – comment is in moderation limbo because of my reference links and in re-reading I noticed I forgot to add the one from nature about the 536,000 unique bacterial genes found in the guts of Europeans.

    http://www.nature.com/nature/journal/v464/n7285/full/nature08821.html

  23. passionlessDrone says:

    Hi Nygbrus –

    PD – the point of “a rounding error” is to imply that the amount of antigens, “toxins,” what-have-you, that are received in the full course of vaccination is so incredibly small when compared to the amount received in the course of living through your first year or two of life that it may as well be rounded to zero. In other words the notion that vaccines overload your immune system is garbage because the antigen load can be comparatively rounded to zero.

    Get it?

    As with geack, if this is true, then why would we consider this statement to have any possible validity:

    One would wonder if vaccines, in our ever so clean modern environment, could not only protect against the plagues of the past, but be a surrogate for our former environmental exposure to microbial squalor?

    If the exposure from vaccines is so overwhelmingly minute, how could it be possibly serve as a surrogate for our former environmental exposure to microbial squalor? How?

    In any case, the antigen overload canard is the equivalent to a T-ball game; fun to swing away at, but not really challenging.

    There is voluminous evidence that early life immune challenges can persistently modify the immune system in ways we don’t understand; this thread was started on a very similar concept. The problem is, with a system as complicated as the immune system, the idea that we can leverage the power of addition, and ignore things like developmental timeframes, or the inclusion of adjuvants for that matter, and claim that we have a good understanding of the effects of our actions is not defendable to the standards usually set forth by this site.

    - pD

  24. nybgrus says:

    “How about this then, aluminum salts included in vaccines to enable a robust immune response are distinctly different than the types of challenges our ancestors evolved with for millions of years. While aluminum is, technically, a natural substance, within a context of instigating an immune response, the presence of aluminum based salts is distinctly unique within the history of mammals.
    Would you like to argue that alumnimum salts as increasers of the immune response are natural?”

    Perhaps you would like to also argue that we live in exactly the same circumstances as our ancestors millions of years ago when aluminum salts were not natural to them? Or that the corn, tomato, canned tuna, nylon clothing, and Nivea face cream we often use are “natural” by the same token? Or perhaps you would like to argue that we haven’t evolved at all since the time when aluminum salts were not natural to our ancestors? Maybe that slurpee with red dye #40 and HFCS is not-natural… or is it? Or we could even go back a bit in time – perhaps cotton was “not-natural” to our ancestors of the industrial revolution? Or the coal and soot from it that was burned? Or maybe the smoke from fire once our distant ancestors mastered that?

    Do you now, perhaps, see why the concept of “that isn’t natural” is not something that can be meaningfully defined?

  25. nybgrus says:

    nobody claimed to have a good understanding. And I don’t believe that Crislip is saying our current level, type, and understanding is CURRENTLY a surrogate. And more so, a surrogate need not completely replace – especially if the entire antigenic load is actually not needed. Just because we have such an onslaught of antigens doesn’t mean that is the minimum number needed to tune our immune systems. As you yourself pointed out – we don’t know enough to answer that question (yet). But since we see a decrease in IBS, Crohn’s, asthma, atopy, etc symptoms from exposure to JUST A FEW ANTIGENS like vaccines or (as in the Aussie study I mentioned) parasitic worms then it seems reasonable to postulate that it MIGHT serve as a surrogate that can be fine tuned once our understanding grows.

  26. passionlessDrone says:

    Hi daedulus2u –

    PD, adjuvants are not natural? Skin lipids have about 12% squalene.

    You are well aware that squalene is in use only in some vaccines, and at that, only in some countries. In the US the only approved adjuvant is aluminum salt based.

    In any case, just because something occurs naturally, that doesn’t mean we can package it up in a vaccine and pretend that all things are considered equal. My statement wasn’t so much about whether or not something was created in a laboratory or not so much as the contextual problems of manipulating a system with a substance unnatural to the immune response and assume that we understand the differences. Our immune systems most definitely did not evolve alongside aluminum salts.

    Cytokines are natural. Mitochondrial DNA is natural. I bet if we were to include those in a vaccine, it would work to help kickstart the immune response too.

    But knowing something does one thing doesn’t allow us to know all of the effects, and my opinion is that we should tread very lightly when making presumptions about how a system as complicated and entangled as the immune system will respond to something that is qualitatively or quantitatively different than the challenges it evolved to face over millions of generations.

    Skin has ~ 1.1 mg squalene/cm2.

    The flu vaccine that had squalene as an adjuvant had ~10 mg.

    OK. Lets think along these lines a little bit; assuming for playtime purposes that one hundred percent of the squalene in your skin got incorporated into your body (i.e.,no external loss) during a laceration. Given that, how large of an area of skin would you have to lose in order to reach one flu vaccine worth of squalene? What happens to the size of our wound necessary if half the skin got removed external to your body?

    How common do you think such injuries are in infants?

    I suspect that the reason the body concentrates squalene in the skin is so that it does act as an adjuvant and accelerate immune activity from skin injuries.

    Clever idea. You may be correct.

    - pD

  27. passionlessDrone says:

    Hi nybgrus –

    Perhaps you would like to also argue that we live in exactly the same circumstances as our ancestors millions of years ago when aluminum salts were not natural to them?. . . Or maybe the smoke from fire once our distant ancestors mastered that?

    Do you now, perhaps, see why the concept of “that isn’t natural” is not something that can be meaningfully defined?

    Um. No.

    Mr. Crislip spends most of the conversation of ‘not natural’ by invoking a very specific component of vaccination, the injection.

    It may be argued that vaccines are not natural, whatever natural is. I am the result of natural selection, so is not everything I do natural? Infection with a needle is not how bacteria, fungi and virus get into the body. I suppose this is a group of people who never had a percutaneous injury with a splinter or a cut from a thorn or a child who did not skin their knee on the dirt. Percutaneous inoculation is a common way to be exposed to environmental antigens, just not as safe a way when sterile technique is avoided.

    When I point out that other very specific properties of the act of vaccination include components absolutely unencountered by our immune systems in mass until the most rapid blink of evolution history, you put in my court the need to defend any poorly thought out difference in our environment and the past of millions of years.

    The rant into existential bullshit has no place in science based medicine, but rather, belongs in a philosophy student’s bong. I could put uranium into a vaccine and insist that it is natural using the exact same sentence. Would you have a difficult time forming an opinion on the validity of that statement, or would you diffuse into semantic wanderings on the history of the human condition?

    Get it?

    I get it alright.

    - pD

  28. passionlessDrone says:

    Hi nybgrus –

    But since we see a decrease in IBS, Crohn’s, asthma, atopy, etc symptoms from exposure to JUST A FEW ANTIGENS like vaccines or (as in the Aussie study I mentioned) parasitic worms then it seems reasonable to postulate that it MIGHT serve as a surrogate that can be fine tuned once our understanding grows.

    I think you misunderstand the current thoughts regarding how hookworms infection is related to reduction in autoimmune conditions with inflammatory components; the hookwork appears to be actively subverting our immune system, altering its properties to create an environment in which it can thrive. Some effects of this modulation appear to be protective for certain autoimmune conditions.

    http://www.ncbi.nlm.nih.gov/pubmed/15681140

    Hookworms infect almost one billion people and are a major cause of iron-deficiency anaemia in developing countries of the tropics. Despite their prevalence and the morbidity they cause, little is known about the immune response to this complex eukaryotic parasite. Recent publications have shed light on the human cellular immune responses to hookworms, as well as mechanisms that hookworms utilize to skew the immune response in its favour. Unlike most other human helminth infections, neither age- nor exposure-related immunity develops in the majority of infected people.

    It doesn’t have anything to do with the number of antigens that a parasite provides, but rather, the processes the organism has evolved to manipulate its host. As such, comparisons to the number of antigens in a vaccine is a poor analogy.

    If you want to see something that will really blow your mind regarding parasites, check out some of the literature on parasite prevelance and IQ.

    - pD

  29. norrisL says:

    Re the reference to a child eating a slug. In my part of the world at 27 degrees South we do have a problem with children who eat a slug or a snail. The tropical and subtropical parasite Angiostrongylus cantonensis, which may be found in slugs and snails, affects the central nervous system resulting in a major inflammatory response which, sadly, does occasionally prove fatal.

    Otherwise, despite a lack of any concrete evidence, I suspect the “exposure to multiple antigens at a young age” hypothesis is probably quite valid.

  30. “Kids on farms live in a haze of bacteria and fungi at levels far higher than their urban counterparts…”

    Really? I’m surprised by this. It challenges my aversion to the crush of humanity in urban landscapes. Maybe on the farm there is more variety, whereas the sheer volume in urban areas might be greater yet is somewhat homogenous?

    I’ll let my kids splash around in mountain streams populated with moose feces and what not, but I get a little twitchy about what they touch in public places in large cities.

    Just an anecdote, but a black lab goes a long way to increasing the haze at our house.

  31. nybgrus says:

    PD – I hate to say this but you are quite off base. Besides not addressing my critique of your “naturalistic” claim of aluminum salts, you really don’t have an in depth appreciation of my point about the hookworms (nor about what the study really says). You cite a study that refers to the disease burden of hookworm in NORMAL people – nothing relating to the use of them in Crohn’s disease. You seem to be quite enamored with the line:

    ” …as well as mechanisms that hookworms utilize to skew the immune response in its favour…”

    Do you even know what that means? What are you implying by your bolding of that statement? And what do you infer from what the statement means? In the context of the article it refers to the ability of the hookworm to evade destruction by the immune system by somehow (not-specified) changing the immune response so it may survive. This is not a terribly uncommon trick by pathogens but it does not mean that there is NO immune response.

    Since the hypothesis postulated is that a LACK of antigenicity is what leads to increased autoimmunity (specifically Crohn’s in this case) then we are left with a couple of interesting postulates. 1) that ANY antigenic stimulus will provide the necessary “re-direction” of immunity to alleviate the autoimmune effects of Crohn’s 2) that not just ANY will do but a specific stimulation will.

    However, rather than citing an article at me that has nothing to do with the topic, does not refer to the population in question, and has some vague statement which you (apparently) mis-interpret as meaning there is no immune response you could have just looked up the article I referenced as showing exactly the correlation I was inferring. So here, I’ll save you the trouble:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856386/

    “Weinstock and colleagues have successfully tested the pig whipworm, Trichuris suis, in patients with inflammatory bowel disease (IBD).4,5 However, repeated inoculation was required and concern has been raised that aberrant migration could occur.6 The haematophagous hookworm, Necator americanus (NA), is proposed as an alternative….After 20 weeks, the IBD questionnaire was improved (mean 151 (14) v 179 (20)) and the four week cumulated CDAI scores was decreased (mean 141 (31) v 87 (15)”

    Let’s see – an antigenic stimulation DECREASED symptoms of Crohn’s! But not just ANY… the Trichuris did not work as well as the Necatur!

    But wait! You said that the hookworms “skewed the immune response” indicating that negated the concept of its antigenicity.

    “In the CD cohort, blood eosinophilia developed from week 5 (mean 2.60×109/l (1.89) v week 1 0.18×109/l (0.10) v week 20 0.59 (0.20))”

    Ah! There was a clinical immune response to the antigenic stimulation by the hookworm!

    So who is it betwixt us that “misunderstand[s] the current thoughts regarding how hookworms infection is related to reduction in autoimmune conditions with inflammatory components”?

    Right… the one who said “…the hookwork appears to be actively subverting our immune system…”

    Finding bits of data to try and fit into your preconceived notions and biases is not science and it is not a way to win favor here.

  32. tomm says:

    What about the risk of in-vivo creation of pathogenic retroviruses from multiple endogenous retroviruses piggybacking along with the purposefully administered attenuated viruses? This theory posits that transposons modify ERVs in vivo to re-awaken them from their dormant slumber.

    This doesn’t appear to be entirely theoretical: though full paper isn’t available yet, this seems rather convincing:

    “Results: PCR assays showed that both cell lines and later passage xenografts contained XMRV but the early passage xenografts did not, indicating that XMRV was not present in either the original CWR22 tumor or associated nude mouse tissue, but became prevalent in later passage xenografts. Retroviral recombination between PreXMRV-1 and PreXMRV-2 involving a few template switching events can generate a replication-competent virus that differs from XMRV by only 5 nucleotides (99.94% identity). Analysis of 15 nude mouse strains indicated that none contained XMRV, but some strains potentially used to passage the xenograft contained both PreXMRV-1 and PreXMRV-2.”
    http://www.retroconference.org/2011/Abstracts/42508.htm

    This paper raises the point that we’ve known about the potential dangers of ERVs for a long time, but have basically ignored them. Full text of “Endogenous retroviruses as potential hazards for vaccines” from Biologics is available here:
    http://www.ecs.umass.edu/~mettu/ece597m/papers/Leung/sdarticle-1.pdf

    Anyone have opinions on the risk of ERVs? I’m new to the board and to the field, please be gentle. :)

    Tomm

  33. Mark Crislip “My fear of unsaturated fats in this context has nothing to do with my diet, but, trust me, you really do not want to know the details.”

    Actually, I didn’t want to know, until you told me that I didn’t want to know. Now I’m curious…

    imagining possible scenarios that would make someone afraid of (any kinds of) fats…

    No, you’re right. I don’t want to know.

  34. Nescio says:

    Re: aluminum salts as adjuvants being “unnatural”; aluminum is the most common element in soil and some of it is in the form of soluble salts (somewhere in the region of 0.2 ppm in some soils depending on pH). Before we started living in concrete jungles, many (perhaps most) injuries would introduce a small quantity of aluminum salts into the wound. Again, perhaps this is why our immune systems have developed to produce a greater response when our skin is inoculated with foreign proteins mixed with aluminum salts than without the aluminum.

  35. DrRobC says:

    “the Amish do not get autism”

    The Amish do have cases of autism and Childrens Hospital of Phila does have an outreach to see them

  36. Mark Crislip says:

    I am aware that the Amish do not get autism and that the increase is due to awareness and a broader definition. I debated that paragraph given it was meant to parrot the popular beliefs.

  37. passionlessDrone says:

    Hi nygbrus -

    Sigh. This is a perfect example of what happens when people want to reduce complicated systems into simplisitc models; i.e., we can understand the impact of vaccination by counting up antigens.

    The effect of a pathogen has many participants up and above the antigen on the outside, the component that our immune system recognizes, and lots to do with how the pathogen actually infects and damages cells.

    There are hundreds, or thousands of bacteria that have LPS in their cell wall and are recognized by TLR4; that doesn’t mean that they all are identical, just that they share some common traits, specific structures on their cell membrances; i.e., antigens, that our immune systems have evolved to track.

    For some reason, you seem to think that all immunology starts and ends with the antigens; it doesn’t. This is probably the result of reading things like the OP. Do you think that tetanus achieves its extremely high fatality rate solely as a result of its antigen profile?

    Check out this NYT article on the issue of hookworms and autoimmune disease. [Note that the scientist here, Pritchard, is an author on the paper you referenced me to!

    http://www.nytimes.com/2008/07/01/health/research/01prof.html

    “The allergic response evolved to help expel parasites, and we think the worms have found a way of switching off the immune system in order to survive,” he said. “That’s why infected people have fewer allergic symptoms.”

    Nearly 20 years later, his musing began to come to fruition. After Dr. Pritchard’s self-infection experiment, the National Health Services ethics committee let him conduct a study in 2006 with 30 participants, 15 of whom received 10 hookworms each. Tests showed that after six weeks, the T-cells of the 15 worm recipients began to produce lower levels of chemicals associated with inflammatory response, indicating that their immune systems were more suppressed than those of the 15 placebo recipients. Despite playing host to small numbers of parasites, worm recipients reported little discomfort.

