Respectful Insolence

ResearchBlogging.orgI wonder what the loons at Age of Autism will say about this.

Actually, I know what they’ll say. Whenever a scientific study like the one just published earlier this week the top tier journal Nature, which examines genetic variations (CNVs) associated with autism and autism spectrum disorders (ASDs), comes out, they have a standard reply. Even though, as of this writing, I haven’t seen yet seen a reply on the anti-vaccine crank blog Age of Autism to the study I’m about to describe, I’m sure it’s coming and I’m sure it will look something like this article from a year ago by Mark “Not A Scientist Not a Doctor” Blaxill entitled Latest Autism Gene Studies Find….Not Very Much:

There’s a familiar rhythm to the most prominent autism gene hunt publications. Their authors hype their newly minted study aggressively in the media. The prestigious journals that publish them lend their imprimatur to press releases that say, “this study is a big deal.” The findings sound impressive in the press release (and the authors get plenty of time on camera and in leading newspapers to tell us how truly impressive they are). In the meantime–in papers that are so densely written that making sense of what they really say requires far more reflection than the media hype cycle permits–skillfully concealed evidence reveals the truly important news in the findings: the authors whisper quietly (if at all) that the new analysis negates the most important findings of some of the most prominent previous gene hunts, while crucial detail on their new findings is often relegated to “supplementary material” that’s not available on the publication date.

Such a declaration is then almost inevitably followed by rants against scientists for concentrating on genes rather than vaccines as a cause of autism, claims of “conflicts of interest,” and an “analysis” of the findings of the study that betray an incredible lack of understanding of molecular biology, genetics, and developmental biology. I expect that the response to this study will be no different and may well appear on AoA by tomorrow morning, quite possibly written by Mark “Not a Scientist Not a Doctor” Blaxill. The study by Pinto et al, looks at the functional impact of global rare copy number variation in autism spectrum disorders.

Before you can understand what this paper found, you need to know what copy number variation is. In basic genetics and biology classes, many of you probably learned, depending on how long ago you took the courses, that we have two copies of each gene, one on each chromosome, one inherited from the father and one inherited from the mother. The exception is that men have a Y-chromosome instead of a second X chromosome and therefore have only one copy of genes on the X and Y chromosome, the X-linked genes inherited from the mother, the Y-linked genes inherited from the father. Of course, nature is seldom quite so neat, and now that we have powerful tools for sequencing the entire genome and probing its entire DNA looking for anomalies, we’re finding that things aren’t quite so simple. It turns out that there is considerable variation in the copy numbers of some genes. This is due to the rare duplication or deletion of a stretch of chromosome during replication. Such errors can leave a person with, for example, one copy on one chromosome and two on another. Although these events are rare for individual stretches of chromosomal DNA, over time and over many generations they can lead to some genes having several. Moreover, there appear to be “hot spots” in various chromosomes that are more prone to duplications or deletions.

Because I’m a cancer surgeon and biologist, I’m mostly familiar with variations in gene copy number associated with cancer, and there are many of these. Duplications and amplifications of stretches of DNA are practically the sine qua non of cancer. Often in cancer the amount of gene product in the form of protein that a given gene makes is proportional to the copy number. For instance, in breast cancer, there is a stretch of DNA known as the 8p11-12 amplicon. Basically, it’s a stretch of DNA on the p arm of chromosome 8 that is commonly amplified in breast cancer. This region of chromosome 8 is under active study, and there appear to be a number of candidate oncogenes there. One consequence of our learning about such amplified regions is that a formerly popular (about 30 years ago) and somewhat simplistic idea that single oncogenes would explain carcinogenesis, an idea that was later supplanted by a less simplistic but still too simple idea of multistage carcinogenesis in which a series of mutations in key oncogenes led to cancer. Now we understand that it is many genes that cause cancer. Whole networks of genes are perturbed.

Cancer is one extreme, though. Although CNVs are associated with many diseases and conditions, the abnormalities in are not as dramatic or numerous as they are in cancer. In the study under discussion, Pinto et al undertook an a survey of as many CNVs as they could identify in autistic children. Basically, they genotyped 1,275 children with ASD and 1,981 neurotypical controls and compared the frequency of single nucleotide polymorphisms (SNPs) according to the following scheme:

i-95751e265193ffd697724198c536a895-schema-thumb-400x369-50898.jpg

It’s not necessary for you to understand what SNPs are, only that by examining them scientists can estimate CNVs. Using a technique that can look for SNPs in 1.2 million loci per sample. This allows the performance of what is known as a genome wide association study (GWAS), which can look at genetic variation over the entire genome. Genetic variations that are more common in people with a disease are said to be associated with that disease. GWAS can be very powerful, but, like much of modern genomic medicine, these studies produce incredible amounts of data, with all the attendant difficulties, both computational and scientific, in interpreting what all the associations that are found may or may not mean.
As the authors note in their introduction, previous attempts at GWAS for autism have identified candidate genetic loci at 5p14.1 and 5p15.2. However, variations in these loci can only account for a relatively small percentage of the heritibility of ASD, hence the desire to examine the entire genome in a large number of children with ASD.

What Pinto et al found was this:

The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours1. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability2. Although ASDs are known to be highly heritable (~90%)3, the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 × 10-4). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.

One interesting finding was that 5.7% of the CNVs discovered appeared not to be inherited; i.e., they were de novo, meaning, basically, new CNVs. More important, though, was the bioinformatic and systems biology analysis of the CNVs. This led to the identification of potential new pathways whose function in ASDs may be abnormal compared to the control group. This is mapped out in the following illustration:

i-500ff6add92ce61ea60c2177fea4c8e9-pathways-thumb-480x204-50901.jpg

Candidate pathways for ASD identified by this method included genes involved with the cytoskeleton and microtubules, as well as genes involved in cell projection and motility, all of which are involved in cell migration. Other candidate pathways included genes involved in cell adhesion. It is not difficult to imagine how defective or altered migration and adhesion of neurons might result in the creation of abnormal neural pathways and thus result in the differences in cognition and behavior observed in ASDs. Of course, I’m putting things very simply. Even if this is true and these pathways are involved in ASDs, we know so little about how neural networks result in cognition and behavior that it will take a very long time and a lot of work to figure out excactly why and how abnormalities in these pathways result in ASDs. The same is true of other potential pathways implicated by these studies. These include GTPase and ras signaling pathways, as well as other kinase pathways. It’s not necessary to understand the significance of these pathways, just to know that they are involved in the transmission of signals from protein receptors on the cell surface into the cell, with the result being a number of processes, such as proliferation, migration, and the transmission of signals between neurons, among others.

Almost as important as the candidate pathways implicated by this study that clearly need further study to validate whether they are truly involved in the pathogenesis of ASDs or not are the pathways that were not implicated. One of the major claims of the “autism biomed” movement, the group of quacks who claim that they can treat autism with all manner of woo ranging from chelation therapy to various antioxidants and supplements, is that there are significant defects in pathways involved in countering the effects of oxidative stress, particularly pathways that result in glutathione production. (Glutathione is one of the major scavengers of reactive oxygen species–a.k.a. free radicals–in the cell.) Such claims were prominently featured by the lawyers for the complainants in the Autism Omnibus. Treatments allegedly targeting “detoxification” pathways involving “Glutathione, Cystathionine, Homocysteine, Methionine” figure prominently on the website of many a quack and are a favorite among the “vaccines cause autism” crowd. Don’t ask me how “vaccine injury” somehow causes oxidative stress sufficient to “cause autism.” Anti-vaccine “scientists” have long and convoluted pseudoscientific explanations that are implausible and unconvincing.

None of these “detoxification” pathways showed up in the analysis of Pinto et al. Big surprise, there. Well, not really. Of course, the fact that Pinto et al failed to find any of these pathways in ASDs in their analysis will no doubt be seized upon as “proof” that their analysis is hopelessly flawed. Just you wait. It’s coming. Because everything old is new again when it comes to the anti-vaccine movement, also coming will be another turd from Mark “Not a Scientist Not a Doctor” Blaxill that will go something like this one from a year ago:

But if the de novo CNV theory was plausible at one level, it was absurd at another. The genetic mutations the theory proposed (because this was the best the available evidence could support) were completely non-specific. The copy variants were spread widely (even randomly) over the genome, the theory went. No individual mutation was responsible for autism, just the unhappy presence of the wrong one. And these non-specific mutations were not only widely spread, they were virtually undetectable in the infant: no dysmorphic features; generally normal birth and (in many cases development); and the beautiful children we so often see affected by autism.

In other words these CNVs were a case of immaculate mutations.

And it was the perfect new project for the genetics research community. A wide open field of research opportunities. Lots of new money. And a chance to explain past failure away as part of the inexorable march towards genetic understanding.

If there’s one thing that annoys the crap out of me, as regular readers know, is likening science to religion. It’s a favorite canard of cranks of all stripes, be they anti-vaccinationists, creationists, alt-med promoters, 9/11 Truthers, and Holocaust deniers. I’ve heard anti-vaccine loons refer to “Vaccinianity“; creationists refer to the “church of Darwin”; and Holocaust deniers refer to “Holocaustianity,” among others. The intent is obvious: Try to paint the science detested as being faith-based rather than science-based.

No doubt when Blaxill or whoever at AoA decides to attack Pinto et al shows up to do it, he’ll also parrot the same breathtaking combination of ignorance and binary thinking. P.Z. Myers put it well when he pointed out that these things are very complicated. So did Pinto et al:

Our findings provide strong support for the involvement of multiple rare genic CNVs, both genome-wide and at specific loci, in ASD. These findings, similar to those recently described in schizophrenia, suggest that at least some of these ASD CNVs (and the genes that they affect) are under purifying selection. Genes previously implicated in ASD by rare variant findings have pointed to functional themes in ASD pathophysiology. Molecules such as NRXN1, NLGN3/4X and SHANK3, localized presynaptically or at the post-synaptic density (PSD), highlight maturation and function of glutamatergic synapses. Our data reveal that SHANK2, SYNGAP1 and DLGAP2 are new ASD loci that also encode proteins in the PSD. We also found intellectual disability genes to be important in ASD. Furthermore, our functional enrichment map identifies new groups such as GTPase/Ras, effectively expanding both the number and connectivity of modules that may be involved in ASD. The next step will be to relate defects or patterns of alterations in these groups to ASD endophenotypes. The combined identification of higher-penetrance rare variants and new biological pathways, including those identified in this study, may broaden the targets amenable to genetic testing and therapeutic intervention.

The problem is that none of this is easy, and none of it is likely to result in effective treatments for ASDs soon. Autism quacks and anti-vaccine zealots, however, can’t accept this. Again, like Blaxill, they demonstrate binary thinking. If a study doesn’t find a single, clear-cut gene causing autism or ASDs, then the study is crap. They also seem completely oblivious to developmental biology. It bothers them that a child with ASD appears normal at birth and then only manifests symptoms between the ages of 2 and 4. Development proceeds, however, according to predictable, sequential steps that are under genetic control, and genetic variations and abnormalities can have a profound impact on development that may not manifest itself until previous parts of the developmental program are complete. They also seem unable to understand that most chronic diseases and conditions with a strong genetic component are multifactorial and due to differences multiple genes. Due to functional redundancy in our cells, there are also often multiple abnormalities that can produce similar phenotypes; it is therefore not surprising that there might be many different gene abnormalities that contribute to ASDs. Systems biology gives us the tools to start to understand these exceedingly complex processes.

While it is possible–even likely–that there is an environmental component to ASDs, the evidence to date has not convincingly implicated any, except for, ironically enough, given how anti-vaccine zealots believe that the MMR vaccine causes autism, maternal rubella infection while the fetus is in the uterus, as a cause of autism. Moreover, as P.Z. pointed out, no transient exposure or exposures to an external agent (such as a vaccine) is known to be able to produce such a consistent pattern of gene duplications and deletions in human cells like the sets detected in Pinto et al. Thus far, the preponderance of evidence points to primarily a genetic cause for autism and ASDs, and Pinto et al is another solid study supporting a genetic basis for autism. It also suggests potential cell signaling pathways that might be abnormal in autism and thus targets for therapeutic intervention. That’s all we can ask of such a study.

Now remains the hard work of validating and replicating these findings and then figuring out which pathways can be targeted for therapy. What I’m afraid of now is that the quacks will look at the pathways identified by Pinto et al and try to come up with new pseudoscientific “biomed treatments” for autism based on these results, after (of course) “showing” how vaccine “injury” can create these same CNVs in children.

That’s coming, too. Just you wait. It wouldn’t surprise me if I were to see this sort of “science” presented at Autism One next year.

REFERENCE:

Pinto, D., Pagnamenta, A., Klei, L., Anney, R., Merico, D., Regan, R., Conroy, J., Magalhaes, T., Correia, C., Abrahams, B., Almeida, J., Bacchelli, E., Bader, G., Bailey, A., Baird, G., Battaglia, A., Berney, T., Bolshakova, N., Bölte, S., Bolton, P., Bourgeron, T., Brennan, S., Brian, J., Bryson, S., Carson, A., Casallo, G., Casey, J., Chung, B., Cochrane, L., Corsello, C., Crawford, E., Crossett, A., Cytrynbaum, C., Dawson, G., de Jonge, M., Delorme, R., Drmic, I., Duketis, E., Duque, F., Estes, A., Farrar, P., Fernandez, B., Folstein, S., Fombonne, E., Freitag, C., Gilbert, J., Gillberg, C., Glessner, J., Goldberg, J., Green, A., Green, J., Guter, S., Hakonarson, H., Heron, E., Hill, M., Holt, R., Howe, J., Hughes, G., Hus, V., Igliozzi, R., Kim, C., Klauck, S., Kolevzon, A., Korvatska, O., Kustanovich, V., Lajonchere, C., Lamb, J., Laskawiec, M., Leboyer, M., Le Couteur, A., Leventhal, B., Lionel, A., Liu, X., Lord, C., Lotspeich, L., Lund, S., Maestrini, E., Mahoney, W., Mantoulan, C., Marshall, C., McConachie, H., McDougle, C., McGrath, J., McMahon, W., Merikangas, A., Migita, O., Minshew, N., Mirza, G., Munson, J., Nelson, S., Noakes, C., Noor, A., Nygren, G., Oliveira, G., Papanikolaou, K., Parr, J., Parrini, B., Paton, T., Pickles, A., Pilorge, M., Piven, J., Ponting, C., Posey, D., Poustka, A., Poustka, F., Prasad, A., Ragoussis, J., Renshaw, K., Rickaby, J., Roberts, W., Roeder, K., Roge, B., Rutter, M., Bierut, L., Rice, J., Salt, J., Sansom, K., Sato, D., Segurado, R., Sequeira, A., Senman, L., Shah, N., Sheffield, V., Soorya, L., Sousa, I., Stein, O., Sykes, N., Stoppioni, V., Strawbridge, C., Tancredi, R., Tansey, K., Thiruvahindrapduram, B., Thompson, A., Thomson, S., Tryfon, A., Tsiantis, J., Van Engeland, H., Vincent, J., Volkmar, F., Wallace, S., Wang, K., Wang, Z., Wassink, T., Webber, C., Weksberg, R., Wing, K., Wittemeyer, K., Wood, S., Wu, J., Yaspan, B., Zurawiecki, D., Zwaigenbaum, L., Buxbaum, J., Cantor, R., Cook, E., Coon, H., Cuccaro, M., Devlin, B., Ennis, S., Gallagher, L., Geschwind, D., Gill, M., Haines, J., Hallmayer, J., Miller, J., Monaco, A., Nurnberger Jr, J., Paterson, A., Pericak-Vance, M., Schellenberg, G., Szatmari, P., Vicente, A., Vieland, V., Wijsman, E., Scherer, S., Sutcliffe, J., & Betancur, C. (2010). Functional impact of global rare copy number variation in autism spectrum disorders Nature DOI: 10.1038/nature09146

Comments

  1. #1 SteveF
    June 11, 2010

    You can get an impression of the AoA response from the comments of John Stone beneath the Guardian reporting of the story. He starts off with:

    Actually, the lady from the National Autistic Society has got it right: this is not an important story and the study only discloses a vague statistical association.

    and then:

    176 authors (if I have counted correctly) and these are the only listed competing interests……

    ….This is the disclosure form for “international medical journals”, although interestingly in this case Nature is not a medical journal:

    http://www.icmje.org/coi_disclosure.pdf

    I think possibly the disclosures here fall a little short.

    and so on:

    http://www.guardian.co.uk/science/2010/jun/09/genetics-autism-story-tracker

  2. #2 SteveF
    June 11, 2010

    whoops, meant to italicise up to the end of “fall a little short”.

  3. #3 redacted
    June 11, 2010

    This isn’t surprising at all to find small subsections given the history of autism. Can we take this as another sign that Wing went too far by creating a box based on “normal traits” and should have gone with the narrower view stated in Wing 1993 that she rejected? Perhaps parents should not use politics to influence science whether DSM construction or other.

  4. #4 codedlife
    June 11, 2010

    I wrote another take on this paper earlier in the week (see link on my name). I have to admit I played down the findings a little as I was a little miffed at all the MSM reports of an imminent genetic test for autism and keep it more superficial (thinking of non-science readers).

  5. #5 codedlife
    June 11, 2010

    Sorry about the URL in comment 4, WordPress seems to have a mind of it’s own and has overridden what I pasted into the URL box (it’s a long story). The link to the article is:

    http://sciblogs.co.nz/code-for-life/2010/06/10/autism-genetics-how-do-you-copy/

  6. #6 Dave Ruddell
    June 11, 2010

    This actually made the front pages of the various Toronto newspapers, although that’s likely more to do with the local angle than anything else.

  7. #7 Grant
    June 11, 2010

    A Paul Maher has commented on my article, who needs a little attending to. I would, but the opening of the World Cup is starting… anyone else is welcome to correct the guy’s notions.

    http://sciblogs.co.nz/code-for-life/2010/06/10/autism-genetics-how-do-you-copy/

    Excuse my repeated posts, I’m doubling this up with trying to track down why WP thinks I’m logged in an old blog…! Let’s see if it’ll let me be me now…

  8. #8 Pablo
    June 11, 2010

    The problem is that none of this is easy

    Indeed, this IS the problem. Too many people want simple, contrite explanations that are 1) easily understood by simpletons (such as surgically enhanced playboy models), and 2) have easy fixes.

    Unfortunately, nature doesn’t always work that way. Sometimes, damn it, science is complicated.

  9. #9 JayZee
    June 11, 2010

    Just stopped by to check in with the medical imperialists to see if anything’s new and all I got was…When all else fails throw it in the genetics trashcan.lolz

    Respectful Somnolence indeed!
    http://www.youtube.com/watch?v=n5ehxdFJUxE&feature=related

  10. #10 passionlessDrone
    June 11, 2010

    Hello friends –

    I am absolutely in love with the data visualization that this paper used, and secondarily am really beginning to appreciate the utility of identifying genetic pathways that are disturbed as opposed to single genes. This is a powerful set of tools.

    That being said, some context may be in order.

    Diagnostic tests based on the work will not be clearcut. Co-author Stephen Scherer of the Hospital for Sick Children in Toronto estimated that genetic clues to the disorder were present in only about ten percent of the families with an autistic member in the Canadian cohort of the study. And, the researchers noted, each patient carried their own unique assortment of copy number variations. Of nearly a thousand variants studied, the most prevalent was still only present in less than 1% of the participants with autism.

    From the nature blog on this paper. Not linking to avoid spam filtering.

    None the less, this is pretty neat and I am in favor of any bioinformatic based approach on anything, but especially autism.

    Does anyone have insight on the pathway, GTPase/Ras, which is supposedly described here as associated with autism for the first time?

    - pD

  11. #11 Denice Walter
    June 11, 2010

    Another factor may be that *genetic* could perhaps be misinterpretted as being somehow “their fault”:implying an imagined type of responsibility as well as the stigma of being “labelled” as “deficient” or somehow “inferior”.This study supports the view that autism derives from some “internal” trait(genes) that is(to a large degree)”beyond personal control”, whereas if the “blame” is assigned to something “external”(vaccines, toxins)the person can salvage self-esteem and maintain the anxious hope that he/she can *do* something to change the situation for the better(bio-medical interventions).In reality,there are therapies that help many people on the ASD spectrum, and sometimes, “time” itself helps.In an interesting parallel,theories of the causation of schizophrenia have undergone an evolution from (pre-scientific)”punishment of the gods”/”possession by demons” to ideas about parental behavior(the “schizophrenigenic mother” being the complement to early “refridgerator mother” hypotheses about autism)and “stress” as causative to those that focus on genetics and physiological development.

  12. #12 Lycanthrope
    June 11, 2010

    Why does Orac single out Mark Blaxill as being “Not a Doctor, Not a Scientist”? I’ve seen him refer to Blaxill thusly many a time, and I’m curious. I always thought that very few of the Age of Autism/antivax crowd were doctors and/or scientists.

  13. #13 Todd W.
    June 11, 2010

    @Lycanthrope

    IIRC, it is because Blaxill has, himself, stated something along the lines of “Now, I’m not a doctor or scientist” and then gone on to pontificate as if he were one or had the equivalent expertise.

  14. #14 snurp
    June 11, 2010

    passionlessDrone

    I did a little bit grunt work in a devo lab as an undergrad with a small GTPase superfamily member in relation to neuronal proliferation and gut colonization (specifically RhoN in zebrafish, which like the other rhos is more cell morphology), but I can’t give you much else than google – signal transduction, involved in many cell growth/differentiation processes, and the Ras subfamily seems to be associated with proliferation.

  15. #15 Kristen
    June 11, 2010

    @Denice,
    From my understanding, some of the copy variations are novel (i.e. not found in the parents). But I don’t expect the anti-vax camp to see or comprehend that idiosyncrasy. I think it is ridiculous to blame oneself for a genetic defect in ones children anyway. I know it doesn’t bother me or my husband, even though he has Aspergers so it would be easy for me to point the proverbial finger.

    One interesting finding was that 5.7% of the CNVs discovered appeared not to be inherited; i.e., they were de novo, meaning, basically, new CNVs.

    ——————————————————————-

    Another thing I found interesting:

    These findings, similar to those recently described in schizophrenia, suggest that at least some of these ASD CNVs (and the genes that they affect) are under purifying selection.

    I don’t know if this is a coincidence or not but IIRC autism was once labeled as a type of schizophrenia. At least according to Wikipedia. This article in Scientific American says:

    Previous research had turned up a few rare copy-number variations in schizophrenic patients, but they “explain only a small fraction of the genetic risk of this common complex disease,”

    So I wonder if the anit-vax community dismisses these findings about schizophrenia because all the genetic variations are not yet understood.

    But, of course, I have very little understanding of this subject. I am going to look up more definitions and resources to help me understand it better.

  16. #16 KWombles
    June 11, 2010

    AoA may not have spoken up on this yet, but Doherty used the study to conclude that “Major Autism Genetic Study Highlights Need for Environmental Autism Research.”

  17. #17 Kate from Iowa
    June 11, 2010

    Orac, just one question, is age of the parents being considered as one of the possible environmental factors?

    (If you know, of course, which I realise you may not.)

    Of course, even if it is, it’ll get thrown out with any of the potential genetic findings by those desperate to believe that thier child’s autism is not thier fault which…nobody (but them) is saying anyway.

  18. #18 Composer99
    June 11, 2010

    Denice @11,

    I suspect a lot of resistance the idea to genetic causes to disorders/diseases is so much latter-day concern over ritual purity.

  19. #19 Todd W.
    June 11, 2010

    @Kate from Iowa

    is age of the parents being considered as one of the possible environmental factors?

