Respectful Insolence

Blogging on Peer-Reviewed ResearchA little more than three months ago there came to pass a very bad day for antivaccinationists.

On that day, in the prestigious New England Journal of Medicine appeared a study that was powerful evidence that vaccines are not associated with adverse neuropsychiatric outcomes in children. Not surprisingly, the usual suspects in the mercury militia went on the attack immediately, not wanting to believe that yet another strong piece of evidence was attacking their hallowed belief that mercury in the thimerosal preservative previously used in vaccines is a major cause or contributer to the development of autism.

Yesterday was another very bad day for antivaccinationists, a very, very bad day indeed. Three months ago, the study released that supported the safety of vaccines did not directly deal with autism and autism spectrum disorders. Yesterday, however, a study was released in the Archives of General Psychiatry that did study the question of whether vaccination with thimerosal-containing vaccines is at all correlated with the development of autism or autism spectrum disorders. Not surprisingly, given the growing number of other studies that have failed to find an association, the answer was a resounding “No!”

Regarding the question of vaccines and autism, we can’t do a double-blind, randomized, control trial of vaccines with and without thimerosal in the face of a pre-existing vaccination program. It wouldn’t be ethical. However, we can do the next best thing, and, indeed, we now have several good studies since 1999 that did just that in other countries that removed thimerosal from their vaccines before the U.S. did. Some of these studies are epidemiological; some are ecological. What allows us to use them to reject the hypothesis that mercury in vaccines is an etiological agent that is either associated with or causes autism is a very simple but powerful prediction that thimerosal hypothesis makes. Quite simply, if the hypothesis is true and thimerosal-containing vaccines (TCVs) cause autism (or are a significant contributing factor), we would expect that the removal of thimerosal from vaccines should lead to a rapid decrease in autism prevalence within 3-5 years.

It really is just that simple. What isn’t so simple is to design a study to ask this question that is sufficiently free of confounding factors to prevent a false positive or false negative result. We are now nearly six years out from the near-complete removal of thimerosal from vaccines. Other than the flu vaccine, there is no more than trace thimerosal in childhood vaccines; overall mercury exposure due to vaccines has not been as low as it is now in decades. Consequently this hypothesis can now be tested in the United States.

In a beautifully ironic twist that makes me smile just thinking about it, Schechter and Grether chose to use a source of data that has frequently been widely abused by advocates claiming a link between TCVs and autism to try to show one where there isn’t one as though the conclusions were foreordained. Although it is not, it has even been referred to as the “gold standard” of autism epidemiology by none other than David Kirby. Indeed, this is the very same database in which David Kirby predicted that there should be a noticeable decrease in new diagnoses of autism by 2007 if the thimerosal hypothesis is true and then later shifted the goalposts to 2011 when it became apparent that there has been no decrease. This source is the California Department of Developmental Services (CDDS) database. The CDDS administers a statewide system of regional centers and developmental centers designed to serve people who are substantially disabled because of autism, mental retardation, or other developmental disabilities. It maintains an archive file of client developmental evaluation reports on clients enrolled in the system. Of course, what’s particularly amusing is how the mercury militia members who once touted the CDDS database as the be-all and end-all of autism epidemiology have, now that it is not showing what they want it to show, suddenly found religion about its shortcomings and the difficulties inherent in deriving autism prevalence rates from it. Among the strengths of the system are that it is a population-based system representing the most populous state in the U.S. Moreover, the client reporting form was consistent throughout the study period, preventing confounders due to changes in reporting. The weaknesses of the CDDS is that its data is derived from an administrative system that was designed to track enrollment and fiscal data and is not as well suited to measuring the occurrence of developmental disabilities in the population. However, with proper statistical analysis, considerable information can still be gleaned from this data for specific birth cohorts.

