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The perils and pitfalls of doing a “vaccinated versus unvaccinated” study

The anti-vaccine movement is nothing if not plastic. It “evolves” very rapidly in response to selective pressures applied to it in the form of science refuting its key beliefs. For instance, when multiple studies looking at the MMR vaccine and autism failed to confirm the myth that the MMR causes autism or “autistic enterocolitis,” most recently late last year, it was not a problem to the anti-vaccine movement. Neither was it a major problem to the movement when multiple studies similarly failed to find a link between mercury in the preservative thimerosal that used to be in most childhood vaccines and is no more (except the flu vaccine) and autism. No problem! Andrew Wakefield is alleged, based on strong evidence, to have falsified his data alleging a link between the MMR vaccine and “autistic enterocolitis”? Fuggedabouddit! The anti-vaccine movement simply pivoted neatly, de-emphasized points that the evidence was so clearly against that even they couldn’t spin it to a positive anymore, and found new bogeymen. These days, it’s the “toxins” (such as formaldehyde and the latest antivax bogeyman, squalene), and “too many too soon” (a gambit given seeming respectability by Dr. Bob Sears and Dr. Jay Gordon, apologists for and supplicants to the anti-vaccine movement both.

However, there is one trait of the anti-vaccine movement that, however its camouflaging plumage may evolve, never, ever changes. It is as immutable as believers say that God is. That trait is that, whatever other claims, the anti-vaccine movement makes, at its core it is always about the vaccines. Always. No matter how often science fails to find a link between vaccines and autism or vaccines and whatever other horreur du jour the anti-vaccine movement tries to pin on vaccines, no matter how many studies do not support the viewpoint that vaccines cause autism, no matter how much the anti-vaccine movement tries to deny and obfuscate by saying that it is not “anti-vaccine” but rather “pro-safe vaccine,” at its core the anti-vaccine movement is about fear and loathing of vaccines. Always. When inconvenient science doesn’t support their views, anti-vaccine activists either ignore the science, distort the science, or launch ad hominems against the people doing the science or citing the science. And, as I said before, the claims of the anti-vaccine movement evolve. Never again will the anti-vaccine movement make the horrific mistake of yoking itself to a hypothesis that is as easily testable as the hypothesis that mercury in vaccines causes autism. The claim that mercury in vaccines causes autism predicted that, if thimerosal were removed from vaccines or reduced to pre-”epidemic levels” of the early 1990s, then autism rates should plummet. Thimerosal was removed from nearly all childhood vaccines (the sole exception being some flu vaccines), reducing infant mercury exposure from vaccines to levels not seen since the 1980s; yet autism rates continue to rise. This is about as resounding a refutation of the hypothesis that mercury in vaccines is a major cause or contributor to autism that even the anti-vaccine movement has backed away from the pure claim, which has now evolved to unnamed “environmental toxins,” either in concert with mercury or with other nasty things, as being the Real One True Cause of Autism.

It’s evolution in action. These new claims are much “fitter” because they are much harder to falsify through scientific research, epidemiology, and clinical trials.

To understand the persistence of the myth that vaccines cause autism, we must consider the myth underlying it, namely the myth of the “autism epidemic.” It is certainly true that the number of autism diagnoses has been increasing at a seemingly inexorable rate ever since the early 1990s. At around the same time, multiple new vaccines were introduced to the schedule. Also around the same time (namely 1994), the diagnostic criteria for autism and autism spectrum disorders were greatly broadened. Also, throughout the 1990s and the 2000s, more resources were invested in screening children for autism. As is the case with other conditions or diseases, the more you screen for something the more you will find, often the less severe cases that would have been missed otherwise. In any case, a combination of diagnostic substitution, increased awareness, increased screening, and increased support services that brought revenue to school districts to help autistic children account for the vast majority, if not all, of the increase in autism prevalence over the last 20 years or so. As Joseph puts it:

Nevertheless, it appears that when ASD is screened thoroughly in a population, or when there’s a lot of awareness and good ascertainment, prevalence is found to be closer to 1%. This is not new. The following is what Lorna Wing and David Potter said on the subject as early as 1999.

Indeed, recent NCSH data do not show any evidence of an “autism epidemic.”

However, the key to the myth that vaccines cause autism is the observation that autism prevalence has increased rapidly since the early 1990s, and that was around the same time when the vaccination schedule was expanded to include more vaccines. Of course, as I’ve pointed out before, this is a classic case of confusing correlation with causation, and, as I’ve also pointed out before, one could point to a number of other things that happened in the 1990s that correlate with increased autism diagnoses. For example, the first easy-to-use web browsers were first introduced in the early 1990s, leading to an astonishingly rapid growth of Internet use outside of universities and work environments. Using the same sort of logic as anti-vaccinationists use, we could just as easily blame the Internet for the “autism epidemic”! In any case, thanks to the human tendency to confuse correlation with causation and desire to have an explanation for anything we consider scary, the myth that vaccines cause autism persists among even highly intelligent people who should know better. Indeed, one person at a recent skeptical meeting I attended was clearly very suspicious of vaccines and not so clearly reassured by what fellow SBM blogger Peter Lipson and I explained. Consistent with the persistence of this myth, refutations of the contention that vaccines cause autism are usually either met with denial or the classic false dichotomy, “Well, if vaccines don’t cause autism, what is causing this huge increase in autism?” as if vaccines were the only plausible option.

Thus, I think, was born the “too many too soon” gambit, in which the anti-vaccine movement, so wedded to the idea that vaccines must cause autism, have latched onto the idea that somehow it’s the “overvaccination” or “too many vaccines.” According to this idea, somehow excessive “immune stimulation” or injection of “toxins” that is leading to and “epidemic” of autism, asthma, and a huge variety of other ailments and conditions.

This “too many too soon” chant has lead to a demand by the anti-vaccine movement that the government conduct a large study of “unvaccinated” versus the “vaccinated” children to compare them for health outcomes and, especially, the prevalence of autism. The expectation, of course, on the part of the anti-vaccine movement is that such a study would show that unvaccinated children are far healthier and don’t suffer from nearly the same rate of autism. I don’t think that people like J.B. Handley realize how risky their gambit is. Such a study would have a very high risk of torpedoing virtually everything the anti-vaccine movement has been working toward in terms of promoting their message of fear about vaccines as being somehow credible (or at least not unreasonable) and based on science (more on that later).

None of these concerns has stopped the drones over at the happy home for anti-vaccine propagandists (Age of Autism) from busily promoting the idea of a “vaxed versus unvaxed” study and, as is their M.O. for any critics, harshly disparaging anyone who dares to point out the difficulties and lack of scientific rationale for such a study, the latest target being Tom Insel of the Interagency Autism Coordinating Committee (IACC), who recently testified in front of Senator Tom Harkin’s comittee (yes, that Tom Harkin).

The misunderstanding and misrepresentation of epidemiology being trotted out to justify this study are astounding. For example, last week on AoA, a mechanical engineer named Catherine Tamaro tried to lecture scientists on statistics and the difference between observational versus experimental studies using quotes from a statistics textbook. She began:

After reading Katie Wright’s summary of the August 3 Senate Committee on Appropriations’ hearing on autism (HERE), I would like to comment on Dr. Insel’s testimony to Senator Harkin on why a study comparing vaccinated vs. unvaccinated children has not been done to date. Dr. Insel claimed that such a study would be “unethical” because, as he apparently envisions it, the study would entail dividing a large cohort of newborns into two groups, vaccinating one cohort but not the other through age two, and then comparing outcomes. This is just a bit disingenuous and I would like to explain why.

Of course, Ms. Tamaro is either ignorant or disingenuous herself in that some anti-vaccine advocates do indeed call for just such a study, even going so far as to demand a randomized, double-blinded study. J.B. Handley himself has attacked people who correctly call demands for such a study “unethical.” Apparently Ms. Tamaro isn’t aware of the strain running through the anti-vaccine movement that does want just such a study, or she herself is being even more disingenuous than she accuses critics of being. Tamaro then continues:

Research studies are divided into two categories, observational studies and experimental studies. An observational study observes individuals and measures variables of interest but does not attempt to influence the responses. (The “epidemiological” studies to which Dr. Insel refers are actually observational studies.) An experimental study, on the other hand, deliberately imposes some treatment on individuals in order to observe their responses; the purpose of an experiment is to study whether the treatment causes a change in the response.

This paragraph just goes to show how a little knowledge is a dangerous thing. There are many flavors of “observational” studies, with varying degrees of power to detect differences and varying degrees of ease with which confounders are accounted for. These include cohort studies (both retrospective and prospective), cross sectional studies, longitudinal studies, and case series. All have their strengths and weaknesses, and the studies of vaccines and autism have used several kinds of methodology. Not that that sways Tamaro:

All studies done to date investigating a correlation between vaccinations and autism have been observational studies, but no observational study has been done comparing the prevalence of autism diagnoses in a vaccinated human population compared to an unvaccinated human population. When Dan Olmsted points out that he has identified large populations of unvaccinated children in the United States and asks why a study has not been done on them, he is actually asking why an observational study has not been done. When Senator Harkin asks Dr. Insel why a study has not been done on vaccinated vs. unvaccinated American children, he too is actually asking why an observational study has not been done to date. Dr. Insel, however, chooses to respond by saying that an experimental study would be required in order to resolve the issue.