    Check that out, one of the authors of your paper says: “we think the worms have found a way of switching off the immune system in order to survive

    Maybe you should contact him and tell him that it’s all about the antigenicity.

    You said:

    Since the hypothesis postulated is that a LACK of antigenicity is what leads to increased autoimmunity (specifically Crohn’s in this case) then we are left with a couple of interesting postulates. 1) that ANY antigenic stimulus will provide the necessary “re-direction” of immunity to alleviate the autoimmune effects of Crohn’s 2) that not just ANY will do but a specific stimulation will.

    What is making you believe that it is the stimulation of a hookworm that is achieving the effect? What? When people take immunosuppressives for Crohns, they aren’t doing it because it stimulates the immune response, but rather, because it downregulates the same response. Please refer to Pritchard, above, for more on this.

    However, rather than citing an article at me that has nothing to do with the topic, does not refer to the population in question, and has some vague statement which you (apparently) mis-interpret as meaning there is no immune response you could have just looked up the article I referenced as showing exactly the correlation I was inferring.

    The idea that a paper entitled Immunobiology of hookworm infection has nothing to do with the mechanism by which hookworm infections may modulate Crohn’s severity is a real laugher.

    Let’s see – an antigenic stimulation DECREASED symptoms of Crohn’s! But not just ANY… the Trichuris did not work as well as the Necatur!

    Why is the fact that different pathogens have different effects of surprise to you? And furthermore, do you assert that the only difference between these two organisms is their antigenicity? If not, if there are other differences between these organisms, what has given you such confidence that it is the structure of the antigen, and that structure alone, that is resulting in immunomodulatory effects?

    But wait! You said that the hookworms “skewed the immune response” indicating that negated the concept of its antigenicity.

    They do appear to skew the immune response, but they do so globally. If you modify the number of T-Cells in circulation, and consequently, the concentration of IL-10, you aren’t just going to affect hookworms, you are globally regulating the immune response. Everything cools off. Your insistence that this effect is achieved solely through the antigenicity is your own to resolve.

    -pD

  38. passionlessDrone says:

    Hi nygbrus -

    Here is another nice one from Pritchard on the topic.

    http://www.ajtmh.org/cgi/content/full/77/5/860

    Basophil Competence during Hookworm (Necator americanus) Infection

    From the discussion:

    Therefore, we now suggest that hookworm-mediated downregulation of immune responses is instead mediated by secreted parasite immune suppressants and the induction of regulatory leukocyte populations rather than at the level of FcRI blockade.

    The parasite is secreting immune suppressants! It isn’t about
    ‘antigenic stimulation’, it is about down regulation, and that has very little to do with antigens.

    - pD

  39. nybgrus says:

    pd – I apologize, I missed your response to the “naturalness” of the aluminum salts. But, you are still completely wrong. In fact Nescio gave a nicely succinct hypothesis as well. And indeed, injecting uranium WOULD be natural. So would injecting cyanide. That is the whole point – natural DOESN’T inherently mean safe, good, or better. It can indeed be quite bad. So whilst the discussion of “are aluminum salts BAD for you” is another topic trying to say “they are unnatural and therefore bad for you” is BS. The fact that YOU can’t understand why defining something as “natural” is not a meaningful exercise is your problem. I shan’t belabor the point, because I am quite frankly getting tired of having these tit-for-tats with antivax idiots.

    But I will address your attempts at science before signing off:

    “There are hundreds, or thousands of bacteria that have LPS in their cell wall and are recognized by TLR4; that doesn’t mean that they all are identical…”

    No, but the LPS is. That is why it is such a phylogenetically old PAMP recognized by the TLR4. What is your point?

    “For some reason, you seem to think that all immunology starts and ends with the antigens; it doesn’t”

    Antigen = antibody generator. Insofar as immunity comprises a cell cytotoxic arm and an innate (complement) arm, yes you would be correct. However, what is it that triggers the complement cascade? Right… binding to specific antigens on the surface bacteria. What triggers the cytotoxic arm? Peptide epitopes of the virus on MHCI. What triggers the Th cell lineage? Epitopes on the MHCII of APCs. So overall, while in the strictest sense they don’t all respond to antigens, they do all respond to protein sequences unique to the pathogen in question. So from that standpoint, yes, it is more or less all about the antigens, since none of those proteins (whether they be defined as antigen or epitope since that definition is only a functional one depending upon the way in which a protein activates the sequence) would be there without the pathogen. The only exception would be NK cells – they are cytotoxic from a lack of MHCI presentation at the cell surface. So in that regard, I guess you can’t say it is all about the antigens since one type of cell is not about them. Pretty close though.

    “Do you think that tetanus achieves its extremely high fatality rate solely as a result of its antigen profile”

    No, in fact it is so lethal because it lacks a good antigen profile and secretes a very potent toxin. What is your point?

    The point of IBD such as Crohn’s is the autoimmune reactivity. We currently use immunosuppressives because that is our only method for turning down the WHOLE of the immune response. The use of these worms creates an increased immune response… away from the autoreactive.

    “These data would indicate that FcRI blockade at the level of the basophil did not occur in this parasitized population despite the presence of possible immunologic blocking agents. This would suggest that this effector arm of the T helper 2 phenotype remains operative in infected populations.”

    “Therefore, we now suggest that hookworm-mediated downregulation of immune responses is instead mediated by secreted parasite immune suppressants and the induction of regulatory leukocyte populations3 rather than at the level of FcRI blockade.”

    So they are hypothesizing from a lack of evidence in the article you cited. There is no confirmation that is actually what is happening.

    And from your NYT article (though I am loath to use popular media reports on science since they are almost always crap, but when it serves to prove you wrong I’ll use your own source):

    “When Dr. Maizels and his colleagues infected a group of mice with the Heligmosomoides polygyrus parasite, a nematode similar to the hookworm that infects humans, they found that the mice started churning out more regulatory T cells for reasons that remain unclear.”

    And now to take a quote you are likely just loving and actually put it into context:

    “There’s a lot of evidence that allergy is just the immune system going a little over the top,” he said. “The worms are just turning down the volume.”

    They are turning down the volume of the inflammatory effects from the prior immune response – but the overall effect of the infection is, yup, an increase in immune response in the presence of the Necatur.

    Lets see, so far we have seen increased eosinophils, increased T cells, and an unencumbered IgE and basophil response…. sure sounds like an increased immune response.

    The key point here is that the pathogenicity of the Necatur is due to its sly way of increasing the immune response in a way that is ineffective in destroying the worm itself but has this added side effect of decreasing symptoms of IBD because that “skewing” of the immune response also happens to skew it away from the autoreactivity and inflammatory arm.

    How on earth might this work, you may ask yourself. Well, happy to answer. The Th2 arm of the immune response is what is overactive in people with allergies. In the immune system the Th2 arm downregulates the Th1 arm and vice versa. So the theory is, since there is a distinct correlation with certain HLA types and a genetic component to allergies, that those individuals who do not have a proper antigenic stimulation at an early age will by default tend to favor a random Th2 response. This is because many viruses and bacteria upregulate the Th1 response, thus decreasing the allergic effects of Th2. Introduction of antigenic stimulation would thus increase immune response…. but away from the Th2 arm.

    How about autoimmune like IBD? That is a Th1 problem and the hypothesis is that a lack of antigenic stimulation from pathogens leaves the body missing the proper T regulatory cells and so the Th1 response turns to self. Introducing an antigenic stimulation of the Th1 arm could thus increase proper regulatory T cell production which is exactly what we have seen in the articles you cited above!

    So, to close:

    “It isn’t about ‘antigenic stimulation’, it is about down regulation, and that has very little to do with antigens.”

    Indeed, it is about the antigens – and I have no shown you exactly how antigens can in fact suppress certain arms of the immune system whilst overal creating an immune response. If the parasite happens to also secrete immune suppressants that further that effect, well that would just make evolutionary sense and could explain why Necatur is better at achieving the effect than Trichius. But it does nothing to dispel the hygiene hypothesis, nor support any of your claims.

    So while on the surface you are correct in your inferences, scratching just a little deeper shows you lack an appreciation for nuance and understanding of exactly what is going on… exactly what I would expect from an antivaxer. Not that I would expect you to actually understand any of this.

  40. nybgrus,

    pD may be barking up the wrong tree by investing effort into trying to determine whether, in theory, vaccination could contribute to autism. Fine. But pD has consistently challenged one particular argument of the anti-anti-vax squad and never received a direct response to the facts or assertions, which I find interesting.

    Anti-anti-vaxxer: Infants are colonized with huge numbers of microorganisms from birth. The antibodies in vaccines couldn’t possibly make a difference.

    pD: The antibodies in vaccines cause inflammation, so they are different in that sense to the normal post-birth colonization.

    Anti-anti-vaxxer: Children get sick. That’s inflammation. They’re also constantly running around and scraping their knees and getting soil organisms under their skin. They get inflammation from that too.

    pD: Infants less than six weeks old don’t actually get sick that often. When they do it tends to be really really serious. And they never run around and scrape their knees. When they get scratched it tends to be by their own fingernails which don’t contain many soil organisms. But infants less than six weeks old do get broken skin and inflammation from vaccinations. That’s different from the normal developmental course.

    Anti-anti-vaxxer: You don’t know what you’re talking about. I just explained that even newborns have bacteria in their guts and on their skin, and that it’s completely developmentally appropriate for children to scrape their knees.

    pD: You aren’t listening. I pointed out that immune challenges causing inflammation are not developmentally normal in infants under six weeks. They never run around and scrape their knees so bringing that up is completely irrelevant. You haven’t responded to that.

    Anti-anti-vaxxer: Wow, you really are dense, aren’t you.

    *** *** ***

    Anyway I think that pD is putting considerable effort into developing a line of thought and very politely laying those thoughts out here for response. It’s fascinating to me to watch this same argument played over and over again, and the same points presented politely and ignored.

    I can’t address them because I don’t have the knowledge; the people who do choose not to, for whatever reason.

    I’m saying this not because I’m anti-vax or think that vaccines cause autism, but because I’m interested in to know if there is a direct science-based response to pD’s observations beyond “there is no autism epidemic” and “we’ve looked for an association between autism and vaccines and not found one.” (I accept these latter statements, by the way.)

  41. passionlessDrone says:

    Hi Nygbrus –

    That is the whole point – natural DOESN’T inherently mean safe, good, or better. It can indeed be quite bad. So whilst the discussion of “are aluminum salts BAD for you” is another topic trying to say “they are unnatural and therefore bad for you” is BS. The fact that YOU can’t understand why defining something as “natural” is not a meaningful exercise is your problem. I shan’t belabor the point, because I am quite frankly getting tired of having these tit-for-tats with antivax idiots.

    I don’t think I made the arguments you are ascribing to me. If you could point out somewhere that I made a specific claim that adjuvants were bad, that would be one thing, but I’m just saying that from an evolutionary standpoint, there are different.

    No, but the LPS is. That is why it is such a phylogenetically old PAMP recognized by the TLR4. What is your point?

    Antigen = antibody generator. Insofar as immunity comprises a cell cytotoxic arm and an innate (complement) arm, yes you would be correct. However, what is it that triggers the complement cascade? Right… binding to specific antigens on the surface bacteria.

    Here is question for you then: Which TLR recognizes aluminum salts? How is it achieving it’s immunological effect, when it does not have antigens on it?

    If our discussion does not hinge on things that occur naturally, but rather, things that our bodies have evolved to react to, this is the salient distinction. Concering Nesicos posting and Daedulus2u, how much dirt would you have to get in a wound to incorporate in 10 mg of aluminum salt from soil?

    If you are infant getting four or five vaccines at once, how much dirt does that involve?

    No, in fact it is so lethal because it lacks a good antigen profile and secretes a very potent toxin. What is your point?

    My point is that there are things other than antigens to be considered in immunology. This is why having considerations other than antigenicity is pertinent towards the question of why one species of hookworm has different immunological effects than other species of hookworms.

    Lets see, so far we have seen increased eosinophils, increased T cells, and an unencumbered IgE and basophil response…. sure sounds like an increased immune response.

    I think you meant, ‘t-regulatory cells’, and that’s a big, BIG distinction. From the paper again:

    Therefore, we now suggest that hookworm-mediated downregulation of immune responses is instead mediated by secreted parasite immune suppressants and the induction of regulatory leukocyte populations rather than at the level of FcRI blockade.

    It is so deliciously ironic that you would read this quote, from the same authors you sent me to originally, and come away thinking that their findings are indicative of an overall increase in the immune response.

    The key point here is that the pathogenicity of the Necatur is due to its sly way of increasing the immune response in a way that is ineffective in destroying the worm itself but has this added side effect of decreasing symptoms of IBD because that “skewing” of the immune response also happens to skew it away from the autoreactivity and inflammatory arm.

    We do seem to see eye to eye here, the Necatur is decreasing the inflammatory arm. To me, that says, ‘decreased immune response’. Also to the authors of the paper, as when they say, ‘downregulation of the immune response’.

    How on earth might this work, you may ask yourself. Well, happy to answer. The Th2 arm of the immune response is what is overactive in people with allergies. In the immune system the Th2 arm downregulates the Th1 arm and vice versa. So the theory is, since there is a distinct correlation with certain HLA types and a genetic component to allergies, that those individuals who do not have a proper antigenic stimulation at an early age will by default tend to favor a random Th2 response. This is because many viruses and bacteria upregulate the Th1 response, thus decreasing the allergic effects of Th2. Introduction of antigenic stimulation would thus increase immune response…. but away from the Th2 arm.

    You seem to have very different ideas than the authors of the paper, the same authors you referred me to originally.

    That is a Th1 problem and the hypothesis is that a lack of antigenic stimulation from pathogens leaves the body missing the proper T regulatory cells and so the Th1 response turns to self.

    Hehe. The authors have stated an increase in T-regulatory cells as a result of hookworm infection! That’s why they think it works, an increase in regulation!

    Indeed, it is about the antigens – and I have no shown you exactly how antigens can in fact suppress certain arms of the immune system whilst overal creating an immune response.

    You have absolutely failed to show that there is something specific about the antigen profile of the hookwork in question that makes their immunosupprsive capabilities possible. After all, if you think vaccines are a rounding error, the antigen presentation from a single worm is a roudning error on that error, and yet they seem to have immune modulating capacities.

    How is this for a though experiement. What makes the antigen presenation by hookworms demonstrably differen than the anitgen presentation by tetanus regarding IBD? Why not just give everyone with IBD a cold to see if their symptoms dissipate? Or the flu? Why bother with hookworms, which have real problems associated with them, if all we need is simple antigenic stimulation? Hell, why not just give them an influenza vaccine every week or so? What is specific about hookworm antigens that achieve this effect

    Just saying that the the innate immune system is the start of the immune cascade (it is), and therefore, the antigens in a pathogen are responsible for all subequent observations (they aren’t) is a gross, gross oversimplification.

    If the parasite happens to also secrete immune suppressants that further that effect, well that would just make evolutionary sense and could explain why Necatur is better at achieving the effect than Trichius

    My original claim was that you don’t understand where the researchers looking at hookworms are driving towards in their research. The fact that the state in their research that they speculate the pathogen is actively secreting substances that are subverting the immune response, something that has nothing to do with antigen presentation, proves that point.

    I have no problems with the hygeine hypothesis proper, in fact, I kind of like it. If you think I have stated otherwise on this thread, please quote me and I will either retract that statement, or try to clarify my meaning.

    So while on the surface you are correct in your inferences, scratching just a little deeper shows you lack an appreciation for nuance and understanding of exactly what is going on… exactly what I would expect from an antivaxer. Not that I would expect you to actually understand any of this.

