Good media, bad media

For what it's worth:

Dear Larry King Live producers,
I am writing to express my dismay at the lineup planned for the December
20th Larry King Live program, scheduled to include Jenny McCarthy and JB
Handley. As a research biologist, it saddens and alarms me that the
scientifically unfounded opinions of McCarthy, Handley and their ilk are
given national air time with no attempt at balance or genuine
journalistic inquiry as to the relationship they are alleging between
childhood vaccinations and autism.

As a parent, I find it unconscionable that repeatedly providing a platform
to Ms. McCarthy's uninformed opinions on this matter have caused equally uninformed
parents to choose against vaccinating their children, leading to a
resurgence of serious, often fatal, and entirely preventable childhood
diseases. Alas, the isolated outbreaks of measles in communities around
the world where vaccine schedule compliance rates have dipped is
apparently not sensational enough to garner coverage on your program. I
shudder to think of how severe a public health crisis would have to be in
order to warrant as much media attention as has been bestowed on the
celebritized antivaccination movement. Unfortunately, a health crisis of
this magnitude will almost certainly occur if Ms. McCarthy and her cohorts
are given continued, unbalanced access to the national media.

I urge you not to contribute further to the decline of children's health care in this
country and around the globe. Please reconsider your open door policy
with regard to the pseudoscientists, and spend some time identifying a few
sexy, telegenic physicians and scientists to provide evidence-based
opinions on these issues. We're not all greybeards in white coats, you
know.

Sincerely,
Danio, Ph.D.

Dear gawd.

Well, look at it this way: If enough parents refrain from vaccinating their kids, lots of kids will die young. This will spare large numbers of autistic children the pain of a lifetime of disability. Voila! Not vaccinating your kids solves the autism problem.

It seems that the program has been postponed -- possibly due to complaints about pandering to anti-vaxers, or maybe just because there's a new Brad Pitt movie coming out this week.

According to a 12/20 article on the anti-vax blog, Age of Autism:

"We regret to inform our readers that Larry King Live's program featuring Jenny McCarthy, Stan Kurtz and J.B. Handley of Generation Rescue has been postponed."

(BTW, I used TinyUrl for the above link.)

Off-topic, but have a look at this:

http://www.edmontonsun.com/Lifestyle/Health/2008/12/20/7813501-sun.html

It's funny how he points out at the end that people should follow their doctor's advice, knowing that hundreds of people will read his column and do exactly the opposite.

Never fear. Larry King will give us some consolation woo:

"Plus! Suzanne Somers. She took control of cancer and beat it!"

Someone needs to call in and point out that if Jenny McCarthy has cured autism with biomedical treatments, then there is no fear of vaccines because the side effects will be cured with ease and problem.

If you want to have fun, point out that it takes $47 to vaccinate a child against childhood diseases compared to $25,000 a year average to provide care for a child crippled by the effects of a childhood pathogen. For bonus points, accuse Jenny McCarthy of being allied with Big Pharma and their plot to destroy vaccines and revive childhood diseases.

Hello friends -

Jenny is certainly an easy target, intellectually. Indeed, she is no friend to critical analysis.

Unfortunately, I doubt that we really have any true answers regarding a relationship between earlier and more aggressive vaccination and autism rates. We do have some OK information on one particular vaccine, and on the presence, or absence of a particular preservative, but that is about it.

The fact is, the claims that this issue has been comprehensively studied are predicated on one, usually unstated, assumption; that no one can think of a mechanism by which vaccines could cause autism. For this reason, proxies, studies of one insult in a series of insults, or studies involving a particular ingredient have been deemed sufficient to redner judgement on the entire vaccine schedule. Unfortunately, new research is telling us that subsets of children with autism are seemingly predisposed to respond to immunological challenges in very different ways than their undiagnosed peers.

I wonder how many people reading this blog would be interested in knowing that subsets of children with autism not only have been shown to have higher levels of pro-inflammatory cytokines, but also have been shown to generate a less robust anti-inflammatory response when challenged with smaller concentrations of bacterial antigens? Very few, I'd bet. But, it is true.

Elevated cytokine levels in children with autism spectrum disorders [http://www.mdconsult.com/das/citation/body/114331904-2/jorg=journal&sou…] found that when measured at baseline, children with autism had increases in inflammatory cytokines, and decreased levels of IL-10. Strangely enough, however, when the researchers spiked drawn blood with tetanus, they observed no difference in IL-10 generation. How might these children have gotten to their observed baseline state when they seem to have no problems generating IL-10 when stimulated?

Another study, Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study [http://www.jneuroinflammation.com/content/5/1/52] found somewhat different results; children with autism showed increased inflammatory cytokines as reported by many others, but some children with autism were found to create significantly less IL-10 when stimulated with TLR4 agonist.

It turns out, the first study used approximately ten times the concentration of antigens than the second study. So, if you are of a particular subtype of child with autism and get lots of bacterial antigen presentation, and you generate a 'normal' anti inflammatory response; get a much smaller concentration of antigens, and you get a reduced anti inflammatory response.

Researchers in areas other than autism have found polymorphisms attached to TLR4 that would seem to have this effect. See IL-10 and toll-like receptor-4 polymorphisms and the in vivo and ex vivo response to endotoxin for more.

