Posts Tagged ‘Gross Over Simplification’
The Fairytale of a Static Rate of Autism Part 4: Troubling Realities Acknowledged, The Incredible Shrinking Gods of the Gaps, and Otherwise Rational People Using ‘Small’ As An Empirical Measure To Answer A Critical Question
Posted August 19, 2011on:
Hello friends –
These have been rough times for the people who are heavily invested in the kissing cousin theories of autism as a predominantly genetic disorder and the static, or near static rate of autism. The California twin study that is old news by the time I get this finished showed much different rates of genetic participation than previously believed. These findings exposed the underlying frailty of gene-based causation theories, namely that some of the most widely referenced studies in the autism literature, studies used repeatedly as a basis for the notion that autism was ‘the most highly heritable neurodevelopmental disorder’, were, in fact, relatively underpowered, and suffered from serious temporal and methodological shortcomings.
By contrast, the California study looked at two hundred twin pairs, a lot more twins than any previous study and actually performed autism diagnostics on all of the participating children, whereas other studies relied on medical records. Performing dedicated ADOS diagnosis prospectively on the children allowed the researchers to discern between autism and PDD-NOS, something that not all previous studies were not able to perform, if for no other reason than the DSM-IV wasn’t even released when several of the most often cited studies were published. This is from the Comment section of the California twin study:
The results suggest that environmental factors common to twins explain about 55% of the liability to autism. Although genetic factors also play an important role, they are of substantially lower magnitude than estimates from prior twin studies of autism. Nearly identical estimates emerged for ASD, suggesting that ASD presents the same liability spectrum as strict autism.
This is on top of the fact that there is a quiet, but growing acknowledgement of the fact that literally decades of genetic studies have failed to be able to explain more than a fraction of autism cases despite sequencing of tens of thousands of genomes. This is a very similar situation to a great number of other disorders which we thought we would cure once the human genome was decoded. [Note: That isn’t to say that we haven’t learned a lot from sequencing the genome, just that we didn’t quite get what we thought we were going to get.]
This ‘double hit’, so to speak, has reached a critical mass such that health officials are making politically shrewd, but refreshingly realistic statements, and dare I say, a sliver of common sense may be about to infiltrate the discussion about autism prevalence. For example, as pointed out by Sullivan, Tom Insel, head of the National Institute of Mental Health keeps a blog where he recently blogged ‘Autism Spring’, which included this nugget within the context of continued failure of genetic studies to explain any substantial part of autism, “It is quite possible that these heritability estimates were too high. . .” Ouch. (I would recommend the entire blog posting by Mr. Insel.)
The high heritability estimates, and implicit genetically-mediated cause of autism, are foundational pillars of the argument that autism rates have not changed over time. Though overused, or used wrongly in many instances, there is a kernel of dispassionate reality behind the statement, ‘there is no such thing as a genetic epidemic’. Without the crutch of exceedingly high heritability to rely on, the notion of a stable rate of autism loses the only hard science (read: replicable, biologically-plausible), i.e.,genetics, it ever had, and must place complete reliance on the softer sciences (read: unquantifiable, ‘greater awareness’), i.e.,sociology. This is great news if you love impossible to estimates of prevalence and anecdotes about crazy uncle George who would have been diagnosed with autism forty years ago. However, if you think we should be relying less on psychologists and cultural anthropologists to answer critical questions, and rely more on hard science, this means that the old narrative on autism prevalence holds even less allure than it did in the past, for those of you who thought this was possible.
Before Kid Autism came around, I would occasionally read discussion boards on the creationism versus evolution ‘debate’. One thing that I noticed was that the creationists would often employ a ‘God of the Gaps’-style argument: anything that couldn’t be explained by science (yet), or anything necessary to support whatever fanciful construct had been erected to protect biblical creation fables, was ascribed to the work of God. That’s one thing you have to give to God, he (or she!) can handle it all; it didn’t matter what primitive logical test biblical creation was failing to pass, the golden parachute clause was always that God could have just made things that way. It was a nifty out on the part of the creationists, kind of like a get out of jail free card. The autism prevalence discussion has been working just like this, and the funny part is that the people that are always claiming to have the intellectual high ground, the supposed skeptics, are playing the part of the creationists! Zing!