Tamaro may have a bit of a point about Insel choosing the easiest to attack, but she is doing the same thing by ignoring the fact that there have been calls from the anti-vaccine movement for experimental studies, which, of course, would be highly unethical because they would leave large numbers of children completely unvaccinated and thus vulnerable to vaccine-preventable diseases. In any case, here’s where Tamara goes right off the deep end:

I would like to point out the epidemiological similarity between smoking/lung cancer and vaccines/autism. Smoking has been proven to cause lung cancer, yet not a single experimental study on humans was ever done – all of the human studies proving that smoking causes lung cancer were observational. The experimental studies were performed on research animals only. Attached at the end of this letter is a lesson taken verbatim from an introductory course in college statistics describing how the connection between smoking and lung cancer was made.

There have been lots of experimental studies on research animals of vaccines trying to show a link between vaccines and autism. I’ve written about some of them right here, and other bloggers have discussed them in detail as well. For example, there was the infamous Mady Hornig “rain mouse” study, in which she claimed that thimerosal at the doses infants received, adjusted for size, caused autistic symptoms. Both Prometheus and Autism Diva enumerated the numerous flaws and ethical lapses in that experiment. Then there was the more recent (and even more unethical) Laura Hewitson experiment looking at vaccinated and unvaccinated Macaque monkey infants. I was appalled at how badly designed and grossly unethical that experiment was, not to mention at the enormous undisclosed conflicts of interest of the investigators. The problem, of course, is that there is not yet a good animal model of autism. If there were, you can bet that there would be a huge amount of research using animal models. It’s not because the NIH is unshakably opposed to animal research on vaccines and autism. Rather it’s because such research is inherently not particularly useful or feasible absent a good animal model or two. Moreover, the history of such research (i.e., Hornig and Hewitson) is not exactly cause for optimism, given how badly done these studies were.

In addition, the tobacco comparison is a favorite canard of anti-vaccinationists (for instance, Dr. Jay Gordon). Certainly, it was primarily epidemiological studies that showed that smoking causes cancer. While she is correct to say that an experimental (i.e., randomized, blinded) study is not always necessary to provide sufficient evidence of causation to conclude that there is causation, she’s picked the wrong example for a number of reasons. For smoking and cancer, the association is very strong, stronger than almost any environmental toxin and cancer that I can think of off the top of my head. Smoking results in a ten-fold increased risk of lung cancer. Such a high magnitude of increased risk is generally not that hard to detect with an epidemiological study of even fairly weak design, as long as there are sufficient numbers and the condition is not extremely uncommon. But more importantly, what Ms. Tamara either doesn’t know or fails to acknowledge is that the very same sorts of studies that identified smoking as a huge risk factor for lung cancer and cardiovascular disease are the same sorts of studies that have failed to find an association between either thimerosal and autism or vaccines and autism. For example, it was a case control study by Sir Richard Doll that was credited with first detecting the link between smoking and lung cancer (although actually Nazy doctors discovered the link with a case control study two decades before Sir Doll did).

In any case, Ms. Tamara is also wrong when she says that a study of the vaccinated and unvaccinated has never been undertaken. First, there have been studies looking at who the unvaccinated are and where they live. One study published in Pediatrics in 2004 found that:

Undervaccinated children tended to be black, to have a younger mother who was not married and did not have a college degree, to live in a household near the poverty level, and to live in a central city. Unvaccinated children tended to be white, to have a mother who was married and had a college degree, to live in a household with an annual income exceeding $75 000, and to have parents who expressed concerns regarding the safety of vaccines and indicated that medical doctors have little influence over vaccination decisions for their children. Unvaccinated children were more likely to be male than female. Annually, 17 000 children were unvaccinated.

In other words, there are a lot of difficult confounders to control for, and the number of unvacccinated children is small, further complicating epidemiological studies. Ironically enough, Generation Rescue itself tried to do it. It was a very bad study, really no more than a phone survey, and its results were amusing in that they found that the highest rates of autism were in the so-called “partially vaccinated” children. The clear implication of the study was drolly described by Kevin Leitch:

There’s no getting away from this. This is a disaster for Generation Rescue and the whole ‘vaccines cause autism’ debacle. Generation Rescue’s data indicates that you are ‘safer’ from autism if you fully vaccinate than partially vaccinate. It also indicates that across the spectrum of autism, you are only 1% more likely to be autistic if you have had any sort of vaccination as oppose to no vaccinations at all – and thats only if you are male. If you are a girl you chances of being on the spectrum are less if you have been vaccinated! Across both boys and girls, your chances of being on the spectrum are less if you have received all vaccinations.

I can only conclude that Ms. Tamara is also quite naive in that she clearly has no clue just how much money and how many children an observational study of the vaccinated versus unvaccinated would require to do properly, much less how tricky it would be to control for confounders, given that the unvaccinated vary in significant ways from the vaccinated. Skeptical blogger extraordinaire Prometheus tells the tale. First, he points out how few completely unvaccinated children there are to study, perhaps around 50,000 in the entire U.S., in the 3-6 year old age cohort that would be most fruitful to do a study looking at autism incidence in the vaccinated and unvaccinated. Prometheus then explains:

Let’s say – for the sake of argument – that we decide that a 10% difference in autism prevalence is enough to convince the skeptics that vaccines might cause autism and that a less than 10% difference will convince the believers that vaccines don’t cause autism. [I know, the latter assumption is pure fantasy.]

Well, plugging those numbers in – along with the current 1 in 150 autism prevalence – we find that we need over 360,000 children in each group to detect a 10% difference (you can try it yourself here). Unfortunately, that is more than the total number of unvaccinated children in the US, so that’s not going to happen.

What can we get with our “sample” of 49,652 unvaccinated children? If we manage to include each and every unvaccinated child in the US in the study, we could detect a 26% or more difference in autism prevalence.

Of course, it’s not even remotely practical to expect to get 100% of the unvaccinated children in the country into a study. How more about a practical number – say, 10% of them? That would allow us to detect a 70% or greater difference – about a three-fold difference in autism prevalence between the fully vaccinated and unvaccinated groups.

Does anyone here think that parents who fervently believe that vaccines cause autism would accept negative results from a study that’s only powered to detect a three-fold difference in autism rates between the vaccinated and unvaccinated as sufficiently reassuring to accept the current vaccination as safe? Prometheus was right when he said that a study powered to find a 10% difference would probably not sufficiently reassure them. Given the religious fervor with which the anti-vaccine movement clings to the myth that vaccines cause autism, I doubt that it would accept a negative result from a study powered to detect a 1% difference in autism rates as sufficiently reassuring to abandon its fear. Moreover, as Prometheus tells us, even the study described above would be inordinately expensive and difficult to do. So he did a “back of the napkin” calculation of what a more feasible study could accomplish:

Finally, let’s “run the numbers” on a more practical study – one where we are able to enroll 500 unvaccinated children and 5000 fully vaccinated controls matched for age, sex, socioeconomic group, geographic location, urban vs rural vs suburban setting and race.

This study – which would still be very difficult and expensive to do – would only be able to detect a more than 15-fold difference in autism prevalence between the two groups. It could detect as little as a 7-fold difference, but only if we were willing to accept a beta error (chance of erroneously saying there is no difference when there is a difference) of over 50%.

I doubt this would “satisfy” the vaccines-cause-autism believers if the results were negative.

I can’t help but note that the study described by Prometheus would probably fail to find the well-known increased risk of lung cancer and heart disease due to smoking, the more so since the incidence of lung cancer in nonsmokers is considerably lower than 1 in 150, which is how many children are estimated to be autistic. Remember, the relative risk of lung cancer due to smoking is on the order of ten-fold.

The only way to get around the problems inherent in designing a study with sufficient numbers of unvaccinated children of sufficient power to detect a difference in autism prevalence between the unvaccinated and vaccinated children small enough to reassure most parents that vaccines do not cause autism would be to expand the study to multiple nations. Of course, doing such a study would be even more enormously expensive, take several years, and, because funding for autism research is pretty much a zero sum game, would divert huge amounts of money from more promising research to chasing down a highly implausible hypothesis that has virtually no credible empirical support behind it, either from basic science, epidemiology, or other evidence, certainly nowhere near enough evidence to justify such a huge expenditure and effort. Alternatively, as Prometheus points out, we could look at dose-response models:

Of course, we wouldn’t have to just look at unvaccinated vs fully vaccinated with this study, which is a large part of its superiority. We could look at a dose response of vaccination - to see if it really is “too many” – as well as the age at youngest vaccination – to see if it really is “too soon”. In fact, a few studies have already looked at those issues and found that there is no difference between the autistic and non-autistic groups. I suspect this is the reason the folks pushing to “put on a study” want to look at vaccinated vs unvaccinated – they hope that the numbers will be different (or, at least, not as definitive) the other way round.

In fact, I rather suspect that the smarter among the anti-vaccinationists know all the problems inherent in doing a study of vaccinated versus unvaccinated children. Certainly the government does, hence its reluctance to spend all sorts of money chasing a highly improbable hypothesis. (If only it would apply that reasoning to NCCAM!) In reality, the “vaccinated versus unvaccinated” gambit is just that–a gambit. The leaders of the anti-vaccine movement probably know that doing a study with sufficient power and numbers to exclude even a modest risk of autism due to the current vaccine schedule is so expensive and impractical that it would probably never be done and that smaller studies that are feasible will have too little power to reassure those who believe that vaccines cause autism that vaccines are in fact safe. Why do it then? It keeps the troops fired up thinking that there is some huge conspiracy to prevent such a study because of the fear of its results or that the government just doesn’t care enough about autistic children to do such a study.