In order to ask the question of whether autism rates had declined, Schechter and Grether examined data for clients with active status reported from January 1, 1995 to March 31, 2007. Using careful statistical analyses, they used two approaches to measure the occurrence of ASD during this period. The second approach, in which ASD prevalence was determined in the 3 to 5 year old cohort, is perhaps the most informative. It shows a continuing increase in autism prevalence without even a blip or decrease in the rate of increase after 2002. Indeed, showing the skill of some bloggers to analyze the same data, the money figure in the paper (Figure 3) looks almost exactly the same as the graph prepared in early 2007, a continually increasing curve since 1995. This result is not only consistent with multiple other published and unpublished studies, including the famous (or, if you’re an antivaccinationist, infamous) Danish and Canadian studies, but it is about as unambiguous evidence as can be obtained from a database like the CDDS database. Indeed, despite the known limitations of the use of this database, it is an excellent example of proponents of a “mercury injury” hypothesis of autism being “hoisted by their own petard,” so to speak.

In a pointed editorial that accompanied the study, Eric Fombonne asked the same question that I’ve been asking for the last two years now about the magical thinking that leads the mercury militia to cling to this failed hypothesis no matter how many studies fail to support it:

Despite the accumulation of scientific evidence rejecting these 2 hypotheses linking autism to various components of childhood vaccines, these theories and the practices that accompany them have not faded away. Why? How many more negative study results are required for the belief to go away, and how much more spending of public funds on this issue could even be justified

This is an excellent question. Millions of dollars of taxpayer money are likely to be spent studying this hypothesis, virtually all thanks to the political clout of activists and antivaccinationists legislators like Indiana’s Dan Burton. Moreover, the hypothesis that mercury in vaccines was the cause of an “autism epidemic” was never particularly scientifically plausible in the first place; it was just barely plausible enough that activists with an agenda could make scientists throw up their hands and say, “All right, let’s take a look.” Powerful forces are at work to keep this hypothesis on life support, to the point where the federal government has even invited known antivaccinationists to sit on the new Interagency Autism Coordinating Committee. It doesn’t matter that, in the face of the onslaught of multiple new studies like this that fail to find even a whiff of a correlation between TCVs and autism, even some of the most diehard zealots are starting to back away from the attitude of “it’s the mercury in vaccines, stupid.” In the meantime, even David Kirby and those more zealous than him were starting to back away from the hypothesis, invoking hand-waving and vague “environmental toxins” or even going so far as to blame mercury from pollution wafting over from China or, even more ludicrously, mercury from the cremation of bodies with mercury amalgam dental fillings.

So what’s an antivaccinationist to do when faced with yet another study that does not support his hypothesis? Well, if you’re Mark Blaxill, one of the commandants of the mercury militia, you could start weaseling away:

Put another way, the epidemiological analysis doesn’t prove that thimerosal exposure cannot cause individual cases of autism. It simply provides evidence that it’s unlikely thimerosal can be the sole cause in all cases.

This is true as far as it goes, but deceiving. Remember, the message two years ago was that autism and ASDs are all “misdiagnoses for mercury poisoning.” That was the claim, not that maybe, just maybe, thimerosal could cause autism in some children. Come on, Mark, what happened to all those pictures of autistic children with skulls and crossbones nearby and the words “mercury-poisoned” underneath? What happened slogans like “AUTISM: It’s the mercury, stupid“? What happened to the comparisons of the “autism epidemic” to the Holocaust?

If you’re Mark Blaxill, you could also stick your fingers in your ear and shout, “Nah, nah, nah! I can’t hear you!” while claiming that the scientific evidence still supports the plausibility of a link between thimerosal and autism:

The evidence regarding the connection with autism and mercury exposure more generally hasn’t changed. The plausible theories regarding the biology of excretion and toxicity of mercury compounds and their different effects on the developing immune system, gastrointestinal system and brain haven’t been affected a single bit.

Except that these hypotheses (they’re not theories, Mark; theories must pass a much higher standard of evidence) are not plausible and are based on dubious scientific studies. Even if they were somewhat plausible, the epidemiological studies are not supporting them. When that happens, real scientists abandon such hypotheses.

Other possible approaches for antivaccinationists present themselves. For example, if you’re Wendy Fournier and Rita Shreffler of the National Autism Association, you can put out press releases repeating the same fallacy of correlation equally causation coupled with canards about biomedical interventions:

  • Why do so many children regress into autism after receiving vaccines, subsequently have symptoms of heavy metal toxicity, then get better when mercury is removed through chelation?
  • How can mercury and other toxic metals be removed from the bodies of our children more safely and efficiently?
  • What biological abnormalities exist that cause some individuals to be unable to detoxify heavy metals?