Here is how it works:
Concerned Parent: It sure does seem like there is more autism than there used to be, what with there being X in a thousand kids with it! That’s much, much more than even ten years ago! My brothers, sisters and I all knew kids with mental retardation and Down’s syndrome, but we just don’t remember kids like we see today.
Supposed Skeptic: It is diagnostic substitution and ‘greater awareness’; autism incidence has been stable. The DSM was changed which resulted in more children being labeled.
Concerned Parent: It sure does seem like there’s more autism than there used to be. Now there are Y kids in a thousand having autism! Why does my son’s preschool teacher keep insisting something is changing?
Supposed Skeptic: It is diagnostic substitution and ‘greater awareness’; autism incidence has been stable. The DSM was changed which resulted in more children being labeled.
Concerned Parent: What the hell? Now there are Z kids in a thousand having autism! When are those genetic studies going to figure autism out, anyway?
Supposed Skeptic: It is diagnostic substitution and ‘greater awareness’; autism incidence has been stable. When does the new DSM come out again?
(Replace X/Y/Z with any progressively larger numbers.)
It doesn’t matter what prevalence number is thrown about–even the astronomical one in thirty-eight figure bandied about for South Korean children didn’t cause so much as a raised eyebrow; the autism equivalent of God of the Gaps, greater awareness and loosening of diagnostic criteria can handle any amount of increase gracefully. It is the equivalent of an uber-absorbent autism paper towel, capable of soaking up any number of new children with a diagnosis; there is, literally, no amount of an increase that the God of the Gaps can’t handle.
If, instead the question was posed like this, ‘How much of the apparent increase in autism is real?’, the answer was always, ‘Zero’, regardless of what the current rates of autism were when you asked the question
Then a funny thing happened, a series of studies from several researchers showed a consistent trend of older parents giving rise to more children with autism than younger parents. There were differences between the studies on just how much of an effect an older parent had, but the overall direction of association was clear. In this instance, there was also the luxury of a plausible biological mechanism that involved the mediator in favor, genetics. The idea is that advancing age in the parent meant more years for gametes to get knocked by a random cosmic zap or other environmental nastygram and this disturbance created genetic problems down the line for the offspring, a theory I think is probably pretty good. Once a couple of these studies started to pile up, there was a small shift in the narrative regarding autism prevalence; after all, nobody could bother to try to deny that parents were getting older compared to past generations. Here is how it looked:
Concerned Parent: What the hell? Now there are X kids in a thousand having autism!
Supposed Skeptic: Greater awareness and diagnostic substitution are primarily responsible for our observations of increased autism, although, ‘a real, small increase’ cannot be ruled out.
And with that, there was a little less autism prevalence for the God of the Gaps to handle. It never seemed to bother anyone that implicit in this argument is an impossible to quantify concept ‘small increase’. If you were to ask someone what rate of autism ‘a small increase’ amounted to with more precision, the answer is whatever amount rises to the level of autism minus the difficult to quantify effect of older parents. That is some lazy stuff.
Here are some examples of prominent online skeptics discussing the possibility of a true rise in autism. See if you can detect a pattern.
Here is Stephen Novella pushing The Fairytale in 2009:
While a real small increase cannot be ruled out by the data, the observed increase in diagnostic rates can be explained based upon increased surveillance and a broadening of the definition – in fact autism is now referred to as autism spectrum disorder.
[Here we see the notion that everything can be explained by the God of the Gaps.]
Here is an example of Orac toying around with this filibuster just the other day, in August of 2011:
True, the studies aren’t so bulletproof that they don’t completely rule out a small real increase in autism/ASD prevalence, but they do pretty authoritatively close the door on their being an autism “epidemic.”