    There was a recent study that found that the age of the parents does play a role. The older the parents were, the greater the risk of having a child with autism. The study built on previous work that suggested age played a role, but, IIRC, used a somewhat larger cohort. While suggestive, additional research on age as a factor wouldn’t hurt.

    Does someone have a link to the study handy?

  20. #20 passionlessDrone
    June 11, 2010

    Hi Todd W –

    There have been several studies that generally found increased risk as your parents get older. Some studies have found only paternal age matters, others only maternal age matters, and others, either matters. I’m not aware of any (?) that found no association.

    Advanced paternal age is associated with impaired neurocognitive outcomes during infancy and childhood. – Saha 2009 (PMID: 19278291)

    Advanced parental age and the risk of autism spectrum disorder – Durkin 2008 (18945690)

    Paternal age at birth and high-functioning autistic-spectrum disorder in offspring – Tsuchiya 2008 (18827294)

    Independent and dependent contributions of advanced maternal and paternal ages to autism risk – Shelton 2010 (20143326)

    Risk of autism and increasing maternal and paternal age in a large north American population – Greither 2009 (19783586)

    I think I missed one or two more. But it does seem likely advanced age is playing a part.

    - pD

  21. #21 Todd W.
    June 11, 2010

    I think the Shelton 2010 study was what I was thinking of. Thanks, pD.

  22. #22 Grant
    June 11, 2010

    @Todd & @Kate,

    The age of the parents has long been considered an environmental factor: autism is more prevalent in children of older parents. Precisely which (the mother or father, or both) parents are the risk factor has been a question.

    It is possible that older parents have a loss or change in DNA methylation or other molecular epigenetic marker in their germ cells (eggs, sperm) which could predispose to autism. This would make for an epigenetic factor that isn’t dependent on anything in the environment as such, just the age of the parents.

    It’s one reason that a few people like me are watching to see if molecular epigenetics will play a role in autism. I’m not sure if there is solid evidence either way on this. While I follow autism research, it isn’t my work so smaller papers will slip by me!

    I thought to add this to my own account of the paper, but decided to keep it simple.

  23. #23 Denice Walter
    June 11, 2010

    (Seems like my response didn’t “take”/ sorry if it doubles)Kristen,I’m referring of course, to parents’ *naive* theories of causation- not always the most rational- wherin external causation(vaccines, toxins) may be easier for some people to accept emotionally.Needless to say, despite our “enlightened” times, stigma about mental and developmental conditions unfortunately,continues.Thus,the *taint* to which Composer99 refers.

  24. #24 passionlessDrone
    June 11, 2010

    Hi Orac (or anyone who might know) –

    Can anyone give some help to a jerk dad on the Internet who’s trying to figure some of the finer points of this paper, the underlying process, and the real take away importance of this paper?

    It seems like the strength of this paper lies in the ability to discern biological pathways affected by the changes that the authors found. But, it also seems that the underlying data they had to plug in to make those calculations was relatively frail.

    For example, one CNV, DDX53, was the most robust single CNV observed, found seven times in the thousand cases, and zero in the controls. In the supplementary materials, the authors mention that this finding was sizeable enough to pass a Bonferroni analysis.

    We also tested for increased global burden of rare CNV regions (CNVRs) in cases compared to controls. Here, 2,181 non-redundant CNVRs were constructed by merging overlapping are CNVs present in the total sample of cases and controls (n=2,283 samples) and taking the outermost boundaries of the union of those CNVs. Statistical significance for each gene or CNVR was assessed by Fisher’s exact test. From these analyses, CNVR at DDX53/PTCHD1 emerged as a significant ASD risk factor (P = 3.1×10-3 for the initial 1,287 EA controls). Specifically, we observed 7 ASD male cases with overlapping deletions at DDX53/PTCHD1 (Xp22.1) and no CNVs were observed at this locus for the initial 1,287 controls (Supplementary Figure 4). We further inspected an additional set of 3,677 European controls amassed from three independent cohorts and none of them showed CNVs at this locus (P = 3.57×10-6 for the 4,964 combined controls (Supplementary Table 6). This result would be significant after Bonferroni correction for
    the total number of 2,181 CNVRs.

    I’ve picked up along the way that if you perform enough analytic tick marks, you need to correct for that large sampling by applying this type of method. But DDX53 was the most common CNV found; would a CNV that was found once, or twice, in a sample this large with this many variables have passed Bonferroni correction?

    By way of example, another gene found with a CNV, SHANK2, was found twice in the 1000 cases, and this was a gene name that made the press report (perhaps due to established SHANK3 associations(?)), but in any case, would SHANK2 have passed Bonefrroni?

    If they cannot, does this affect our confidence in the pathway results that came out when they pushed these individual CNVs in as our input parameters?

    It seems like most of these pathways were already associated with autism, and also had some overlap with gene networks known to be associated with intellectual development, so this is meaningful to an extent. But we already knew most of this, and most of us already knew that autism was very complicated.

    I guess I always thought journals like Nature were for really groundbreaking stuff, and while the biological pathway stuff is nice, is the hype these results are getting really justified for a paper with a bazillion authors and full genotyping of two thousand individuals?

    Any insight is appreciated.

    - pD

  25. #25 RJ
    June 11, 2010

    pD,

    Good questions. I, myself, have read through the paper once…without a focus on detail. So, I’m going to hold off on addressing your questions at this time. However, it might be worthwhile to email some of those on the publication (particularly those involved in the statistical analysis). I am sure they could give you answers to your questions.

    This approach has worked for me in the past. I have found that (in most cases) those individuals publishing their work are very amendable to addressing questions, clarifying, and elaborating. This is a much better approach than asking random folks on a message board (although this is a VERY sharp group as far as message boards go).

    Perhaps you could send an email and share their responses.

  26. #26 Todd W.
    June 11, 2010

    From the competing financial interests section:

    L.J. Bierut and J.P. Rice are inventors on the patent “Markers for Addiction” (US 20070258898) covering the use of certain SNPs in determining the diagnosis, prognosis and treatment of addiction. L.J. Bierut served as a consultant for Pfizer Inc. in 2008.

    I wonder how long it will take AoA or similar antivaxers to point at this, claim that it is Bierut’s study (he’s firmly in the middle of the pack) and that this consequently invalidates the whole study. Or try to equate his holding a patent for genetic markers of addiction with Wakefield’s patent for a measles vaccine in some addled attempt to turn our valid criticism of Wakefield back at us.

  27. #27 mikerattlesnake
    June 11, 2010

    @pd

    There’s also a good summary on http://www.scienceblogs.com/pharyngula

    PZ does a long version and a short version. A big point seems to be that while there may be no single CNV that is prevalent in this group, all the CNV’s seem to affect similar functions in the brain. I am not a statistician and can’t answer your questions about significance, but looking at the data set as a whole seems to show a pattern.

  28. #28 Dedj
    June 11, 2010

    “I wonder how long it will take AoA or similar antivaxers to point at this”

    J()hn St()ne has already done somethng similar over at the Gruniad online article.

  29. #29 David N. Brown
    June 11, 2010

    I find it ironic how reception of autism/gene studies contrasts with that of the “gay gene” theory. The case for the former has so far been modest, but it has been trumpeted by “liberals” and given respectful attention by conservatives. The evidence of genetic factors for autism, on the other hand, is much stronger, and has accumulated for decades, yet it seems like the wider world took notice only after the “vaccines cause autism” scare played out.

  30. #30 David N. Brown
    June 11, 2010

    Correction: “Case for the latter”, not “former”.
    A further thought: When pressed, anti-vaxxers will acknowledge the role of genetics, with “spin” along the lines that a biological factor could predispose certain people to become autistic after receiving vaccines. Hence, they concede the obvious, while making a virtually arbitrary assumption seem credible.

  31. #31 diatom
    June 11, 2010

    Stanley Nelson, co-author of the Nature paper, cautions that these findings explain only 3.3 percent of the genetic origins of autism.

    http://www.genengnews.com/gen-news-highlights/study-finds-increased-numbers-of-gene-disrupting-cnvs-in-autism/81243515/

    Other scientists suggest that the cause of autism is most likely a complex interaction between genes and environmental factors

    “There’s genetics and there’s environment. And genetics don’t change in such short periods of time,” (one researcher on the dramatic increase in autism diagnosis in California in the past 15 years)

    http://www.scientificamerican.com/article.cfm?id=autism-rise-driven-by-environment

  32. #32 D. C. Sessions
    June 11, 2010

    They also seem completely oblivious to developmental biology. It bothers them that a child with ASD appears normal at birth and then only manifests symptoms between the ages of 2 and 4.

    You mean, like Tay-Sachs? That’s a genetic disease where we know exactly which genetic defect causes it and have been testing for it since the 1970s. And despite the objections of Balxill et al, TS babies are born perfectly normal and only start showing neurological degeneration months later.

  33. #33 Scott
    June 11, 2010

    Other scientists suggest that the cause of autism is most likely a complex interaction between genes and environmental factors

    “There’s genetics and there’s environment. And genetics don’t change in such short periods of time,” (one researcher on the dramatic increase in autism diagnosis in California in the past 15 years)

    http://www.scientificamerican.com/article.cfm?id=autism-rise-driven-by-environment

    You might want to take a look at why that study doesn’t say that. For instance,

    This study did not control for all possible artifacts resulting in higher diagnosis rates. Specifically, it did not address surveillance, which is likely the dominant factor. It also did not control for shifting diagnosis, diagnostic substitution, and dual-diagnosis.

  34. #34 Todd W.
    June 11, 2010

    @diatom

    Yes, the genetic interactions are likely to be quite complex. And there may very well be environmental aspects.

    “There’s genetics and there’s environment. And genetics don’t change in such short periods of time,” (one researcher on the dramatic increase in autism diagnosis in California in the past 15 years)

    The researcher is right. Genetics alone don’t account for the change in number of autism diagnoses. The biggest environmental factors in that increase are changes in diagnostic criteria, changes in tools used to diagnose, increased awareness, etc. Now, the big question is how much has the actual incidence changed. Current studies suggest, not much.

  35. #35 Scott
    June 11, 2010

    Bleh, HTML fail. That post should have included this link:

    http://www.sciencebasedmedicine.org/?p=340

    Apologies.

  36. #36 RJ
    June 11, 2010

    diatom,

    The second sentence from the Nelson quote is relevant and must be included for context:

    “Yet these findings explain only 3.3 percent of the genetic origins of autism. In order to identify all of autism’s genetic causes, we need tens of thousands of families to volunteer their DNA samples for sequencing.””

    Key omission:
    “In order to identify all of autism’s genetic causes…”

    In other words, it’s not that 3.3% of autism cases are explained by genetics. It’s that the genes examined comprise a small sub-set of all that contribute to ASDs.

  37. #37 passionlessDrone
    June 11, 2010

    Hi RJ –

    I emailed the author with my real world email, and he was quite nice, but mostly just sent me a copy of the supplementary material and told me the answers I sought were in there. I guess I need to get a lot smarter.

    Regarding what you wrote to diatom:

    In other words, it’s not that 3.3% of autism cases are explained by genetics. It’s that the genes examined comprise a small sub-set of all that contribute to ASDs.

    Maybe you (or someone?) can help me out here, and largely is what is stuck in my craw regarding this is; didn’t they examine the entire genome? Which genes got left out? Maybe I’m missing something and they didn’t actually perform a full scan?

    I guess it just seems to me that with this number of subjets, that if these types of alterations could account for a substantial portion of autism, we’d have found more hits. The authors seem to acknowledge that this type of study was undertaken precisely because SNP studies were largely unable to produce robust results.

    Genome-wide association studies using single nucleotide polymorphisms (SNPs) have highlighted two potential ASD risk loci at 5p14.1 (ref. 13) and 5p15.2 (ref. 14), but these data indicate that common variation will account for only a small proportion of the heritability in ASD.

    I’m not seeing anything indicating that these findings are demonstrably different in terms of defining a large proportion of heritability. Does anyone else see this in these results?

    Lets say we scaled up a few more thousand people, or whatever number we want, it seems like we might find more specific CNVs, but I can’t figure out why we might expect to see a greater percentage of cases with the CNVs? And without that optimism, we still can’t explain very much of the heritability of autism, despite throwing thousands of genomes at supercomputers. Does this bug anyone else?

    I’m not arguing for a simple solution here, but is there a time at which we consider using these findings as a jumping off point; perhaps to investigate if there might be external factors that could interferre with the biological pathways identified, and thus, produce similar results as having one of these CNVs?

    Thanks.

    - pD

  38. #38 Andreas Schaefer
    June 11, 2010

    ouch that is WAY over my head. ( and I do have a generic scientific background ) Would the following comparison be somewhat true ?

    It is said success has many fathers – I think failure does too.
    This is true for companies and countries – it takes more than one idiot ( with the poossible exception of sole owner and CEO ) to ruin them: only when a certain percentage of ‘diots work at it the whole company (or country ) manages to become dangerous or selfdestructive. ( Enron, BP, the recent financial bubble but also Germany during WW2 spring to mind. )
    What you and the research seem to say ( to my limited understanding ) is that Cancer and Autism ( and presumably several other things ) have multiple reasons: only when many of these come together the machinery of the body fails spectacularly.
    Given the long stretches of human history in which no healthcare was availiable at all one muwst assume that the human body does come with double and triple checked self-repair mechanisms that statistically do keep us alive. ( and explain the base percentage of people who get better even in the absence of treatment or despite wrong treatment )

  39. #39 Prometheus
    June 11, 2010

    One thing that this study (and previous papers on autism and CNV’s) explains particularly well is the oft-noted observation that there is frequently more difference between individual autistic children than there is between autistic children and typical children. [Note: the same is also probably true about autistic adults.]

    In other words, autism isn’t a very consistent “syndrome” in its presentation, prognosis or natural history. Contrast this to disorders – such as Guacher’s disease, Tay-Sachs disease, Wilson’s disease, etc – that have a known monogenic cause and have – unlike autism – relatively few variations in their presentation, prognosis and natural history.

    The “take away message” here – even before all the genetic work was done – was that autism was very unlikely to be a simple, monogenic disorder. Given the extreme range of severity, symptom complexes, disabilities, and developmental trajectories, it should have been expected that autism would be polygenic.

    Of course, an expert in international business like Mark Blaxill can’t be expected to understand that he had hit the proverbial nail on the head when he said:

    “No individual mutation was responsible for autism, just the unhappy presence of the wrong one.”

    Mr. Blaxill sees that as “evidence” that there is no genetic cause for autism; real scientists see it as evidence that there is no single genetic cause.

    As I’ve said above, finding a single mutation – or even a small number of mutations – that was the cause of autism would have flown in the face of what we know about autism. Finding that there are dozens, if not thousands of genes that, when mutated, can cause autism is actually more plausible. “Autism”, it seems, is not a syndrome, it is a symptom.

    Of course, the situation isn’t made any easier by the dramatic broadening of the autism diagnosis that has occurred over the past two (or more) decades. It would be a fascinating exercise to take the CNV data and see if there is any particular clustering of genes according to severity, age at diagnosis, or developmental trajectory.

    The copy number variation data are signaling “GAME OVER!” to those who persist in denying the genetic nature of autism, much in the same way that the Madsen et al (2003) data signaled the end of the “thimerosal-causes-autism” movement. This is not to say that there won’t be some – like Mr. Blaxill – who carry on with their denial of the facts in evidence, but it is likely that their numbers will gradually wane.

    Although I don’t generally agree with Kuhn, these data on CNV in autism should generate a paradigm shift among the autism (and anti-autism) advocacy community away from simplistic environmental and genetic explanations and toward seeing autism as the “final common pathway” for many mutations. And it is ironic that Kuhn’s quotation of Max Planck is terribly relevant to the continued objections of Mr. Blaxill (and so many others):

    “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it.”

    How ironic that Mr. Blaxill is in the category of those who will not be convinced and will not see the light.

    Prometheus

  40. #40 jen
    June 11, 2010

    yeah, but if it’s so genetic (and I remember that the study said that no two people with autism would have the same genetic variations) AND considering the case of regressive autism (the child is developing normally and then, whammo, the parent says the kid suddently is anything but normal -and as someone who has worked in the field of early intervention I have no reason to disbelieve parents’ accounts) then what the hell is so genetic about it? What is so new about this study. Previous studies have shown approx. 10% of autism cases to be genetic and that’s about it. Lastly, why does biomedical treatment and chelating actually help some kids to the point where they recover?

  41. #41 jen
    June 11, 2010

    p.s. the BP video actually reminds me of the whack jobs that are involved in autism research. (yeah, it’s all genetic, a vaccine could never be unsafe… how dare we question vaccine safety)

  42. #42 red pepper
    June 11, 2010

    What you and the research seem to say ( to my limited understanding ) is that Cancer and Autism ( and presumably several other things ) have multiple reasons: only when many of these come together the machinery of the body fails spectacularly.

  43. #43 Dedj
    June 11, 2010

    “then what the hell is so genetic about it? ”

    Well, as I’m sure someone will come along and explain a lot better, genes do not simply switch on on Day One and stay on, but they vary their activity in response to various factors including the activity of other genes.

    A gene which is involved in autism getting switched on, or read more often, by another gene or another gene process (or having its’ product altered by a result of another gene coming online) could feasibly account for a change in a persons ‘autismness’.

    This is, of course, assuming Non-Retts ‘regressive autism’ is real and not an artifact of developmental stages.

    Sorry for the lack of specific terms, but it’s not my field of study.

  44. #44 Prometheus
    June 11, 2010

    Jen asks:

    “considering the case of regressive autism (the child is developing normally and then, whammo, the parent says the kid suddently is anything but normal -and as someone who has worked in the field of early intervention I have no reason to disbelieve parents’ accounts) then what the hell is so genetic about it?”

    Look up “Tay-Sachs disease” or “Gaucher’s disease”. These are simple, monogenic disorders which can (and usually do) have what appears to be a sudden onset (i.e. “whammo”) after a period of normal development.

    Jen continues:

    ” Lastly, why does biomedical treatment and chelating actually help some kids to the point where they recover?”

    A better question would be “Do biomedical treatments and chelation actually help autistic children to the point where they recover?” I’ve seen no data that they do, so I’m hoping that Jen can provide the data.

    In fact, as we discover more and more data pointing to genetic causes for autism that aren’t likely to be affected by the more popular “alternative” treatments, the “treatments” start looking more and more like placebos.

    pD asks:

    “…didn’t they examine the entire genome? Which genes got left out? Maybe I’m missing something and they didn’t actually perform a full scan? “

    The researchers used the Illumina Infinium 1M array, which covers the entire human genome (centromeres and telomeres excepted) at a resolution of about 1.5 kbp. So, the answer to pD’s question is “yes – they examined the entire genome”.

    The matter of a “subset of genes” comes up because the researchers only genotyped 1275 autism (ASD) cases. That’s a huge number, given that they looked at 1256 trios (autistic child and both parents) and 1981 unrelated control subjects. In addition, they restricted their data to CNV’s of 30 kbp or larger, in order to reduce spurious results. Given the low frequency of repeats, we can tell that they are nowhere near the final number (if you don’t understand why, look up rarefaction as it pertains to ecology).

    In just the US, there are an estimated 1 – 2 million autistic people. Given the number of CNV’s found in this and previous studies, we’ve just seen the tip of the iceberg. So far, we can account for at least 10% of all cases of autism with known mutations – most of which were found in cases of familial autism (the rarest kind). What the CNV data should be telling people is that autism is genetic.

    Prometheus

  45. #45 RJ
    June 11, 2010

    pD,

    “didn’t they examine the entire genome?”

    No. From the interview (and found in the supplementary portion of the paper):

    “We know that 10 million gene variants consistently exist in every individual’s genome,” explained Rita Cantor, UCLA professor of human genetics. “We used DNA chips to collect and analyze data on 1 million of these variations to shed light on how autism develops.”

    I think it’s important for you to keep in mind that they went beyond just looking at (expressed) genes. They looked at replicate and deleted portions of the genome.

    “The authors seem to acknowledge that this type of study was undertaken precisely because SNP studies were largely unable to produce robust results.”

    That is correct. It’s not ‘A’ gene or a couple of genes with mutations that lead to ASDs, rather, chunks of DNA with repeats of genes and/or their regulatory elements (hence the term copy number variants). It is the imbalance in the number of genes that result in dis-regulated neuronal physiology and/or function.

    “but I can’t figure out why we might expect to see a greater percentage of cases with the CNVs? ”

    Because we are not looking at all of them. We may not yet have the gene chips to do so.

  46. #46 RJ
    June 11, 2010

    “One thing that this study (and previous papers on autism and CNV’s) explains particularly well is the oft-noted observation that there is frequently more difference between individual autistic children than there is between autistic children and typical children. [Note: the same is also probably true about autistic adults.]”

    As usual Prometheus, you hit the nail on the head. Very well stated!

  47. #47 RJ
    June 11, 2010

    @40

    jen,

    Your statements are clearly illustrating your lack of understanding. Please, I don’t mean to be personal. But you need to ask yourself, “do I really understand molecular biology?”. Consider the possibility that you do not understand what is being discussed here.

    “the child is developing normally and then, whammo, the parent says the kid suddently is anything but normal”

    Have you ever noticed how kids change as they grow up? Ever notice how we get old? How we have a tendency to have certain types of diseases, like cancer, later in life? This is because genes are turned on and off in stages throughout our lives. As mentioned with other examples above, many kids/people are born ‘normal’, then “whammo”, there is a change. Schizophrenia, for example, typically hits people in early adulthood. I assure you, it is not that they are allowed to vote that induces the disease. There are countless diseases and disorders that illustrate this point.

    This study is one of many that show that having extra portions of some chromosomes affects a sub-set of other genes that influence neurite outgrowth, migration, and synapse formation in specific parts of the brain. It is likely stage-specific. Just as changes in brain physiology occur in the same way in adults who “regress” (to use your term) into schizophrenia.

    “Lastly, why does biomedical treatment and chelating actually help some kids to the point where they recover?”

    What percentage do recover through these treatments?
    What percentage do not recover?
    What is the percentage compared to placebo?

    We don’t know. No one does. There haven’t been any formal clinical trials to show this. How can anyone claim that it is effective if it hasn’t been demonstrated scientifically? Because, otherwise, it’s merely opinion and anecdote.

    If the people performing these treatments really, truly believed that they do work, they would show it through a properly conducted trial. The fact is, if they do think it really works, and they do not share it with the rest of the medical community and those who can benefit from it, then they are low-life pieces of shit. As medical practitioners, they are OBLIGATED to share proven means of helping people. But, they do not. And it’s for a reason. It’s because they are selling snake oil.

    Anyone who is serious about helping people is obligated to do so by performing trials and sharing the data. Otherwise, making claims about unfounded treatments is just another way of selling hope to desperate people.

  48. #48 DW
    June 11, 2010

    Some general websites-NARSAD:the Brain and Behavior Research Fund(NARSAD.org) and the Lab of Neuro Imaging(loni.ucla.edu) that show where research is leading.

  49. #49 Jud
    June 11, 2010

    jen writes:

    (the child is developing normally and then, whammo, the parent says the kid suddently is anything but normal -and as someone who has worked in the field of early intervention I have no reason to disbelieve parents’ accounts) then what the hell is so genetic about it?

    The child is growing normally, then whammo, secondary sex characteristics – guess human maturation must not have anything to do with genes, eh?

    Guys are walking around with hair, then whammo, bald. Guess baldness must not have any hereditary component.

    jen, have you ever had the occasion to think about what you write?

  50. #50 Kate from Iowa
    June 11, 2010

    Thanks everyone who posted/directed me to those papers! I`ve got some reading to do, looks like!

