Everything is genetic, isn't it?

There is hardly a trait, physical or behavioral, for which there is not at least some familial resemblance, especially among close relatives.  And I'm talking about what is meant when someone scolds you saying, "You're just like your mother!"  The more distant the relatives in terms of generations of separation, the less the similarity.  So you really can resist when told, "You're just like your great-grandmother!" The genetic effects decline in a systematic way with more distant kinship.

The 'heritability' of a trait refers to the relative degree to which its variation is the result of variation in genes, the rest being due to variation in non-genetic factors we call 'environment'.  Heritability is a ratio that ranges from zero when genes have nothing to do with the trait, to 1.0 when all the variation is genetic.  The measure applies to a sample or population and cannot automatically be extended to other samples or populations, where both genetic and environmental variation will be different, often to an unknown extent.

Most quantitative traits, like stature or blood pressure or IQ scores show some amount, often quite substantial, of genetic influence.  It often happens that we are interested in some trait that we think must be produced or affected by genes, but that no relevant factor, like a protein, is known.  The idea arose decades ago that if we could scan the genome, and compare those with different manifestations of the trait, using mapping techniques like GWAS (genomewide association studies), we could identify those sites, genomewide, whose variation in our chosen sample may affect the trait's variation.  Qualitative traits like the presence or absence of a disease (say, diabetes or hypertension), may often be due to the presence of some set of genetic variants whose joint impact exceeds some diagnostic threshold, and mapping studies can compare genotypes in affected cases to unaffected controls to identify those sites.

Genes are involved in everything. . . . .
Many things can affect the amount of similarity among relatives, so one has to try to think carefully about attributing ideas of similarity and cause.  Some traits, like stature (height) have very high heritability, sometimes estimated to be about 0.9, that is, 90% of the variation being due to the effects of genetic variation.  Other traits have much lower heritability, but there's generally familial similarity.  And, that's because we each develop from a single fertilized egg cell, which includes transmission of each of our parent's genomes, plus ingredients provided by the egg (and perhaps to a tiny degree sperm), much of which were the result of gene action in our parents when they produced that sperm or egg (e.g., RNA, proteins).  This is why traits can usually be found to have some heritability--some contribution due to genetic variation among the sampled individuals.  In that sense, we can say that genes are involved in everything.

Understanding the genetic factors involved in disease can be important and laudatory, even if tracking them down is a frustrating challenge.  But because genes are involved in everything, our society also seems to have an unending lust for investigators to overstate the value of their findings or, in particular, to estimate or declaim on the heritability, and hence genetic determination, of the most societally sensitive traits, like sexuality, criminality, race, intelligence, physical abuse and the like.

. . . . . but not everything is 'genetic'!
If the estimated heritability for a trait we care about is substantial, then this does suggest the obvious: genes are contributing to the mechanisms of the trait and so it is reasonable to acknowledge that genetic variation contributes to variation in the trait.  However, the mapping industry implies a somewhat different claim: it is that genes are a major factor in the sense that individual variants can be identified that are useful predictors of the trait of interest (NIH's lobbying machine has been saying we'll be able to predict future disease with 'precision').  There has been little constraint on the types of trait for which this approach, sometimes little more than belief or wishful-thinking, is appropriate.

It is important to understand that our standard measures of genes' relative effect are affected both by genetic variation and environmental lifestyle factors.  That means that if environments were to change, the relative genetic effects, even in the very same individuals, would also change.  But it isn't just environments that change; genotypes change, too, when mutations occur, and as with environmental factors, these change in ways that we cannot  predict even in principle.  That means that we cannot legitimately extrapolate, to a knowable extent, the genetic or environmental factors we observe in a given sample or population, to other, much less to future samples or populations.  This is not a secret problem, but it doesn't seem to temper claims of dramatic discoveries, in regard to disease or perhaps even more for societally sensitive traits.

But let's assume, correctly, that genetic variation affects a trait.  How does it work?  The usual finding is that tens or even hundreds of genome locations affect variation in the test trait.  Yet most of the effects of individual genes are very small or rare in the sample.  At least as important is that the bulk of the estimated heritability remains unaccounted for, and unless we're far off base somehow, the unaccounted fraction is due to the leaf-litter of variants individually too weak or too rare to reach significance.

Often it's also asserted that all the effects are additive, which makes things tractable: for every new person, not part of the study, just identify their variants and add up their estimated individual effects to get the total effect on the new person for whatever publishable trait you're interested in.  That's the predictive objective of the mapping studies.  However, I think that for many reasons one cannot accept that these variable sites' actions are truly additive. The reasons have to with actual biology, not the statistical convenience of using the results to diagnose or predict traits.  Cells and their compounds vary in concentrations per volume (3D), binding properties (multiple dimensions), surface areas (2D) and some in various ways that affect how how proteins are assembled and work, and so on.  In aggregate, additivity may come out in the wash, but the usual goal of applied measures is to extrapolate these average results to prediction in individuals.  There are many reasons to wish that were true, but few to believe it very strongly.

Even if they were really additive, the clearly very different leaf-litter background that together accounts for the bulk of the heritability can obscure the numerical amount of that additivity from sample to sample and person to person.  That is, what you estimated from this sample, may not apply, to an unknowable extent, to the next sample.  If and when it does works, we're lucky that our assumptions weren't too far off.

Of course, the focus and promises from the genetics interests assume that environment has nothing serious to do with the genetic effects.  But it's a major, often by far the major, factor, and it may even in principle be far more changeable than genetic variation.  One would have to say that environmental rather than genetic measures are likely to be, by far, the most important things to change in society's interest.

We regularly write these things here not just to be nay-sayers, but to try to stress what the issues are, hoping that someone, by luck or insight, finds better solutions or different ways to approach the problem that a century of genetics, despite its incredibly huge progress, has not yet done.  What it has done is in exquisite detail to show us what the problems are.

A friend and himself a good scientist in relevant areas, Michael Joyner, has passed on a rather apt suggestion to me, that he says he saw in work by Denis Noble.  We might be better off if we thought of the genome as a keyboard rather than as a code or program.  That is a good way to think about the subtle point that, in the end, yes, Virginia, there really are genomic effects: genes affect every trait....but not every trait is 'genetic'!

Genetics in an age of fundamentalism

I heard a program the other day on the BBC Radio 4's In Our Time about the origins, rise, and persistence of Chinese Legalism. Introduced in the 4th century BC, and the hallmark of the rule of the first emperor, the philosophy of Legalism was based on laws and their strict implementation.  It was the basis of a brutal, authoritarian state, elements of which have lasted 2500 years.

Here's one description (found here):

...Legalism is a Classical Chinese philosophy that emphasizes the need for order above all other human concerns. The political doctrine developed during the brutal years of the Fourth Century BCE. The Legalists believed that government could only become a science if rulers were not deceived by pious, impossible ideals such as "tradition" and "humanity." In the view of the Legalists, attempts to improve the human situation by noble example, education, and ethical precepts were useless. Instead, the people needed a strong government and a carefully devised code of law, along with a policing force that would stringently and impartially enforce these rules and punish harshly even the most minor infractions. 

                                                                                              L. Kip Wheeler 

To overly simplify, but I'm just trying to make a point, in Legalism, allegiance must be paid to the role of the ruler, rather than to a particular leader.  And, the system of rulership is absolute.  Further, Legalism views people as much easier to control if they are uneducated, and there's no sense in which they are expected to improve themselves.

In contrast, another ancient Chinese philosophy, Confucianism, was much more benevolent, with an optimistic view of human potential; people are basically good, and if taught new things they can be cultivated into better people.  Confucians see authority and leadership as something everyone has the potential to achieve, whereas in Legalism, the ruler dictates and people are expected to follow.

This contrast between people as good and improvable vs inherently evil, the absolute vs the relative, is of course a familiar dialectic, not at all restricted to philosophy of nation states.  Theism vs agnosticism,  laissez faire or free market vs regulation, the US Constitution as fixed or as flexible, cultural relativism vs universal human rights, free will vs predetermination, and of course tabula rasa or blank slate vs inherency, or nature vs nurture.

Confucius

The consistency with which people view the world in either absolute or relative terms is curious to me, and indicates that we aren't necessarily learning from observation, evaluating and interpreting the facts as we see them as we go about choosing our favorite economic system, or whether cultural practices that are alien to our own have any merit.  It seems instead that we've got an a priori view of the world that informs those decisions, an ideology that guides us in what turns out to be a fairly predictable direction.  In a loopy sort of way, those with an absolutist ideology would say that that ideology is genetic (and, indeed, that things like how we vote are genetic), while those with a relativist ideology would disagree, saying it's learned.

But at least our mythology about science is that it's supposed to be fact-driven, not ideological.  Often it is, though how do most people decide whether or not they accept that humans are driving climate change, or that all life evolved from a common ancestor?  Unless we're climate scientists or evolutionary biologists, we generally don't have the knowledge to evaluate the data in any meaningful way.  So these decisions become ideological.  In that sense, facts do not rule, not even in relation to science.