These aren’t the only examples, far from it. Check it out:
It should be noted that the data cannot rule out a small true increase in autism prevalence. (Stephen Novella in 2008)
It should also be noted that all of this research, while supporting the hypothesis that the rise in autism diagnoses is not due to a true increase in the incidence but rather is due to a broadening of the definition increased surveillance, does not rule out a small genuine increase in the true incidence. A small real increase can be hiding in the data. (Stephen Novella, 2008)
We should have the curiosity to wonder, what, exactly, does small mean in these contexts? What percentage size increase should we consider small enough to hide within the data? Five percent? Ten percent? What does ‘small’ mean, numerically, within a range? Is a ten to twenty percent rise in autism rates reason for us to take comfort in the fact that the effect of greater awareness is real? At what level does the percentage of ‘real’ autism increase mandate more than superficial lip service, more than a paragraph about ‘gene-environment interactions’ at the end of a two-thousand word blog post that takes pride in the intellectual chops of outthinking Jenny McCarthy? You won’t get anyone to answer this question; they can’t, because they don’t really know what they mean when they say, ‘small’, other than, ‘it can’t be vaccination’.
How do we know the amount of this increase must, in fact, even be ‘small’? This becomes especially problematic when we consider the smackdown that the canard of autism as ‘among the most heritable neurological conditions’ has taken as of late. If the high heritability estimates of autism are incorrect, yet so often repeated as gospel, why should we also assign confidence to the idea that the increase is trivial? Isn’t one argument the foundation of the other? Did either really have quality data behind them?
This is a terrible, awful, horrible, completely fucking idiotic way to address a question as important as whether or not a generation of children is fundamentally different. We cannot afford the ramifications of being wrong on this, but we seem to find ourselves in an epidemic of otherwise intelligent people willing to accept the pontifications of cultural anthropologists and the feebleness of social scientists on this critical question. I am not arguing against the realities of diagnostic switching and greater awareness affecting autism diagnosis rates. But we can understand that while they are a factor, we must also admit that we have little more than a rudimentary understanding of these impacts, and when we consider the implications of being incorrect, the potential disaster of a very real, not ‘small’ increase in the number of children with autism, we shouldn’t be overselling our knowledge for the sake of expedient arrival at a comforting conclusion. We should be doing the opposite.
If we can’t have the robustly defendable values on autism rates right now, that’s fine, because that is the reality, but we should at least have the courage to acknowledge this truth. This is the nature of still learning about something, which we are obviously doing in terms of autism, but in that situation, we don’t have the currency of scientific debate, decent data, to be saying with authority that any true increase in autism is small.
Unfortunately for the purveyors of The Fairytale, things are going to get a lot worse. The problem is that we are starting to identify extremely common, in some cases, recently more common, environmental influences that subtly increase the risk of autism. These are further problems for a genetic dominant model and effectively mandate that the ‘small increase’ is going to have to start getting bigger as a measurement, with a correlated decrease in the amount of autism that cultural shuffling can be held responsible for. Will anyone notice?
By way of example, we now have several studies that link the seasons of gestation with neurodevelopmental disorders including autism and schizophrenia; i.e., Season of birth in Danish children with language disorder born in the 1958-1976 period, Month of conception and risk of autism, or Variation in season of birth in singleton and multiple births concordant for autism spectrum disorders, which includes in the abstract, “The presence of seasonal trends in ASD singletons and concordant multiple births suggests a role for non-heritable factors operating during the pre- or perinatal period, even among cases with a genetic susceptibility.” Right! As I looked up some of these titles, I found that the evidence for this type of relationship has been well known for a long time; schizophrenia, in particular has a lot of studies in this regard, i.e., Seasonality of births in schizophrenia and bipolar disorder: a review of the literature, which is a review of over 250 studies that show an effect, and I also found Birth seasonality in developmentally disabled children, which includes children with autism and was published in 1989, which is like 1889 in autism research years.
Our seasons have remained constant (but probably won’t stay too constant for much longer. . . ), but this still throws a whole barrel of monkey wrenches into the meme of a disorder primarily mediated through genetics.
More damning for the Fairytale are some studies presented at this year’s IMFAR, and some others just published, that tell us that abnormal immune profiles during pregnancy appear to provide slightly increased risk for autism, roughly doubling the chance of a child receiving a diagnosis. The groovy part is that the studies utilized both direct and indirect measurements of an activated immune system to draw similar conclusions, a sort of biomarker / phenotype crossfire.