The answer to question #1 is because the ages at which the symptoms of autism often first manifest themselves overlaps the ages at which children are getting most of their vaccinations. Moreover, there is no evidence that “heavy metal poisoning” causes autism or that chelation therapy cures it; so asking how mercury and “other toxic metals can be removed from the bodies of our children” is not the right question.

Of course, if there’s one thing, though that I predicted a long time ago, it’s that, should the evidence finally start forcing the mercury militia to face the reality that thimerosal does not cause autism, they would show their true antivaccinationist colors, because it’s really not about the mercury. It’s about vaccines in general. If the weight of scientific evidence becomes so crushingly overwhelming that even Ferrous Cranus reluctantly, slowly, and painfully must yield, they’ll start blaming other “toxins” in vaccines or vaccination in general for autism. And, indeed, that’s just what these antivaccinationists do.

Quoth Mark Blaxill:

Most importantly, and this is a point that escapes Fombonne’s Lilliputian mind entirely, the evidence from the California natural experiment doesn’t exonerate the broader childhood immunization program. Quite the opposite, it brings the overall escalation in the vaccine program even more strongly under suspicion. While thimerosal was removed from hepatitis B, Hib and DPT/DTaP vaccines (but not from influenza vaccines), the vaccines themselves didn’t go away. Indeed the total count of vaccine doses has gone from 15 to 45 by the first grade and this increased exposure is strongly associated with the increases in autism rates.

Never mind that non-thimerosal-containing vaccines are not associated with autism either.

Quoth Wendy Fournier:

NAA also cited confounding factors associated with the study, which includedthe failure to address synergistic effects of mercury, aluminum and other toxic ingredients. “Thimerosal isn’t completely gone from vaccines. It is still present in trace amounts. Since no safe level of neurotoxins such as mercury and aluminum have been established, trace amounts cannot be cleared of having caused injury, especially in susceptible children,” according to NAA board member Scott Bono.

Except that thimerosal exposure from vaccines is lower now than it has been in decades. If thimerosal is such a strong cause of autism that even trace amounts can cause as much autism and ASDs as we see today, then there should have been as many cases noted in the 1980s. There weren’t.

Most telling are two statements. The first is by über-antivaccinationist Barbara Loe Fisher, who, while claiming that the rates of increase of new cases is leveling off (which, even if true, is (1) moving the goalposts post hoc, given that the prediction was the autism prevalence would rapidly fall once thimerosal was removed from vaccines, and (2) to be expected if, in the face of expanded awareness and the broadening of diagnostic criteria for autism and ASDs, autism prevalence under the new criteria was finally approaching the true prevalance rate):

During the past quarter century, the CDC and AAP increased the numbers of vaccinations doctors are told to give American children from 23 doses of 7 vaccines to 48 doses of 14 vaccnies by age five. Although today almost all childhood vaccines contain only trace amounts of mercury or never contained mercury preservatives, such as polio, pneumococcal, hepatitis A and live virus MMR, chicken pox and rotavirus vaccines, parents around the nation continue to report that their children are regressing physically, mentally and emotionally following receipt of multiple vaccines. These parents report their children are becoming chronically ill and disabled, suffering with autism, learning disabilities, ADHD, asthma, diabetes, intestinal bowel disorders and other brain and immune system dysfunction.

How many more children will be hurt before government, industry and pediatricians open their eyes and see what too much vaccination has done to our children?

Once again: Neither the MMR nor other non-thimerosal-containing vaccines are associated with autism, either. Not that facts or reality have any effect on Fisher’s irrational belief that vaccines are dangerous.

Rick Rollens, co-founder U. C. Davis M.I.N.D. Institute (as he loves to point out), in an e-mail sent to several autism activists (and that was forwarded to me) is even more blunt:

If by 2009-2010 there has not been ANY change in the rate of increase of new cases of autism entering California’s developmental services system, then we can scratch mercury in vaccines off our list of agents contained in vaccines as a cause, and; then begin concentrating on the numerous other poisons and toxic agents in vaccines such as aluminum, formaldehyde, MSG, live viruses, etc., and most importantly, the interaction of these and other toxic agents contained in the 34 doses of vaccines children receive from birth to two years old today.