    Yawn.

    - pD

  42. passionlessDrone says:

    Hi Allison Cummings –

    Anyway I think that pD is putting considerable effort into developing a line of thought and very politely laying those thoughts out here for response. It’s fascinating to me to watch this same argument played over and over again, and the same points presented politely and ignored.

    You get it.

    I can’t address them because I don’t have the knowledge; the people who do choose not to, for whatever reason.

    You really get it. When TH1/TH2 shows up, he gets an avalanche of responses. Mr. Crislip will respond to him, as will Mr. Gorski. The sinking feeling you are getting is the realization that this is a function of the fact that they don’t have any real answers to my questions.

    I’m saying this not because I’m anti-vax or think that vaccines cause autism, but because I’m interested in to know if there is a direct science-based response to pD’s observations beyond “there is no autism epidemic” and “we’ve looked for an association between autism and vaccines and not found one.” (I accept these latter statements, by the way.)

    If you’ve been paying attention, you realize that we haven’t really studied vaccines, just thimerosal, and one vaccine (the MMR). But I won’t go there now. It is late and I am tired. It’s nice to know that someone has noticed that I’ve put some effort and courteous consideration into my posts. Thank you.

    Anyway, have you ever read any Kurt Vonegut? Welcome to the monkey house.

    - pD

  43. nybgrus says:

    @pd: you make a few valid points and I have not done a terribly great job of presenting the argument and evidence. For that I apologize. It stands, however, that it simply boils down do that shift in which arm of the immune system is currently being active. There are certain antigens which preferentially stimulate a Th1 response, others a Th2, others still eosinophil. However, there is much variation in person to person as to the extent of which pathway will take over – do remember that it is not all or nothing, it is always a balancing act. To claim that inoculation with Necator does not produce an immune response is simply wrong. Since parasites stimulate an eosinophilic response, and it seems that Necator specifically also stimulates in increase in T regulatory cells (yes, you were correct in my omission here) and may also have some sort of immunosuppressive attributes that easily explains why the immune response would shift away from an autoimmune response to a different one – thus alleviating the symptoms of IBD. Your claim is that the total overall level of immune response post-inoculation is lower. In writing this and thinking about it I think you could be correct in that assumption, but not in the way you think. Just to be clear in my thoughts lets speak in math for a minute – I will assign arbitrary numbers to indicate relative state of immune activity (0-100).

    Lets say a person with no allergies, atopy, IBD, etc has an average healthy immune state of 20. We could then say a person with an autoimmune disorder such as IBD would have a higher number – maybe 30 if mild or say 60 if severe. For arguments sake, lets say a person in acute sepsis is close to 100. Lets take a Crohn’s patient with a score of 50. That would indicate 30 is due to the autoimmune portion and 20 is normal background. We now inoculate with Necator and the score becomes 30. That would indeed be an overall decrease in immune activity, but 20 would be normal background, 30 from the autoimmunity (now turned to 0) and 10 would be from the worm. In a mild case, say IBD with score of 30 the level could go to 40.

    What I am trying to say is that while the overall level of immune activity could possibly go down that would be reflective of the shift in immune response away from autoimmune to combat the worm which is itself causing an increased immune response.

    The way I have been understanding you is that the worm acts as an immune suppressant and decreases the immune response much like prednisone or cyclosporine. That is incorrect.

    This obviously leads us to why the worm specifically would be useful and not just the common cold – because the worm’s antigenicity is one that would activate the pathway that would skew the immune response away from the autoimmunity going on. The cold would not do this. Furthermore, since the worm is in the GUT and IBD is obviously a gut problem that further explains why a URTI would have less (if any) effect. The worm is not acting like living cyclosporine.

    “We do seem to see eye to eye here, the Necatur is decreasing the inflammatory arm. To me, that says, ‘decreased immune response’. Also to the authors of the paper, as when they say, ‘downregulation of the immune response’.”

    Perhaps what I wrote above will now clarify that “turning down” the immune activity of one arm does not equate to an overall decreased immune response – though as I explained above it can coincide for those reasons. An important nuance.

    “You seem to have very different ideas than the authors of the paper…”

    How does my description of the activity of Th responses in any way contradict what the authors are saying? I am simply paraphrasing Janeway’s immunology in describing how we know the Th response to work.

    “You have absolutely failed to show that there is something specific about the antigen profile of the hookwork in question that makes their immunosupprsive capabilities possible.”

    Perhaps it is more clear now?

    “The fact that the state in their research that they speculate the pathogen is actively secreting substances that are subverting the immune response, something that has nothing to do with antigen presentation, proves that point.”

    That is because the things I have been explaining to you above are known to be factors in shifting immune responses… the fact that they are seeing even more is what is interesting and leading to a hypothesis about additional immune suppression. The fact that you believe the Necator is overall subverting an immune response shows that you do not understand what the authors are trying to say. Once again, clinical eosinophilia in the post-inoculation means that the worm is generating an immune response via its antigens!

    As for your claims about the aluminum salts – whether they are “natural” or “intended” stimulators of the immune system is irrelevant. If you were to take Nescio’s hypothesis at face value your questioning as to how much dirt would it take to get 10mg of aluminum salts in your wound is still pointless. Go ahead and throw his hypothesis out the window. The point is regardless of how, why, how much “natural” exposure, etc aluminum salts have been shown to increase the immune response. This allows for vaccines with a smaller antigenic load to have the same effect and thus make them safer. The only thing that matters is it works. Why did the muscarine mushrooms develop a protein that selectively inhibits muscarinic cholinergic receptors? Who knows? Who cares? The point is it works. How about 3rd and 4th generation penicillins that are mostly man made? Same thing… so I am missing your point as to questioning how “natural” aluminum salts are in increasing an immune response. It does, there is no toxicity at the levels given, ergo we give it.

    As for the hygiene hypothesis – I skimmed over quickly but do not have the wherewithal to dig deep enough. I will concede that you did not directly say it, and may have erroneously inferred that you are against the hypothesis. My apologies.

    @allison: The crux of the mistake, I believe, is in the assumption made here:

    Infants less than six weeks old don’t actually get sick that often. When they do it tends to be really really serious. And they never run around and scrape their knees. When they get scratched it tends to be by their own fingernails which don’t contain many soil organisms. But infants less than six weeks old do get broken skin and inflammation from vaccinations. That’s different from the normal developmental course.

    The reason that it is very serious for an infant to get sick at such a young age is because their immune system is (as of yet) undeveloped and indeed they rely primarily on the IgA from breastmilk and IgG from placental transfer for most of their immunity. However, if a pathogen should take hold in such an infant then that means it has been successful in evading the maternal Ig’s and the (tiny) hurdle of the infant’s own immune system. Thus, there is nothing left to stop said pathogen from reproducing wildly and that is what makes such infections so severe and life threatening. It has nothing to do with the infant simply having an inflammatory response but with that response becoming unlimited.

    Giving a vaccine to the infant (at least the ones given) has been shown to produce an immune response. The localized reaction to antigen stimulation is inflammation and thus you can see that reaction in infants (fever as well). That is the same as if the infant had an actual infection. The difference is that with the vaccine, since it is just the subunits there is no chance that the pathogen will multiply and thus the local inflammation/fever will subside and the infant will be no worse for the wear but have gained immunity.

    The assertion that an inflammatory reaction is not developmentally normal for a 6 week old is correct. Simply based on that one might reasonably conjecture that it could have negative developmental effects. However, while biologically plausible that it could have such effects, there is little reason to believe that it would, especially in light of all the studies finding no link between autism and other developmental disorders and vaccination.

    Hopefully that clears all that up and Allison has an answer now to pd’s questions.

  44. Nescio says:

    There is in the region of 0.2 ppm or 0.2 mg of soluble aluminum per kg of soil – levels of 0.5 ppm cause growth restriction in plants. It is clearly impossible that any accidental injury could introduce 10 mg of aluminum salts into a wound in soil.

    However, I was responding to PD’s question, “Would you like to argue that aluminum salts as increasers of the immune response are natural?” and PD’s assertion, “Our immune systems most definitely did not evolve alongside aluminum salts.”

    I am suggesting that it may be “natural” (i.e. the direct result of evolutionary processes) that aluminum salts increase immune response. I think it is undeniable that our immune systems evolved alongside aluminum salts, as aluminum salts were ubiquitous in the environment we evolved in.

  45. Alison Cummins:
    “I’m interested in to know if there is a direct science-based response to pD’s observations beyond “there is no autism epidemic” and “we’ve looked for an association between autism and vaccines and not found one.” (I accept these latter statements, by the way.)”

    nybgrus:
    [paraphrased] “No.”

    “The assertion that an inflammatory reaction is not developmentally normal for a 6 week old is correct. Simply based on that one might reasonably conjecture that it could have negative developmental effects. However, while biologically plausible that it could have such effects, there is little reason to believe that it would.”

    Ok, so pD is correct in saying that the skin-and-gut-colonization-with-huge-numbers-of-microorganisms argument is misleading wrt newborns.

    Which would be why nobody is arguing this point. Interesting that you are the first to concede it.

    The rest we all understand. For all I know, pD considers the risk/benefit profile of newborn vaccination against Hepatitis B to be acceptable, even believing that there is a theoretical plausible mechanism for it to interfere with normal development. I do not recall pD asserting otherwise.

  46. nybgrus says:

    @allison: I am unsure as to why my response is so succinctly paraphrased as “no.” Science can and does also work by exclusion. In other words, I was stated that with no other information except that fever and inflammation is not, per se, a normal developmental event by 6 weeks of age, there is no reason to assume that it would be detrimental. Standing absolutely alone that could leave it up to being a testable hypothesis – one that has been tested in the most ethical ways possible; namely examining outcomes.

    When you look for developmental problems and find no correlation between vaccines and said problems, and yet it is known that there is a non-zero incidence of fever and inflammatory responses due to vaccines, then from that alone it is reasonable to conclude that the science tells us there is no developmental detriment. However, one can also look at children who had developed infections and even sepsis as neonates and seen what the outcomes are. This is not something I am familiar with, but I reckon that there is no correlation there either, otherwise we likely would have heard about it. It is too late now, but I’ll try and dig up some data on that. My hypothesis would be that severe sepsis cases would have some effect since that would likely effect metabolism, nutrient intake, and many other factors but anything less than severe sepsis for a relatively long period would be the same as background noise.

    Additionally, I don’t believe that pd is correct in his “skin-and-gut-colonization-with-huge-numbers-of-microorganisms argument is misleading wrt newborns.” The fact is that in the process of colonization the immune system does and will mount an response including the same inflammatory cytokines, Ig production, etc. The fact that this doesn’t alter development is a reasonable starting point for asserting that fever/inflammatory response in and of itself (i.e. via the cytokine production) does not lead to developmental problems. Tack on cases of mild illness contracted by infants of that age and there is already pretty good evidence that a fever response is not ipso facto harmful at that age. In other words, the simple background levels that we see make the argument that pd is postulating (at least as how you paraphrased it and he agreed) moot. There is such a large number of infections, colonization, etc in the normal population at large that it seems absurd to think that a vaccine related fever could lead to harm.

    Remember, I said that if all we asserted was that illness in a 6 week old is not a common event then one could conjecture such a hypothesis. It is handily dismissed, and as such is handily dismissed by the SBM crowd. Colonization is enough, everything else is gravy.

  47. Alison Cummins – Thanks you so much for the cliff notes version of the discussion. I was getting that sense too, but your clarity helped.

  48. Mark Crislip says:

    After I write the posts I rarely respond in the comments as I am a slow writer and do not have buckets of time to compose responses, what with work and family and all. These three paragraphs took about 30 minutes to write. I use the comments for my own education and read them all on every post.

    I will admit to one thing, being a thin skinned primadonna. I live in the Pac NW where things are causal. Most people at work call me Mark, or Crislip, or hey you, and I have been called an arrogant closed minded tool of the medical industrial complex. ER nurses have a wonderful way of saying ‘Doctor’ as if it were actually ‘idiot’. All fine and good. I never use my title outside the hospital. But.

    In the context of the blog, when I am referred to as Mr, I cannot help but see a major league contemptuous passive-aggressive screw you asshole; I know, I do it myself. I stop reading the content of comments past the Mr. and skip those commenters in the future. I know I should try to pay attention to the message, not the messenger. Odd bit of psychology, since that is the only adjective in from of my name, and only in the context of the blog, to which I respond that way. I am not responding to questions? I am not reading them, and as a result is probably missing profound insights. My loss. Small minded? Yep. But transparently and honestly small-minded.

    Yours
    Crislip

  49. Chris says:

    Dr. Crislip:

    In the context of the blog, when I am referred to as Mr, I cannot help but see a major league contemptuous passive-aggressive screw you asshole; I know, I do it myself. I stop reading the content of comments past the Mr. and skip those commenters in the future.

    Interesting. I also live in the Pacific Northwest, and I still have trouble with the casualness of greetings. Even though our son’s were in the same kindergarten class I could never bring myself to calling his neurologist “Brien.” But I blame being an Army brat, where I grew up where all women were called either “Miss” or “Missus”, men were addressed as “Sgt.”, “Captain” and on and on… to the point I thought “Mister” was the official rank of a male school employee.

    But, point taken that using the handy dandy “Ctrl f” I see that pD has addressed you as “Mr. Crislip” three times. Every where else you are referred to as either “Crislip”, “Mark Crislip” and “Dr. Crislip.” So I see your reasons. My reasons for ignoring pD is that she/he seems to be determined to blame vaccines for autism with any tiny correlation, despite being told that they are specious and inaccurate. For some reasons it must be vaccines, and nothing else. When questioned “why the vaccine” a while ago, pD did waver, but is back to being single minded about vaccines. End of story

    Thank you Nescio for the explanation of aluminum in soil and kid scrapes. I have tried that argument in the past and have been told that toddlers know better to play in the dirt since they know sidewalks are safer (which can scrape more, and also contain aluminum salts since they are not sterile).

    Also, since I live in eco-friendly of the country, and from a very frugal family: one of my children and one of my sister’s have both experienced diaper pin stab by sleep deprived parent at least once (hurray for velcro diaper covers!). So, yeah, they can get hurt by sharp non-sterile objects when they are not mobile.

  50. Chris says:

    (comment in moderation… but now I notice a stupid extraneous apostrophe… it should read “Even though our sons were in the same kindergarten class I could never bring myself to calling his neurologist “Brien.” )

  51. Chris says:

    Wow, that un-moderation was fast!

  52. passionlessDrone says:

    Hi nygbrus –

    you make a few valid points and I have not done a terribly great job of presenting the argument and evidence. For that I apologize.

    There are uncounted instances wherein I have thought I’ve stated something concisely only to later find that it was less than clear. No apologies are necessary.

    It stands, however, that it simply boils down do that shift in which arm of the immune system is currently being active. There are certain antigens which preferentially stimulate a Th1 response, others a Th2, others still eosinophil. However, there is much variation in person to person as to the extent of which pathway will take over – do remember that it is not all or nothing, it is always a balancing act

    Good stuff! In fact, the delicate balance of the immune system, which we are only starting to unravel, is what bothers me so much about this debate. My position ultimately rests on the difficult to overstate complexity of the system we are interacting with during vaccination, and given a system with that level of complexity, models that utilize addition in order to gauge our effects are not useful.

    To claim that inoculation with Necator does not produce an immune response is simply wrong.

    If I gave you the idea that I though there was no immune response at all from Necator, I apologize. I merely meant to indicate my understanding of the research was that at a systemic level, the net effect was a reduction in inflammation. I think we can probably (?) agree that this is still a work in progress.