From the direct measurement end, we have Cytokine Levels In Amniotic Fluid : a Marker of Maternal Immune Activation In Autism?, which reports that mothers with the highest decile of tnf-alpha levels in the amniotic fluid had about a one and a half times increased risk for autism in their children. This makes a lot of sense considering the robustness of animal models of an acute inflammatory response during pregnancy and its impact on behavior.
Another study, this one from the MIND Institute in California (which I love), is Increased mid-gestational IFN-gamma, IL-4, and IL-5 in women giving birth to a child with autism: a case-control study (full paper). They found that in pregnant mothers, increased levels of IFN-gamma led to a roughly 50% increased risk of an autism diagnosis. Here is a snipet:
The profile of elevated serum IFN-γ, IL-4 and IL-5 was more common in women who gave birth to a child subsequently diagnosed with ASD. An alternative profile of increased IL-2, IL-4 and IL-6 was more common for women who gave birth to a child subsequently diagnosed with DD without autism.
This study took a lot of measurements, and goes to great lengths to explicitly call for additional analysis into the phenomena. IFN-gamma is typically considered pro-inflammatory, while IL-4 and IL-5 are considered regulatory cytokines. In order to determine if these findings were chance or not, the researchers determined if there was a correlation between the levels of IFN-gamma, IL-4, and IL-5, which they reported with very robust results. Less clear is what might be causing these profiles, or how, precisely, they might give rise to an increased risk of autism. The interconnectedness of the brain and the immune systemwould be a good place to start looking for an answer to the last question though.
What about indirect measurements? It just so happens, another paper was published at IMFAR this year that observed the flip side of the coin, conditions associated with altered cytokine profiles in the mother and this study also found an increased risk of autism. The Role of Maternal Diabetes and Related Conditions In Autism and Other Developmental Delays, studied a thousand children and the presence of diabetes, hypertension, and obesity in their mothers in regards to the risk of a childhood autism diagnosis. The findings indicate that having a mother with one or more of those conditions roughly doubles the chances of autism in the offspring. Obesity, in particular, has an intriguing animal model Enduring consequences of maternal obesity for brain inflammation and behavior of offspring, a crazy study that I blogged about when it was published. A variety of auto immune disorders in the parents have been associated with an autism diagnosis in several studies.
The obesity data is particularly troublesome for the idea of a ‘small’ increase in autism, just like parents have been getting older, parents have also been getting fatter, waaaay fatter, (and more likely to have diabetes) the last few decades. There isn’t any squirming out of these facts. If, indeed, being obese or carrying associated metabolic profiles is associated with an increased risk of autism, ‘small’ is getting ready to absorb a big chunk of real increase. But is there any clinical data to support this possible relationship, do we have any way to link obesity data with this autism data from the perspective of harder figures?
It further turns out, there are some very simple to navigate logical jumps between the above studies. Remembering that our clinical measurements indicated that increased INF-gamma, IL-4, and IL-5 from the plasma of the mothers was associated with increased risk, we can see very similar patterns in Increased levels of both Th1 and Th2 cytokines in subjects with metabolic syndrome (CURES-103). Here is part of the abstract, with my emphasis.
Metabolic syndrome (MS) is a cluster of metabolic abnormalities associated with obesity, insulin resistance (IR), dyslipidemia, and hypertension in which inflammation plays an important role. Few studies have addressed the role played by T cell-derived cytokines in MS. The aim of the tudy was to look at the T-helper (Th) 1 (interleukin [IL]-12, IL-2, and interferon-gamma [IFN-gamma]) and Th2 (IL-4, IL-5, and IL-13) cytokines in MS in the high-risk Asian Indian population.
Both Th1 and Th2 cytokines showed up-regulation in MS. IL-12 (5.40 pg/mL in MS vs. 3.24 pg/mL in non-MS; P < 0.01), IFN-gamma (6.8 pg/mL in MS vs. 4.7 pg/mL in non-MS; P < 0.05), IL-4 (0.61 pg/mL in MS vs. 0.34 pg/mL in non-MS; P < 0.001), IL-5 (4.39 pg/mL in MS vs. 2.36 pg/mL in non-MS; P < 0.001), and IL-13 (3.42 pg in MS vs. 2.72 pg/mL in non-MS; P < 0.01) were significantly increased in subjects with MS compared with those without. Both Th1 and Th2 cytokines showed a significant association with fasting plasma glucose level even after adjusting for age and gender. The Th1 and Th2 cytokines also showed a negative association with adiponectin and a positive association with the homeostasis model of assessment of IR and high-sensitivity C-reactive protein.