Amazingly, elsewhere, he even parrots the “hidden hordes” canard, which has been debunked many times before. Rollen’s handwaving is nothing more than moving the goalposts once again and failing to recognize that the claim that mercury in vaccines causes autism is a failed hypothesis. Not that that stops zealots like Rollens. His attitude is particularly telling, especially his blatant statement that, if mercury is finally cleared, then it must be some other “toxin” in vaccines. It’s an attitude identical to the one that I pointed out two years ago and then made fun of a mere month and a half ago. Rollens’ statment shows that, for the antivaccinationists of the mercury militia, it really, truly isn’t about the mercury, their claims that they are not “antivaccine” notwithstanding. Always remember, for them, it is about vaccines themselves. If mercury in vaccines is exonerated as the cause of autism, they’ll blame the aluminum adjuvant. If aluminum is exonerated, they’ll blame the traces of formaldehyde. If the traces of formaldehyde are exonerated, they’ll either make the almost impossible to test claim that it is the “synergistic” interactions between multiple “toxins” in vaccines, or they’ll blame the one thing that can’t be removed from vaccines, the fragments of killed virus or bacteria used to provoke the specific immune response to the disease for which a vaccine is designed. The only thing they won’t blame is the water in vaccines, and even then, I’m not so sure about that. After all, it is dihydromonoxide.

Comments

  1. #1 DrFrank
    January 8, 2008

    …and then, even if you showed conclusively that it wasn’t a single ingredient of vaccines or any possible combination, they’d probably blame it on unhealthy vibrations.

  2. #2 wfjag
    January 8, 2008

    Dihydrogen Monoxide is demonstratably dangerous, sometimes lethal, and there should be serious study of its properties and effects. See http://thestatsblog.wordpress.com/2007/12/12/isn%e2%80%99t-it-time-we-banned-dihydrogen-monoxide/

  3. #3 Joseph
    January 8, 2008

    Rollens: “If by 2009-2010 there has not been ANY change in the rate of increase of new cases of autism entering California’s developmental services system, then we can scratch mercury in vaccines off our list of agents

    Rollens doesn’t know what in the hell he’s talking about, does he? What would be unusual about the rate of increase of “new cases” dropping, or even “new cases” dropping altogether, considering that ascertained prevalence obviously cannot continue to increase indefinitely?

    Nice goalpost-shifting though. In 2010, when the administrative 3-5 prevalence hasn’t dropped statistically (save for a change in the definition or our understanding of autism) will they shift it again to 2015? 2020?

    Regarding the confounds usually mentioned as an excuse, what they don’t appear to realize is that none of those confounds can explain the straight line that is the 3-5 administrative prevalence in the last 6 years or so. The drop in thimerosal exposure was quite sharp and rapid. Which confound had a sharp and rapid increase that coincided with the timing of thimeorosal removal?

  4. #4 Laurel
    January 8, 2008

    Wish I could convince the guy who writes this comic. I know him.

    http://www.webcomicsnation.com/taillefer/chelation_kid/series.php

  5. #5 DLC
    January 8, 2008

    And if a definitive study comes out which indicates that ASDs are a genetic disorder, what will the Mercury Militia
    and their allies the Anti-Vaxers do?

    Or, if it is proven that ASDs are due to exposure to illudium phosdex, which is only seen in cases where the parents are abducted and probed extensively by the Grey Aliens ?

    Okay, I know, I know — it’s not Genetic and it’s not illudium phosdex exposure, it’s toxic dihidrogen monoxide poisoning.

    Right. I’m going back to bed now.
    Damn night shift.

  6. #6 Prometheus
    January 8, 2008

    Ah, it’s so nice of Mark to provide a perfect example of “the arrogance of ignorance”.

    Orac, I’ll gaze into my crystal ball and predict the next move of the scientific Illiterati as genetic causes are shown to be the primary (if not only) source of autism.