And what about the role of genes in making us who we are?  Ken and I have been sneeringly called "blank slaters" more than once, because we don't embrace the idea that who we are is determined by our genes.  The assumption is that if one doesn't accept that genes are always destiny, one must accept that they never are.

But, there's another way, and it's more subtle, and more nuanced, and that is to recognize that there's a continuum of gene action, from predictable to unpredictable.  Some alleles pretty reliably are associated with a given trait (alleles associated with Tay Sachs or cystic fibrosis), while others are not (APOE4 and dementia, HFE and  hemochromatosis).  With a few exceptions, specific genetic variants can't be predicted from most complex traits, and vice versa.  So, sometimes Legalism might be a good analogy for the relationship between genes and traits -- dictator, strong-arm genes -- and sometimes Confucianism; genes interacting with environment.  But there's also Daoism, another ancient Chinese philosophy, which taught that people were to live in harmony with nature, that government is unnatural, and that the best government is a weak government -- no dictator genes, mostly environment.

It used to be said that one's politics could be predicted from one's stand on genetic determinism, but determinism has become so pervasive that this is no longer true.  Atheist free-market constitutional modernist cultural relativist Bernie Sanders supporters are as likely to be genetic determinists these days as are, well, the opposite.  Determinism has become a pervasive ideology, and this despite a lot of evidence to the contrary.  Philosophers of science have long tried to define and describe how science is done, but I think fundamentally, while science is different from a lot of other human endeavors in that we do have ways of verifying that we're learning things, the role of ideology in what we think we've learned should not be underestimated.  And in many ways, it is heavily affected by emotions and by scientists' personal situations (careers, biases, and so on), even when they try to be 'objective'.  In recent decades, some 'science studies' work has clearly shown this (even if the practitioners have their own sociocultural axes to grind); given human nature, it should be no surprise. 

When did Lyndon Johnson propose the Great Society in the US?  It was in the mid 1960's, when we saw communism as a huge threat.  We reacted by becoming more like our 'enemy'.  Is it too simplistic to suggest that the same could be happening now, when our 'enemy' is religious fundamentalism?  

How do we know what we think we know?

Two stories collided yesterday to make me wonder, yet again, how we know what we think we know.  The first was from the latest BBC Radio 4 program The Inquiry, an episode called "Can we learn to live with nuclear power?" which discusses the repercussions of the 2011 disaster in the Fukushima nuclear power plant in Japan. It seems that some of us can live with nuclear power and some of us can't, even when we're looking at the same events and the same facts.  So, for example, Germans were convinced by the disaster that nuclear power isn't reliably safe and so they are abandoning it, but in France, nuclear power is still an acceptable option.  Indeed most of the electricity in France comes from nuclear power.

Why didn't the disaster convince everyone that nuclear power is unsafe?  Indeed, some saw the fact that there were no confirmed deaths attributable to the disaster as proof that nuclear power is safe, while others saw the whole event as confirmation that nuclear power is a disaster waiting to happen.  According to The Inquiry, a nation's history has a lot to do with how it reads the facts.  Germany's history is one of division and war, and nuclear power associated with bombs, but French researchers and engineers have long been involved in the development of nuclear power, so there's a certain amount of national pride in this form of energy.  It may not be an unrelated point that therefore many people in France have vested interests in nuclear power.  Still, same picture, different reading of it.

Cattenom nuclear power plant, France; Wikipedia

Reading ability is entirely genetic
And, I was alerted to yet another paper reporting that intelligence is genetic (h/t Mel Bartley); this time it's reading ability, for which no environmental effect was found (or acknowledged).  (This idea of little to no environmental effect is an interesting one, though, given that the authors, who are Dutch, report that heritability of dyslexia and reading fluency is higher among Dutch readers -- 80% compared with 45-70% elsewhere -- they suggest because Dutch orthography is simpler than that of English.  This sounds like an environmental effect to me.)

The authors assessed reading scores for twins, parents and siblings, and used these to evaluate additive and non-additive genetic effects, and family environmental factors.  As far as I can tell, subjects were asked to read aloud from a list of Dutch words, and the number they read correctly within a minute constituted their score.  And again, as far as I can tell, they did not test for nor select for children or parents with dyslexia, but they seem to be reporting results as though they apply to dyslexia.

The authors report a high correlation in reading ability between monozygotic twins, a lower correlation between dizygotic twins, and between twins and siblings, and a higher correlation between spouses, which to the authors is evidence of assortative mating (choice of mate based on traits associated with reading ability).  They conclude:

Such a pattern of correlation among family members is consistent with a model that attributes resemblance to additive genetic factors, these are the factors that contribute to resemblance among all biological relatives, and to non-additive genetic factors. Non-additive genetic factors, or genetic dominance, contributes to resemblance among siblings, but not to the resemblance of parents and offspring.  Maximum likelihood estimates for the additive genetic factors were 28% (CI: 0–43%) and for dominant genetic factors 36% (CI: 18–65%), resulting in a broad-sense heritability estimate of 64%. The remainder of the variance is attributed to unique environmental factors and measurement error (35%, CI: 29–44%).

Despite this evidence for environmental effect (right?), the authors conclude, "Our results suggest that the precursors for reading disability observed in familial risk studies are caused by genetic, not environ- mental, liability from parents. That is, having family risk does not reflect experiencing a less favorable literacy environment, but receiving less favorable genetic variants."

The ideas about additivity are technical and subtle.  Dominant effects, that is, non-additive interactions among alleles within a gene in the diploid copies of an individual, are not inherited as additive ones are (if you are a Dd and that determines your trait, only one of those alleles, and hence not enough to determine the trait, is transmitted to any of your offspring).  Likewise, interactions (between loci), called epistasis, is also not directly transmitted.

There are many practical as well as political reasons to believe that interactions can be ignored.  In a practical sense, even multiple 2-way interactions make impossible sample size and structure demands.  But in a political sense, additive effects mean that traits can be reliably predicted from genotype data (meaning, even at birth): you estimate the effects of each allele at each place in the genome, and add them to get the predicted phenotype.  There is money to be made by that, so to speak.  But it doesn't really work with complex interactions.  Strong incentives, indeed, to report additive effects and very understandable!

Secondly, all these various effects are estimated from samples, not derived from basic theory about molecular-level physiology, and often they are hardly informed by the latter at all.  This means that replication is not to be expected in any rigorous sense.  For example, dominance is estimated by the deviation of average traits in AA, Aa, and aa individuals from being in 0, 1, 2 proportions if (say) the 'a' allele contributed 1-unit of trait measure.  Dominance deviations are thoroughly sample-dependent.  It is not easy to interpret those results when samples cannot be replicated (the concepts are very useful in agricultural and experimental breeding contexts, but far less so in natural human populations). And this conveniently overlooks the environmental effects.

This study is of a small sample, especially since for many traits it now seems de rigueur to have samples of hundreds of thousands to get reliable mapping results, not to mention a confusingly defined trait, so it's difficult, at least for me, to make sense of the results.  In theory, it wouldn't be terribly surprising to find a genetic component to risk of reading disability, but it would be surprising, particularly since disability is defined only by test score in this study, if none of that ability was  substantially affected by environment.  In the extreme, if a child hasn't been to school or otherwise learned to read, that inability would be largely determined by environmental factors, right?  Even if an entire family couldn't read, it's not possible to know whether it's because no one ever had the chance to learn, or they share some genetic risk allele.

In people, unlike in other animals, assortative mating has a huge cultural component, so, again, it wouldn't be surprising if two illiterate adults married, or if they then had no books in the house, and didn't teach their children that reading was valuable.  But this doesn't mean either reading or their mate-choice necessarily has any genetic component.  

So, again, same data, different interpretations  
But why?  Indeed, what makes some Americans hear Donald Trump and resonate with his message, while others cringe?  Why do we need 9 Supreme Court justices if the idea is that evidence for determination of the constitutionality of a law is to be found in the Constitution?  Why doesn't just one justice suffice?  And, why do they look at the same evidence and reliably and predictably vote along political lines?

Or, more uncomfortably for scientists, why did some people consider it good news when it was announced that only 34% of replicated psychology experiments agreed with the original results, while others considered this unfortunate?  Again, same facts, different conclusions.

Why do our beliefs determine our opinions, even in science, which is supposed to be based on the scientific method, and sober, unbiased assessment of the data?  Statistics, like anything, can be manipulated, but done properly they at least don't lie.  But, is IQ real or isn't it?  Are behavioral traits genetically determined or aren't they?  Have genome wide association studies been successful or not?

As Ken often writes, much of how we view these things is certainly determined by vested interest and careerism, not to mention the emotional positions we inevitably take on human affairs.  If your lab spends its time and money on GWAS, you're more likely to see them as successful.  That's undeniable if you are candid.  But, I think it's more than that.  I think we're too often prisoners of induction, based on our experience, training, predilections of what observations we make or count as significant; our conclusions are often underdetermined, but we don't know it.  Underdetermined systems are those that are accounted for with not enough evidence.  It's the all-swans-are-white problem; they're all white until we see a black one. At which point we either conclude we were wrong, or give the black swan a different species name.  But, we never know if or when we're going to see a black one.  Or a purple one.