As for vaccines; we have a situation wherein we give our infants a very small concentration of bacterial antigens, and include some aluminum based adjuvants to insure a more robust and lengthy immune response. We aren't adding the aluminum for kicks; but rather, because without it, people did not generate an immune response with sufficient power to generate a immunological memory; in other words, the bacteria in a vaccine are not in sufficient concentration to generate an immune response by themselves. But, if we add some aluminum salts, and bypass the TLRs in order to toggle the inflammasomes directly, this problem is overcome; as long as the only problem we are worried about is generating an immune memory. This is a situation completely unknown to any member of animal kingdom from whom we have inherited our highly complicated, and still somewhat poorly understood immune system.

What might be the effect on neural development of generating an inflammatory response that does not get reduced appropriately on a newborn, at two months, four months, and six months? If there is anyone out there who would like to claim that we have research that can give us the slightest clue as to the effect of generating a pro-inflammatory immune response with a less robust corresponding anti inflammatory response on an infant, I'd love to see it.

For starters we can eliminate every single study thus far performed on autism and vaccination, because the relationship defined above is completely invisible to every single one of them. Studying the presence, or absence of thimerosal would have no effect on if the child got a larger, or smaller concentration of antigens and adjuvant. The other bulk of autism studies, involving the MMR, use viral proteins that are detected by a different TLR than bacterial proteins. [That isn't to say children with autism don't react differentially to the viral proteins included in the MMR, they do, see the second paper above for more on the different immune response generated in response to agonists to TLR3/7/9.] There are no other types of studies regarding autism and vaccination. If this is an inaccurate statement, it should be simple to falsify.

- pD

These autism pseudoscientists have cornered the "top experts in autism" market. It galls me that a "DAN doctor" --who might be an ENT, pathologist, ER doc, or chiropracter who happened to take a weekend DAN seminar-- can claim greater autism expertise than a child psychiatrist or child neurologist.

The alt.med ghost writers help, I think. We working doctors can't compete with the output of the alt.med doctors writing for the general public.

I had a long talk with a mother about Healing the New Childhood Epidemics, a book which is basically a lengthy advertisement for chelation and vitamins. She was shocked by my assertion that the claims in the book lacked evidence. Was I crazy? Hadn't I heard of the Autism Research Institute?

We've got to hit the evidence message hard. We've got to ask, "What evidence exists for your claim?" repeatedly. And we've got to teach people why anecdotes, self-report questionnaires, and treatment outcome measures without controls do not count as evidence.

We have reasons for not accepting hearsay in court: it's not reliable. Same reason we can't accept clinical anecdotes.

"Evidence" means prospective studies with adequate controls.

I love the smell of woo in the morning (even if it is early afternoon when I read this). I did like the idea that Larry King would actually challenge anything (except reality and critical thinking as he normally does).

passionless drone, you're pleading a kind of "god of the gaps" or "Eric Von Daniken" argument. There will always be gaps in what we know. Human knowledge is finite and contingent upon future discoveries.

We do know that polio, measles, mumps, rubella, totally suck and the rate of adverse reactions to vaccines is very, very low.

Did you notice that the prevalence of autism among people over 60 years of age has increased since the 1990s?

I thoroughly detest the notion that the use of vaccines is somehow controversial because of some made-up association with autism. The term "manufactoversy" is all too apropos. All pD is doing is attempt to flame up the controversy with ungrounded speculation.

I don't even bother reading what pD writes anymore. I will suggest he read this again (unless he neglected to read it the first time):
http://photoninthedarkness.com/?p=154#comment-20139 ... "Frankly, I think that I've expended enough effort on pD. I welcome questions, but I think that pD is looking for an education. I'd suggest looking at the local university or community college to see if they have a course in immunology. Or, he can simply convince himself that he already knows enough. Either way, I think I need a "time out" from tutoring this reluctant student."

"Did you notice that the prevalence of autism among people over 60 years of age has increased since the 1990s?" (Dr Benway)

Thank you for pointing that out. The rates of older people being dx with ASDs is increasing quite quickly as knowledge grows in the field. I was dx with "childhood schizophrenia" when I was 6 years old (parents refused any follow up-didn't believe it), and when I was 45 was formally diagnosed as having Asperger's Syndrome.

I have met a man who was 60 yo and one who is 70 who were just diagnosed. How do we fit into the vaccine controversy when we didn't have vaccines?

I was so glad to see those interviews on Larry King postponed.

Hi Dr. Benway -

passionless drone, you're pleading a kind of "god of the gaps" or "Eric Von Daniken" argument. There will always be gaps in what we know. Human knowledge is finite and contingent upon future discoveries.

I agree with you. The argument usually forwarded is that our knowledge of vaccines and autism is sufficient. What is no longer a knowledge gap is the question as to if children with autism respond differently to immune insults than their undiagnosed peers. I find this pertinent towards our ability to have confidence in our existing research and public proclomations. Perhaps you do not feel this way.

We do know that polio, measles, mumps, rubella, totally suck and the rate of adverse reactions to vaccines is very, very low.