  51. #51 jen
    June 11, 2010

    Prometheus: I find autism to be very consistent in its presentation, having worked with many children with autism. I can’t believe you would actually say otherwise. Do you know many children/adults with autism?

  52. #52 Chris
    June 11, 2010

    From his comments, I am very certain that Promethesus has much more experience with autism, along with biomedical issues than you, jen.

  53. #53 Kristen
    June 11, 2010

    Jen says:

    Prometheus: I find autism to be very consistent in its presentation, having worked with many children with autism. I can’t believe you would actually say otherwise. Do you know many children/adults with autism?

    This just shows your mentality. You don’t need to bother getting to know the individual once you know they have autism, then they are the same as every other autistic.

    I have never met another autistic child quite like my son. Many have similar behaviors, true, but they are different in cognitive ability, gross motor skills, fine motor skills, speech etc… Their autism presents in very different ways.

    IIRC Prometheus knows some autistic children and adults. I do know that his knowledge of ASDs is by far more profound then yours.

  54. #54 Chris
    June 11, 2010

    Exactly, Kristen. I have known many autistic children over the course of my son’s education… they are all very different from each other.

  55. #55 Autistic Lurker
    June 11, 2010

    Jen, you work with autistic childs? What are you doing exactly with them and what kind of training do you have? (that is a sincere question)

    My point is that you may have different perceptions of them as compared to a psychiatrist. I worked with a psychiatrist (who’s also the head of a research group doing research on autism and asperger) and he taught me some clinical knowledge such that asperger’s persons are more prone to mental illness such as depression and anxiety as compared to autistic peoples and such knowledge is not something which would get picked up by a teacher aid for example.

    A.L.

  56. #56 Autistic Lurker
    June 11, 2010

    Forgot to add that the psychiatrist I worked for and myself for the record, think that autism is a developmental disability and not a mental illness per se.

  57. #57 Dianne
    June 11, 2010

    if it’s so genetic (and I remember that the study said that no two people with autism would have the same genetic variations) AND considering the case of regressive autism (the child is developing normally and then, whammo, the parent says the kid suddently is anything but normal -and as someone who has worked in the field of early intervention I have no reason to disbelieve parents’ accounts) then what the hell is so genetic about it?

    You’re confusing genetic and congenital. Not all genetic illness shows at birth. Consider Tay-Sachs disease. A clearly 100% genetic illness with a known mutation which occurs in all people with TS…yet children born with this condition appear at birth to be perfectly normal but begin to regress in the first few months of life. Would you claim that it is really caused by vaccines because it presents with a “regressive” picture?

  58. #58 David N. Brown
    June 11, 2010

    “considering the case of regressive autism (the child is developing normally and then, whammo, the parent says the kid suddently is anything but normal -and as someone who has worked in the field of early intervention I have no reason to disbelieve parents’ accounts) then what the hell is so genetic about it?”
    Other commenters have already pointed out genetic disorders that don’t manifest until well after birth. I will nominate another: schizophrenia, which does not manifest symptoms until adolescence. Spreading the field to the nonhuman, I have heard of an amphibian species in which certain individuals appear to have a gene for cannibalism, but the behavior itself doesn’t start until the overall population becomes overcrowded. In short, the expression of genes is complex, and timing and environment are known variables.

    An additional thought: As you say yourself, manifestations of autism are reasonably consistent, including age of onset. The administration of vaccines, on the other hand, is highly variable with time and geography. For example, different health departments at different times have recommended the MMR vaccine before age 1 or after age 2. So, if vaccines are the main variable, why is there so little variation in when autism is diagnosed (and what differences there are explicable by improved diagnostic methods)? The only way to prop up vaccine causation is to say that a vaccine only causes autism when administered at a specific time.

  59. #59 a-non
    June 11, 2010

    Prometheus: I find autism to be very consistent in its presentation, having worked with many children with autism

    You say that, Jen, because it suits your position. Anyone with even a cursory knowledge of autism understands that the presentation varies widely. That’s why it’s called a freakin’ spectrum disorder.

    Just when I thought you couldn’t be any more intellectually dishonest, you go and raise the bar. Either that or you’re blindingly dumb.

  60. #60 David N. Brown
    June 11, 2010

    One more thought: I have long felt that certain features of autism (esp. “hand flapping”) would not be so unusual in earlier life, which is a reason I have reservations about autism diagnoses in the very young. This could be considered a behavioral parallel to peadomorphosis (where a sp. doesn’t metamorphose, but retains an ancestral subadult form throughout life). Another example of timing as a variable in gene expression.

  61. #61 Joseph
    June 11, 2010

    Lets say we scaled up a few more thousand people, or whatever number we want, it seems like we might find more specific CNVs, but I can’t figure out why we might expect to see a greater percentage of cases with the CNVs? And without that optimism, we still can’t explain very much of the heritability of autism, despite throwing thousands of genomes at supercomputers. Does this bug anyone else?

    Well, yes. It appears to be an intriguing and computationally non-trivial classification problem.

  62. #62 Chris
    June 11, 2010

    HCM is another genetic disorder that is not always present at birth. Though it sometimes does present itself in newborns, which is why my paternal grandparents’ first child died before she was a month old. My oldest son was found to have a heart murmur when he was fourteen years old during a well child checkup and a tetanus booster. He had a soccer practice after the echocardiology appointment, but I got a call just before I was going to take him there from the doctor telling me to not let him go (the echo technician called him after we left because she saw the anomaly!).

    My son’s only symptom was that he seemed to have trouble running. He was literally slowing down.

    My son’s cardiologist has told me that there is a possibility that my younger kids could develop HCM when they are old (like their 30s!), and that they should be screened again later even though both were cleared with echocardiograms after my oldest was diagnosed.

    Add HCM to the list of genetic diseases that do not show up until later.

    By the way, jen, how exactly do you know that what the parents say is accurate? How do you know that they did not remember correctly? The Cedillos claim their daughter was developing normally until a vaccine, but the videos shown in court indicate otherwise:

    They look at video of Michelle, Fombonne introduces his comments by noting that he is not meaning to say anything mean to the parents by pointing out the signs of autism in Michelle before the MMR. The videos show that before, even long before she received the MMR vaccine she was showing signs of autism, including not making eye contact, not responding to her name (even when adults called her name over and over), fixating on Sesame Street video to an unusual degree, flapping her hands and flicking her hands in front of her eyes. She’s not using normal baby gestures. Her babbling is unusual, and she never says any words in the videos, even though a normal baby might say words in the same situations shown on the videos. The parents of autistic children frequently use compensatory strategies to engage autistic children. Michelle’s parents are shown using these strategies to engage her.

  63. #63 mary podlesak
    June 11, 2010

    @Dianne,
    In answer to your question whether Tay Sachs could be caused by vaccines, I would give a tragic yes! As could be true of any number of “regressive” child hood illeness, including diabetes, muscular dystrophy, cerebral palsy, etc. The reason is because valid vaccine case control double blind studies using the unvaccinated or never vaccinated as controls have never been performed. Without such studies, there is an absence of evidence of the short and long term safety of vaccines. Solumn assertions of such safety based on medical authority cannot substitute for genuine study.

  64. #64 jen
    June 11, 2010

    I can’t believe that you guys are having to stoop so low as to paint me as some kind callous person who can’t see that everyone is indeed an individual, no matter their diagnosis. “Once you know they have autism they are the same as every autistic.” Nice try, Kristin. In the same way that I don’t think that everyone who has cancer is the same but they do all HAVE cancer,I think that people with autism SHARE alot of characteristics while of course being their own unique person. Funny that the DSM actually has a criteria for autism and that,oh my God,the children all share alot of characteristics,like,hmmn, let me see: impairment in reciprocal social interactions, repetitive attachment to objects, no or impaired imitation, no or abnormal social play, no mode of communication or spoken language, marked abnormalities in speech, stereotyped body movements, restricted range of interests, to name a few. If you don’t agree you should let the good folks at the DSM know that they are wasting their time lumping these people all together as they are. Seriously, get a fucking grip. As I said before, look at the funny BP video up on this site and see yourselves when it comes to autism research. I’m outta here; tonight it’s a waste of my time.

  65. #65 Shay
    June 11, 2010

    Jen, I don’t think they are painting you as callous. I think they are painting you as stupid.

  66. #66 Chris
    June 12, 2010

    Ms. Podlesak:

    The reason is because valid vaccine case control double blind studies using the unvaccinated or never vaccinated as controls have never been performed.

    You don’t seem to be bothered by ethics, are you?

    Do you think that my grandparents’ first child developed HCM in the early 1920s because of a vaccine? Or that a condition first described in 1860, cerebral palsy, is caused by a vaccine? Did you even understand what Orac wrote? Would it help if you read this description?

    Someone has proposed a study, all he needs is someone to pay for it: Let’s Put on on Study!

    Perhaps you and friends can pony up the cash.

  67. #67 Damien
    June 12, 2010

    @Shay, I don’t think it’s a painting. A painting is just a rendering of reality.

    However, jen, I don’t think you’re stupid, nor do I think you’re callous, nor do I think you’re maliciously pursuing this anti-vaccine agenda as some weird, tortuous form of population control; I think you are far, far out of your depth and instead of admitting it and staying out the conversation, you’ve elected to Dunning-Kruger it up.

    There’s a saying on many internet message boards, which I’m going to adapt to this instance: scientific evidence or GTFO.

  68. #68 Claire
    June 12, 2010

    Well, GTFO probably applies to me too. But can I ask a naive question? My daughter has quite severe anoxic brain damage – and many of her behaviours are “autistic”. Do I assume a genetic component as well?

  69. #69 David N. Brown
    June 12, 2010

    Jen et al,
    This should be quite simple to explain:
    Children were displaying behaviors consistent with autism before MMR, thimerosal or any other scapegoat of choice existed.

    Diagnoses of autism are made at the same or similar ages regardless of if or when they receive a vaccine.

    Some children are diagnosed with autism, whether or not they are vaccinated.

    A SURVEY BY GENERATION RESCUE SHOWS THAT A SAMPLE OF WHOLLY UNVACCINATED CHILDREN HAVE A “NORMAL” CA. 1-2% AUTISM RATE.

    Whether or not you are willing to accept this as evidence of NO vaccine causation, you ought to be able to appreciate just how pointless it will seem to anyone else to invest more time and research on this “issue”.

  70. #70 Kristen
    June 12, 2010

    Jen says:

    Prometheus: I find autism to be very consistent in its presentation, having worked with many children with autism. I can’t believe you would actually say otherwise. Do you know many children/adults with autism?

    This just shows your mentality. You don’t need to bother getting to know the individual once you know they have autism, then they are the same as every other autistic.

    I have never met another autistic child quite like my son. Many have similar behaviors, true, but they are different in cognitive ability, gross motor skills, fine motor skills, speech etc… Their autism presents in very different ways.

    IIRC Prometheus knows some autistic children and adults. I do know that his knowledge of ASDs is by far more profound then yours.

  71. #71 bensmyson
    June 12, 2010

    The biggest problem I have with all these breakthroughs linking autism to genetics is why wouldnt the numbers be higher. I mean if a specific gene or a group of mutated genes are responsible for causing autism then why arent they found in 100% of those with autism?

    And got me thinking about abortion.

    Are doctors 100% certain that they can predict a baby being born with a serious or untreatable health problem from a prenatal test that diagnoses the genetic material? Is or can there be a significant margin of error in some of these screening tests?

  72. #72 DLC
    June 12, 2010

    an interesting study.
    My general sense is that we’re approaching a conclusion that autism is in some cases genetic and in others still a mystery.
    however — for the person who bleated that Tay sachs might be caused by vaccines — please go read the bloody literature before making such an idiotic pronouncement!
    Tay sachs has been studied extensively, and has been fairly conclusively shown to be a genetic disorder. Good googly moogly, go freakin at least read the blasted wikipedia article!

  73. #73 Kristen
    June 12, 2010

    Okay, I don’t know why my comment from last night posted again, sorry.

    Claire,

    I don’t have a formal education, either. They are referring to persons who come here and keep spouting the same nonsense without considering any evidence contrary to their understanding.

    You might find this article interesting. I just found it on a google search, but it is by a reputable (IMO) author and is well referenced. In part it says:

    Many studies have repeatedly confirmed an increased risk of autism correlated with certain types of pre- and perinatal complications, such as low birth weight, differences in gestational duration, intrapartum hypoxia, increased infant distress, and so on.

    Has your child been diagnosed with autism? My heart goes out to you, caring for special needs children is such a difficult job.

  74. #74 Dianne
    June 12, 2010

    In answer to your question whether Tay Sachs could be caused by vaccines, I would give a tragic yes!

    FSM, that’s wrong on so many levels it’s hard to know where to start.

    Tay Sachs is caused by a single gene mutation that is autosomal recessive. All people with 2 copies of the mutant gene will develop TSD, no one without two mutant copies will develop it. It was first described in the 19th century long before routine vaccination. There is no correlation with vaccines, cell phones, or being cursed by your neighbor involved. It’s strictly genetic.

  75. #75 Dianne
    June 12, 2010

    In the same way that I don’t think that everyone who has cancer is the same but they do all HAVE cancer,I think that people with autism SHARE alot of characteristics while of course being their own unique person.

    Interesting analogy. Cancer’s not a single disease and treating it as such invites disaster. Perhaps one could say the same of autism.

  76. #76 JKW
    June 12, 2010

    A question was posed as to the genome coverage. Here’s the array used:
    http://www.illumina.com/products/human1m_duo_dna_analysis_beadchip_kits.ilmn

    It would be quite unlikely to “find” a single CNV being trustworthy after the MTC (Bonferroni) when looking at the ensemble of samples as long as it was significant and trustworthy in only a couple of samples. However further analysis of individuals would pick it up if it passed the stringency filters placed by the analyst.

  77. #77 jen
    June 12, 2010

    Kristen: it’s THAN yours (73). Sorry, couldn’t resist. Yes, I’m sure your son has none of the characteristics listed per post # 64. By the way, your list of pre and peri-natal complications being associated with autism could easily be answered by adding vaccines into that mix of vulnerabilities(i.e. giving vaccines to premies could equal trouble). I know you will reject that possibility, though.

  78. #78 dedicated lurker
    June 12, 2010

    benismyson – There are a lot of genetic conditions that can be screened for with amniocentesis or chorionic villi sampling. The most common ones are routinely screened, but a bunch of other conditions are only screened for with family history. And all these conditions are one hundred percent genetic; while false positives are possible if the screen is correct then the fetus does in fact have that condition.

  79. #79 bensmyson
    June 12, 2010

    Wondering how many false positives have resulted in unnecessary abortions. Considering that something like 10% (or is it less, there was something about 1%) of those with this identified CNV have autism it would hardly be something to say with certainty that a newborn or preterm baby is destined to a life of autism.

  80. #80 mary podlesak
    June 12, 2010

    @Diane, I don’t need to go to Wikipedia to look up the chromosonal genetic view of Tay Sachs. I have “The Principles of Genetics” in my home library. It’s an older edition and I know by current research standards terribly out of date, nevertheless, even if I know ALL of the particulars of the current genetic understanding of Tay Sachs I still maintain that Tay Sachs is caused by vaccination not by genes alone. As with autism, it is enivironmentally triggered only in those with a genetic predisposition. Vaccines are well over 200 years old now. The smallpox vaccine was notorious for have immediate catastrophic side effects, including death and smallpox itself. Is it so far fetched to believe that it might also have had long term adverse effects, including, immunnological, hemotological and neurological? Vaccines are injected directly into the tissues of the body. They are expected to provoke an immune reaction. What is to stop them from penetrating the blood-brain barrier?
    I am a hertic from the religion of medicine. A dissenter of Luther might say, not by faith alone are we saved but also by our works in union with the saving action of Jesus. As a medical heretic, I also assert that genes alone cannot account for the changes in human neurology, hemotology, immunology end endrocranology observed increasingly in this modern era. More is at work than genes, food sources or other enivornmental toxins alone. Only something injected into the blood could account for all of these new diseases.

  81. #81 Dianne
    June 12, 2010

    Mary: For Tay Sachs to have a non-genetic component you’d have to have at a minimum examples of people with both genes who did not develop the disease. Have you ever heard of someone with the genetic syndrome who did not develop the clinical syndrome?

    Additionally, if the smallpox vaccine-your desperation example of a vaccination used prior to the 20th century-was responsible for TSD then you’d have to demonstrate that it was administered to people who developed TSD and not those who did not. TSD occurs in the Jewish population and in a few places in Canada and Louisiana primarily. Do you have any evidence that any of those populations vaccinated for small pox more often than other populations?

    What is to stop them from penetrating the blood-brain barrier?

    The purpose of the blood brain barrier is to stop proteins that shouldn’t be getting into the brain from getting into the brain. There is no way that the BBB even knows whether the protein or other substance got there by direct injection into the blood, injection into the subcutaneous or intramuscular tissue, or via the oral route. Or any other method.

    I also assert that genes alone cannot account for the changes in human neurology, hem[a]tology, immunology end endrocr[i]nology observed increasingly in this modern era.

    What specific changes are you talking about? What is your hypothesis for a mechanism of action?

    Only something injected into the blood could account for all of these new diseases.

    If this is true then vaccinations are definitely not to blame: Vaccines are injected subcutaneously, intramuscularly, orally, or intranasally. I can’t think of any that are injected IV.

  82. #82 Jarred C
    June 12, 2010

    Dianne,

    For Tay Sachs to have a non-genetic component you’d have to have at a minimum examples of people with both genes who did not develop the disease. Have you ever heard of someone with the genetic syndrome who did not develop the clinical syndrome?

    To be fair, how would anyone know? Isn’t testing voluntary and not conducted on a regular basis? Then again, if that hypothesis is correct, a large enough sample of the population tested should show evidence of someone with the genetic syndrome who did not develop the clinical syndrome. I’m just speculating, here.

  83. #83 Pablo
    June 12, 2010
    Only something injected into the blood could account for all of these new diseases.

    If this is true then vaccinations are definitely not to blame: Vaccines are injected subcutaneously, intramuscularly, orally, or intranasally. I can’t think of any that are injected IV.

    Awesome pwnage.

    It’s great when the clueless are hoisted by their own ignorant petards.

  84. #84 MI Dawn
    June 12, 2010

    @Dianne: you may as well ignore Mary. She is a hard-core antivax denier, who has her fingers so far in her ears that she can’t even hear herself singing “La, La, La…”

    However, your points are very nice and clear for someone to read who is open to information and wants to learn the truth.

  85. #85 Dianne
    June 12, 2010

    To be fair, how would anyone know? Isn’t testing voluntary and not conducted on a regular basis?

    Technically, you’re correct, but it seems rather improbable. People with sibs who have TSD or are in high risk groups frequently get tested. Not to mention that there have been multiple genetic studies of families in which the disease runs. If there were an environmental component one would expect that at an example of a person with both genes mutated without TSD would show up at least once. And conversely that some child with the classic TS syndrome would show up some time somewhere without the gene (and virtually all kids with TSD do get genetic testing to confirm the diagnosis.)

  86. #86 T. Bruce McNeely
    June 12, 2010

    mary podlesak:

    Go be crazy someplace else.

  87. #87 Chris
    June 12, 2010

    Even over twenty years ago there was a couple in the class the hospital had for new parents before birth that had done genetic testing due to something that ran in their families (I forgot what it was, but it mostly affected boys).

    Next thing Ms. Podlesak will blame on vaccines is Huntington’s disease. She may even start blaming the side effects of the actual diseases like encephalopathy and meningitis on vaccines (even if the child never had the vaccine!).

  88. #88 T. Bruce McNeely
    June 12, 2010

    Only something injected into the blood could account for all of these new diseases.

    Tay-Sachs – first recognized in 1887
    Cerebral Palsy – first described in 1860
    Muscular Dystrophy – first described in 1860
    Diabetes Mellitus – first described in the 6th Century BCE

    New diseases, eh?

  89. #89 Chris
    June 12, 2010

    If you are having a boring weekend you can catch up on the craziness of Ms. Podlesak from a few months ago here and here. Classic Podlesak is her demanding to know everyone’s identity before revealing any actual evidence she claimed to have.

    Now that I have finished downloading the Skeptic’s Zone, the Skeptic’s Guide to the Universe, and some other podcasts I am now going to go finish cleaning out the garage (which really should be done every ten years or so). It is finally time to get ride of the bike trailer used to transport kids, since the youngest is now sixteen years old!

  90. #90 Diane-with-one-N
    June 12, 2010

    @Chris, just finished listening to SGU while weeding in the (finally) sunny morning. I keep the kid’s bike trailer thinking that maybe someday I can use it for bike touring, even though it would be tougher to pull than those new gear-only trailers. So it continues to gather dust in the garage…

  91. #91 Nick
    June 12, 2010

    After reading Chris’ complied history of Mary’s illustrious career as science-blogs poster, I would recommend that everyone just leave her alone and try to ignore her posts. She doesn’t need further provocation. She isn’t a conscious charlatan like Jay Gordon, Andrew Wakefield, Blaxill or Handley- but rather a mentally ill individual taking her anger out on blogs.

    Mary’s delusions of grandeur, paranoia (government officials are trying to getting her for antivax views) and violent threats (constant refers to nuclear war against the pharma companies, beating up her pharma-related opposition on the streets)- are signs of a profoundly disrupted individual. It really has all the tall-tale signs of schizophrenia and reminds me of some of my old clients on their bad days without medication. I would just recommend to Mary that she find a good physician and/or therapist. It can be resolved in this day and age.

  92. #92 realinterrobang
    June 12, 2010

    There are a lot of communities (Orthodox Jewish ones) where pretty well everyone undergoes screening for Tay-Sachs; you’d think that if such a thing were possible, they would have found a TS+ person who didn’t have the disease by now.

    As far as I’m concerned, you might as well say that Judaism is caused by vaccines. And that same-sex marriage causes Islam.

    I was showing signs of cerebral palsy long before I ever got any vaccines; it wasn’t habitual to vaccinate neonates back then.

  93. #93 Nick
    June 12, 2010

    Besides SGU are there any other good science/skeptical podcasts? I listen to QuackCast, SGU, and Dr. Dean Edell- but otherwise haven’t been able unearth a great amount of other worthwhile skeptical podcasts. Skepticality seems popular, but I find it pretty shallow.

    Anyone have some recommendations?

  94. #94 Toxicology Kat
    June 12, 2010

    Could the PhDs on this list confirm that I understand the original article correctly:

    There is a wide variety of genetic changes found in people with autism, but these different genes have one major thing in common: they affect the way neurons grow and connect in the brain. This is possible because there are so many steps in brain development that affecting different parts of these pathways can cause similar results. Or, they can cause problems at slightly different times during brain development when different parts of the brain are growing. That’s how autism can affect different people differently.

  95. #95 Chris
    June 12, 2010

    Nick, try one of these:
    http://forums.randi.org/forumdisplay.php?f=72 … on that list I enjoy Skeptoid, The Skeptic Zone (which I am listening to) and the SETI’s “Are We Alone?” radio broadcast.

    Not on that list is the radio show out of the University of Alberta: http://skepticallyspeaking.com/

    I am at my link limit, but I have recently found some fun podcasts from the UK (so use these words to Google): Righteous Indignation, The Pod Delusion, and the Merseyside Skeptics Society’s “Skeptics with a K”, plus their skeptical game show, InKredulous.

    Also, there are NPR’s “Science Friday” and “Wait, Wait! Don’t Tell Me!” shows. Along the science theme there is also Scientific American’s short podcasts (and occasionally longer ones), Dr. Mark Crislip’s “A Gobbet ‘o Pus”, the Nature podcast and “The Naked Scientist.”