    The fact that you believe the Necator is overall subverting an immune response shows that you do not understand what the authors are trying to say. Once again, clinical eosinophilia in the post-inoculation means that the worm is generating an immune response via its antigens!

    I think we are falling into semantic holes here. I’d agree to the idea that eosonphilia is an ultimate end product of antigen presentation, but would counter that the overall effect of infection, by mechanisms currently not well understood, is more systemic than an increase in eosiphonils, and further, that the researchers in question believe that this larger, more global modification is driven by properties other than the antigens on the worm. The hookworm adventure was fun, and I learned a little bit along the way, but ultimately is keeping me from discussinig autism, which is my focus. Perhaps we could agree that there is much left to learn. Fair enough?

    The point is regardless of how, why, how much natural exposure, etc aluminum salts have been shown to increase the immune response. This allows for vaccines with a smaller antigenic load to have the same effect and thus make them safer. The only thing that matters is it works. Why did the muscarine mushrooms develop a protein that selectively inhibits muscarinic cholinergic receptors? Who knows? Who cares? The point is it works. How about 3rd and 4th generation penicillins that are mostly man made? Same thing so I am missing your point as to questioning how natural aluminum salts are in increasing an immune response. It does, there is no toxicity at the levels given, ergo we give it.

    Oh snap. Now we are getting somewhere interesting! Your thought process here encapsulates exactly what I think is so wrong about the autism / vaccine discussion; a seemingly cavallier attitude towards our level of understanding. Who cares how it works? The funny thing is, we seem to have come to some level of agreement on this issue when we discuss worms; nuance are important. The details are important.

    In the first place, what gives you the belief that a larger ‘antigenic load’ would be less safe? How units of measurement would you use to quantify safety if we had a vaccine with no adjuvant, half of todays adjuvant, or four times todays adjuvant in it? If you have a good understanding of why adjuvants make vaccines safer, I’d think that providing a layer of detail in this regard should be straightforward. As I think we have discovered with our foray into hoookworm land, just saying ‘antigens’ isn’t enough; it is the satellite level view of a very complicated process.

    For starters, this would seem to be mixing units when compared to the OP. Check out what Mr.Crislip wrote:

    There are, by my counting, 5 live attenuated viruses and 21 different antigens in the vaccine schedule by age 6, for a total of 26 or twice thirteen.

    Adding or removing adjuvants from a vaccine will have absolutely no effects on these numbers, just the relative concentration of how many physical epitopes of a particular antigen are within a vaccine. If you have concerns over the safety on increased levels of antigens, what are your thoughts on a five pound infant getting the same vaccine that an eight pound infant gets? If you have real concerns about safety, you should be able to quantify why this isn’t a problem, but a vaccine without adjuvants and a greater concentration of antigens would be a problem. Anything else is just hand waving about safety without any underlying frameworks, a poor approach towards understanding something as complicated as our systems of interest.

    Secondly, I’m pleased to see someone acknowledge the dirty little secret of adjuvants, we really don’t have a good idea of how they work. You are taking the position that this is not important, I am taking the position that it might be important. How many times is the history of medicine littered with the illumination of unpleasant side effects of interventions only after years or decades of use, and only once we gleaned a more complete understanding of the mechanism of action? I don’t dispute that adjuvants work, I do dispute that this is the only thing we need to be concerned with, and I absolutely dispute the notion that because something is an element in the earth that it can be packaged up into a vaccine and we can draw equivalencies to that process with natural infection.

    It does, there is no toxicity at the levels given, ergo we give it.

    This belief absolutely strikes to the heart of why I think honest discussions about vaccination are important. I’ll speak to that in a little bit.

    As for the hygiene hypothesis I skimmed over quickly but do not have the wherewithal to dig deep enough. I will concede that you did not directly say it, and may have erroneously inferred that you are against the hypothesis. My apologies.

    Very well. It’s funny, because I happen to have what I consider to be very skeptical views on the narrative over vaccination, I tend to get cast as scientifically illterate and/or solely interested in vaccination a lot. That is very, very untrue and burns a lot deeper than just getting called a loon or an idiot.

    I’m going to mix in some things you wrote to Allison, because it speaks towards my concerns. We are largely in agreement on some points.

    It has nothing to do with the infant simply having an inflammatory response but with that response becoming unlimited.

    I would argue that we have a substantial body of literature that tells us that just having an inflammatory response during critical developmental timeframes is not necessarily harmless, even if such inflammation does not become unlimited; and because of this literature, the fact that we have a large number of studies indicating a heightened inflammatory response in the autism cohort, they are a subgroup particularly susceptible to this type of insult. You are making the assumption that a transient, limiting inflammatory response is always harmless. I am making the argument that this may not be the case; especially during specific developmental windows.

    The most elegant of these studies is this one, which I’ve discussed on this site several times.

    http://www.jneurosci.org/content/28/27/6904.full

    Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats

    In it, the author describe a tnf-alhpa mediated mechanism of altered glial excitability in adult animals exposed to LPS during the second week of life. Here are the quick hits:

    1) Animals were given LPS in the periphery on postnatal day 14.
    2) Animals were given LPS on PND14 and were also given tnf-alpha antibodies.
    3) Animals were given direct inejections of TNF alpha into the CNS on PND14.
    4) Animals were given sham in all of the above cases.
    5) When effects were objserved, they only occurred if the insult was specifically timed on PND14. PND1 and PND20 showed no effect. [this is important!]

    What the authors reported was that in instances 1 – 3, the animals in adulthood exhibited an increased susceptibility to seizures, abnormal EEG readings and hippocampul excitability. This is from the discussions section:

    The most exciting finding of the present study is that a mild inflammatory response evoked by LPS during a critical period of development causes a long-lasting increase in hippocampal excitability in vitro, and enhanced seizure susceptibility to the convulsants LI-PILO, KA, and PTZ in vivo. The latter effect was observed over a range of mildly inflammatory doses of LPS and was only evident if administered during the second postnatal week (P7 and P14), and not before (P1) or after (P20) this time. Importantly, inactivation of the proinflammatory cytokine TNFa with an intracerebroventricular TNFa antibody blocked the long-term changes to seizure susceptibility induced by LPS, whereas intracerebroventricular administration of rrTNFa alone mimicked the effect of LPS on seizure susceptibility. These novel results indicate that a single transient inflammatory episode during development can modify the brain through a TNFa-dependant mechanism, making it more susceptible to generate seizures in adulthood.

    That’s pretty crazy stuff. (Did you know that children with autism go on to develop epilepsy at rates approaching 20%?) But saliently towards vaccination, these animals did not get sick, and if the immune response was blocked, there was no effect! That’s very pertinent towards the autism population, who have several studies showing increased production of inflammatory cytokines compared to their non diagnosed peers. See the references I provided to gaeck for more on this. There are no less than a dozen studies that similarly show very difficult to predict effects of early life immune challenge that all postdate our increase in the vaccine schedule by a decade or more. Since that time, our knowledge on the interplay between the immune system and the CNS has grown leaps and bounds.

    Giving a vaccine to the infant (at least the ones given) has been shown to produce an immune response. The localized reaction to antigen stimulation is inflammation and thus you can see that reaction in infants (fever as well). That is the same as if the infant had an actual infection.

    We are largely in agreement on this point; though I bet you couldn’t show me a study that measured the degree of the inflammatory response as a result of vaccination in an infant. In other words, I am asserting that we have no meaningful mesaurements of the degree of increase in inflammatory cytokines following vaccination in the pediatric population. I’d be happy to be proven wrong on this point, but I’ve offered the challenge dozens of times, and so far, no one has been able to do so.

    However, while biologically plausible that it could have such effects, there is little reason to believe that it would, especially in light of all the studies finding no link between autism and other developmental disorders and vaccination.

    This is the biggest oversight in the entire discussion; there are no studies of the vast majority of our vaccines taking endpoints like autism into consideration. There are lots of thimerosal studies, tons, but that is qualitatively different than studying the difference between and inflammatory event and no inflammatory event. All you have left is MMR studies, but these studies are completely unable to allocate for time dependent effects! You seem to acknowledge that a six week infant is demonstrably different than a year old infant (another near first!), but if this is true, why should we safely equate MMR studies (given at 12 months, earliest), with the DTAP/HIB/HEP-B/POLIO/PNUEMOCOCCAL shots given at two months? You seem to have an OK handle on the scientific method, we only learn what we study, and I am telling you that we just haven’t studied the act of earlier vaccination and autism. That’s a difficult task, but it is absolutely incorrect to assert that we have studied the beginnings of our shot schedule. If this is incorrect, why not post a link to a study that does this?

    Your response to Allison is telling:

    However, one can also look at children who had developed infections and even sepsis as neonates and seen what the outcomes are. This is not something I am familiar with, but I reckon that there is no correlation there either, otherwise we likely would have heard about it

    You might consider this:

    Adverse neurodevelopmental outcome in preterm infants: risk factor profiles for different gestational ages [PMID: 19191762]

    Two hundred and fifty infants were eligible for follow-up, and 205 (82.0%) completed the follow-up visit. Intracerebral haemorrhage, small for gestational age and late-onset sepsis were associated with an increased risk for delayed development in Group I (p < 0.05, each). Premature rupture of membranes was a risk condition relevant to Group II. Antenatal steroids were associated with a decreased risk of neurodevelopmental delay in both groups.

    Premies are a tough model, there’s lots going on there, perhaps this is a function of early births being more suscptible to sepsis. (?) I do note that steroid treatment is benificial, indicating that the immune response is what is causing the problem. Note that this was 2009.

    Remember, I said that if all we asserted was that illness in a 6 week old is not a common event then one could conjecture such a hypothesis. It is handily dismissed, and as such is handily dismissed by the SBM crowd. Colonization is enough, everything else is gravy.

    Hah. I wonder if you could show some evidence of the frequency of infection in six week old infants? Does it approach the high 90% of our vaccination rates? What about 2 day old infants, who are also getting the Hep B within a few days of birth? Do you suppose you could provide some SBM detailing the frequency with which they get infections in the range of 90%? If my concerns can be so easily dismissed by such knoweledge, it shouldn’t be difficult to find a link detailing it.

    Fun discussion.

    Whew!

    - pD

  53. David Gorski says:

    In the context of the blog, when I am referred to as Mr, I cannot help but see a major league contemptuous passive-aggressive screw you asshole; I know, I do it myself.

    Exactly.

    During the six years I’ve been blogging, I can immediately recognize the technique because I’ve been at the receiving end many times and have on occasion, when I’m in a particularly bad mood, used it on naturopaths and homeopaths. Of course, I never use the technique with a fellow physician. As much contempt as I have for him, I’ll still call Joe Mercola “Dr. Mercola,” at least once or twice in any post about him, even though I think he’s proven that he is no longer worthy of the title. Still, whenever I see someone refer to me as “Mr. Gorski” it’s so obviously transparent a dig at me that, like you, I pretty much tune out the rest as not being worth reading, and I make no apologies for doing so. In fact, often I just stop reading and move on to the next comment.

  54. passionlessDrone says:

    Hi Dr. Crislip –

    I certainly did not mean to insult you.

    - pD

  55. passionlessDrone says:

    Hi Dr. Gorski –

    I have commented several times that I appreciate a great deal of your non autism related posts; your posts on Avastin and mitochondrial interaction with cancer were two that specifically strike me as good.

    Your other blog is part and parcel with the idea that the facts on the ground are what matters, and if that is insulting to someone, that’s tough cookies. Well, right back at you. You don’t skip over TH1/TH2 posts when he doesn’t address you as anything at all. I’ve seen you write no less than a half a dozen threads towards Jay Gordon, who calls you ‘David’ all the time.

    Here’s a question for everyone out there who wants to practice in intellectual honesty, has Jake Crosby ever called Dr. Gorski, ‘Dr. Gorski’? And yet, you’ve written bible sized responses to his attacks. [I think you were largely correct in those writings.]

    When JB Handley doesn’t only not call you ‘Dr.’, but actively calls you names, you respond with three thousand word screeds. [Again, an easy target, but one that generally deserves it.]

    But suddenly, when you don’t get called ‘Dr’ by pD, well then, the content of my posts isn”t worth reading. I’ve hurt your feelings. It is as if you have no memory of any of your previous writings. it is the height of hypocrisy.

    - pD

  56. David Gorski says:

    Oh, spare me the indignation. I wasn’t even referring to you directly. I was referring to the general principle that Mark was complaining about and agreeing with him about it. Truth be told, I wasn’t even sure who had pulled the “calling a doctor ‘Mr.’” gambit when I wrote my response, as I didn’t scroll up to find out. Perhaps I should have, but, quite frankly, it didn’t matter enough to me to bother.

  57. Dr Benway says:

    pD,

    You don’t know the literature as well as Dr. Crislip and other immunologists, so if they say you’re wrong you’re very, very, very, very probably wrong.

    You remind me of kids asked to decide which container holds more water, the tall skinny one or the short fat one. In fact, both hold the same amount of water but the young child focuses upon one dimension at a time –either the height or the width of the container– and so the bigger picture is missed.

    It’s pointless to argue with people who dive into details without appreciating how those details relate to the bigger picture.

    Vaccines do not cause autism.

  58. nybgrus says:

    pD: First off, I also noticed the use of “Mr. Crislip” and was intent to comment on it in my response, but halfway through writing it my computer locked up and I almost lost my writings so in my relief at getting back I forgot. It is not hypocritical and it is clearly and intentional dig on your part. JB Handley et al are the targets of Gorski’s refutations. He finds them to dissect and dismantle. But when you come onto his blog and take the time to write a title and use Mr. instead of Dr. (only one letter difference) then what are you trying to say? Either you truly are completely clueless or you are sending the signal that the author has no reason to deserve the title Dr. nor the respect for his knowledge that goes along with that. Jay Gordon calling him “David” is not an insult – it is his name, at worst implies familiarity, and in reality (sad as it is) Gordon is also a physician and it is often quite acceptable for physician’s to refer to each other by first name. I am in medical school, and when I write and refer to them, I would love to be able to call them by first name, but simply cannot do it since their proper title is doctor and that is a sign of respect for how incredibly much more they know than me. Once again, taking the extra effort to misuse a title is de facto insulting.

    Moving on…

    I will agree to move on from the hookworm ideas. I still don’t think you fully grasp the idea that antigens alone can swing immune responses in different ways and that alone can modulate the response. But you seem to have at least a better grasp of it now.

    I will try and be succinct with the following points:

    “In the first place, what gives you the belief that a larger ‘antigenic load’ would be less safe?”

    The principle here is that vaccination is an attempt to get APCs to stimulate a memory B cell line. You can do that through either bombarding with higher levels of antigen or with an adjuvant. In the former you risk more non-specific effects and a greater overall immune response since there is more antigen, therefore more cytokine production. In the latter, uptake is better and individual cells are stimulated more. Thus, there is less immune response overall and less cytokine production but there is still a satisfactory stimulation of memory B cell production. By your own arguments this makes it safer.

    “a seemingly cavallier attitude towards our level of understanding. Who cares how it works?”

    Seemingly is the operative word here. I am not an end all be all authority by any stretch. And I do not have the time nor the care to look up and learn every tidbit of biochemistry and immunology you posit. Suffice it to say, basic knowledge and understanding of human physiology gained through my first year and half of med school (and 4 years of undergrad and year of post-grad research) means that I can safely say even if the mechanism is not precisely elucidated it can (and has) been shown that there is no toxic effect, that basic science principle clearly support that notion, and that it works. That alone is enough.

    “If you have concerns over the safety on increased levels of antigens, what are your thoughts on a five pound infant getting the same vaccine that an eight pound infant gets?”