    They will immediately (even before the embargo on the article expires) claim that these “genetic causes” result in sensitivity to vaccines – perhaps even to “various combinations and permutations of vaccine components”.

    The game is up, folks! The argument about adjuvants doesn’t hold water, either, since they haven’t been increased in a steady amount that would account for the linear increase in “autism” in the California DDS or US Dept. of Education (IDEA) databases.

    It’s the attack of the zombi hypothesis! The vaccines-cause-autism hypothesis died from lack of data, but now it’s back from the grave and hungry for brains!

    Clearly it’s already snacked on a few.

    Prometheus

  7. #7 daedalus2u
    January 8, 2008

    The “mercury causes autism” idea isn’t a hypothesis. A hypothesis has to be consistent with reality, including everything that is well known. The “mercury causes autism” idea isn’t. It is a failed hypothesis, otherwise known as a wrong idea.

    There is an explanation of why some children are seen to regress following a vaccination that has to do with nitric oxide physiology, what I call the “low NO ratchet” and which I discuss in my blog.

    http://daedalus2u.blogspot.com/2008/01/resolution-of-asd-symptoms-with-fever.html

    Any immune system stimulation causes the expression of iNOS which drives NO levels high. A vaccination will do it because the purpose of a vaccination is to stimulate the immune system. Virtually any type of infection will do it too. It may be that in susceptible children a particular vaccination may be associated with another click of the low NO ratchet, but any of the zillions of childhood infections can do it too. That we see no difference in incidence of ASDs in vaccinated vs. unvaccinated children shows that there is nothing unique about the immune system stimulation of a vaccine (which we already knew).

    The low NO hypothesis of autism (yes it is a hypothesis because it is consistent with all known facts including those about autism and NO physiology) suggests that high NO levels will restore more normal function. The recent paper on fevers in children with autism suggests this may be the case.

    Fever therapy was once used to treat a lot of neurological disorders including neurosyphilis. It was the standard of care for decades. I am not suggesting that fever therapy would be an appropriate treatment for autism, but there are a number of more benign ways to increase NO levels than inoculation with malaria.

    A transient NO increase may well activate the low NO ratchet, so rushing out and giving children with autism fevers is not a good idea.

    Research into the connections between NO physiology and autism spectrum disorders would be a good idea.

  8. #8 isles
    January 9, 2008

    Eric Fombonne rocks the catbox.

    Schechter and Grether too, but Fombonne has such a remarkably keen sense of what needs to be said, and he’s not afraid to say it.

  9. #9 Luna_the_cat
    January 9, 2008

    daedalus — I don’t think I’ve seen a topic come up on SB where you haven’t hypothesized some link to NO metabolism. I know how easy it is to see everything in the world in terms of your current research — I’ve done it myself — but you are really in danger of the “to a man who only has a hammer, everything looks like a nail” syndrome.

  10. #10 daedalus2u
    January 9, 2008

    LTC, I do understand the problem of seeing every problem as one which can be fixed with the tool at hand. Were NO not involved in the pathways that are disrupted in the issue being discussed, I wouldn’t bring it up (and haven’t). My research is focused on NO, but NO is well known to be involved in many thousands of pathways. In many disorders it appears that physiology is shifted in the direction one would expect if the basal NO level was lower than it “should” be. The known association of NO with these pathways is from the literature, not from any data I have collected.

    The importance of the “correct” basal NO level is not well appreciated, largely because it is very difficult to measure (it is less than 10 nM/L), and it is not constant either over time or across different tissue compartments. There simply are no techniques to measure it on the time (sub second) and length (sub micron) scales that are known to be important.

    NO is an ideal signaling molecule. It is small, diffuses rapidly, permeates lipid and aqueous phases, is extremely reactive with some species (near diffusion limited kinetics), binds to heme and blocks coordination of O2, binds to Fe and other Fenton active metals and modifies their chemistry and does many other things too. It is not surprising (in hindsight) that physiology has evolved to use it in so many different pathways (many thousands).