On the other hand, antivaccinationists should be very careful what they ask for. They may just make enough of a pain of themselves to get it. True, getting the resources necessary to do a study the like of what Prometheus described intially would monopolize autism research funding for years, but the anti-vaccine movement doesn’t really care about that, because it’s always been all about the vaccines more than helping autistic children. Worse, if the government ever did spend the money on such an enormous study and it was resoundingly negative, it’s easy to predict that it would make no difference. As they have done before for other large studies, anti-vaccinationists would discount the results and cry bias. Still, if the government caves and decides to do such a study, it is up to us in the scientific community to make sure that it’s done by no one but the best epidemiologists, in other words, that it’s a proper study that correctly controls for confounders and can answer the question being asked, not the dubious study custom designed to have the maximal chance of a false positive result, which is of course what the anti-vaccine movement really wants.

Posted in: Clinical Trials, Medical Ethics, Public Health, Science and Medicine, Vaccines

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56 thoughts on “The perils and pitfalls of doing a “vaccinated versus unvaccinated” study

  1. Todd W. says:

    What would a study like the 70% difference one actually be likely to cost?

    I’ve run into people claiming these studies wouldn’t be that hard or expensive, so it would be nice to give them a ballpark figure as to why it would be unreasonably expensive.

  2. seemstome says:

    You don’t need an animal model of autism in order to do animal research. The anti-vaccine people believe that toxins in vaccines, or getting too many vaccines at once, damages the immune system, which can in turn lead to autism. So animal research doesn’t have to look for signs of autism in animals; just look for more easily measurable signs of immune system damage. Look for any kind of apparently important differences between the experimental and control animals.

    If the experimental animals are just as healthy as the control animals over a reasonable period of time, and if the vaccine doses reasonably approximate human doses, that would lend support to the pro-vaccine advocates.

    This is all based on the assumption that if vaccines could cause autism, they would cause other problems in addition. Which seems reasonable enough.

    So why can’t a pro-vaccine organization do this?

  3. passionlessDrone says:

    Hi David Gorski –

    According to this idea, somehow excessive “immune stimulation” or injection of “toxins” that is leading to and “epidemic” of autism, asthma, and a huge variety of other ailments and conditions.

    You might be interested in taking a look at some animal experiments that have demonstrated permenant changes in immune function, behavior, seizure succeptibility, and stress response in animals that experience early life immune stimulation during critical windows of development.

    Postnatal Programming of the Innate Immune System just came out and is a review of several papers that indicate that demonstrate alterations in fever response in animals challenged during specific developmental timeframes.

    The postnatal period represents a malleable phase in which the long-term behavior and physiology of the developing organism, including its immune responses, can be influenced. Postnatal challenge of the immune system by introduction of live replicating infections, or administration of bacterial and viral mimetics, can result in a multidomain alteration to the defenses of the adult host. Findings from our laboratory and others’ indicate that the postnatal administration of lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (PolyI:C), which mimic bacterial and viral infections respectively,
    can influence the neuroimmune response (generation of fever and production of cytokines) to a second challenge to
    the immune system in adulthood. This long-lasting alteration in the innate immune response is associated with myriad
    other effects on the animal’s physiology and appears to be primarily mediated by a sensitized hypothalamic-pituitaryadrenal
    axis. Thus, a transient immunological perturbation to a developing animal may program the organism for subsequent
    health complications as an adult. In this review we discuss some of the potential mechanisms for these phenomena.

    While several of the papers reviewed seemed to have one subset of clinical findings opposite to what we see in autism; a reduced immune response as a result of secondary challenge, acknowledging this does nothing to bolster our knowledge of if we are having subtle, but none the less real effects on some of our infants up and above the laudable goals of disease erradication.

    Simlarly, in 2008, Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats found that rats exposed to LPS, or Tnf-Alpha during critical periods were subsequently more succeptible to seizures than animals given saline, or those that were concurrently administered tnf-alpha antibodies.

    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.

    It may be worth noting that children with autism are known to initiate a much more robust immune response than their undiagnosed peers when examined in vitro; including highly increased levels of tnf-alpha, and IL-6, both of which are recently implicated in creating seizures. Considering the very high number of children with autism and seizures, the known correlations between having infantile seizures and a subsequent autism diagnosis, there might be valuable lessons to be learned in gaining a more solid understanding of this type of relationship.

    Several studies included in the review, and the 2008 Galic paper found a time dependent effect; such that animals challenged at different times had much different outcomes.

    There are several others that observed behavioral changes, increased succeptibility to colitis, and alterations to COX-2 production in animals given LPS during early development.

    I’m not sure how cavaleirly I would rail about the lack of substance behind the ‘too many too soon’ mantra; though the people originating that claim almost certainly weren’t aware of this type of research, that does nothing to invalidate it. One thing is for certain, studies analyzing thimerosal or its absence tell us nothing about the observations described above. Likewise, the MMR, while studied, is given much later in life than the bulk of our existing vaccine schedule; it has received attention due to parental reports of wild changes in their children. Just because an unintended effect doesn’t manifest itself in immediately obvious ways doesn’t mean there isn’t a problem.

    I think what might help is more basic research in the area of vaccines in regards to the robustness of the innate immune response generated, the differences in neonatal, infant, and childhood immune responses, furhter understanding of the mechanisms behind an increased immune response in the autism population, and the possiblity of evaluating for time dependent effects in populations that for one reason or another might have altered vaccine schedules. In this fashion, we could keep learing while avoiding some of the problems you detail.

    - pD

  4. Todd W. says:

    @pD

    Several studies included in the review, and the 2008 Galic paper found a time dependent effect; such that animals challenged at different times had much different outcomes.

    Do you have links to those studies so we can see what the effects were? I.e., what pattern did the effects follow? Was there a greater impact with early administration vs. late administration across the board? Or the opposite? Or did it start with low impact, higher impact, then lower impact? Or high-low-high?

    @seemstome

    You don’t need an animal model of autism in order to do animal research.

    It depends on the question you’re trying to answer. If you are trying to answer the question “Do vaccines have a causal role in autism?”, then you would need an animal model of autism.

    So animal research doesn’t have to look for signs of autism in animals; just look for more easily measurable signs of immune system damage.

    What you suggest only looks at the question “Do vaccines cause immune system damage?” This wouldn’t answer the question we’re really interested in, which I mentioned above. Suppose you find that there is no immune damage. What does that say about autism? Nothing. Suppose that it finds that there is immune damage. Then it would also say nothing about autism.

    If there were alterations in the immune system, you could, I suppose, then look at whether a) there were alterations in the immune systems of people with autism who have been vaccinated and b) if those alterations are the same as those in the animals. But, then you’d also need to control against the general vaccinated, autism-free population, as well as the unvaccinated autism-free population and unvaccinated autistic populations.

    So, not having an appropriate animal model for autism (and which form?) makes for a much more complex and convoluted path of research, with lots more room for error.

  5. seemstome says:

    There is no animal model for autism because animals can’t speak our languages. But it makes no sense to use that as an excuse for not doing animal studies. Experiments cannot usually be done on humans, so either you do animal research or you give up and join either the pro-vaccine or the anti-vaccine group based on your emotional preference.

    If animals are given appropriate doses of the vaccines and their health suffers in some way, that indicates that maybe there is some danger in giving vaccines to human infants, and maybe more caution would be recommended. Researchers could take it from their and look deeper into the question.

    If, on the other hand, animals are not harmed in any way at all from various doses of vaccines, received at various ages, that would help to vindicate the pro-vaccine advocates.

    It might not be easy (worthwhile research seldom is easy), but it’s better than hearing the 2 sides yell at each other without having good data for either position.

  6. Todd W. says:

    @seemstome

    There is no animal model for autism because animals can’t speak our languages.

    There’s more to autism than just language. E.g., stereotypy, self-injurious behavior, stimming, etc.

    But it makes no sense to use that as an excuse for not doing animal studies.

    No one is using that [lack of human language] as an excuse for not doing animal studies. Rather, the lack of identifiable autistic traits in non-human animals is what’s keeping scientists from doing proper animal studies, I’d think.

    so either you do animal research or you give up and join either the pro-vaccine or the anti-vaccine group based on your emotional preference.

    I’d hope that the science of vaccines is what leads a person to the appropriate group, rather than emotional preference.

    If animals are given appropriate doses of the vaccines and their health suffers in some way, that indicates that maybe there is some danger in giving vaccines to human infants, and maybe more caution would be recommended.

    Perhaps. It could also stem from results unique to the animal, which do not translate to humans.

    If, on the other hand, animals are not harmed in any way at all from various doses of vaccines, received at various ages, that would help to vindicate the pro-vaccine advocates.

    Perhaps. Similar to above, it could also be that lack of harm is unique to the animal, and, again, does not translate to humans. There have been instances in the past where a drug has not shown cause for concern after testing in animals but had disastrous effects in Phase I trials. I can’t remember the drug, but there was one that did fine in pre-clinical animal trials, but when tested in 8 healthy adult humans, I think 6 of them died, and the other two survived, but didn’t fare too well.

    It might not be easy (worthwhile research seldom is easy), but it’s better than hearing the 2 sides yell at each other without having good data for either position.

    Well, there’s pretty good data showing that vaccines (in general) are safe. There is not much data showing that vaccines (in general) are unsafe, keeping in mind that “safe” is determined by the benefit:risk balance. Certainly, there is no good evidence that vaccines cause autism, despite many studies looking at the question.

  7. Scott says:

    So all of the original safety studies, and ongoing safety monitoring, aren’t good data?

