One of the great things about having declared Vaccine Awareness Week is that it gives me a convenient excuse to revisit topics and blog posts that I had meant to address but that somehow didn’t make the cut the first time around. This is the sort of thing that happens fairly frequently in blogging, where there is far too much woo and idiocy for one blogger to have even a hope of ever addressing it all.
And that’s just the anti-vaccine movement.
In any case, if there’s one thing about the anti-vaccine movement that I’ve noticed, it’s that its members have a very warped view of both science and ethics. Last week on the anti-vaccine crank propaganda blog Age of Autism in the form of two posts within two days of each other. The first was by Kent Heckenlively, who is notorious for having taken his autistic daughter to Costa Rica for stem cell quackery and for subjecting her to all manner of biomedical woo. His post is entitled “Science Stoppers” and the Question of Autism. In this post, Heckenlively tries to liken those who criticize his pseudoscientific pontifications about autism and vaccines to creationists–evolution deniers!–and labels them, like creationists, as “science stoppers.” The second post is by the ever-clueless Jake Crosby, who tries to amp up the moronicity even higher by attacking Art Caplan and Paul Offit for “endangering children” through their unrelenting defense of vaccines. It would be hilarious if it weren’t so pathetic, particularly given how much arrogance it takes for Jake to think that he can actually stand his own arguing ethics with an internationally respected senior bioethicist and how Jake tries to parody the title of Paul Offit’s forthcoming book by entitling his post How Vaccine Damage Deniers Threaten Us All.
Denialism. You both keep using that word. I do not think it means what you think it means.
Let’s deal with Heckenlively first. He starts out by proudly trying to burnish his scientific cred by pointing out how much he loves evolution:
Professor Padian was one of the chief expert witnesses in the Dover trial in which a local school board was trying to adopt a creationist textbook. Now I should probably confess I’ve been an evolution freak since the age of three when I fell in love with dinosaurs. My job as a science teacher gives me free rein to talk about such issues and also get paid for my eccentric interests.
Heckenlively also doesn’t want to piss off the religious too much; so he tries to have it both ways by invoking without naming Stephen J. Gould’s “non-overlapping magesteria”:
I don’t have much energy for attacking creationists, being a Catholic, and knowing our own tumultuous history of trying to mix faith with science. Although I went to a Catholic college with a Galileo Science Hall, it would still be several years after I graduated that the Catholic Church finally rescinded his excommunication. After a couple centuries wrestling with the issue I think we’ve come up with a pretty good formulation that “science without faith is blind, and faith without science is lame.” I believe in God (I’m actually a eucharistic minister in my parish) and science, but they live in different zip codes.
Wow! That sounds so…reasonable–or at least accommodationist. Now, don’t worry. I’m really not going to get into the whole “militant” versus “accommodationist” wars over how best to overcome resistance to science that derives from religious beliefs or ideology. I’m really not. Although I leapt head first into the “framing wars” back in the day, these days I find such discussions tiresome in the extreme and now almost actively avoid such discussions. I’m far more interested in using Heckenlively’s utter missing of the point to demonstrate something about the anti-vaccine movement. First, here’s where Heckenlively introduces his point:
What really interested me in professor Padian’s talk was the masterful way in which he showed multiple lines of evidence for the turning of a fin into a foot, the development of feathers in theropod dinosaurs, and how whales went from land to water animals. Then he said something about creationist arguments against evolution which I felt went to the heart of why so many of us don’t trust the medical authorities when it comes to the vaccine-autism issue.
He said that creationist arguments against evolution are “science stoppers” because they discourage the efforts of the human mind to understand evolution in all its complexity.
It’s true, too, of course. Creationist arguments against evolution, when stripped of all their science-y sounding glitz, basically boil down to “God did it” or a “God of the gaps” argument. Such arguments are indeed “science stoppers.” Unfortunately, as we say in the science biz, what we have here is a massive failure to generalize the example of creationism to other forms of science. Instead of understanding that vaccine denialism is every bit as much of a “science stopper” as the anti-evolution arguments favored by creationists, a-vaccine activists like Kent Heckenlively yoke the same sorts of fallacious arguments in the service of their anti-science agenda. As I described yesterday, they twist science to serve their agenda, favor anecdotes over epidemiology and science, cherry pick data, and make liberal use of logical fallacies when arguing. Kent often goes one further, though, in representing his pseudoscientific flitting from one woo to another based on whatever he’s happened to heave heard about through the autism biomed quackery grapevine as being real scientific investigation, rather than disordered flights of fancy.
I also can’t resist pointing out that, for all his transparent attempts otherwise, so toxic is the issue of evolution that Heckenlively managed to royally piss off some of his AoA readers. Indeed, there are several comments taking Heckenlively to task for having chosen the particular analogy that he chose, although they are just as hilariously off-base as Heckenlively’s himself. Indeed, a commenter named Willie was particularly outraged that Heckenlively gave “the reader the impression that you believe that the theory of evolution has merit and creation and God do not in a similiar way that biomedical is discounted by pro vaccine idiots.” Truly, this is crank magnetism in action. Heck, it’s a veritable crank schism over the issue of evolution. In any case, Heckenlively accuses scientists of the same sins against science that evolution denialists commit because they don’t accept the pseudoscience:
With voluminous accounts of parents detailing how the problems of their children began after a vaccination it’s nothing less than a crime that the medical authorities stop the science by claiming that the question has been “asked and answered.” Nothing could be further from the truth. They have refrained from doing the type of population studies of vaccinated and unvaccinated populations which might yield promising information. How about also doing extensive biological studies of their immune systems to see what is going wrong?
Because, perhaps, we need some actual–oh, you know–scientifically convincing preliminary data that there is something going wrong? You know, just like we need actual evidence more convincing that small studies showing correlations between XMRV and both autism and chronic fatigue syndrome before doing huge studies to see if XMRV is actually a causative or contributing factor to either of these conditions.. Once again, Heckenlively values anecdote over science and doesn’t understand that both science, practical, and ethical concerns actually do limit the sorts of science that can be done. We can’t, for example, do a randomized, double blind of vaccinated versus unvaccinated children, even though that would be most bulletproof study. The logistics of even doing just an epidemiological study of vaccinated versus unvaccinated children are completely unappreciatedby the likes of Heckenlively and other anti-vaccine loons. So is the simple consideration that there has to be a biologically plausible mechanism, coupled with preclinical data including animal studies, to justify doing a human study.
Which brings us to Jake Crosby’s attempt to take on a respected bioethicist, Art Caplan. Given Jake’s past conspiracy-laden excretions, the results are ugly. Very, very ugly. I’m almost embarrassed for Jake. Well, not really. The kid’s got to learn, except that, unfortunately, I don’t think he’s teachable.
The straw men fly fast and furious right out of the box. But first Jake can’t resist his usual invocation of the pharma shill gambit. Really, Jake is so predictable that it wouldn’t be hard to write a program to generate Jake Crosby posts. Simply program it to mention pharmaceutical companies any time a vaccine defender like Paul Offit or Art Caplan is mentioned, couple it with a whole lot of conspiracies mentioning big pharma, and add a dash of referring to vaccine science as “tobacco science” Ã la Dr. Jay Gordon. Actually, making a Jake Crosby AoA Post Generator would be so trivial that it would be unlikely that any decent programmer would want to do it. Too boring. After all, Jake seems to think that coopting the title of Paul Offit’s book Deadly Choices: How the Anti-Vaccine Movement Threatens Us All is the height of cleverness and wit.
Jake tries to counter Art Caplan’s argument that vaccines are good because they not only protect the recipient but protect others, thanks to herd immunity, which is a fairly simple ethical argument to make. Jake, showing that he’s never taken an ethics course (or if he did he didn’t retain anything from it), tries to turn that argument on its head:
What Caplan does not acknowledge, just setting aside efficacy and duration of vaccinations that also come into play, is that any adverse reaction associated with a vaccine will have a higher attributable risk by virtue of the fact that it is recommended for the general population as opposed to specific individuals. So, by holding vaccines to a lower standard of safety and stating people should have no choice over whether or not they get vaccinated as bio”ethicists” such as Caplan argue, the result is much more potentially devastating than it would be for a prescription pharmaceutical not administered to the population at large. In compelling everyone to vaccinate to protect herd immunity, there would also be a substantially greater herd risk. Perhaps this highlights the inherent conflict of public health officials being charged with both vaccinating as many people as possible and making sure the shots are safe.
Now that’s a hunk of burning stupid, even by Jake’s previous flaming standards.
First, Jake clearly doesn’t seem to realize that attributable risk is defined as the difference in the incidence rate of a condition between an exposed and unexposed population. In other words, it’s a fraction (as in 1 out of 100 or 1 out of 1000). I suppose, based on Jake’s later statements, that he’s trying to argue that vaccinating the entire population will endanger a greater fraction due to vaccine shedding (more below), but even that argument doesn’t help him. Still, this is the least confused of Jake’s confused argument that all derives from Jake’s misconception that vaccines are somehow held to a lower standard of safety than other pharmaceutical medicines, which is absolutely ridiculous. It’s actually because vaccines are administered to healthy children in order to prevent disease that necessitates holding vaccines to a very high degree of safety indeed. In order to make an argument that vaccines can cause a high attributable risk in the general population, it is necessary for Jake to rely on the usual anti-vaccine exaggerations of the true risk of vaccinating. Indeed, he’s taken a page from AoA in vastly overplaying the potential harm and, more importantly, in exaggerating the chances that vaccines will cause harm. There are very real ethical issues regarding vaccinating populations against disease given that there is the very possibility of rare severe reactions. Jake’s cartoonish treatment of the issue does none of these issues credit. In fact, Jake intentionally spits on the real ethical dilemmas that lie at the heart of public health interventions, so anxious is he to argue that vaccins do more harm than good.
He then spits on science, too, by doing what we in the biz call “making shit up.” Well, not exactly. What he does is to cite all manner of pseudoscience as though it were true in order to pump up the apparent risk of vaccinating. He does this by trying to attack the herd immunity argument by claiming a “herd” harm due to vaccines:
Moving on to the MMR now, this vaccine may not pose the same kind of health threat – being a live-virus vaccine free of thimerosal – but it may very well adversely affect more than just those who take it. Research has confirmed the presence of vaccine-strain measles in the guts, blood, and cerebrospinal fluid of children with autism and bowel disease. However, no studies have been done to determine if the vaccine-strain causing these persistent infections can be communicable to others like wild measles, which is highly contagious. Despite the absence of proof, there is evidence that this may well be the case, based on what we already know about both the measles and live-virus vaccines. It has been known that virions from the latter can be shed from the recipient, causing other people to become sick, as is the case with smallpox vaccines. It is certainly plausible, at the very least, that this can happen with the MMR, too, and who knows what other live-virus childhood vaccines. The recipients of the chicken pox vaccine, for instance, are known to shed virus, causing shingles.
There’s a famous line in Animal House in which Dean Wormer tells Flounder, “Fat, drunk and stupid is no way to go through life, son.” My advice to Jake would be “Proudly and arrogantly ignorant is no way to go through life, son.” There is a tool known as PubMed, which is your friend. Use it. Love it. Heed it. If you do, you’ll find that secondary transmission of measles due to vaccination has never been documented despite the millions, if not billions, of doses of MMR given over the last 40 years. That’s actually pretty persuasive evidence that virus shedding due to vaccines is not a significant risk to children who come in contact with vaccinated children. Moreover, if there were some cases reported–even just cases that were suspicious for secondary transmission through vaccine sheddnig–you can bet that scientists would want to study them. Even if it’s possible, epidemiological evidence, specifically the lack of even a single well-documented case even after l’affaire Wakefield strongly suggests that it’s really rare–possibly even nonexistent–even though virus shedding has been measured by PCR and documented.
Meanwhile, new measles vaccines are being developed, and scientists are testing them for vaccine-strain measles shedding, while there are occasional case reports of measles being detected away from the injection site after vaccination. In fact, there are studies looking at new vaccines, and these studies include–yes–measurements of vaccine shedding by various means. Seriously, one might argue whether adequate studies have been done, but to claim that no studies have been done is so ludicrously wrong that it beggars the imagination that someone would make such a claim when some fairly easy PubMed and Google searches easily show otherwise.
After echoing Heckenlively’s invocation of XMRV as a new way to cause autism, Jake then proceeds to dive into tinfoil hat territory. In particular he parrots the claim that the CHAT polio vaccine used 50 years ago in Africa is the origin of HIV and AIDS, a claim that refuses to die despite multiple refutations (1, 2, 3, 4, 5). Basically, testimony by eyewitnesses, documents from the time, epidemiological analysis, as well as phylogenetic, virologic and PCR data all converge to reject as false the hypothesis that HIV/AIDS was derived from this polio vaccine.
Adding these up, Jake concludes:
But even setting aside all of these emerging scientific realities – adverse vaccine events still pose a grave public threat beyond just those who have negative reactions. That threat lies in the enormous costs of care for those people that society will incur – because everyone is recommended to receive vaccines; thus, a very high number of people are adversely affected, even if not directly. Society will be obligated to pay the tab for the immense morbidity caused – putting a strain on the healthcare system by raising everybody’s insurance premiums while diverting funds from other health services. The net result is an adverse effect on care, and ultimately on the collective health of society. We don’t think about it this way as much as we do about herd immunity, even though the net impacts of the former stretch far beyond the latter.
Basically, here Jake is taking estimates of vaccine complications not supported by science (such as his belief that vaccines cause autism) and problems exaggerated beyond all plausibility, mixing them with pure fantasy (the HIV/AIDS connection, for example) and putsthem all together in a blender to create a smoothie of non-data-based estimates of how much harm vaccines allegedly cause. He then compares this estimate to herd immunity and declares that his fairy dust has won out over science. It’s pathetic and desperate, really. Jake knows that the herd immunity argument used by Art Caplan is a very, very powerful ethical argument; so he tries to dismantle it. Unfortunately for him, the argument is so powerful that the only way he can take it on is through the massive application of cherry picking, pseudoscience, and the massive exaggeration of vaccine risks, coupled with risks he can make up or twist to claim that vaccines cause harm to other people the way vaccines protect other people through herd immunity.
He fails spectacularly, as always. If this sort of essay is the best reasoning he can come up with, I shudder to think about what he’s turning in to his professors. Let’s put it this way: Learning at the feet of David Kirby, Kent Heckenlively, Dan Olmsted, and J.B. Handley is not a good way to bolster your academic credibility. Science stopper, indeed.
93 replies on “The strange science and ethics of the anti-vaccine movement”
I winced when I read Crosby’s remarks. We Autistics are supposed to be LOGICAL in our thinking. And those were just the extracts you showed. I shudder to think just how execrable that post really is.