    However, because there are no barriers to NO diffusion, all NO sensors only “sense” the sum of NO from all NO sources. That makes all NO mediated pathways “coupled” to each other. In a very real sense, NO can be looked at as the “glue” that couples physiology together so that all the pathways are regulated together in sync. This is especially evident in stress where NO is lowered to decrease inhibition of cytochrome c oxidase and so maximize aerobic production of ATP. The low NO triggers other stress pathways that mediate stress responses. Low NO lowers ATP via sGC, that triggers ischemic preconditioning, and ATP conservation. In the short term, all of those stress responses are adaptive. In the long term, none of them are (otherwise they would have evolved to be the default state, not a stress response state). Low NO triggers those stress responses, and a low basal NO level lowers the threshold for triggering of those responses and activates some of them continuously. The basal NO level adds to what ever signal level is generated and modulates the effect. That is exactly how physiology has evolved to control global physiology via changes in basal NO levels. When basal NO is low, some stress responses are activated continuously, and that causes adverse effects.

    The effects of changing basal NO on one pathway cannot be separated from the effects on another pathway. In many of these diseases, you can see the effects of low basal NO on multiple systems in multiple organs simultaneously. But like all things, you can only see them if you look for them. You can’t measure the basal NO directly, but you can see the effects of not enough basal NO, what I call nitropenia.

  11. #11 Prometheus
    January 9, 2008

    Laurel,

    Don’t hold out too much hope for the writer and/or artist of “The Chelation Kid”. That “comic strip” is so full of anger and hatred that I doubt they will ever be able to sit down and rationally contemplate the issues.

    For the rest of us, the good news is that the ‘strip seems to have ended. Nothing posted since 21 September 2007.

    Prometheus

  12. #12 Brian
    January 9, 2008

    The funny thing is (and I’m sure you’re right about how they would react in the final analysis to the killed virus/bacteria) is that you’re only putting those toxic, disgusting antigens in you so that you hopefully won’t have large amounts of fully-functional versions of these antigens in you one day.

  13. #13 Coin
    January 9, 2008

    On a related note– Do you know anything about this, is this “new” news?

    ‘Bio Identical’ Hormone Therapy Has No Safety Advantage, FDA Says

  14. #14 MommaData.blogspot.com
    January 10, 2008

    Where were the front-page stories this week? Is anyone else amazed that the media has virtually ignored this latest, very convincing study? We’ve been waiting six years for this data – all the while listening to the ever desperate mercury-causes-autism camp, many parents hesitant to immunize their kids despite good studies finding no link – and so here’s the first study of the post-thimerosal vaccines and the media have nearly ignored it. Sure, the New York Times put a story in the Health Section. But honestly, this is front page news. Anyone else notice this? I know it’s only regional data, but there’s no reason to suspect autism rates would show a different pattern in other parts of the country.

  15. #15 Luna_the_cat
    January 10, 2008

    daedalus — You’re right, it is likely that NO-mediated stress pathways, at least, come into play in a wide variety of situations. However, I tend to think that they operate peripherally to the situations in question, that is, as something which is affected by different individual sources, not something which is so much affecting the unique pathology of any given problem.

    OK, I’m very sleep deprived and coming off a migraine, so I beg indulgence for my crappy attempt to explain myself. Let me try again.

    An analogy, maybe. I like analogies.

    When I’m stressed, I have a common set of symptoms — upset stomach, tension in my shoulders, shortened temper. However, these symptoms manifest whether it’s because I’ve had a fight with my husband or because I’m in danger of missing a deadline on something. Knowing that I am, in fact, stressed, does not necessarily help understand the underlying situation.

    In such a way, I think that NO metabolism is probably affected by a variety of underlying conditions, but understanding this probably only contributes marginally to an overall understanding of these conditions.

  16. #16 daedalus2u
    January 10, 2008

    LTC, I understand your analogy, and while analogies are sometimes appropriate, they have their limits. NO is unique in that it is uncharged, highly mobile and not blocked by anything. It diffuses very rapidly everywhere. NO is not at all peripheral to these stress pathways, NO is one of the major signals that mediates the communication of those stress pathways between cells (if not the major signal). If cells are in an inappropriately low NO environment, their physiology will be skewed to elicit a higher stress response with no threshold. The “compensatory” pathways can’t compensate because it is the compensatory pathways that are affected.