We are in agreement again, to a point. However, your assessement of the numbers of adverse reactions to vaccines in regards to children who generate differential responses due to polymorphisms is completely speculative. We simply have no studies on the vast majority of vaccines regarding developmental trajectories involving autism; excepting those involving the MMR and thimerosal. By way of example, you cannot not show me a study evaluating for polio vaccination and autism rates. Or DTAP, Hib, or Hep B. The reason this is usually stated as unnecessary is that there is no mechanism of action; or it is logistically or ethically difficult to perform such a study. While true, that is a very different beast from having the certainty often proclaimed.

Did you notice that the prevalence of autism among people over 60 years of age has increased since the 1990s?

Only relevant if I were to make the argument that all of the perceived increase must be due to vaccines. I do not make that case. It would not suprize me to find that some older people were not diagnosed, or mis diagnosed. However, all of the chart reviews and 'found' autistics do nothing to change the observations; that children with autism are predisposed to respond differnetly to immune challenges.

I appreciate your cordial tone.

- pD

AoA's followers are sending disappointed e-mails to Larry King's producers. I'm sending an e-mail requesting that Larry moderate a discussion between Jenny et al, and Dr. Offitt and Amanda Peet (because Larry loves the celebrities).

For anyone who's interested: larrykingguests at cnn dot com

passionless drone, you're pleading a kind of "god of the gaps" or "Eric Von Daniken" argument. There will always be gaps in what we know. Human knowledge is finite and contingent upon future discoveries.

Yes, that's what he's doing, but it's more than that. He seems also to be arguing for the "precautionary principle" taken to a ridiculous extreme. The usual argument for the precautionary principle is that "we don't know so let's not take the chance." When misused, as it has been frequently regarding thimerosal in vaccines and now vaccines themselves, the precautionary principle misuses the fact that no scientific study can ever with 100% certainty prove a negative; in this case, absolutely no correlation between vaccines and autism. It further tends to inflate that level of uncertainty beyond what it is.

The problem is that in many cases, while we may not be able to absolutely disprove a correlation, we do know enough to make a very reasonable and accurate risk-benefit assessment. In the case of vaccines and autism, the existing data clearly do not support a link to a certainty that is quite high for epidemiological studies. The data don't even show a whiff of a hint that there might be subgroups who are more susceptible to complications from vaccination. Indeed, much money and a lot of resources have been wasted doing more and more studies after there was already enough evidence.

I know there's one more big study in progress and scheduled to publish in 2009 (probably). It should be the most definitive one yet; but assuming it's negative I doubt it'll silence the antivaccine loons.

I know there's one more big study in progress and scheduled to publish in 2009 (probably). It should be the most definitive one yet; but assuming it's negative I doubt it'll silence the antivaccine loons.

Is that your psychic prediction for 2009? I don't think that one will win the JREF million.

Unfortunately, I doubt that we really have any true answers regarding a relationship between earlier and more aggressive vaccination and autism rates.

Yes, your doubt is unfortunate in that it has wasted a lot of your (and others') time. A "relationship between earlier and more aggressive vaccination and autism" is exactly what several whole-population epidemiological studies have disproven.

Not that you're at all likely to spare us in the future, of course.

As has been pointed out to PD many times, exposure to antigens from vaccines is a a drop in a very large bucket. Vaccinations produce less of an immune response--and less symptoms of immune activation--than hundreds of normal childhood illnesses that every child is exposed to, so the notion that somehow vaccines are producing an excessive immune response is implausible on the face of it.

No study has documented any association of vaccination with autism. Even a survey by the antivax group Generation Rescue found that vaccinated kids are no more likely to have autism spectrum disorders than unvaccinated kids, and unvaccinated girls are actually more likely to have ASD than vaccinated girls.

What is no longer a knowledge gap is the question as to if children with autism respond differently to immune insults than their undiagnosed peers.

I wasn't sure what "immune insults" were. So I Googled and found these examples:

"Hey immune system... you're so slow that it takes you an hour and a half to watch 60 minutes!"

"Hey immune system... you're so dim you think TacoBell is a Mexican phone company."

"Hey immune system... you're so dumb when you saw a sign that said, 'wet floor', you did."

HTH

Dr. Benway wins...hands down!...funniest comment of '08!

For what it is worth, the This American Life piece was fairly sympathetic to antivaxers without actually agreeing with their stance. I found some equivalence between "both sides" to be dubious at times, but on the whole it is so friendly to antivaxers while explaining the harm they can bring that it probably would be more effective at persuading them than cogent refutations of their arguments ever will.

Yeah, while I like NPR for a lot of things, medical reporting (or even storytelling, like on This American Life) is not one of them. My local station carries The Parents' Journal and The People's Pharmacy, which are both very high on the woo scale. I cringe any time Diane Rehm brings on someone talking about alt med, because that's one of the classes of guest that she absolutely refuses to challenge.

The last thing I heard that was even remotely skeptical was a report on the "detox foot pads" that the skeptical community had taken apart close to a year earlier. Why, oh, why did the Skepchick's show not get picked up?

Dr. Benway wins teh internets.

Darn, I just sent you the NPR link thinking you hadn't seen it. Squished as it is among the Larry King star power post.

What is sad is, the mother whose child contaminated the other children has not changed her mind. Is it even worth commenting on them, if 11 children become infected and it changed no ones mind? Nothing will change their minds, nothing.

The only course is to prevent them from promoting it, by getting speakers to show up on Larry King. There is one cute actress, perhaps there is a hottie male to do it too?

Annie

Aw shucks. U can use internets, eben do iz mine. I sharez.