@Orac: I really don’t understand what this sentence is saying:
Are you saying the data rejects the false hypothesis? (I am reading this as a double negative).
Or are you saying the data rejects that the hypothesis is true?
I’m so confused, I can’t even parse the sentence. I usually don’t have trouble with your writing, but I am today. Sorry!
MI Dawn
As Orac states, Crosby has repeatedly made these attacks. His shtick includes what I’d call ‘The Shell of Mastery’. He has got the jargon and presentation of a master but none of the structural support. He paints a beautiful scene on the egg but after a while the contents begin to smell.
Actually, making a Jake Crosby AoA Post Generator would be so trivial that it would be unlikely that any decent programmer would want to do it.
Ad Libs are even easier.
No one, not even an ardent believer in a god, should labor to believe in science. Science, at least the observables and analysis that make up what most people call Science, should be either accepted or not accepted (hopefully based on the scientific process). Save the beliefs for either the invisible white men in the sky who appear to a chosen few on the weekend, or maybe even that Flying Spaghetti Monster.
Given that most kids are being vaccinated, we should already be bearing the brunt of most of these supposed “herd problems” of vaccination. Topping up our vaccination rate by covering the remaining minority of the population, therefore, would presumably cause fewer problems than those we’ve already caused for ourselves anyways. Acting on the assumption, of course, that there are such problems.
As to the argument that it will be expensive to cover all the healthcare costs, if that were true, you’d expect bureaucrats in countries with national health insurance schemes to be first in line to restrict vaccines (and insurance companies in countries with private insurance, naturally). Oddly enough, that doesn’t seem to be happening. They must all be drinking the “science stopper” Kool-aid!
@Dawn/triskelethecat: It seems straightforward to me. I parse “reject X as false” as an idiomatic way of saying “establish X to be false, and therefore reject it”. Here X = “the hypothesis that HIV/AIDS derived from this polio vaccine”. This is the hypothesis that the data sources Orac lists converge to refute. (The data doesn’t literally reject the hypothesis, but that’s another idiomatic shorthand for “contradict the hypothesis to the extent that a reasonable person would be justified in rejecting it”.)
Since the anti-vax movement really blossomed following changes in the DSM in the mid-nineties and subsequent increases in diagnosis, I wonder what its advocates’ reaction will be when the DSM V appears? Suppose the changes lead to a *reduction* in diagnoses ? Perhaps they’ll account for it by the removal of Thimerisol and people’s increasing decision to stop vaccinating: for which they can credit themselves. Knowing their general drift in explication, I venture that we might hear an entangled plot, worthy of a *noir* novella, involving how the developers of the manual were *paid* to make it *appear* that ASD’s were diminishing when in *fact*, they were continuing to increase by *magnitudes*. Similarly, if the new manual leads to an *increase*, we might hear about the increase in toxins that *they* exposed and how the massive cover-up failed due to the anti-vax crusaders’ valiant investigative reportage.Oh joy!
Even with a new vaccine strain that eliminates virus shedding Jake won’t be happy. He subscribes to vaccine homeopathy, whereby every ingredient once added to vaccines (like Thimerosal) permanently stays with the vaccine, maybe diluted out to non-analyzable levels, but still there and highly potentized. If there would just stop shaking the vaccine vials.
What Kent Heckenlively fails to understand is that there needs to be a “science starter” to justify the study of an idea. Saying there is no science starter is not the same as being a science stopper.
The same could be said regarding your post about Dr. Zilberberg a few days ago. Her call for “equipoise” in the study of CAM treatments fails to recognize the need for preliminary evidence or an established biological link to justify starting the science.
Kent’s argument can be summed up as an inappropriate argument from authority: “I am for the established scientific position on X [in his case evolution] so that gives me special authority to comment on, or even reject, the established position on Y [in his case, vaccines].” Or, “Hey, look at how sciency I am!”
I believe the denialism blog called this the use of ‘fake experts’.
Incidentally, since getting on the bandwagon preparing content for this week, I have a new respect for Orac’s ability to churn out a post like this every day during the weekday despite work commitments, other appointments, household responsibilities, and the requirements for eating and sleeping.
Henkenlively has been chelating his daughter since 2005, http://www.autismstreet.org/images/blog/2009jan/graph2.jpg
alongside several other “biomed treatments”.
His objective is to “cure” his daughter from autism.
Heckenlively is still abusing his daughter in this way? That girl must be remarkably resilient. I wonder how long the quacks have told Kent it will take until the autism will be cured? What will he accept as an end game? His daughter’s death? Usually people who fail again and again try something new. Poor girl.
The author apparently does not even understand the theory that he’s attempting to refute. Unless by “chimpanzees
from the vicinity of Stanleyville” he means captive chimps from other parts of Africa.
Thank you so much for taking these dolts to task on such a regular basis. Reading this made my morning.
Kent Heckenlively’s agonised attempt to establish his scientific bona fides through his acceptance of evolution is a wonderful analogy for his attitudes about autism and vaccines. Heckenlively repeatedly points out that while he “believes” in evolution (evolution, by the way, happens whether you believe in it or no – just like gravity), he goes to great lengths to demonstrate that he hasn’t let science (or, at least, his “acceptance” of evolution) alter his religious beliefs one whit.
Likewise, Mr. Heckenlively has not let his putative “belief” in science and the scientific method interfere with his dogmatic insistence that something in vaccines (mercury, XMRV, “toxins”, evil spirits, profit motive, etc.) causes autism. As Mr. Heckenlively might say, science and autism causation (and “cure”) are non-overlapping magisteria for him.
How else could you explain why he casually dismisses all of the high quality studies showing no correlation between vaccines and autism with fact-free statements like:
If anything in the “vaccines-cause-autism” debate could be called a “science stopper”, it would be the irrational refusal of the “true believers” to acknowledge the mountain of data refuting their position.
Of course, Jake Crosby – that perseverating parrot of pompous prose – weighs in with his intellectual nanowattage:
Um, no. Actually, only one research group has been able to “find” vaccine-strain measles in children with autism and bowel disease, and those findings have never been replicated by any other group, despite vigorous effort. It seems unavoidable to conclude that these finding were in error. As is Mr. Crosby – not for the first time and not for the last.
Mr. Crosby continues parroting:
Actually, there have been studies looking to see if vaccine-strain measles can be passed from person-to-person. All of these studies have found that although the vaccine-strain measles virus can be found in urine and saliva, it has never been detected in an unvaccinated person. It has something to do with the process of attenuation, although the exact mechanism is still under study.
Mr. Crosby squawks on:
Small quibble – the current measles vaccine is a live-virus vaccine. And “based on what we already know”, the measles vaccine strain is not communicable. If Mr. Crosby has data showing this is not so, he should show it.
The parroting continues:
The smallpox vaccine is a bit of an exception – as anyone with a modicum of virology education knows. To begin with, the vaccinia virus is one of the most dangerous of all the attenuated viruses – and the one that has been used the longest (see: Edward Jenner, 1796). It is also inocculated in a unique fashion, which results in an open sore with virus replicating in it.
Even so, vaccinia can only be transmitted person-to-person via breaks in the skin. Smallpox (wild-type), on the other hand, spreads easily from person-to-person with no need for body fluid contact.
Finally, it needs to be mentioned that the smallpox vaccine hasn’t been a routine childhood vaccination anywhere on the planet since 1979.
Actually, no. Not really. All of the live-attenuated virus vaccines used in children in this country have been shown to be non-communicable. Mr. Crosby, in his parroting of “chicken-pox vaccine causes shingles” is confusing – as his trainers have – two different issues.
Prior to the introduction of the chicken-pox vaccine, adults (95+% of whom had chickenpox as children) were periodically re-exposed to the chicken-pox virus, “boosting” their level of anti-bodies against the virus. Because the chickenpox vaccine strain virus isn’t communicable, this re-exposure has dropped significantly in the past decade.
Once you have had chickenpox, you are never free of the virus – it “hides out” in the dorsal root ganglia of your spinal cord (the nerve cell bodies of peripheral sensory nerves) and waits. If your circulating antibody levels drop – due to lack of exposure, immune suppression (chemotherapy, illness, cancer, etc.) or age, the virus reactivates and causes a recurrent infection we know as “shingles”.
People who have been vaccinated will not suffer from recurrent infections (unless their immunity drops and they get infected with wild-type chicken pox – a really bad thing) – only those who were previously exposed to wild-type chickenpox can get shingles. That’s why the current recommendation is for adults over a certain age (60-ish, generally) to get a “booster” of the chickenpox vaccine to prevent shingles.
As usual, Jake got everything completely backwards, but it’s not his fault. Jake isn’t coming up with these ideas – he’s simply repeating what he’s been told by people he trusts. Why he trusts them after all of the times they’ve led him astray is another interesting but probably fruitless line of discussion.
Prometheus
Sid,
Your comment makes no sense.
Stanleyville, aka Kisangani, is right in the middle of the central African jungle.
This picture (http://en.wikipedia.org/wiki/File:Pan.png) shows the ranges for chimpanzee species (the common chimpanzee – Pan troglodytes – and the bonobo – Pan paniscus, including P. troglodytes sub-species).
As you can see from the ranges, the bonobo and one sub-species of common chimpanzee both happen to be quite close to Kisangani. No need to go and capture chimps from elsewhere. Indeed, in the map included in their article, the Worobey et al. authors show that Kinsangani is located within the geographic range of P. troglodytes troglodytes.
And besides, how does your (incorrect) quibble over chimpanzee geographic distribution demonstrate that the authors of Worobey et al don’t understand the theory they are trying to refute?
I think this section of a wikipedia discussion may help elucidate my point
http://en.wikipedia.org/wiki/Talk:OPV_AIDS_hypothesis
Furthermore, the part about chimps around Lindi camp not having the correct type of SIV is a strawman. Hooper states that “More importantly, however, Hahn and Worobey’s assertion that the OPV theory claims that chimps from around Stanleyville were the source of the AIDS pandemic is, quite simply, false. In fact, as I have reported several times, the Lindi chimps were collected from a huge swathe of rain forest covering some 300,000 square miles – from Zapai in the north to Wanie Rukula in the south, and from Mambasa in the east to Mbandaka in the west. If Hahn and Worobey want to claim that they have sampled chimp SIVs from the areas that supplied chimps to Lindi, they would need first to collect chimp samples from right across the DRC rain forest and the savannah belt to the north
More Crosby idiocy:
This would be this article.
http://www.cdc.gov/ncidod/eid/vol6no5/srugo.htm
Trouble is, antivaxers consistently mangle the paper and haven’t a clue what it means, preferring, like Jake, to invent their own fantastic interpretation of the data.
Nowhere does this paper even begin to suggest vaccination leads to increased pertussis carriage, it merely demonstrates that prior vaccination does not preclude later carriage of the organism (because, as immunity wanes, kids become more susceptible to colonisation).
The paper looked at 46 fully vaccinated kids aged 2-6 years who had been exposed on a daily basis for 5 weeks to index cases of 2 children with pertussis disease and persistent paroxysmal cough.
Without vaccine protection, one could predict that all 46 would become infected and develop clinical pertussis considering the massive exposure they had been exposed to.
However, only 5 (11%)of the children were found to be colonised by B. pertussis. This confirms how effective vaccination is at protecting infants from both colonisation and infection. Protection against colonisation was not absolute however, probably because of waning immunity as kids got older.
The paper says nothing about these 11 kids becoming some type of super-source for new onward transmission (the antivax interpretation). Yes, these 11 kids could serve as a source of onward transmission, but remember that without any vaccination, all of them would have become colonised and then clinically infected, and there would have been 46 kids with prolonged coughing who would certainly be a “super source” for transmission.
Once again, Jake Crosby shows his inimitable ability to cock up the comprehension of a simple science paper.
Sorry, meant “5” kids, and not “11” kids (they were 11% of the total)
Prometheus,
Perhaps you could convert your shingles segment into a blogpost for Vaccine Awareness Week. It seems that Mercola has picked just that topic for today.
http://articles.mercola.com/sites/articles/archive/2010/11/02/chicken-pox-vaccine-creates-shingles-epidemic.aspx
In a bizarre paragraph, he seems to simultaneously argue that chickenpox and shingles are caused by separate viruses AND the same virus.
Emphasis mine:
When in error, obsfucate with Orwellian doublespeak.
Orange Lantern with a Mercola Alert:
Oh, dear! As most of you probably already know, chickenpox (herpes zoster virus) and shingles (herpes zoster virus) are caused by the same virus. Of course, that would make them very “similar” – as similar as my right hand is to my right hand (i.e. identical).
Orange Lantern – I will travel to the pit of ignorance and superstition that is Mercola and see what I can come up with.
Prometheus
Did you say that correctly? I believe the virus is “varicella zoster virus,” (a member of the herpesvirus family) and when it manifests as chickenpox it is formally called “varicella zoster” disease, while shingles disease is formally called “herpes zoster.”
Orange Lantern: Lots of different names, same virus. I think it would have been hilarious if Mercola said that chicken pox was caused by varicella-zoster virus, and that shingles was caused by human herpesvirus type 3. 🙂
Sid @ 18:
Yes, of course, because some Wikipedia volunteer editor’s opinion (or the opinion of one of the originators of the notion of a causal relationship between polio vaccination and HIV) is equal to the peer-reviewed literature.
As for their ethics, or lack thereof, notably Crosby’s lack, these critters are notorious for whining censorship! Conspiracy! Etc! but when you post a negative comment, young Joke censors it.
If Orac were to do that, they would be up in arms. J posted several comments on Jokes dexent episodic diarrhea.
Be careful… In case you didn[‘t notice, Tim Bolen has been saying that you and Liz Ditz will be added as defendants in DDI v. Barrett cuz encouraging other writers to express their views on a subject is equivalent to conspiracy. Therfore, according to Bolen, BLF will sue you and Orac too.
Seriously, I am trying to find a way to have Bolen forced to take down posts in which he claimed that bloggers would be added as defendants just for condemning the suit. I believe a precedent needs to be set that such misuse of an actual proceeding for the purpose of undermining free speech is unacceptable. I have sent a complaint to Orange County authorities reporting his threats as possible violations of California Penal Code 526, which prohibits simulating legal process. I strongly recommend that Orac, Liz Ditz and anyone else whom Bolen has tried to threaten do the same. Or just take away Bolen’s web domain and his mail box in small claims court.
Enkidu,
That would have been great, but still there’s no lack of hilarity when it comes to Mercola. I do apologize if I was being annoyingly pedantic above.
So, is BLF doing anything in this alleged Vaccine Awareness partnership? I haven’t found anything on the NVIC site and I don’t get the newsletter.