Check that shit out! Seriously, check that out; increased IFN-gamma, IL-4, and IL-5 in the ‘metabolic syndrome’ group, comprised of people with, among other things, obesity, insulin resistance, and hypertension; the same increased cytokines and risk factors found to increase the risk of autism.
If we look to studies that have measured for TNF-alpha in the amniotic fluid during pregnancy, we quickly find, Second-trimester amniotic fluid proinflammatory cytokine levels in normal and overweight women
There were significant differences in amniotic fluid CRP and TNF-alpha levels among the studied groups: CRP, 0.018 (+/-0.010), 0.019 (+/-0.013), and 0.035 (+/-0.028) mg/dL (P=.007); and TNF-alpha, 3.98 (+/-1.63), 3.53 (+/-1.38), and 5.46 (+/-1.69) pg/mL (P=.003), for lean, overweight, and obese women, respectively. Both proinflammatory mediators increased in women with obesity compared with both overweight and normal women (P=.01 and P=.008 for CRP; P=.003 and P=.01 for TNF-alpha, respectively). There were significant correlations between maternal BMI and amniotic fluid CRP (r=0.396; P=.001), TNF-alpha (r=0.357; P=.003) and resistin (r=0.353; P=.003).
What we are really looking at are five studies the findings of which speak directly to one another; a link to metabolic syndrome during pregnancy and increased IFN-gamma, IL-4, and IL-5, a link to obesity and hypertension in pregnant mothers and autism risk, and an increased risk of autism in mothers wherein IFN-gamma, IL-4, and IL-5 were found to be increased outside of placenta. Further, we have a link between amniotic fluid levels of TNF-alpha and metabolic syndrome, metabolic syndrome in mothers and autism risk, and increased risk from increased tnf-alpha in the amniotic fluid.
As I have said previously, one thing that I have learned during this journey is that when we look at a problem in different ways and see the same thing, it speaks well towards validity of the observations. What we see above is a tough set of data to overcome; we need several types of studies looking at the relationship between metabolic syndrome, immune profiles during pregnancy, and autism from different angles to have reached the same wrong conclusion, something that is increasingly unlikely. We are in an epidemic of obesity and the associated endocrine mish mash of metabolic syndrome, there simply isn’t any diagnostic fuzziness on this. It is happening all around us. Even though the total increase in risk is relatively small, the sheer quantity of people experiencing this condition of risk mandates that the numbers game looks favorable towards a real increase in autism. If we acknowledge this, how can we continue to have faith in the concept that any true increase in the autism rates must be ‘small’?
Is the next argument going to be that besides increased parental age, and heavier or more diabetic mothers, the rest of the autism increase is the result of diagnostic three card monte? (Just how much is the rest, anyways?)
And even though these studies, and likely more in the future, expose the crystal delicate backbone of the ‘small true increase’ argument, I have great pessimism that the people so enamored with invoking this phrase will ever acknowledge its shifting size, much less the implications of being wrong on such a grand scale.
Posted April 14, 2010on:
I hate to write another vaccination related post, but I keep on running into the same, tired argument, and thought it might be nice to have a single place to list and link the reasons that one of the most commonly used defenses of why we don’t need to study the vaccination schedule can be dismantled. The scary part, the really fucking scary part, is how easy it is to deconstruct the metrics being provided by experts as to why questioning the process of vaccination need not be thoroughly evaluated, and how people that ought to know better keep regurgitating the antigen gambit despite its obvious shortcomings when held to the most primitive logical tests.
For some background, lets start with basic immunology and the hows and whys of how vaccines actually work. But even before that, lets be clear: Vaccines work. I have absolutely no doubt that the purpose of vaccines, providing protection against microbial invaders is successful, and saves millions of lives every year. What I’m not so sure of, is whether or not this is the only thing our increasingly aggressive vaccination schedule has been accomplishing.