    I have also recently found “The Conspiracy Skeptic” by Karl Mamer.

    Those should keep you busy for a while.

  96. #96 mary podlesak
    June 12, 2010

    It is absurd to blame Jews or anyone for diseases “caused” by genes without first performing long term double blind case control studies using the unvaccinated or never vaccinated as controls. Children with Tay Sachs genes could be divided into two groups, the vaccinated and the never vaccinated, then observed for Tay Sachs symptoms. To suggest that gene testing could have been done in the 19th century to ascertain whether vaccination or something else was the source of Tay Sachs is beyond ridicule.

  97. #97 Joseph
    June 12, 2010

    Funny that the DSM actually has a criteria for autism and that,oh my God,the children all share alot of characteristics,like,hmmn, let me see: impairment in reciprocal social interactions, repetitive attachment to objects, no or impaired imitation, no or abnormal social play, no mode of communication or spoken language, marked abnormalities in speech, stereotyped body movements, restricted range of interests, to name a few. If you don’t agree you should let the good folks at the DSM know that they are wasting their time lumping these people all together as they are. Seriously, get a fucking grip.

    It’s not as simple as Jen seems to think it is. If it were, creating a screening tool for autism would be trivial. You would only need a few questions. As things stand, you need to ask dozens of questions to screen someone for autism, and in the end a good instrument might have 80% or 90% accuracy.

  98. #98 David N. Brown
    June 12, 2010

    @80: “The smallpox vaccine was notorious for have immediate catastrophic side effects, including death and smallpox itself. ”
    Keywords: “Immediate” and “catastrophic”, not “delayed” and/or “subtle”. In my view, any claim of vaccine injury manifested more than a week after vaccination isn’t worth discussing.

    As for TS, you have one plausible point: Even if 100% of cases have the defective gene (in duplicate), it’s still at least conceivable that some with the gene dominant don’t develop the condition. If examples were to be found, one would need look no farther than immediate family of known cases. But, there’s no justification for describing it as “environmentally triggered” without this evidence in hand. Furthermore, if a single “trigger” were responsible (NOT a given), it would NOT be a vaccine, because no one vaccine has been used continuously and without modification since the late 1800s.

  99. #99 Archangl508
    June 12, 2010

    Ms. (or Mrs.) Podlesak,

    So let me get this straight. What you are suggesting is that an individual with 2 recessive copies of the gene for acetylhexosaminidase A that results in the production of a protein unable to breakdown gangliosides in the brain will somehow produce the proper functional protein up until they are vaccinated? Do you have any idea how much that defies what is understood about biochemistry and molecular biology?

    But who needs biochemistry when you’ve got irrational beliefs, right?

  100. #100 Matthew Cline
    June 12, 2010

    @Mary Podlesak:

    The smallpox vaccine was notorious for have immediate catastrophic side effects, including death and smallpox itself.

    If someone got smallpox itself from an immunological treatment, then that was variolation, the practice of intentionally infecting someone with the least virulent strain of smallpox. What most people think of smallpox vaccination was intentionally infecting someone with the cowpox virus. Cowpox can cause serious symptoms (which is why the general population isn’t being vaccinated against the possibility of a terrorist smallpox attack), but cowpox doesn’t cause smallpox.

    Only something injected into the blood could account for all of these new diseases.

    Variolation wasn’t done via injections, and when the cowpox treatment was started it wasn’t done via injections either. I don’t know all of the methods used for variolation, but one of them was to inhale dried and ground up smallpox pustules. The cowpox treatment was originally done by giving someone a scratch and putting a bit of cowpox pus onto it.

  101. #101 JustaTech
    June 12, 2010

    @Matthew Cline: actually, smallpox vaccination is still sub-cutaneous, rather than intra-muscular. It’s rather like being attacked with a very small pitchfork.

  102. #102 Johnq
    June 12, 2010

    Guys, Mary Podlesak is a grade-A lunatic. There’s no point in debating her, since her views are considerably crazier than vaccination denial or even 9/11 Truthiness, for that matter.

    Last month she posted a comment on a website called “The Flu Case:” [http://theflucase.com/index.php?option=com_content&view=article&id=3378%3Apolish-health-minister-testifies-against-swine-flu-jabs-half-polish-government-wiped-out-in-plane-crash-days-later&catid=41%3Ahighlighted-news&Itemid=105&lang=en]

    The blog post she commented on posited that the tragic plane crash in Smolensk that wiped out much of the Polish government was actually an act of mass murder designed to clear the way for flu vaccination in Poland. No, seriously. Follow the link if you don’t believe me. And while you’re at it, take a look at the rest of the site, which is premised on the belief that an international conspiracy intends to commit genocide by engineering a global pandemic and then forcibly vaccinating the entire human race with poison.

    Mary’s comment follows:

    “Russia was never specifically consecrated to the Immaculate Heart of Mary by the Holy Father in union with the world’s bishops as pleaded for by Our Lady of Fatima…isn’t the resulting evil of this negligence obvious? I’m in no position to judge any Holy Father or his actions, but the “downfall” of the Soviet Union did not by itself bring about peace, harmony and moral reform of communists. The deceptions and obfuscations surrounding the Smolensk events testifies to the Russians’ moral vacuity. Marek Podlecki, unfortunately, will have many other tragic events and funerals to cover in the future.”

    It seems our Mary believes that pro-vaccination forces murdered the Polish government, and that this resulted, in some way, from Russia’s failure to follow the dictates of Our Lady of Fatima.

    There’s no point in arguing with this person. She’s a nut. Taking her seriously makes about as much sense as trying to have a meaningful conversation with the guy who’s screaming on the downtown street corner about how the Freemasons are responsible for everything wrong in his life. I suppose you could ask him for detailed citations supporting the proposition, but actually expecting a rational response from someone like that is, well, irrational.

    Orac would be well within his rights to ban her, since she’s both crazy and abusive. If he chooses instead to allow complete freedom of expression, my advice is to stop responding to her as if she’s sane, and instead simply note that she’s crazy, with the above link as evidence. That way you all can stop spending time arguing with a lunatic, while making sure that no rational person will give her screeds any credibility at all.

    Plus, this will probably drive her even further around the bend than she already is. I’m thinking she’s now going to tell us that Orac killed the Polish government. Or maybe I did.

  103. #103 Johnq
    June 12, 2010

    Another entry in Mary’s scrapbook of insanity: http://theflucase.com/index.php?option=com_content&view=article&id=3375%3Apolish-elite-diverted-to-another-smolensk-airport-and-abducted-argues-gerhard-wisnewski&catid=1%3Alatest-news&Itemid=64&lang=en

    In this one, she’s commenting on another blog entry in The Flu Case. This entry somewhat contradicts the one I posted to earlier, in that this one alleges that the Polish government ministers weren’t killed, but were instead kidnapped by the Russians, with the plane crash staged to cover up the kidnapping. All of this, again, in the service of clearing the way for flu vaccinations.

    Mary’s comment:

    “OK, now where is Lech K? …in one of the “closed” Soviet gulags?”

    I wish I could say this was ironic, but unfortunately it’s pretty clear that our Mary takes the premise seriously, and really wants to know where the forces of genocidal vaccine banditry are holding the Polish government.

    I suppose I could demand to see her evidence for this somewhat dubious proposition, but I suspect she’d merely demand to debate me in person. Possibly with nuclear weapons.

  104. #104 Agent Smith
    June 12, 2010

    Message: By nearly every measure, Mary is a nutter. She needs help, not ridicule. I recommend sectioning her.

    Encrypted Message: Fellow pharma-shrills and corporate sycophants, I have been sent by the american government (or New World Order via the Protocols of Zion) to track down one Mary Podlesak. Her anti-vaccine views have become so influential on public opinion that many parents all around the country have become suspicious of our program to pollute american’s precious bodily fluids (or PBFs). She also seems on the verge of uncovering our plot to kidnap the leadership of the polish government in order to institute a special vaccine program in Poland. Their government was on the verge of rejecting the very profitable pharma package we had offered. Unacceptable. We cannot let Mary interrupt our program to thrust our hand into the past and annihilate the existence of autism. Remember our slogan! “Who controls the present controls the past”

    I will be in contact with Agent Orac to gain more information about Mary and her connection’s IP address. We need to “convince” Mary with the best devices science-based medicine has to offer that Big Brother has her best interests at heart.

    War is peace
    Freedom is slavery
    Ignorance is strength,
    etc

    !Agent Smith of Thought Police Unit Alpha signing out of this terminal!

  105. #105 raven
    June 12, 2010

    Funny that the DSM actually has a criteria for autism and that,oh my God,the children all share alot of characteristics,like,hmmn, let me see: impairment in reciprocal social interactions, repetitive attachment to objects, no or impaired imitation, no or abnormal social play, no mode of communication or spoken language,
    and
    marked abnormalities in speech, stereotyped body movements, restricted range of interests, to name a few. If you don’t agree you should let the good folks at the DSM know that they are wasting their time lumping these people all together as they are. Seriously, get a fucking grip.

    Whoever wrote that is either lying or stupid or both. How could a patient have “no spoken language” and also “marked abnormalities in speech”. You can’t be nonverbal and also show abnormal speech patterns.

    The DSM criteria are the most common symptoms one would see in severe autism and the patients will have various combinations of them. None will have all. It is called autism spectrum disorders because there is a huge range of variation. Some will never be able to take care of themselves while Aspies may end up tenured full professors in science departments.

    Sign of a crackpot. When they get cornered, they start making stuff up. I dealt once with AIDS denialists. It didn’t take too long to discover they would do things like make up quotes from a paper that weren’t actually in the paper. It is almost impossible to turn a crank, waste of time.

  106. #106 raven
    June 12, 2010

    crosspost from pharyngula:

    Although ASDs are known to be highly heritable (~90%), the underlying genetic determinants are still largely unknown.

    Fri, Oct 9 2009More kids have autism than thought: U.S. study Mon, Oct 5 2009NEW YORK (Reuters Health) –
    When one identical twin develops the developmental disorder autism, the risk of the other developing it is high — substantially higher than it is for fraternal twins, a new study confirms.

    Health

    The study, which gathered information from 277 twin pairs in which at least one had an autistic disorder, found that when one identical twin developed an autistic disorder, the other one also did 88 percent of the time.

    That compared with 31 percent among fraternal twins. Unlike identical twins, fraternal twins are no more genetically similar than non-twin siblings.

    What’s more, researchers found, identical twins also had greater similarities in the form of autism that they developed, their level of day-to-day functioning and the risk of intellectual impairment.

    The findings, reported in the Archives of Pediatrics & Adolescent Medicine, confirm the importance of genes in autism development.

    It’s been known for some time that autism has a high genetic component. 90% is extraordinarily high for something as complicated as a mental disorder. IIRC, SZ which is the classical inherited illness has an identical twin concordance of ca. 50%.

    Clearly there are other factors because the concordance isn’t 100%. Could be epigenetic, developmental, or environmental. It could also be a stochastic phenomenon, a matter of chance, the term for that is penetrance of a trait. These can’t be the major determinants though.

    The antivaxxers could learn this with 5 minutes on google. In fact they have probably had it shoved in their face many times. They do what all crackpots do, put their fingers in their ears and sing La La La, I can’t hear anything.

  107. #107 Allie
    June 12, 2010

    Agent Smith @ 104–you, sir, win the internet!

  108. #108 Matthew Cline
    June 12, 2010

    There’s no point in debating her, since her views are considerably crazier than vaccination denial or even 9/11 Truthiness, for that matter.

    Some of the arguments she makes (like the smallpox vaccine actually causing smallpox) are arguments that other anti-vaxxers make, so I’ll just ignore the source of the arguments and pay attention to content. Additionally, she herself has said that she won’t put forward her arguments unless she knows exactly who she’s debating with, so I think I’m not going to go down that route.

    Of course, if she starts arguing in this blog that vaccines are a plot by the shapeshifting reptilian aliens, then I’ll start ignoring her.

  109. #109 Militant Agnostic
    June 12, 2010

    Matthew Cline on Mary Podlesak

    Of course, if she starts arguing in this blog that vaccines are a plot by the shapeshifting reptilian aliens, then I’ll start ignoring her.

    In other words if she indicates she has discovered the truth, then you will be afraid to debate her.

  110. #110 Dianne
    June 12, 2010

    In other words if she indicates she has discovered the truth, then you will be afraid to debate her.

    Nonsense. Our pharma overlords are squid-like cthuloid creatures. The lizard people are responsible for the trilateral commission. Keep it straight.

  111. #111 Matthew Cline
    June 12, 2010

    Our pharma overlords are squid-like cthuloid creatures.

    Ph’nglui mglw’nafh Big Pharma R’lyeh wgah’nagl fhtagn.

  112. #112 sarkeizen
    June 13, 2010

    I’m kind of interested in Jens comments.

    “yeah, but if it’s so genetic (and I remember that the study said that no two people with autism would have the same genetic variations)”

    How then do you explain (using vaccines) the rather large difference in occurrence in autism between MZ and DZ twins? Even if we assume that vaccines are some kind of co-factor (which I figure you are implying or will eventually get boxed into asserting – but are somehow blind to the logical problem there) and considering that the majority of the population are vaccinated to some extent. Then you’re going to have to assume that the correlation is accidental. Which while possible is sticking to the least probable of the two theories. Can you clarify why you are doing that?

    “considering the case of regressive autism (the child is developing normally”

    As others have made the case, we already have pretty copious evidence for regressive diseases that are well understood to be genetic (i.e. strongly correlated to genes). Your only choices here are either to retreat to a position that diseases like Tay-Sachs also have vaccines as a co-factor or give up the argument that a regressive disease is evidence of a disease being something other than genetic. I’d really like to hear which you picked (especially since the first choice is impossible to defend since there have been studies on mouse models of Tay-Sachs)

    “then, whammo, the parent says the kid suddently is anything but normal -and as someone who has worked in the field of early intervention I have no reason to disbelieve parents’ accounts”

    Do you have any reason to believe them? I mean are the parents experts in child development? In fact the very statement “X was developing normally” doesn’t sound very much like a parent from my small samples. Parents, again in my experience seem to focus on all sorts of statistically insignificant things (above average and below) about their child.

    “In the same way that I don’t think that everyone who has cancer is the same but they do all HAVE cancer”

    As I’m sure everyone else has pointed out. This is also an error. Treating cancer like it’s a single disease is ridiculous. Especially since you were originally referring to how autism *presents*. For example if you were to add up the symptoms in common between colon cancer and lung cancer you would find few in common. Not only that but there are a good half dozen differentials for the colon cancer symptoms.

    “impairment in reciprocal social interactions, repetitive attachment to objects, no or impaired imitation, no or abnormal social play, no mode of communication or spoken language, marked abnormalities in speech, stereotyped body movements, restricted range of interests, to name a few.”

    Right but you seemed to be saying that they present in a consistent way. Assuming that the DSM IV criteria is complete (which is probably isn’t) it states that you need two from (A) features and one each from (B) and (C). Under those definitions alone there are ninety-six possible unique presentations….and that’s assuming *blammo* these all happen or get noticed at once. If you assume that what you and these parents are seeing are any partial set of those symptoms then the total number of possible presentations are in the several hundreds.

    So this isn’t about characterizing you as someone who is failing to understand the uniqueness of *people* but rather someone who is failing to understand the uniqueness of a presentation.

    “If you don’t agree you should let the good folks at the DSM know that they are wasting their time lumping these people all together as they are.”

    This just seems like you getting it for a poor use of language on your part. If someone said to be that all “molerats” are similar but there were about a hundred different sets of characteristics by which something could be called a “molerat” I probably hesitate to call them similar.

    “see yourselves when it comes to autism research.”

    Just a question…exactly what piece of autism research have you referenced in this thread? The only thing I’ve seen you do is give your opinion as to how a regressive disease can’t be genetic, how autism presents similarly and how parental evaluations of autism symptoms should be trusted implicitly. Am I missing anything? How is any of this research? And if none of it is…doesn’t your criticism apply to you as well?

  113. #113 David N. Brown
    June 13, 2010

    “This entry somewhat contradicts the one I posted to earlier, in that this one alleges that the Polish government ministers weren’t killed, but were instead kidnapped by the Russians, with the plane crash staged to cover up the kidnapping. ”

    This is the same site was where it was first claimed that Poul Thorsen “vanished in March 2009″, even though he held three positions, had two listed addresses and published twenty papers after that time. I am satisfied that this was after the author Burgemeister posted the claim that K Madsen was “missing” and a forgery suspect (making the then-unverifiable claim that Thorsen was a suspect seem all the more dubious). In short, Burgemeister has a penchant for reporting mysteries where there are none.

  114. #114 Gil
    June 13, 2010

    The new “V” series is preparing us for the real life power change to our new leaders and I, for one, welcome our new reptilian overlords.

  115. #115 David N. Brown
    June 13, 2010

    @108:
    “if she starts arguing in this blog that vaccines are a plot by the shapeshifting reptilian aliens, then I’ll start ignoring her.”
    If she’s a fan of Burgemeister’s, she’s already close to that source: In investigating Burgemeister’s possible associates, I discovered a “recommendation” of her work by David Icke.
    Note to AoA et al: Use Burgemeister as a source again, and you will be viciously mocked.

  116. #116 Cracking up Here
    June 13, 2010

    You guys crack me up. Are you unable to hold more than one competing thought in your head at once? For example, let’s go on the theory that autism is in fact a “genetic disease” (genetic at it’s roots). Ok super. Who’s to say that children with a “genetic” background for autism… (again going with the theory) are perhaps more prone to environmental assaults than the non-autistic population? Where am I losing you? I’m not saying that this IS the answer but you guys act as if this genetic study actually means something for your side… Ah, newsflash… It doesn’t.

  117. #117 Dianne
    June 13, 2010

    Who’s to say that children with a “genetic” background for autism… (again going with the theory) are perhaps more prone to environmental assaults than the non-autistic population?

    Fair enough. There is that 10% discordance between monozygous twins to explain. What environmental trigger are you postulating? What is the evidence that it is that trigger versus anything else? What do you propose as a way to study the hypothesis?

  118. #118 raven
    June 13, 2010

    Who’s to say that children with a “genetic” background for autism… (again going with the theory) are perhaps more prone to environmental assaults than the non-autistic population? Where am I losing you? I’m not saying that this IS the answer but you guys act as if this genetic study actually means something for your side… Ah, newsflash… It doesn’t.

    Clearly you are not a scientist or even a coherent thinker.

    Who is to say that autism isn’t a genetic disease triggered by Reptiloid aliens with Dark Matter rays?

    Perhaps it is triggered by television or rock music or food cooked on electric stoves?

    It could be children with a genetic predisposition to Demonic possession followed by an invasion of demons, a popular and biblical based theory 2,000 years ago and still in vogue today in much of the USA.

    There is a crucial difference between wild ass guesses, delusions, fantasies, and scientific theories. DATA!!! Without data, you’ve got nothing. You have nothing reasonable.

    The twin concordance is extraordinarily high for a mental disorder. In fact, I’m not aware of any other mental disorder with anything approaching 90%. That 10% difference is cause unknown right now. It could be an environmental influence. Or it could be epigenetic differences. Or developmental differences.

    Most likely it is stochastic, a matter of chance. The developing brain isn’t put together like a car. Neurons are sprouting, migrating, making connections, undergoing apoptosis following general developmental rules such that it is rule based, guided chaos. This is called differential penetrance of a trait. It is common with many traits in all organisms that the same genotype doesn’t give exactly the same phenotype. It isn’t usually known why.

    The classic genetic mental disorder is schizophrenia. Here the twin concordance is only 50%. We don’t know why. And like autism, it has a delayed expression. Kids are fine until 14 to 20′s. Then wham, their thinking goes haywire. It is quite common for genetic diseases to show delayed onset, Wilson’s disease, Gauchers, schizophrenia, autism. A very common one, hematochromatosis often shows up in people in their 40′s, early onset Alzheimers, heart disease risk factors even later.

    What we do know is that autism has nothing to do with mercury in vaccines or vaccines themselves. That is what the data says. Mercury was taken out of vaccines years ago. It made no difference. Scientists have looked at the data for a link between vaccines and autism. There is none.

  119. #119 Cracking up Here
    June 13, 2010

    “Who is to say that autism isn’t a genetic disease triggered by Reptiloid aliens with Dark Matter rays?

    Perhaps it is triggered by television or rock music or food cooked on electric stoves?”

    Is this really your response? I have to give you a standing LOL! on that one. First of all, we know that there is a basis to assume that environmental toxins (vaccines or not) cause problems for many people. Lead poisoning, mercury from fish, etc. etc… Now, of course we also know that vaccines can trigger seizures in children and on those rare occasions, children are permanently injured by vaccines… So, to start off spouting nonsense about television, rock music, etc. etc… is just MORONIC… yet par for the course….

  120. #120 jen
    June 13, 2010

    More evidence for a genetic basis for autism? More like more try. The try is very desperate. Wow, so this study had 176 authors and did not disclose competing interests. I am embarrassed that this has come from Canada. I must confess that I am not a genetics specialist, however, the bottom line here is that if, as one of the 176 authors say, you couldn’t find any two persons with autism with the same genetic pattern, then it really isn’t heritable (other than maybe in the 10% of cases that has been previously found). THis study bolsters that finding and nothing more. Nothing new. End of story.

  121. #121 raven
    June 13, 2010

    crackpot here:

    Is this really your response? I have to give you a standing LOL!

    No. I said, “Mercury was taken out of vaccines years ago. It made no difference.” That is DATA.

    Here is some more DATA from the abstract below looking at 537,303 children and vaccines. There was no association between age at vaccination, time since vaccination or calendar period at time of vaccination and development of autistic disorder.

    crackpot up:

    First of all, we know that there is a basis to assume that environmental toxins (vaccines or not) cause problems for many people. Lead poisoning, mercury from fish, etc. etc..

    This is just words strung together and makes no sense. We know that lead causes…lead poisoning. Not autism. Same thing for mercury poisoning. Where is your data that lead,or mercury causes autism? There isn’t any. In fact the available data says they don’t.

    We do know what lack of vaccines cause. Death to children and adults. In societies without vaccines and antibiotics, up to half of all children can die of infectious diseaes.

    Where is your data? You don’t have any because it doesn’t exist.

    Ugeskr Laeger. 2002 Dec 2;164(49):5741-4.

    [MMR vaccination and autism--a population-based follow-up study]
    [Article in Danish]

    Madsen KM, Hviid A, Vestergaard M, Schendel D, Wohlfahrt J, Thorsen P, Olsen J, Melbye M.

    Center for Epidemiologisk Grundforskning, Institut for Epidemiologi og Socialmedicin, Aarhus Universitet, DK-8000 Arhus C.

    Abstract
    INTRODUCTION: It has been suggested that the measles-mumps-rubella (MMR) vaccination causes autism. MATERIAL AND METHODS: We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was established based on data from the Danish Civil Registration System. A unique person identifiable number given to all subjects enabled linkage with other national registries. MMR vaccination status was obtained from the Danish National Board of Health. Information on the children’s autism status was obtained from the Danish Psychiatric Central Register which contains information on all diagnoses received from psychiatric hospitals, psychiatric wards, and outpatient clinics in Denmark. We obtained information on potential confounders from the Danish Medical Birth Registry, the National Hospital Registry, and Statistics Denmark. RESULTS: In the cohort of 537,303 children (2,129,864 person-years), 440,655 children had been MMR vaccinated. We identified 316 children with a diagnosis of autistic disorder and 442 with a diagnosis of other spectrum disorders. After adjusting for potential confounders, the risk for autistic disorder and other spectrum disorders was not increased in vaccinated compared with unvaccinated children (relative risk 0.92; 95 percent confidence interval, 0.68 to 1.24 and relative risk 0.83; 95 percent confidence interval, 0.65 to 1.07). There was no association between age at vaccination, time since vaccination or calendar period at time of vaccination and development of autistic disorder. DISCUSSION: This study provides strong evidence against the hypothesis that MMR vaccination causes autism.