Prometheus, I love your turn of phrase: ‘perseverating parrot of pompous prose’
It describes young Master Crosby so well!
I actually don’t see creationists as “science stoppers.” At worst, they are science annoyers. Science moves forward, relentlessly, regardless of creationists.
Anti-vaxers are a public health menace, but not even they are “science stoppers.”
These people haven’t got enough to do for them to be such wind bags – Here, it is simple, I don’t know of any anti-vax movement except the one that exists in the fevered brows of vaccine hacks who see a threat to their cosy incomes from challenges to the status quo over vaccs. I don’t know of a single person who is paid or receives income from challenging vaccination. For those of you I can hear shouting ‘Wakefield’ you should actually read the Lancet paper then rethink. What I do know is this ‘there is grave and beyond reasonable doubt of the safety of vaccines in relation to autism’, there is strong evidence of the absence of unvaccinated people in the autistic population, there is recent laboratory research evidence of what happens to mercury induced into animals – it bears striking parallels with human experience and can be seen any day of the week in millions of autism sufferers whose lives have been sacrificed to gung ho vaccine zealots.
Tony Bateson, Oxford, UK.
Tony Bateson:
What vacuum do you live in? AoA, GenR, NVIC, and many other websites receive money for spouting anti-vax crap. So do many doctors sadly.
There is no relationship proven scientifically showing a causal connection between vaccines and autism.
What is it with you loons and mercury? It’s been gone almost 10 years.
Do you really live so close to the academic excellence of Oxford and continue to spray stupid like this?
Hey look Tony Bateson the illiterate pro-disease crusader still ignores the fact that unvaccinated people have autism (eg Kim Stagliano, his cohort in stupidity, has unvaccinated autistic daughters).
@Joseph,
The science stopper part of creationism is that when you get to the dicey bits, you just say goddidit and call it a day. No more research is required, requested or desired.
Pretty stupid but there it is and that is why ID and its kissing cousin creationism are not, and can never be, science.
Ha, I have a friend who has two autistic kids, the younger one unvaccinated. The explanation? The fact SHE was vaccinated. Also, her mercury fillings.
So even though there are undisputably unvaccinated people who are also autistic, they just shift things backwards so it’s mom’s fault. It’s always mom’s fault.
Hello friends –
From the post:
So is the simple consideration that there has to be a biologically plausible mechanism, coupled with preclinical data including animal studies, to justify doing a human study.
It seems that most people here are sure that there is not evidence of such a biologically plausible mechanism or animal studies of interest. But I wonder if they have spent much time really considering what the potential mechanisms of action might be comprised of?
Given that, I’d be curious in understanding what some of you out there might consider biologically plausible mechanisms and/or the types of preclinical animal studies that might justify investigation of vaccination and autism? Are there any immunological findings that might be pertinent? What types of biomarkers would be of interest? What type of data would be sufficiently compelling to convince you that a closer look at vaccination, as opposed to thimerosal or the MMR should be studied?
– pD
I find this claim intriguing. Dr. Gordon does the same thing, simultaneously claiming that the MMR vaccine causes autism and that thimerosal, which the MMR does not contain, causes autism. The only way I see to hold both unrelated ideas simultaneously (other than a religious conviction against vaccines) is to believe that some people are so predisposed towards autism that even the tiniest environmental insult will cause them to develop autism.
In which case, of course, you cannot reasonably claim that any particular case of autism was caused by a vaccine, for it might have been caused by a tuna fish sandwich last week, or mercury in the atmosphere, or a cold that they got at day care, or that scratch that they got crawling around last month, or … anything, really.
Mr. Bateson, I’m one of those millions of autistic people, and I’m still alive. Please don’t act like I’m not.
@ pD:
If you think carefully about your question, what you’re really asking is that we come up with such a plausible mechanism on the spot. The precise nature of the (e.g.) animal data needed to support it would depend on the details of the mechanism proposed.
So there’s not really anything further that can be said until and unless someone DOES come up with a plausible mechanism. Once proposed, it may be evaluated and the necessary evidence to support it discussed.
That said, there’s also a subtle difference between what you quoted and the question asked. While one needs a mechanism and preclinical evidence in order to justify human studies, they are NOT necessary in order to conclude that vaccination should be studied as a cause of autism. One obvious potential line of evidence which could support that conclusion, even in the absence of a proposed mechanism, would be epidemiological studies demonstrating that the incidence of autism is correlated with changes in the recommended vaccine schedule. If vaccination is implicated, then one would expect to see an increase in the incidence in the years following a new vaccine being added, with little change when the vaccine schedule was static. If such a signature were strongly supported by data, then it would be pretty compelling evidence suggesting a link of some sort.
Oh Joy! A visit from Tony “no such thing as unvaccinated, autistic people because they won’t come to my house with complete medical records” Bateson. How lucky can Orac get?
@pD: part of the problem is that autism/ASD seems to be a)caused by too many things and b)manifests itself in too many ways. You can’t eliminate everything and determine the cause or causes. You have to remain within the medical ethics and provide appropriate care. All you can do is look at the probabilities.
Is it possible that in a very small amount of children, a vaccine/number of vaccines/food/drink/prenatal influence causes autism? Sure. Anything is possible. However, in the studies that have been done, no definitive link has been found. We had to focus on thimerosol and the MMR because that’s where the clamour was. But studies cost a lot of money and take time and nothing was found. So, it’s not probable that vaccines contribute to autism. With the studies that were done, any sort of possibility would have been looked at if any outlier was found.
We need to move on and focus on how we can best care for these children rather than keep chasing after will-o-the-wisps.
MI Dawn
@PD. First you have to show a correlation between vaccination and autism before you even consider a mechanism; looking for a mechanism implies a correlation. No correlation between vaccination and autism has been found, so why look for a mechanism? Would you look for a valid mechanism between washing your car and the formation of thunder storms?
Hi Scott –
If you think carefully about your question, what you’re really asking is that we come up with such a plausible mechanism on the spot.
Not really. Orac, presumably, has put some thought into this issue other than the low hanging fruit of trashing Jake Crosby or Kent or rest of the AOA dorks. (?) In any case, this is a forum of relatively smart people, I’d find it hard to imagine that no one can come with any ideas on their own.
The precise nature of the (e.g.) animal data needed to support it would depend on the details of the mechanism proposed.
Well, we have a growing body of animal data showing that a robust immune response during critical developmental timeframes can cause a lot difficult to predict, persistent effects that have similarities to findings in the autism realm. I’ve been accused of Gish Gallosh here in the past, which I’d hate to repeat; take a look at the studies from Quinton Pittman, Staci Bilbo, or try looking up the concept of immune programming. I’d be happy to get more in detail as my time permits, but don’t want to blast away unless you are interested. The studies are there.
We also have a lot of data showing that people with autism react more vigorously to immune challenges when compared to their undiagnosed peers.
If you’d like to read a nice paper that has an hypothesis involving an immune mediated mechanism of autism causation, I would recommend “Macrophage Migration Inhibitory Factor in Autism Spectrum Disorders”, which perhaps coincidentally, found that as known promoters of the innate immune system increased, so too, did the severity of autism in the children studied. From that paper:
Thus, the central hypothesis underlying this research was that a genetic predisposition to a particular level of MIF production may lead to a proinflammatory profile of cell activation that, if present during a neurodevelopmentally sensitive period, might contribute to the etiopathogenesis of autism.
This is largely similar with what is being found in some of the animal studies from the authors I mentioned above; an inflammatory response during development persistently altering areas such as neuroimmune response, HPA-axis reactivity, and ultimately, behaviors.
That said, there’s also a subtle difference between what you quoted and the question asked.
That’s true, but I didn’t want to be seen as pushing for a vaccinated / unvaccinated study. In fact, I’m not sure we have a good enough reason to do that yet, but I was more interested in seeing what someone might consider digging deeper without going whole hog.
If vaccination is implicated, then one would expect to see an increase in the incidence in the years following a new vaccine being added, with little change when the vaccine schedule was static. If such a signature were strongly supported by data, then it would be pretty compelling evidence suggesting a link of some sort.
Unfortunately, our prevlance data is such a mess that it seems very unlikely such a study could be completed, IMO. We can’t even agree if autism is actually rising or not, and given that, I don’t see how we can overlay on top vaccination rates and come up with a meaningful answer.
– pD
Hi MI Dawn –
part of the problem is that autism/ASD seems to be a)caused by too many things and b)manifests itself in too many ways. You can’t eliminate everything and determine the cause or causes. You have to remain within the medical ethics and provide appropriate care. All you can do is look at the probabilities.
That is problematic. As I tried to describe above, I’m not advocating for a vaccinated / unvaccinated study, just trying to tease out if anyone has given any thought towards what a biologically plausible mechanism might look like.
However, in the studies that have been done, no definitive link has been found. We had to focus on thimerosol and the MMR because that’s where the clamour was.
Said clamor was very, very unfortunate, in my opinion. It kind of reminds me of the election. Ouch.
With the studies that were done, any sort of possibility would have been looked at if any outlier was found.
But what if we were studying the wrong thing? We weren’t studying vaccination, we were studying thimerosal, and we studied one vaccine; one of the last ones given. Sure there was clamor. But take a look at the MIF paper I referenced above and the focus on a pro-inflammatory cell activation profile during critical timeframes; any vaccine is going to generate an immune response. Yet, we’ve really only studied one vaccine, the MMR, which happens at very different timeframes than the rest of the schedule; unless we have a good reason to think that something will affect a twelve month old in the same way it will affect a two month old, I’m not sure why we should expect to learn much about the earliest vaccinations from MMR studies. In fact, several aniimal studies show quite distinct time dependent effects such that older animals seem not to acquire persistent effects compared to younger animals.
– pD
Orange Lantern,
RE: herpes zoster virus
That was a bit sloppy on my part – “herpes zoster virus” was a popular name for HHV-3 when I first took virology, so it tends to be the term my brain “reaches for” first.
Other names for this virus are varicellovirus, varicella virus, varicella-zoster virus and, of course, the current preferred term, human herpes virus 3 (HHV-3).
On your recommendation, I’ve posted a brief deconstruction of my favorite three anti-vaccine myths on my ‘blog.
Prometheus
Hi Richard Wolford –
First you have to show a correlation between vaccination and autism before you even consider a mechanism; looking for a mechanism implies a correlation. No correlation between vaccination and autism has been found, so why look for a mechanism? Would you look for a valid mechanism between washing your car and the formation of thunder storms?
As I stated above, the inherent messiness in our prevalance data makes a quality analysis almost impossible.
Right now, what I could do is a gross over simplification; show autism rates and the increase in the vaccination schedule and note the rise in both. What then, though? If I were to do this and claim it had validity, I’d be told that our autism prevalance rates for the past were notoriously inaccurate to the point where the comparison wasn’t useful.
But your post is a great example of exactly what I’m trying to get people to consider; the narrative is long on beating up the AOA guys, but the details fall apart against very primitive logical filters.
It’s a catch-22. We cannot move forward with human studies on humans without a biological mechanism. OK. We cannot looking for a mechanism without appropriate data showing a correlation. OK. But our existing data is impossibly noisy on which to base an opinion. OK. (?)
– pD
@ pD:
At the risk of belaboring the obvious, I’ll point out that “immune response might be relevant” is a very long way from an actual mechanism. And, to be perfectly honest, I wouldn’t place all that much faith in Orac’s musings on mechanisms. It’s not his specialty, and these questions are VERY hard.
That’s not a catch-22. It would be a catch-22 if we needed human studies in order to posit a mechanism, but demanded the mechanism prior to doing human studies. That’s not hte situation.
The conclusion from the points mentioned is that there’s no good reason to move forward until and unless the data provides motivation to do so, or unless somebody comes up with some clever brainstorm based on the limited resources that it makes sense to devote to the idea in the absence of supporting evidence. Which is not only reasonable, but a very, very, very, very, very common status for ideas in science.
Which has been done. The MMR and thimerosal research are a result of this. Since that didn’t pan out, you’d need something better.
It’s a naive way to do things too, and pretty easy to dismiss. After all, what didn’t increase in the 80s and 90s? (There are statistically more sophisticated ways to analyze the cross-correlation of time series.)
It’s even worse when “researchers” like the Geiers resort to what I can only describe as fraud to try to make the association appear more plausible than “both increased.”
The way I see it, if there was anything there to be found, it would’ve already been found after 12 years.
pD comments:
I’d have to agree with you on that – comparing the autism prevalence data from today and even five years ago is like comparing apples and orangutans. But this has been discussed and explained ad nauseum, so I won’t go into it again (unless you really want me to).
Another problematic part of your comparison is that “the vaccine schedule” isn’t even a good surrogate for actual vaccine uptake, which typically lags years behind changes in the vaccine schedule.
Finally, having already shown that one vaccine-related variable (thimerosal) isn’t correlated with autism (or “neurological disorders”), it seems a bit much to ask the research community to potentially waste more time and money chasing down what seems to be – to me at least – merely a “fall-back” position for people trying to blame autism on vaccines.
The immune system changes/differences in autism that you cite aren’t nearly as convincing as you seem think they are – there are a number of alternative hypotheses that are equally plausible, including the one where the causal arrow is reversed, i.e. where autism causes the immune differences, rather than the other way ’round.
pD continues:
I have to ask whose “details fall apart against very primitive logical filters”? Beating up on “the AoA guys”, while satisfying in its own way, is not the basis of the objections to further expenditure of time and treasure on what is exceedingly likely to be another “dry hole”.
In fact, it was the response of “the AoA guys” (and “gals”) to well-designed and rigorous research studies that has led many researchers in the field to refuse further participation. Their argument, which I cannot refute, is that since “the AoA guys” – who were a major reason the thimerosal studies were done – didn’t “believe” the results, there is little point in doing another study at their behest, since they’ll likely ignore those results, too.
I realise that I am merely a research scientist, so my views may not be relevant, but it seems rather “cart-before-the-horse” to be charging after hypothetical causes of autism before we know what autism is, i.e. before we know what anatomic, physiological or genetic factors(s) lead(s) to autism. It also seems to me that looking for causes before we even know if autism is one disorder or a thousand different disorders is also a recipe for wasted effort.
I also realise the strong desire a number of people have to find a/the “cause” of autism, primarily because they think that will lead to a “cure” (which is not a logical conclusion). However, randomly choosing to investigate something that correlates (or seems to) with autism will work only by accident. Going through and investigating just the correlations reported (not all of which are reliable) between the immune system and autism would take decades of research with little chance of success (again, except purely by accident).
It seems that more research into the etiology of autism should be done before looking at causes, because you can’t even tell if a proposed mechanism is plausible without it (although the converse is not necessarily true).