The functional success of vaccination is that we have crafted a technique that allows us to train our immune system to recognize some very nasty, dangerous, and deadly bacterial and viral pathogens. How is this done? Well, it turns out that at a very detailed molecular level, many bacteria and viruses have very specific patterns on their exterior, for our purposes, an immunological fingerprint that identifies, for example, the tetanus bacteria from the diphtheria bacteria. These fingerprints are known as antigens, and our immune systems use them to store a memory of particular pathogens we have been exposed to, so the next time such a pattern is encountered, a robust immune response can be mounted rapidly, before the pathogen gets a chance to reproduce and get us sick. The memorization of these molecular patterns, the fingerprints of specific bacteria and viruses, is the foundational premise of vaccination; by presenting these antigens to our immune system in a hopefully(?) harmless way, we train our immune system to respond to these invaders without actually having to endure the virulence of the actual bacteria or virus. Making things a bit more complicated, some pathogens have more than one molecular face to present, and as such, more than one fingerprint is necessary for our immune system to recognize. Some others, such as flu, regularly shift their molecular fingerprint; this is why there are seasonal flu shots, each year scientists must make educated guesses as to which particular influenza fingerprints will be most prevalent; when they guess correctly, the vaccine mostly works, because we have trained our immune system to see that particular antigen pattern. Other pathogens, like HIV, undergo such rapid transformation of their outward facing molecular structure that tailoring a molecular portrait of them has proven exceedingly difficult.
So, again at a very high level, vaccines work because they present antigens, immune fingerprints, from viruses or bacteria to our bodies, without the associated virulence of the organisms. The hows of creating the antigens without the problems of actual infection aren’t necessary for this discussion; lets just assume that for our purposes, you can have bacterial or viral fingerprints introduced in a vaccine without having to worry about the traditional ramifications of the actual bacteria or virus they came from. Great!
Given that, lets imagine you are a skeptic and are a bit bothered by the fact that our existing vaccine and autism research seems to be wholly comprised of studies involving either thimerosal, or the MMR. It seems a bit confusing that these two types of studies are sufficient for us to have certainty that the act of vaccination itself, or other vaccines administered at very different ages might be contributing to our apparent observations of increases in autism (or other behavioral or autoimmune disorders). If you raise a question involving this glaring blind spot in our research, a lot of the time you’ll see a response like some of these:
The only thing that makes biological sense in the discussion really is antigens and excipients and if you look at that, today’s kids get FAR fewer than say, my generation.
What is relevant is the number of antigens, and not the number of vaccines, that matters. Antigens are the active part of the vaccine which stimulates the immune response.
Another point directed to those who think that multiple vaccines overload the immune system. In actual fact, even though we are vaccinating against more diseases than in the past, we are actually using fewer antigens (the part of the vaccine which stimulates the immune response) in these vaccines than was previously the case.
You get the picture; the only measurement of interest is the number of antigens in vaccines. To be completely fair to some people that use the antigen gambit, it is in response to its equally simplistic counterpart, the ‘Vaccines Overload The Immune System’ gambit. That’s no excuse, at the end of the day, the people using crank arguments are supposed to be the cranks. What worries me is the people using the antigen gambit, are in many cases, the experts, and in the rest of the cases, folks that have listened to the experts, and parrot something that sounds sciency. It is a frightening day when you realize that if infectious disease experts had a reason, a real reason, we shouldn’t study the entire vaccination schedule, they’d provide one better than the antigen gambit.
The tour de force take down of the Vaccines Overload the Immune System gambit is “Addressing Parents’ Concerns: Do Multiple Vaccines Overwhelm or Weaken the Infant’s Immune System?“, by Paul Offit and others. It’s my guess that this document, published in the highly read Pediatrics journal, plays a big part in people believing that the only important thing about the vaccine schedule is the number of antigens involved. Here is the abstract:
Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines. Implicit in this concern is that the infant’s immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system. In this review, we will examine the following: 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines; 2) the theoretic capacity of an infant’s immune system; 3) data that demonstrate that mild or moderate illness does not interfere with an infant’s ability to generate protective immune responses to vaccines; 4) how infants respond to vaccines given in combination compared with the same vaccines given separately; 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children; and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago.