    Most of the enteric nervous system is nitrergic. Decreased NO levels decrease the range and duration of NO signals in the enteric nervous system. All neural networks self-regulate their functional connectivity to be in the near percolation threshold. That is a critical point where the properties of the network change exponentially with respect to connectivity in the near percolation threshold. When the network gets too sensitive, it can lead to instability. If the network drops below the percolation threshold, the functionality of the network falls apart. I think this behavior in the CNS is both the source of the “savant” abilities in the ASDs (getting closer to the percolation threshold), but also of the severe dysfunction in “low functioning autism” (falling below the percolation threshold). If the percolation of the brain self-regulates below the percolation threshold because of a “bad setpoint”, that brain cannot function properly. When that low functionality is brought upon by “stress”, it is called a meltdown.

    Migraines are likely mediated by low NO in the CNS. They vary with the menstrual cycle, with a minimum around the time of ovulation which is when NO levels are highest due to NO produced by increased estrogen. They show up as white matter hyperintensities in MRI. They look a lot like ischemic preconditioning. Ischemic preconditioning is triggered by ROS. The main ROS, superoxide is charged and so can’t pass through a cell membrane. So how is ischemic preconditioning signaled between cells? NO, which is destroyed at diffusion limited kinetics by superoxide can diffuse everywhere. Ischemic preconditioning and migraines can be observed to spread between cells. That is the behavior that would be expected by a diffusible signal that is not mediated through cell surface receptors, or communicated via action potentials.

    Cognitive understanding that stress is a low NO state doesn’t help one to resolve that low NO state.

    I discuss white matter hyperintensities in my recent blog on fever and autism. Anything that lowers basal NO levels is going to lower the threshold for triggering low NO mediated stress pathways. When you are stressed, it takes less of a trigger to make it worse. That is exactly what would be expected if NO were the central player, and if the basal NO level were integrating all the different stressors and triggering stress responses when the sum of all of them hits a critical level. That critical level will depend on the sum of NO produced by all sources, and the destruction of NO by all sinks with no threshold.

  17. #17 Tom Steele
    January 14, 2008

    I think in your effort to criticize the people who look at vaccinations and/or thimerosal as a possible trigger for autism, you overlook the emotional and frustrating elements that face parents.

    As the father of a newborn (boy, no less) seeing the apparently skyrocketing rates of autism, I am looking for any reasonable cause of autism triggering so I can avoid it.

    I’ve read it all. Sonograms/ultrasound (which scares me because we had extra [un-needed] exposure and didn’t know to avoid this.) Too much tv. Parents that are too analytical. Vaccines/thimerosal. We’ve seen it all.

    So when I’m at the doctor’s office and they want to hit my kid with over a dozen vaccines at once, I’m wondering – “are all of these necessary?”

    I’m not a scientist but I have an analytical mind (engineer) and I am pretty sure that you are right, thimerosal in particular and probably vaccines in general have nothing to do with autism.

    But parents facing the prospect of “possibly giving their kid autism” or maybe putting their kid at risk for (mostly) exotic, rare (polio) or almost-never-fatal (rotavirus, chicken pox, whooping cough) diseases have a tough decision to make.

    Furthermore, even if thimerosal doesn’t cause or trigger autism, it sure seems to go against common sense to be injecting an infant child with anything mercury-related.

    If a kid breaks open a mercury thermometer in a school they will evacuate it and send in a environmental hazard team to clean the place. But we are told in vaccines it is “ok.” It certainly sounds contradictory. Even the new CF bulbs have all kinds of warnings and stories about hazards going around and they have very little mercury in them.

    Add to that the the CDC and WHO were painfully slow to even make the most basic attempts to see if there might be a correlation between autism and thimerosal, plus extremely misleading information on the vaccine forms that you are given at the doctor’s office and you end up with a public that does not trust the organizations entrusted with protecting their children.

    In the end, the real problem is that we seem to have NO IDEA where to even look for the cause of autism and parents are left to make difficult decisions on ways to HOPEFULLY reduce their child’s risk of getting autism.

    This is a horrible disease and we need to be working very hard to find the cause.