Prometheus
Nope, that’s not correct. You’re still trying to show a correlation that doesn’t exist; there are simpler explanations, such as changes in diagnostic criteria. You also ignore the rise in autism among unvaccinated groups, which is cherry-picking. You have failed to demonstrate correlation. If you could show rise in autism rates in vaccinated groups was statistically greater than the rise in unvaccinated groups then you would have a correlation which could then be examined. However, these data do not exist. And if these data did exist, correlation still does not equal causation, or you could argue global temperature increases result from a decreased number of pirates.
How is it noisy? You need to explain, you can’t simply assert. First, the AoA site is propaganda plain and simple; there is no data to support a link to autism and there are plenty of data which refute a possible link. So that’s it, end of story, no more research required. It is not a catch-22 unless you’re don’t know what a catch-22 really is. If you find a correlation you can then examine a plausible mechanism. If you find a plausible mechanism you can begin doing studies. It’s actually quite simple; the problem is that there is not a correlation, so there’s no reason to move further. Your logic is not at all sound I’m sorry to say.
@pD: yes, there is a lot of noise. To add to the noise, the way ASD/autism is diagnosed changed during that time also. We already KNOW that there has been an inverse relationship between the diagnosis of “mental retardation” and “ASD” or “Autism”. And, as Joseph said, so many OTHER things changed in the 80’s and 90’s. It would be very hard to start from ground zero. However, someone pointed out today,(and, I apologize, but I’ve been reading a lot of posts today and don’t recall where I saw this), one thing we have not seen is a correlation between the addition of new vaccines in recent years with a jump in autism diagnoses.
I have often said that if autism was diagnosed back in the 60’s and 70’s as it is today, that I could have named several kids in classes with me or in my neighborhood with an autism/ASD diagnosis (based on behaviors). And the vaccine load was much less in those days. But kids didn’t get a diagnosis unless they were really “classic Kanner”. They were just ‘naughty’ or ‘slow’ or ‘weird’ or ‘difficult’ kids (even my brother would probably fall on the spectrum.)
I just don’t think, from my age and experiences, that there is an increase in prevalence. In diagnosis, yes, in recognition, yes. But not in prevalence.
@ Richard, MI Dawn:
I think pD gets that, and in fact means that by the “noise.” We’re just going from there to “no reason to pursue it” while pD is going to “but then how do I justify pursuing it?” To which the answer, of course, is “you can’t”, but those with an ideological commitment to the theory don’t accept that reality.
Obviously,I still have some catching up to do.in regards to AoA,I had not read any of those earlier posts from Mr.Henkenlively,that bit about “The bugs are making metals” ,is gold pressed latinum woo for the ages.His obsessiveness about his daughter’s metals charts,body temperature from different orifaces,is very typical of the behavior of such parents.I would just toss out there that COMT mutations are a big part of both OCDs,and chromosome 22q11.2 disorders, the latter being a known cause of both autism,developmental delay,and immune disorders in children.
Orac,even before reading this newest column,I was struck by how your critiques of Jake Crosby’s columns,come across like a high school teacher,or a college professor taking a student aside,before giving an “F” to a poorly researched, and shoddily written paper.I’m sure a lot of us have wondered if columns like this one,are any indication of the type of work he does at school/college,and if so,how has he managed to hang in there as long as he has.Some of us with both autism,and learning disabilities,know better than to go where we cannot hack it,and therefore not make a fool of ourselves.
Julian @1,you are right.Crosby is an embarassment to autistics everywhere.
Hi Prometheus –
It’s been a long time since we’ve talked.
The immune system changes/differences in autism that you cite aren’t nearly as convincing as you seem think they are – there are a number of alternative hypotheses that are equally plausible, including the one where the causal arrow is reversed, i.e. where autism causes the immune differences, rather than the other way ’round.
I won’t disagree per se. I blogged about one that occurred to me involving an epigenetics paper and people with PTSD.
But the problem is that we do have evidence that immune challenges in early life can cause very similar physiological endpoints to what is observed in autism. The mechanism I am proposing isn’t about hand waving, it is about taking a dispassionate look at the animal studies we have available and seeing if our existing thimerosal based studies are of any help or not. I’d really recommend that you take a look at some of the animal studies that I’m trying not to spam with.
For example, this study was posted a few months ago, Early life activation of toll-like receptor 4 reprograms neural anti-inflammatory pathways that was published in the Journal of Neuroscience, which if I understand impact factors correctly, is relatively prestigous.
Here is the abstract:
A single postnatal exposure to the bacterial endotoxin, lipopolysaccharide (LPS), reduces the neuroimmune response to a subsequent LPS exposure in the adult rat. The attenuated fever and proinflammatory response is caused by a paradoxical, amplified, early corticosterone response to LPS. Here we identify the mechanisms underlying the heightened corticosterone response to LPS in adults after early life exposure to LPS. In postnatal LPS-treated rats, hypothalamic corticotrophin-releasing hormone mRNA, pituitary proopiomelanocortin mRNA, and circulating adrenocorticotrophic hormone were all increased after adult exposure to LPS without significant modification to hippocampal or hypothalamic glucocorticoid receptor mRNA or protein or vagally mediated afferent signaling to the brain. Postnatal LPS administration did cause a persistent upregulation of the LPS Toll-like receptor-4 (TLR4) mRNA in liver and spleen, but not in brain, pituitary, or adrenal gland. In addition, cyclooxygenase-2 (COX-2), which is a prostaglandin biosynthetic enzyme and is normally undetectable in most peripheral tissue, was constitutively expressed in the liver. Adult immune activation of the upregulated TLR4 and COX-2 caused a rapid, amplified rise in circulating, but not brain, prostaglandin E(2) that induced an early, enhanced activation of the hypothalamic-pituitary-adrenal (HPA) axis. Thus, postnatal LPS reprograms the neuroimmune axis by priming peripheral tissues to create a novel, prostaglandin-mediated activation of the HPA axis brought about by increased constitutive expression of TLR4 and COX-2.
Check out how casually the authors and peer reviewers at the Journal of Neuroscience were with the opening sentence: A single postnatal exposure to the bacterial endotoxin, lipopolysaccharide (LPS), reduces the neuroimmune response to a subsequent LPS exposure in the adult rat.. This wasn’t an investigation of if an immune challenge during early life can reprogram the neural immune functions, but how such effects are achieved.
For another very gracefully written paper, you might check out “Postnatal Inflammation Increases Seizure Susceptibility in the Adult Rat” by the same group, which went to great lengths to elucidate on a tnf-alpha driven mechanism by which LPS exposure permenantly caused animals to be more susceptible to seizures into adulthood. At the end of the day, the data on immune programming isn’t going away just because people screamed about thimerosal and there are alternative hypothesis on immune activation observed in autism. Sooner or later we are going to have to reconcile the fact that an increasing number of studies tell us that the immune system is maleable during development with far flung consequences, and our existing research tells us almost nothing about this phenomena.
I realise that I am merely a research scientist, so my views may not be relevant, but it seems rather “cart-before-the-horse” to be charging after hypothetical causes of autism before we know what autism is, i.e. before we know what anatomic, physiological or genetic factors(s) lead(s) to autism.
We’ve had this discussion previously and in some ways I agree with you. You left out ‘environmental’ in your list though. 🙂 BTW – I’m not advocating for stopping looking at what autism is by any stretch.
It seems that more research into the etiology of autism should be done before looking at causes, because you can’t even tell if a proposed mechanism is plausible without it (although the converse is not necessarily true).
OK, though there seem to be a great number of other researchers, editors, peer reviewers, and study funders seem a little more willing to entertain studies like this. It’s a mixed bag.
– pD
Hi Robert Wolford –
Nope, that’s not correct. You’re still trying to show a correlation that doesn’t exist; there are simpler explanations, such as changes in diagnostic criteria. You also ignore the rise in autism among unvaccinated groups, which is cherry-picking.
I’m not trying to use that data to show anything; my argument is that we have no quality data; and because of that we cannot attempt correlative analysis. For someone who so demands You need to explain, you can’t simply assert, I’m going to have to ask you what studies you can post showing a ‘rise in autism among unvaccinated groups’. [What is your definition of ‘unvaccinated’?]
How is it noisy? You need to explain, you can’t simply assert.
Hehe. In one paragraph you allude to the problems of diagnostic expansion infiltrating into our prevalance values, thus making true determinations of incidence difficult, and in the next, you don’t understand why our data is noisy. If I were you, I might be a little more cautious about acusing people of having unsound logic.
– pD
The term “noisy” generally refers to the amount of random error, whereas diagnostic expansion would be a type of systematic error or bias.
I’ll also note that neither random error nor bias prevents statistical analysis, although it does make it less accurate.
Really? Could you provide some relevant examples? The examples you’ve given so far aren’t very similar to the physiological endpoints observed in autism. Then again, it could be that I’ve been looking at the wrong studies in those instances where you only gave names of researchers.
pD, one question- why do you feel that vaccines are more LIKELY to be a cause of autism than other hypotheses? To borrow someone else’s example, the percentage of mothers working outside the home has increased over the past few decades, and so has the reported rate of autism. So why shouldn’t we fund studies to try to determine if working mothers are a leading cause of autism? IOW, we can’t study everything that POSSIBLY could be a cause of autism- there’s not enough time, researchers, money,etc. We have to focus on the most likely hypotheses. What makes you think that vaccines are likely enough to merit further research?
@Michael
Not to mention why “vaccines in general” rather than specific vaccines or a specific subset of vaccines.
Hi W. Kevin Vickland –
Could you provide some relevant examples? The examples you’ve given so far aren’t very similar to the physiological endpoints observed in autism. Then again, it could be that I’ve been looking at the wrong studies in those instances where you only gave names of researchers
Sure. Well, in the first place, the “Postnatal Inflammation Increases Seizure Susceptibility In Adult Rats” study finds increased brain excitability; and an increase in epilepsy and/or abnormal EEGs is widely reported in the autism realm. There are tons and tons of papers on this, but at the high level, epilepsy prevalance in autism is believed to be in the 20 – 40% range, with even higher values observed for abnormal EEGs in the absence of epilepsy proper. You might also look at Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats which had similar findings, though used diffferent triggering agents, and different anti inflammatory agents to further implicate the immune response as the culprit in persistent changes.
The neural programming paper refers to altered HPA axis responses as a result of immune challenge; while I’m not aware of any in the autism realm that utilize TLR4 as a trigger point, again, altered HPA axis responses to novel stumuli have several papers associated with them. In any situation, I suppose you could argue that I have failed to show in this case a direct correlation to known autism findings, but the fact that we know altered febrile responses can be caused by early life immune challenge, but don’t have direct evidence for this in autism is hardly something to celebrate. We do have some very limited evidence of improved behavioral correlations in autism, during times of fever. [See Behaviors associated with fever in children with autism spectrum disorders for more on this.]
Or, why not take a look at Early-Life Programming of Later-Life Brain and Behavior: A Critical Role for the Immune System which describes potential mechanisms by which early life immune activation could result in chronically activated microglia, something that has been observed in the autism realm. From that paper:
We believe that cytokines are important not only for behavioral changes during acute illness, but may also underlie long-term changes in behavior as a consequence of infection early in life. Thus, the purpose of this review is to: (1) summarize the evidence that infections occurring during the perinatal period can produce effects on brain and subsequent behavior that endure throughout an organism’s life span, and (2) discuss the potential role of cytokines and glia in these long-term changes. Cytokines are produced within the brain during normal brain development, but are expressed at much higher levels during the course of an immune response. In contrast to overt neural damage, we present data indicating that increased cytokine exposure during key periods of brain development may also act as a âvulnerabilityâ factor for later-life pathology, by sensitizing the underlying neural substrates and altering the way that the brain responds to a subsequent immune challenge in adulthood. In turn, this altered immune response has significant and enduring consequences for behavior, including social, cognitive, and affective abilities. We discuss the evidence that one mechanism responsible for enduring cytokine changes is chronic activation of brain microglia, the primary immunocompetent cells of the CNS.
I would refer you to Vargas 2005, or Morgan 2010 for references of direct observation of chronically activated microglia in autism. Or, you could look to Li 2009, Chez 2007, or Garbett 2008 for other studies that clearly indicate an ongoing immune response in the CNS of people with autim; a condition almost certainly administered by said chronically activated microglia.
Alternatively, you might look at Early-Life Immune Challenge: Defining a Critical Window for Effects on Adult Responses to Immune Challenge which showed increased anxiety behavior in animals exposed to LPS.
Sorry I’m not linking, but I’m trying to get to the gym.
HTH
– pD
Hi Michael –
why do you feel that vaccines are more LIKELY to be a cause of autism than other hypotheses? To borrow someone else’s example, the percentage of mothers working outside the home has increased over the past few decades, and so has the reported rate of autism. So why shouldn’t we fund studies to try to determine if working mothers are a leading cause of autism? IOW, we can’t study everything that POSSIBLY could be a cause of autism- there’s not enough time, researchers, money,etc. We have to focus on the most likely hypotheses. What makes you think that vaccines are likely enough to merit further research?
Great question. I would state that I’m not advocating an autism only causation route. I have no problems with pure genetic cases of autism, increasing diagnosis contributing to our apparent observations of increase, and/or other environmental participants. That being said, I condiser myself a skeptic, and our study on vaccination is very limited compared to the narrative being sold.
Regarding why vaccines might merit attention, I would refer you to our animal studies that I referenced in previous posts, as well as the numerous studies that indicate an altered immune responses in the autism population. Regarding working mothers, you might take a look at some effects of maternal seperation in pubmed and see what you find.
@ Todd W –
Not to mention why “vaccines in general” rather than specific vaccines or a specific subset of vaccines.
You are hitting on the blind spot in our research, but you can’t see it. All vaccines are going to generate an immune response. If they don’t, they don’t work. If that immune response, as indicated by the animal studies above, in an of itself, is capable of causing problems given specific individual and developmental conditions, our existing research would be completely blind to it. Seriously, take a look at “Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats” and “Viral Like Brain Inflammation Causes Increased Seizure Susceptibility in Adult Rats” for examples. It didn’t matter what the triggering agent was, all that mattered was if there was an immune response or not. Adminitration of different anti inflammatory agents attenuated the effects. It is “vaccines in general” because vaccines in general all generate an immune response.
Everyone admits that we haven’t studied the schedule in whole. We just haven’t. There is good reason for that, though. Instead, we’ve added one component at a time to our testing, but if there is an effect that is related to something all vaccines share in common, our ability to discern a problem becomes very problematic with an incremental approach that the vaccine safety testing route has taken.