Can a small injection of foreign protein into the skin "insult" the immune system?

How about tooth brushing? Tooth brushing invites lots of foreign bits into the blood stream. Is that an insult to the immune system?

Well, it'd be my guess a true insult to the immune system would involve things like obliterating the bone marrow and maybe excising a neonatal thymus.

My immune system is quite insulted by the idea that it wouldn't be able to handle a load of vaccines. Hell, my immune system is insulted by the woo wizards' collective stupidity.

Just to add:
"Hey immune system... you're so stupid, you got locked in a supermarket and starved to death."
"Hey immune system... you're so stupid, you climbed over a chain-link fence to see what was on the other side"

"...Stan Kurtz and JB Handley will publish candid letters on how to lower your risks of having a child with autism."

If they were truly candid, they'd say that they didn't have a clue and were just making it up as they went along. Failing that, another candid response would be to say that the only surefire way to prevent having a child with autism is to remain childless.

Seriously, how low has the culture sunk when parents are taking medical advice from people who didn't even take upper division biology?

Prometheus

Hi Orac -

In the case of vaccines and autism, the existing data clearly do not support a link to a certainty that is quite high for epidemiological studies. The data don't even show a whiff of a hint that there might be subgroups who are more susceptible to complications from vaccination. Indeed, much money and a lot of resources have been wasted doing more and more studies after there was already enough evidence.

Please take a look at what I actually posted, as opposed to the argument that seems to have been attributed to me, and explain to me how any of the existing epiediological studies could possibly detect a subgroup wherein the functional problem is the generation of a less robust anti inflammatory response when challenged with bacterial proteins. We have zero studies that can give us the slightest hint of information as to this. Zero. Studies involving thimerosal do not do this; the generation of an immune response and corresponding anti inflammatory response (or lack there of) are invisible to a study evaluating the presence of thimerosal. Am I incorrect?

Likewise, existing MMR studies do not address what has been observed; the changes involved stimulation of a toll like receptor that does not respond to viral proteins. Am I incorrect?

I may be wrong; there may be a study that fits the critereia you claim exist. Can you please, please post a link to it? This should be easy if such a study exists.

- pD

Hi Trrll -

As has been pointed out to PD many times, exposure to antigens from vaccines is a a drop in a very large bucket.

The implication here is that just because an argument that fails the simpliest logical tests has been provided to me previously, it should somehow become more pertinent, or that I should ignore the logical fallacies in it. Why?

If the exposure to vaccines is so small, why do children get a fever 20 - 30% of the time they get a vaccination, but don't get a fever 20-30% of the time every other day? Could it have anything, at all, to do with the fact that antigens in a vaccine bypass the skin, mucous, and stomach acid? Could the fact that these antigens come alongside aluminum salts whereas those in the environment do not have any impact on our ability to add things up meaningfully? For some strange reason, my pediatrican recommended I give my son Tylenol on the days he was vaccinated in the office, but not on well visit days when he wasn't. How strange, one would think he'd be well aware of all those other antigens out there!

Children are exposed to hundreds of illnesses, eventually; but not on the day they are born, and the day they are two, four, and six months. And none of the antigens my child is exposed to normally bypass the immune mechanisms we have developed to respond to bacteria and viruses over hundreds of millions of years; the toll like receptors. Am I incorrect in any of these statements? Which ones?

If you don't think these make a difference, why not ask your pediatrician for a vaccine that your child gets a normal exposure (i.e., doesn't bypass the skin or mucous) and doesn't come with any aluminum based adjuvants in it; when you get some, then we can start using the power of addition of antigens to get meaningful conclusions; otherwise we are mixing apples to oranges. I can honestly say I'm not sure I know if you knew better or not when you made this post.

Vaccinations produce less of an immune response--and less symptoms of immune activation--than hundreds of normal childhood illnesses that every child is exposed to, so the notion that somehow vaccines are producing an excessive immune response is implausible on the face of it.

The specific argument I posted above represents a case where there is insufficient bacteria protein concentrations to initiate an appropriate anti inflammatory response. It is no wonder your response makes so little sense, you apparently didn't bother to read what I'd written.

In any case, are you aware that children with autism have been shown to create differential immune responses than their undiagnosed peers? Completely true; in some cases it is an increase in pro-inflammatory cytokines, in others, it is a decrease in the corresponding anti inflammatory cytokines. If a child is predisposed to generate inflammatory cytokines at greater rates than others, what does that tell us about our ability to apply findings from a non autistic population set? If a child is predisposed to create cytokines that are responsible for countering an inflammatory response at lower rates than normal children, does this have any impact at all on our ability to use existing 'normal' findings for them? If childen with autism have been found to have exceedingly high levels of pro-inflammatory cytokines in their CNS when compared to undiagnosed peers, what reason do we have to believe this is not related to the pathology of the disease? What if our existing set of epidemiology regarding intentional and artificial stimulations of these systems was completely blind to these associations? Are the powers of addition so powerful that we can simply add the number of antigens up and ignore all of this?

-pD

If the exposure to vaccines is so small, why do children get a fever 20 - 30% of the time they get a vaccination, but don't get a fever 20-30% of the time every other day?

In fact, vaccines account for only a tiny fraction of childhood fevers, and as you acknowledge most children do not experience fever from vaccination at all.