John Snow determined to his own satisfaction during the cholera epidemic in London in 1854 that cholera was transmitted by a contagion in the water.  But in fact he didn't prove it.  The miasmatists, who believed cholera was caused by bad air, had stacks of evidence of their own -- e.g., infection was more common in smoggy, smelly cities, and in fact in the dirtier sections of cities.  But both Snow and the miasmatists had only circumstantial evidence, correlations, not enough data to definitively prove their were right.  Both arguments were underdetermined.  As it happened, John Snow was right, but that wasn't to be widely known for another few decades when vibrio cholerae was identified under Robert Koch's microscope.

"The scent lies strong here; do you see anything?"; Wikipedia

Both sides strongly (emotionally!) believed they were right, believed they had the evidence to support their argument. They weren't cherry-picking the data to better support their side, they were looking at the same data and drawing different conclusions.  They based their conclusions on the data they had, but they had no idea it wasn't enough.  

But it's not just that, either.  It's also that we're predisposed by our beliefs to form our opinions.  And that's when we're likely to cherry pick the evidence that supports our beliefs.  Who's right about immigrants to the US, Donald Trump or Bernie Sanders?  Who's right about whether corporations are people or not?  Who's right about genetically modified organisms?  Or climate change?  Who's right about behavior and genetic determinism?  

And it's even more than that! If genetics and evolutionary biology have taught us anything, they've taught us about complexity.  Even simple traits turn out to be complex.  There are multiple pathways to most traits, most traits are due to interacting polygenes and environmental factors, and so on. Simple explanations are less likely to be correct than explanations that acknowledge complexity, and that's because evolution doesn't follow rules, except that what works works, and to an important degree that's what is here to be examined today.  

Simplistic explanations are probably wrong.   But they are so appealing. 

Would you still go into the lab if you knew life on Earth was going to end tomorrow?

One of the most stubborn tenets of a strict Darwinian view of the world is that we are inherently selfish.  Thus, everything we do is to enhance our fitness, to get as many of our genes into the next generation as we possibly can, by hook, by crook, by wile and deceit.  Even if we help relatives, we are doing it only because they share our genes and, therefore, it's good for us. If we help strangers, that, too, is rationalized by the notion of reciprocity--we do it only because they'll help us later.  It's a 'theory' that can rationalize anything that seems at odds with it, a theory that can't be falsified!

Given all this, the June 29 episode of the BBC Radio 4 program Analysis, a discussion with philosopher Steven Scheffler of the idea of the collective afterlife, is an interesting one.  Scheffler recently published a book called Death and the Afterlife, drawn from a series of lectures, in which he in no sense means that we will have any kind of life after we have died.  He is concerned instead with the life that continues on without us, after our deaths.  He proposes a number of thought experiments to help elucidate how we feel about just that.

The BBC program began with two questions for the audience -- "Do you believe that people and the earth will continue to exist after your own death?"  And the second, "If you knew that Earth would be destroyed 30 days after your death by a collision with a large asteroid, would that change how you live your life?"  Another perspective on the same sort of question is what the detective novelist P.D. James wrote about in her 1992 book, The Children of Men, about the end of fertility in the human race.  The disease didn't threaten living people, but did mean the end of the entire human race. Would knowing that no humans would follow you on Earth change how you live your life?

Artist's impression of impact from a major meteor; Wikipedia

Scheffler believes that the afterlife, knowing that generations of people will follow us, matters more to us than we suspect and that upon pondering the question of how knowing the Earth would be destroyed soon after we die might change the way we live, most of us will come to realize that we might very well lose any sense of purpose, despite the fact that it's not our own life that is threatened. And this would change the way we live.  This means, says Scheffler, that much of what we do we do not for ourselves or even our children or grandchildren, but for unknown people who will come after us, because there will be people who come after us, and not just those we love.

Most obviously, if what you do now is something that isn't going to make a difference now but might in the future, would you continue doing it?  Would it make sense to keep working on finding a cure for cancer or reversing climate change if you knew there would be no one left to benefit?  But there would be other effects, Scheffler believes.  We would stop making art, or music, or creating literature, or writing history or doing any kind of scientific research.  If the issue was the infertility scenario posited by PD James, she suggests people would stop having sex, even when, as in her book, governments keep urging people to try, just in case someone somewhere hasn't been affected.  Scheffler says that he himself is sure he would stop writing papers about political philosophy.

He says, too, that the sense of horror we have about the end of the human race is different from the relative complacency most of us feel about the fact that everyone living now will one day be dead.

Boston Review quotes from his book:

My argument has been that personal survival already does matter to us less than we tend to suppose, and that the survival of humanity matters to us more. In saying this, I am not underestimating our powerful impulses to personal survival or the deep terror that many people feel when contemplating their own deaths. Nor am I denying the importance of self-interested motivations in ordinary human behavior. My point is that despite the power of these attitudes, there is a very specific sense in which our own survival is less important to us than the survival of the human race. The prospect of the imminent disappearance of the race poses a far greater threat to our ability to treat other things as mattering to us and, in so doing, it poses a far greater threat to our continued ability to lead value-laden lives.

Well, think about this from a Darwinian perspective.  A strict Darwinian could certainly twist it to fit theory perfectly well -- caring about the welfare of those who survive is completely in keeping with the urge to perpetuate our genes while we can.  Or, perhaps, we don't really believe we're going to die, so our caring is really about the usual reasons.

But I was talking about this with a friend the other day who is on the board of a number of conservation organizations, and is very active himself in nature preservation.  He said, "I have no children, so I sometimes wonder why I care so much about conservation.  Clearly, it has nothing to do with me."

A Darwinian might argue that he's doing it for his sister's descendants, to whom he's related, or even that he's related to the whole human race, so of course he cares.  But if we're related to everyone, and anything we do perpetuates our own genes, because all humans share genes, this trivializes the whole idea of "survival of the fittest," the backbone of Darwinian determinism.  It makes the 'theory' so generic that it loses any specificity and hence becomes in that sense essentially vacuous.

I think that there are so many exceptions to the Darwinian view of life as inherently selfish and self-perpetuating by now that it's past time to stop believing that these are exceptions rather than the rule. Humans aren't mere automatons driven by our genes' need to replicate themselves. Abortion, suicide bombing, birth control and the decision to remain childless, infanticide, altruism, even much human genetic or medical lab work which is unlikely to yield results for ourselves or even our children or grandchildren, are all behaviors that make no sense in a Darwinian world of direct self-interest.  And they aren't rare.

Culture is a powerful force.  With culture, we can talk ourselves into all manner of behaviors that have nothing to do with enhancing our survival or fitness, nor that of our relatives, and in fact might do just the opposite.  We can imagine an afterlife in the 72 virgins (or raisins, depending on your translation of the Koran) sense rather than Scheffler's, we can imagine future happiness without children, we can feel good about bringing a drowning swimmer to shore without expecting he or she will do something for us in return.  Janes can avoid killing anything at all, for spiritual reasons.  We need not kludge the argument to make all this into selfishness.  Culture, what we learn and agree with others about, matters.

Why isn't anyone looking for the culture gene?

Are we still doing 'beanbag' eu(genetics)? Part III. Culpably ignored nuances?

Part I of this series was about the particulate view of genes and their role in evolution and the determination of traits that are here because they were screened by evolution.  Many view all traits as being in this category, and genetic determinism of those traits to be very strong and specific.  But the data are less clear by far than the commitment to that idea.

Ernst Mayr criticized the one-gene-at-a-time focus of much of population genetics as 'beanbag' genetics.  Mayr said that this was wrong for reasons we mentioned in Part I.  As we discussed there, JBS Haldane, one of the grand ol' men who developed population genetics, wrote in defense of the field, in response to Mayr's criticism.

Haldane was a highly educated, thoughtful, perceptive British biologist whose life was nuanced in many ways that make telling a clear-cut story difficult.  He was brilliant and exceedingly skilled.  But he was also a product of his times, as are we all.  In the early 20th century he became a Marxist, as did many other British aristocrats, accepting all that implies about what determines the structure of human society.  Marxism was materialist but it was about improvability of individuals--an egalitarian view that claimed that position in a class-based society was due to class, not inherent inferiority of the lower classes, and thus that social inequity could--indeed would be erased by the processes of history.  At the time, the Soviet Union seemed a Great Hope to many in heavily unfair empirical Britain.  That essential malleability was one reason that the Russian plant geneticist Lysenko rejected Mendelian/Darwinian models of genetics in favor of a more Lamarckian mode of inheritance by which plants could be conditioned to have desired properties, and those would then be inherited. That proved in many ways to be a disaster for the Soviet Union.