    Either you’re suggesting looking generally at overall safety, in which case it’s already been done quite thoroughly, or you’re suggesting a targeted study for autism, which can’t be done due to lack of an animal model of autism, or you’re suggesting a targeted study of something else, which would be pointless (no foundation to suspect relevance AND no solid connection to what people are worried about).

  8. Todd W. says:

    @Scott

    or you’re suggesting a targeted study of something else, which would be pointless (no foundation to suspect relevance AND no solid connection to what people are worried about).

    I have noticed that the anti-vax types are starting to incorporate non-autism conditions into their arguments against vaccines (e.g., asthma, allergies, autoimmune disorders, etc.).

  9. seemstome says:

    “Well, there’s pretty good data showing that vaccines (in general) are safe. ”

    No there isn’t, and you obviously prefer making excuses. Maybe you’re afraid animal research might show that vaccines can be harmful, especially if received in excess at an early age.

    Animal subjects are NEVER the same as human subjects, so that objection is ridiculous. Animals are used as a substitute when using human subjects would be unethical.

    And when I said animals don’t speak our language it should have been obvious that I know more than language is involved in autism. All the human social skills, for example.

    But I should not have to explain all that because we ALL KNOW the reasons for using animal subjects in order to study human diseases. And we ALL KNOW research isn’t perfect.

    And everyone should STOP making all these excuses for not doing the experiments and finding out, rather than taking sides based on emotion, rather than science.

  10. Scott says:

    “No there isn’t, and you obviously prefer making excuses.”

    Please explain why pre-approval safety testing and post-approval monitoring do not constitute good data showing that vaccines are, in general, safe (in the “acceptable risk/benefit” meaning of safe, not the unachievable “no risk” meaning).

  11. Todd W. says:

    @seemstome

    No there isn’t, and you obviously prefer making excuses.

    So, the safety and efficacy testing done on all products before they are approved for market is not good evidence? The epidemiologic studies aren’t good? Please point out specific criticisms of the studies that have been done showing the safety and efficacy of vaccines.

    Animals are used as a substitute when using human subjects would be unethical.

    True, but they are also used to test everything before being tested in humans. As I said, much of the time, it works. We have pretty good animal models (and when testing a product as it relates to a particular disease, we generally have an animal model of the disease against which to test), but occasionally the results don’t translate.

    And everyone should STOP making all these excuses for not doing the experiments and finding out, rather than taking sides based on emotion, rather than science.

    You’re sounding a bit emotional (what with the increasing use of capitals). At any rate, we are not making excuses; rather, we are pointing out the current shortcomings of using animals (e.g., no adequate non-human animal model of autism). But, hey, if someone wants to do the studies and find their own funding for it, more power to ‘em. Just be sure to put proper controls in place, ask the right questions, and use methods that are appropriate to the questions being asked.

    But, agreed. People should not base their decisions on emotion. They should base it on the science. Which is what we’ve been saying all along.

  12. SF Mom and Scientist says:

    @seemstone – you talk about animal studies being necessary when human studies are impossible. I work in the medical device field, and for us animal studies are performed before human clinical trials, in order to have enough data to indicate whether or not it would be worthwhile and ethical to perform human studies. We can not get definitive data from animal studies alone.

    Therefore, performing the type of animal studies you discuss (especially since there is not a good animal model for autism) would not be able to answer your questions. The studies performed on vaccines prior to release are more thorough than the animal studies you propose.

    I would like to know what specifically is lacking, in your opinion, in the studies already completed.

  13. seemstome says:

    “I would like to know what specifically is lacking, in your opinion, in the studies already completed.”

    The research mentioned by Gorski, showing that vaccines are unrelated to autism, is all correlational. Autism rates increased even after thimerisol was removed, and the conclusion was that vaccines cannot cause autism. But, as Gorski says, autism rates rose at least partly because of increasing diagnosis, not necessarily because of increasing incidence. And we don’t know what other factors may have caused autism rates to rise after mercury was removed. And we don’t know if something else about vaccines might be harmful to infants, in excessive amounts.

    Safety testing may have been done, but it may have ignored important factors.

    Gorski doesn’t like the animal studies that have been done, but that doesn’t mean they should not be done. Obviously, autism in animals would not be the same as the human syndrome. This kind of problem always occurs in animal research.

    It would make sense to look at how receiving a large number of vaccines within a short period of time might effect very young animals’ immune systems. As someone posted above, there might be reasons to suspect that excessive vaccines could effect infants’ immune systems in ways not understood.

    I do not see why past vaccine safety tests should be accepted uncritically. Maybe vaccines never cause death or severe reactions, but that doesn’t mean there aren’t more subtle dangers.

    Infants are much more vulnerable and sensitive than adults, and I can’t imagine why there is such intense opposition when people question the safety of vaccines. Of course vaccines should not be blamed for autism without good evidence. But what’s wrong with doing animal studies and trying to find out?

    Maybe more care should be taken in the use of vaccines. Hardly and sane reasonable person would question the need for at least some vaccines. But there is nothing insane or unreasonable about wanting to collect good quality experimental evidence.

    No, you can’t have a perfect animal model of autism, or any other human disease. No, research can’t ever be perfect. But the correlational autism studies are not convincing, and that’s one reason the anti-vaccine movement hasn’t died.

    If you want people to have confidence in the safety of vaccines, be open-minded about animal research. Even without the perfect animal model of autism you seem to think would be required.

  14. Scott says:

    “The research mentioned by Gorski, showing that vaccines are unrelated to autism, is all correlational. Autism rates increased even after thimerisol was removed, and the conclusion was that vaccines cannot cause autism. But, as Gorski says, autism rates rose at least partly because of increasing diagnosis, not necessarily because of increasing incidence. And we don’t know what other factors may have caused autism rates to rise after mercury was removed.”

    Argument from ignorance. Nothing can ever be proven 100%, and there is simply no cause whatsoever to suspect vaccines.

    “And we don’t know if something else about vaccines might be harmful to infants, in excessive amounts.
    Safety testing may have been done, but it may have ignored important factors.
    Gorski doesn’t like the animal studies that have been done, but that doesn’t mean they should not be done. Obviously, autism in animals would not be the same as the human syndrome. This kind of problem always occurs in animal research.
    It would make sense to look at how receiving a large number of vaccines within a short period of time might effect very young animals’ immune systems. As someone posted above, there might be reasons to suspect that excessive vaccines could effect infants’ immune systems in ways not understood.”

    So your argument is that the human testing may have missed something, and therefore animal testing is needed? That’s exactly backwards. What makes you think that animal testing would be more robust? Particularly when you’re invoking some nebulous “infants’ immune systems may be affected in some not-understood way.” That’s precisely the sort of effect animal studies can’t hope to address.

    “I do not see why past vaccine safety tests should be accepted uncritically. Maybe vaccines never cause death or severe reactions, but that doesn’t mean there aren’t more subtle dangers.
    Infants are much more vulnerable and sensitive than adults,”

    Straw man. They ARE tested in infants, are NOT accepted uncritically, and ARE the best way to find any subtle dangers.

    “and I can’t imagine why there is such intense opposition when people question the safety of vaccines. Of course vaccines should not be blamed for autism without good evidence. But what’s wrong with doing animal studies and trying to find out?”

    Because they’re a useless waste of money in light of the evidence we already have. And therefore, they take resources away from research into autism or vaccine safety that might actually be fruitful.

    “Maybe more care should be taken in the use of vaccines. Hardly and sane reasonable person would question the need for at least some vaccines. But there is nothing insane or unreasonable about wanting to collect good quality experimental evidence.”

    Indeed, which is why so much good quality experimental evidence has already been collected, and continues to be collected.

    “No, you can’t have a perfect animal model of autism, or any other human disease. No, research can’t ever be perfect. But the correlational autism studies are not convincing, and that’s one reason the anti-vaccine movement hasn’t died.”

    So research can’t ever be perfect, but we have to assume that vaccines cause autism until it is proven perfectly. Quite hypocritical of you.

    “If you want people to have confidence in the safety of vaccines, be open-minded about animal research. Even without the perfect animal model of autism you seem to think would be required.”

    Open-minded is not the same as mindlessly accepting anything anybody suggests. You’re advocating a “brains fall out” level of credulity here. It has been open-mindedly considered, and rejected on sound scientific grounds.

  15. Henry says:

    “Infants are much more vulnerable and sensitive than adults, and I can’t imagine why there is such intense opposition when people question the safety of vaccines”

    Because there is no solid evidence nor plausible mechanism suggesting vaccines may cause autism other than mere conjecture from the public. And it is absurd for scientific community to perform an experiment just because a few laypeople are questioning them. To please the public is the job of the service industry not science.

  16. seemstome says:

    “which is why so much good quality experimental evidence has already been collected, and continues to be collected.”

    Then why not say what has been done? The why does Gorski only mention the correlational studies, and never the good quality experimental evidence you say exists?

  17. passionlessDrone says:

    Hi Todd W –

    Do you have links to those studies so we can see what the effects were? I.e., what pattern did the effects follow? Was there a greater impact with early administration vs. late administration across the board? Or the opposite? Or did it start with low impact, higher impact, then lower impact? Or high-low-high?

    Sure. The patterns tended to differ somewhat depending on the outcome being measured.

    Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats

    In general, a curve was observed, such that increased neuronal excitability in vitro, and seizure succeptibility in vivo was increased if challenged between day 7 and day 14, but not if challenged on day 1 or day 20.

    Early-Life Immune Challenge: Defining a Critical Window for Effects on Adult Responses to Immune Challenge

    Here, febrile and COX-2 responses were seen to be attenuated in animals challenged on day 14 and 21, but not 7 or 28.