Could it have anything, at all, to do with the fact that antigens in a vaccine bypass the skin, mucous, and stomach acid?

I suppose that this might be relevant if you were considering a population of children that never fall down and skin their knees or get splinters. For most kids, these are frequent occurrences.

Could the fact that these antigens come alongside aluminum salts whereas those in the environment do not have any impact on our ability to add things up meaningfully?

Adjuvants such as aluminum salts are used to enable the immune system to mount a sufficient response to a tiny amount of antigen so as to produce lasting immunity. Exposure to natural pathogens, of course, results in massively greater exposure to foreign antigens.

For some strange reason, my pediatrican recommended I give my son Tylenol on the days he was vaccinated in the office, but not on well visit days when he wasn't.

And you don't think that your pediatrician would make similar recommendations if he could anticipate the many days when your child would be exposed to potentially fever-inducing viruses or bacteria from other children or in the environment?

Children are exposed to hundreds of illnesses, eventually; but not on the day they are born, and the day they are two, four, and six months.

What makes these days magic? They are exposed to immense quantities of foreign antigens on all of those days and many others besides--and on many of those days, a sufficient infection develops to result in a fever.

And none of the antigens my child is exposed to normally bypass the immune mechanisms we have developed to respond to bacteria and viruses over hundreds of millions of years; the toll like receptors.

You apparently have a very unusual child who doesn't experience the routine scrapes, scratches, and cuts that other children are subject to.

Am I incorrect in any of these statements? Which ones?

So far, all of them.

If you don't think these make a difference, why not ask your pediatrician for a vaccine that your child gets a normal exposure (i.e., doesn't bypass the skin or mucous) and doesn't come with any aluminum based adjuvants in it

So you want to expose your child to the massively greater quantities of antigens in an actual infection, with the attendant much greater risk of ill effects such as fever, instead of using an adjuvant that enables children to develop robust immunity from a small amount of antigen with ill effects much less than a typical childhood illness?

The specific argument I posted above represents a case where there is insufficient bacteria protein concentrations to initiate an appropriate anti inflammatory response.

So now you are arguing that ill effects result because of the small quantity of antigen? You must have a very strong emotional attachment to this hypothesis to be willing to postulate such an unlikely reversal of normal dose-effect relationships.

In any case, are you aware that children with autism have been shown to create differential immune responses than their undiagnosed peers? Completely true; in some cases it is an increase in pro-inflammatory cytokines, in others, it is a decrease in the corresponding anti inflammatory cytokines.

Considering the strong evidence that autism is mostly genetic, it would not be surprising if autistic children exhibited a number of biological differences from undiagnosed peers. But none of this particularly implicates vaccines.

I notice that you did not respond to the Generation Rescue survey that found that autistic spectrum disorders were at least as common in unvaccinated children as in vaccinated children.

Indeed, based upon your own argument, one could argue that autistic children might be particularly susceptible to being harmed by routine childhood infections, and thus it is more important to protect them by vaccination. Indeed, the above-mentioned Generation Rescue survey found that autistic spectrum disorders were substantially more common in unvaccinated than vaccinated girls.

Hi Trrll -

In fact, vaccines account for only a tiny fraction of childhood fevers, and as you acknowledge most children do not experience fever from vaccination at all.

You are missing the point, perhaps intentionally. Everyday expsore to antigens is not likely to cause a fever, yet exposure to a vaccine can cause a fever up to thirty percent of the time. Put it this way, how about we make a bet? Take one hundred children. We agree in advance that these children will get normal vaccines at two months, four months, and six months after the day they are born. There are 180 days in our bet. We each get to pick three days on which we think each child will get a fever. I pick the days immediately following their vaccinations, you pick any other days. For each time a child has a fever on the day I picked, you give me $100, and vice versa.

If there is no difference in everyday exposure to antigens on a daily basis and the days after vaccinations, randomness should allow this to be a more or less even bet. Would you accept such an offer?

I suppose that this might be relevant if you were considering a population of children that never fall down and skin their knees or get splinters. For most kids, these are frequent occurrences.

Two month olds very rarely fall down, skin their knees, or get splinters; yet every single one of them receives a series of vaccines at age two months. Likewise at four and six months. You seem to be unable to decouple childhood from infancy. How many splinters have you ever pulled from a two month old? Seriously. How are you defining 'childhood'?

Adjuvants such as aluminum salts are used to enable the immune system to mount a sufficient response to a tiny amount of antigen so as to produce lasting immunity. Exposure to natural pathogens, of course, results in massively greater exposure to foreign antigens.

No kidding. Thanks. They also happen to bypass the bodies natural mechanisms for identifying and responding to pathogens, the toll like receptors. [For example, see http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedi…] for more. These components of the immune system are highly conserved from our vetebrate ancestors, but we have found a way to bypass them in order to generate immunity with a very small amount of antigen.

And you don't think that your pediatrician would make similar recommendations if he could anticipate the many days when your child would be exposed to potentially fever-inducing viruses or bacteria from other children or in the environment?

Why should he be anticipate that a vaccination day is any different, if we are able to adequately add normal exposures up and compare them with vaccine exposures; which is the absolute heart of your argument?

If normal exposure is the same as vaccine exposure, what makes the day a child is vaccinated different from any other day?