Nonetheless, Haldane, who was a leading popularizer of science in his day, published a collection of reprinted essays in 1932 entitled The Inequality of Man.  Ironic for a Marxist, but he was not simplistic.  He dealt with, and accepted, the idea of eugenics in those essays, and that was largely what the title referred to.  He acknowledged the major role of environment in making people what they turned out to be. But he stressed that genetics was part of human makeup, too. Rather than a more balanced treatment, at points he lapsed into the aristocratic view about intelligence and in that sense, inherent societal worth.  The upper classes were what they are because of their abilities, and were under-reproducing compared to the lower classes.  He even wrote of society not having the guts to kill its lesser citizens: despite warning about too much stress on inherency, in one article he wrote:

"The danger to democracy to-day lies not in the recognition of a plain biological fact [of inherent inequality] but in a lack of will in certain countries to kill persons who obstruct the declared wishes of the majority of the people."  Further, "The only clear task of eugenics is to prevent the inevitably inefficient one per cent of the population from being born, and to encourage the breeding of persons of exceptional ability where that ability is known to be hereditary."  There should not be a democracy except of a better minority.

There is a mix of views in Haldane's chapters, ranging from the autocratic extreme to something more humane and nuanced.  He discusses social class, race, and intelligence as related to achievement, and even within Europe he makes distinctions about intelligence between (guess who!) northern and southern Europeans.  But he also promotes improved opportunities and acknowledges that we don't know the nature or extent of hereditary control of traits like intelligence.  In these popularized articles on many sociocultural issues, he is a softened genetic determinist. Perhaps this could be a Marxist 'from each according to his abilities, to each according to his needs' view; but that was always paternalistic when pronounced from on high.  Haldane, like many scientists who are given a public forum, strays far and wide beyond what he knows best, and nearly a hundred years on we can see his only too human opinions.  Life is complicated!

In any case, though the rhetoric is generally changed, we see roughly the same spectrum of views today, but that is in many ways implicitly a bean-bag model of inheritance.  In his day, the idea of identifying the genes that cause the traits of interest was technically not possible.  Now, in the excitement of 'omic technologies, the beanbagger approach is more explicit, noting this or that genetic variant that causes some socially relevant behavioral trait.  This viewpoint is widespread, despite some occasional caveats about complexity and even if there are many labs working on more integrative approaches to that complexity.

The difficulties
These are not simple issues.  People are different in physical, metabolic, and behavioral ways and clearly genetic variation is involved.  Depending on one's social politics, that can be a central or an uncomfortable fact.  But let us assume, for the moment and for argument's sake, that all the genetic determinism that has been proposed were perfectly true.  Then what?

The idea in the writings of various authors, from the past and today, is essentially about what 'we' should do to mold society this way or that.  But who are that 'we'?  They're the professors, politicians, and so on, who in positions of influence make the judgments about what 'we' as a society 'need' to do. 'We' want more intelligence and less addiction and crime (as defined by 'us', of course; usually 'we' aren't talking about white-collar crime).  'We' decide what would be 'good' for society and what should be discouraged.  And there is always the temptation to attribute inherent causation to these differences.

So, for example, we decide what do to with (or to?) those of higher and lesser inborn intelligence. This is rather indisputably arrogant and presumptuous, isn't it?  Or, perhaps, one can ask whether it is any different from what has gone on heretofore.

If the minority of the privileged have the power to decide on societal action, it is rather moot whether the criteria used to justify that action are presumed genotypic ones or just the arbitrary wielding of power.  Does it matter whether Divine Right or 'good genes' is credited with the power of the elite, and the subservience of the rest?  The powers-that-be define the value judgments.

Genotypes may have more, or less, determinative roles than is widely being claimed these days. Eugenics was a particular kind of social control, that had regularly dreadful, indeed lethal, consequences for many people for various reasons. But whether that was any worse than religious or other political dominance is an open question.

Does it matter if it's an ISIS member who chops your head off because of your religion, or a Nazi who gasses you because of your ethnicity, or a physician who decides what genotypes need to be screened prenatally and eliminated, or who gets educational resources?

We have our own personal view, which is that the data generally do not support the making of such decisions based on genotypes and their presumed predictive value--and decisions related to those genetic variants that really do have such value should only be made privately, rather than by public policy.  But the public pays for the treatment of genetic disease, so at what point is coercion within the scope of such an idea?

It is not clear whether these issues really ever get 'solved', or whether rational, measured discussion is even possible.  But it does seem clear that questions about how genes control, or don't control, the traits in organisms are worth understanding, rather than action being taken on vague assumptions about inherent causality before the questions are even answered.

Are we still doing 'beanbag' eu(genetics)? Part II. History's unlearned lessons?

Yesterday we discussed some of the ways in which particularized views of genomic control and evolution were controversial and that, despite much more knowledge now than when the issues first surfaced nearly a century ago, they are still with us in largely unchanged form--even if with massive amounts of data and lots of chest-thumping about how modern our current view is.

One consequence of a genomic causation as highly deterministic and specific is that one comes to believe that once a person is conceived, his or her genome essentially predicts his/her life so that, in particular, we can (a) work preventive miracles in regard to disease, and (b) think of designing the traits we would like to engineer in our offspring.  But the issues of genomic determinism are not at all new.

A new paper by Donald Fosdyke, a Peer J pre-print ("The relative roles of politics and science: William Bateson, black slavery, eugenics and speciation"), shows how controversies about genomic causation began in the late 1800s, not that long after Darwin's Origin of Species was published. Insufficiently circumspect appropriation of Darwinian ideas that occurred, contained within it the horrors of human abuse that would occur, under the rubric of eugenics, in genetics' and evolution's name.  And those issues, like the ones we discussed yesterday, are very much still with us.  Now, in principle at least, we have a chance to learn from history rather than repeat it.  But the signs that such a benign outcome is likely are not very favorable.

Wm Bateson.  From nndb.com, on Google images

William Bateson (1861-1926) was a leading biologist in the formative decades after Darwin's ideas of evolution and Mendel's of genetic inheritance were swirling in scientific circles.  Mendel showed how stable, discrete traits were heritable, and essentially determined--to wit, the presence or absence of traits in his peas.  Mendelian inheritance was 'rediscovered' in 1900 and seemed to provide a sound idea of inheritance.  However, discrete Mendelian traits seemed at the time to be inherited without change.  Such stability and discreteness were inconsistent with the apparent nature of adaptive evolution that Darwin had suggested.  His idea was that traits vary infinitesimally among individuals and selection very gradually moves the resulting traits in a population to adapt to environmental change.

What was 'eugenics'?
The idea that society is composed of the ordinary and their betters is not new.  It has long been part of the rhetorical, religious, and material ways in which the minority justify their position and dominance over the masses.  That the role of the upper classes in pursuits like gluttony, debauchery, and warfare might be a danger to them, and hence to society as a whole if it must suffer without those lost in such endeavors, was a concern even to the classical Greek philosophers (well, they mainly worried about the warfare part).

In the years after Darwin's ideas were published, these concerns about what was good in bad in human nature, or who were the good or bad individuals in society, took on the panache of science, replaying, one might say, similar judgments made by invoking the will of God--the Divine Right of the upper classes, the inherent inferiority of non-Europeans that justified slavery, and so on.  If evolution generated the truly-better, and that means genetically better, then the loss of the social elite to disease or warfare deprived society and its future patrimony of the best genes in the gene pool.  And in any case, it is problematic that the masses outnumber the elites, yet have inferior genes.  Or, to be a bit more charitable, it was thought that it was possible to distinguish between individuals who really were lesser--inherently criminal, drug-abusers, amoral, slovenly and the like--vs those who were better.  The latter were the intellectual, scientific, military and other such leaders.

Now that Darwin had showed us how evolution worked, and that its workings were all about Nature making mortal value judgments (survival of the fittest), modern science could be used to further Nature's plan, speed it up, and ensure that bad luck didn't thwart that plan.  The effort to use science for human and evolution's betterment was called eugenics. The key factor, of course, was reproductive success.  Thus, if differences in individual character could be discerned, we could impose incentives to enhance the reproductive efforts of the better and lead the lessers to voluntarily restrain their own proliferation; that was called positive eugenics.  If this didn't work, we could screen the population for those with better and lesser inherent qualities, and use social mechanisms to impose restricted reproduction on the latter.  This was called negative eugenics.

The idea that genes specify who we are, implicitly meaning that even through the fog of culture, environment, and experience, has great appeal.  It's simple.  It leads to effective prediction.  It can be built into policy.  The eugenics movement was an application of Darwinian thinking that assumed many simplistic and/or unverifiable ideas about what Nature 'wanted' and which genotypes (and, of course, their specified traits) were good and which weren't, led textbook authors and research institutes to declare these things and this in turn reflected and/or led to policy imposed by society onto its citizens.  We know what happened in nearly a century of the imposition of 'science' to manufacture such ends.

The temptation was to think of traits as single-gene, or clearly 'genetic'.  Traits that are complex, such as we know many behavioral and common diseases are, can't be attributed to single genes or even a small list of additive contributors (though they can be modeled that way in statistical studies). Because the many components of complex genotypes recombine and shuffle their components among individuals and across generations.  For that reason, thinking of these traits as due to a bean or two from the beanbag is misleading and, essentially, erroneous relative to the underlying causal principles (themselves not yet very well understood).