– pD
Hello pD, Have you looked at cytokine expression profiles for H. influenzae, K. pneumoniae, N. meningitidis, K. pneumoniae and Salmonella spp. for example and their relationship to seizure disorders and/or autism if any?
pD:
But if it’s the immune response itself which poses the problem, doesn’t normal illness pose at least as much of a threat as a vaccine, if not more (given that actual illness tends to provoke a much more robust immune response)?
@pD
But we don’t need to look at all vaccines. For example, we don’t need to look at HPV or meningococcal, since they are given long after the age of autism onset. Influenza vaccine is a very recent addition and is unlikely to be connected in any way. Likewise rotavirus vaccine. MMR has already been examined and found to have no connection. IIRC, some of the thimerosal studies had individuals who received less thimerosal because they did not get certain vaccines, with no difference in autism rates.
While it is possible that some of the other vaccines may play a role (e.g., HiB or DTaP), the risks posed by those diseases would, to me, outweigh the potential for autism, since it is likely that the vaccines play any significant role in the overall rates, just thinking about the complexity of autism and the potential range of causes.
Further, if the issue is immune response, itself, then it seems, from my lay perspective, that vaccines are still better than the risk of natural infection, since vaccines are designed to provide a more limited immune response than would occur with a full infection.
And, if it is even more specific, being limited to the inflammatory process, again, vaccines would seem to me to be a relatively minor player in the whole thing.
Again, from my lay perspective, vaccines would seem to be one of the less promising avenues of research into the cause(s) of autism.
And also all the immune responses produced by other things – skinned knees, the common cold, etc. It is an extraordinary stretch to go from making the suggestion of a general immune-mediated causation to vaccine causation. Certainly far too much of a stretch to justify research dollars.
Hi Science Mom –
Hello pD, Have you looked at cytokine expression profiles for H. influenzae, K. pneumoniae, N. meningitidis, K. pneumoniae and Salmonella spp. for example and their relationship to seizure disorders and/or autism if any?
I have not, but I think I’ll poke around and see how little I know about those areas this afternoon.
Thank you!
– pD
Hi Calli Arcade –
But if it’s the immune response itself which poses the problem, doesn’t normal illness pose at least as much of a threat as a vaccine, if not more (given that actual illness tends to provoke a much more robust immune response)?
Only if said immune response occurs within the early infancy. Several of the animal studies show quite distinct time dependent effects, such that an animal challenged postnatally at day 14 showed persistent effects, but an animal challenged at postnatal day 21 showed no such effects. Our vaccine uptake rate hovers ~ 90%; this means that 90% (or so) of infants are vaccinated sixty days after birth. [For now, lets ignore Hep-B, which is usually given within a few days of birth].
What percentage of sixty day olds do you believe got pertussis, or diptheria, or polio, or Hib in the pre-vaccination era? Do you think it was anywhere close to 90%?
Also, I think you’d be suprized at how utterly lacking our data is regarding the innate immune response as a result of vaccination. We simply haven’t studied it. A few weeks ago there was a similar discussion here where I asked someone, anyone, to show me a pre and post vaccine study that showed inflammatory cytokine values for a pediatric population. No one could, excepting Dangerous Bacon, who tried to use a study that used a challenge technique for specific antigens several months after vaccination.
There’s another reason this analogy might be an over simplification; namely that we are discovering that if the body detects that it is under attack by several types of pathogens simultaneously, the resultant innate immune response is increased synergistically. From a survival standpoint, this makes a lot of sense to the organism, it is better to risk increased inflammation if several invaders are present. But this mechanism works like this for a good reason; inflammation is something needs to be controlled, and only under extreme circumstances should an even more robust response be mounted.
For example, this came out this week, TLR ligands induce synergistic interferon-β and interferon-λ1 gene expression in human monocyte-derived dendritic cells.
Toll-like receptors (TLRs) are pattern-recognition receptors of the innate immune system that recognize various pathogen-associated molecules. TLR ligands are potent activators of immune cells and certain TLR ligands have a synergistic ability to induce the production of pro-inflammatory cytokines. In the present study we have analyzed the potential synergy between TLR3, TLR4 and TLR7/8 ligands in type I and type III interferon (IFN) gene expression in human monocyte-derived dendritic cells (moDCs). We show that stimulation of moDCs with TLR7/8 ligand R848 together with TLR3 or TLR4 ligands, polyI:C or LPS, respectively, leads to a synergistic expression of IFN-β and IFN-λ1 mRNAs. Neutralization of type I IFNs as well as IFN priming prior to stimulation suggest that IFN-dependent positive feedback loop is at least partly responsible for the mechanism of synergy. Enhanced expression of TLR3 and especially TLR7, which are both under the regulation of type I IFNs, correlated to synergistic TLR ligand-dependent induction of IFN-β and IFN-λ1 genes. NF-κB, PI3 kinase and MAP kinase pathways were involved in TLR ligand-induced IFN gene expression as evidenced by pharmacological signaling inhibitors. The data indicates that IFNs contribute to TLR-dependent gene activation in human DCs stimulated with multiple TLR ligands
When we get a natural infection, we are only under attack by one type of pathogen, generally. That isn’t what our bodies think is what is happening when we get exposed to vaccination for several bacteria types and viruses simultaneously. We make broad assumptions with systems as complicated as this at great risk to valid conclusions.
Of course, it is possible that there is no increase in inflammatory cytokines in vivo as a result of a combined shot schedule, but the facts on the ground are, we just don’t have any data one way or the other.
BTW – A few weeks ago we had a similar discussion and you asked a neat question, regarding the prevelance of inflammatory auto immune conditions in autism. It later occurred to me that we do have evidence of the opposite, namely that having some types of inflammatory conditions does appear to be associated with an autism diagnosis. This paper, Autism spectrum disorders and mastocytosis reports a nearly 1/10 incidence of autism in patients with mastocytosis. (!)
– pD
Hi Scott –
And also all the immune responses produced by other things – skinned knees, the common cold, etc. It is an extraordinary stretch to go from making the suggestion of a general immune-mediated causation to vaccine causation. Certainly far too much of a stretch to justify research dollars.
I don’t know how many two, four, or six month olds you’ve been around, but in my experience, they generally aren’t even crawling yet; much less finding ways to get their knees skinned. How many infants do you know that have gotten a skinned knee? There is an inability to decouople infancy with childhood in these discussions with alarming frequency.
In any case, you don’t think that additional research is justified. OK. We may disagree, I suppose, but that’s also OK. Restore santiy et all.
– pD
@pD: you asked:
What do you mean by the pre-vaccination era? I was born in 1962; I could show you my vaccination record that I got the DTP at 2 months, 4 months, 6 months. In the 1980’s, my kids got the same schedule, along with OPV.
While that is anecdotal, I honestly can’t point to anyone I knew as a child or as a young parent who didn’t have/have their child get the vaccines on schedule. So I would imagine, at least for the DTP, the percentage of infants who got it at ~60 days of age was pretty high. While not 90%, according to the CDC, in 1962, 67% of children had completed the DTP3+
It’s weird that they didn’t collect data from 1986-1990 (the years of my children’s births). I wonder what the percentages were for those years since they’d been fluctuating between the 64-78% ranges then, in the early 1990’s,jumped to over 90%. Of course, I also note HOW the data collected also changed, which makes you wonder about whether one might be comparing apples and oranges.
http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/G/coverage.pdf
Ah, so you’re only saying it could be significant if it’s in a newborn. I thought you were saying any vaccine prior to onset could be potentially implicated, which is a much larger area. Note, however, that animal brain maturation does not closely model human brain maturation. There are similarities, but our brains so vastly different from most animal brains that it’s difficult to draw conclusions. You can’t just scale the numbers and expect it to match — so, fourteen days in an animal model can’t be assumed to map to 60 days in humans. We’re unusual in that our brains even continue to mature after we reach sexual maturity (though note that some of the longer-lived and intelligent species, such as elephants, also reach sexual maturity before intellectual maturity). If you think there could be an effect, why limit it just to newborns?
That said, I expect the number of newborns who got pertussis, or diptheria, or polio, or HiB in the pre-vaccine era was considerably larger than today. Pertussis used to be a big killer of newborns; a lot of them did catch it. It seems a bit disingenuous to suggest that would be the full list, though, or to suggest that vaccination has eradicated even the majority of infectious diseases likely to strike newborns. Cuts and scrapes do happen. Yeah, they’re not skinning their knees on the playground, but newborns have a nasty habit of scratching themselves all over with their razor-sharp fingernails, as they flail. Eye infections are fairly common, complicated by the fact that a lot of newborns have a tendency to get plugged tear ducts. Oral thrush is extremely common, though not universal. (My firstborn got it before she was a month old. That certainly makes nursing interesting.) Inflamed diaper rashes are ubiquitous, and can become infected. Colds and flus can strike newborns just as they can grownups, and they do come down with them. Pertussis still strikes newborns, who are not yet vaccinated. I had chickenpox in this time period.
Incidentally, how many vaccines do children normally receive prior to 60 days anyway? My daughters both received their first vaccines *after* 60 days, apart from the birth dose of HepB (which I need to check in my records at home whether or not they actually got — unfortunately, my files are in a mess right now after my basement remodeling project). That includes the one who is on the spectrum. Per the CDC, at present the only vaccine even recommended prior to 60 days is one or two Hep B doses. Which means that if you are interested in studying the possibility of autism caused by a vaccine prior to 60 days, you should not be calling for a study of all vaccines; this would be a waste of effort. You should instead be calling just for a study of Hep B, which would have the bonus of being much easier to do.
Hi Calli Arcade –
Ah, so you’re only saying it could be significant if it’s in a newborn.
Emphasis on could, but essentially yes. [Thanks for noticing the nuance, btw.]
Note, however, that animal brain maturation does not closely model human brain maturation. There are similarities, but our brains so vastly different from most animal brains that it’s difficult to draw conclusions.
That’s a big problem and I would definitely agree that all decisions must be tempered with caution. Unfortunately, our animal studies are what we have available. My experience in reading a lot of these are that the estimates on rodent to human equivalencies is all over the map, from second trimester to first year of life. This is an area where we still have lots to learn.
It seems a bit disingenuous to suggest that would be the full list, though, or to suggest that vaccination has eradicated even the majority of infectious diseases likely to strike newborns.
Well, I’d hate to be considered disingenuous, but the point I was trying to make is that our schedule of vaccines is different than an exposure model based on random interactions. Sure kids got sick in the past; sometimes as infants. But in terms of initiating an immune response, we have turned a curve into a straight line, and assuming all things are equal seems a bit too simple for the system we are interacting with.
Regarding diaper rash, thrush, and the rest of the ways kids can get an immune response, this is true to an extent, but vaccines are designed from the ground up to insure a robust immune response. They don’t work without one. Fever is associated in varying degrees with vaccination, in some instances up to 25% of the time (DTaP), with inflammatory cytokine generation as the likely mechanism; I do not believe that twenty five percent of children with diaper rash get fevers.
Which means that if you are interested in studying the possibility of autism caused by a vaccine prior to 60 days, you should not be calling for a study of all vaccines; this would be a waste of effort.
I only used sixty days as a measuring point because this is generally the first well check up that involves vaccination for a large number of diseases. The Hep-B discussion gets bogged down quickly into back and forths on necessity.
@MI Dawn/ Trisket –
Calli Arcade has illustrated my concerns over what I meant by ‘pre-vaccination’ nicely, I think.
– pD
This is true, but they have something in common with things like oral thrush and infected diaper rashes — they are generally localized. Now, fevers, I realize, are systemic, and you mention fevers as a side-effect of DTaP. Fevers would be different, and high fevers are known to be inherently dangerous, no matter what their cause (which may very well be dangerous on its own). One thing that complicates information on this subject is that babies’ core body temperature is far more variable than an adult’s. The contradictory data on whether teething actually causes low-grade fevers is a case in point. Small trends may be masked by the natural variability in infant body temperature. Don’t take that as an argument that we shouldn’t look into it; I’m just saying it’s hard to draw conclusions from what we’ve got.
About Hep B — you’re quite right that such discussion gets bogged down quickly, but it would be a good choice for piloting the research. It is given earlier than any other vaccine, which is significant for three reasons. One is that *if* the brain is more vulnerable at this early stage, Hep B would have a better chance of showing it. Another is that since no other vaccines are given at this stage, there are fewer variables to worry about. The third is that in the first two months of life, most babies get multiple well-child checkups, providing more uniform data over this time period. Obviously, they would need to be followed up later to see how many develop autism and such, but it seems like it would be a good group to start with.
I see that pD is back, riding the same old horse.
“I’d be curious in understanding what some of you out there might consider biologically plausible mechanisms and/or the types of preclinical animal studies that might justify investigation of vaccination and autism? Are there any immunological findings that might be pertinent? What types of biomarkers would be of interest? What type of data would be sufficiently compelling to convince you that a closer look at vaccination, as opposed to thimerosal or the MMR should be studied?”
So while evidence is lacking of a vaccine-autism connection (and there is abundant evidence refuting the hypothesis), pD thinks we should be generating “biologically plausible” mechanisms for why there could be a connection (the implication being that we’re lazy or denialist for not doing so).
Michael said “pD, one question- why do you feel that vaccines are more LIKELY to be a cause of autism than other hypotheses? “
That’s a good question. Recently in another discussion here, pD berated us for focusing on antivaxers and their false claims about vaccines and autism, suggesting that we need to get down to the nitty gritty about what actually causes autism. pD was reminded that his/her own emphasis here has been almost exclusively on finding a way to link vaccines and autism, and it was proposed that he/she discuss some alternate mechanisms or autism causation, something to which he/she agreed.
That was then – now pD is back again honing in on vaccines.
I too would be interested in commentary by pD about how toxins generated by actual live disease organisms and their inflammatory cytokines may influence development of autism, and why we should be more worried about the “robust immune response” generated by vaccines (which (gasp) cause fever in a minority of recipients), as opposed to the immune response caused when kids get a whopping dose of illness with multisystem implications.
By the way, pD, the technique of throwing out links to or quotes from a big batch of sources (most or all of which are irrelevant, outdated, and/or deceptively cherry-picked) is known as a Gish gallop (after Duane Gish, a creationist who loved to use it in debates). What you’re doing now is not precisely Gish galloping…but loading up on long abstracts full of science-y terms but which have extremely tenuous or absent connections to immunization practice, does little more than to show you know how to cut and paste.
Again, I look forward to your answering Science Mom’s question about cytokine profiles associated with disease organisms. You can use that data to generate a list of priorities for immune system research, justifying if possible your determined focus on vaccines as the source of Bad Things.
@pD
Why mention only serious diseases? If you’re concerned about the timing of immune responses, you need think about all immune responses in infancy, not just those diseases the early vaccinations protect against.