    My thoughts are very simple – at the dosages given the difference between an 8lb and 5ln infant is negligible. However, in the interest of continuing to improve on the safety of everything we do (not just vaccines) it would make sense to make that margin even more negligible – that would work well via use of adjuvants.

    “Secondly, I’m pleased to see someone acknowledge the dirty little secret of adjuvants, we really don’t have a good idea of how they work. You are taking the position that this is not important, I am taking the position that it might be important. How many times is the history of medicine littered with the illumination of unpleasant side effects of interventions only after years or decades of use, and only once we gleaned a more complete understanding of the mechanism of action?

    I have revealed no “dirty little secret” and I am not the authority – saying that I personally don’t know how it works reveals that I did not care to try and find the mechanism. This is because my level of understanding leads me to believe that is not a vital piece of information. This is because we do have decades of use and large overview of epidimiology and find no reason to assume that these adjuvants could be causing some sort of problems. Why? Because the vast majority of children in a large number of countries are vaccinated and we do not see a vast increase in developmental or neurological problems in children. That fact alone tells us that there is no systematic danger of adjuvant use. Period. The exact mechanisms by which they work are interesting – to biochemists who would want to exploit that to make vaccines even better. But it is completely immaterial to the discussion in a clinical setting when we have no impetus for looking into it. Take a look at things like lead paint – we did see neuro changes and and wondered what caused it – we looked, found lead paint, and voila! There is no such thing telling us to look at adjuvants in vaccines (nor the vaccines themselves).

    ” tend to get cast as scientifically illterate and/or solely interested in vaccination a lot. That is very, very untrue and burns a lot deeper than just getting called a loon or an idiot.”

    IMHO you are certainly the most scientifically literate of the anti-vaxxers here, but don’t oversell yourself.

    “and because of this literature, the fact that we have a large number of studies indicating a heightened inflammatory response in the autism cohort, they are a subgroup particularly susceptible to this type of insult.”

    Think about what you are saying here. You are asserting that the autism cohort is more susceptible to neuro changes due to inflammatory exposure. Even if this were true (and I’m not saying it isn’t – I just don’t know) it still gives us good reason to vaccinate these children! The inflammatory profile of vaccines is extremely low- it is a marginal side effect. The meta-data show us no increase in overall neuro changes. Therefore, even if the vaccine did trigger such a neuro change in a more susceptible individual that would be such a small subset of the cohort that the risk of contracting a preventable disease far outweighs the risk of administering the vaccine.

    “I am making the argument that this may not be the case; especially during specific developmental windows.
    The most elegant of these studies is this one, which I’ve discussed on this site several times.”

    The fact that you think this is an elegant study to use for your current argument is why I cautioned you to not oversell yourself. It is a very nice study and very interesting. However, it simply cannot be used to further your autism claim or really any sort of neuro claim.

    First off, it is a study in rats – great as a starting point but cannot be translated to humans. Secondly, it uses LPS as the stimulus. LPS selectively activates TLR4 which in turn produces much larger quantities of TNF-alpha than other pathways. From the paper, it is clear that it is not the inflammatory response that is the cause but specifically the presence of TNF-alpha in the brain at a very specific developmental window. You cannot translate that knowledge to humans to determine the analogous window. Lastly, this paper refers to seizure activity only – your inference that 20% of autistic children develop seizure disorders does not allow you to reverse the application here – that seizure disorder causes autism. The most this paper could do is make us think that vaccines might cause an increase in seizure disorders not autism. But, since the vaccines administered do not produce the same high levels of TNF-alpha as LPS, and since we see no epidemiological evidence of increased seizure disorders in the population at large, we can conclude that is not the case either.

    To sum up, your reference says absolutely nothing about autism, does not relate to the population in question (humans with vaccinations vs rats with LPS injections), and based on epidemiological data either the vaccines do not produce the same effect and/or are not given in the analogous critical window in humans.

    ” But saliently towards vaccination, these animals did not get sick, and if the immune response was blocked, there was no effect! That’s very pertinent towards the autism population, who have several studies showing increased production of inflammatory cytokines compared to their non diagnosed peers.

    It is not salient as vaccinated children do not get sick and it is not immune response that was blocked it was specifically TNF-alpha that was blocked. The fact that autistic children have an increasing production of cytokines also does nothing to further your argument for the reasons I wrote above.

    “In other words, I am asserting that we have no meaningful mesaurements of the degree of increase in inflammatory cytokines following vaccination in the pediatric population.”

    Measuring the increase of inflammatory cytokines in vivo is not something that has been done to my knowledge. However, once again, I will point out the fact that we have no reason to conduct such studies since there is no data showing us increased incidence of developmental or neuro deficits in vaccinated populations. That alone is a meaningful measurement – i.e. whatever that level is, it is insignificant.

    “This is the biggest oversight in the entire discussion; there are no studies of the vast majority of our vaccines taking endpoints like autism into consideration.”

    Once again, I will refer you to the concept of epidemiology – there is no data to tell us to look there. Your statement is akin to saying “There are no studies of the vast majority of our vaccines taking endpoints like turning into the hulk into consideration.” Indeed there are not, because we see no evidence that such an event is occurring at higher than background rates (which in the case of hulkism is zero, of course). The anti-vax assertion that there is an “autism epidemic” does not bear scientific weight. Simply because you believe there to be an increased incidence does not make it so, and in fact that data show us that there is no such increase and that the rates of autism have been steady for quite a few decades (taking into account the change in diagnostic criteria of course). During this time we have seen quite a few cohorts of children be born, vaccinated under different schedules, and grow to an age where diagnosis should be made – with no differences!

    ” Intracerebral haemorrhage, small for gestational age and late-onset sepsis were associated with an increased risk for delayed development in Group I (p < 0.05, each)"

    Sepsis is a vastly different thing from transient fever. I even said a few comments back that sepsis in an infant would almost certainly lead to serious issues. I wont go into it, but I suggest you look up what the definition of sepsis is and educate yourself before you start trying to compare it to a transient fever from a vaccine. That is like comparing a mosquito bite to being mauled by a dog.

    “I wonder if you could show some evidence of the frequency of infection in six week old infants? Does it approach the high 90% of our vaccination rates? What about 2 day old infants, who are also getting the Hep B within a few days of birth? Do you suppose you could provide some SBM detailing the frequency with which they get infections in the range of 90%? If my concerns can be so easily dismissed by such knoweledge, it shouldn’t be difficult to find a link detailing it.”

    But your questions make no sense in the first place. You are implicitly equating vaccination with infection – they are not the same thing. So why would it be required for 90% of infants to have infections to somehow dispel your notions about vaccines? I have said before that infection in an infant is not common and dangerous because of the usual sequelae. I have also asserted that the background colonization of an infant is on par with whatever side effects of vaccines may arise (do recall, only a small percentage of infants who receive vaccines actually get local inflammatory reactions or fevers, most are completely clinically unaffected). So trying to equate the level of vaccination with the level of naturally occurring infection is an absolutely pointless exercise.

  59. weing says:

    nybgrus,

    I can’t figure out what he/she means by frequency of infection in six week old infants either. Does he/she mean in modern western societies, preindustrial societies, neo or even paleolithic? He/she appears to want us to obtain the data to test his/her theories. I have heard case reports of tetanus in infants from an infected umbilical cord remnant. Are we also to assume that the current approach to infant care in the western world has been in place forever?

  60. nybgrus says:

    weing,

    My take has been that the argument is essentially:

    “In general healthy young infants dont get sick with things like the flu or colds or much of anything these days. Therefore, wouldn’t giving a vaccine which could produce a fever and/or localized inflammation response be like making the infant sick”

    This is in contrast to older infants and toddlers who do often get colds and whatnot. I believe pd’s argument is hinging on the notion that the first 6 weeks are the critical developmental window and since infection rates in that age group are typically much less than older children that opens the door to developmental problems.

    But I agree… the argument itself just doesn’t make much sense. In good faith I have been trying to approach it as best I can since the critique has been that we SBM types don’t have a good answer and just tell people like pd to shut up and accept the answer as obvious. The tricky part is that it is so complex, with so much needed knowledge to bring to the party that it is very difficult to answer the questions in whole for someone not educated in the relevant material. It leads to missing the forest for the trees and focusing on levels of detail that distract from the reality of the situation, which is exactly what I have been seeing with pd. That is why most SBMers will just throw up their hands and say to accept it, because getting a quality answer at the depth pd wants would require actually getting a degree in medicine.

  61. Th1Th2 says:

    “… that newborns begin to be colonized by microbes at birth, coincident with a period of rapid development of the immune system and lungs. These symbiotic organisms can be beneficial (e.g., gut bacteria that synthesize vitamin K) or pathogenic, or they may have no effect on the host (commensals). The authors propose that microbes found on farms adeptly stimulate innate immune receptors in early life and thereby favor the generation of regulatory T cells that promote immunologic tolerance.”

    Nice article. It shows the importance of the innate immune system.

  62. daedalus2u says:

    I noticed the Mr when I first saw it too. PD’s style reminds me a lot of Glen Beck’s “just asking a question”.

    PD, the simplistic counting of antigens was to counter the even more simplistic (and wrong) idea of “too many too soon” and the simplistic (and wrong) idea of “overwhelming” the infant’s immune system. Those simplistic (and wrong) ideas of vaccines are convincing misguided parents to not vaccinate their children and people have died as a consequence.

    The most important symptom that infants have that demonstrates a robust immune system is that they don’t die from exposure the the thousands of different bacteria that inhabit their gut. If the infant immune system didn’t hold those microorganisms in check, any one of them would happily take over and consume the infant. Even lactic acid bacteria will produce abscesses in individuals with an insufficient immune response. The reason you (or anyone) can eat yogurt and not get abscesses is because you have enough of an immune system.

    The number of bacteria that can actually infect otherwise healthy humans is only a few thousand. The number of bacteria that otherwise healthy humans require the assistance of someone like Dr Crislip to deal with is even smaller. The idea that dead antigens in sterile vaccines could wreck an infant’s immune system because it “overwhelms” the immune system more than rolling in mud and consuming dirt and bugs (and slugs) is fact and data-free.

    If infants did get hundreds or thousands or tens of thousands of “infections” in their first few weeks of life as their immune system adapts to living in a non-sterile environment, then we might think their immune system was “stressed”. That infants don’t get thousands of infections proves beyond any reasonable doubt that their immune systems can easily handle it.

  63. nybgrus says:

    daedalus – so much more succinct than I. Hopefully between the two of us, pd can come away being enlightened and undertand how the “too many too soon” argument and any link between vaccine and autism is totally bogus.

    I doubt it though.

  64. JMB says:

    @pD

    One of the most common mistakes in the vaccine debate is the attempt to draw conclusions about the clinical risks and benefits from basic science observations. Because of the complexity of the immune system, we do not have a model that we can reliably predict clinical response from various parameters of the immune system. However, that does not mean that we don’t have reliable estimates of risks versus benefits. The risks and benefits have been directly measured. Ultimately, any model of the immune system will have to correctly calculate the clinical risks and benefits that have already been measured. The decision about the vaccine schedule is still based on what has been tested. Basic science will allow us to make a model of the process from the pieces of several observations. On the left side of the equation will be the combination of the basic science pieces (not necessarily an addition), on the right side will be the quantity already measured.

    Since I’m always a big fan of analogies (but not an infectious disease specialist or a rheumatologist), I would give this analogy for the rural/urban observation. Imagine you have a rural child and an urban child trying to learn how to hit a ball. The urban child has the advantage of a pitching machine that throws a strike every time. The rural child has to rely on a friend who throws a lot of balls for every strike delivered. Now the rural child is going to have an advantage at bat because the child has learned to not swing at those wild balls that won’t count against them (and possibly hurt themselves when they hit themselves with the bat after swinging at a really high ball). The urban child tends to swing at every pitch, whether a ball or strike.

    So perhaps the strength of the immune response is not only being developed by exercise, but the control of the process is also being learned.

    By the way, birth is not exactly an aseptic process. Also, plenty of infants develop diaper rashes as well. Heaven forbid your infant gets constipated, imagine how much bacteria gets past the integument when you see a little blood on the wipes!

  65. pmoran says:

    Chris “One of the most common mistakes in the vaccine debate is the attempt to draw conclusions about the clinical risks and benefits from basic science observations.”

    Yes. The relevant science is very interesting in relation to how the immune system might mature, but arguing about it against a vaccine-autism background, as herein, can only serve to sustain the impression that there remains a case to be answered.

    Probably the best, but by no means the only evidence that there is no correlation between vaccines (of any kind and number) and autism –

    http://www.ic.nhs.uk/statistics-and-data-collections/mental-health/mental-health-surveys/autism-spectrum-disorders-in-adults-living-in-households-throughout-england–report-from-the-adult-psychiatric-morbidity-survey-2007

    or

    http://tinyurl.com/lx8auq

  66. pmoran says:

    Sorry JMB, Wrong attribution to Chris. It was you I was agreeing with.

  67. Chris says:

    Thank you, pmoran, I was a bit confused. But I agree with you when you say:

    Probably the best, but by no means the only evidence that there is no correlation between vaccines (of any kind and number) and autism –

    And I don’t think that is the only evidence there are adults with autism. There have always been those with autism, one can see them if you read historical fiction and non-fiction (like Not Even Wrong by Paul Collins).

    The thing I don’t get is that several large epidemiological studies done in several countries have found no casual correlation between vaccines and autism: why all the effort to figure how vaccines through obscure immunological processes can cause autism? It does not make sense.

    It is pointless and a waste of time and effort.

  68. passionlessDrone says:

    Hi pmoran –

    Probably the best, but by no means the only evidence that there is no correlation between vaccines (of any kind and number) and autism

    You are making my case for me! The study you cite probably is the best evidence we have, and that study is a piece of junk. If we want to have confidence in the results, we have to have confidence in the methodologies used to obtain those results. I won’t disagree that the England study you reference found adult rates approaching 1%, but I would disagree vigorously that the underlying methodologies founding that conclusion are valid.

    Take a look at the study, and you’ll find that the male to female ratio is astoundingly high; 9:1!

    The ASD prevalence rate was higher in men (1.8 per cent) than women (0.2 per cent). This fits with the gender profile found in childhood population studies.

    Now compare that to what the CDC found when they surveyed 1252 children:

    For 2000, across six sites, a total of 1,252 children aged 8 years were identified as having an ASD. The overall prevalence of ASDs per 1,000 children aged 8 years ranged from 4.5 in West Virginia to 9.9 in New Jersey. With the exception of one surveillance site (Georgia), no statistically significant (p<0.05) differences were identified in the rate of ASDs between non-Hispanic black and non-Hispanic white children. The ratio of male-to-female prevalence varied (range: 2.8:1.0–5.5:1.0).

    http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5601a1.htm

    This is a problem, or it ought to be, for anyone who is coming from a direction other than starting at a preferred conclusion (“autism rates are stable”), and looking for a study that supports that conclusion.

    For the English study to come anywhere close to being in line with all of the children studies on the male to female ratio, they’d need to at least double their number of females; but once they do that, their prevalance numbers start sky rocketing past 1%.

    The English study did not evaluate anyone who was homeless, in an institution, or in jail, which I think we all can agree have percentage wise, numbers of people with mental illnesses. What direction does that push our incidence numbers when we include those populations?

    Should we take this to mean that the incidence of autism in adults actually far exceeds the 1% we think we are observing in adults? I think that is what a fair reading of the England study would lead us to, if we really have confidence in the methodology in use.