    Neonatal inflammation produces selective behavioural deficits and alters N-methyl-D-aspartate receptor subunit mRNA in the adult rat brain

    Where a variety of different behavioral and gene expression patterns were observed according to challenge date.

    While not explicitly testing for a time dependent variable, there are other studies that indicate modified immune function in animals challenged during early postnatal life. You might also check out:

    Neonatal programming of the rat neuroimmune response: stimulus specific changes elicited by bacterial and viral mimetics

    where evidence that the changes were TLR / antigen class specific by cross testing bacterial and viral mimics.

    Neonatal bacterial infection alters fever to live and simulated infections in adulthood

    Long-Term Alterations in Neuroimmune Responses after Neonatal Exposure to Lipopolysaccharide

    or

    Neonatal Infection-Induced Memory Impairment after Lipopolysaccharide in Adulthood Is Prevented via Caspase-1 Inhibition

    - pD

  18. passionlessDrone says:

    Hi Seemstone –

    You don’t need an animal model of autism in order to do animal research. The anti-vaccine people believe that toxins in vaccines, or getting too many vaccines at once, damages the immune system, which can in turn lead to autism. So animal research doesn’t have to look for signs of autism in animals; just look for more easily measurable signs of immune system damage. Look for any kind of apparently important differences between the experimental and control animals.

    I’m not sure that ‘damage’ is correct, so much as modification; as tinkering with something as delicate and central as the immune system can have effects that might not manifest as a classical autoimmune disorder. But again, this doesn’t mean we haven’t had an impact, just that it’s symptoms aren’t immediately observable unless we look in the right way.

    Take a look at some of the studies I posted above regarding early life immune activation in animals and consequent changes to immune function.

    - pD

  19. Todd W. says:

    @seemstome

    Then why not say what has been done? The why does Gorski only mention the correlational studies, and never the good quality experimental evidence you say exists?

    From your posts, you seem to have things backward. You seem to be of the opinion that scientists should prove that vaccines do not cause autism. That’s the wrong way to be asking the question. It would be like me asking you to prove that an invisible pink unicorn is not in my garage. You won’t be able to do it.

    The right question to ask is, do vaccines cause autism? The anti-vax crowd is claiming that vaccines do cause autism, yet they have not produced any evidence to back up that claim. See, one of the first claims was that MMR causes autism. That was based on Wakefield’s fraudulent study and subsequent PR statements. When that failed to pan out, thimerosal became the spectre. Clearly, the argument goes, since the number of vaccines increased in the ’90s, children were being exposed to more thimerosal, which metabolizes into ethylmercury, and mercury is bad, they say, in any amount whatsoever. The mercury (eeep!) therefore causes autism. Yet, again, they didn’t produce any valid studies to back up the claim. Instead, scientists had to spend time and money on epidemiological studies to examine whether there was any difference between populations receiving thimerosal vs. those that didn’t. And guess what? No correlation! Yet despite the lack of evidence, the FDA, under pressure from lobbyists and Congress critters, suggested thimerosal be removed from vaccines. It’s now been 7 years since the last thimerosal-containing vaccines were being given to kids (barring flu vaccine), which means exposure to thimerosal is less than what they got even in the ’80s. And, guess what? No changes in autism rates!

    So with yet another stab in the dark missing the mark by a long shot, they move the goalposts again. Not only have they moved them, but they’ve built new ones off to the side. Aluminum, squalene, formaldehyde, fetal tissue, too many too soon. They’re grasping at straws, demanding that scientists use their time and money to examine all these other things, still with no plausible basis from which to even start.

    All the time, they ignore the research that has shown that changes to the diagnostic criteria, screening, tools, awareness, etc., explain the sudden jump since the ’90s. As Barbara Loe Fisher of the National Vaccine (mis)Information Center put it, “If it’s not thimerosal, it must be something else [about the vaccines].” They have become convinced that they are absolutely right, all evidence to the contrary be damned. “The researchers are biased! They’re shills for big pharma! They want to kill our children!” Those are the types of statements that you find from the anti-vax crowd about people who are actually doing all this research they’re demanding, when that research comes up negative.

    The focus on vaccines is taking time and money away from more promising avenues of research, like genetics.

    Sorry for the long screed, but seemstome doesn’t really appear to get how medical science works, or what has already been done. Here’s a suggestion, seemstome. At the very top of the page is a tab labeled “SBM Topic-Based Reference”. Click on that and read through all the stuff that’s been written before. A lot of the questions you ask can be answered there. It may take you a while to get through it all; there’s a lot.

  20. Todd W. says:

    @pD

    Thanks for the links. So, it would seem that those studies would suggest paying attention to when we deliver vaccines, but doesn’t really support a “too many, too soon” argument, since there were some earlier days when there was no impact, followed by a period of increased impact.

  21. passionlessDrone says:

    Hi SF Mom and Scientist –

    I would like to know what specifically is lacking, in your opinion, in the studies already completed.

    What I’d love to see are more measurements before and after vaccination in terms immunological markers up to above seriopositivity; things like future innate immune responses to challenges, basal rates of inflammatory cytokines and chemokines, and investigation of time dependent effects.

    I found a remarkable lack of research in common childhood vaccines for any of those variables. Perhaps this is a function of my improper searching more than anything else. (?)

    What I did find seemed to fly in the face of several foundational arguments supporting the notion that our existing safety testing is sufficient to the point where we understand all effects of global vaccination.

    For example, here is a study from Russia that actually measured cytokines pre and post vaccination:

    Cytokine profile after rubella vaccine inoculation: evidence of the immunosuppressive effect of vaccination

    Where researchers observed significant increased in tnf-alpha and IL-10 one full month after vaccination in teenagers, along with decreased lymphocyte response. If there is a study out there measuring similar values for the common vaccines given at two months, four months, or six months, I can’t find them. Do you know of any? Considering what we are learning about the neuro communicative properties of some cytokines, I’d also be interested in your thoughts on how we can measure the impact of such changes on an infant.

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

    Here’s one where researchers observed distinct TH1/TH2 differneces depending on if the child got DTP or DTAP as infants. This observation was made nearly a full decade after DTAP was licensed. I’d be interested in knowing if you feel this change is important to understand, and indeed, why this observation was even made if our existing safety studies had already taken it into account.

    As far as timing of vaccination is concerned, it seems we are still learning a lot about the differences between the innate immune response in adults, children, and neonates.

    Innate immunity of the human newborn: distinct cytokine responses to LPS and other Toll-like receptor agonists

    Innate immunity of the human newborn is polarized toward a high ratio of IL-6/TNF-alpha production in vitro and in vivo

    Combined Toll-like receptor agonists synergistically increase production of inflammatory cytokines in human neonatal dendritic cells

    Considering the relative recent publication dates on these studies, it seems unlikely that this type of knowledge was incorporated into existing safety studies. An understanding, or at least a WAG, of the intereactions in the developing immune system would be what I think are lacking in the existing studies.

    - pD

  22. passionlessDrone says:

    Hi Todd W –

    So, it would seem that those studies would suggest paying attention to when we deliver vaccines, but doesn’t really support a “too many, too soon” argument, since there were some earlier days when there was no impact, followed by a period of increased impact.

    Fair enough. I believe that my call wouldn’t be too many too soon, so much as, we don’t really know what we are doing all that well and details are important when we are talking about national health policy for infants. Of course, that doesn’t fit out a billboard as nicely.

    - pD

  23. daedalus2u says:

    pD, The problem is that the immune system is very very very very complicated. The immune system is working all the time. Every day everyone is exposed to countless bacteria, that if each and every one of those bacteria was not dealt with properly by the immune system the organism would die of a massive infection.

    The immune system parameters that you want to test are not constant, they change from day to day and from individual to individual. Is a difference of X% due to a different exposure? A different genotype? A different exposure in utero resulting in different epigenetic programming? Different maternal exposure to chemicals, food, stress, viruses, bacteria, or something else?

    If immune system stimulation causes a long term change in the immune system, was it the vaccine that prevented measles? Or was it the flu that was caught because the child was not vaccinated for flu? Or was it a cold that can’t be vaccinated for? Was it the peanut oil used in a lotion? Or was it something else?

    The problem with the “too many too soon” mantra is that when ever there is an adverse effect, it can and will be blamed on a vaccine as being “too soon”, or for being one of “too many”. Every other thing is ignored, diet, genetics, every other antigen in food, air, water.

    Suggest an experimental plan. How many tests of what immune parameters would you test for in how many individuals? What do we do until your plan produces enough results? Stop all vaccines and accept injuries and deaths because we don’t know what effects vaccines might be having other than stopping injuries and deaths?

  24. weing says:

    Anyone who really knows anything about autism, knows the evidence is pretty overwhelming that this is a genetic group of disorders and vaccines have nothing to do with them.

  25. weing says:

    Does anyone else besides me hold the hypothesis that seemstome is pec?

    1. David Gorski says:

      Does anyone else besides me hold the hypothesis that seemstome is pec?

      Good call. I think you may well be right. The IP addresses are different, but they are in the same block and resolve to the same city.

      I will consult with my fellow bloggers and see if they think the evidence that seemstome is pec is strong enough to ban seemstome. I vote yes.

  26. qetzal says:

    @ passionlessDrone,

    A few comments on your various citations and points about the immune system.