Whether or not one holds a eugenic view of this sort, the policies in the name of eugenic 'science'--even if that was just a rationalization for what  politicians would do anyway--led to some of the worst horrors in human history, both to individuals and to whole groups.  The lesson was learned, and led to a prevalent environmentalism after WWII, where explicit eugenics was basically itself 'blacklisted'. But memory is short, and the hubris of scientists powerful.  Eugenics, in various new forms, is back.

Neo-eugenics: modernizing a ghastly idea (oh, no harm of course!)
Many readers may have seen the 19th-century-like OpEd in the recent NYTimes ("The downside of resilience," Jay Belsky), that advocated screening all children for a couple of markers of their personality and response to education.  Of course, it was all couched in terms of salubrious value to society--eugenics started out and was often proclaimed that way.  'We' just have to test 'them' (all school children) to find those who need special help to respond to schooling as well as others (another value judgment that the 'we' make about the 'them'), and then we can devote extra resources to those with sub-par performance.  Sure!  That is about as naive as believing in Santa Claus.  What history shows will likely happen is that the well-off will argue, with demagogues in politics at their side, that this is a waste of resources, which should be devoted instead to those like us, who will deliver for society's betterment.  If you think it will be otherwise, then you should go straight to the Mall and tell Santa what you want for Christmas.

In a sense, from our point of view, it doesn't matter if these sub-par-performance traits are 'genetic' or not.  The point is we have zero serious need to 'diagnose' them by genotyping.  We know that even for the vast majority of diseases, actual phenotypes are better predictors by far than genotypes.  So, if a trait is harmful, as disease or other limitations, we need only observe the trait itself or its prodrome--the signs it is coming.  We can learn to identify these things earlier, but at least we only 'treat' those who actually have the trait.

Since such traits are at most only partly, usually slightly genetic, we have no real need to do the genotyping afterwards, either.  Such traits might need therapy the way any disease needs therapy. There is not much gain in knowledge.  A 'beanbag' approach or conceptualization makes policy decisions seem easy but in fact makes much of the inference at best inaccurate to an unknown (perhaps unknowable) degree.

The reason for restraint is that, as history clearly shows , social engineering to protect those in power and influence is typically detrimental to those with 'undesirable' traits.  The value judgments are sometimes, if not perhaps often, based on irrelevant correlates (such as 'race').  But the consequences are that some group of 'we' decides what to do for (or to) some group of 'them'.

As the Fosdyke paper shows, these issues are not new, and even Bateson himself (who coined the term 'genetics') warned about the lack of knowledge of the complexities of biological trait determination, and the tendency towards unjustified eugenics a century ago. Fosdyke quotes Bateson from a 1905 piece of his in The Speaker:

What ... will happen when ... enlightenment actually comes to pass and the facts of heredity are ... commonly known? One thing is certain: mankind will begin to interfere; perhaps not in England, but in some country more ready to break with the past and eager for ‘national efficiency.’ ... Ignorance of the remoter consequences of interference has never long postponed such experiments. When power is discovered man always turns to it. The science of heredity will soon provide power on a stupendous scale; and in some country, at some time, not, perhaps, far distant, that power will be applied to control the composition of a nation. Whether the institution of such control will ultimately be good or bad for that nation, or for humanity at large, is a separate question.

                   W. Bateson, ‘Heredity in the physiology of nations.’ The Speaker, 14th Oct (1905).

Bateson had many different ideas on genetics, but in a sense his approach was rather beanbag in nature, thinking of 'gene' as an independent causal agent (though so far before actual genes or their actual particulate nature were known that 'beanbag genetics' really can't apply to him). He was not convinced that Mendelian factors could even account for evolution.

Things are complex and so were the commenters during the eugenics era. Even JBS Haldane, about whom we wrote yesterday in Part I of this series, was a mix of viewpoints. He was a founder of the genetically based area of population genetics that became and still generally is viewed as 'the' formal theory of evolution. It rests on genetic determinism to a great extent, and the idea that what is here is because the relevant causal agents--the genetic 'beanbags'--were closely scrutinized and favored by natural selection. That idea, which certainly has much truth behind it, makes it complex when it comes to judgments about human traits that affected the eugenicists then (and their descendants today). We'll deal with that in Part III.

Bateson warned us about the issues before the major abuses that led to the disasters of the mid-century--human experimentation, Nazi genocide, forced sterilizations and institutionalization. Of course, in the hubris of the new genetics and evolutionary theories of the time, nobody listened to warnings. Too many listened to pompous, self-assured scientific 'experts' who were, of course, always speaking for the public good. And we all know what happened.

However, it is also fair to say that in the absence of relevant information, many different views were circulating around at that time, as the new ideas and discoveries were being assessed. One must be judicious in giving too much hindsight-based credit to views that seem now to have been prophetic. Nonetheless, when a cycle seems to be repeating, it is proper to note how history unfolded even within living memory.

Are these statements too cautious? Is there no chance of a return of the last century? Maybe. Of course a 'return' will have its own form, its own rhetoric, and its own consequences. Some may be quite good (such as effective genetic prenatal counseling for clearly known devastating genetic disorders). But in science as in politics, religion, or other areas of human affairs, the hubris and excitement of such success historically leads to excesses. There are many things we are not allowed to do, such as falsely shout Fire! in a crowded theater. The restrictions on science an always be revised and where risks may exceed benefit, work should just not be done: there are plenty of less ambiguous ways to invest in science for human betterment.

The time to take care of your horse is before it leaves the barn.

What if Rev Jenyns had agreed? Part II. Would evolutionary theory be different from a population perspective?

In yesterday's post I noted some general differences between Darwin's individual-centered theory of evolution, and AR Wallace's more population-focused ideas.  Of course they both developed their ideas with the kinds of knowledge and technology then available, so we can use them to represent differing points of view we might hold today, but must realize that that is symbolic rather than literal. They were who they were, both skilled and perceptive, but their ideas were subject to modification with subsequent knowledge. One major piece of knowledge that emerged after their time was that genes are point causes of biological function, that is, single locations in DNA with distinct activity.
But that knowledge was derived from Mendel, Morgan, Watson, Crick and a host of others, who, following Mendel, pursued genetic function with independent point causation as the assumed starting point that drove their study designs.  DNA may be atoms on a string, but the assumption was misleading then, and still is today.

Alfred Russel Wallace

The modern theory of evolution, population genetics, is based on genes as point causes, and it recognizes the local nature of evolution in time and space.  A genetic variant's chances of spreading in a population are, naturally enough, seen in population perspective.  But by and large that perspective is about a genetic variant, and indeed attempts to explain functional and adaptive evolution from a single gene's point of view.  The variant's success depends on the relative success of other variants at the same locus--competition.  Of course that success depends on many things, but this perspective basically just 'integrates' away all factors other than the gene itself, computing a net-result picture.  It is very 'Darwinian' in the sense of being strongly deterministic and considering genes as points individually competing with each other for success.

This is not a fallacious picture, but I think it's not terribly relevant to the kinds of questions most people are asking these days, both in evolution and in biomedical genetics.  One needn't deny that individual genetic variants don't have their differential success over time, or that we can't or shouldn't be aware of nucleotide differences.  To do so would be something like denying that a house is made of bricks, the bricks can be identified and enumerated, and they have something to do with the nature of the house.  The question is the degree to which you can explain or predict the house from the enumeration of the bricks.

There are those who suggest that evolution is more about interaction at the genome level than it is about single alleles; enumerating bricks is not enough. However, the allele-focused view would have it that it is only the 'additive' aspect of each individual allele's effect on its own, that is transmitted. The idea is that even if the combination of alleles at and among loci affect an individual's traits (roughly, this is called 'epistasis'), s/he only transmits a roughly random half of those to each offspring.  Thus, the combination effect is not inherited.  Epistatic holism is an evolutionary hoax.

This venerable riposte to those arguing for a more 'holistic' or complex genomic viewpoint may be mathematically true in the abstract, but misses an important point.  In fact, the fitness (reproductive success) of a given allele entirely depends on the rest of the genome and the external environment.  If you just think about how life works (that is, metabolism, morphology, and many other complex interactions), the dependency is very unlikely to be simply additive. Things work, things adapt in combinations.  But we'll see below how this squares with the additive-only view.

In fact, the collective context-dependency of each allele's functional effects means that the evolution of a population is dependent on its mix of genomic variation--which brings us back to Wallace, and is what group selection is properly about.

Group selection: why a bad reputation?
Group selection got a bad reputation in part when a book by VC Wynne-Edwards was published in 1964 that claimed that in many species, individuals restrained their reproduction essentially for the good of the group (whether or not this was done knowingly for that purpose).  This was a kind of fitness-related altruism that was ridiculed on the grounds that if I restrain my reproduction for the good of the group, others may not be so restrained and any genetic variant that led me to do what I did would thus be out-competed.  So group selection was out, but WD Hamilton introduced concepts of extended kinship to explain altruistic behavior, such as why I might help someone at a cost to myself--if that someone were a relative, for example.  Hamilton's rule became dogma and explains much of the sociobiology of our era still today (though the rule doesn't really work very well when closely tested).