Anecdote alert: My second child got his first bad cold at 3 weeks of age – less than 60 days, and before any vaccinations apart from the birth HepB – mild fever and congestion. His reaction (i.e., immune response) to that cold was larger than any reaction he ever had to any of his vaccines (with the possible exception of DTaP he just got, which made his leg ache and I had to carry him around half the day – no fever involved however).
I have no data to back me up on this and no idea where I could get it, but let’s speculate. In the days before we all sterilized our homes and obsessively isolated our newborns to avoid illness (or at least we did that with our first-borns), how may infants were exposed to pathogens at levels higher than vaccine levels during that first 60 days of life?
My guess is most of them. In the pre-vaccinaton era, newborns were not living in a germ-free bubble.
pD, think about it.
HI Dangerous Bacon –
So while evidence is lacking of a vaccine-autism connection (and there is abundant evidence refuting the hypothesis), pD thinks we should be generating “biologically plausible” mechanisms for why there could be a connection (the implication being that we’re lazy or denialist for not doing so).
There is abudant evidence concerning thimerosal and the MMR, as opposed to vaccination. Further, I am not saying you should be generating mechanisms, but rather, I am proposing one; though I do note with some amusement the fact that you put “biologically plausible” in quotes.
That’s a good question. Recently in another discussion here, pD berated us for focusing on antivaxers and their false claims about vaccines and autism, suggesting that we need to get down to the nitty gritty about what actually causes autism. pD was reminded that his/her own emphasis here has been almost exclusively on finding a way to link vaccines and autism, and it was proposed that he/she discuss some alternate mechanisms or autism causation, something to which he/she agreed.
This is a reflection of the reality here, anything with a tag of ‘Autism’ comes alongside a tag of ‘Anti vaccination Lunacy’. I do occassionally learn something here, and even more rarely, delude myself into thinking that I might get someone to think honestly about the strength of our knowledge versus the narrative being sold. One can dream.
I’d be interested in your thoughts on my blog posting, Implications for Autism Or Just Interesting? âEpigenetic and immune function profiles associated with posttraumatic stress disorderâ
if you would like an example of some of my thought processes outside of the vaccine realm.
I too would be interested in commentary by pD about how toxins generated by actual live disease organisms and their inflammatory cytokines may influence development of autism, and why we should be more worried about the “robust immune response” generated by vaccines (which (gasp) cause fever in a minority of recipients), as opposed to the immune response caused when kids get a whopping dose of illness with multisystem implications.
I think I’m starting to see where some of the problem may lay. You don’t appear to have bothered to actually read anything I write. For example, in the last thread in which we discussed this, I said:
For the record, I’d clearly state that if my theory is to hold water, infections early in life would have the same propensity for harm. I have no problems with admitting this. (Post 305)
By this part of the discussion, you had evaporated, refusing to post a link to a mysterious paper you insisted existed on pubmed, and refusing to speculate aloud as to whether vaccination resulted in an innate immune response or not.
But even here, just six posts above I told Calli Arcade that infections during early infancy would have the same functional effect. Furthermore, I was quite verbose regarding the problems of time dependent effects, something which seems to be curiously elusive, and the findings of synergistic effects of triggering multiple toll like receptors simultaneously, as reasons why apples to apples comparisons between natural infections and vaccines might contain faulty assumptions that in turn, lead to incorrect conclusions.
By the way, pD, the technique of throwing out links to or quotes from a big batch of sources (most or all of which are irrelevant, outdated, and/or deceptively cherry-picked) is known as a Gish gallop (after Duane Gish, a creationist who loved to use it in debates). What you’re doing now is not precisely Gish galloping…but loading up on long abstracts full of science-y terms but which have extremely tenuous or absent connections to immunization practice, does little more than to show you know how to cut and paste.
Considering the fact that in our last discussion, you attempted to pass off a specific antigen response, in vitro measurement of cytokine generation from blood taken from children twelve to twenty four weeks after vaccination as evidence that we have studied the pro-inflammatory response to vaccination, I’m going to take your advice on intellectually honest references with a statistically significant grain of salt.
Regarding ‘tenous or absent connections to immunization practice’, there are some foundational components of the immune system that I fear you may not understand. The animal studies I referenced above were studing the effect of the innate immune response, we’ve only got one innate arm of the immune system. One of the results of stimulating the innate immune system is the generation of inflammatory cytokines; which were the observed mechanism of action in affecting change in Postnatal Inflammation Increases Seizure Susceptibility In Adult Rats. Natural infection, LPS, and vaccines all trigger the innate immune system, you aren’t getting around that simple, simple fact, and one of the results of that is the creation of pro-inflammatory cytokines.
From Postnatal Inflammation Increases Seizure Susceptibility In Adult Rats:
The most exciting finding of the present study is that a mild inflammatory response evoked by LPS during a critical period of development causes a long-lasting increase in hippocampal excitability in vitro, and enhanced seizure susceptibility to the convulsants LI-PILO, KA, and PTZ in vivo. The latter effect was observed over a range of mildly inflammatory doses of LPS and was only evident if administered during the second postnatal week (P7 and P14), and not before (P1) or after (P20) this time. Importantly, inactivation of the proinflammatory cytokine TNF with an intracerebroventricular TNF antibody blocked the long-term changes to seizure susceptibility induced by LPS, whereas intracerebroventricular administration of rrTNF alone mimicked the effect of LPS on seizure susceptibility. These novel results indicate that a single transient inflammatory episode during development can modify the brain through a TNF-dependant mechanism, making it more susceptible to generate seizures in adulthood.
Now I’m just a nitwit who only knows how to cut and paste, but from my viewpoint, it looks like the authors took two elegant steps to validate that it was tnf-alpha, and tnf-alpha alone that was resopnsible for the changes observed in the animals.
1) Blocked tnf-alpha with antibodies and observed an attenuation of effect.
2) Administered tnf-alpha in the absence of LPS challenge, and observed an effect.
That being said, I’d be interested in your commentary as towards whether there is a functional difference in creation of pro-inflammatory cytokines resulting from vaccination, versus those described above? If you think that there is a difference between tnf-alpha from a vaccination, and what was described in the study above, I’d love to see you use some references to make your point for once. If there isn’t a difference between the two, then why are the studies I am referencing so tenously related to immunization practices? What are the functional differences between inflammatory cytokine creation from vaccination compared to what was described above?
You’ve made a real habit of asking me questions you’d like to see answered, while disappearing from similar requests from me. I’ve responded to you; do you have the intellectual honesty to reciprocate?
Again, I look forward to your answering Science Mom’s question about cytokine profiles associated with disease organisms. You can use that data to generate a list of priorities for immune system research, justifying if possible your determined focus on vaccines as the source of Bad Things.
If I wind up writing a blog posting about it, I’ll send you a note. If Orac, or you, or Science Mom were to write a blog posting about it, I absolutely would love to participate.
– pD
pD: “There is abudant evidence concerning thimerosal and the MMR, as opposed to vaccination.
What on earth does this mean? Evidence of and for what? There was never any thimerosal in the MMR vaccine, nor any solid evidence of a link between MMR and autism (read up on Andy Wakefield’s failed, unethical research).
“I’d be interested in your thoughts on my blog posting…if you would like an example of some of my thought processes outside of the vaccine realm.”
My interest is in seeing you mention any alternate theories of autism etiology here, as you previously indicated you’d do (but instead have been repeatedly flogging the dead vaccine-autism horse).
It’s nice that you’re conceding some possibility that early childhood infections may have propensity for causing neurologic impairment. But my question remains: why you are ever so much more concerned about what you think vaccines may do in inducing a “robust inflammatory response” as compared to full-blown infections?
It’s gotta be the vaccines, of course. It’s the antivaxers creed.
“Considering the fact that in our last discussion, you attempted to pass off a specific antigen response, in vitro measurement of cytokine generation from blood taken from children twelve to twenty four weeks after vaccination as evidence that we have studied the pro-inflammatory response to vaccination, I’m going to take your advice on intellectually honest references with a statistically significant grain of salt.”
Another irony meter explodes in a shower of sparks. If you’re going to revisit that previous discussion, recall this: first you suggested that no research whatsoever had been done on specific immune responnse markers in vaccination other than antibody titers. Then, when I pointed out multiple examples of this being done (including evaluation of your favorite, “inflammatory cytokines”, you repeatedly shifted the goalposts*, demanding particular parameters you deem important. Never did we see a concession from you that you were wrong about the research in the first place.
So, accusations of intellectural dishonesty have an odd ring coming from you.
I also see that in your latest lengthy followup comment, you’ve somehow avoided Science Mom’s pertinent question. To refresh your memory, I said in my last post:
“Again, I look forward to your answering Science Mom’s question about cytokine profiles associated with disease organisms. You can use that data to generate a list of priorities for immune system research, justifying if possible your determined focus on vaccines as the source of Bad Things.”
Another reminder: you’re the one who’s attempting to demonstrate a link between vaccination and autism via cytokines (or whatever the evil molecules du jour are that are supposedly especially bad when stimulated by vaccines, but not worthy of equal concern when generated by infectious disease). It’s not up to me or other skeptics to “prove you wrong” or to create “plausible mechanisms” to debate with you. If you’d got evidence to counter the many studies debunking a vaccine-autism link (that we’ve discussed here time and again), bring it. Your LPS-rat study (which is not about vaccines) doesn’t cut it.
*another classic antivaxer tactic.
Dangerous Bacon:
What I believe she means is that there is plenty of research exonerating thimerosal, and plenty of research exonerating MMR. But none exonerating vaccines as a whole. She is objecting to people saying “we proved it wasn’t thimerosal, we proved it wasn’t MMR, therefore vaccines don’t cause autism”, because this does leave some possibilities unteseted.
This does have parallels to the antivax movement’s shifting to other possible “toxins” and the “too many too soon” claims. As some things are proven guiltless, the moving finger points at other things.
Now, the *problem* is that just as there is no evidence proving that, for instance, thimerosal-free formulations of DTaP can’t cause autism, there is also no evidence suggesting that it does in the first place. This is why you and I think she’s beating a dead horse. I think she makes a fair point that exonerating thimerosal and MMR does not exonerate all vaccines. I just don’t think there’s really much point to driving this continually narrowing search for something that there’s no evidence exists in the first place. It seems a bit like a snipe hunt to me, though I could be proven wrong eventually. (After all, though the classic snipe hunt is a prank, snipes are actually real animals and can be hunted. Most snipe hunt pranksters do not know this. My brother did an extensive paper on them after we all got pranked on a snipe hunt once. Revenge of the nerd!)
I do agree with you that skeptics have no responsibility to come up with plausible mechanisms for how vaccines could cause autism. I think it’s probably a safe assumption that most people who doubt vaccines cause autism doubt it precisely because they *can’t* come up with any plausible mechanisms.
Hi Dangerous Bacon –
What on earth does this mean? Evidence of and for what? There was never any thimerosal in the MMR vaccine, nor any solid evidence of a link between MMR and autism (read up on Andy Wakefield’s failed, unethical research).
We have negative studies on thimerosal, and negative studies on the MMR. For whatever reason, however, the idea that this somehow is representative of vaccination continues to persist. There is a difference between the two, you know.
My interest is in seeing you mention any alternate theories of autism etiology here, as you previously indicated you’d do (but instead have been repeatedly flogging the dead vaccine-autism horse).
When that happens, people are generally accused of thread hijacking. I’m not sure if you noticed this or not, but this particular thread is about vaccines and autism.
It’s nice that you’re conceding some possibility that early childhood infections may have propensity for causing neurologic impairment. But my question remains: why you are ever so much more concerned about what you think vaccines may do in inducing a “robust inflammatory response” as compared to full-blown infections?
Well, this is a form of progress, as you seem to have started to read some of my postings. There are things we can reasonable control, the frequency and composition of our vaccine schedule, and those that we cannot control, exposure to the dozens or hundreds of wild pathogens. Unless we take a good look at our actions, we will be unable to discern if they are having impacts other than what might be expected. We have yet to do this.
Another irony meter explodes in a shower of sparks. If you’re going to revisit that previous discussion, recall this: first you suggested that no research whatsoever had been done on specific immune responnse markers in vaccination other than antibody titers. Then, when I pointed out multiple examples of this being done (including evaluation of your favorite, “inflammatory cytokines”, you repeatedly shifted the goalposts*, demanding particular parameters you deem important. Never did we see a concession from you that you were wrong about the research in the first place
You can hide behind this Pyrrhic victory if you’d like, but there are really only two options:
1) You understood full and well that a study that involved in vitro stimulation of blood taken from children months after vaccination has absolutely nothing to do with the generation of an innate immune response and corresponding state of inflammation from vacciation, but you were so desperate to post anything, you pushed this study and did a victory dance, only to disappear when questioned about the validity of the study within the context of what I was proposing.
2) You still don’t understand the concept that the effects of an inflammatory response in vivo as an immediate consequence of a vaccination (or natural stimulation of the immune response) are the focus of my concerns, and why a study that involved months old blood stimulated in vitro to measure responses is a very, very different type of measurement. Considering the lack of attention you seem to pay towards the details of my postings, this seems increasingly possible.
I posted why this is such a poor equivalency on our previous thread, but here is a snipet from the methods section of Postnatal Inflammation Increases Seizure Susceptibility In Adult Rats
To determine whether a single inflammatory event during development can influence seizure susceptibility in later life, male rats were injected intraperitoneally on P14 with LPS (Escherichia coli, serotype O26:B6; 25, 100, or 250 µg/kg) or pyrogen-free saline.
To assess the acute effects of LPS on P14 rat microglia and cytokine (IL-1β and TNF) levels, we collected blood plasma at 2 h after injection, as well as hippocampal tissue 3 and 6 h after LPS (100 µg/kg) or saline injection (n = 4â6/group).
By comparsion, the study you provided involved vaccination, and subsequent evaluation of cytokine production in response to specific antigen stimulation, months after the vaccination. Your argument is the equivalent of people holding onto the ‘trace amounts of thimerosal’ card; technically accurate as a measurement of inflammatory cytokine generation, but completely missing the point. Keep it up!
So, accusations of intellectural dishonesty have an odd ring coming from you.
LOL!
By the way, you are still running scared from what I asked you to comment on. WHY?
That being said, I’d be interested in your commentary as towards whether there is a functional difference in creation of pro-inflammatory cytokines resulting from vaccination, versus those described above? If you think that there is a difference between tnf-alpha from a vaccination, and what was described in the study above, I’d love to see you use some references to make your point for once. If there isn’t a difference between the two, then why are the studies I am referencing so tenously related to immunization practices? What are the functional differences between inflammatory cytokine creation from vaccination compared to what was described above?
