Thursday, February 18, 2016

Somatic mutation and neurological traits. Part III. Behavioral implications

I've been discussing a new paper in Cell that describes a detailed study of mouse embryonic neural cell culture that finds evidence for widespread mutations of a particular sort, occurring across the genome.  The detected effects often involve genes that are involved in the function of synapses, the connections between neurons that are fundamental to the way the brain works.  I am interested in the possibility that these changes may be contributors to epilepsy.  But these are in the same genes in which inherited mutations could have potentially relevant effects on intelligence, behavior, or personality.

In epilepsy as in other psychiatric, behavioral, and neurological traits, the total etiology of any given instance is likely to involve many genetic variants with mainly minor individual effects (that is clearly what mapping has consistently shown),  The somatic mutation would be contributors to the mix.

The relevance of the paper to neurological and psychiatric diseases in general, is obvious.  If the genetically driven behavior of enough neurons goes awry, the person as a whole may manifest the result in the form of important impaired function, or even serious disease that threatens not just aspects of lifestyle but viability as well.  Another way to put it is to say that these somatic mutations may contribute to our individuality as people.  I have suggested in the two previous parts of this series that epilepsies, not mentioned by the Cell authors, may be added to their list.

But things could have much more profound impact than on occasional dysfunctional traits.  Neural somatic mutation of the sort reported in cell culture might also have important effects on a much broader array of normal mental traits.  Indeed, that is far more likely than that somatic mutation only affects abnormal traits.  And the broader range of non-pathological effects, which I think likely, has potentially deep societal implications.

Beyond psychological disorders
Personality and what we call 'intelligence', typically as measured by IQ tests, are important to our social fabric. Personality affects the way one interacts with others and fits within the constraints of society, and can have serious implications for the quality of life.  Indeed, personality traits, including but not limited to intelligence, are used by society to sort out access to resources--wealth, power, influence, health, safety, and even basic rights.  Those with impaired mental function are, for example, more likely to be homeless or perhaps in some instances to commit violent acts or to act sociopathically.  Of course, we should not just think in terms of the stereotypical social bad guys:  it is not usually recognized, but some who have wealth and power and are nominally considered successful could in every sense be called sociopaths, as well.

Beyond this, and even more sensitive, is the issue of group characteristics, especially those putatively attributed to 'race' or ethnicity.  There has been discussion going back at least to Plato, and including Darwin and his followers up to the present day, about how the 'better' (privileged upper) classes were the ones who are the important leaders, but whose valuable patrimony (that is, genes) are transmitted less often than those of their lesser compatriots. Whole classes of people might be superior or inferior because of genetic variants found disproportionately in one class and not in others.

To be blunt: the professoriate and other privileged classes, who often invoke class-based genetic value inherency as if they are the Darwinian favorites, don't like to acknowledge the fact that the slovenly masses out-reproduce the well-groomed elite.  The elite naturally find this threatening and unpleasant, and even concoct evolutionary arguments why this is a problem that needs curing (e.g., to  keep our species from going downhill).  That's weird, since by any reasonable Darwinian criterion the masses are the evolutionarily successful ones, as I've recently written (a copy available from me on request)--but we'll set that truth aside for the moment.

Anyway, the relevance to this series of posts on neural somatic mutation is direct. That's because the issues just discussed are often if not typically couched in terms of the inherent worth of the worthies relative to their inferiors, and that in our time, routinely attributes the difference to genes.  Not only are there issues about individuals and whether specific genes confer behavioral traits (like how you vote, how you respond to abuse, sociopathic behavior, and of course intelligence), but these traits are often, and persistently, applied to groups--in the US this means 'races'.  Members of this race are often said to be smarter than members of that race because of their better genes.  This is, of course, nothing new.

There has been more than a century of heated debate about whether traits of individuals are inherited, inborn, and therefore largely unchangeable, or whether they are the result of circumstances of each person's life and can be molded by environments and experience.  This is now often called the 'Nature-Nurture' debate, but it goes back in history (some biblical tribes were supposedly cursed, and hence made inferior, by God for their sins, for example).  Scientific rather than blatantly political views on the subject can be traced, for example, to Linnaeus and his time's ranking of human races.

Moving toward an attempt to make differences and evolution scientific, Lamarck suggested around 1800 that traits were modified by individuals' habitual behaviors, the result then being inherited in their offspring. Darwin's ideas about natural selection changed the putative mechanism a bit, but not the idea of adaptive change, meaning improvement.  Racial hierarchies were a part of the assertions, and often still are.  Then and since, major political movements across the political spectrum, each bolstered by some form of 'theory', including both eugenics and Marxism, have largely rested on opposing arguments within this purportedly scientific context.

