Wednesday, December 30, 2015

Wee willies that no longer respond to a warm globe

               "If the idea spreads that pollution is affecting not just whales but also willies, 
                   I think we might witness sudden conversions to environmentalism."**

Environmental effects of human activity remain controversial, particularly because of the active opposition of conservative political groups. We've been slow to halt or reverse air pollution, and we're dragging our feet one climate change--the two are of course connected because of the burning of fossil fuels.  Because it has economic implications, the problem clearly mixes science and social politics.  But if some consequences of climate change were to be more in hand, and thus very clear, the otherwise rather vague idea might, by being brought so closely home, be a springboard to corrective action.  A recent report** alerted us to a consequence of environmental degradation that, if more widely known, might help reduce the controversy, and get everyone moving toward the same goal, reversing the damage.

Global warming has many consequences, but most of them rather general, gradual and of only ambiguous long-term implications.  Thus, perhaps no implication can hit home more poignantly and persuasively than one that directly impacts our most intimate personal lives.  As background to this report, we know that carbon (denoted C) and oxygen (O) in molecular combination are greenhouse gasses that are accumulating in our atmosphere, arguably at least in major part because of human combustion of fossil fuels.

Briefly, excess carbon dioxide (CO2) in the upper atmosphere, and carbon monoxide (CO) lower down have been steadily increasing and are widely believed to have caused many changes in both natural and human ecology.  But the data are so complex, involving sensitive measurement challenges of many different global factors, that they are rather hard to get one's head around.  The result has enabled opponents of environmental action to dispute whether climate change is real, and even if so, whether it has done more than cause things like occasional smog alerts in Beijing and overall mean global temperature to increase, with consequent glacial melting.  The skeptical opposing view is that all that the data are suggesting, at most, is temporary natural variation in the normal earthly ecology.

Those who resist the climate scientists' idea that we need to change our behavior to prevent further damage, or who may even think the whole idea is some sort of plot by Democrats (or worse, tree-huggers), do not react to these climate changes with alarm. Even if they believe the data, and indeed even if they say, for the purposes of argument, that climate change is caused by humans, they simply point out that people have always had to deal with one sort of crisis or another, often even ecological ones like the decline of Mayan or Mesopotamian or Indus Valley civilizations.  It's the natural course of events, whose personal consequences for us are hardly experienced.  As for future human generations, the argument is, they will just have to adapt, as humans have always done, even if that means major dislocation, food or resource wars, or societal disruption.  We ourselves should not be asked to give up our quality of life to give future generations a kind of free pass that neither we nor our forebears ever had.  Future quality of life may be different from ours, but people will recover or adjust in their own way.

However, the new report** hits right at the heart of the latter assumption, the very notion of future generations!

COnic section (dotted line); schematic
'Does size matter?' is no longer just a joke!
The new data differ from the existing climate reports because they finally show an important effect of ecological damage.  It is a rather sensitive or awkward finding to discuss and perhaps has received less publicity as a result.  But the fact is that there is a strong correlation between reduction in penis size and global warming.  We find that this is based on COnic section samples from the organ at birth (shown in a hopefully respectful schematic way in the above figure).  These appear to be hard data, not just whimsical speculation with a political agenda in mind.

The second figure, below, shows the relationship over the past 50 years, the period for which there are reliable data.  Clearly, as air pollution levels rise the cross-section size declined.  The smaller size may be a direct ecological effect on the quality of life or, indeed, on the very future of humanity. Whereas in the past, climate change data were rather abstract, the new data hit so close to home that one would expect sensitive people finally to stand up and take note.  Even scientists care about such things in a way that goes beyond the impersonal nature of Big Data spewing from their computers. "These wee willies just give me the willies!" one investigator said as part of our inquiry.

Pollution (black) vs organ size (red), 1957-2013

Genital size is relatively easy to measure, a single, simple indicator that does not require the expensive instrumentation, not to mention computer modeling that is required to analyze more general figures on global warming.  While scientists are careful to caution that it is very difficult to claim that global warming is causally responsive for the observed organic change, the  clarity of the data suggest that one can at least hope that some parts of our society will try to rise to the challenge.  Even if one dismisses the association as not clearly being a directly causal one because, for example, it is ultimately due to a correlation with some unmeasured factor(s), a reduction in global warming could also reduce those intermediate influences, and thus halt the observed trend.

Many effects of ecological change have been dismissed as fads, falsely reported 'trends', or even faked evidence, a kind of self-supporting conspiracy for funding and attention among the climate and ecological scientists, who urge their view as a political tactic to rankle their politically conservative opponents.  Communication on the subject has become so angry that in our society today the one hand doesn't really know what the other hand is up to.