    For some reason, in the heart of skepticism, a single study that gives diagnosis to less than twenty adults is sufficient cause for otherwise smart people to conclude that what we have observed in tens of thousands of children is the same thing. Worse, in a place where studies are routinely dissected for flaws in methodology and news stories are admonished for the overstrecthing of findings beyond what the science can really dictate, no one seems bothered by the fact that, indeed, this is the “best” evidence we have to suggest a static rate of autism.

    Since this thread has suddenly taken on the approach that the appeal to authority is a valid line of argument, there are real authorities in autism that are unconvinced that there is no real increase. One is Tom Insel, who is the appointed by the NIH to run the IACC. If there is anyone that is an authority on autism, and what our existing studies are capable of telling us, it’s him. Here’s what he says about incidence:

    The question is not whether diagnosis and awareness has changed, but how much of the reported increase can be explained by changes in diagnosis and awareness, and how much of the reported increase is due to a rising incidence. One recent study using disability services data for California estimated that 24 percent of the increase in prevalence can be attributed to the changing diagnostic criteria for ASD, including its use with other developmental disabilities.1 While other factors appear to explain additional fractions of the increase in prevalence, there is still no complete explanation for the increase from 1 in 1500 to potentially 1 in 100 based on any of these factors. Thus, we cannot exclude the possibility that reports of increased prevalence reflect real increases in the numbers of children affected. Additional research will need to investigate this possibility using careful, consistent clinical assessments, carried out over a period of time in a well-defined population.

    Or does the appeal to authority only have relevance if the authority in question supports your preferred conclusion?

    I’m consistently painted as ‘anti-vaccine’, I’m more worried about a non trivial, real increase in the number of children with autism. Vaccines get discussed a lot, and I think there is a huge blind spot in our research. That being said, we need not invoke an ‘epidemic’, and I do not deny that diagnostic substition is a real phenomena, but the quality of the data you would like to use to make the claim of a static rate of autism is insufficiently powered to address a problem with the potentially dramatic consequences of a real increase.

    - pD

  69. passionlessDrone says:

    Hi JMB –

    One of the most common mistakes in the vaccine debate is the attempt to draw conclusions about the clinical risks and benefits from basic science observations. Because of the complexity of the immune system, we do not have a model that we can reliably predict clinical response from various parameters of the immune system. However, that does not mean that we don’t have reliable estimates of risks versus benefits. The risks and benefits have been directly measured. Ultimately, any model of the immune system will have to correctly calculate the clinical risksand benefits that have already been measured. The decision about the vaccine schedule is still based on what has been tested. Basic science will allow us to make a model of the process from the pieces of several observations. On the left side of the equation will be the combination of the basic science pieces (not necessarily an addition), on the right side will be the quantity already measured.

    Please allow me to state that I absolutely believe vaccines work, and further, that the benifits from vaccination is great. I believe in herd immunity. And I’d also agree with you that this is a difficult, difficult process. If I have somehow given anyone the idea that I do not think vaccines provide a critical service, please accept my apologies. What concerns me is that, despite lamentations to the opposite, we just haven’t studied this that well. If you go and look through this thread, I’ve made the assertion several times that our literature on autism and vaccination is segreated into two camps, thimerosal based, and MMR based. No one, not one person, has decided to counter that argument with a study. Why do you think that is? It is because there are no such studies. Given that, how do we appropriately measure the risks?

    Further, to answer a question from a post that will take significant time to respond to, that doesn’t mean I am advocating stopping vaccination; just learning more. There are likely lots of ways to insure that a susceptible group, if one exists, could be vaccinated safely, or later in infancy; but only if we know that there is a problem.

    So perhaps the strength of the immune response is not only being developed by exercise, but the control of the process is also being learned.

    Indeed. Have you read much about developmental programming of the immune system and/or glial priming? There is actually quite a bit of literature on this, and it speaks somewhat towards your analogy; and again, it appears that there are specific developmental timeframes during which the immune system can be programmed. Our existing analysis is blind to this kind of thing because it tests specific vaccines, or specific components of vaccines; as opposed to the act of stimulating the immune system itself.

    For example, you might consider this paper:

    Early-life programming of later-life brain and behavior: a critical role for the immune system

    This is from the Introduction:

    We believe that cytokines are important not only for behavioral changes during acute illness, but may also underlie long-term changes in behavior as a consequence of infection early in life. Thus, the purpose of this review is to: (1) summarize the evidence that infections occurring during the perinatal period can produce effects on brain and subsequent behavior that endure throughout an organism’s life span, and (2) discuss the potential role of cytokines and glia in these long-term changes. Cytokines are produced within the brain during normal brain development, but are expressed at much higher levels during the course of an immune response. In contrast to overt neural damage, we present data indicating that increased cytokine exposure during key periods of brain development may also act as a “vulnerability” factor for later-life pathology, by sensitizing the underlying neural substrates and altering the way that the brain responds to a subsequent immune challenge in adulthood. In turn, this altered immune response has significant and enduring consequences for behavior, including social, cognitive, and affective abilities. We discuss the evidence that one mechanism responsible for enduring cytokine changes is chronic activation of brain microglia, the primary immunocompetent cells of the CNS.

    It’s a neat paper that I would recommend. The authors here also describe time dependent effects of immune stimulation that can result in persistent changes to the brains immune system and associations with behavioral impairments. This group has been using infection as a model, as opposed to faux infection, but the resultant immune response is the same, differing by dose, and perhaps (?) by other qualities.

    Note that this paper was published only in 2009; the notion that early life infection could have such long lasting and widespread effects in the CNS is a relatively new one, and post dates the increase in our vaccination schedule by at least a decade.

    By the way, birth is not exactly an aseptic process. Also, plenty of infants develop diaper rashes as well. Heaven forbid your infant gets constipated, imagine how much bacteria gets past the integument when you see a little blood on the wipes!

    OK.

    - pD

  70. Dr Benway says:

    pD, I wouldn’t get so excited about the fact that autism prevalence rates show local variations with respect to males verses females and total prevalence. We know that a number of factors –access to care, living near another autistic person, SES, education, etc.– have an impact upon prevalence.

  71. Dr Benway says:

    We believe that cytokines…

    I can’t believe the editor of a scientific paper didn’t rage at the first three words of that sentence.

  72. @passionlessDrone:
    “This is a problem, or it ought to be, for anyone who is coming from a direction other than starting at a preferred conclusion (“autism rates are stable”), and looking for a study that supports that conclusion.”

    It’s called the null hypothesis. One assumes that autism rates are stable and then tries to disprove it. If the best study we have 1) underestimates autism prevalence in adults and 2) shows the same prevalence in adults and children, then starting from the null hypothesis all we have is a trend toward decreasing autism rates.

    (This isn’t all we have, but taken together I don’t know if the preponderance of the evidence supports a change in rates either way. Last I heard it was inconclusive, but that was a while ago.)

    You are the one starting from a conclusion (“autism rates are rising”) and asserting that everyone else is under an obligation to prove that they aren’t.

    It doesn’t work that way.

  73. passionlessDrone says:

    Hi everyone -

    IMHO you are certainly the most scientifically literate of the anti-vaxxers here, but don’t oversell yourself.

    Hehe. I appreciate the time you took on your responses to me.

    I’ve gotten carried away on this thing and am going to focus on real life for a while. It was fun though.

    Anyone who would like to continue to believe that studying a vaccination that happens at twelve months of age is just like studying a vaccine that happens a week after birth is free to do so. Anyone who wants to believe that studying thimerosal is equivalent to studying vaccination should also not feel encumbered by considering how the scientific method actually works.

    Anyone who thinks a study of twenty adults in England is a good reason not to worry about what seems to be happening to a generation of children are free to continue in that belief.

    Anyonewho thinks we might have lots to learn can take a look at the recent work on immune programming and the very tightly intertwined communications between the immune system in the brain before deciding if our knowledge is complete.

    @allison cummins –

    http://www.autismspeaks.org/science/science_news/dawson_year_in_science_2009.php

    As far as I can tell, the burden of proof is upon anybody who feels that there is not a real increase here in the number of kids affected.” He went on to say, “you really have to take this increase very seriously – from everything they are looking at, this is not something that can be explained away by methodology, by diagnosis.” Later, he added, “There is no question that there has to be an environmental component here.”

    I will leave it to the individual reader to discern if bloggers or the man the NIH put in charge of the Interagency Autism Coordinating Committee have the most realistic worldview of our observations of autism rates in children.

    @daedulus2u – Cold, cold stuff comparing me to Beck. Uncalled for, man.

    - pD

  74. daedalus2u says:

    Pd, everything an infant experiences has effects on the brain. That is the whole function of neurodevelopment, to prime the brain to respond to everything that the infant might experience during its lifetime. Looking at stuff has an effect, not looking at stuff has an effect. Listening to voices speaking in one language has an effect, listening to voices speaking in another language has a different effect.

    “Having an effect” does not mean the same as “might cause autism”.

    What we know is not affected by anything that infants experience is the number of minicolumns in their brains. That is fixed at ~8 weeks in utero. Since a larger number of minicolumns is very reliably associated with autism, and we know that anything that infants do after they are born can’t increase the number of minicolums, we know that anything that infants experience after they are born can’t cause the main type of autism. If you want to find the cause of autism, look to the time periods we know it occurs in.

    If you don’t want to be compared to Beck, don’t channel him.

  75. dt says:

    Sorry to join the party late. I felt I had to respond to the allegation by Alison Cummings and pD that his question about systemic antigenic challenges in infants was never addressed.

    Yes, as infants develop and crawl about more as they age, they will experience more “scrapes” capable of introducing antigens into the tissues, lymphatic and systemic circulation.

    But from birth there is an extensive exposure.
    The first thing they forget is that skin breaches capable of introducing antigens are often microscopic. If I had a dollar for every staph or strep cellulitis I have treated where there has never been a visible triggering skin breach I would be stinking rich.
    Secondly, there are still numerous visible or measurable breaches. With the passage through the birth canal, several breaks occur and these are quite visible as any parent will tell you. Then the umbilical cord is cut, and left to heal naturally, but before it does so it is likely to provide an entry point for many different bugs. Then, assuming there are absolutely no bumps or scrapes in the first couple of months of life (unlikely) from that point we enter the grizzly teething stage. With each new tooth that is cut, showers of commensal mouth bacteria enter the human host, never mind all the antigenic proteins and lipopolysaccharides from other things that enter the mouth.

    In short, the human infant is exposed throughout infancy, and the scale of exposure in early infancy is such that even a trebling, or 10- or 20-fold increase with the onset of multiple “skin scapes” from crawling/falling in the older infant is unlikely to particularly extend the range of antigenic stimuli, merely increasing their number.

  76. dt — too late, pD ran out of time and left as soon as their questions were addressed directly. It was pretty much instantaneous. Fun to watch!

  77. dt – I guess pD isn’t around, but I was follow the discussion (to the best of my ability) and appreciate the points.

  78. passionlessDrone says:

    Hello friends –

    I’m still here, but I found that I was spending too much time focusing on trying convince Internet strangers of things instead of applying time on real world things. Tough to balance. I’d hate for anyone to think that any points had been ‘addressed directly’, though, so lets discuss some of said points.

    @daedulus2u:

    Pd, everything an infant experiences has effects on the brain. That is the whole function of neurodevelopment, to prime the brain to respond to everything that the infant might experience during its lifetime.

    In the study I posted above, only one group of animals experienced persistent effects of unimpeded tnf-alpha exposure, those exposed at PND14. The same dose at PND1 and PND20 had no effect. We have experiemental evidence that the effects were different based on time, so while ‘everything an infant experiences has effects on the brain’, that does not mean that all experiences are equal.

    Regarding minicolumns, again, I don’t know why you think this necessariliy invalidates any other exposure as contributory; I believe in complicated systems with lots of influences. Further, I do not believe that the literature on minicolumns is as ironclad as you do. I don’t have a problem with Casanova’s work, in fact, I sort of like some of it, but I think it is a little disingenous to insist that this particular theory on causation must explain every facet of autism, and every case of autism. Autism manifests extremely heterogeneously, and as such, there will be many roads to causation. You understand this.

    @dt: Yes, as infants develop and crawl about more as they age, they will experience more scrapes capable of introducing antigens into the tissues, lymphatic and systemic circulation.

    The overwhelming majority of our vaccine schedule is given by by six months of age, predating crawling, and extensive crawling with scrapes signifiantly. Yet again we seem to observe a disconnect with how infants actually progress.

    In short, the human infant is exposed throughout infancy, and the scale of exposure in early infancy is such that even a trebling, or 10- or 20-fold increase with the onset of multiple “skin scapes” from crawling/falling in the older infant is unlikely to particularly extend the range of antigenic stimuli, merely increasing their number.

    Check this study out:

    Modulation of the infant immune responses by the first pertussis vaccine administrations

    Many efforts are currently made to prepare combined vaccines against most infectious pathogens, that may be administered early in life to protect infants against infectious diseases as early as possible. However, little is known about the general immune modulation induced by early vaccination. Here, we have analyzed the cytokine secretion profiles of two groups of 6-month-old infants having received as primary immunization either a whole-cell (Pw) or an acellular (Pa) pertussis vaccine in a tetravalent formulation of pertussis-tetanus-diphtheria-poliomyelitis vaccines. Both groups of infants secreted IFN-? in response to the Bordetella pertussis antigens filamentous haemagglutinin and pertussis toxin, and this response was correlated with antigen-specific IL-12p70 secretion, indicating that both pertussis vaccines induced Th1 cytokines. However, Pa recipients also developed a strong Th2-type cytokine response to the B. pertussis antigens, as noted previously. In addition, they induced Th2-type cytokines to the co-administrated antigen tetanus toxoïd, as well as to the food antigen beta-lactoglobulin. Furthermore, the general cytokine profile of the Pa recipients was strongly Th2-skewed at 6 months, as indicated by the cytokines induced by the mitogen phytohaemagglutinin. These data demonstrate that the cytokine profile of 6-month-old infants is influenced by the type of formulation of the pertussis vaccine they received at 2, 3 and 4 months of life. Large prospective studies would be warranted to evaluate the possible long-term consequences of this early modulation of the cytokine responses in infants.

    Using blood cytokine profiles alone, the researchers could distinguish which vaccine infants got two months after their last shot. In the intervening months since the last vaccination, the infants were exposed to multitudes of antigens, and yet, the researchers still could understand which vaccine the infants got by immune profiles. How do you suppose this is possible if the impact of vaccination is so minute compared to everyday exposure? Please consider this question seriously.

    @Dr Benway:

    Regardess of your thoughts on how an editor may have performed poorly, the underlying science regarding developmental programming is robust and growing. For some examples, I might direct you to the following studies:

    Early life activation of toll-like receptor 4 reprograms neural anti-inflammatory pathways
    Neonatal programming of innate immune function
    Neonatal immune challenge exacerbates experimental colitis in adult rats: potential role for TNF-alpha
    Early-life infection leads to altered BDNF and IL-1beta mRNA expression in rat hippocampus following learning in adulthood
    Neonatal bacterial infection alters fever to live and simulated infections in adulthood
    Early-life infection leads to altered BDNF and IL-1beta mRNA expression in rat hippocampus following learning in adulthood
    Reduced stress fever is accompanied by increased glucocorticoids and reduced PGE2 in adult rats exposed to endotoxin as neonates
    Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats.
    Early-life immune challenge: defining a critical window for effects on adult responses to immune challenge
    Long-term disorders of behavior in rats induced by administration of tumor necrosis factor during early postnatal ontogenesis
    Neonatal bacterial endotoxin challenge interacts with stress in the adult male rat to modify KLH specific antibody production but not KLH stimulated ex vivo cytokine release

    Either lots of editors are making decisions that would shock you, or, alternatively, the data supports a link between early life immune challenges and persistent changes into adulthood that affect neuroimmune function, hpa-axis metabolism, and behaviors. There are lots, lots more, pithy statements or not.

