passionless Droning about autism

Hello friends –

We keep on finding things that seem to very gently alter developmental trajectory towards (or away from) an eventual diagnosis of autism; a genetic variant here or there, an environmental exposure, or one of our very many experiments in cultural engineering.  When these nudges are founded on genetic variances, they are often referred to as “low penetrance” risk factors; here is a snipet from the wiki definition for “Penetrance”

An allele with low penetrance will only sometimes produce the symptom or trait with which it has been associated at a detectable level.

I would argue, and have previously on this blog, that there isn’t a good reason that the descriptive of low penetrance should be relegated solely to genetic inputs.  The ‘non-genetic’ factors we seem to have associated with autism risk, or protection, seem to inherit the same quality of a low grade impact; the risk of an autism diagnosis isn’t altered by too much, but instead, just a little. 

There are a great number of examples of environmental impacts that seem to follow a low penetrance model of effect; maternal obesity, paternal age, cesarean section, maternal asthma, maternal folate ingestion [protective!], maternal use of anti-depressants (or being depressed?), low birth weight, and some perhaps some drugs given during pregnancy.

[Please, please note:  I’m not “blaming the mother” here, but we do not have the luxury of invoking Bettleheim as a mechanism for avoiding evident truths.   A dispassionate analysis of the data mandates we accept that the prenatal environment is critical.

If you think that some percentage of the autism ‘epidemic’ is real, you should realize that this issue is too important to be scuttled by emotional hotspots.  You cannot blame yourself for things that were unknown to you during your pregnancy.  If, instead, you don’t think autism rates have changed, none of the above impacts can be meaningful.  Finally, if you believe that autism is more gift than disorder, then you aren’t getting blamed for anything anyways.]

Unfortunately, a mixture of subtle changes makes for a messy situation for our researchers for a few reasons; environmental studies contain a difficult to contend with set of confounders; knowing what to measure, when to measure it, and the often times necessary evil of usage of self reporting, computer models, or other proxies for exposure measurements.  Making things even worse, it is biologically plausible, indeed, mandatory, that low penetrant effects operate with each other.  What we will eventually need to be working on, for example, is determining the specific genetic dispositions that act in concert with a low birth weight and with gestational anti-depressant exposure to perturb neurodevelopment toward autism.  That’s a tough thing to do.

Throwing this kind of disparate data into a blender at study time looks to be largely beyond our current capacities; researchers are struggling to identify single gene-environment interactions, for example, MET-C/pollutants, or the terrifying notion of RORA demythlation/endocrine disruptors interacting together.  Looking at more, or a handful, as is likely necessary, is a long ways off.

I’ve been thinking about the intersection of these two things lately; our relative inability to evaluate for several, subtle, interacting forces, with the growing evidence that a great many mysterious conditions, including autism, seem to be governed by lots of small things occurring differently.   I am left with the idea that are woefully unready to understand the participating factors in any particular case of autism, with similar reservations regarding our ability to know how much, if any, of the autism ‘epidemic’ is real.

A few weeks ago, there was an Op-Ed in the New York Times that speculated on the link between an in-utero environment characterized by increased inflammation and an eventual diagnosis of autism.  I was largely in agreement with Moises Velasquez-Manoff on a the basic premise of his argument; especially regarding the state of the science on the immune findings in the autism realm, the use of helminths, not so much. A very widely read response by Emily Willingham accused the author of the piece of invoking a naturalist theory of the past:

Whether he means to or not, Velasquez-Manoff then echoes one of the favorite refrains of the anti-vaccine movement, that back when the world was a beautiful place of dirty, worm-infested children, clean water, 100% breastfeeding, and no television, it was a place where the immune system could do its work peacefully and with presumably Zen-like calm, weeding out the weak among us and leaving behind the strong.

I don’t think that the NYT article did anything of the sort, the author merely stated that there seem to be fewer signs of immune dysregulation and autoimmune conditions in some types of living conditions.

Then, a few weeks later, a widely publicized metadata study on organic eating came out.  Again, the skeptics were ready to pummel the bruised body of the naturalistic fallacy, in this case, Stephen Novella at SBM:

Environmental claims for organic farming are complex and controversial – I will just say that such claims largely fall prey to the naturalistic and false dichotomy fallacies.

Stephen Novella’s version here is terse, but I think it is fair to say that in this context, the idea is that that if something is labeled as ‘natural’, that it then must be somehow superior to a ‘non-natural’ alternative, is a fair characterization of a naturalistic fallacy.

[The masochist could read through a few comments on that thread to see my take on the organic/non organic study; but the TL;DR version is, the study could have just as easily been titled, “Evaluations of Organic Eating Insufficiently Powered Or Designed To Know More Than The Most Primitive Endpoints, At Best”.  Here is an NPR transcript where the presenter is a little more up front in that the state of the science is that health benefits have not been evaluated for.

But what I should point out here is that the studies of people were very limited. They were short-term and, like, narrowly focused. So they would look at pregnant women, for instance, and say, are pregnant women eating organic, are their children – did their children have left eczema or allergic conditions? So these are sort of narrowly focused studies. They were short-term, and there weren’t very many of them.