In this sense, group selection was viewed or modeled as driven by single genes and the argument was how an individual 'altruism' gene could possibly sacrifice itself and still get ahead, the one coin of the realm recognized by the most strident of Darwinists.  In recent years, various defenses of the idea and proposed mechanisms have been offered, usually with no reference to Wallace's more ecological concept.  The reason his views might be relevant is not that he thought about this in modern terms, but because he recognized that the collective qualities of the group--its overall members' traits--are what affects the group's chances of confronting the environment or other populations that it faces.

But in fact I think that while the evolution of altruism is an interesting question, it is a red herring that has given group selection a bad name.  Because there is a lot more about group selection than that gene-centered, restricted argument would suggest, and it's fundamental to life.  Indeed, it is possible that Wallace's idea, that the properties of the group determine its success, is more cogent than the gene-focused version--but for different, wholly non-mystical reasons.

Group selection, more properly conceived
The answer in brief is not a new fact but a different way of weighing the facts.  It is based on the indisputable fact that DNA is, by itself, quite an inert molecule. Anything it does is only in context.  The chance of an allele being successful depends on what else it finds itself combined with.  If in that context, the allele's effects are harmful, it has reduced prospects.  But if it finds itself in genomic and environmental circumstances in which it functions well, it can proliferate.

But what determines those genomes?  It's the relative frequency of their alleles in the population.  This is the result of the genomic history of the population as a reproducing unit.  Unless quickly removed, our new allele will see itself, probabilistically, in the company of other variants in the individuals who carry it.  If the number of those variants, and/or their frequencies, in which it can have positive effect is high enough, it has an increased chance of proliferating.  This is, in a legitimate sense group selection, because genomewide the success of the group depends on its collective distribution of alleles.  (Here we're not considering how that collective success operates, whether in terms of mating, avoiding predators, finding food, dealing with local climate, etc.).

The same variant that does very well in one genomic or environmental setting may do very poorly in another.  This is another manifestation of the central fact that a variant has no predetermined effect on its own.  It's why personalized medicine, based on predicting disease from genotypes, has a long way to go, at best, for other than very severe, largely early onset traits.

It is not that the individual variant, or the individual person, isn't important, or that we can't trace the frequency change of the variant, just as has been done for decades by population genetics theory.   But it misses the important collective aspect of an allele's success.  It's like the fact that we can count the bricks that make up our building, but we are hard-pressed to understand the building that way.

Over time, a successful population accumulates enough variants in enough genes that enough newly arising alleles are in favorable 'soil' to confer viable effects on individuals who bear them.  A population depauperate of enough of an allelic mix, genomewide, dies out.  This is, in every meaningful and non-mystical sense, a group phenomenon and if the term hadn't already been abused, group selection.  If a population perspective is really the most important one for understanding genome dynamics, then our usual genetic reductionism is misplaced.  

The Normal (bell-shaped) distribution of so many traits, like stature; UConn WWI recruits

Everyone in a population differs a bit but most people, for most traits, are rather near the middle.  The roughly Normal (bell-shaped) distribution of traits like human stature is a reflection of this.  There are those in the high- or low-end tails (very tall or very short), but most are near the middle.  There is a strong 'central tendency'.  Where does that come from?  It is a direct reflection of an evolution that makes most people inherit what in their collective ancestry has evolved as a 'fit' state for that population's circumstances.  There are always new mutational variants arising, and if the population--the 'group'--had not evolved this central tendency, it would not be a healthy one, and that would affect the likely fate of new mutations.  There are exceptions, but the restricted variance of natural populations, the tendency of most individuals to be quite similar, reflects what is, in fact, a form of group-selection history.

A major way in which this can arise, given that we have genomes made of multiple chromosomes and there is recombination and we are diploid but pass on only half our genome complement, is for many different genomic factors to affect a trait--for it to be 'polygenic'.   I think that it is the assembly of many more or less equivalent parts, independently segregating, that enables most individuals to inherit what the population's previous history has proved viable, that is, multiple independent contributors is why such central-tendency, limited-variance characteristics are so widespread.  Gene duplication and other processes help generate this state of affairs.  It's the way molecular interaction works; if things had been too genetically unitary, survival would have been more precarious.

From this perspective, the standard 'selfish gene' viewpoint's denial of the importance of epistasis and other contextual elements of gene function is off the mark.  It misperceives the nature and vital importance of the population in which these combinations exist, and the necessity that those factors be there, in enough numbers and/or with high enough frequency.

So, Wallace again?  But wait--isn't it individuals who reproduce or not?
But what about those individuals, on whom a century of population geneticists and countless popular science writers, have placed their hyper-competitive hyper-individualized stress?  The individual, driven by some critical genetic variant survives or not.  Individuals as wholes are viewed (or should we say dismissed), essentially, as mere carriers of the gene whose evolution is being tracked.  The context of population may be real, as discussed above, but the individual, basically a manifestation if its genotype, is what selfishly acts and determines success. No?

Sure, in a sense.  But the variant's prospects depend on the collective, and it's mutual, or relative.  Variant One is affected by Variant Two--but Variant Two is affected by Variant One, and so on.  The individual, or worse, individual gene focus is something one can compute, but it is misleading.  And, in fact, the situation is even more problematic in respect to what individuals actually are, genomically.

In Part III, I'll discuss how individuals, too, are being misperceived as the ultimate functional units based on their individual genotypes, either as wholes or in terms of specific genes.  Again a group or population perspective has an important, largely unrecognized role to play in individuals' and hence groups' success.

Wallace was onto something that's rather absent in Darwin, and still absent today as a result of the fact that the particularist aspect of Darwin's and Mendel's view prevailed.

Insanity: genes 'versus' environment as causes

There are two statements about humans, or other organisms for that matter, that may seem inconsistent but that are both as solid as the Rock of Gibraltar, as fundamental and central as atoms to chemistry. Because of their deep importance, we feel that we must go beyond just stating these bedrock findings, and give rigorous proof of their truth.

Theorem 1. Genes cause every human trait!
Proof:  Without genes cells could not function, embryos could not develop, and there would be no humans to have any traits.

Theorem 2. Environment causes every human trait!
Proof:  Without their surroundings, differential gene expression would not occur, tissues would not differentiate, and there would be no humans to have any traits.

Given these incontrovertible proofs, it should seem rather trivially obvious that the search for the causation of any trait, should never be couched in one term or the other (genes or environment).  It is always genes and environment.  The legitimate interest in any search for biological causation should be clarified, first of all in the investigator's mind.  But this seems often, or even usually, not what happens when studies are designed, funding requested, or results reported.

Rock of Gibraltar; Wikimedia

As a result, there is a lot of needless contention and, sometimes, even abusive dismissal of points of view, in discussions of both the evolution and presence of human traits--be they normal or disease traits.

Unfortunately, it is not easy--even in principle--to separate these issues neatly.  For example, those who cling to genetic essentialism dismiss environmental causation as largely incidental or beside the point. Even 'epigenetics' is too close to environmental causation to be acceptable.  True enough, like many things in today's world of science (indeed, probably always typical of human affairs), we have fads and current epigenetic studies are in part just that--a way to get grants, get papers in the 'name' journals and get news attention.

However, epigenetics refers to the means by which gene expression is regulated.  Cells are always sensing their environment in various ways that lead to modification of their chromosomes that controls which genes are used and which are shut down.  In that very fundamental sense, every trait is an epigenetic trait.  Indeed, a given gene's 'environment' includes what's going on in the rest of the genome in that same cell.  The nontrivial scientific questions concern when, where, and how epigenetic mechanisms are at work in some context of interest--how the environment affects gene usage and its results.

Pure environmentalism is, however, also a fantasy.  Cells are genetically programmed to respond to their environments in various ways, ignoring some signals from the outside world, but responding to others, depending on its developmental stage and context.  Likewise intracellular conditions.  Genetic variation simply must be related to and circumscribes these responses.  It's this kind of sensing of environment-specific signals that causes one cell to become a stomach cell and another a brain cell, or for cells to divide or not, or produce particular proteins. Multicellular organisms wouldn't exist without differential cellular responses to environmental signals.

In this context, genomic causation and the evolution of genomic causation are similar.  Evolution only affects genotypes and environments that exist at any given time and place.  That variation changes in terms of its proliferation in its immediately local ecological context, which for convenience and perhaps having no better ideas, we usually consider as a phenomenon of relative frequency in some specified population. But these are abstractions of convenience whose relevance should be (but often rarely is) tested.  In any case, biomedical causation--like the genomic basis of autism or any trait you want to consider--similarly refers to some specific local context.