    First, the vast majority of your links look at what happens when you inject lipopolysaccharide (LPS) into animals. Maybe you’re not aware, but injected LPS is not very analogous to injecting a vaccine. LPS is recognized by the innate immune system. Vaccines work by stimulating the adaptive immune system. Sure, it’s much more complicated than that, and there are lots of overlaps. The point is merely that you can’t generalize from all your links to an average vaccine.

    Second, and much more important, you’re begging the question. To my knowledge, there is no good evidence anywhere that vaccines have anything to do with autism. So, pointing out all the immune system changes that might possibly occur after vaccination is a red herring. If your point is that we don’t understand everything about the immune system and vaccination, that’s completely right. But if you think that supports a possible link with autism, you’re completely wrong. There are hundreds of things that babies are exposed to these days that they generally weren’t exposed to 3-4 decades ago. There’s no rational reason to focus on vaccines versus any of those other hundreds of things.

  27. David Gorski says:

    Does anyone else besides me hold the hypothesis that seemstome is pec?

    Good call. I think you may well be right. The IP addresses are different, but they are in the same block and resolve to the same city.

    I will consult with my fellow bloggers and see if they think the evidence that seemstome is pec is strong enough to ban seemstome, given the similarity in style. I vote yes.

  28. trrll says:

    What I’d love to see are more measurements before and after vaccination in terms immunological markers up to above seriopositivity; things like future innate immune responses to challenges, basal rates of inflammatory cytokines and chemokines, and investigation of time dependent effects.
    I found a remarkable lack of research in common childhood vaccines for any of those variables. Perhaps this is a function of my improper searching more than anything else.

    Since vaccination is intended to produce alterations in the immune system, it stands to reason that there will be all sorts of changes in immunological markers after vaccination, regardless of whether vaccination is good for you or bad for you. The changes may be of considerable academic interest, but unless you have some sort of evidence to tell you which changes in these markers are harmful and which changes are beneficial, this won’t tell you anything at all regarding the safety of vaccines. less in making j

  29. trrll says:

    With respect to diseases for which the most characteristic features are changes in behaviors that are unique to humans, there has been little if any success in developing reliable animal models. Of course problems in communication aren’t the only symptoms of autism. How about stereotypy? Well, it turns out that there are all types of things that can produce stereotypy in animals–amphetamines or opiates, for example. So how about giving an animal an amphetamine and calling it a model of autism? Well, no, because humans take amphetamines and opiates, and sure enough they exhibit stereotypy–but they don’t become autistic.

    The most successful animal models of human behavioral disorders are those where there is an effective drug for the human disorder that can be used to validate the model. For example, if you put a rat in a bucket of water that it can’t get out of, and measure how long it keeps struggling before it gives up and just floats, you find that drugs that make people feel less depressed make the rat struggle longer. You can use that to find new antidepressants. So is giving up on trying to get out of the bucket a model for depression? Seems doubtful. After all, a human being would eventually figure out that they couldn’t get out of the bucket, and stop wasting energy–that’s not depressed, that’s intelligent. Besides, antidepressants work immediately in the swim model, but take weeks to make people feel better, so chances are that it’s not even really the same neurochemistry. And anyway, there are no drugs that are more than marginally effective in treating the core symptoms of autism. None. So there’s not even a drug that you can use to validate the model.

    That doesn’t mean that people aren’t trying to develop animal models of autism. There’s actually quite a lot of work going on. The most interesting work looks at mice that have mutations similar to those that have been found to be associated with autism. But so far, there is no evidence that those models have any real predictive value (e.g. for developing therapies), and until there is, few people are going to be willing to trust them for anything. And in any case, while there are a number of mutations that are more common in autism, it has not been shown that they are actually sufficient to cause autism.

  30. David Gorski says:

    Since vaccination is intended to produce alterations in the immune system, it stands to reason that there will be all sorts of changes in immunological markers after vaccination, regardless of whether vaccination is good for you or bad for you. The changes may be of considerable academic interest, but unless you have some sort of evidence to tell you which changes in these markers are harmful and which changes are beneficial, this won’t tell you anything at all regarding the safety of vaccines. less in making j

    Moreover, this line of attack by the anti-vaccine movement assumes that there haven’t already been extensive studies of the immune changes that various vaccines cause. There have.

  31. passionlessDrone says:

    Hi Daedulus2u –

    The immune system parameters that you want to test are not constant, they change from day to day and from individual to individual. Is a difference of X% due to a different exposure? A different genotype? A different exposure in utero resulting in different epigenetic programming? Different maternal exposure to chemicals, food, stress, viruses, bacteria, or something else?

    I’ve had people tell me previously of large variations on a time dependent scale for things like inflammatory cytokines, but never seen a reference. Can you provide one?

    What about the study I posted above from Russia where researchers observed persistent immune suppression following ruebella vaccination? In that case, genetics, diet, or utereo expsosures didn’t seem to matter; immune profiles changed after vaccination, and this was in teenagers.

    I’m not arguing against any of the other potential participants you list there, and in fact, I think all are important players in autism.

    If immune system stimulation causes a long term change in the immune system, was it the vaccine that prevented measles? Or was it the flu that was caught because the child was not vaccinated for flu? Or was it a cold that can’t be vaccinated for? Was it the peanut oil used in a lotion? Or was it something else?

    I do not argue that vaccines are not effective at preventing disease. I do argue that most of our existing research is about evaluating for antibody generation, as opposed to other components of the immune system; especially in the pediatric population.

    Suggest an experimental plan. How many tests of what immune parameters would you test for in how many individuals? What do we do until your plan produces enough results? Stop all vaccines and accept injuries and deaths because we don’t know what effects vaccines might be having other than stopping injuries and deaths?

    I am not advocating stopping vaccines.

    As far as experimental plans go, how about testing pre and post vaccine measurements for cytokines or chemokine changes? I’ve heard time and time again, including on this thread that this type of research has been performed, but I am unable to find it. Again, I’m willing to admit this is possibly a result of poor searching on my part. (?) Do you know of any such studies in a pediatric population?

    How about looking for time dependent changes among children, who for external reasons miss their two month well check ups; i.e., do pre and post cytokine values vary in children first vaccinated at two months versus those first vaccinated at four months?

    How about pre and post cytokine levels in children who go on to develop autism, to see if there is a difference compared to ‘normal’ children?

    The CHARGE or MARBLES studies could be places where this kind of thing could be done.

    Perhaps there are problems with these experiments as outlined above. I’m honestly just trying to come up with ways to advance our basic understanding of how we are affecting what you and I agree is a deeply complicated system, the intracicies of which are still largely mysterious to us. It isn’t that I think I’m smart, it’s that I think we, as a species, are just too dumb to get a free lunch without doing more homework.

    I appreciate your response. Thank you.

    - pD

  32. passionlessDrone says:

    Hi queztal –

    First, the vast majority of your links look at what happens when you inject lipopolysaccharide (LPS) into animals. Maybe you’re not aware, but injected LPS is not very analogous to injecting a vaccine. LPS is recognized by the innate immune system. Vaccines work by stimulating the adaptive immune system. Sure, it’s much more complicated than that, and there are lots of overlaps. The point is merely that you can’t generalize from all your links to an average vaccine.

    LPS is a well established mechanism for imitating a bacterial infection in animal models. Likewise, a vaccine is essentially fooling the body into thinking that it is infected with a particular bacteria or virus so that antibodies are developed. I don’t think they are all that different if our measurement of interest is the development of an immune response and what happens as a result of that immune response. Vaccines cause an immune response, don’t they?

    Several papers above used PolyIC to mimic a viral infection and saw similar results, but they weren’t cross referenable; i.e., LPS/PolyIC showed no effect, but LPS/LPS did, and PolyIC/PolyIC did. This speaks towards a training the TLRs in a antigen class specific fashion.

    The Galic 2008 paper above achieved the same result by giving straight TNF-Alpha; doesn’t it stand to reason that anything causing a rise in tnf-alpha would have a similar effect?

    As far as ‘stimulating the adaptive immune system’, you don’t get there unless you stimulate the innate immune system first. Bacterial or viral antigens in a vaccine are the first step in generating an antibody response, but they do that by first cranking up the innate immune response. I’m curious if you could provide a reference that indicated you could generate an adaptive response without first having an innate response; especially in the case of pediatic administered vaccines.

    As far as generalization goes, I can’t help but notice you don’t seem concerned when the argument seems to be that we can generalize the MMR vaccine to all vaccines.

    Second, and much more important, you’re begging the question. To my knowledge, there is no good evidence anywhere that vaccines have anything to do with autism. So, pointing out all the immune system changes that might possibly occur after vaccination is a red herring.

    What we have is an absence of evaluations, as opposed to the presence of evaluations with negative findings. As far as red herrings, the problem is that we have dozens of papers telling us that the immune system is dysregulated in autism.

    There are hundreds of things that babies are exposed to these days that they generally weren’t exposed to 3-4 decades ago. There’s no rational reason to focus on vaccines versus any of those other hundreds of things.

    I am generally in agreement with you concerning our infants increased exposures to a variety of compounds that can disrupt development. Again, however, with respect, I’m wondering if you are aware of how robust and deep our current knowledge is of the variations in immune system functioning in autism? This is why there is a rational reason to focus on vaccines; they are directly tied to a system that is fundamentally imbalanced in autism, and the fact of the matter is we really haven’t studied it all that well.

    I appreciate your response.

    - pD

  33. passionlessDrone says:

    HI Trrl –

    Since vaccination is intended to produce alterations in the immune system, it stands to reason that there will be all sorts of changes in immunological markers after vaccination, regardless of whether vaccination is good for you or bad for you.