One of the few human studies in this metadata analysis involved a dietary intervention of one apple.  What we have is a lack of evaluation, as opposed to a lack of findings, a familiar situation.]

Even so, it must be stated: The naturalistic fallacy(ies), as presented by the skeptics, and as believed by some fraction of grape-nut-eating-tarot-card-flipping people out there, is bogus.  Things weren’t better way back then.  Just because something is ‘natural’ doesn’t mean it is better, or without unknown consequences.  Washing your hands is good, but antibiotics are also good, and work better when necessary.  Breastfeeding is good, but it doesn’t keep your infant from getting cholera.  Vaccines work.  Modern agriculture is feeding a lot more of us than we used to be able to feed, and the hard truth be told, it is policies and habits that are leaving lots of people hungry.  I don’t know if eating a organic diet is better for you or not, but I do know that I do like supermarkets.

But.

Our history is littered with the discarded arguments of people just as smart as us using rudimentary tools to understand complicated systems, declaring a lack of effect and throwing a contemptuous look over their shoulder at the rubes who long for the hilariously outdated solutions of yesteryear.  We shouldn’t be concerned with the fact that the naturalistic fallacy is intellectually bankrupt; we should be concerned with the fact that our incredibly stupid species is changing our environment with reckless abandon on the assumption that we are smart enough to understand what we are doing.  If the naturalistic fallacy is bad, the perfection-of-progess fallacy is almost as bad, with bonus negative points of being invoked by people who should know better.

How many examples do we need of our previous hubris until we realize that we are just barely less dumb now than we were then? 

First we thought lead was safe as a pesticide, in paint, and as a gasoline additive.  Then, we figured out it was only safe for paint and gasoline; then just in gasoline.  Now, we know that any amount of measurable levels of lead are associated with cognitive effects.  Any individual reader of this column was very likely an adult in 2002, and at that time, the state of our knowledge didn’t tell us that any amount of lead was less safe than no amount of lead.  Ten goddamn years ago, the FDA thought there was a level of lead that in the bloodstream that did not affect cognitive function in children.

We have been performing increasingly optional cesarean sections for decades before starting to figure out that they are associated with adverse health effects for the lifespan.  Only within the past few years have we discovered that this procedure is associated with altered microbiomes,  obesity, and asthma.

We have been so successful at distributing products with based on plastic  that over 90% of every human on the planet has detectable levels of component chemicals in their bloodstream.  Only now that we have insured that nearly every human has been touched, we consistently find associations with metabolic and reproductive changes.

After near thirty years, the recommendations over administering Tylenol to infants was changed.  In the 1980s we saw Reyes syndrome, made the association with aspirin, failed to observe any acute differences in infants given Tylenol, and pulled the trigger on global recommendation to replace aspirin with acetaminophen.  It took decades before we were clever enough realize that eliminating Reyes might not have been the only thing we did, because we were too stupid to realize that effects do not have to be immediately obvious in order to have profound outcomes.

Human bodies were forged through the crucible of evolution, thousands of generations of adaptation, to be ready to start reproducing by the teens, and we have decided to start putting that process of for a decade, or two.

All of these examples are founded of the specificity of our analytical abilities, or rather a relative lack of specificity.  We weren’t clever enough to understand to look for associations, so they remained invisible to us.  A question never asked is never answered.  Even worse, some of these are discrete events, disturbances orders of magnitude more simplistic to analyze compared to ‘eating organic’.

A lot of the skeptical sites will utilize the idea that humans are ‘pattern seekers’, especially when it comes to people reporting temporal associations with development of autistic behaviors and vaccination.  I kind of like the idea of the pattern seeking human in general; the biggest pattern we seem to be seeing is the one that tells us that our current state of knowledge gives us enough information to understand what we are doing, a type of uber-pattern.

The idea that we have a decent understanding the effect of ingesting increased pesticide residue, a finding included in the organic metadata study, is a joke.  The idea that we have the faintest clue of the outcomes of replacing infection with inflammation, a practice we have embraced with great enthusiasm, is a total fucking joke.  We have barely bothered to look.  Do not believe anyone who tells you otherwise.

This is what bothers me so much about a casual wielding of the naturalistic fallacy; it is so frequently a feint from critical questions.  The discordance with reality of the naturalist fallacy has been established.  It is great how much less suffering there is now, compared to then, but let’s not rest on our laurels.  Am I the only one worried about how wrong we are here, now? 

I don’t know if eating less pesticide is better than eating more pesticide, and I also can’t be sure that a lifestyle characterized by increased inflammation is a risk factor for developmental differences.  I do know that the rules implemented by the natural world have no care for our hubris.  Those same rules have violated our once pristine knowledge so dispassionately and with such regularity that I can find no pleasure in hurling the accusation of the naturalistic fallacy at anyone.  Instead, the idea fills me with a sense of honorable mention at best; we are more capable than last century, last generation, last year, but we remain at the mercy of machinations which hold no regard for such incremental progress in knowledge in the face of unprecedented changes to our environment.

–       pD