The reason you haven’t pushed out a resopnse is that you know the answer as well as I do; there is no functional difference. There isn’t.
I also see that in your latest lengthy followup comment, you’ve somehow avoided Science Mom’s pertinent question. To refresh your memory, I said in my last post:
“Again, I look forward to your answering Science Mom’s question about cytokine profiles associated with disease organisms. You can use that data to generate a list of priorities for immune system research, justifying if possible your determined focus on vaccines as the source of Bad Things.”
ScienceMom’s recommendation is a lengthy endeavor.
If you’d got evidence to counter the many studies debunking a vaccine-autism link (that we’ve discussed here time and again), bring it. Your LPS-rat study (which is not about vaccines) doesn’t cut it.
What is the functional difference between the inflammatory cytokines generated via LPS (or direct tnf-alpha injection) comapred to inflammatory cytokines generated by vaccination? These studies are about inflammation and that is the same regardless of the trigger. You can’t dance around this simple fact no matter how much you would like to.
– pD
Hi Calli Arcade –
I think it’s probably a safe assumption that most people who doubt vaccines cause autism doubt it precisely because they *can’t* come up with any plausible mechanisms.
I think you are largely correct. In a very similar vein, I think that it seems likely that this is the same reason that we have no research on the immediate, innate immune response as a result of vaccination in the pediatric population. The assumption has always been that immune activation in the absence of the problems introduced by pathogens themselves, a transitory inflammatory event was harmless.
That isn’t a luxury we can afford to have any longer.
As luck would have it, a review of the points I’m trying to make came out this morning.
Neonatal programming of innate immune function
The early life environment can be crucial in influencing the development of an animal’s long-term physiology. There is now much evidence to suggest that perinatal challenges to an animal’s immune system will result in changes in adult rat behavior, physiology, and molecular pathways following a single inflammatory event during development caused by the bacterial endotoxin, lipopolysaccharide (LPS). In particular, it is now apparent that neonatal LPS administration can influence the adult neuroimmune response to a second LPS challenge through hypothalamic-pituitary-adrenal axis modifications, some of which are caused by alterations in peripheral prostaglandin synthesis. These pronounced changes are accompanied by a variety of alterations in a number of disparate aspects of endocrine physiology, with significant implications for the health and wellbeing of the adult animal. In this review, we will discuss the newly elucidated mechanisms by which neonatal immune challenge can permanently alter an animal’s endocrine and metabolic physiology and the implications this has for various disease states.
Given the caveats we discussed and I agree to regarding the problems with rodent to human studies in a system as complicatd as brain development, vaccines are certainly an immune challenge during infancy.
What are your thoughts on the fact that the editors and peer reviewers of the Journal of Endocrinology feel OK about publishing a paper with an abstract that states with great clarity: we will discuss the newly elucidated mechanisms by which neonatal immune challenge can permanently alter an animal’s endocrine and metabolic physiology and the implications this has for various disease states?
This is data that isn’t going to go away. It is brand new, the concept that an immune challenge during early life could have lifelong effects is very recent, with the overwhelming bulk of the research appearing since 2007; long after we’d begun to increase the number and types of vaccines in our schedule. The idea that a single inflammatory even during development could cause lifelong effects is a black swan; not impossible, just thought to be impossible because we hadn’t looked for it.
– pD
pD:: “When that happens (posters mentioning other possible etiologies of autism), people are generally accused of thread hijacking.”
Can you cite examples of this occurring? I don’t see how a fear of being accused of hijacking a thread should prevent you from doing as you promised here – talking about other lines of research instead of just honing in on vaccines.
“ScienceMom’s recommendation is a lengthy endeavor.”
As you’ve been been busy churning out lengthy posts to justify your antivax suspicions, I can see why you haven’t had time to answer ScienceMom’s question.
“What is the functional difference between the inflammatory cytokines generated via LPS (or direct tnf-alpha injection) comapred to inflammatory cytokines generated by vaccination?”
Beats me. Did you somewhere along the line demonstrate that any of your cited research has pointed a finger at vaccines (or even vaguely referred to them) in this regard? Where’s the relevance?
pD: “There are things we can reasonable control, the frequency and composition of our vaccine schedule, and those that we cannot control, exposure to the dozens or hundreds of wild pathogens. Unless we take a good look at our actions, we will be unable to discern if they are having impacts other than what might be expected.”
So we should ignore the role of infectious disease (in generating immune responses potentially harmful to the host), because it’s a factor we can’t control as opposed to vaccination? This is the silliest justification you’ve yet provided for obsessing about vaccines. Of course we can do something about disease exposures – we can look at prevention and treatment of disease (clinical and subclinical) induced by these infectious agents. We might discover that organisms hitherto thought harmless actually have detrimental potential, even extending to neurodevelopment. You might remember that in a previous discussion I cited a paper that discussed constant release of inflammatory cytokines in humans due to antigenic stimulation in the G.I. tract. Should children’s diets be manipulated to modulate such exposures?
This brings us back to the second question I asked you, about research priorities. Personally, I think it’s good to discover as much as we can about the human immune system, in order to have it work for us as beneficially as possible. There are lots of areas to investigate, and limited money to do so. It’d be great to discover ways to make ever more effective and safe vaccines via this knowledge. The kicker, again, is prioritization due to limited resources.
Let’s say pD is charged with allocating scarce dollars and time towards research into the etiology of autism. What percentage of research do you want applied to investigation of immune response parameters as opposed to genetic and other factors? 50%? 10%? 1%? And of that dollar figure applied to immune response research, what percentage of that do you wish to devote to investigating vaccines instead of infectious disease, bearing in mind the ample research that has already debunked a vaccine-autism connection?
This is not a trick question.
pD – first I do want to let you know that I admire the way you dig into the scientific literature and take the time to present your arguments in a coherent manner.
I do have one big problem with your argument, however, stemming from your comments last night. This morning you add:
Can you convince me that the number and types of vaccines in the schedule present more of a challenge to an infant’s immune system than a run-of-the-mill cold? And are you going to try to convince me that pre-vaccination infants never caught colds?
Yeah, I know I don’t have real data. All I have is my one data point: my modern-day infant, who got sick with a cold within your 60-day window. Oh, and this was in August – not even during the winter cold and flu season. Do you honestly believe that historically an infant catching a cold was a rare event?
The idea that early immune challenges might have lifelong consequences may be new, but the immune challenges facing infants are not. They’ve always been there.
Hi Chommono –
I saw your comment last night then got back into a discussion with Bacon. Sorry for not responding yet. Your words regarding my presentation are very kind and I appreciate your tone.
Can you convince me that the number and types of vaccines in the schedule present more of a challenge to an infant’s immune system than a run-of-the-mill cold?
I cannot; but this is largely an artifact of a relative paucity of data. Here is an experiment for you; try to find a study that shows the in vivo inflammatory response as a result of any vaccine on the pediatric schedule, much less several at once. So that I’m clear, for example, the model that would be consistent with what I am proposing would involve, taking blood, vaccinating, then taking blood in a few hours/days, and check to see if you can observe differences in inflammation markers; i.e., these cytokines I keep harping about. These studies just aren’t present. [there are a few for some vaccines that are not pediatric, or are optional, like HPV or influenza, that I could post if you were intersted, but don’t want the dreaded ‘Gish Whatever’ tag applied.]
Unfortunately, without this data, we really don’t have a good way of knowing how this can be answered one way or the other. From a common sense standpoint, the fact that children get sick and stay sick from an actual infection looks good, but this site is (usually) dedicated to reminding us that observational studies like this are among the most rudimentary techniques, and those the most prone to provide inaccurate results. This is especially true with a system as complicated as the developing immune system.
Also, try taking a look at the study I posted on 67 regarding the synergistic effects of triggering multiple toll like receptors simultaneously. A toll like receptor is a component of the immune system responsible for identifying particular classes of molecular pathogens, and initiating an immune response when it is identified. Our shot schedule at two, four, and six months convinces the immune system that invaders from many different bacterial and viral classifications have entered the body. Our available in vitro evidence suggests that as an evolutionarily developed measure, a very robust immune response is generated that does not follow an additive model. And again, it has only been within the last two years that we have gained any experimental evidence on this phenomena. We gloss over this messy reality at great risk.
And are you going to try to convince me that pre-vaccination infants never caught colds?
Yeah, I know I don’t have real data. All I have is my one data point: my modern-day infant, who got sick with a cold within your 60-day window. Oh, and this was in August – not even during the winter cold and flu season. Do you honestly believe that historically an infant catching a cold was a rare event?
Of course not! But I would argue that no where near 90% of them caught one in the first few days of life, then had one at two months, then again at four months, and again at six months. A few of them did, but nowhere close to all of them. Plus, our children are continuing to get most of these infections (except, of course, the ones they vaccinate again). Your son got a cold early in his life; did he have three more by the time he was six months old? On a percentage basis, what percentage of children historically got sick four times by the time they were found months old?
The idea that early immune challenges might have lifelong consequences may be new, but the immune challenges facing infants are not. They’ve always been there.
I absolutely agree. But that doesn’t mean we should necessarily pile on without taking the time to evaluate if our actions could be having unintended consequences. We can both be more intelligent about vaccinating and develop safer vaccines, but only if we admit that we have things to learn which may be inconvenient.
– pD
And yet, you seem completely convinced of what they would show if they were present. Or at least, sufficiently convinced to argue that research funding and priorities should be based off of it.
Hi Dangerous Bacon –
As you’ve been been busy churning out lengthy posts to justify your antivax suspicions, I can see why you haven’t had time to answer ScienceMom’s question.
I already know the autism literature. I’m pretty up to speed on the early immune activation literature. The specifics on the particular pathogens Science Mom listed are deeper still. Presumably you understand that it takes time, and effort, to learn about things of this complexity. (?)
Beats me. Did you somewhere along the line demonstrate that any of your cited research has pointed a finger at vaccines (or even vaguely referred to them) in this regard? Where’s the relevance?
Lets imagine that we weren’t discussing inflammation, but blunt force trauma. Imagine, further, that I argued that the source of the blunt force trauma was unimportant to the effect of the blunt force trauma. You agreed. But when I provided a paper that said being hit with a hammer caused blunt force trauma, you replied that this was fine and good, but you couldn’t see the relevance of how this would relate to the blunt force trauma of falling of the roof.
I honestly don’t know if you are being intentionally oblique here or not.
So we should ignore the role of infectious disease (in generating immune responses potentially harmful to the host), because it’s a factor we can’t control as opposed to vaccination? This is the silliest justification you’ve yet provided for obsessing about vaccines. Of course we can do something about disease exposures – we can look at prevention and treatment of disease (clinical and subclinical) induced by these infectious agents. We might discover that organisms hitherto thought harmless actually have detrimental potential, even extending to neurodevelopment. You might remember that in a previous discussion I cited a paper that discussed constant release of inflammatory cytokines in humans due to antigenic stimulation in the G.I. tract. Should children’s diets be manipulated to modulate such exposures?
Controlling and / or measuring the environment is notoriously difficult. On the other hand, vaccines are discrete events that mandate record tracking.
I don’t remember the paper you mention here, would you be willing to repost it? I’m not advocating manipulating diets, but I’d bet we could be doing smarter things if we learned more. That’s all I’m going for.
This brings us back to the second question I asked you, about research priorities. Personally, I think it’s good to discover as much as we can about the human immune system, in order to have it work for us as beneficially as possible.
We are in complete agreement.
Percentages are tricky, but I have thought about this in some ways.
I’d immediately double, or quadrouple (or more) the resources attached to the MARBLES and CHARGE projects, which are following pregnant mothers and children in families already with an autistic family member. These types of projects are going to be important in discerning what, if any, environmental factors are participating in autism.
A big problem is a relative lack of tissue and / or banked blood / plasma / ect; especially in regards to a common diagnostic range. This makes it very difficult for researchers to adequately measure biomarkers with autistic severity unless they are going to perform the diagnostics themselves on all inbound children. This is time consuming, cumbersome, and expensive. California is making progress in this area, but we could do better.
We should be spending much more dollars in the bioinformatics area; especially in conjunction with studies like MARBLES and CHARGE. A couple of really cool examples of papers that have touched on this in the autism realm would include Immune transcriptome alterations in the temporal cortex of subjects with autism and Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain which used computational approaches to identify differentially expressed proteins in brain tissue to identify gene networks that were active / inactive. I believe that this kind of finding (genetic expression) is going to be more useful in the long run than the SNP / CNV style of genetic tests that have been being run for a long time now.
If we were going to find specific snps responsible for the bulk of autism, we’d have seen them now. The CNV paper that came out the other month was cool, and had a bioinformatic approach, but still largely failed to find repeats or deletions in roughly 97% of the people scanned. If, on the other hand, we’d run tests on genetic expression on these individuals, we’d have learned lots. It isn’t necessarily about what genes you have, it can be about what genes you use.
From a pure vaccine point of view, I think by this point you’d understand I think that at a minimum, it might be appropriate to measure the inflammatory response as a result of a combined visit to the pediatrician. Perhaps, though, highly unlikely, we’d find that no inflammatory cytokines are generated at all.
I’d definitely give Daedulus2u a couple of million to figure out once and for all if NO was the cause of autism.
From a maternal immune activation standpoint, it might help a lot if we could identify the antigens that are found in approximately 10% of mothers that have an autistic child would seem to be neural antibodies to fetal brain tissue. With that, a test that could give some good information about the likelyhood of having a child with autism.
The microbiome of children with autism would get a lot of attention.
Also, sensory perception / integration problems deserve a lot of attention and dollars.
These are all things that I’d like to have conversations about, but there just isn’t really an environment in which to do it. I’ve been looking. How do these responses fit within your meme of me as an ‘antivaxxer’? What are your thoughts on my priorities?
– pD
Hi Scott –
And yet, you seem completely convinced of what they would show if they were present. Or at least, sufficiently convinced to argue that research funding and priorities should be based off of it.
Well, we do have evidence of this in vaccines outside of the pediatric model. For example in HPV-16 L1 VLP vaccine elicits a broad-spectrum of cytokine responses in whole blood the authors report: Cytokine profiles from WB samples clearly discriminated between vaccine and placebo recipients and between pre and post-vaccination responses. Significant increases in Th1, Th2 and inflammatory cytokines were observed in WB assays following vaccination
Also, if you are interested in proposing a mechanism wherein the adaptive arm of the immune system is alerted to the presence of foreign protein structures for immunological memory, without communicating with the innate arm of the immune system, you are going to have to rewrite some significant portions of immunology textbooks.
You will also need to find a way to explain the presence of adverse events like fever post vaccination if you don’t think that an increase in pyrogenic cytokines is participating.