The biggest problem here is that the acknowledged, ‘implicit’ concern is that multiple vaccines may overwhelm the immune system. The concern we should be more concerned with is, can vaccines modify the immune system in ways that we cannot predict? This is a question that is not addressed here, but if your premise starts with the wrong question, or in this case, a bad question your conclusions shouldn’t be worth much.
All of the bullet points provided suffer from one or more maladies, including a foundational structure of gross over simplifications, insulting the intelligence of the reader, or in one case, wildly optimistic claims of a study conclusions; the same kind of thing what would get you a special article by the Chicago Tribune if you recommended children with autism try not to eat wheat for a few weeks and see what happens.
For this post, we’ll just focus on the last bullet point, and the text that supports it:
6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago
This is the lead in for this question:
Parents who are worried about the increasing number of recommended vaccines may take comfort in knowing that children are exposed to fewer antigens (proteins and polysaccharides) in vaccines today than in the past.
To prove this comforting point, the authors provide this fancy table:
(Bigger view on the link to full paper – they don’t have this table exploded as its own supplement link). The good news is in green here, as noted in the text, the only reduction count in the vaccine schedule after 1960 was the change from DTP to DTAP.
The bad news is that, if counting antigens were a meaningful metric, of well, anything, the chicken pox vaccine, Varicella, now contains more antigens than the rest of the shot schedule combined.
This puts us in somewhat of a conundrum. If the ‘number of antigens’ in vaccines is what is relevant, does this mean that the Varicella vaccine puts nine times more stress on the immune system than the Pneumococcus vaccine? Does the Varicella vaccine initiate an immune response sixty nine times more strenuous than the diphtheria component of the DTAP vaccine? [Good luck finding a study to measure the innate immune response to any of those vaccines in a pediatric population.]
The DTAP was licensed in the 1980s, but Varicella didn’t get licensed until 1990; so this means that children who got DTAP, but didn’t get Varicella, got far fewer antigens, half as many, than children born just a few years later. Is this meaningful?
Here is an interesting way to view the question. Imagine the CDC was addressing a set of parents whose children was born in 1985 who were concerned about those vaccinations overloading the immune system of their children, and this was the response:
Parents who are worried about the increasing number of recommended vaccines may take comfort in knowing that your children were exposed to fewer antigens (proteins and polysaccharides) than in vaccines today.
Does this sound like a good argument?
We might also take a look at how frequently children experience mild side effects from vaccination, according to the CDC web site. Fever is an indicator of innate immune activation, though you will occasionally see arguments made that it is insufficiently characterized to draw conclusions from, but if we are trying to understand if addition of antigens is a useful measurement or not, it would seem the rates of side effects are valid goalposts. Here are some quotes; there isn’t a fancy table of this information yet.
- Varicella: Fever (1 person out of 10, or less) [69 antigens]
- Pneumococcal: Up to about 1 out of 3 had a fever of over 100.4 degrees Fahrenheit, and up to about 1 in 50 had a higher fever (over 102.2 degrees Fahrenheit). [8 antigens]
- MMR Fever (up to 1 person out of 6) [24 antigens]
- DTAP: Fever (up to about 1 child in 4) [4 – 7 antigens]
Now that is curious. According to the CDC, the vaccine with the most antigens causes fever far less frequently than vaccines with many times fewer antigens in them. If we can use addition to gain comfort from the fact that the current vaccine schedule includes fewer antigens than it used to, how do we incorporate in this information?
But if we can’t use addition for our purposes? What if, in fact, the system we are interacting with is much, much too complicated to be usefully outlined with simple addition? What if antigens aren’t the only relevant measuring point in evaluating vaccine impact on the immune system? In this case, why use the reduction in antigens in vaccines as an argument to ‘address parents concerns’? Why has such a gross over simplification achieved ubiquity in the blogosphere and indeed, why was it promulgated by the most frequently interviewed physician when the subject is autism and vaccination?
Ponder the above at your own risk.