    We are in agreement. I just am not convinced we understand the effects of all of these changes. The good ones, we’ve got a pretty good handle on, the subtle ones, I’m not so sure.

    The changes may be of considerable academic interest, but unless you have some sort of evidence to tell you which changes in these markers are harmful and which changes are beneficial, this won’t tell you anything at all regarding the safety of vaccines. less in making j

    OK. Good point.

    What about looking for values for which we’ve observed abnormalities in autism; i.e., tnf-alpha, IL-6, IL-1B, TGB-beta1, MCP-1, that kind of thing? That might not speak directly towards dangerous or safety, but might give us an idea if vaccination could cause changes in immunological profiles similar to what have been observed in autism.

    As far as dangerous, we have some very recent research to indicate that, for example, cytokines including tnf-alpha, il-6, and il-1b can be implicated in the generation of seizures. That isn’t to say that these messengers are always ‘bad’, but if we have a population of children known to produce these in exaggerated amounts, it is a clue.

    In any case, I’m interested in the advancement of knowledge that may only be of academic interest, because it is often the case that this type of seemingly discovery leads to something more substantial.

    Take care.

    - pD

  34. passionlessDrone says:

    Hi David Gorski –

    Moreover, this line of attack by the anti-vaccine movement assumes that there haven’t already been extensive studies of the immune changes that various vaccines cause. There have.

    Can you provide some references towards this claim? I’ve seen the claim made again and again, but the details aren’t ever provided. Specifically, can you show me anything from a pediatric population regarding immune changes other than antibody recognition rates for any vaccines in our current schedule?

    I’m genuinely interested in seeing something along these lines.

    Thanks.

    - pD

  35. seemstome says:

    I don’t have any idea who pec is. Probably someone who doesn’t always agree with you. I see a strong emotional component on the prop-vaccine side. That doesn’t mean I’m against vaccines, or that I agree with the ant-vaccine movement. I just think you are too quick to declare vaccines perfectly safe, in any amount or combination, and for all ages of children. I agree with passionlessDrone that doubts and worries have not all be addressed and controversies have not all been settled.

  36. weing says:

    Those cytokines are also implicated in atherosclerosis. Whether there are abnormalities in these in autism maybe totally unrelated to autism. I agree with you that these are fascinating things to study in and of themselves. I doubt that you can take a normal child or teenager and have them become autistic by altering their cytokine profiles. I doubt even more that you could do this with vaccines.

  37. weing says:

    “I just think you are too quick to declare vaccines perfectly safe, in any amount or combination, and for all ages of children.”
    Who says this?

  38. trrll says:

    What about looking for values for which we’ve observed abnormalities in autism; i.e., tnf-alpha, IL-6, IL-1B, TGB-beta1, MCP-1, that kind of thing? That might not speak directly towards dangerous or safety, but might give us an idea if vaccination could cause changes in immunological profiles similar to what have been observed in autism.

    This runs into the usual problem of correlational studies, and is similar to the difficulty of identifying genetic markers of autism. A substantial number of people with autism have gene deletions, which means that they are likely to exhibit alterations in multiple aspects of physiology. So just as you can’t conclude that because a gene is more likely to be mutated or missing in autistic patients, it is therefore causative in autism, you also cannot conclude that a change in the level of one of the many immunological markers is causative. Moreover, such changes could easily occur downstream of genetic changes. For example, if a transcription factor is altered in autism (which is a particularly plausible hypothesis), it would produce changes in the levels of every protein that is directly or indirectly regulated by that transcription factor, and could also affect how those levels are regulated in response to environment or drugs. Some of those changes could be causative in autism, while others would be completely coincidental. Moreover, the vast majority of autistic patients have been treated with multiple drugs, each of which has the potential to alter all sorts of biomarkers. Now you are proposing to look at a correlation between two different things, vaccination and autism, both of which are associated in wide-ranging changes in multiple biological markers. Statistically, it seems almost certain that there would be some overlap, even if there is not a causal connection.

    In other words, to draw conclusions from data of this nature, correlations are pretty much useless–you really need to know what changes are actually causative in autism, and which are not.

  39. daedalus2u says:

    pD, if you look at figure 2 of that Russian paper, which values are “abnormal”? As I read the graph, the first tests at t=0 had a range from 100 to 1100, the second had a range from 200 to 1100, the third had a range from 150 to 1400. The hypothesis that a change of 100 or so units in a parameter that has a range of over 1,000 is clinically significant doesn’t seem credible to me.

    This paper is a good example of how variable some immune system parameters are. A range of an order of magnitude is not a small range.

    We don’t know what those 18 individuals were eating, we don’t know they didn’t have another infection, what levels of stress they were under, or what else was going on in their lives because it wasn’t disclosed. We don’t know what happened at 15 days, at 60 days, at 120 days, or at any other times because no measurements were made.

    Maybe a depression of the immune system is a good thing; maybe it prevents autoimmune sensitization during the acute viremia. Maybe that is how the immune system is supposed to work.

    Better understanding of the immune system is going to come from basic research, not by focusing a microscope on vaccines. Vaccines are a tiny, tiny, tiny fraction of the antigens the immune system is exposed to. If there are immune system problems caused by immune system stimulation it is much more likely that the stimulation was not from vaccines.

    There is no a priori reason to suspect there is a connection between vaccines and autism.

    There is no credible evidence of a connection between vaccines and autism.

    There is no credible mechanism by which vaccines could be a specific inducer of generic immune system problems in autism.

    The only reason that vaccines are the target is because of the deep pockets of vaccine manufacturers and the government backing them up through the vaccine compensation program. Vaccines are a useful scapegoat for the anti-vaxers, they can whip the believers up into a frenzy over the evils of Big Pharma killing and maiming children to enrich themselves by a few pennies.

    It is from the same mentality as the attacks on the government “death panels” by those who want the government to keep out of Medicare and Medicaid.

  40. seemstome says:

    “The only reason that vaccines are the target is because of the deep pockets of vaccine manufacturers and the government backing them up through the vaccine compensation program. Vaccines are a useful scapegoat for the anti-vaxers, they can whip the believers up into a frenzy over the evils of Big Pharma killing and maiming children to enrich themselves by a few pennies.”

    It isn’t crazy to be skeptical about the safety of vaccines. Big Pharma is enriching itself by billions of dollars, not a few pennies. This controversy won’t be resolved by your kind of either-or, us-vs-them thinking. If it is ever resolved, it will be because of scientific evidence. And right now I don’t see that enough is known about vaccine safety for the decision to be obvious. You point out that big money could be involved, and then dismiss the idea as ludicrous.

    What exactly is that “same mentality” you are talking about? People who distrust vaccines are not any different in any way from people who are uninformed about government health programs? There can’t be any difference between them?

    It seems like you need to keep all ideas in neat simple boxes. But complex problems will never be solved that way.

  41. weing says:

    “And right now I don’t see that enough is known about vaccine safety for the decision to be obvious. ”
    Again, who says vaccines are absolutely safe? That is totally different from saying that they do not cause autism.

  42. daedalus2u says:

    It isn’t crazy to be skeptical about the safety of vaccines. It is crazy to be skeptical about the safety of vaccines because of things that vaccines DO NOT CONTAIN such as “antifreeze”.

    The anti-vax zealots didn’t arrive at their skepticism of vaccine safety through facts and logic, facts and logic will be useless at convincing them vaccines are safe enough to use. This has already been demonstrated empirically, and no anti-vax zealot is willing to go on record to say what facts would be sufficient to convince him/her that vaccines would be safe enough.

  43. Todd W. says:

    @seemstome

    You point out that big money could be involved, and then dismiss the idea as ludicrous.

    Probably because, when you actually sit down and think about it, the industry stands to make more money if vaccination rates drop. Why? Because if vaccination rates drop, infection rates increase, leading to greater demand for the drugs necessary to help those infected (fever reducers, anti-virals or antibiotics, saline) plus the costs of hospitalization, and potentially surgical requirements.

    And right now I don’t see that enough is known about vaccine safety for the decision to be obvious.

    How much have you actually researched on this topic? What sources have you looked at? Did you read the info that I pointed you to?

  44. Henry says:

    seemstomeon 25 Aug 2009 at 11:00 am

    “It isn’t crazy to be skeptical about the safety of vaccines. Big Pharma is enriching itself by billions of dollars, not a few pennies. This controversy won’t be resolved by your kind of either-or, us-vs-them thinking.”

    As I have said, as long as there isn’t any plausible mechanism nor solid evidence suggesting a fair possibility that vaccines may cause autism, it IS crazy to be skeptical about the safety of vaccines. You don’t just make up a hypothesis from the mind of average Joe and demand an experiment, you make up a hypothesis based on observed phenomenons. Whether an animal model for autism is available in the future or not, it is pointless to perform such an experiment because we have nothing to explain.

    And if your doubt the safety of vaccines because of the wealth of pharmaceutical industries, that is even crazier. Questioning the motive behind a theory is totally idiotic and pseudoscientific. A theory or hypothesis is developed either based on scientific methods or isn’t, that’s the sole standard you used to judge the credibility of a theory. The motivation behind the theory does NOT change anything. Historians could tomorrow discover letters from Issac Newton that he invented the theory of gravity in order to prove the British were supreme and pagans were inferior, that would not damage the credibility of theory of gravity one bit.

  45. qetzal says:

    Hi pD,

    Let me preface by saying that I’m a molecular biologist, not an immunologist (nor an MD). My knowledge of immunology is relatively superficial. I don’t want to give any impression than I’m an expert on this.