If they are different, we cannot simply perform addition on the number of antigens a child is exposed to and make valid comparisons.

What makes these days magic? They are exposed to immense quantities of foreign antigens on all of those days and many others besides--and on many of those days, a sufficient infection develops to result in a fever.
Those days are magic because they are the days infants are scheduled to receive well check up vaccinations. If you believe that there is no difference in those days and others, accept my offer in regards to predicting a fever.

You apparently have a very unusual child who doesn't experience the routine scrapes, scratches, and cuts that other children are subject to.

Your infant must have been doing a lot of crazy stuff mine wasn't doing when he was two months old, four months old, and six months old. What they hell were you doing with that kid?

So you want to expose your child to the massively greater quantities of antigens in an actual infection, with the attendant much greater risk of ill effects such as fever, instead of using an adjuvant that enables children to develop robust immunity from a small amount of antigen with ill effects much less than a typical childhood illness

So many gross over simplifications here.

With autism, timing is everything; you don't just get it when you are four or five. Is Hepatitis B a 'typical childhood illness'? Or tetanus? My child is very, very unlikely to be exposed to Hepatitis B on the first day of his life. Likewise with tetanus, diptheria or pertussis sixty days after he is born, or even one hundred and twenty or one hundred and eighty days. The results of such an exposure might be very problematic, but the chances of such an exposure are vanishingly minute.

Also, did you know that we have at least two studies showing not only dysfunction with key cytokines and immunological signalling factors; but as those dysfunctions skew farther and farther from normal, autism symptoms correspondingly increase? See http://pediatrics.aappublications.org/cgi/content/abstract/122/2/e438?r… and http://www.ncbi.nlm.nih.gov/pubmed/18762342?ordinalpos=1&itool=EntrezSy… for more. Of course, we have many, many other studies showing abnormal immunological findings, but these are the only two I am aware of that show a direct correlation between autism severity and these measurements. In the first study, the increased levels of MIF were caused by known promoter genes, so please hold off on the 'correlation does not prove causation' answer.

So now you are arguing that ill effects result because of the small quantity of antigen? You must have a very strong emotional attachment to this hypothesis to be willing to postulate such an unlikely reversal of normal dose-effect relationships.

http://www.ncbi.nlm.nih.gov/pubmed/15760678 - Carriers of the IL-10 promoter -1330G, -1082A, -819T, -592A (GATA) haplotype had lower IL-10 production ex vivo upon stimulation with 10 and 100 ng/mL LPS and higher EC50 values (the estimated LPS concentration at which 50% of the maximal IL-10 response is reached) as compared to carriers of the other haplotypes combined, indicating decreased LPS sensitivity ex vivo. These individuals did not differ from the others in interleukin-10 production capacity upon stimulation with a high LPS concentration (i.e., 1000 ng/mL) and the estimated IL-10(max) values, were similar, indicating unimpaired maximal IL-10 production capacity ex vivo.

If you carry a particular polymorphsm on IL-10 , you have lower IL-10 production on stimulation with 10 and 100 ng/ml lps; but upon high LPS concentration, you have the same IL-10 production capacity. Do you still feel this is unlikely?

But none of this particularly implicates vaccines.

The argument being proffered is that vaccination has been sufficiently analyzed. Because the effect of additional, artificial stimulations on the immune system are invisible to the overwhelming majority of existing studies, I tend to disagree.

I notice that you did not respond to the Generation Rescue survey that found that autistic spectrum disorders were at least as common in unvaccinated children as in vaccinated children.

It seems probable that you are as aware of the significant limitations of that "study". It does seem pretty funny that you would seemingly believe this study to be of sufficient quality to merit mention.

- pD

"Children are exposed to hundreds of illnesses, eventually; but not on the day they are born, and the day they are two, four, and six months."

Nice guess, but wrong.

At the moment of birth, children are exposed to all of the viruses, bacteria and fungi floating in the air at the moment. Before the day is out, they have been exposed to whatever viruses, bacteria and fungi are being carried by the various doctors, nurses, aides, parents, siblings and other well-wishing relatives they come in contact with.

Taking a child to any place where a group of people congregate exposes them to dozens of novel pathogens and potential pathogens at a single go. Malls, churches, schools, and public transportation are all marvelous ways of "sampling" the community virosphere.

Taking a child on an airline flight exposes them to every virus, bacteria and fungus carried by every person on the flight due to the extensive recirculation of cabin air. This is why people often come down sick a few days after a flight, especially during the "cold and flu season".

While it may seem to a parent that children are exposed to a single virus at a time - probably because their children aren't continuously ill - the reality is that children (and adults) are continuously exposed to countless infectious agents. Not all of these can gain a foothold adequate to cause overt disease and many may have adapted ways to escape the immune system and so not provoke the symptoms that parents associate with diease.

But, you'd have to know something about microbiology and immunology to be aware of that.

As I have pointed out to PD in the past, the Internet is not the place to get an in-depth education in immunology - not even on this excellent 'blog. PD's comments repeatedly disclose his lack of knowledge on the subject, yet he refuses to accept the fact that his failure to "agree" with people who clearly know more than he does is not because they are wrong.