  122. #122 Johnq
    June 13, 2010

    Cracking Up Here’s point is one that I immediately thought of when I read the initial information on this new study, and I’ve seen nothing here, or anywhere else, that addresses that point. This latest study increases the evidence for a genetic basis in at least some cases of autism. This increases the likelihood that a genetic basis will be found to underlie all cases of autism, though it remains possible that what we refer to as “autism” actually consists of multiple syndromes that may have different causes.

    What I don’t think we can say, however, is that this new study provides much additional evidence that vaccines don’t “cause” autism. Many (or possibly most) medical conditions result from an interaction between genome and environment. That a set of genetic abnormalities correlate with a particular physiological condition doesn’t negate the possibility that the condition is triggered by a particular environmental factor, since the genetic abnormalities may increase the vulnerability of the individual to that factor. Thus, the fact that some cases of autism correlate with certain genetic abnormalities does not, in and of itself, tell us whether vaccines play some role in autism.

    The only information I could find in Orac’s original post that addresses this issue is the following quote:

    “Moreover, as P.Z. pointed out, no transient exposure or exposures to an external agent (such as a vaccine) is known to be able to produce such a consistent pattern of gene duplications and deletions in human cells like the sets detected in Pinto et al. Thus far, the preponderance of evidence points to primarily a genetic cause for autism and ASDs, and Pinto et al is another solid study supporting a genetic basis for autism.”

    This, however, doesn’t help much. It’s clear that vaccines don’t cause these genetic abnormalities, but neither Orac nor anyone else I’ve read has established (or even argued) that these pre-existing genetic abnormalities couldn’t predispose an individual to autism caused by vaccines or any other environmental insult.

    So what I’m left with is this: there’s no evidence that vaccines cause autism, and overwhelming evidence that no link exists. The present study is interesting and important for all sorts of reasons, but doesn’t add much to the vaccine issue.

    I’m perfectly willing to believe that I’ve missed something, my conclusion is wrong, and this study is actually relevant to disproving a vaccine-autism link, so if someone can point me to some information on this I’d appreciate it. For right now, however, the analysis on the pro-reason side seems somewhat simplistic, and I’m not sure that the air of triumphalism is justified. That vaccines don’t cause autism is clear. That this study provides anything more than very tangential evidence for that proposition is less clear, at least to me.

    Note: I’m not looking for independent evidence that vaccines don’t cause autism (e.g., Dianne’s point about twins). I already know that vaccines don’t cause autism. And I hope that anyone intelligent enough to follow this far will understand that my position here has nothing to do with Jen’s latest stupidity. (Note to Jen: as the New York Times reported today, many genetically-based diseases correlate with confusingly large numbers of distinct genetic abnormalities: http://www.nytimes.com/2010/06/13/health/research/13genome.html?ref=todayspaper.)

  123. #123 Dedj
    June 13, 2010

    Jen wrote: “I must confess that I am not a genetics specialist, however, the bottom line here is that if, as one of the 176 authors say, you couldn’t find any two persons with autism with the same genetic pattern, then it really isn’t heritable”

    That doesn’t mean it isn’t heritable, or that de novo mutations are not a factor.

    If there are multiple genes that do not individually cause autism, but which may contibute towards allowing the mechanisms that cause autism to occur, then differing people may have differing sets of these genes but with the same or similar results.

    In other words, the findings are exactly as one would expect if autism was a spectrum disorder with a polygenic/genetic cause.

    So, basically, you’re disagreeing with the study for no other reason than you lack enough knowledge and understanding of genetics to be able to understand what the study is talking about, despite the clear and accurate explanation given in the opening post.

  124. #124 Chris
    June 13, 2010

    It looks like neither jen nor the morphing Crackpot have never taken any biology past high school, and nothing for at least the past ten years. Nor have they kept up with any relevant literature, which they cannot even understand.

  125. #125 Joseph
    June 13, 2010

    Here’s an analogy for Jen. No two humans (except twins) have the same exact genotype. Yet, being human is 100% heritable.

    (At another level, it’s important to consider that autism is a social construct whose definition was never based on anything biological.)

  126. #126 Calli Arcale
    June 13, 2010

    Ben’s Parents:

    The biggest problem I have with all these breakthroughs linking autism to genetics is why wouldnt the numbers be higher. I mean if a specific gene or a group of mutated genes are responsible for causing autism then why arent they found in 100% of those with autism?

    And got me thinking about abortion.

    Are doctors 100% certain that they can predict a baby being born with a serious or untreatable health problem from a prenatal test that diagnoses the genetic material? Is or can there be a significant margin of error in some of these screening tests?

    That’s the disturbing side of genetic research, of course. While it definitely leads to better scientific understanding, and has the potential of leading to better treatment options, it also offers the possibility of identifying affected fetuses in time to terminate them.

    I do not believe it is right to terminate a child for this, or for Down’s, for that matter. And Down’s terminations do already happen, even in the United States. I can see terminating a child with a fatal defect, but not something like this. For non-fatal conditions, I think the value in genetic testing is the opportunity to know of the child’s needs in advance so that preparations can be made. One rare genetic condition is “glass baby” syndrome, where the child’s bones are extraordinarily fragile; knowing before the child is born could save a lot of lives (and stress; a lot of parents of such children wind up accused of child abuse, because no one can believe them when they say they had nothing to do with the hundreds of healed bone fractures the child has). If it was known before the child was born, they could plan on a c-section, sparing the child the trauma of being pushed out, which will certainly break some bones (even softened as they are at birth).

    But raising such a child would be difficult and expensive. I can see why a family, knowing the child has that sometimes-fatal and certainly painful condition, might choose abortion. It is not an easy problem to solve.

    Fortunately, we do not need to face that for autism, at least not yet. This study does not suggest that we need to worry about that for now. The genetic origins of these particular autistics are complex; creating a genetic test for autism would require far better understanding of genetics and how it relates to neurological development, because except in some rare situations like Rett’s Syndrome, it’s probably not a simple genetic change. It’s the interaction between dozens, perhaps hundreds or even thousands of genes, and that’s even assuming there *isn’t* an environment component. (Note: environment is more than chemicals. I would consider social exposure part of environment.) It’s forseeable, but we are not there yet, and I don’t think we’ll be there for a while. There’s an awful lot of data to crunch.

  127. #127 Enkidu
    June 13, 2010

    @ jen 77: ” By the way, your list of pre and peri-natal complications being associated with autism could easily be answered by adding vaccines into that mix of vulnerabilities(i.e. giving vaccines to premies could equal trouble)”

    Preemies are routinely given vaccines, because they are at the highest risk and need the best protection. In particluar, their lungs are extremely vulnerable to disease. My daughter, for example, was 3 months early and got every vax on-time (except the at-birth HepB was given at 2 months). She got her first flu shot at 8 months old, and she got montly anti-RSV shots through her first two winters.

  128. #128 jen
    June 13, 2010

    well, good luck with all of that, Enkidu. Poor kid.

  129. #129 trrll
    June 13, 2010

    @Cracking up Here

    First of all, we know that there is a basis to assume that environmental toxins (vaccines or not) cause problems for many people. Lead poisoning, mercury from fish, etc. etc… Now, of course we also know that vaccines can trigger seizures in children and on those rare occasions, children are permanently injured by vaccines… So, to start off spouting nonsense about television, rock music, etc. etc… is just MORONIC…

    And because there have been numerous documented cases of environmental heavy metal poisoning, we know exactly what the symptoms of neurotoxicity from these agents looks like–and we know that they don’t include autism. So to suggest in the face of this enormous body of data that mercury or lead causes autism is just MORONIC. So while TV or rock music is far-fetched, it is not as nonsensical as lead or mercury.

    Now of course, there is no good reason to believe in an environmental trigger at all. We know, for example, that Rett syndrome produces autism with regression, and the specific gene defect has been clearly identified. We also know that individuals with the identical Rett syndrome mutation can differ in severity of symptoms, due to random epigenetic variation (X-inactivation). So the major characteristics of classical autism are reproduced by a known genetic mutation.

    But if one really wants to believe in an environmental trigger, even in the absence of any evidence, there are lots of possible candidates. After all, over the last few decades exposure to an immense number of compounds has increased: dioxins, pesticides, plasticizers, plastic precursors, pharmaceuticals in the water supply, etc., etc. And TV is not such a crazy idea, either, certainly not as MORONIC as lead or mercury. Remember the Pokemon episode that induced seizures and other neurological symptoms in 600 children in Japan?

  130. #130 David N. Brown
    June 14, 2010

    @129,
    Sensory issues are huge for autistics, and the media are an obvious source of stressors. Another practical problem which anti-vax groups ignore in favor of conspiracy theories.

  131. #131 Cracking up Here
    June 14, 2010

    “But if one really wants to believe in an environmental trigger, even in the absence of any evidence, there are lots of possible candidates. After all, over the last few decades exposure to an immense number of compounds has increased: dioxins, pesticides, plasticizers, plastic precursors, pharmaceuticals in the water supply, etc., etc.”

    Yup, I know trrll…. Basically the environmental trigger can be anything OTHER than vaccines. Got it.

  132. #132 Kristen
    June 14, 2010

    Enkidu,

    Obviously Jen doesn’t know what it is like to have a very vulnerable child, in whom even a “minor” infectious disease can have a tragic outcome.

    IMO, the slight discomfort your child had to endure to be protected is well worth it because the outcome is a living vaccinated child, not a dead unvaccinated one.

    Jen’s pathetic attempt at painting you as cruel for keeping your child safe just shows (again) how low she will go to get her point across.

  133. #133 Dianne
    June 14, 2010

    Sensory issues are huge for autistics, and the media are an obvious source of stressors.

    So maybe stressors such as sensory overload from media could put someone with a genetic tendency toward autism over from the asymptomatic to the symptomatic side? I can see that as plausible. It wouldn’t be causing the autism but it might unmask a mild case, particularly of asperger’s. One caveat, though: autistic sensory problems don’t necessarily correlate well with what neurotypicals find problematic. So an autistic toddler (for example) might ignore the sensory overload of the media as simply uninteresting but be freaked out by the wrong color of orange in someone’s shirt.

    Vaguely related: Has anyone ever tried screening an asymptomatic population for autism? That is, put random people through the screening tests for things like ability to detect emotion through expression and so on? I wonder if the “true” incidence of autism might actually be higher than currently suspected simply because some people have a very mild condition which is not enough of a problem to bring them to the attention of a psychologist.

  134. #134 Dianne
    June 14, 2010

    Basically the environmental trigger can be anything OTHER than vaccines.

    There is no a priori reason that vaccines couldn’t be an environmental trigger of autism. However, after dozens of studies of the question virtually all of which found no connection, the idea is no longer tenable. Vaccines don’t cause autism. Cell phones don’t cause brain cancer. Laetrile doesn’t cure cancer. Time to move on.

    It’s not even clear that there is an environmental trigger per se. The 10% discordance in identical twins could be diagnostic error (ie one twin being diagnosed in a marginal case, the other not quite meeting criteria), variable penetration of genes, etc.

  135. #135 Dan Weber
    June 14, 2010

    A 90% concordance between for identical twins with autism is pretty large. With homosexuality (widely regarded to have a large genetic component), one identical twin being gay is about 50% likely to also be gay.

  136. #136 Elizabeth Reid
    June 14, 2010

    Another thing to consider is that not even ‘identical’ twins are necessarily precisely genetically identical, although it sounds funny to say so. I have read, for example, a case concerning a set of monozygotic twins who were discordant for neurofibromatosis, a genetic disease.

  137. #137 sarkeizen
    June 14, 2010

    “More evidence for a genetic basis for autism? More like more try. The try is very desperate.”

    So what exactly are you asserting? That 176 authors are desperately committed to a genetic etiology for autism that they did some sham study?

    “Wow, so this study had 176 authors and did not disclose competing interests. I am embarrassed that this has come from Canada.”

    As far as I’ve seen a study this large rarely has disclosure for that many investigators. Can you cite resources to the contrary? Are you asserting that the majority of the 176 have financial incentive to demonstrate this idea. Are you sure that’s an objective point of view?

    “I must confess that I am not a genetics specialist,”

    I rather think that despite explicit denial of expertise you are implicitly asserting expertise. After all how come there’s no “Jenn simply doesn’t know enough about genetics to understand this” theory in your list of possibilities?

    “the bottom line here is that if, as one of the 176 authors say, you couldn’t find any two persons with autism with the same genetic pattern, then it really isn’t heritable”

    So in your expert opinion about genetics if 1000-2000 people suffering from a disease don’t have an identical shared genetic pattern between two people. Then it is impossible for the disease to be heritable. No matter how wide or varied the symptoms of the disease (such as having a hundred or more unique presentations). That’s just over a million pairings. Is that the extent of the genetic diversity you are willing to give any disease.

    “THis study bolsters that finding and nothing more. Nothing new. End of story.”

    But you’re not claiming any expertise in genetics.

    You also forget FXS which is both responsible for some percentage of autism and is well-established as genetic (and was probably not part of this study).

  138. #138 David N. Brown
    June 14, 2010

    @133,
    “So maybe stressors such as sensory overload from media could put someone with a genetic tendency toward autism over from the asymptomatic to the symptomatic side?”

    I don’t think so; I would say from less to more severe symptoms. But, for practical purposes, one may say that a high-functioning individual would be “normal” except when exposed to a stressor.

    I’ve summarized my thoughts on this in an essay titled, “Vicious When Poked With a Stick”.

  139. #139 sarkeizen
    June 14, 2010

    @Cracking

    “Basically the environmental trigger can be anything OTHER than vaccines. Got it.”

    No, the point is that an environmental trigger – if necessary to the etiology – *could* be one (or some combination of) a huge number of things. It’s more your disproportionate allocating probability to vaccines that is being highlighted here. Personally I find the idea conceivable but highly improbable. Weight-for-weight the number of potential “toxins” a child is exposed to by the time they manifest symptoms so vastly outweighs the exposure to any ingredient in vaccines. That without further objective evidence it’s difficult to justify your position.

  140. #140 sarkeizen
    June 14, 2010

    @Cracking

    “Basically the environmental trigger can be anything OTHER than vaccines. Got it.”

    No, the point is that an environmental trigger – if necessary to the etiology – *could* be one (or some combination of) a huge number of things. It’s more your disproportionate allocating probability to vaccines that is being highlighted here. Personally I find the idea conceivable but highly improbable. Weight-for-weight the number of potential “toxins” a child is exposed to by the time they manifest symptoms so vastly outweighs the exposure to any ingredient in vaccines. That without further objective evidence it’s difficult to justify your position.

  141. #141 ScienceCat
    June 14, 2010

    @trrll hmm, actually a number of the big bad environmental triggers are on their way *down*, at least in North America, and have been for the last couple of decades or so. Lead comes to mind since it was removed from gasoline in 1990 here, dioxins are down in many areas too now that we know not to incinerate plastics at low temperature. A lot of the other things on your list are still on the uptick, although a lot of the “new” exposures are still likely due to increased observation and vigilance. *Perception* of chemical contamination and prominence in the news are at an all-time high, which increases the fear level at the same time that exposures to many substances are actually decreasing. The fear can serve some purpose, if the response to fear is to reduce exposures in a sensible manner (mercury exposure via fish consumption is more generally known, so more people avoid high fish consumption or avoid fish from certain sources when pregnant) but a lot of the reactions to the fear are not sensible and can be harmful (eating less healthy foods instead, substituting a large but unpublicized risk for a low-level publicized one). There’s a general problem with the way most people make risk-based decisions because they don’t understand and weigh the real risks and real benefits of a given activity or choice and the vaccine manufactroversy is part of that. Even risk experts make questionable risk decisions – if I thought about it too hard and let myself get worked up, I’d never get into my car, let alone pump gasoline for it (benzene!) and I’d end up dropping a good number of my outdoor recreational activities. I trade some risk of losing my life prematurely for the benefit of having a life that I enjoy living. Don’t we all do this? The fear response seems to be turned up to 11 these days for the most trivial chemical exposures and I’m wondering if the ‘chemical worry’ fills the need that people have to be scared of something, now that the Cold War is vanishing from personal memory.

    I’d like to ask the non-troll, non-nutjob (I guess that means jen, who is either genuinely concerned and wanting to learn or a particularly good troll, and not many others?) vaccine-fixated folks something, if I may. When looking around for something to blame for an “epidemic” that the overwhelming majority of experts see as being due to a diagnostic change, *why* do you all seem stuck on one of the most successful health-care technologies ever devised, no matter how much evidence piles up against there being any connection? Why not fixate any of the other things that have changed in the last 20 years? You could be just as wrong in blaming video games but at least that wouldn’t cause as much harm as this inexplicable focus on blaming vaccines. Is it just because you don’t really understand vaccines or autism (or biochemistry, or toxicology or genetics, all of which are complex subjects where a little knowledge can lead you very much astray when trying to apply it to the more complicated aspects) and things that people don’t understand or that seem novel are automatically scarier? Is it the needles? Needles are a bit scary to me too because they do break the skin and can be a vector for disease if re-used. I always catch myself watching carefully as they open the seal on the needle package draw liquid from the vial. I’m even a bit paranoid about the sterility seals on the blood donation needles that they use on me, and goodness knows that’s a low-risk-of-blood-transmittable-diseases screened population if there ever was one. It’s not really a rational fear and I know it, so I don’t let it stop me from getting vaccinated or donating blood. Fortunately, I’m relatively tolerant of the pain from the needle and I’ve never had syncope, although I do tend to get a very sore arm from some vaccines and sometimes a fever spike a day or so later. I can certainly sympathize with those who are more sensitive or who are subject to vaccination syncope – fainting from a vaccination has to be managed carefully so that you don’t fall and get hurt and can be very embarassing for an older child or adult. It’s also hard to stand by as someone causes even a small amount of pain to a child, especially a very young one where you cannot explain *why* they are getting a jab and that the pain won’t last long. So yes – vaccinations scary. Measles, polio, whooping cough, hepA/B, meningitis,tetanus, even chicken pox and mumps – far scarier. I’m also still vexed at being over the current age limit for the HPV vaccine, because cervical cancer is scary too.

    I don’t find the concept of autism scary at all, certainly less scary than measles-induced brain damage or deafness or a host of other sublethal disease outcomes. The diagnosis and therapies that we have now for autism are an immense improvement over bygone days, even though there’s still a long way to go. Autism isn’t really new. Think about how cruelly people with severe autism must have been treated in the past before it was understood that yes, there were thinking, feeling, intelligent *people* behind those social barriers? Can you imagine what it must have been like for someone of normal or even genius intellect to be shut away for life as an idiot or deranged mental patient because they had a communication problem? THAT is scary.

    Anyhow just my personal opinion, except for the environmental contamination stuff – that bit is also professional opinion and judgement (and access to datasets). Meow!

  142. #142 ScienceCat
    June 14, 2010

    .. hmm, and why did I type “deafness” when I had meant to type “blindness”? Maybe it was too scary a thought – I’m rather visual and used to being visual, so the idea of losing that ability at this point in life to a preventable disease (or anything else) was perhaps a bit too scary for the part of my brain that was doing the typing. Mea culpa and I will start previewing posts from now on.

  143. #143 trrll
    June 14, 2010

    Yup, I know trrll…. Basically the environmental trigger can be anything OTHER than vaccines. Got it.

    Considering that there have been many studies of possible effects of vaccines, and the results have been overwhelmingly negative, whereas there are hundreds and hundreds of other environmental substances for which exposure has increased over the past few decades, and for which a possible impact on autism has never been investigated at all, I’d say that is a pretty reasonable assessment. If one were to make a list of possible candidates for an environmental trigger (while keeping in mind that there is no actual evidence for an environmental trigger of any sort, and no biological reason to believe that one must exist), then any reasonable person would put vaccines near the bottom of a long, long list of suspects.

  144. #144 passionlessDrone
    June 15, 2010

    Hi ScienceCat –

    I’d like to ask the non-troll, non-nutjob (I guess that means jen, who is either genuinely concerned and wanting to learn or a particularly good troll, and not many others?) vaccine-fixated folks something, if I may. When looking around for something to blame for an “epidemic” that the overwhelming majority of experts see as being due to a diagnostic change, *why* do you all seem stuck on one of the most successful health-care technologies ever devised, no matter how much evidence piles up against there being any connection?

    I’d like to think that I’m not a nut job, and will state for the record my concerns over environmental participation in autism go far beyond vaccines. But for whatever reason, vaccines get discussed a lot.

    We all recognize that vaccines have the ability to persistently modify the immune system; it is, after all, their primary purpose, generation of pathogen memory in the adaptive arm of the immune system. The canard of an ‘overwhelmed immune system’ gets thrown around a lot in this debate, I don’t think it is very meaningful, to be fair to the skeptics, this phrase is used a lot in some of the more conspiratorial areas, and should be addressed as such. But I think the more meaningful discussion might be in determining if it is possible that vaccines can modify the immune system in ways up and above generation of antibodies. What if, the innate immune system could be modified through vaccination, or indeed, any immune challenge during critical timeframes?

    There is increasing evidence that other environmental forces can participate like this, for example, inclusion in daycare and subsequent increases in asthma diagnosis, or also, exposure to chlorine in swimming pools as infants and wheezing / asthma later in childhood. Unfortunately, studies on the effect of vaccines on the innate immune system are simply not available for the pediatric population, and are very, very sparse in any population. By way of example, I would encourage you to try to find a single study in a pediatric population that measured generation of proinflammatory cytokines pre and post vaccination; not antibodies, mind you, but cytokines like IL-6, TNF-alpha, or IL-1B. I am asserting these studies do not exist.

    So what? Well, it turns out, we have increasing evidence that a single, transitory innate immune response during critical timeframes can persistently modify immune function into adulthood in ways other than adaptive memory. Whats more, some of these observations include phsyiological or behavioral correlations to autism.

    For example, on Friday, Early Life Activation of Toll-Like Receptor 4 Reprograms Neural Anti-Inflammatory Pathways [PMID: 20534845] was published.

    A single postnatal exposure to the bacterial endotoxin, lipopolysaccharide (LPS), reduces the neuroimmune response to a subsequent LPS exposure in the adult rat. The attenuated fever and proinflammatory response is caused by a paradoxical, amplified, early corticosterone response to LPS. Here we identify the mechanisms underlying the heightened corticosterone response to LPS in adults after early life exposure to LPS. In postnatal LPS-treated rats, hypothalamic corticotrophin-releasing hormone mRNA, pituitary proopiomelanocortin mRNA, and circulating adrenocorticotrophic hormone were all increased after adult exposure to LPS without significant modification to hippocampal or hypothalamic glucocorticoid receptor mRNA or protein or vagally mediated afferent signaling to the brain. Postnatal LPS administration did cause a persistent upregulation of the LPS Toll-like receptor-4 (TLR4) mRNA in liver and spleen, but not in brain, pituitary, or adrenal gland. In addition, cyclooxygenase-2 (COX-2), which is a prostaglandin biosynthetic enzyme and is normally undetectable in most peripheral tissue, was constitutively expressed in the liver. Adult immune activation of the upregulated TLR4 and COX-2 caused a rapid, amplified rise in circulating, but not brain, prostaglandin E(2) that induced an early, enhanced activation of the hypothalamic-pituitary-adrenal (HPA) axis. Thus, postnatal LPS reprograms the neuroimmune axis by priming peripheral tissues to create a novel, prostaglandin-mediated activation of the HPA axis brought about by increased constitutive expression of TLR4 and COX-2.