  18. #18 grenouille
    January 14, 2008

    Tom Steele said:

    almost-never-fatal (rotavirus, chicken pox, whooping cough

    Tom, this statement is simply incorrect. Rotavirus kills an estimated 600,000 children a year according to the WHO and CDC. In the US, fatalities are rare, but that is not so in other countries. The AAP says that rotavirus accounts for 13% of all hospitalizations of kids under 5 in the US. My son was hospitalized as an infant because of severe rotavirus. It was scary and not something I would trivialize.

    I understand your confusion about what to do, but I have also seen this exact post before–was it from you?

  19. #19 MartinM
    January 14, 2008

    If a kid breaks open a mercury thermometer in a school they will evacuate it and send in a environmental hazard team to clean the place. But we are told in vaccines it is “ok.” It certainly sounds contradictory.

    No more contradictory than handling, say, chlorine with care, but thinking nothing of pouring a chlorine-containing compound all over your chips.

  20. #20 HCN
    January 14, 2008

    Tom Steele said “maybe putting their kid at risk for (mostly) exotic, rare (polio) or almost-never-fatal (rotavirus, chicken pox, whooping cough) diseases have a tough decision to make.”

    Please explain very carefully why you now consider polio to be exotic and rare. Why is that? Why did it come back to a community in Minnesota in 2005?

    Whooping cough is a known killer of babies under the age of one year old. Are you one of those who do not feel that children are real people until they reach a certain age? According to this:
    http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5450a3.htm … most of the deaths were for infancts under 6 months of age. It says “Among persons of all ages with pertussis, 33 cases of encephalopathy and 56 pertussis-related deaths were reported during 2001–2003. Fifty-one (91%) of the deaths were among infants aged <6 months, and 42 (75%) of the deaths were among infants aged <2 months.”

    So do you consider the 51 babies who died to be of no consequence?

    Also, my oldest son did contract a rotavirus and became dehydrated. He had a grand-mal seizure, and had a trip by ambulance to the hospital. I think I would rather have had him vaccinated then to go through that (and that seizure may be one of the reasons for his several learning disability).

    Also, all my kids got chicken pox a year before the vaccine was available. That included teh 6 month old baby, who got it an age when it is dangerous. Chicken pox went through the kids’ school, and one child did end up hospitalized with a bacterial infection. Why would anyone want to wish that eperience on a parent?

  21. #21 HCN
    January 14, 2008

    Tom Steele also said “This is a horrible disease and we need to be working very hard to find the cause.”

    But autism is NOT a disease, it is a developmental disability that does not cause death. There is plenty of genetic research that is showing it is genetic, and there is plenty of research in educational methods.

    I would like you to tell me why we should let tetanus, diphtheria, polio, measles, rubella, pertussis, Hib, and mumps to come back in the numbers we used to see in the middle of the 20th century.

    To get a feel for some of those numbers, check out the case and death summary of some vaccine prevented diseases:
    http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/G/cases&deaths.pdf

    Do you really want us to go back to the days of over 200 deaths from diphtheria, around 500 deaths from tetanus, around a 1000 deaths from pertussis (vaccine came out in the 1940s) and over a 1000 deaths from polio?

    Because the experience of stopping vaccines has shown that the diseases come back. It did in Japan, they decided to make vaccination voluntary in the early 1990s. So they went from a low of around 900 cases of measles to over 30000 cases:
    http://www.who.int/immunization_monitoring/en/globalsummary/timeseries/TSincidenceByCountry.cfm?country=Japan

    Oh, and autism still increased in that country (with the additional burden of more deaths and disability from vaccine preventable diseases).

  22. #22 Freddy the Pig
    January 15, 2008

    Tom there is no evidence that “the apparently skyrocketing rates of autism” are anything other than the effects of both a broader definition of autism and better detection of autism (many autistic children were previously considered mentally retarded). Like nearly anything to do with the human mind autism is a fuzzy concept at the edges so prevalence is a function of the definition. By analogy the geological input parameters (pay thickness, porosity and water saturation) I use in a gas well test analysis are dependant on what cutoffs the geologist used to determine these values. If they use a 6% porosity 40% water saturation as cutoffs they will calculate a larger net pay thickness than if they use 8% and 20%.

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