I think that the time has come to speak truth to ignorance - to be frank and open with people who have been wrongly convinced that their "parental intuition" and "Google PhD's" are as valid as an actual scientific education. It's time to face the fact that "alternative ways of knowing" are as real as "the Emperor's new clothes". It's time to tell people that they are entitled to their own opinion, but not their own reality.

This may seem a bit harsh to some folks - after all, we are encouraged to be "tolerant" of "diversity" in opinions. However, we are doing nobody any favors by allowing them to spout nonsense unchallenged. Data may not convince the "true believers", but challenging fantasy with reality will help those who are sitting on the sidelines, trying to make up their minds.

Prometheus

You are missing the point, perhaps intentionally. Everyday expsore to antigens is not likely to cause a fever, yet exposure to a vaccine can cause a fever up to thirty percent of the time. Put it this way, how about we make a bet? Take one hundred children. We agree in advance that these children will get normal vaccines at two months, four months, and six months after the day they are born. There are 180 days in our bet. We each get to pick three days on which we think each child will get a fever. I pick the days immediately following their vaccinations, you pick any other days. For each time a child has a fever on the day I picked, you give me $100, and vice versa.

Fine, I'll pick the days when they show symptoms of an infection that would result in sufficient exposure to foreign antigens to provoke a robust immune response--runny noses, cough, vomiting. After all, if you can pick days correlated with an external event, then I should be able to do so as well. But to be really fair, you should allow me to pick not just the same number of occasions, but all such occasions over the same period of time, because what is obviously relevant is the total exposure to antigens over a period of time, not the exposure on a few selected days. So lets say that every day when they experience a fever associated with vaccination, I pay you $100, and every day they experience a fever associated with other symptoms of some kind of infection, or evidence of natural exposure to a foreign antigen, such as a bee sting, splinter, or skin infection, you pay me $100.

With autism, timing is everything; you don't just get it when you are four or five. Is Hepatitis B a 'typical childhood illness'? Or tetanus?

If you are talking about a risk of immune activation, then why does it matter what the antigen is? Are you saying that there is something special about an immune response to tetanus or hep B antigens that is not present in the immune response to rhinovirus or coronavirus?

Two month olds very rarely fall down, skin their knees, or get splinters; yet every single one of them receives a series of vaccines at age two months.

Or get diaper rash?

No kidding. Thanks. They also happen to bypass the bodies natural mechanisms for identifying and responding to pathogens, the toll like receptors. [For example, see http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedi…] for more.

This really falls into the "Well, duh" category. You take a study of mice in which the TLR signalling has been genetically knocked out and who are hence genetically incapable of TLR activation, and acclaim this as evidence that vaccination of an individual with normal TLR somehow "bypasses" them. In fact, if you were not so blinded by your own personal obsession as to be unable to follow what the paper actually says, you would have realized that the article is actually saying is that current vaccines do activate TLR, but this may not be necessary for a robust immune response, and that it might be a good idea to change vaccines to intentionally bypass TLR in order to minimize TLR associated side effects (such as fever).

Why should he be anticipate that a vaccination day is any different, if we are able to adequately add normal exposures up and compare them with vaccine exposures; which is the absolute heart of your argument?

We know that a vaccine day is a day in which a child will experience a robust immune response. Other such days are the days when the child experiences other symptoms of infection, as discussed above.

With autism, timing is everything; you don't just get it when you are four or five. Is Hepatitis B a 'typical childhood illness'? Or tetanus? My child is very, very unlikely to be exposed to Hepatitis B on the first day of his life. Likewise with tetanus, diptheria or pertussis sixty days after he is born, or even one hundred and twenty or one hundred and eighty days. The results of such an exposure might be very problematic, but the chances of such an exposure are vanishingly minute.

Yes, it is clear that autism develops in this time frame even in children that have received no vaccinations. There is no evidence whatsoever to indicate that the timing of vaccinations is important.

Also, did you know that we have at least two studies showing not only dysfunction with key cytokines and immunological signalling factors; but as those dysfunctions skew farther and farther from normal, autism symptoms correspondingly increase?

Yes, given that there is evidence that autism is almost entirely a genetic disease, it would not be surprising if autistic individuals have biochemical abnormalities, or if the magnitude of the abnormality is correlated with severity. There is nothing about this that implicates vaccines in autism. If there is immune system dysfunction, a more rational conclusion is that vaccines might be more necessary in such individuals, who might be more subject to harm from routine childhood infections.

http://www.ncbi.nlm.nih.gov/pubmed/15760678 - Carriers of the IL-10 promoter -1330G, -1082A, -819T, -592A (GATA) haplotype had lower IL-10 production ex vivo upon stimulation with 10 and 100 ng/mL LPS and higher EC50 values (the estimated LPS concentration at which 50% of the maximal IL-10 response is reached) as compared to carriers of the other haplotypes combined, indicating decreased LPS sensitivity ex vivo.

This describes reduced sensitivity to LPS. What it does not describe is a case where a low dose of LPS produces an effect that is not present with a high dose--such a reversed dose-effect relationship is quite unlikely. Needless to say, there is nothing here relevant to vaccines or autism.

It seems probable that you are as aware of the significant limitations of that "study". It does seem pretty funny that you would seemingly believe this study to be of sufficient quality to merit mention.