    Check that out! A single triggering of TLR4 during development caused lifelong alterations in the neuroimmune response in adults, with one suggested endpoint as modified HPA axis functioning. Alterations in the HPA axis are well documented in the autism population (though, they do not appear represented in the CNV samples identified here), and it may be of interest to note that there is at least one study documenting increased functioning in children with autism when they get a fever. But the bigger issue here is that this type of mechanism would be common for any vaccines (well, any that touch TLR4), and would be invisible to thimerosal studies, and potentially invisible to MMR studies, as there is a significant window of time between the bulk of our schedule (2 4 6 months) and the MMR 12 – 18 months. Unfortunately, these are the only types of studies we have involving autism and vaccination.

    What’s more, this isn’t the first study to suggest that early life immune activation can have persistence and difficult to predict consequences in immune functioning and behaviors, far from it. If fact, this group and others have over well over a dozen studies in this area. For example, increased seizure succeptibility after LPS [PMID: 18596165], and Poly:IC [PMID: 19660546] have both been demonstrated, and in fact, different anti-inflammatory agents were capable of attenuating the effect. This implicates that just having a robust innate immune response was sufficient to permentantly modify the brains succeptiblity to seizures. (The LPS study demonstrated a time dependent effect.) The very high co-morbidity of epilepsy, and high incidence of abnormal EEGs in the autism population is well established. Other findings include precursors to the latest, which showed altered neuroimmune functions [PMID: 15163684], behaviors [16125259, 16395304, 18383727], peripheral immune function [16973935], fever response [19682802], and growth factor and cytokine alterations [17997277].

    Further complicating matters, we have a wealth of clinical data from the autism population indicating that a dysregulated immune response plays a critical part in autism; including known promoters of TLR expression, and increased generation of pro-inflammatory cytokines to a variety of stimulants. I can provide PMIDs if you’d like, but this is already a pretty long posting.

    Unfortunately, the underlying assumption of vaccination has always been that a robust innate immune response is harmless as long as the pathogenic mechanisms of the actual bacteria or viruses were not present. This is why, for example, you cannot post a single study on the innate immune response for shots in the pediatric schedule. As the genome posting yesterday should be telling us, however, things are rarely so clean cut in biology, and assumptions of simplicity rarely survive actual analysis. In the case of the heart of vaccination, stimulating the immune response, our existing research is relatively frail.

    It is entirely possible to accept the fact that vaccines work, save millions of lives and concurrently have the intellectual honesty to admit that we just haven’t done this type of research. It also doesn’t mean that genetic studies such as this aren’t useful and meaningful. The irony is that this study, which absolutely highlights the complexity of autism, will get bandied about as evidence that we need not perform rudimentary research into vaccination and autism. Who knew complexity is only useful when it supports a preferred conclusion?

    - pD
    (I like your handle)

  145. #145 raven
    June 15, 2010

    PD:

    The irony is that this study, which absolutely highlights the complexity of autism, will get bandied about as evidence that we need not perform rudimentary research into vaccination and autism. Who knew complexity is only useful when it supports a preferred conclusion?

    1. We have done research into vaccination and autism. I posted one study of 1/2 million children above. We have done a multi-millions child study by removing mercury from vaccines years ago and seeing what happened. Nothing.

    2. There is nothing unusual or unnatural about vaccination. It simply mimics an infection without the live, virulent organism pathogenesis.

    Getting infections and mounting immune defenses is something we all do constantly. How many antigenically distinct cold viruses are there, 150 or so of several different clades, picornaviruses, reoviruses, adenoviruses and so on. How many times do we get antigenically distinct influenza in our lifetimes. Or various mysterious and self limiting GI ailments.

    Any thery of vaccination induced autism has to deal with the fact that “natural vaccination” occurs constantly in all humans not living in sterile bubbles and most of us don’t come down with autism.

    It is not enough to hand wave and hypothesize “environmental triggers”. There are a near infinite number of possible environmental triggers and no evidence that environmental triggers for autism even exist. Without a working theory and some data, it is more or less irrelevant and useless.

  146. #146 passionlessDrone
    June 15, 2010

    Hi Raven –

    1. We have done research into vaccination and autism. I posted one study of 1/2 million children above. We have done a multi-millions child study by removing mercury from vaccines years ago and seeing what happened. Nothing.

    Remember the take away from this study: Autism is complex. That means that gross over simplifications (i.e., studying the MMR at 12 months is just like studying the six vaccinations given at two, four, and six months), or nonsense analogies (studying thimerosal is studying vaccination), aren’t likely to serve us well. Isn’t this straightforward?

    2. There is nothing unusual or unnatural about vaccination. It simply mimics an infection without the live, virulent organism pathogenesis.

    The timing of vaccination is very unusual, and very unnatural. How many infants prior to 1980 experienced infection by diptheria, tetanus, pertussis, hep b, hib, polio, and influenza the day they turned sixty days old? Several of the studies I posted above found distinct time dependent effects.

    Any thery of vaccination induced autism has to deal with the fact that “natural vaccination” occurs constantly in all humans not living in sterile bubbles and most of us don’t come down with autism.

    Well, your theory needs to deal with the fact that is composed of nothing more than hyperbole, and we have evidence of the opposite. For example, HPV-16 L1 VLP vaccine elicits a broad-spectrum of cytokine responses in whole blood. [PMID: 15855014] found:

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

    How does your theory of ‘constant vaccination’ deal with the fact that a single vaccine seems capable of causing significant rises in pro-inflammatory cytokines? Why hasn’t our ‘constant vaccination’ made this particular insult a blip of static in an environment filled with immunological noise?

    It is not enough to hand wave and hypothesize “environmental triggers”. There are a near infinite number of possible environmental triggers and no evidence that environmental triggers for autism even exist. Without a working theory and some data, it is more or less irrelevant and useless.

    But I’m not just waving my hands; I am making very specific claims about the trigger, why autism would be a succeptible subgroup, and why our existing studies are incapable of detecting any associations. Did you read any of what I posted?

    Here is the theory: A robust innate immune response during critical developmental timeframes can cause persistent changes to immune function and physiology. The data is the studies that I referenced above, and the multitude of studies detailing dysregulated immune system in autism; most importantly including those that detail an exaggerated production of pro-inflammatory cytokines.

    - pD

  147. #147 Chris
    June 15, 2010

    Why is it so important to prove that vaccines cause autism?

  148. #148 raven
    June 15, 2010

    Why is it so important to prove that vaccines cause autism?

    For the same reason it is important to prove that:
    1. the earth is 6,000 years old
    2. HIV doesn’t cause AIDS
    3. Obama is a Kenyan born Moslem terrorist
    4. Quantum mechanics is a delusion except when it explains why we have an afterlife
    5. UFOs exist and are piloted by demons from hell
    6. Fairies dance at the edge of the garden at night

  149. #149 passionlessDrone
    June 16, 2010

    Hi Chris –

    Why is it so important to prove that vaccines cause autism?

    I think it is more important that we fully understand the consequences of our actions, and I don’t think we have enough knowledge to do this yet.

    As an example of this, you might have noticed that instead of addressing my concerns that Raven’s ‘constant vaccination’ analogy is fatally flawed, or that ignoring time dependent effects of vaccinations is a gross over simplification for a system we know to be very complex, Raven chose only to respond with flippancy.

    Does this give you any insight on the underlying strength of his or her arguments?

    - pD

  150. #150 historygeek
    June 16, 2010

    PD@
    but how do u know what deases a child was exposed to and when through out all of history to make the statment that children wheren’t exposed to these dieses at brith. and some of these vaccines where given before 1980. oh and autism has exsisted pre industrial revolution. all of this complecats your agruments at least for me. and that is the problem not only do the vacines are evil arguments must hold up to the seintific method they must be suported by the historical record. and so far i have read nothing that does.

  151. #151 Chris
    June 16, 2010

    pD:

    think it is more important that we fully understand the consequences of our actions, and I don’t think we have enough knowledge to do this yet.

    Except we do know that reduction of vaccine levels brings back actual diseases. Measles became endemic in the UK, pertussis and Hib is killing children in the USA, and mumps is now quite common in Japan. Why is that acceptable?

    Look at all the research that shows that autism is not really related to vaccines that has been done over the past ten years, and that it is more likely a very complicated combination of genetics with some environment impact that occurs before the child is more than a few cells past being a zygote. I have a list of almost thirty papers on a text file that I can post (but I will resist my version of the Gish Gallop)… so the your answer that we need to know has been asked and answered and yet you persist on insisting that it must be vaccines for the most mundane and unlikely reasons.

    Why? Why is it so important that vaccines be blamed, even though the diseases themselves are returning? What do you hope to gain? Why be so persistent? How does persevering on vaccines help kids who need services that are not available because too much time and money is going after a question that has been answered in several countries multiple times over the past decade?

  152. #152 passionlessDrone
    June 16, 2010

    Hi Chris –

    Except we do know that reduction of vaccine levels brings back actual diseases. Measles became endemic in the UK, pertussis and Hib is killing children in the USA, and mumps is now quite common in Japan. Why is that acceptable?

    Have I said that it is acceptable? I have no problem with the the idea of herd immunity, nor that vaccines work at preventing infection. I’m not advocating stopping vaccination.

    I have a list of almost thirty papers on a text file that I can post (but I will resist my version of the Gish Gallop)… so the your answer that we need to know has been asked and answered and yet you persist on insisting that it must be vaccines for the most mundane and unlikely reasons.

    But none of them test vaccination, Chris. Not one of them. They test either: the presence or absence of thimerosal, or a single vaccine, the MMR. As I’ve tried to make clear, because the overwhelming bulk of our schedule is given long, long before the MMR, this means that making broad equivalancies is fraught with gross oversimplifications, assumptions which almost never pan in out.

    Do you understand what I am going after here?

    For example, check out PMID:18596165, where the authors identified time dependent effects of immune stimulation wherein affected animals were more succeptible to seizures as adults, but only if they were challenged during specific timeframes.

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

    The full paper is available online, and I would encourage you to take a look at it.

    In this study, had the authors only studied animals that got a challenge at postnatal day 20, they would have observed no effect. Does that mean there wasn’t any effect at day 14? This is why we cannot safely draw equivalencies between the MMR, given between 12 and 24 months, and the rest of the schedule, give between 2 and 6 months. Unfortunately, in your list of thirty studies, not one of them can give us any insight into this.

    Tell you what, if you can look in that list of over thirty papers and find a single one that isn’t about thimerosal or the MMR, post the title and PMID here. Take a look at them. You might be surprised at what you find.

    You might also take a look at PMID: 19666104. Here the authors triggered the same immune system gatekeeper, TLR4, as the authors did in the paper I just referenced. What they observed was that the children with autism created more tnf-alpha, the same cytokine associated with risk of increased seizures in the animal study, than their peers without autism.

    After in vitro challenge with TLR ligands, differential cytokine responses were observed in monocyte cultures from children with ASD compared with TD control children. In particular, there was a marked increase in pro-inflammatory IL-1beta, IL-6, and TNFalpha responses following TLR 2, and IL-1beta response following TLR 4 stimulation in monocyte cultures from children with ASD (p<0.04).

    I’m not waving my hands around for no reason, Chris. I am making very specific claims about why this might be a problem.

    Why is it so important that vaccines be blamed, even though the diseases themselves are returning? What do you hope to gain? Why be so persistent?

    I’m not blaming anything other than the pervasive groupthing that seems to allow you, and many others, to bypass the foundation of the scientific method; that you only learn about something you study. Studying thimerosal isn’t the same as studying vaccination. It just isn’t. Likewise, studying a vaccine given at twelve months doesn’t necessarily tell you how a different vaccine might impact a child at two months. Isn’t this straightforward logic? I’m not sure how I can get much clearer on this. (?)

    What I hope to gain is some intellectual honesty. There is a chance, perhaps small, that we are having unforseen impacts on our infants. Our existing studies are not properly designed to discern if this is happening or not. The first step in understanding if our actions are having unitended consequences is the simple acknoledgement that our existing research suite is insufficient, and there is reason to believe it may be missing something important. We can do this while simultaneously believe in the importance of vaccination and the real problems involved with a drop in herd immunity.

    - pD

  153. #153 Chris
    June 16, 2010

    You really have not answered my question. Perhaps I did not phrase it well enough: Why find proof that any vaccine is the cause of autism?

    As far as I can see you shown no reason that vaccines would cause any more problems than the diseases, which also cause inflammatory responses but even more so. In fact the MMR has been preventing autism since 1971, since rubella is a known environmental cause of autism in unborn children. Going on about thimerosal a decade after it was removed from vaccines kind of shows no real evidence will ever convince you.

    So why does it have to be vaccines?

    Oh, the papers:

    Neurotox Res. 2010 Jul;18(1):59-68. Epub 2009 Sep 16.
    Are neuropathological conditions relevant to ethylmercury exposure?
    Aschner M, Ceccatelli S.

    Pediatr Infect Dis J. 2010 May;29(5):397-400.
    Lack of association between measles-mumps-rubella vaccination and autism in children: a case-control study.
    Mrozek-Budzyn D, Kiełtyka A, Majewska R.

    Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study.
    Hornig M et al.
    PLoS ONE 2008; 3(9): e3140 doi:10.1371/journal.pone.0003140
    *Subjects: 25 children with autism and GI disturbances and 13 children with GI disturbances alone (controls)

    Measles Vaccination and Antibody Response in Autism Spectrum Disorders.
    Baird G et al.
    Arch Dis Child 2008; 93(10):832-7.
    Subjects: 98 vaccinated children aged 10-12 years in the UK with autism spectrum disorder (ASD); two control groups of similar age: 52 children with special educational needs but no ASD and 90 children in the typically developing group

    MMR-Vaccine and Regression in Autism Spectrum Disorders: Negative Results Presented from Japan.
    Uchiyama T et al.
    J Autism Dev Disord 2007; 37(2):210-7
    *Subjects: 904 children with autism spectrum disorder
    (Note: MMR was used in Japan only between 1989 and 1993.)

    No Evidence of Persisting Measles Virus in Peripheral Blood Mononuclear Cells from Children with Autism Spectrum Disorder.
    D’Souza Y et al.
    Pediatrics 2006; 118(4):1664-75
    *Subjects: 54 children with autism spectrum disorder and 34 developmentally normal children

    Immunizations and Autism: A Review of the Literature.
    Doja A, Roberts W.
    Can J Neurol Sci. 2006; 33(4):341-6
    *Literature review

    Pervasive Developmental Disorders in Montreal, Quebec, Canada: Prevalence and Links with Immunizations.
    Fombonne E et al.
    Pediatrics. 2006;118(1):e139-50
    *Subjects: 27,749 children born from 1987 to 1998 attending 55 schools

    Relationship between MMR Vaccine and Autism.
    Klein KC, Diehl EB.
    Ann Pharmacother. 2004; 38(7-8):1297-300
    *Literature review of 10 studies

    Immunization Safety Review: Vaccines and Autism. Institute of Medicine.
    The National Academies Press: 2004
    (w w w . nap.edu/books/030909237X/html) *Literature review

    MMR Vaccination and Pervasive Developmental Disorders: A Case-Control Study.
    Smeeth L et al.
    Lancet 2004; 364(9438):963-9
    *Subjects: 1294 cases and 4469 controls

    Age at First Measles-Mumps-Rubella Vaccination in Children with Autism and School-Matched Control Subjects: A Population-Based Study in Metropolitan Atlanta.
    DeStefano F et al. Pediatrics 2004; 113(2): 259-66
    *Subjects: 624 children with autism and 1,824 controls

    Prevalence of Autism and Parentally Reported Triggers in a North East London Population.
    Lingam R et al.
    Arch Dis Child 2003; 88(8):666-70
    *Subjects: 567 children with autistic spectrum disorder

    Neurologic Disorders after Measles-Mumps-Rubella Vaccination.
    Makela A et al.
    Pediatrics 2002; 110:957-63
    *Subjects: 535,544 children vaccinated between November 1982 and June 1986 in Finland

    A Population-Based Study of Measles, Mumps, and Rubella Vaccination and Autism.
    Madsen KM et al.
    N Engl J Med 2002; 347(19):1477-82
    *Subjects: All 537,303 children born 1/91–12/98 in Denmark

    Relation of Childhood Gastrointestinal Disorders to Autism: Nested Case Control Study Using Data from the UK General Practice Research Database.
    Black C et al.
    BMJ 2002; 325:419-21
    *Subjects: 96 children diagnosed with autism and 449 controls

    Measles, Mumps, and Rubella Vaccination and Bowel Problems or Developmental Regression in Children with Autism: Population Study.
    Taylor B et al.
    BMJ 2002; 324(7334):393-6
    *Subjects: 278 children with core autism and 195 with atypical autism

    No Evidence for a New Variant of Measles-Mumps-Rubella-Induced Autism.
    Fombonne E et al.
    Pediatrics 2001;108(4):E58
    *Subjects: 262 autistic children (pre- and post-MMR samples)

    Measles-Mumps-Rubella and Other Measles-Containing Vaccines Do Not Increase the Risk for Inflammatory Bowel Disease: A Case-Control Study from the Vaccine Safety Datalink Project.
    Davis RL et al.
    Arch Pediatr Adolesc Med 2001;155(3):354-9
    *Subjects: 155 persons with IBD with up to 5 controls each

    Time Trends in Autism and in MMR Immunization Coverage in California.
    Dales L et al.
    JAMA 2001; 285(9):1183-5
    *Subjects: Children born in 1980-94 who were enrolled in California kindergartens (survey samples of 600–1,900 children each year)

    Mumps, Measles, and Rubella Vaccine and the Incidence of Autism Recorded by General Practitioners: A Time Trend Analysis.
    Kaye JA et al.
    BMJ 2001; 322:460-63
    *Subjects: 305 children with autism

    Further Evidence of the Absence of Measles Virus Genome Sequence in Full Thickness Intestinal Specimens from Patients with Crohn’s Disease.
    Afzal MA, et al.
    J Med Virol 2000; 62(3):377-82
    *Subjects: Specimens from patients with Crohn’s disease

    Autism and Measles, Mumps, and Rubella Vaccine: No Epidemiological Evidence for a Causal Association.
    Taylor B et al.
    Lancet 1999;353 (9169):2026-9
    *Subjects: 498 children with autism

    Absence of Detectable Measles Virus Genome Sequence in Inflammatory Bowel Disease Tissues and Peripheral Blood Lymphocytes.
    Afzal MA et al.
    J Med Virol 1998; 55(3):243-9
    *Subjects: 93 colonoscopic biopsies and 31 peripheral blood lymphocyte preparations

    No Evidence for Measles, Mumps, and Rubella Vaccine-Associated Inflammatory Bowel Disease or Autism in a 14-year Prospective Study.
    Peltola H et al.
    Lancet 1998; 351:1327-8
    *Subjects: 3,000,000 doses of MMR vaccine

    Exposure to Measles in Utero and Crohn’s Disease: Danish Register Study.
    Nielsen LL et al.
    BMJ 1998; 316(7126):196-7
    *Subjects: 472 women with measles

    Immunocytochemical Evidence of Listeria, Escherichia coli, and Streptococcus Antigens in Crohn’s Disease.
    Liu Y et al.
    Gastroenterology 1995; 108(5):1396-1404
    *Subjects: Intestines and mesenteric lymph node specimens from 21 persons from families with a high frequency of Crohn’s disease

    Neuropsychological Performance 10 years after Immunization in Infancy with Thimerosal-Containing Vaccines
    Tozzi AE, Bisiacchi P, Tarantino V, De Mei B, D’Elia L, Chiarotti F, Salmaso S.
    Pediatrics, February 2009, Vol. 123(2):475-82

    Mercury Levels in Newborns and Infants after Receipt of Thimerosal-Containing Vaccines
    Pichichero ME, Gentile A, Giglio N, et al
    Pediatrics, February 2008; 121(2) e208-214

    Mercury, Vaccines, And Autism: One Controversy, Three Histories
    Baker JP
    American Journal of Public Health, February 2008;98(2): 244-253

    Continuing Increases in Autism Reported to California’s Developmental Services System: Mercury in Retrograde
    Schechter R, Grether JK
    Arch Gen Psychiatry, January 2008; 65(1):19-24

    Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years
    Thompson WW, Price C, Goodson B, et al; Vaccine Safety Datalink Team
    N Engl J Med, Sep 27, 2007; 357(13):1281-1292

    Pervasive Developmental Disorders in Montreal, Quebec, Canada: Prevalence and Links with Immunizations
    Fombonne E, Zakarian R, Bennett A, Meng L, McLean-Heywood D
    Pediatrics, July 2006, Vol. 118(1):e139-e150

    Vaccine Adverse Event Reporting System Reporting Source: A Possible Source of Bias in Longitudinal Studies
    Goodman MJ, Nordin J
    Pediatrics, February 2006, Vol. 117(2):387-390

    MMR-Vaccine and Regression in Autism Spectrum Disorders: Negative Results Presented from Japan
    Authors: Uchiyama T, Kurosawa M, Inaba Y
    Source: J Autism Dev Disord, February 2007; 37(2):210-217

    No effect of MMR withdrawal on the incidence of autism: a total population study.
    Honda H, Shimizu Y, Rutter M.
    J Child Psychol Psychiatry. 2005 Jun;46(6):572-9.

    Thimerosal in Vaccines: Balancing the Risk of Adverse Effects with the Risk of Vaccine-Preventable Disease
    Bigham M, Copes R
    Drug Safety, 2005, Vol. 28(2):89-101

    Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal
    Burbacher TM, Shen DD, Liberato N, Grant KS, Cernichiari E, Clarkson T
    National Institute of Environmental Health Sciences, April 21, 2005

    Thimerosal Exposure in Infants and Developmental Disorders: A Prospective Cohort Study in the United Kingdom Does Not Support a Causal Association
    Heron J, Golding J, ALSPAC Study Team
    Pediatrics, September 2004, Vol. 114(3):577-583

    Thimerosal Exposure in Infants and Developmental Disorders: A Retrospective Cohort Study in the United Kingdom Does Not Support a Causal Association
    Andrews N, Miller E, Grant A, Stowe J, Osborne V, Taylor B
    Pediatrics, September 2004, Vol. 114(3):584-591

    Thimerosal-Containing Vaccines and Autistic Spectrum Disorder: A Critical Review of Published Original Data
    Parker SK, Schwartz B, Todd J, Pickering LK
    Pediatrics, September 2004, Vol. 114(3):793-804

    The Evidence for the Safety of Thimerosal in Newborn and Infant Vaccines
    Clements CJ
    Vaccine, May 7, 2004, Vol. 22(15-16):1854-1861

    Safety of Thimerosal-Containing Vaccines: A Two-Phased Study of Computerized Health Maintenance Organization Databases
    Verstraeten T, Davis RL, DeStefano F, et al
    Pediatrics, November 2003, Vol. 112(5):1039-1048

    The Toxicology of Mercury–Current Exposures and Clinical Manifestations
    Clarkson TW, Magos L, Myers GJ
    New England Journal of Medicine, October 30, 2003, Vol. 349(18):1731-7

    Association Between Thimerosal-Containing Vaccine and Autism
    Hviid A, Stellfeld M, Wohlfahrt J, Melbye M
    Journal of the American Medical Association, October 1, 2003, Vol. 290(13):1763-6

    Thimerosal and the Occurrence of Autism: Negative Ecological Evidence from Danish Population-Based Data
    Madsen KM, Lauritsen MB, Pedersen CB, et al
    Pediatrics, Sept. 2003, Vol. 112(3 Pt 1):604-606

    Autism and Thimerosal-Containing Vaccines. Lack of Consistent Evidence for an Association
    Stehr-Green P, Tull P, Stellfeld M, Mortenson PB, Simpson D
    American Journal of Preventive Medicine, August 2003, Vol. 25(2):101-6

    Impact of the Thimerosal Controversy on Hepatitis B Vaccine Coverage of Infants Born to Women of Unknown Hepatitis B Surface Antigen Status in Michigan
    Biroscak BJ, Fiore AE, Fasano N, Fineis P, Collins MP, Stoltman G
    Pediatrics, June 2003, Vol. 111(6):e645-9

    Vaccine Safety Policy Analysis in Three European Countries: The Case of Thimerosal
    Freed GL, Andreae MC, Cowan AE, et al
    Health Policy, December 2002, Vol. 62(3):291-307

    Mercury Concentrations and Metabolism in Infants Receiving Vaccines Containing Thimerosal: A Descriptive Study
    Pichichero ME, Cernichiari E, Lopreiato J, Treanor J
    The Lancet, November 30, 2002, Vol. 360:1737-1741

    An Assessment of Thimerosal Use in Childhood Vaccines
    Ball LK, Ball R, Pratt RD
    Pediatrics, May 2001, Vol. 107(5):1147-1154

    Economic Evaluation of the 7-Vaccine Routine Childhood Immunization Schedule in the United States, 2001
    Zhou F, Santoli J, Messonnier ML, Yusuf HR, Shefer A, Chu SY, Rodewald L, Harpaz R.
    Arch Pediatr Adolesc Med. 2005;159:1136-1144.