Do you have any ideas on this?
Vaccines are designed to invoke an immune response. They don’t work without one. What we lack is qualitiative values; this is especially tricky in pediatric and/or neonatal populations, who may and do show distinct variability in immune responses.
– pD
Chemmomo
Offspring Mine Younger got his first cold at 3 weeks old after only a hepB shot. No other vaccines and breastfed.
Basically, right after Offspring the Elder started going back to the Germ Factory of daycare.
The MonkeyBoy recovered mostly but OtE keeps challenging him with variations of the cold virus.
@pD Sorry about my long delay in replying.
Actually, it’s quite possible that he did. I didn’t document every cold, because he ended up with a lot of them thanks to the older one’s activities. I did document his first ear infection, which he got at 5 months. That’s 2 more infections: respiratory virus followed by ear bacteria.
I think you are vastly underestimating the disease prevalence of “the good old days.”
@Pablo. Mine too was breastfed (never did take a bottle, in fact), but I was afraid that mentioning it would open a different can of worms. At our house, the older one would get the sniffles from friends or preschool, then the younger one would get full blown sick, with fever. The good news is that now that he’s in preschool himself, apart from last fall’s swine flu, he’s missed very few days due to illness.
pD: “What are your thoughts on my (research) priorities?
First, you do get some credit for mentioning things that don’t directly relate to your well-known focus on vaccination. But priorities? Where did you prioritize anything?
You listed a bunch of “cool” things you think we should be spending more money on. This assumes that the money is there to spend, and that there are not other facets of autism research that are equally or more deserving of scarce research dollars (and time).
Here again is what I’m asking you:
“What percentage of research do you want applied to investigation of immune response parameters as opposed to genetic and other factors? 50%? 10%? 1%? And of that dollar figure applied to immune response research, what percentage of that do you wish to devote to investigating vaccines instead of infectious disease, bearing in mind the ample research that has already debunked a vaccine-autism connection?
As far as the paper I previously linked to that discussed constant release of inflammatory cytokines in humans, I believe it was this one:
http://physiologyonline.physiology.org/cgi/content/full/15/6/298
“Defining the role of cytokines in nonpathological states requires careful definition of what constitutes the pathological state. Bacteremia (i.e., viable bacteria in the bloodstream) is clearly an example of an extreme pathological condition. There is no question that cytokines are produced, circulate, and have profound influences on physiological function in sepsis. One might propose that the other extreme, namely absolutely no bacterial burden, would represent a purely physiological condition. But such a condition does not exist in nature. A small but steady influx of microorganisms and their toxins through the gastrointestinal mucosa and other epithelial barriers is constantly and effectively handled by resident macrophages and local lymphoid tissues. Therefore, we always exist in some relative state of infection.”
This doesn’t support a view that children exist in a pristine state devoid of harmful inflammatory cytokines, which we are to particularly worry about (in your view) when multiple vaccines are given. In reality, we exist in a complex environment where there are continual challenges from various antigens, some involving polymicrobial flora, and which cause variably strong immune system stimulation.
Your exposition of the “too much” portion of the “too much, too soon” antivaxer meme does have a nice science-y air. It just doesn’t make sense based on our knowledge of human physiology and molecular biology. Just Asking Questions about the subject is dandy, but again – what specific percentage of autism research dollars should we feel compelled to invest in this area?
Hi Dangerous Bacon –
I was travelling this weekend, so it took me a while to get back to you.
First, you do get some credit for mentioning things that don’t directly relate to your well-known focus on vaccination. But priorities? Where did you prioritize anything?
Bacon credits, eh? Great.
This assumes that the money is there to spend, and that there are not other facets of autism research that are equally or more deserving of scarce research dollars (and time).
If you are going to ask me which facets of autism research you want me to work on, you cannot come back one sentence later and lecture me on the availability of dollars and how wrong I might be regarding researcher time or money. The fact that you cannot even get your question out before starting to bash me says a lot about your debate style, and not in a good way.
Here again is what I’m asking you:
“What percentage of research do you want applied to investigation of immune response parameters as opposed to genetic and other factors? 50%? 10%? 1%? And of that dollar figure applied to immune response research, what percentage of that do you wish to devote to investigating vaccines instead of infectious disease, bearing in mind the ample research that has already debunked a vaccine-autism connection?
Please stop confusing thimerosal, and the MMR with vaccination. This is a very, very simple concept; especially for someone who seems so caught up with specifics when it comes to spending percentages.
Considering your sudden focus on specific information, I guess I’d need more specific information from you. Which dollars are we considering? Government and state dollars? Private funds from foundations, such as the Autism Science Foundation or Autism Speaks? I’d also really need to understand what that breakdown looks like currently on an absolute and percentage basis. How would I assign a study, for example, that evaluated for genetic expression indicators of immune activation? Is that half and half? What about a study such as Macrophage Migration Inhibitory Factor in ASD, which was a combination of a genetic test, blood test for ciculating levels of MIF, and then made analysis against behavioral severity? Would this be half genetics and half immune system related? What about a study that evaluated for functioning of specific kinases as they related to individual TLR responses; something that could have implications far beyond the immune system. How would these dollars break down?
As far as the paper I previously linked to that discussed constant release of inflammatory cytokines in humans, I believe it was this one:
Neat paper, which unfortunately misses the point that vaccines are designed to initiate an immune response, and is contraindicated by the data I keep on posting. You are confusing baseline levels of inflammation with a challenge. If you don’t believe me, why not take a look at what Stephen Novella says, at this blog posting titled: Vaccines Too Few, Too Late
Vaccines are designed to trigger a robust immune response, enough in some cases to cause minor symptoms. Whereas, our daily exposure to antigens is a constant background of activity and of course we donât notice it, because itâs our baseline.
Do you think Stephen Novella has it wrong? Why not go post this paper on his blog, and ask him to explain why he seems to think we exist in a pristine environment devoid of an immune response?
This doesn’t support a view that children exist in a pristine state devoid of harmful inflammatory cytokines, which we are to particularly worry about (in your view) when multiple vaccines are given. In reality, we exist in a complex environment where there are continual challenges from various antigens, some involving polymicrobial flora, and which cause variably strong immune system stimulation.
You don’t seem to understand the difference between normal, everyday exposure and a specific challenge, but I can’t figure out why this is such a difficult concept for you to grasp. By way of example, in all of the animal studies I’ve posted, are you positing that the control group had zero cytokines and only the treatment group had any level of immune activation? [I’d suggest you read one of them if you think this is the case.] Please refrain from putting the bubble boy argument in my mouth; it is largely equivalent of me asserting that you have claimed that you believe vaccines are 100% safe. You know full and well that I’m clever enough not to believe we exist in a state of “pristine state devoid of harmful inflammatory cytokines”.
Your exposition of the “too much” portion of the “too much, too soon” antivaxer meme does have a nice science-y air. It just doesn’t make sense based on our knowledge of human physiology and molecular biology.
You are arguing with me, but what you really need to do is argue with the data. At the end of the day, the editors and peer reviewers of the Journal of Neuroscience published Postnatal Inflammation Increases Seizure Susceptibility in Adult Rats and were completely OK with this setence in the concluding remarks:
However, based on the novel data presented here, relatively mild early-life inflammation may be associated with permanent modifications in seizure susceptibility that persist well into adulthood. This may warrant additional patient history review to ascertain whether such a relationship exists. Our data raise the possibility that the known differences in adult seizure susceptibility to very similar insults may have their etiology in a common postnatal infection.
Similarly, the editors and peer reviewers of the Journal of Endocrinology decided to publish Neonatal programming of innate immune function with this in the abstract:
In this review, we will discuss the newly elucidated mechanisms by which neonatal immune challenge can permanently alter an animal’s endocrine and metabolic physiology and the implications this has for various disease states.
Do you honestly believe that the editors and peer reviewers of all of the papers that comprise that review are unaware of “our knowledge of human physiology and molecular biology” that makes the results of these papers invalid? Whatever problems exist in the peer review process and literature publication process, we still have to have some trust in the results; especially when they are replicated. This is why, for example, arguments involving thimerosal and collusion and/or courruption within the scientific community are so pathetic. I’m just reporting on what has been published; if you don’t like that, your problems lay at the feet of the people who believed these experiments were worthy of publication.
The science I am putting forth is at the cutting edge of that knoweldge; this is why you are reduced to attacking my proposal as having “a nice science-y air”; as opposed to posting any studies that actually discount them. Skeptics are supposed to realize that if this is the only thing they can muster against an argument supported by the literature, perhaps their skepticism needs to be applied towards their own beliefs, and question why instead of having the ability to produce data to counter a claim, the last refuge is to call it ‘scienc-ey’. You are grasping at straws.
– pD
To summarize the flailings in pD‘s latest post:
He/she is once again unwilling to specify what proportion of autism research funding should be directed towards his/her favorite target(s) of suspicion, immune system activation particularly as generated by vaccines.
The obstacles to getting a direct answer are that I didn’t ask the question right (it should be clear enough; I’ll refrain from repeating it yet again – see post 88), and that sources of funding weren’t specified. Why do you require a breakdown of all potential sources of funding? Just give us what percentage of total available research dollars you think should go towards your focus on inflammatory cytokines and how vaccines conjure them up as opposed to other challenges of daily living.
“Please stop confusing thimerosal, and the MMR with vaccination. This is a very, very simple concept”
There’s no confusion involved. Your pretense that no studies exist on vaccine safety other than to exonerate the MMR and thimerosal is akin to your previous insistence that no one had ever studied specifics of the immune response in vaccination outside of antibody titers. It breaks down on the simplest examination. Try Googling or Pub Med searching under “vaccine safety efficacy” and you’ll be busy quite awhile. A plus is that it’ll give you more excuses for not answering ScienceMom’s question about inflammatory cytokine production in infectious disease states or providing specifics about what proportion of autism research funding should go towards your pet projects.
At this point we should probably despair of ever convincing you that kids actually get sick, get rashes, allergic attacks and have immune system activation that generates those nasty cytokines, which are not confined to response to vaccination. A lovely calm baseline interrupted only by the perils of immunization is a fantasy.
“The science I am putting forth is at the cutting edge of that knoweldge”
Yep. It’s so “cutting edge” that it doesn’t even address vaccination, but we’re apparently supposed to obssess about vaccines and connect nonexistent dots anyway.
How many antivaxers have you gotten to switch over from the Mercury Militia and Horrors of the MMR and demand that we prove that vaccines don’t cause autism through induction of Evil Inflammatory Cytokines? I fear that most of the goalpost-shifters are still hung up on formaldehyde and the various toxins du jour.
Hi Dangerous Bacon –
Just give us what percentage of total available research dollars you think should go towards your focus on inflammatory cytokines and how vaccines conjure them up as opposed to other challenges of daily living.
Your insistence on breaking down a very complicated subject into bullet points is having an effect on your credibilty, and not in a good way. [Are you a member of the Tea Party?]
Lets say our current rate of research on autism is one hundred million, would you honestly argue that my percentage assigments should be the same if our budget was five hundred million? Does that really make sense?
Understanding the amount of dollars available, and how that money is already allocated is important. Considering how many other logic poor statements you’ve thrown around, I am actually starting to come around to the belief that it is possible you do not understand this as a potential problem, to tell the truth.
There’s no confusion involved. Your pretense that no studies exist on vaccine safety other than to exonerate the MMR and thimerosal is akin to your previous insistence that no one had ever studied specifics of the immune response in vaccination outside of antibody titers. It breaks down on the simplest examination. Try Googling or Pub Med searching under “vaccine safety efficacy” and you’ll be busy quite awhile.
That is a great idea. But I think you have just stumbled onto a large waste of resources that apparently, the entire scientific community was unaware of. (!) When folks clamored for MMR and thimerosal analysis, why did the scientific community perform retrospective studies at all? Why not just whip out all of our great “safety and efficacy” studies, as, presumably, they took autism into account as a measurement end point? Think of all of the wasted resources, if only they’d come to Dangerous Bacon, who could have told them about all of these wonderful safety and efficacy studies that held these answers?
The ridiculous attempt to conflate ‘safety and efficacy’ with the types of studies I say are missing from the literature has been tried before, and hasn’t gotten any better with time.
I used to think that you knew full well that our existing research doesn’t address the questions I’m raising, which is why you continue to hide behind an in vitro study of stimulated blood taken months after vaccination. Now, I’m not so sure you are capable of making that distinction, but it doesn’t really matter.
How many antivaxers have you gotten to switch over from the Mercury Militia and Horrors of the MMR and demand that we prove that vaccines don’t cause autism through induction of Evil Inflammatory Cytokines? I fear that most of the goalpost-shifters are still hung up on formaldehyde and the various toxins du jour.
I don’t think any. Maybe one. But I could care less. The funny thing, Dangerous Bacon, is that you have gotten just as boring as that group, hiding behind semantics, insistence on repeating questions founded upon gross over simplifications, and the seemingly inexplicable inability to discern the difference between safety studies and studies on particular biomarkers or specific outcomes.
– pD
So you’re continuing to dodge the questions.
Pretty simple stuff. But I can see how candor might prove embarassing to you.
I can’t belive some people still don’t understand the inflamatory response differences between subcutaenous delivery and oral/respiratory communication.
first all of vaccine interfere to a great extent with the bodys natural method of learning itself in the immune system development stage of the first 2 years. Most usefull antibodys come from the mother during initial breastfeeding, but these are temporary at best and are not permanent.
the reason they are not persistent is becuase each body has to learn itself.
We bypass this entire mechanism in the vaccination scheme.
Basically we interfere with a finely tunned and well developed system that is designed to learn itself and in some case it is very likely we cuase mistraining of the immune system.
while we can measure antibodys, I know of a case at ohio state of 3000 cases of measles with a 99% vacination rate.
Point is, vaccine likely don’t really work and naturally virus’s come and go and we start to kill off the weaker poritions of the species with low survival and high complication rates.
for instance Polio was exceedingly rare, typically presented with flu symptoms and respiratory distress and paralysis were exceedingly uncommon.
Yet e hear today what a epidemic it was, it was not. It was no worse then the flu of 1912 and actually that flu was substantially worse.
Also a 11% infection rate with pertusis is a rather unsubstantial challenge of a vaccines effectiveness.
The infection rate in Japan and other countrys that do not vaccinate fo pretussis is actually lower by percentage.
Basically. We have no good conclusive control group data of vaccinate versus unvaccinate populations with similar exporsure rates.
Until that data is actually presented with controls, I find the case for vaccination ambigous, potential deterimental and at its worst persistent damaging to our microbiology and our interaction with our enviroment.
We simply don’t know enough to make many of the assumptions we do.