Really? So what "limitations" do you have in mind, and how, specifically would these particular limitations have caused the incidence of autism spectrum disorders in unvaccinated individuals to appear to be as great or greater than in vaccinated individuals? You certainly can't blame it on bias on the part of the investigators, considering that the survey in question was conducted by the antivax group Generation Rescue. If vaccination really is a major contributor to autism, then shouldn't the incidence of autism in the unvaccinated kids have been much, much lower--so much so that it would be obvious even in a study with such "limitations?"

Hi Trrl -

Fine, I'll pick the days when they show symptoms of an infection that would result in sufficient exposure to foreign antigens to provoke a robust immune response--runny noses, cough, vomiting. After all, if you can pick days correlated with an external event, then I should be able to do so as well.

You are cheating, I can make my predictions in advance and you cannot. Why should this be the case if everyday exposure is no different than vaccine exposure? Am I psychic? Also, if your child is at risk of getting a bee sting at two months old, check your windows.

If you are talking about a risk of immune activation, then why does it matter what the antigen is? Are you saying that there is something special about an immune response to tetanus or hep B antigens that is not present in the immune response to rhinovirus or coronavirus?

Because these are the antigens that we are vaccinated against! What is special about these antigens is that they bypass the skin, mucuos, and gastro intestinal track when they come from a needle. What is special about these antigens is that they come with aluminum in order to insure an immune response; rhinovirus or coronavirus do not have these qualities.

In fact, if you were not so blinded by your own personal obsession as to be unable to follow what the paper actually says, you would have realized that the article is actually saying is that current vaccines do activate TLR, but this may not be necessary for a robust immune response, and that it might be a good idea to change vaccines to intentionally bypass TLR in order to minimize TLR associated side effects (such as fever).

From the paper:

We therefore conclude that TLR signaling does not account for the action of classical adjuvants, nor does it fully explain the action of a strong adjuvant that contains a TLR ligand. What else should we take from this sentence other than classical adjuvants are not using TLR signalling to initiate an immune response? Are you intentionally substituting vaccines for adjuvants in your response?

Adjuvants promote inflammatory responses of leukocytes in ways that presumablymimic natural infection.

But when I say that we aren't smart enough to understand the consequences, or for that matter, the mechanisms of action of vaccination, I'm accused of being a Google PhD. Perhaps you or Prometheus ought to set the authors of this paper straight.

There is no evidence whatsoever to indicate that the timing of vaccinations is important.

We are in agreement, but only in such that there is no evidence whatsoever. There are no studies of schedules at all, so the fact that there is no evidence to benifit (or risk) of timing vaccinations is not surprizing. By the way, did you know that delaying DTP by two months reduces your asthma risk by 2, and by 4 if you delay another two months?

http://www.ncbi.nlm.nih.gov/pubmed/18207561?ordinalpos=2&itool=EntrezSy…

We simply don't have corresponding studies for neurological outcomes. If we do, why not provide a link instead of claiming such a study exists.

What it does not describe is a case where a low dose of LPS produces an effect that is not present with a high dose--such a reversed dose-effect relationship is quite unlikely

The creation of IL-10 was different depending on polymorphism and dose! With lose doses of LPS there was less IL-10 created with the polymorphism than without. With a high dose of LPS, the creation of IL-10 was the same regardless of polymoprhism. It isn't a reversed dose-effect; it is a minimized response effect, only at low concentrations of bacteria. Now, can you conceive on a situation where we have low concentrations of antigen, but somehow manage to inititate an inflammatory response anyways?

- pD

You are cheating, I can make my predictions in advance and you cannot. Why should this be the case if everyday exposure is no different than vaccine exposure?

The claim was not that every single day is equivalent to vaccine exposure, it was that numerous common childhood infections produce exposure to antigens and immune system activation equal or greater to a vaccine

Because these are the antigens that we are vaccinated against! What is special about these antigens is that they bypass the skin, mucuos, and gastro intestinal track when they come from a needle.

But it is very easy for antigens to get across the skin from scratches, scrapes, skin infections such as diaper rash. If our immune system could not deal with antigens that bypass the skin, it would be virtually useless.

We therefore conclude that TLR signaling does not account for the action of classical adjuvants, nor does it fully explain the action of a strong adjuvant that contains a TLR ligand.

Yes, the beneficial effect of adjuvants does not require TLR signaling. That is not at all the same as saying that vaccinations with adjuvant do not activate TLR. If you were not so obsessed as to cherry-pick isolated statements without thinking about what the paper actually means, this very elementary point of logic would not escape you. In fact, the article specifically points out that vaccinations do activate TLR, and suggests that this may be undesirable, as TLR activation can responsible for vaccine side effects. Fever, a common vaccine side effect, and one that seems to particularly concern you, is a common effect of TLR activation. If vaccines did not activate TLR, would they really be suggesting that vaccines should be reformulated to avoid TLR activation? Think!

The creation of IL-10 was different depending on polymorphism and dose! With lose doses of LPS there was less IL-10 created with the polymorphism than without.

Reduced sensitivity, so that lower doses produce less of an effect with the polymorphism than without is not a reversed dose-effect relationship. What would be a reversed dose effect relationship would be if low doses of an antigen produced an adverse effect that did not occur at higher doses. This is highly unlikely.

And I'm still awaiting your explanation as to what specific limitations of the Generation Rescue survey could explain a finding that unvaccinated children show as much or greater Autism Spectrum Disorders than vaccinated children....