    An economic analysis of the current universal 2-dose measles-mumps-rubella vaccination program in the United States.
    Zhou F, Reef S, Massoudi M, Papania MJ, Yusuf HR, Bardenheier B, Zimmerman L, McCauley MM.
    J Infect Dis. 2004 May 1;189 Suppl 1:S131-45.

    Impact of universal Haemophilus influenzae type b vaccination starting at 2 months of age in the United States: an economic analysis.
    Zhou F, Bisgard KM, Yusuf HR, Deuson RR, Bath SK, Murphy TV.
    Pediatrics. 2002 Oct;110(4):653-61.

    Impact of specific medical interventions on reducing the prevalence of mental retardation.
    Brosco JP, Mattingly M, Sanders LM.
    Arch Pediatr Adolesc Med. 2006;160:302-309.

    Encephalopathy after whole-cell pertussis or measles vaccination: lack of evidence for a causal association in a retrospective case-control study.
    Ray P, Hayward J, Michelson D, Lewis E, Schwalbe J, Black S, Shinefield H, Marcy M, Huff K, Ward J, Mullooly J, Chen R, Davis R; Vaccine Safety Datalink Group.
    Pediatr Infect Dis J. 2006 Sep;25(9):768-73.

  154. #154 passionlessDrone
    June 16, 2010

    Hi Chris –

    You really have not answered my question. Perhaps I did not phrase it well enough: Why find proof that any vaccine is the cause of autism?

    Imagine someone asking something along the lines of ‘why find proof that any lead in gasoline is the cause of lowered IQs in our children?’.

    In any case, as I tried to explain, I’m not looking for proof; I’m looking for some intellectual honesty in a place that is supposedly built around a rationalist viewpoint.

    If our national health policy is affecting our children in ways we don’t want it to, this is important information to have. We won’t get there as long as we insist that we can bypass the scientific method because our potential findings are highly inconvenient.

    As far as I can see you shown no reason that vaccines would cause any more problems than the diseases, which also cause inflammatory responses but even more so. In fact the MMR has been preventing autism since 1971, since rubella is a known environmental cause of autism in unborn children.

    What about the time dependent effect though, Chris? For example, tetanus. This is one deadly bug. It is deadly about 1 in 5 cases. Do you honestly believe that every child was exposed to tetanus when they were sixty days out of the womb? No? What about Hib, Hep-B, influenza, diptheria, pertussis, and polio? What percentage of children do you think were exposed to all of these pathogens by the time they were two months old previous to vaccination? 100%? 95%? Seriously.

    You are comparing a very minute number, the number of children exposed to disease at the earliest stages of life, with a very big number, the number of children vaccinated, and delcaring them equal for no reason at all. Why do you think these numbers can be safely equated?

    Regarding a vaccine causing a less inflammatory response than the disease, I’d like to see you try to support that with evidence. Do you have any?

    Did you know, for example, that the immune system responds synergistically when multiple types of pathogens are encountered simultaneously? Our vaccination schedule simulates an invasion that it would almost never encounter in real life. For examples of this, see PMID: 19164128 or 20360404

    Going on about thimerosal a decade after it was removed from vaccines kind of shows no real evidence will ever convince you.

    Could you show me a single place in this thread where I have made the thimerosal argument? It doesn’t bode well for your credibility when you go out of your way to prove that you haven’t read anything I’ve written. Your cutting and pasting skills seem good, can you point out where I have made the thimerosal argument?

    Regarding your list of studies, I’m really confused as to how to proceed. Thus far, you seem incapable of acknowledging, for example, that there is a difference between studying thimerosal, and studying vaccination. Do you understand that these are two fundamentally different things? I think you do understand this, but I have to tell you, I’m honestly not sure.

    In a similar fashion, do you understand that there are differences in an infant that is two months old, or one day old, versus and infant that is twelve months old? I really think that this pretty straightforward, but you keep on acting as if you do not understand the concept of time dependent effects, which is why, for example, studying something that happens at twelve months of age is not necessarily meaningful towards something that happens at two months of age. The study I posted above went to pains to define specific windows of development during which an impact was noted. Do you understand this?

    Your list is entirely composed of two types of studies: thimerosal based, and MMR based. Continuing to insist that this is representative of the entire vaccine schedule doesn’t make it so, but it does make it look like you can’t tell the difference.

    - pD

  155. #155 Nicholas Diazz
    June 16, 2010

    I have what is known as Asperger’s Syndrome, a type of high functioning autism. I believe autism spectrum disorders are a result of genetics and differences in neurology that are present at birth but may not become apparent until later in life. I am firmly opposed to, as is the reputable scientific community, the concept that autism is in any way caused by vaccines. The only study supposedly linking the two was done under the most improper investigative conditions and was later recanted by nine out of the ten authors.
    http://www.articlesbase.com/health-articles/quick-trim-diet-pills-reviews-where-to-buy-2630183.html

  156. #156 mary podlesak
    June 17, 2010

    Great analysis, passionless drone. The medical establishment is unwilling to concede the distinctions that need to be made in order to do valid vaccine science. When I met with my biostatistician professor friend at Yale in the Public Health Department, he was adamant that it was the vaccines themselves at fault, that is, the attenuated viruses, even without the other toxic ingredients, phenol, formeldehyde, aluminum, etc. I have not read the studies of vaccines cited here, but I know none of them could prove or even confirm a hypothesis of no adverse effects from a vaccine.

  157. #157 Chris
    June 17, 2010

    blah, blah, PMID 19164128: not about vaccines, done in a petri dish…blah, blah, PMID 20360404: not about vaccines, done in a petri dish, blah blah… lots of words and no real answers.

    I apologize, you never said anything about thimerosal. It seems you just have a problem with vaccines. Period.

    The study you told me to read, “Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats” … was on rats, was not about vaccines and was something I already knew about from personal experience.

    You see you said:

    You are comparing a very minute number, the number of children exposed to disease at the earliest stages of life, with a very big number, the number of children vaccinated, and delcaring them equal for no reason at all.

    Except one of those “minute number” is my oldest child.

    My son had seizures when he was 48 hours old, and spent the first four days in the hospital on antibiotics until the cultures showed no actual bacterial growth (the IV location had to be changed every day because the antibiotic was nasty and the vein was affected, so it went on both legs, both arms and they decided to stop just before having to put the IV into a vein in his head). There was no reason given for his seizures.

    There was no vaccine given at birth 21 years ago. Plus the kid suffered more seizures when he was a bit over a year old from another now vaccine preventable disease.

    He also has a severe genetic heart condition, and some intractable mental health issues along with severe learning disabilities (the latter two may or may not be related to a history of seizures according to the neurologist). Your kid only has autism. Do you want to trade children?

    You are going to have to work very very very hard to convince me that the vaccines are worse than the diseases, and that they are the cause of all inflammation and seizures (which is implied from the papers you keep citing… have I mentioned that none of them have anything to do with vaccines?). Especially with increases in infant deaths from pertussis and Hib.

    My list of studies included kids who had received all their vaccines. It is not ethical to deny medical prevention to children, though it has happened in Japan. The Japanese papers on MMR were possible because they did not even have an MMR to give, and yet autism (along with measles and mumps) increased. There is also the older experience the Japanese had with pertussis: After two infants died within 24 h of the vaccination from 1974 to 1975, the Japanese government temporarily suspended vaccinations. Subsequently, the public and the government witnessed the re-emergence of whooping cough, with 41 deaths in 1979. This series of unfortunate events revealed to the public that the vaccine had, in fact, been beneficial.

    Since my kid had seizures he was denied protection from pertussis because of the scare started by Barbara Loe Fisher Arthur (note one of last studies on that list is not about thimerosal, but directly refutes that DTP and MMR cause encephalopathy, which often includes seizures). This was at a time when our county had a pertussis epidemic, and is also at about the time over 120 Americans died from measles.

    All the more reason you really really need to tell me that the vaccines post a greater threat than pertussis, tetanus (to which there is not herd immunity), Hib, measles, mumps, etc. And yes, infants can be exposed to tetanus a few days from birth (it was suspected for my son), especially when a special clay is applied to the umbilical cord!

    Why do you obsessively persevere on vaccines when there are other more obvious reasons, like genetics? Or infections experienced by the mother while pregnant, like rubella or varicella?

    Why must it be vaccines only?

  158. #158 Chris
    June 17, 2010

    My last post addresses passionlessDrone, just in case anyone is confused.

    And, no, Ms. Podlesak (if that is indeed you, and not some spiteful PTA mom trying to make you look bad), he is not making good points. None of the copious studies he links to are about vaccines. They are about inflammation responses, which actually occur more accutely with real infections. Plus those are more likely to happen with certain pathogens than the vaccines! No surface or piece of skin is truly sterile.

    Just look up what happened to the brother of Henry David Thoreau after shaving.

  159. #159 skeptiquette
    June 17, 2010

    Hey pD,

    It’s funny when the regulars try to be conversant on a topic they are absolutely illiterate on, Isn’t it?

    I don’t suspect you are going to make any breakthroughs with chris the robot, she’ll just keep posting the same old list of studies and confusing just about everything you have written.

    You are making excellent points that are being taken very seriously by actual scientists and labs around the world. Chris is not qualified both from an educational standpoint and a critical thinking standpoint to make any meaningful rebuttal. I am pretty sure she is a engineer who sits at her computer gish galloping about, thinking that she knows what you’re talking about.

    The science is moving too fast for her, and as the old sang goes, “you can’t teach and old dog new tricks”

    I have a lot of things to add to your analysis, I just have to find the time to write.

    And again to those of you who have you’re heads up your asses. Both pD and I have focused on vaccines because vaccines can affect cognitive functioning and could possibly contribute to neurodevelopmental disorders. Chris can’t understand this because she lacks critical thinking skills, she just doesn’t understand how science works. Evidently she needs a study to tell her what to think, and it has to have to do with vaccines, otherwise you can’t learn anything about vaccines. For those of you who are inept at critical thinking like chris, why don’t you go quietly wait in a corner until another study comes out and tells you what to think.

  160. #160 MI Dawn
    June 17, 2010

    @skeptiquette: OK. Educate me. How is inflammation from a vaccine or any injection the same or worse than inflammation from the disease? I am willing to be given that information. You have not proven anything yet, but I’m willing to be taught. Show me.

    @pD: guess what? Infants CAN be exposed to tetanus at birth, shortly after going home from the hospital or after a home birth, within 2 months of birth. I’ve seen it. Do you really want to see a newborn in a tetanic spasm? It’s horrible, and even now the memory can make me cry. Yeah, it’s a crap shoot who will be exposed. Most won’t. But can you predict who will be? (The 2 week old baby I saw die was from a very wealthy family, who was accidently pricked with a needle left in a handmade blanket. Who would have thought tetanus was on that needle? Who would have thought that tiny, unsterile needle prick could kill a baby in today’s world?)

  161. #161 passionlessDrone
    June 17, 2010

    Hi Chris –
    I think I see part of the problem here. You don’t understand my position fully. For starters, why not look at the first paragraph I wrote in responding to ScienceCat:

    I’d like to think that I’m not a nut job, and will state for the record my concerns over environmental participation in autism go far beyond vaccines.

    But that is pretty tame stuff. For example, the work by Patterson and some others involving IL-6 during pregnancy is pretty good. Likewise, the work by Van de Water on specific neural antigens during pregnancy is very compelling. I have no problem with a pure genetic driving factor either; I rather like the findings in the Nature paper, by the way. No one wants to discuss the proliferation of endocrine disrupters, but several are known to interferre with thyroid metabolism, and hypothyroidism is well established as a risk factor for autism. I happen to think that the fattening of our population might even be playing a factor [try out PMID: 20124437] for why.

    I am by no means solely hung up on vaccines. But the fact that there are lots of potential environmental contributors doesn’t mean we should ignore vaccines just because they are very good at what they do. “The environment” is very difficult for us to control at this point, but if needed, we could make targeted choices regarding vaccinations.

    blah, blah, PMID 19164128: not about vaccines, done in a petri dish…blah, blah, PMID 20360404: not about vaccines, done in a petri dish, blah blah… lots of words and no real answers.

    Heh. In case you didn’t notice, the original topic of this thread is that autism is highly complicated, and in fact, there aren’t any answers coming anytime soon. Why not direct the same ‘no real answers’ to Orac, or the authors of the paper in Nature? As far as ‘done in a petri dish’, we need only look at the study I posted in #146 to show in vivo a pro-inflammatory response to a vaccine. If you have an in vivo study for a pedaitric vaccine in a pediatric population, please post it. As far as “not about vaccines”, these were studies involving ‘immune challenges’, what do you think a vaccine is, if not a powerful stimulation of the immune response?

    I apologize, you never said anything about thimerosal. It seems you just have a problem with vaccines. Period.

    Well this is some progress, I supposed. But, I believe I have stated on several occassions that I believe vaccines work, that herd immunity is real, and that there are very real and potent dangers for the recurrence of pathogens. I guess I can only keep saying that. A failure on your point to acknowledge this doesn’t really change my standpoint.

    The study you told me to read, “Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats” … was on rats, was not about vaccines and was something I already knew about from personal experience.

    Well, in that case, I’m wondering why the fact that it has to do with rats is bothering you so much? Do you really think that the scientists involved were interested in what happens to rats, under the belief that their experiment would have no value in understanding human physiology?

    Except one of those “minute number” is my oldest child.

    My son had seizures when he was 48 hours old, and spent the first four days in the hospital on antibiotics until the cultures showed no actual bacterial growth (the IV location had to be changed every day because the antibiotic was nasty and the vein was affected, so it went on both legs, both arms and they decided to stop just before having to put the IV into a vein in his head). There was no reason given for his seizures.

    That is very sad, and I’m truly sorry you and yoru child had to go through this. But surely you realize that this particular situation represents the vast, vast minority of children right? In most cases, the use of personal annectodes is frowned upon in this forum.

    There was no vaccine given at birth 21 years ago. Plus the kid suffered more seizures when he was a bit over a year old from another now vaccine preventable disease.

    I am sorry to hear this.

    He also has a severe genetic heart condition, and some intractable mental health issues along with severe learning disabilities (the latter two may or may not be related to a history of seizures according to the neurologist). Your kid only has autism. Do you want to trade children?

    You have know idea what my child has. And again, in most instances, this type of debating style is frowned upon here. In most instances, for example, when an ‘anti-vaxxer’ says something discouraging of their child, they are immediately attacked.

    You are going to have to work very very very hard to convince me that the vaccines are worse than the diseases, and that they are the cause of all inflammation and seizures (which is implied from the papers you keep citing… have I mentioned that none of them have anything to do with vaccines?). Especially with increases in infant deaths from pertussis and Hib.

    But I’m not trying to convince you, or anyone, of any such thing. I am trying to convince you that there is a danger that our national health policy is having unintended consequences, the mechanism by which this may be happening, and the reasons that our existing research is unable to detect such consequences. The papers I am citing are regarding early life immune challenges, and what you don’t seem to understand is that it is the result of those challenges, an inflammatory response, that is causing the outcomes. As I have shown in #146, an inflammatory repsonse is generated by vaccination. Do you believe that a vaccination stimulates an immune response?

    My list of studies included kids who had received all their vaccines. It is not ethical to deny medical prevention to children, though it has happened in Japan. The Japanese papers on MMR were possible because they did not even have an MMR to give, and yet autism (along with measles and mumps) increased. There is also the older experience the Japanese had with pertussis: After two infants died within 24 h of the vaccination from 1974 to 1975, the Japanese government temporarily suspended vaccinations. Subsequently, the public and the government witnessed the re-emergence of whooping cough, with 41 deaths in 1979. This series of unfortunate events revealed to the public that the vaccine had, in fact, been beneficial.

    You are making assumptions as to the ways we might be able to proceed. I am not advocating stopping vaccination.
    What your list does not include is a set of children who got their vaccines, and another set of children who did not. There may be ways other than a strick vaccination / unvaccinated study to gain more knowledge.

    Since my kid had seizures he was denied protection from pertussis because of the scare started by Barbara Loe Fisher Arthur (note one of last studies on that list is not about thimerosal, but directly refutes that DTP and MMR cause encephalopathy, which often includes seizures). This was at a time when our county had a pertussis epidemic, and is also at about the time over 120 Americans died from measles.

    This is not really pertinent towards whether or not an immune response generated by vaccination has been sufficiently studied.

    All the more reason you really really need to tell me that the vaccines post a greater threat than pertussis, tetanus (to which there is not herd immunity), Hib, measles, mumps, etc. And yes, infants can be exposed to tetanus a few days from birth (it was suspected for my son), especially when a special clay is applied to the umbilical cord!

    Why do I need to tell you that? I am not advocating a cessation of vaccination, but rather, a more intelligent approach towards understanding the consequences of our actions. I’m not sure how many more times I can repeat this.

    - pD

  162. #162 passionlessDrone
    June 17, 2010

    Hi MI Dawn –

    How is inflammation from a vaccine or any injection the same or worse than inflammation from the disease? I am willing to be given that information. You have not proven anything yet, but I’m willing to be taught. Show me

    Well, the potential issue is the timing of the inflammation. For example, the study I posted in 152 observed distinct time dependent effects; in other words, the animals were only effected if they experienced increased TNF-Alpha during very specific timeframes. It isn’t that the inflammation is qualitatively different, it is that the developmental window during which that challenge occurs can have an influence.

    There idea of critical periods of development that subsequently train the immune system is increasingly supported by empirical evidence. I would be happy to post more links if you would like. (?)

    guess what? Infants CAN be exposed to tetanus at birth, shortly after going home from the hospital or after a home birth, within 2 months of birth. I’ve seen it. Do you really want to see a newborn in a tetanic spasm? It’s horrible, and even now the memory can make me cry. Yeah, it’s a crap shoot who will be exposed.

    This is very sad and I am very sorry. But the last sentence is what makes vaccination such a change in our environment, unlike anything our ancestors encountered. It isn’t a crap shoot whether or not an infant will experience a vaccination within two months; it is almost guaranteed. Your annectode, while touching, does nothing to make our existing studies on vaccination any more robust, I am afraid.

    Unfortunately, the infant you referred to could not have been saved by vaccination, at least in the US schedule. I’m not aware of anyplace that vaccinates for tetanus at this early an age. As pointed out by Chris, there is no herd immunity for tetanus.

    - pD

  163. #163 Chris
    June 17, 2010

    blah, blah, blah… This article is about autism and genetics, not vaccines.

    The reason you missed why the level of disease is low is because vaccines. There is no reason that inflammation from vaccine should be greater than the diseases.

    You don’t seem to understand that the consequences the actions of the folks like Blaxill, Geiers, Wakefield, Redwood, Handley, McCarthy, Binstock, Haley, McTaggart, Stott, Buttar, Fisher Arthur, Fournier, Stagliano, Kirby, Olmsted, Stone and a bunch of others is bringing disease back. And the consequences is that real babies are dying.

    So why does it have to be vaccines versus the subject of the article, genetics?

  164. #164 Tim
    June 17, 2010

    There are literally hundreds if not thousands of environmental factors that our kids are exposed to daily that did not exist 50 years ago. Vaccines are the only one of these that has to my knowledge received any amount of scientific investigation. Time to move on to looking at other things besides vaccines.

  165. #165 passionlessDrone
    June 17, 2010

    Hi Chris –

    So why does it have to be vaccines versus the subject of the article, genetics?

    You should pose this question to ScienceCat. The first time I brought up vaccines, in post 144, was in response to ScienceCat’s post in 141, where he/she asked:

    I’d like to ask the non-troll, non-nutjob (I guess that means jen, who is either genuinely concerned and wanting to learn or a particularly good troll, and not many others?) vaccine-fixated folks something, if I may. When looking around for something to blame for an “epidemic” that the overwhelming majority of experts see as being due to a diagnostic change, *why* do you all seem stuck on one of the most successful health-care technologies ever devised, no matter how much evidence piles up against there being any connection?

    I simply attempted to answer ScienceCat’s question.

    If the substantive content of your responses are to increasingly consist of blah, blah, blah, it may not be meaningful for us to continue. Your continuing, seemingly inexplicable inability to understand the concept of time dependent effects, or an any type of nuanced opinion on the subject on my part are also becoming barriers in my opinion.

    I wish you well.

    - pD

  166. #166 Orange Lantern
    June 17, 2010

    Sorry, this thing got pretty long…
    pD,

    I’ve always read your posts with interest and appreciate your understanding of science and logic. You recognize the research that’s already been done and are not prone to fall in to too many logical fallacies, at least that I have seen. Among people that support and autism/vaccine link, these are difficult qualities to find. I agree with you that every aspect of the vaccine schedule has not been studies specifically for autism, though I think it is somewhat disingenious to criticize that, for reasons that will be mentioned below, among others.

    That being said, I find some points that go against your theory in the larger picture. I have read several of your posts and perused your blog, though I have not read every post. So do correct me if I missed something.

    First, and most interesting to me, is that the primary driving force behind the suspicion of a vaccine/autism link in the first place is parent testimony of development of regression or autism-like symptoms after vaccination before 12-18 months. The MMR studies of course, do not support this as a true phenomenon (though I recognize that there are other vaccines in this period). As far as I can tell, your theory does not seem to support such a phenomenon either. You seem to discount vaccination between 12-18 months as being a factor, and believe autism may be caused by vaccine exposure between 2-6 months. Interestingly, your theory then essentially eliminates the reason that parents have come to suspect vaccines as related to autism in the first place.

    So the first point is really more of a question: Do you believe that vaccination can cause sudden onset of autistic symptoms or regression after 12 months? If so, what model or studies have you read that support such a phenomenon? If not, then I do hope you are willing to dispute misinformation regarding vaccines such as the MMR in conversations in which you might participate.

    Second, as you are aware, it has not been established that there is an increase in true autism at all, in fact the research to date that I am aware of does not support such an increase, including Brugha 2009, Bishop 2008, Chakrabarti 2005, Rutter 2005, Taylor 2006, and others. I can provide PMIDs later if needed, but I suspect you are aware of these studies. The UC Davis study in 2009 did not explain all the increase in diagnosis of autism in California by artifacts, but accounted for the majority of it, and did not study artifacts such as increased surveillance and diagnostic substitution. None of this is locked-down proof that there is not a true increase in autism, but does not support the theory, and by extension does not support any theory that vaccines cause autism.