    Regarding male to female variability; there isn’t really that much variability, we have one study in adults that shows a 9:1 male to female ratio, and dozens or hundreds of studies in children with ratios of 4:1. That isnt’ variability, it is an outlier; and one that doesn’t seem to bother anyone in this one particular instance. Furthermore, all of the factors you list as possible reasons aren’t in play in the England study, which involved door to door questionairres and diagnosis. Instead, if you would like to believe in the conclusions of the England study, you must have the multitudes of other studies all be incorrect in the same way; but if you do that, the numbers no longer add up between the two groups.

    @Several People:

    Regarding the time dependency / six weeks issue, I apologize for not being clear. Here are my thoughts:

    1) Percent of children getting Hep-B within a week of birth. ~ 90%
    2) Percent of children getting an infection within a week of birth. ?% [I doubt anywhere close to 90%]
    3) Percent of children getting standard two month well visit vaccine set. ~90%
    4) Percent of children getting an infection within two months of birth. ?% [Still exceedingly likely much less than 90%, but more than at one week].

    I hope that’s clear.

    @Nygbrus:

    And I do not have the time nor the care to look up and learn every tidbit of biochemistry and immunology you posit.

    Fair enough. Advances have been made in the past three years on the probable mechanisms of action of aluminum salts. This speaks towards my overarching concern, the difficult to understand gulf between what we think we know as a species, versus what we actually know. I just don’t think we are smart enough to understand all of our actions without quality evaluations. As we really haven’t evaluated vaccination, that fits within this classification.

    First off, it is a study in rats great as a starting point but cannot be translated to humans.

    The researchers in question are interested in what happens to rats as a proxy for learning about what happens in people. Rats are useful tools, but ultimately, researchers are not striving to understand the rat. I won’t argue with the problems of hopping from rat to human, but to imply that there is nothing to learn from rodent studies would mean that tens of thousands of studies in pubmed have nothing to teach us outside of the rodent kingdon. I am not stating that this research translates directly to humans; I am positing biological plausibility for a susceptible subgroup that is invisible to our current suite of research.

    Secondly, it uses LPS as the stimulus. LPS selectively activates TLR4 which in turn produces much larger quantities of TNF-alpha than other pathways

    If the mechanism in question is tnf-alpha, it doesn’t matter what the stimulus is. Regarding other pathways, what pathways do you suggest initiate the innate immune response following vaccination if not TLRs? Do you have some particular reason to think that vaccines do not activate TLR4?

    From the paper, it is clear that it is not the inflammatory response that is the cause but specifically the presence of TNF-alpha in the brain at a very specific developmental window. You cannot translate that knowledge to humans to determine the analogous window.

    You are correct! But we also haven’t studied vaccination subtly enough to detect for this, we’ve studied one particular vaccine alongside other vaccines, but if they all initiate the innate immune response, and all generate TNF-alpha, then it doesn’t do you any good to give a child four vaccines and study them against children that got five vaccines. Your point regarding timeframes is valid, but must be put within a context of having no studies that evaluate vaccination as opposed to specific vaccines, or presence or absence of thimerosal. We both have zero studies, but you are proposing we base national health policy on zero studies, not me.

    Lastly, this paper refers to seizure activity only your inference that 20% of autistic children develop seizure disorders does not allow you to reverse the application here that seizure disorder causes autism. The most this paper could do is make us think that vaccines might cause an increase in seizure disorders not autism.

    I’ve been accused of ‘gish gallop’ in the past; for that reason, I didn’t post a lot of the other studies that have similar findings; i.e., persistent neuro-immune effects, behavioral, and HPA-Axis modifications as the result of early life challenges. See the list I posted for Dr. Benway above for a partial list. In any case, the thought that vaccination might, only, predispose towards seizures, and thefefore, no worries, is pretty chilling, and illustrates the lengths people are willing to go to in order to defend a lack of studies.

    But, since the vaccines administered do not produce the same high levels of TNF-alpha as LPS, and since we see no epidemiological evidence of increased seizure disorders in the population at large, we can conclude that is not the case either.

    Considering we have no evidence one way or the other how much tnf-alpha is produced by vaccination, your statements regarding rates of production versus LPS are likely, but not driven empirically. Of course, if you would like to provide some evidence of how much tnf-alpha is generated post vaccination from the pediatric vaccine schedule, that would be a good starting point. However, we must remember that we have good reason to believe that children with autism create more tnf-alpha than their undiagnosed peers.

    As most people with autism develop seizure behavior only in the teen years and early adulthood, a group that is just now aging in, I don’t think we know enough about the epiemiology of epilepsy to make your case.

    It is not salient as vaccinated children do not get sick and it is not immune response that was blocked it was specifically TNF-alpha that was blocked.

    Neither group got sick, so it is salient, because it demonstrates that the underlying mechanism of action in this study, and many of those I listed for Dr. Benway, was the immune response itself. You get one of those if you get a vaccine. We can quibble about dosages, but considering we have no data on the dose of the inflammatory response following vaccination, you don’t have much to bring to the table evidence wise. Furthermore, tf-alpha is a component of the immune response.

    Measuring the increase of inflammatory cytokines in vivo is not something that has been done to my knowledge

    Your knowledge is correct; at least in the pediatric population. There are some studies showing the expected; increases in inflammatory cytokines following vaccination for some other vaccines.

    However, once again, I will point out the fact that we have no reason to conduct such studies since there is no data showing us increased incidence of developmental or neuro deficits in vaccinated populations

    We have not performed the research that you describe here. If I am incorrect, why not post it? Remember, thimerosal based studies are of no use to us. Furthermore, MMR studies, while potentially useful, treat an immune challenge at 12 months as equivalent to one at one week. This is a poor analogy, and indeed, one that fails completely to address time dependent effects, which as we can see from above, can be extreme. If you don’t think we are observing developmental problems or neuro deficits in vaccinated populations, I don’t think you are paying attention. Please see the quote from Mr. Insel for more on this.

    Simply because you believe there to be an increased incidence does not make it so, and in fact that data show us that there is no such increase and that the rates of autism have been steady for quite a few decades (taking into account the change in diagnostic criteria of course).

    Poppycock. Have you looked into any of the literature on advanced parental age and autism? There is a fair bit of it and it all points one direction, having an older parent is a rsk factor for future autism diagnosis. It makes good sense, gametes hang around long enough and get genes knocked out and there you go. What this really means is that we have good epidemiology (as opposed to no epidemiology), and a biologically plausible mechanism for some of the increase. Some people say 10%, some say 5%, it’s still being debated. But the important point is, some; at this point, the standard response is along the lines of ‘well, the rest of the increase is the result of diagnostic changes’. But if I were to ask you to validate that statement, you could not, it is all ether. It is the ultimate in unfalsifiable theories, capable of sucking up any amount of increase. If autism rates went up ten times tomorrow, you could use the exact same argument; it would make just as much sense and have the same amount of backing.

    You absolutely cannot provide a study that claims that one hundred percent of our observed increases are the result of diagnostic changes. If such a study exists, you or someone else here should be able to post it. I am asserting no such studies exist. See the quote I posted from Mr. Insel on the issue, who believes, at most diagnostic changes can account for half of what we seem to be observing. Do you know of somes studies he does not?

    Sepsis is a vastly different thing from transient fever

    OK. You brought it up; I felt it was an interesting alley and poked around.

    But your questions make no sense in the first place. You are implicitly equating vaccination with infection they are not the same thing.

    If the mechanism of action is the innate immune response, tnf-alpha, they are the same thing. Are you asserting that there is the difference between the tnf-alpha generated from a vaccine response, and the tnf-alpha generated by an infection? If so, what is it? If there isn’t one, then the trigger does not matter.

    I have also asserted that the background colonization of an infant is on par with whatever side effects of vaccines may arise (do recall, only a small percentage of infants who receive vaccines actually get local inflammatory reactions or fevers, most are completely clinically unaffected).

    The CDC says that fever is expected up to twenty five percent of the time with some infant vaccines:

    http://www.cdc.gov/vaccines/vac-gen/side-effects.htm

    Of particular amusement, you will find that the chicken pox vaccine, which has 75 scary antigens causes fever far less frequently than DTAP which has only 5 antigens. Yet another reason to dismiss counting antigens as a useful metric.

    So trying to equate the level of vaccination with the level of naturally occurring infection is an absolutely pointless exercise.

    You have admitted yourself that we have no measurments of inflammatory cytokine generation post vaccination in infants. We know that the innate immune response components are functionally the same thing from infection and vaccines; that’s why vaccination works.

    - pD

  79. dt says:

    @pD

    The overwhelming majority of our vaccine schedule is given by by six months of age, predating crawling, and extensive crawling with scrapes signifiantly. Yet again we seem to observe a disconnect with how infants actually progress.

    It might help if you read my post before responding. I agreed that once infants become more “mobile” their chance of exposures increases. You are starting to sound like the Th troll with his ideas that children only walk on concrete paths and never play in dirt. You (deliberately) ignore all the points I make about how many opportunities there are within the first 6 months of life for systemic/transcutaneous antigen challenge. They are numerous and likely to lead to antigenic challenges that vastly outnumber anything achievable via a vaccine schedule.

    It is also unhelpful to consider antigen challenge by the mechanism. Antigen exposure is antigen exposure, whether the organism induces a clinical infection, becomes a harmless commesnal or causes asymptomatic infection. Pointing out that infants suffer few clinical significant infections in the first few months of life is irrelevant. If each and every antigenic exposure capable of inducing an appropriate immune response had to cause serious illness, we would be sick from the day we are born until the day we die.

    To paraphrase you, here are my thoughts:
    Here are my thoughts:

    1) Percent of children getting Hep-B within a week of birth. ~ 90%
    2) Percent of children getting an antigen exposure from a non-vaccination source within a week of birth – 100%
    3) Percent of children getting standard two month well visit vaccine set. ~90%
    4) Percent of children getting an antigen exposure from a non-vaccination source within two months of birth. Still 100%.

    I hope that’s clear.

  80. passionlessDrone says:

    Hi dt –

    They are numerous and likely to lead to antigenic challenges that vastly outnumber anything achievable via a vaccine schedule.

    You are ignoring where I presented evidence that your models are over simplisitic to explain our findings. What is your explanation for the findings in Modulation of the infant immune responses by the first pertussis vaccine administrations wherein the researchers could tell which version of a vaccine an infant received based on cytokine profiles? In six months of life the infants in this study were exposed to three discrete events, DTP or DTAP, and tens, hundreds, or thousands of microabrasians, dirt eating exercises, trips on the floor, dirty fingers, and cat hair. And whatever else. Yet, somehow, all of these the numerous antigenic challenges, which I absolutely agree happened, did were unable to mask which vaccine the infants received. How is this possible within your model?

    It is also unhelpful to consider antigen challenge by the mechanism. Antigen exposure is antigen exposure, whether the organism induces a clinical infection, becomes a harmless commesnal or causes asymptomatic infection.

    Not true; for the argument I am making the only important thing is, does it induce a significant immune response? As I pointed out to nygbrus, vaccines cause fevers in up to 25% of the cases; but we can’t predict which vacccination will cause fevers by just counting up their antigens, in fact, the pattern seems to go the opposite way. The chicken pox vaccine, with the most antigens (69, not 75), causes fever far, far less frequently than the vaccine with only 5 antigens.

    How do you explain this discrepancy, if indeed, ‘antigen exposure is antigen exposure’. Where have I heard that phrase before I wonder. . . . ?

    Similarly, if we look to trials of simultaneous triggering of multiple TLRs, we find that the resultant increase in inflammatory cytokines is not linear, but rather, synergistic.

    Multiple signaling pathways contribute to synergistic TLR ligand-dependent cytokine gene expression in human monocyte-derived macrophages and dendritic cells.

    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.

    [snipping for sake of brevity]

    Once again, the grade school tool of addition has failed us. How would you explain these findings, if indeed, ‘antigen exposure is antigen exposure’. Why would we observe non linear responses if your model was correct?

    From a suvival standpoint, triggering an non linear, increasingly robust immune response when detecting multiple pathogens simultaneously makes good evoluationary sense; better to risk the effects of a large inflammatory event than sucumb to several types of microbial invaders, but it causes big problems with the idea that all challenges are created equal.

    Your framework rests of feeble underpinnings, that all antigenic challenges are equal, and thus, can be added together. But they aren’t equal. Nygbrus argues above that TLR4 stimulation with LPS produces a particularly vigorous response in inflammatory cytokines. [he's right] Would you disagree with him and say, ‘antigen exposure is antigen exposure’?

    If each and every antigenic exposure capable of inducing an appropriate immune response had to cause serious illness, we would be sick from the day we are born until the day we die.

    Even more reason for us to believe that vaccination, which induces fever with great regularity, is qualitatively different than scrapes, or the undetectable abrasions that we all encounter. I Most children don’t have fevers almost all of the time, but as many as 25% are expected to get one within a day or two of getting the DTAP; that tells us that everyday exposure and vaccination are different animals.

    All of the animals in the experiment I posted above received shots; breaking the skin and introducing bunches of antigens. For some reason, however, those animals that got saline developed no persistent effects at any timeframe. How come those antigens didn’t do anything? And weren’t all of the rats in those experiements getting the same types of undetectable abrasions that infants get? Yet, the treatment group clearly stands out in the results. How is this possible if all antigen exposure is equivalent?

    I hope that’s clear.

    You can craft a model with simplistic parameters that is clear; but all that means is that you made a simplisitic model. If we have reason to believe that the drill baby drill mantra of ‘antigen exposure is antigen exposure’ is not meaningful in terms of initiating an immune response, then what you have done is describe a model that fails to help us understand the real world. I doubt that was your intention, however.

    - pD

  81. weing says:

    “What is your explanation for the findings in Modulation of the infant immune responses by the first pertussis vaccine administrations wherein the researchers could tell which version of a vaccine an infant received based on cytokine profiles? In six months of life the infants in this study were exposed to three discrete events, DTP or DTAP, and tens, hundreds, or thousands of microabrasians, dirt eating exercises, trips on the floor, dirty fingers, and cat hair. And whatever else. Yet, somehow, all of these the numerous antigenic challenges, which I absolutely agree happened, did were unable to mask which vaccine the infants received. How is this possible within your model?”

    What is your point? Infants have a Th2 biased response to most infections and antigens, BCG, the whole pertussis vaccine, and actual pertussis being the notable exceptions.

  82. JMB says:

    @pD

    I like reading your posts because they are educational. However,
    the complexity of a model does not indicate that it is a better model. If you try to predict numerous different observations from a model, you may need a more complex model. However, to address a specific question, such complex models often reduce to simple models because so many factors prove to be insignificant for the specific question.

    It is possible to take almost any successful medical intervention, and find basic science studies that would seem to predict that the known successful intervention should not be successful.

  83. dt says:

    pD, you mistake my arrival on this thread to explain you were wrong about the antigen exposure load in early infancy with an attempt to refute every immunological point you make.

    I note you now seem to accept that the exposure in early infancy may be significant in terms of opportunity and quantity (something you previously denied) and are now goal-post shifting to say the type of immune response is somehow different.

    Some of your points are quite reasonable, but you tend to use the “blind them with science” gambit, where you quote extensively from papers to prove a point but underneath it all the point you try to make is somehow lost, or the question evaded. You also appear to have a problem with perseveration and confirmation bias – a search shows the paper you cite on DTaP has been quoted innumerable times by you over the last 4 years on various science blogs, but looking at your citations of it I see you appear not to have read beyond the abstract (or at least you only ever quote the abstract, and never from the paper).