Today, there are scientists and other authors who passionately deny the existence of race and who argue that most of societally relevant behavioral traits are the result of circumstances, while others argue that, no, we are what we inherit. The latter point to the clear evidence of 'heritability' of behavioral traits, especially including but by far not limited to, intelligence.  Parent-offspring or sib-sib correlations, for example, suggest that up to, say, 50% of variation in these traits can be accounted for by genetic variation.  This is then extended to assertions of inherent traits of groups, such as traditional 'races', attributing societal success to inherent worth.  This in turn is used, for example, to justify differential resource allocations, such as of educational funds.  Many scientists, even prominent ones who actually know some genetics, as well as passionate racists and other hyper-determinists, take this position.

Meanwhile, others point with equal passion to shared household environments and rigid social structures, and argue that if those in the poor, lower-achieving parts of society had as many books, ballet lessons, and resources, Kaplan test-prepping courses, and learned as many different words as those in more privileged parts of society, and inherited as much from their parents, they'd end up just as successful.  They argue that genetic Darwinism is being abused to justify societal inequality.

But what does neural somatic mutation have to do with any of this?

Somatic mutation and you are what has happened
For the purposes of argument, let's assume that genetic variants do provide important aspects of one's personality, abilities, and psychological health.  There is plenty of evidence from known genes in which variants (alleles) can essentially cause at least some severe psychological problems, so why not more generally?  Persons inheriting harmful variants in those genes are, truly, impaired.  If they reproduce, their children would have the usual Mendelian odds of inheriting the same effects. This doesn't by any means justify depriving the victims of resources and, indeed, a more benign societal view would be that they should be provided more resources so they can reach their potential. However, that is a purely societal question, unrelated to the fact of causation.  The genetic determinist view would ask: How can the same sort of genetic effects not apply also for traits within the normal range?

Those who counter with environmental accounts of personality and the like argue that you are what has happened in your life, from gestation onward, and that is malleable but not heritable in your children.  Scars from early childhood may doom someone's lifetime success, but while unfortunate or even tragic, they're not biologically inherited (unless they are in utero environmental effects, but even those can be 'erased' with better environments because they're not etched into the DNA).   If society will but apply them, environmental improvements will lead to performance improvements: our brains are not hard-wired for specific functions but are hard-wired as learning devices.  We are what we learn: that is the whole 'point' of the evolution of intelligence!

Somatic mutation falls in between these two views.  In a sense, though not due to any specific environmental exposure or experience, the effect of somatic mutations is to make you be what has happened during the genesis of your neural system.  Somatic mutations could affect what one can achieve, just as rabid genetic determinists argue.  Of course, it isn't just impairments that might be involved, because exceptionally positive effects are likely, but we have far less genetic information on that than on disease or impaired function. In any case, performance abilities due to somatic mutation would not be heritable, just as the angry environmentalists insist.

In fact, and I think the Cell authors mentioned something like this, one can envision reasons why high mutability could generate high mental flexibility and adaptability, much as the immune system generates high antibody diversity to be able to respond to unforeseeable pathogens.  Non-heritable, environmentally non-specific neural variation could be a generic adaptation akin to immunity.

Somatic mutations are not inherited, so those relentlessly searching genomewide mapping data, or those searching socioeconomic data, will similarly fail to account for the apparently built-in, yet non-heritable mental and neurological traits of individuals.  In a sense, both groups are right.  This, however, says nothing whatever about the divided views on what society should do about our individual differences,

The Cell paper is just one paper and though it cites other relevant literature, its importance for me is that it shows the potential value of thinking about somatic mutation in the neurological context. As I finished writing this post, my copy of the January Nature Reviews Genetics arrived.  An article by Vissers et al. describes genomewide mapping results for 'intellectual disability and related disorders. One figure shows that, if you believe the strength and credibility of the evidence, around 700 'genes' (whatever that means--e.g.., whether just genome regions or only protein-coding regions) associated with these traits.  The identification pattern doesn't suggest that most genes have as yet been identified.  And this is only about disorders.

With this huge range of potentially functional targets, it is simply not credible to doubt that somatic mutation is a major contributing factor to psychological variation, normal and otherwise.  Even more convincing is the finding that these genes 'overlap' in functional effects, that is, are individually associated with more than one disorder.  Here we needn't even get into issues about diagnosis and definition.  That's because, at the very least, somatic mutation in the 700+ genes makes a hearty target, and this is undoubtedly just a fraction of the real target (because mapping really only accounts for a fraction of the occurrence of the traits, as we've posted on many times before),

It will be some time before technologies allow neural somatic mutations to be detected in any way relevant to predicting psychological traits in living individuals, much less intervening in any way.  At most, techniques for somehow identifying somatic mutations in living individuals may be developed so we can at least assess how and how much this source of otherwise cryptic causation affects who we are as individuals.

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