    I believe I read on your blog a statement to the effect that any increase in autism due to vaccines is extremely important. This is no doubt true, but the issue is how voraciously we need to pursue these small risks in the absence of evidence that they exist, and the clear risk of vaccine-preventable disease. The primary “evidence” is parental reports of autistic symptoms or regression after vaccination, which your theory does not seem to support.

    Finally, you are aware of Smith 2010 which found no association between timely vaccination reception in the first year and neurodevelopmental outcomes. Again, not locked-down proof against your theory, and I recognize the study’s limitations, but if you are asserting that the development of autism is so intimately time-sensitive, I would expect a difference in outcomes.

    Related to this, your theory is dependent on immune stimulation at these sensitive times, not on exposure to preservatives, etc. I appreciate your recognition that these are unlikely to be factors based on existing research. However, I don’t know how you reconcile your theory with the fact that the number of antigens in vaccines has been dramatically decreasing over the past decades. (I suspect you would point to adjuvants to explain this, and would be interested in seeing research you have seen to support this).

    OK, there is more that could be said, but I need to wrap this beast up. From my perspective, you have a theory where you have connected some dots of studies, mostly in animals, to assert that vaccines can cause autism. I do not feel versed enough in neuroimmunology to tell you how strong your theory actually is. I would love to hear the opinion of an immunologist (perhaps you are one, I don’t know, in which case I apologize). I don’t mean that as ad hominem, but the fact is that I can read all I want about a topic, come up with what seems like a plausible theory to me, and then get laughed out of the room by an expert who has the experience, context, and depth of knowledge to show how weak my theory is.

    So the concern I have, as I alluded to above, is how fervently must we disprove an autism/vaccine link at all, in the absence of compelling evidence that autism is truly increasing, or any reputable research that suggests such a link. As well-researched as you present your case, I don’t feel it provides a strong reason to suspect a link in light of the existing research. I’m appreciative of your constructive comments on this blog and others. I hope that you continue to critically re-evaluate your attachment to this theory as the science develops.

  167. #167 passionlessDrone
    June 18, 2010

    Hi Orange Lantern –

    It’s a shame you’ve been lurking, because your post is exactly the type of discussion I’d like to be having, but struggle to find. Do you blog somewhere?

    In any case, I’ve started crafting a response, but the real world intruded before I could complete it. This evening or sometime tomorrow I’ll try to post something trying to address your points.

    Very nicely done.

    Thank you.

    - pD

  168. #168 passionlessDrone
    June 18, 2010

    Hi Orange Latern –

    Interestingly, your theory then essentially eliminates the reason that parents have come to suspect vaccines as related to autism in the first place.

    Indeed. By way of explanation, I got here by what I consider to be applying a skeptical eye towards what I was being told (the vaccine schedule was thoroughly tested), with what I was able to validate (the opposite). Coupled with the very pecuiliar immunological findings observed in autism, I was really bothered by the significant flaws in the narrative being pushed by people who were supposed to have stories that could be validated beyond window shopping analysis.

    Do you believe that vaccination can cause sudden onset of autistic symptoms or regression after 12 months? If so, what model or studies have you read that support such a phenomenon? If not, then I do hope you are willing to dispute misinformation regarding vaccines such as the MMR in conversations in which you might participate

    I think it is possible in some cases, but I don’t really have a mechanism mapped out that can be defended to the level it needs to be. The problem here as I see it is that people that claim to have witnessed a drastic regression are a very small, but clamoring minority; I can see why, but to my mind, the bigger picture is more important. If vaccines can cause autism later, I imagine it is a very rare event. Regarding the MMR science, I wouldn’t say it is suberb, but it does at least exist. Wakefields findings will almost never be replicated, though I feel it is likely a matter of incomptence, than malice.

    Second, as you are aware, it has not been established that there is an increase in true autism at all, in fact the research to date that I am aware of does not support such an increase, including Brugha 2009, Bishop 2008, Chakrabarti 2005, Rutter 2005, Taylor 2006, and others.

    This is similar to ScienceCat’s original query, which I didn’t get sufficient time to address. I’ll admit that diagnostic substitution is respopnsible for some part of our increase, as well as ‘greater awareness’.

    Here is the crux of my problem with assigning all of our increase to this kind of thing: Earlier in this thread I posted a pile of PMIDs on the effect of greater parental age and autism risk; the proposed mechanism of action is accumulated mutations (tying in nicely with the Nature study), and the finding appears replicated in several areas. If you’ve been paying attention long enough, you’ll notice that the narrative on the increase has changed just a little, from ‘it all can be explained by diagnostics, to ‘most of it can be explained by diagnostics, except the very minor part concerning parental age’. But if you try to dig deeper, to see, for example, how these conclusions can be made, there isn’t anything there other than the nebulous, ‘greater awareness’. It sucks up everything that can’t be explained by environmental exposures. That’s not science, it is hope and faith.

    The other problem is that I’m starting to have a crisis in certainty over our prevelance studies. The only way that our latest values (~ 1 in 100) are correct, is if all of our previous studies were wildly inaccurate, and increasingly inaccurate over time. While this is possible, it doesn’t fill me with confidence that ‘the overwhemling majority of experts’ (ScienceCat’s phrase) aren’t worried; the only thing consistent about any of their findings is that they’ve undershot the count when compared to the next count. Imagine if your stockbroker had the same success rate the experts who have been telling us how common autism is?

    For example, Autism in the Faroe Islands: an epidemiological study [PMID:: 17029020], studied every child in the school system in the Faroes in 2002 and found a prevelance of .56%. This eight years after the switch to DSMIV. [This paper used to get dragged out a lot when the thimerosal theory was being used a lot, and the latest US numbers were in line with .56%.] 2006 numbers from the US found prevalence of around 1% [PMID: 20023608]. In 2009, Fombonne is reporting over 1% [PMID: 20164529]

    What gives you confidence in any particular set of these numbers? Without this confidence, it seems that running calculations that allow us to believe that the increase is artificial seems to be putting the cart before the horse. If autism rates jumped to one in 75 tomorrow, the call that it is ‘greater awareness’ would have exactly the same evidence it does now; metadata analysis on numbers that never stand in one place, but for which we always seem to be able to make up the difference by assigning them unquantifiable properties. I think our potential ramifications of this being a real problem are just too important to leave up to this kind of soft science.

    Finally, you are aware of Smith 2010 which found no association between timely vaccination reception in the first year and neurodevelopmental outcomes. Again, not locked-down proof against your theory, and I recognize the study’s limitations, but if you are asserting that the development of autism is so intimately time-sensitive, I would expect a difference in outcomes.

    Regarging Smith, my theory only survives if the subset of children who are affected by vaccines is a number capable of passing through their highest versus lowest filter without detection. Even at one in one hundred, and I am by no means suggesting every child with ‘autism’ is affected by vaccines, this would leave only three children in the low group, and seven in the high group. If our number of vulnerable children is less, you know what happens. None the less, this study does speak against my theory.

    But ‘my theory’ also allows for modifications in physiology that may not necessarily manifest in ways that would be captured by Smith.
    For example, PMID: 20534845, and 20546941, both published in the past two weeks, showed that neonatal challenge by LPS resulted in altered prostoglandin 2 synthesis in adulthood; these are changes that, if present due to vaccination, might not necessarily show up on a battery of cognitive tests as applied for the base study by Smith. At this point, unfortunately, I can legitimately be accused of wanting to study everything, but on the other hand, things are complicated, as they say. [Autism is characterized by abnormal stress response, in which the HPA axis plays a key role]

    However, I don’t know how you reconcile your theory with the fact that the number of antigens in vaccines has been dramatically decreasing over the past decades. (I suspect you would point to adjuvants to explain this, and would be interested in seeing research you have seen to support this).

    You might want to take a look at my blog posting, “The Antigen Gambit Part 1 – Or Can We Learn About the Immune System Through Addition” for a more comprehensive explanation of why this argument seems particularly flacid to me, but here is the short version.

    1) If we look at the number of vaccines in a particular shot, and compare that to the frequency of adverse effects such as fever, we don’t see a pattern you would expect if strict numerical counting was meaningful. For example, the DTAP with 5 antigens causes fevers much more frequently than the Varicella vaccine, with 75 antigens. The production of inflammatory cytokines, my proposed mechanism of possible harm, is almost certainly the means, or at least a big participant in fever generation; and yet we see exactly the opposite of what you would expect if simply counting the number of antigens were a good way to gauge the impact on the immune system.

    [both links available on my posting, not linking due to spam filter concerns].

    2) We have serveral very new studies that indicate that when your body detects multiple types of pathogens simultaneously, it reacts in a synergistic fashion with the production of inflammatory cytokines. See my post on #154 for some PMIDs on this. This is another example of the pitfalls of trying to use addition to understand a system as complicated as the immune system.

    In fact, if you read Smith 2010 very closely, they make the acknowledgement that the way different antigens interact to produce an immune response is not well understood.

    Some antigens are more reactogenic than others in the first day or 2 after injection, but how such “short-term” differences may or may not translate or relate to any differences in neurologic or immunologic development are unknown

    Of course, that doesn’t stop them from inferring that a redcution in antigens is meaningful one sentence later.

    But you’ve hit on something here that is what really started me pulling on this particular thread to see where it leads, the idea that something so simplistic as counting antigens is meaningful has been propogated out by a lot of people, including the peer review of Pediatrics, and folks who are on speed dial everytime the media needs someone to ‘prove’ vaccines aren’t associated with autism. If one of the most widely distributed ‘reasons’ for why the current schedule is ‘better’ than the earlier generations fails the most rudimentary logical tests, what does that tell you about the real state of our knowledge on the area?
    That thought scares the hell out of me.

    Regarding adjuvants, they are an area of interest to me, but they aren’t really necessary for my theory. I do find it a bit scary that it was not until 2008 that we started to unravel the mechanism of how adjuvants actually work. It was, to my mind, just more evidence that while we know that vaccines work at what we want them to do, our ability to discern if they also do things we don’t want them to is nascent.

    OK, there is more that could be said, but I need to wrap this beast up. From my perspective, you have a theory where you have connected some dots of studies, mostly in animals, to assert that vaccines can cause autism. I do not feel versed enough in neuroimmunology to tell you how strong your theory actually is. I would love to hear the opinion of an immunologist (perhaps you are one, I don’t know, in which case I apologize). I don’t mean that as ad hominem, but the fact is that I can read all I want about a topic, come up with what seems like a plausible theory to me, and then get laughed out of the room by an expert who has the experience, context, and depth of knowledge to show how weak my theory is.

    Hehe. I think you just insutled a lot of immunologists out there. I’m just a computer programmer by day, autism dad by night, and some jerk on the internet inbetween.

    I think what we have are two theories:

    1) Early life immune disturbances can result in long term alterations to immune function, neurophysiology, HPA-axis function, and ultimately, behavior. This theory would seem to have a lot of empirical data behind it, a set of data that is getting bigger fast. For example, between the time that you started this post, and I managed to finish a response, another paper came out, “Neonatal programming by neuroimmune challenge: effects on responses and tolerance to septic doses of lipopolysaccharide in adult male and female rats” [PMID: 20136690]. That is three new papers on this topic [also, 20534845, and 20546941] since Orac posted this thread. (!) While I’m not an immunologist, I think the issue is that you don’t really have to be classically trained in order to get some take away conclusions from these papers regarding theory. I think that one problem with some of my presentation was trying to be a bit too technical, if we step away, and ask ourselves if the data supports a link between early life immune responses and impacts into adulthood, the conclusions of these studies are pretty clear on the matter.

    In summary, we have provided evidence that a single neonatal immune challenge can program the innate immune response to an adult LPS challenge. Here we have shown that this occurs through a mechanism involving a corticosterone-mediated suppression of cytokine synthesis, which can reduce the CNS-mediated febrile responses to an adult LPS challenge. [PMID: 15972802]

    Long-term alterations initiated by an early life LPS challenge are not limited to neuroimmune responses, but can also affect recovery after cerebral ischaemia (Spencer et al. 2006), impair tumour immunity (Hodgson et al. 2001), attenuate allergic sensitization (Blumer et al. 2005) and inhibit the development of experimental arthritis (Shanks et al. 2000). Additionally, it has been shown that neonatal immune challenges alter memory, cognitive ability and pain sensitivity as adults (Gilmore et al. 2003,2005; Zuckerman & Weiner, 2005; Bilbo et al. 2005; Boisse et al. 2005). Taken together, these studies indicate that early life bacterial stimuli can lead to altered susceptibility to inflammatory and psychological disorders later in life. In light of the present findings regarding the programming effects of neonatal PolyIC, it will be important for future studies to examine the effects, if any, that early life viral immune challenges have on these other centrally mediated responses. [PMID: 16423854]

    In this study, we provide evidence that the innate immune system can be modified well into adulthood after exposure to LPS as a neonate. Our finding of attenuated fever in neonatally challenged rats sets the stage for a number of future investigations. The early activation of the neuroimmune response could alter, in the adult, the many CNS pathways and mechanisms that are known to be involved in fever as well as other autonomic and behavioral functions affected by LPS or cytokines (Oladehin and Blatteis, 1995; Elmquist et al., 1996; Tkacs et al., 1997; Dantzer et al., 1998; Zhang et al., 2000; Xia and Krukoff, 2001; Reyes and Sawchenko, 2002). [PMID: 15163684]

    These novel results indicate that a single transient inflammatory episode during development can modify the brain through a TNF-dependant mechanism, making it more susceptible to generate seizures in adulthood.

    Currently, there is limited clinical evidence to suggest that peripheral childhood infection contributes to the etiology of adult epilepsies. However, based on the novel data presented here, relatively mild early-life inflammation may be associated with permanent modifications in seizure susceptibility that persist well into adulthood. [PMID: 18596165]

    The available data indicate a number of common influences of early-life immune activation on later life brain and behavior, namely mechanisms such as cytokine production and glial activation. Thus, while we have been working specifically with a model of bacterial infection in neonatal rats, we believe the results we have reported likely apply more generally to brain-immune interactions [PMID: 19738918]

    All of the above are for articles that are fully available for free. There are, as I referenced, many many others, but I feel that the point is made: the evidence that early life immune activation can have lifelong consequences is strong and growing. Many of these observations have correlations of varying strength to what is observed in autism.

    The second theory is, can these interactions cause, or contribute to autism, and could vaccination initiate one of these interactions? [i.e., my theory]. What I am proposing is, ‘maybe’, and that our available data is largely insufficiently designed to give us much insight, and that is what really bugs me; especially when the prevailing narrative is ‘the question has been answered’. What makes me continue to think this is a ‘maybe’ is that our knowledge of exaggerated immune responses and ongoing immune activity within the CNS would seemingly make our population of interest a good candidate to be showing effects from this type of impact.

    Regarding a critical eye, here are, as I see them, the weakest links in my thought process:

    1) The time period of immune system maleability is completely pre-natal; not even the hep-b shot given within a few days of birth could cause these kinds of changes in people. The jump from rat to human in terms of brain development is a steep hurdle, and one that is still largely not well understood. While this is possible, I don’t think a tight argument can be made that we understand the developmental processes well enough to say only prenatal effects can be present. Perhaps there is someone out there that can prove me wrong. The fact that our population of interest responds differently to immune challenges makes this a more problematic problem to untangle; i.e., are there time and dose relationships?

    2) What we are seeing in rats, just doesn’t happen in people, regardless of timeframe. This would seem to be argued against by several pre-natal rat models that seem to model pre-natal human models, research such as the Patterson IL-6 rat models, or the Van de Water chimp models involving antibodies collected from mothers of human autistic children. The IL-6 model, in any case, involves the innate immune response. However in lots of areas the jump from rat to human is a remarkable failure.

    3) The pediatric vaccine schedule doesn’t cause an increase in inflammatory cytokines. Without this, my theory is dead, dead, dead. Again, this seems unlikely considering the intent of vaccines, and the very limited in vivo studies we have on non pediatric vaccines regarding innate immune responses, but it is, none the less, possible. I’m not comfortable with the idea that no research is good news, and thus far, no one has been able to show me any studies one way or the other on the innate immune response for the pediatric vaccine schedule. There are a bazillion hits for the adaptive arm.

    4) The effects can happen in people, can happen postnatally, and can be caused by vaccines, but they are not sufficient to cause autism. At this point the gradient of what is a meaningful ‘change’ becomes very murky. (?)

    This is a lot of unknowns, but this must be contextualized against our actions and observations, vaccinating every child in the country and observations of unprecendented increases in conditions like autism or bi-polar disorder in children. We seem to have different ideas on how to proceed.

    So the concern I have, as I alluded to above, is how fervently must we disprove an autism/vaccine link at all, in the absence of compelling evidence that autism is truly increasing, or any reputable research that suggests such a link. As well-researched as you present your case, I don’t feel it provides a strong reason to suspect a link in light of the existing research. I’m appreciative of your constructive comments on this blog and others. I hope that you continue to critically re-evaluate your attachment to this theory as the science develops.

    I understand your position and appreciate your thoughtfulness. Are you aware that some people with significant knowledge, such as Tom Insel, have been paraphrased as saying that the burden of proof remains on those that would argue that the increase is not real. Unfortunately, at this point, it becomes difficult to agree on what constitutes a meaningful increase.

    As far as a critical eye, I’m curious as to what type of research you might feel could be presented that would cause you to re-evaluate your position? Disregarding a vaccinated / unvaccinated study, are there other clinical findings that might convince you this line of reasoning is worth investigating?

    This was a massive post. I’m may re-post it on my blog. I hope you respond. I’m also working on a posting regarding a PTSD and immunological epigenetics study that will have a mea-culpa of unknown size in it. I’d be interested in your thoughts on it when I can get a chance to finish it up.

    - pD

  169. #169 Orange Lantern
    June 25, 2010

    pD,

    I got here by what I consider to be applying a skeptical eye towards what I was being told (the vaccine schedule was thoroughly tested), with what I was able to validate (the opposite).

    Interesting. I haven’t noticed the same. I feel that the major science-based pro-vaccine sites tend to bend over backwards to state specifically what has and has not been studied, and allow for the possibility of an environmental influence, filtered through the research indicating that such an influence is likely modest. This is just my subjective perception, of course.

    Now, commenters may not be as nuanced, and news stories oversimplify for drama, etc., and even in science blog posts things might get generalized. “Lack of evidence of a true rise of autism” + “existing studies for MMR and thimerosal show no causation” + “supporting studies do not indicate that autism caused by vaccines is likely” = “science does not support an an autism/vaccine link”. But that does not mean that the authors, or medical experts in general, do not understand the nuances of the vaccine/autism controversy.

    you’ll notice that the narrative on the increase has changed just a little, from ‘it all can be explained by diagnostics, to ‘most of it can be explained by diagnostics, except the very minor part concerning parental age

    Only if you oversimplify it. The possiblity of an environmental component to the rise in autism has been discussed in scientific circles since the controversy began. I just read an early 2008 SBM article where Dr. Novella concludes by saying

    It should also be noted that all of this research, while supporting the hypothesis that the rise in autism diagnoses is not due to a true increase in the incidence but rather is due to a broadening of the definition and increased surveillance, does not rule out a small genuine increase in the true incidence. A small real increase can be hiding in the data.

    This would be prior to most of the research you cited regarding parental age.

    What gives you confidence in any particular set of these numbers? Without this confidence, it seems that running calculations that allow us to believe that the increase is artificial seems to be putting the cart before the horse.

    Hmmm… but neither should it give us more concern about a true increase. If anything, we should be concerned about our ability to accurately diagnose and count autistic children.

    Our studies were not “wildly inaccurate” in the past any more than our studies were “wildly inaccurate” to say that we had nine planets (OK – that analogy may be bad as I am even less of an astronomer than a neuroimmunologist). The studies reflect the abilities of medical professionals or education systems to identify children with an ASD. This ability has been changing over time. Not due to (again oversimplified) “greater awareness”, but to a radical changing of definition and diagnostic criteria, as well as medical, educational, and parental surveillance and diagnostic skill.

    Also the studies I cited did not rely on any one “number” you’re concerned about.

    Chakbarti used the same methods to look at autism diagnoses in the same population over a roughly five-year period and found a stable incidence.
    Shattuck and Bishop speak to the significant component of diagnostic substitution over the years (this is mostly to show how importat that omitted factor is in the UC Davis study.
    Rutter and Taylor looked at historic records and found that applying modern diagnostic criteria yielded a rate of ASDs that approaches current estimates.
    Brugha et al indicates that the prevalence of autistic adults approximates current estimates of the prevalence of autistic children.

    Are you aware that some people with significant knowledge, such as Tom Insel, have been paraphrased as saying that the burden of proof remains on those that would argue that the increase is not real.

    I am aware that people can be paraphrased to say a lot of things. I am not, however, aware of any way that science can prove a negative.

    As far as a critical eye, I’m curious as to what type of research you might feel could be presented that would cause you to re-evaluate your position? Disregarding a vaccinated / unvaccinated study, are there other clinical findings that might convince you this line of reasoning is worth investigating?

    No additional evidence is needed, as I feel that the possibility of a modest environmental cause exists and should be investigated. The question, as I said before, is how aggressively to pursue any one particular possibility, especially vaccines, and how much credence to give to personalities that strive to make such a connection (especially given the ramifications of decreased vaccination). Even though each vaccine (or the schedule as a whole) has not been specifically studied long-term for an autism association, there is increasing supporting evidence to show that such an association is unlikely, and that an environmental influence is modest, if it exists at all. You must admit that out of the numerous plausible environmental influences, vaccines are the one that has been studied the most.

    I would much rather have research dollars spent where experts, not celebrities or internet personalities, believe the research is most likely to yield productive results. Further, as you know from a recent LBRB post, there is at least one large government-funded investigation underway regarding environmental exposures (including vaccines) and autism. Indeed, research in the area of your particular theory is continuing, as you have cited studies that were released within the past few weeks. Certainly, this is not being studied with the fervor of MMR or thimerosal, but this is natural, since the evidence that has accumulated in the last decade makes a vaccine connection increasingly remote.

    However, I still fear you are making more out of your internet research than is warranted. I appreciate that you attempt to identify your own theory’s flaws, but I am doubtful that you have identified all of its flaws. Perhaps someday when I have an abundance of time I can look deeper into your blog and the studies you reference, but I will still not be an adequate expert to critique your theory.

  170. #170 Aspbergers_Steve
    September 16, 2010

    It’s like watching a herd of Lemmings hurrying to throw themselves over a cliff.
    Instead, I’m watching scientists racing around trying to find a way to screen for Autism so that prospective parents can have the “imperfect” foetus aborted. Then there will be no more Autism and the Human Race will be happy. Right?
    Wrong.
    The fact that Autism-spectrum disorders are so widespread tells us that, in some way, these disorders are useful to the Human Race. Maybe it’s the fact that Leonardo Da Vinci, Michelangelo and others probably had Aspbergers’ Syndrome. Who knows how many other inventors and free-thinkers have also had Aspbergers. Natural Selection has therefore “ruled-in” Autism as something that is, on balance, useful for the Human Race.

  171. #171 daedalus2u
    September 16, 2010

    Steve, You might be interested in this blog post.

    http://daedalus2u.blogspot.com/2008/10/theory-of-mind-vs-theory-of-reality.html

    I completely agree. Autism is a property of a phenotype, not a genotype. I think that every human genotype can produce an autism phenotype given a certain in utero environment. If you modified the genome so it couldn’t support an autism phenotype, then the organism that resulted wouldn’t be human.

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