    If you rely on this one paper so much to persuade people that the rest of immunology is somehow defective in its interpretation of the infant immune response to vaccines, you’d do better to enlighten us to some of the authors’ more detailed views, and maybe tell us what caveats the authors mentioned, and you should really try and find a paper or two that provide independent corroboration of your interpretation.

    You accuse me of oversimplifying when I call an antigenic response an “antigenic response”, yet your own model is very simplistic. You assume that a response which causes a febrile reaction is somehow unique and representative of a single particular immune response; but when an infection occurs, or exposure to antigens happens naturally or through vaccination, there are multiple effects, and only some immunogens need act as pyrogens. Some may act as superantigens and generate a significant pyrogenic response – this may be quite independent of the underlying immune response to antigens that generate protective immunity.

    As you are no doubt aware, there are both endogenus pyrogenic cytokines (TNFalpha, IL-1 and IL-6 and a few others), and the exogenous pyrogens such as LPS which in turn can generate IL-1 and IL-6 from macrophages. That vaccines may stimulate a pyrogenic response more often than other antigenic exposures in infancy is a distraction/straw man.

    It is quite wrong to assume or imply that the only immune response that generates a substantial immune response is one which also generates fever, yet that is what you appear to imply. This is untrue.

  84. passionlessDrone says:

    Hi Weing –

    What is your point? Infants have a Th2 biased response to most infections and antigens, BCG, the whole pertussis vaccine, and actual pertussis being the notable exceptions.

    My point is that three discrete events seem to have overcome the effect of all day long, everyday, antigen exposure for several months. Clearly, then, these three discrete events are qualitatively different than the hundreds, thousands, tens of thousands, or whatever number you want to insert standard run of the mill exposures to foreign particles. Once we admit this, however, we must conclude that not all exposures to antigens are equivalent. Once this is acknowledged, the framework that dt has built, that 100% of children have had ‘antigen exposure’ by the same time that our vaccination schedule proceeds, is meaningless, for it cannot accomodate exposures that cause differential effects.

    Also, don’t forget the measurements were not just in response to challenge, but baseline cytokine levels were different between the two groups.

    - pD

  85. passionlessDrone says:

    Hi JMB –

    I like reading your posts because they are educational. However,the complexity of a model does not indicate that it is a better model.

    OK. I guess I would argue that once a simple model has proven to be insufficient to understand reality, this makes it an even poorer candidate than a complicated model.

    It is possible to take almost any successful medical intervention, and find basic science studies that would seem to predict that the known successful intervention should not be successful.

    I’m not arguing with you, but would you be willing to provide an example? I am curious to this point.

    If you like learning about things, you might be interested in a paper that showed up as a result of one of my pubmed alerts tangential to autism.

    Alzheimer’s disease (AD) like pathology in aged monkeys following infantile exposure to environmental metal lead (Pb): Evidence for a developmental origin and environmental link for AD

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2486412/?tool=pubmed [full paper]

    Monkeys exposed to lead as infants developed differential expression of amyloid proteins and oxidative damage when measured, twenty three years later. The authors note that there were no outward signs of lead poisoning during exposure, though blood lead levels during exposure were high by todays standards (though not that high by yesteryears standards). Adolescent blood work and post mortem brain tissue analysis revealed no differences in lead levels; in fact, lead was not detectable in either group in the CNS in post mortem studies. I would argue that a simple model of environmental exposure would fail to even see a reason to perform this type of long term study.

    These are the types of findings that lead me to believe that our tinkering with the immune system during development with certainty that we have eliminated unexpected consequences is a dangerous game considering our relative lack of analysis. End soapbox.

    - pD

  86. passionlessDrone says:

    Hi dt -

    I note you now seem to accept that the exposure in early infancy may be significant in terms of opportunity and quantity (something you previously denied) and are now goal-post shifting to say the type of immune response is somehow different.

    If you think I denied that ‘exposure in infancy may be significant in terms of opportunity and quantity’ in the past, I’ve been doing an even worse job at explaining my position than I thought. My position involves the cross talk between the immune system and CNS, and a little more specifically, the possiblity that an increase in inflammatory cytokines during developmental periods can have difficult to predict consequences. My position is that the numerous microscopic breaks, dirty floors, and diaper rashes that infants encounter produce different amounts of inflammatory cytokines when compared to vaccinations. If I have been insufficiently clear, I apologize. If that doesn’t mesh with how you think the immune response is ‘somehow different’, I guess I’d have to ask you to point out my statements and I’ll try to be more concise.

    If you rely on this one paper so much to persuade people that the rest of immunology is somehow defective in its interpretation of the infant immune response to vaccines, you’d do better to enlighten us to some of the authors’ more detailed views, and maybe tell us what caveats the authors mentioned, and you should really try and find a paper or two that provide independent corroboration of your interpretation.

    I only use that paper a lot because it serves quite well illustrate the fatal flaws of the argument that ‘all antigen exposures are equivalent’, or sometimes, ‘antigen exposure is antigen exposure’. They aren’t. Vaccines are a qualitatively different thing that just normal everday baseline exposure to the dirty world. If only people would stop trying to use the bubble boy / everyday exposure involves millions of antigens canard, I wouldn’t have to try to use empirical findings to demonstrate the failings of that model.

    Thus far, the authors have decided not to provide me a copy of the paper. I usually get ~ 75% return ratio with my standard, ‘I’m an autism dad . . . ‘ request.

    The other thing I think this abstract does quite well is expound on what is my biggest concern; the very real lack of data we have collected on the act of vaccination on the immune system in ways other than antigen memory. The authors are quite clear on this: However, little is known about the general immune modulation induced by early vaccination. . This paper was published in 2007 in the journal ‘Vaccine’.

    What I found when I went looking in pubmed was largely a vindication of this statement, there is almost nothing in pubbmed on this type of thing. That is what bugs me about this discussion.

    Most people, it seems, are completely undisturbed by the fact that it was not until 2007 that someone decided it might be worthwhile to evaluate for immunological profiles up and above antibody generation in response to vaccination. You might be surprised to learn that I’ve spent some very real time trying to consider why, exactly, I find this of concern, but lots of other people, apparently, do not. I think (?) this might be a sort of black swan for a lot of people, the idea that modifying the immune system in ways other than providing an immunological memory might be possible, or meaningful if possible, just doesn’t occur. I must admit that confirmation bias on my end could be participating.

    What drives me to my thought process is the reading I’ve done regarding just how intertwined the immune system and CNS are, and similarly, the relative infancy of our understanding of the communication between the two systems. Nearly every common neurological disorder is being discovered to have strong immunological participation, ALS, Alzheimers, Parkinsons, autism, schizophrenia, bi-polar disorder, depression, CFS, dementia, epilepsy, migraines, all have varying degrees evidence of immune involvement. Our knowledge base is only now starting to come to terms with the fact that there is significant bidirectional crosstalk between the CNS and immune system, and that indeed, many of the molecules that our bodies use in pathogen defense also have functionality, often times in areas other than pathogen protection, in the CNS. Within that context, we have the reality that we just haven’t evaluated the act of vaccination itself.

    Think about it like this, were you surprised to find that the authors of that study claimed that so little knowledge had been generated outside of antibody generation from vaccines? I pose this as a genuine question. I must admit it is possible that everyone but me already knew we hadn’t studied this in detail.

    You assume that a response which causes a febrile reaction is somehow unique and representative of a single particular immune response; but when an infection occurs, or exposure to antigens happens naturally or through vaccination, there are multiple effects, and only some immunogens need act as pyrogens.

    Again, I only invoke the frequency of fever as a means to demonstrate the feebleness of the everyday exposure argument. If I have given the impression somehow that fever is the only thing that happens as a result of infection, other exposure, or vaccination, let me apologize for a lack of clarity.

    Some may act as superantigens and generate a significant pyrogenic response this may be quite independent of the underlying immune response to antigens that generate protective immunity.

    OK. But my thoughts that a significant pyrogenic response; i.e., a large influx of inflammatory cytokines, the piece that happens before protective immunity occurs, is largely what has me concerned.

    As you are no doubt aware, there are both endogenus pyrogenic cytokines (TNFalpha, IL-1 and IL-6 and a few others), and the exogenous pyrogens such as LPS which in turn can generate IL-1 and IL-6 from macrophages. That vaccines may stimulate a pyrogenic response more often than other antigenic exposures in infancy is a distraction/straw man.

    I am aware of that, but I am honestly confused as to why you think this is a strawman within the context of someone arguing that all exposures are the same. Some of the animal models I have referenced have observed attenutation of effect by blocking the immune response; eithter by specifically blocking one particular pyrogen, tnf-alpha, or more globally; i.e., minocycline administration. If vaccines are stimulating a pyrogenic resopnse more often than other antigenic exposures, that’s making my point; vaccines are a change from the baseline, and in a way that speaks towards the blind spot in our research and towards troublesome animal models.

    It is quite wrong to assume or imply that the only immune response that generates a substantial immune response is one which also generates fever, yet that is what you appear to imply. This is untrue.

    Hm. OK. But vaccination is intended and designed to generate an immune response, we don’t get the memory unless we first invoke the innate immune system. While lots of things also do that, vaccines are better at it than most everyday experiences. If I recall our previous discussion correctly, your point hinged on the ability of lots of things, things we encouter with some frequency, but perhaps not everyday, of being capable of causing the innate immune response to respond, but don’t generate a fever. Is that more or less correct? I’m inclined to believe that this is somewhat true, but again, would go back to the animal findings; the animals in question likely (?) were exposed to some of the same types of things along the way. but only those who received an input specifically designed to trigger the immune response had effects that were detectable. I can’t rule out what I think is your argument, but I would be interested in your ideas as to why we seem to be able to consistently tell what the treatment group is in the types of studies I’ve referenced from the rodent arena. Could you provide some references on this kind of thing?

    - pD

  87. weing says:

    “My point is that three discrete events seem to have overcome the effect of all day long, everyday, antigen exposure for several months. ”

    What 3 events are you talking about? The vaccine shots? Your point is that exposure to the various bacteria and their antigens that infants are exposed to doesn’t confer immunity against bacteria that they were not exposed to? That still doesn’t make sense. What effect has been overcome?

  88. Th1Th2 says:

    passionlessDrone,

    “Hm. OK. But vaccination is intended and designed to generate an immune response, we don’t get the memory unless we first invoke the innate immune system.”

    What particular immune response are you referring to? Also what does the innate immune system have to do with the “memory” thingy?

  89. “Thus far, the authors have decided not to provide me a copy of the paper. I usually get ~ 75% return ratio with my standard, ‘I’m an autism dad . . . ‘ request.”

    Can’t you get a copy from a library?

  90. Calli Arcale says:

    pD:

    Regarding the time dependency / six weeks issue, I apologize for not being clear. Here are my thoughts:

    1) Percent of children getting Hep-B within a week of birth. ~ 90%
    2) Percent of children getting an infection within a week of birth. ?% [I doubt anywhere close to 90%]
    3) Percent of children getting standard two month well visit vaccine set. ~90%
    4) Percent of children getting an infection within two months of birth. ?% [Still exceedingly likely much less than 90%, but more than at one week].

    Well, if we’re comparing what an average childhood experience is like today (vaccines, clean household, etc) with what it was like before the advent of civilization, then you might find this a lot more shocking than you may expect. Obviously, no one was getting vaccinated in those days, but infections were commonplace. We know that in Medieval Europe, the infant mortality rate was around 20%. This is not easily sorted out into neonatal, perinatal, etc, but it shows that things were rough. I would expect infections would have been common in infants in those days — both infections by communicable disease and more prosaic infections. Eye infections remain very common in infants today, even with modern hygiene practices, and it would have been more so then. It *is* more so in communities living in such conditions today, actually.

    It is not common for a one-week-old baby to skin its knee. This is very true. It is, however, very common for any baby to get scratches all over its face. This is why companies have produced a huge range of baby mittens, and baby shirts with pockets that can be flipped over the hands — their nails are razor-sharp at birth, and the babies have absolutely no control over them. It’s not that unusual for a baby to look like it’s been scratched by a cat, when in fact it was all the baby’s own nails. This is not a major problem for an affluent American family. Now imagine how that pans out for an impoverished Tibetan family, or a Kyrgyz nomad, or a Haitian living under a tarp. That will give you an idea of what it was like for human babies for most of our species’ history on this planet. Cutaneous infection is not common in American newborns today. But it had to have been commonplace among our hunter-gatherer ancestors in ancient times. It beggars imagination to think otherwise. Now, most of these infections wouldn’t cause any serious harm to the baby, but they’d still be an immunological challenge, which is the point of this discussion.

  91. passionlessDrone says:

    Hi weing –

    What 3 events are you talking about? The vaccine shots? Your point is that exposure to the various bacteria and their antigens that infants are exposed to doesn’t confer immunity against bacteria that they were not exposed to? That still doesn’t make sense. What effect has been overcome?

    Yes, the three vaccine shots. But, that isn’t my point. Here is how the argument usually goes:

    pD: “we haven’t tested the practice of vaccination, just some vaccines given relatively late in the schedule, and one vaccine ingredient”

    someone: “the amount of antigenic exposure within a vaccine is completely insignificant to the antigens a baby is exposed to through scraped knees, dirt floors, bee stings, the birth process, and generally just being alive.”

    pD: “If the exposure from everyday experience is so insignificant, how come these three discrete events, DTP or DTAP vaccination, appear to be able to maniuplate blood cytokine levels after two solid months ‘everyday exposure’. Shoudn’t the everyday exposure have rendered the vaccine event a drop in the bucket? How come I can tell which vaccine an infant got based on blood cytokine profiles?”

    It doesn’t have anything to do with memory, both DTP and DTAP appear to work for that. It has to do with other modifications to the immune system, something insignificant compared to everyday exposure shouldn’t be able to do that.

    ‘What has been overcome’ is the boatloads of antigens infants are exposed to everytime they touch a surface ,nurse or do whatever.

    I hope that helps.

    - pD

  92. passionlessDrone says:

    Hi Allison Cummings –

    Can’t you get a copy from a library?

    I probably could. But I generally get about 70% return rate from people willing to send me articles and I’ve got lots to read.

    There isn’t any nuance in the discussion section that is going to make the fact that blood cytokine levels were modified for two months based on vaccine type, and with that knowledge, the argument that vaccine exposure can be safely equated to normal everday exposure disintegrates.

    Similarly, there isn’t anything in the discussion section that is going to change the fact that it wasn’t until 2007 that this type of modification was being looked for by anyone. I don’t need to goto my library to check pubmed, and the data isn’t there.

    - pD

  93. passionlessDrone says:

    Hi Callie Arcade –

    Obviously, no one was getting vaccinated in those days, but infections were commonplace. We know that in Medieval Europe, the infant mortality rate was around 20%.

    I am in agreement with you.

    I’ve got absolutely no problem with the idea that increased survival rates today, as compared to then, could be participating in a possible increase in autism today. Likely, any infant getting a serious infection in those times faced a difficult road to survival.

    We must also onsider the possiblity that lots of people with autoimmune disorders that are todays parents might not have survived long enough to procreate in generations past. There are several studies that indicate an autoimmune disorder in the mother is a risk factor for an autism diagnosis.

    Now, most of these infections wouldn’t cause any serious harm to the baby, but they’d still be an immunological challenge, which is the point of this discussion.

    Indeed. Well, I guess some empirical data might help. And that’s one of my concerns, there would be problems getting good data on how much, if any, of an immune response was marshalled after the type of cuts you describe. But we just haven’t done the work in the vaccine arena.

    If we had good, clinical evidence that the degree of an immune response from baby nail cutting and immunization was the same, my ideas would be dead in the water.

    - pD

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