    That said, I’ll address what I can from your previous response.

    LPS injection is suitable for imitating one facet of a bacterial infection. Just because LPS and a vaccine both cause an immune response doesn’t mean that the responses are comparable. At the most proximal level, they aren’t. LPS is recognized by TLR4. Vaccine antigens are not.

    Poly(I-C) is another molecule that is recognized by TLR – TLR3. It’s more relevant to viruses, esp. RNA viruses.

    Regardless, it’s incorrect to talk about “training the TLRs in a antigen class specific fashion.” If you’re only injection LPS and/or poly(I-C), you aren’t injecting any antigens. Antigens are molecules that stimulate production of antibodies.

    No, it doesn’t stand to reason that anything that causes a rise in TNF-alpha will have the same effect as injecting TNF-alpha. How much TNF-alpha is present, for what period of time, with what time profile, and in conjunction with what other cytokines and immune system components – all of that is going to matter.

    Regarding stimulating the adaptive response without stimulating the innate response, that wasn’t my intended point. The point is that LPS injections are not a suitable model for a vaccine that lacks LPS. That includes all viral vaccines, since LPS is a bacterial product. (I don’t know the details of the various anti-bacterial vaccines, and don’t have the time to look them all up, so I can’t say for sure whether any of them might contain LPS.)

    I don’t understand your point about generalizing the MMR vaccine to all vaccines. Are you saying that even if MMR has no role in autism, that doesn’t exonerate all vaccines? If so, I agree.

    However, I disagree that ” What we have is an absence of evaluations, as opposed to the presence of evaluations with negative findings.” We have some rather definitive evaluations that demonstrate no causal link between thimerosal and autism. We also have a plethora of evaluations that indicate no causal link between MMR and autism (e.g., 12 different studies reviewed here).

    Do we have comprehensive evaluations of all relevant childhood vaccines, in all relevant combinations and doses, to demonstrate no realistic causal link to autism, or to some subset of autism? Certainly not. The problem is that we have no good reason (that I know of) to suspect vaccines as causative in the first place. Yes, I’m aware that autism is associated with immunological disfunction (though I freely admit I’m ignorant of the full robustness and depth of our understanding). But that alone is not a reason to assume that vaccines are likely to be causative, and to devote the very considerable resources it would take to test other vaccines the same way that thimerosal and MMR have been tested.

    If there’s decent evidence to suspect some vaccines, I’d be interested to see it. But simply noting that autism correlates with immune problems, or citing studies involving injection of LPS or poly(I-C) or TNF-a, doesn’t qualify. At least, not in my opinion.

  46. passionlessDrone says:

    Hi qetzal –

    I’m just a jerk parent trying to cure autism, so please, you have no reason to apologize for your credentials; at a biological level you almost certainly know lots more than me. I am trying to learn, though it may not seem like it at times.

    LPS injection is suitable for imitating one facet of a bacterial infection. Just because LPS and a vaccine both cause an immune response doesn’t mean that the responses are comparable. At the most proximal level, they aren’t. LPS is recognized by TLR4. Vaccine antigens are not.

    TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T cells

    These data provide the first definitive evidence of a role for TLRs in protective immunity induced by a human vaccine. Our findings also demonstrate that activation of innate immune cells through TLR4 helps to direct the induction of Th1 and Th-17 cells, which mediate protective cellular immunity to B. pertussis.

    There looks to be differences in whole cell versus accelular product lines here, but considering this research was published in 2006, I am not confident that we’ve really got a good handle on if or how vaccines interact with TLRs. (?)

    In any case, I would acknowledge that a one to one comparison between LPS and vaccination is an over simplification; but if our knowledge base on innate immune responses after vaccination is entirely vapor, why not use something as a starting point as opposed to nothing?

    Regardless, it’s incorrect to talk about “training the TLRs in a antigen class specific fashion.” If you’re only injection LPS and/or poly(I-C), you aren’t injecting any antigens. Antigens are molecules that stimulate production of antibodies.

    Don’t they only stimulate production of antibodies, after being recognized by a TLR though? (?) If those TLR recognize classes of antigens, would it be more appropriate to speak of training receptors that understand and initiate immune responses to classes of antigens? From Postnatal Programming of the Innate Immune Response:

    As seen with LPS, PolyI:C treatment at P14 was associated with reduced fevers and with an exaggerated corticosterone response to PolyI:C in adulthood. An equally interesting question is whether or not the postnatal animal treated with a viral mimetic will show an altered response to LPS as an adult. In contrast to what was seen with the
    homotypic challenge (LPS-LPS or PolyI:C-PolyI:C), there was no crossover between the two different TLR activators. That is, P14 PolyI:C, followed by adult LPS (and vice versa) neither attenuated fever nor altered the circulating-corticosterone response in the adult. These findings highlight the specificity
    of the programming capacity of early-life immune stimulation and suggest that these long-lasting changes to fever and corticosterone secretion may be tied to the individual TLR being activated.

    I may have made some errors in my interpretation, my wording, or the authors may have drawn incorrect conclusions on which I based my statement. (?) My take on this was that the authors felt they were observing specific training at a TLR level, and as such, future stimulations of that TLR were affected. Another study found that somewhat disimilar strains of gram negative bacteria had future effects; i.e.,enteritidis LPS in early life and e. coli later in life == altered febrile response. [Boisse, 2004]

    No, it doesn’t stand to reason that anything that causes a rise in TNF-alpha will have the same effect as injecting TNF-alpha. How much TNF-alpha is present, for what period of time, with what time profile, and in conjunction with what other cytokines and immune system components – all of that is going to matter.

    The complexity is there, but on the other side, I can’t find anything that tells me what the innate immune response looks like in regards to common childhood vaccines; i.e., is there an increase in tnf-alpha? Just because something is complex, I hate the idea of no evidence as evidence of no effect. Some people, like daedulus2u would claim that such readings would be meaningless to interpret. Others, like David Gorski seem to indicate that such studies exist. I honestly don’t know the answer. (?)

    We have some rather definitive evaluations that demonstrate no causal link between thimerosal and autism. We also have a plethora of evaluations that indicate no causal link between MMR and autism (e.g., 12 different studies reviewed here).

    Thimerosal is not of concern to me. It has been studied and in any case, is largely removed from distribution. As far as the MMR, OK, but again, this is my point about generalization; the MMR is different in a lot of ways, but especially timing wise to the vast majority of our current shot schedule.

    If there’s decent evidence to suspect some vaccines, I’d be interested to see it. But simply noting that autism correlates with immune problems, or citing studies involving injection of LPS or poly(I-C) or TNF-a, doesn’t qualify. At least, not in my opinion.

    Very well! Thanks for your comments.

    - pD

  47. trrll says:

    It is also worth noting that whereas it is not practical to do an observational study to exclude a modest increase in autism risk after vaccination, the Generation Rescue Survey pretty clearly excludes the more extreme claims of the antivax crowd that virtually nobody gets autism who has not been vaccinated (e.g. the bogus “Amish don’t have autism” claim of Dan Olmstead)

  48. The Blind Watchmaker says:

    I would worry about lowering the threshold of herd immunity by allowing such a large cohort of people to be unvaccinated.

    Look at what is happening now with measles and H. flu meningitis. If a portion of the cohort lives close to one another, the 90% threshold of herd immunity could very well not be obtained in that community (not just for these 2 infections, but for all of the vaccine preventable infection).

    Hope its not in my neighborhood.

  49. swampwaffle says:

    The other major ethical issues is that in order to do the study correctly you’d have to challenge both vax and unvax with pathogen. Can we honestly reconcile making kids sick because parents don’t understand science?

    I guess is it post-zygotic selection in action. Of course, when they all got sick the anti-vaxers would move the goalpost and claim that the kids were infected with engineered monkey viruses from Merck.

    Capitulating to non scientific demands is as anti-science as it comes.

  50. trrll says:

    The other major ethical issues is that in order to do the study correctly you’d have to challenge both vax and unvax with pathogen. Can we honestly reconcile making kids sick because parents don’t understand science?

    Not really. The idea was a study of vaccine side-effects, not a study of vaccine efficacy, so there would be no reason for pathogen challenge. It would be a reasonable thing to do if it could be done ethically. But it can’t. Leaving a large cohort of kids unprotected against vaccine-preventable diseases is unacceptable, particularly since, with the exception of a very low frequency of acute reactions, there is no evidence that vaccines contribute to any disease.

  51. Todd W. says:

    @trrll

    The idea was a study of vaccine side-effects, not a study of vaccine efficacy, so there would be no reason for pathogen challenge.

    However, that brings up a question. How would infection affect the outcome measures? Would it be grounds for exclusion from the study?

  52. trrll says:

    However, that brings up a question. How would infection affect the outcome measures? Would it be grounds for exclusion from the study?

    You’d probably want to exclude anybody who had actually had a vaccine-preventable disease, since those could conceivably induce encephalopathy with autistic symptoms. If they weren’t excluded, it could make the incidence of autism higher in the unvaccinated group. Perhaps this could explain the odd outcome of the Generation Rescue phone survey, which found that unvaccinated girls were much more likely to be autistic than vaccinated girls.

    Fortunately, in most parts of the country antivaccinationism has not taken over sufficiently for those diseases to go epidemic again, so plenty of unvaccinated kids are still safely freeloading on the vaccinated population. So excluding people who’d had vaccine-preventable illnesses wouldn’t knock the potential subject pool down too much.

  53. dugmaze says:

    If you want to study vax vs unvaxed, then why don’t you ask the unvaxed population?

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