When incidence of a disease changes very rapidly, even if the trait has a genomic underpinning--and as we said above, every trait does--the change in incidence is very unlikely to be due to major changes in the local gene pool.  In that sense, it would be properly said to be 'environmental'.  Traits like autism, obesity, asthma, the success of Chinese ping-pong players, and many others are in this category.  Such attributions get under the collar of those whose careers and worldview are centered around genomes as the sole important determinants of life.  The response to rapid change may be acknowledged to be environmental, but in what seems to be a rather trivializing sense (yes, they might agree, China has manufactured millions of ping-pong tables which didn't before exist, but the champions are champions because of their Chinese genes).

A defense of the largesse of medical genomic research is that increased prevalence of disease is due to specific genotypes responding to the environmental change.  That is, environmental variation is leading to an epidemic of obesity because McFood triggers responses from some tractably few variants in the population that, before McFood, did not lead to disease.  Thus, the justification for expecting genomic 'causation' even when environment is the real 'cause'.

In fact, genomic variation changes just as fast as environments.  In a population (however you choose to specify it), alleles are coming and going.  A trait may in large part be the result of action of many different, individually rare, elements in the genome acting in their particular environment.  This coming and going means that the genes are as fluid in many ways as is the environment (however you may specify that).

The same applies to evolution
The same applies to much of the selectionist arguments for traits we see today.  Environmental change is of course the 'cause' of natural selection, and in a new environment selection will favor those few genes that confer major advantage (and will remove the alternative variants that, in the new environment, don't function well any longer).  So, our traits today should reflect selection history in a tractable way and we can see what is 'good' and not so good based on Nature's past decisions.

You can see the tangle of interests and rhetoric in contending views that are prevalent these days and soak up a lot of resources that might be devoted to things that are overwhelmingly 'genetic' (like cystic fibrosis) or 'environmental' (like the effects of exposure to CT scans).  But even this is a bit of false reasoning in defense of vested interests, because even most such traits are not so genetic rather than environmental or vice versa.

"What?  You don't think even a broken gene, that doesn't even work at all, doesn't lead to consequences that are purely genetic?  You don't think even smoking is an environmental cause of disease?"  The answer is: that's right.  For example, most of us are walking around with many 'broken' genes that have been identified as causes of disease, yet we don't have the disease.  We do a gene knockout in lab mice and they may get the same disease as found with the same mutation in humans---but it may have little, different, or even no effect in other strains of mice.  And, of course, most smokers don't get lung cancer.

If the arguments for simple genomic selective or biomedical expectations were accurate, then mapping would identify those few genes that responded to selection pressures or that respond to environments and make us sick.  Instead, what we typically find is that traits like obesity and autism and many others (we fancy that Chinese ping-pong ability would be similar) are not arising in those with particular alleles in a few genes.  Instead, variation in tens or hundreds of genome regions contribute to the trait, in the current environment.

It is in this sense that one can make the argument that a trait like autism or obesity is mainly an environmental trait.  Even if the responses of many genes lead to the manifestation of the trait in those individuals, the genotype is different in each, and what is in common is some aspect(s) of the environment.   Similarly, environmental 'causes' may be as individual, and diverse.  So the chase for explanations makes no sense if one insists on denying one or the other category or type of causation.

Not so simple
How one relates Theorem 1 to Theorem 2 in a real-world problem is not at all easy, even to think about clearly.  It is not enough to say we'll do regression on all genomic and environmental variables (G1, G2,...Gn, E1, E2,...En), assuming such enumeration and identification could actually be done, and then add some product (non-linear) 'interaction' terms:  G1 x E1, G1 x E2,.....   This quickly leads to essentially infinitely many things to test, even with just the product assumption.  And then there is how to measure the factors.  If one gene is part of another gene's environment (in some types of cell, under some conditions) then genes can be both genes and environments.

Saying these factors 'interact' may mean there is some complex sort of network of factors that, acting in some ways as a unit, affects some other network in each individual, each uniquely, to generate some output--like a disease--and then you have to decide what the right measure is.  Are 'blood pressure', 'IQ', 'average ping-pong victory differential', or 'stature' reasonable measures of a 'trait' for which you wish to understand the causal basis? Maybe, say, the square of blood pressure or the 2/3 power, more accurately reflect what is going on.

So how genetic variants  and environmental exposures 'cause' outcomes deeply depends on definitions and what one chooses to study.  It is far from clear what to do even once you've made decisions about that.   In this light, scientists' confident assertions and grandiose study design claims are very far from actually even acknowledging much less reflecting the depth of the problem we want to solve.  So we can just say "it's genes and environment" or "only genes really matter", and try to buffalo our way through.

The question may be scientific, but the problem is sociocultural
The problem, as we often note, is the polarized view of contending parties in the face of what is so obvious.  And the explanation has to do with human society and psychology and resources.  The explanations are choices in that sense, and that makes them sociopolitical.  Each of us somehow formulates a view about what is important, what we mean by 'genes' and 'environment' and how they relate to each other.  We have to judge what is most important, what risk effects matter, where to put research resources.  Nature herself doesn't provide a guide.  Facing up to complex, uncertain causal situations is more difficult than carrying on with what one knows and has been doing....and an keep one's lab running and churning out papers.  But the ability to face up is also something a culture itself may affect.  Often, we do what we learned or what has fed us, avoiding the risk of acknowledging that there may be something better or very different to do.

Albert Einstein famously quipped that the definition of insanity is doing the same thing over and over again and expecting different results.  Maybe he was wrong.  Maybe that's the definition of human nature.

Adaptive inverse slavery in human evolution: a new evolutionary paradigm

History is generally written by the winners. The social and academic elite, the winners, have written evolutionary theory as well.  Here we rewrite evolutionary theory from the point of view of the lower classes, and turn the idea of evolutionary success, properly, on its head.  This also raises the point that plausibility isn't the same as proof.

The air is spinning with fervor over various treatments of human genetic variation that seem to serve as closet cover for classical racism.  A coterie of investigators, some of them even willing to be publicly identified, is looking under every bed, so to speak, not for Commies but for traits that vary among humans because they are assumed to be the result of specific natural selection (and the bedroom is more than a metaphoric element of the traits chosen to study).

Here, we’ll look at human evolution in a way that takes very seriously their idea that essentially all our traits, or at least all traits about which a good story can be fed to the news media, are primarily chiseled into our genomes. Behavior is, of course, the ultimately juicy realm for such searches.  How can one not look at such traits with a modern scientific eye?  Here, we'll see the implications of this strong selectionist view: they’re very surprising, and form an entirely new theory of human evolution.  But first, some background.

Prologue to our new theory

The underlying axiom (that is, an assumption, or unquestioned belief) is that since we are the product of evolution, any of our traits must have been molded by natural selection specifically to make it like it is, or else it wouldn't be here.  And since selection only fosters genes, what is here is here because it's genetic.  The fact that culture can over-ride many traits, especially behavioral ones, is not of consequence if you accept this axiom, because an axiom is taken as true and universal.  It's not to be questioned any more than, say, the Resurrection or Genesis.

One major belief is that humans occur in distinct groups; we've got bananas, that is humans, and they're bunched into distinct groups (no, please!, don't over interpret 'banana' in this evolutionary discussion!).  You can call these bunches by their historic name, 'races', or you can use euphemisms to cover your political tracts (if that is relevant here) and say 'geographic' or 'ethnic' groups.  You may even note some small-print disclaimers from those who choose to say 'race', such as that the proponents of this view are not 'racist', or that, yes, the groups blur at their edges, but never mind those details. The discrete-category view is more convenient for the objectives of analysis which minimizes overlap because overlap gets in the way of tidy explanations by requiring nuances, caveats, and undermining assertions too subtle enough for reporters to understand.

There are many banana traits that this cadre of investigators work on.  No main point is lost here, however, if we just generalize and say that they rarely involve boring traits like, say, ankle width or relative length of ring fingers or the number of intestinal villi.  Mostly, investigators entice attention to their wisdom by stressing socially important (that is, divisive) traits like sexual behavior, intelligence, sociopathy, drug abuse, resemblance to Playboy bunnies, and so on.  The analysts in this arena and the news media seem to be concerned with who's good and beneficial to society, and who drags it (that is, us) down with their inferiority--or whose sexual appetites we need fear (or envy).

None of this is new.  Though probably widely written about by many others throughout history, we can start symbolically with Plato, whose Republic dealt with the obvious problem that society's finest specimens (that is, men!) are sent off to fight the Persians or Spartans, where these Adonises are often killed, depriving society and the next generation of their inherent, superior worth.  Of course many others, including Darwin, worried greatly about this problem.  These issues were a centerpiece of what was beneficently called racial 'hygiene' in the first half of the 20^th century, emanating out of England, traveling to the US and even Asia, and of course being adopted enthusiastically in Germany.  They noted, for example, that genetically unworthy perverts, psychotics (and Jews and Gypsies), stayed home, draining society's wealth (and bedding its women) while the real manly men spilled their guts at Passchendaele.

The perceived problem was real.  History shows that the great hordes of people avoid making solid contributions to society, sow crime, disease, immorality, harmful antisocial behavior and so on, undermining society’s best.  In its most benign form this realization of our species' problem and how to fix it, was called eugenics, a purportedly sincere attempt to use the new tools of science, to read Nature’s mind and foster the traits she favored, gently helping the superior to reproduce while encouraging the inferiors to keep their pants on.

The idea was simple and has immediate appeal.  If we can see what’s good and makes us more adaptive in the Darwinian sense, and if it’s genetic (and, under the working axiom, it must be genetic), then why not help those with good genotypes and, well, you know what else in regard to the others.   

Of course, there is the problem of identifying what’s “good”, and therein lies the rub.  Usually, and historically, the definitions have been made by the scholars in the elite parts of society.  They naturally tend to assume they and their peers reflect the ‘good’, and it is equally natural to denigrate the smelly masses of the hoi polloi as the less-good.  “If”, a professor or journalist might think, “everyone was like me” society would be so much better off.  Of course, little thought is given to what a society in which everyone was an Einstein or Michael Jordan or Beethoven would actually be like, but we’ll pass on that question.

The standard fear, and a very natural one it is, on the part of the quality elite is that they will be overwhelmed by their inferiors, who greatly outnumber them.  Unfortunately, not only do the inferiors hugely outnumber their superiors, but they reproduce like bunnies, eat up resources--those of the elite, not their own since they have little--yielding nothing good to show for it, and might even cause risk (theft, disease, and even….gulp….rape) to their superiors.  That is the often-unstated judgment lying behind eugenic thinking.

In many posts on our blog, we have tried to combat this kind of reflexively-deterministic thinking, because we’ve felt it is both scientifically naive, and awful for society.  It can get out of hand.  For example, the Islamic world was the most advanced for centuries relative to the rest of Europe, but now the Islamic world is treated as nearly subhuman in their lowly lifestyles and wanton (crusade-like) killing.  Similarly among the Europeans, often touted as the world's superiors, the Romans were superior relative to the barbarians in the north before the Legions were overwhelmed by pure Nordic legions wearing Viking helmets. These exemplify the changeability of position even over short time periods, which we think should be at least a bit worrying if one actually wants to take a scientific perspective and assert inherent genetically based group value differences. That's in part because these switches of fortune occurred far too rapidly to have a genomic explanation.

Still, the working assumption, again rarely actually stated, is that social discrimination that keeps the inferiors in their place is fully justified on evolutionary grounds.  In one way or another, this has been a prevailing view, as we’ve said, since the beginning of recorded history. What religions justified before, Darwin did in modern terms.  In fact, the idea of slavery was entirely consistent with this viewpoint—as long as the those in bondage stayed that way, and didn’t get uppity, they were like cattle and not really a threat to the good sort of humans.

But we’ve been thinking about all of this, in evolutionary terms and the selective axiom, and it suddenly dawned on us that in a profound and fundamental way, we and our intellectual ancestors in Darwinian biology, have had it wrong—indeed, have had it exactly reversed.  To correct that error, we think that an entirely new theory—a true paradigm shift—is in order and, indeed, is hardly even disputable.

A paradigm shifting new theory, modestly proposed

In fact, this new theory is an evolutionary valid inverse of the ages-old justification for slavery and other forms of bondage.  We still agree that societal inequality is a fundamental part of evolution and indeed, as before, is a good thing that has led to our globally overwhelmingly successful species.  Forget the Occupy movement and their groans about the unfair 1%.  Instead, it is that very 1% kind of figure that reveals the previously mistaken truth.  Social inequality is at the very foundation of human evolution….but in a way you never realized!

As scholars from time immemorial have observed, society is awash in reeking huddled masses. The intellectuals have better houses and cars, it’s true, and they enjoy quality wine rather than Thunderbird, and reading the NY Times to learn what is presented as the Truth.  The 1%ers enjoy softer jobs for more money, and make laws that allow them to gain their way into an ever-increasingly disproportionate share of the available wealth without it being called 'cheating' (which is defined as a welfare-collector's offense).  Their kids have a chance to get into the fabled halls of learning, so as to stay in their inherited social class; but since that’s expensive, and indeed rather a nuisance, they don’t have too many of children, and they wait to conceive them until they can start putting away those tuition funds.

Meanwhile the poor, miasmatic masses have less wealth, more unpleasant jobs (if any), and less savory diversions to while away the time…so they spend their lives, early and often, doing the bunny thing. As a result, of our species' billions, the vast majority increase faster than you can believe.  But how can they do that if they are inferior, as they so manifestly are, to the better sort of people?

Evolution is drunk.  Evolution has found a wickedly clever ruse: the lower classes are not inferior after all. Instead, they have corralled and enslaved the upper classes.  By various demonically indirect means, the upper classes are kept to small minimal numbers relative to the lower classes, so that they (the uppers) can devise things like industrial agriculture, vaccination, welfare programs and the like to nurture the lower, more reproductively successful classes.

How the lower classes managed to enhance their Darwinian fitness by enslaving a small group of upper classes who have lower fitness, and have done this for millennia, is quite remarkable. 

One might expect that since all behavior is genetically driven, the upper class genes would have been out-reproduced and made extinct long ago.  So the evolutionary determinist, needing an adaptive explanation to suit his axiom, might say this was a balanced polymorphism: genotypes for those who produce the resources are kept around, but at very low frequency, relative to genotypes generating the successful masses.  In this very implicit and indirect manner, like aphids farmed by ants, or ants zombified by fungi, the elites are the slaves of the main denizens of the human hives. And, remarkably, as educated as they are, the snoots don't even realize it--so, naturally, they don't rebel!

Marx said that religion was the opiate of the masses, a tool imposed on them by the outnumbered elites to keep them in their place.  In reality, wealth is the opiate of the elite.  There’s nothing like a Lexus, an opera (or Fox News) to pacify an investment banker.  And gated communities? The psychiatrists and lawyers who live in them fancy that these are to keep the stinking riff-raff out, but really it’s the other way round: it’s a very clever fear tactic generated by the proverbial huddled to keep the ivory folks penned in and away from the tawnier, more evolutionarily successful women.  Stupefying delusions of luxury keep the low-reproductive servant class in their safely restricted neighborhoods, an evolutionary finesse long ago imposed on them by the teeming and, even if grimier and ill-colored, rutting masses.

But this kind of evolutionary balance is hard to maintain given the persistently delayed and reluctant reproduction among the elites. They should always be at risk of extinction by simply spending resources on privilege rather than progeny. From a neo-eugnic point of view, now that we at last really understand evolutionary determination (the axiom we've referred to), we can see that the human species no longer needs this awkward balance: it's hard to maintain, and dangerous to the evolutionarily successful genotypes, because the elites often try to sneak out of their cages in the dark of night, into the realm of their superiors, to buy the occasional reproductive favors, which pollute the recipients' superior gene pool.  Clearly our species would be much better off if we simply used robotic technology to set up the world as an automated feeding ground for the masses, and eliminated the elites who, after all, just exhaust resources (like grassland, that could feed favelas by the thousands, to produce their fancy T-bone dinners, or fuel their Beemers and yachts) while contributing only feebly to the overall human patrimony. 

A modern eugenic policy, fully informed by rigorous genomics as those in the benighted 20th century were not, and truly based on the selectionist evolutionary axiom, should use what science has now, finally, discovered, and employ that technology to foster what Nature herself manifestly has always favored.  We know very well which races are the ones cleverly deluded into thinking of themselves as superior, which enabled them (us) to be led into serfdom by their more numerous masters. We in the decision-making positions behind our ivory towered isolation, in our rarefied numbers, should overlook the unsavory color, vulgar language, carnality, criminality, and stench of the masses and treat them for what they are:  Nature’s choice.

This may be an inverse realization relative to the theory you've heard about but remember the Darwinian axiom: the one principle is that they who reproduce most are the 'best' in evolution's eyes. There is no obligation to like them.  They need not be intelligent or even healthy.  But they are the evolutionary successes, empirically and theoretically.

This inverse truth may seem strange but it is in fact not surprising that even staunch Darwinians have had things 180 degrees wrong for more than a century.  They believe in their science, but it is only natural that they have seen the world filtered from their professorial on-campus perspective, and their being treated as knowing elites has flattered whatever they said, no matter how wrong.  Indeed, this longstanding error shows how subjective even science can be!

Yes, they're right: human behavior is all genetic and if their axiomatic genetic determinism is correct, we know very well how it works and what to do to help enhance Nature’s manifest choice.  The dream of the 19^th and 20^th century eugenicists and race hygienists, to use science to take over the chores that evolution has shown us, can now be realized, but in the proper rather than a dated and incorrect direction.  And in this electronic automated age, we no longer need the smug parasites, the small fringe of wealthy serfs, to make this happen.  We can eliminate the upper classes.  But this is evolution, not social science, so this should not be done by redistribution of resources! Instead, in the benign spirit of the original eugenic movement, the upper classes who should now understand this can help us improve our species voluntarily by refusing to reproduce.  

Or, other measures could be taken…..