The importance of the new data is that even after many years of steady stories on climate change and its implications, as a society in general, we seem not to have been able to take abstract facts, like sea-level height or the bushel yield of wheat, seriously, because they don't appeal to our deepest or more immediate emotions.  We must acknowledge even as we urge respect for the sciences that face complex analytic data problems, that not all the abstract science in the world can change that.  But wee willies may entail the emotions that one needs to reach, if widespread political change is to be hoped for.

This new report gets to the nub of the effects on human behavior of our wanton destruction of the environment.  But, sensitive though the subject is, or perhaps because of that, we may finally have the kind of hard-hitting report required to shake the complacency and stir up a call to action.

**This post reflects my reading of original reporting by U. Eco, as published in the recent issue of Numero Zero, which is widely available.  Interpretations are of course my own.

Wednesday, December 23, 2015

Good Tidings from Jolly Ol' St Nickase!

Here are some good tidings for the season!


I saw three SNPs come sequenced in
On CRISPR day, on CRISPR day
Yes all three SNPs came sequenced in
On CRISPR day in the morning
On CRISPR day in the morning
And what was with those SNPs all three
On CRISPR day, on CRISPR day?
And what was with those SNPs all three
On CRISPR day in the morning?
On CRISPR day in the morning
The TracrRNAs were there
On CRISPR day, on CRISPR day
The Spacers and Repeats were there
On CRISPR day in the morning
And HDR the changes made
On CRISPR day, on CRISPR day
Oh, with all the target changes made!
On CRISPR day in the morning

Then let all the lab rejoice again
On CRISPR day, on CRISPR day
Then let all the lab rejoice again
On CRISPR day in the morning!


Good news, ye merry gentlemen,
Now nothing you’ll dismay,
Remember that our Savior
Was born on CRISPR-day
To save poor souls from Mutant’s power,
Which long had gone awry.
And it is tidings of comfort and joy.

In genes that were our father's
The blessed changes came
Unto some certain Cas9 kit,
With tidings of the same;
That he was born in perfect health
The Son-of-CRISPR, named.   
Oh! tidings of comfort and joy, etc.

Thursday, December 17, 2015

In our book, THE BABY MAKERS, we wonder about wondering about where babies come from

Many of you know that Anne and I are writing a head-trip-of-a book together.*

The first popular article to come from our project is now published on-line at Scientific American

I did much of the work on this years ago. So you can imagine how excited I am to see it get out and into the light.

The piece asks whether Koko the gorilla, and other animals, could possibly link sex and babies. 

Whether your gut says of course not or of course, let us show your gut the actual evidence.

The printed January issue should hit the shelves in a week...

Oh, baby.
... our book, The Baby Makers, which has more space for us to explore more curious territory, should hit the shelves a bit later, geologically speaking.

*which is still without contract. Here's how to fix that:

Wednesday, December 16, 2015

Let's be intelligent about intelligence

A lot of confusion reins over assertions about whether a physical or even behavioral trait is  'genetic'. There are several reasons for this.  One is the difference between mechanism and variation. Every human trait is genetic in the first sense: an organism develops from a fertilized egg because it has genes, and without its genes it could do or even be nothing.  So every trait is 'genetic' in the mechanism sense. But the other meaning of 'genetic' has to do with variation, and that is where the difficulty and often the contention lies.  The assertion that a trait is 'genetic' in this sense means that some people with a trait, or a particular trait measure, have it because of some particular genotype. That is, we all differ in the trait because of causal genetic differences.  Identifying genetic mechanisms or demonstrating that genetic variation is responsible for variation in a trait are genuine challenges.

Searching for genetic mechanisms responsible for, say, heart disease is one of those challenges.  It's difficult scientifically, but unlike with some other traits, the scientific question isn't politically loaded. Many people fervently want to stress the genetic role in intelligence, for example, and it's often for thinly disguised racist or elitist reasons.  A common response to almost any suggestion that an individual's intelligence might not be inborn, due to variants in his/her inherited genotype (meaning built-into the person's DNA sequence), is an accusation that the person is in denial of reality (but see our Dec 14 post about genetics and dialectics).  But who is really denying reality in such cases?  In our view, it is those who misperceive or misuse measures like heritability and have deep, emotional commitment to inborn destiny.

And, again, it's pretty clear that just slightly beneath the surface is often a racist or other discriminatory agenda: "let's identify 'them' and do something about it, to 'improve' them or prevent them from harming everybody else" (Trump's throw the Muslims out campaign, or the reluctance to invest 'our' resources in groups with inferior IQ, or in the worst case, eliminate them). If it's important to understand why people behave as they do (intelligence being just one aspect of behavior; there are of course many others), the argument goes, then one needs to know if it's genetic, that is, built into the genome at conception!  Again, then depending on who such knowledge is important to, individuals in the population can (should, must) be tested.

Of course, it's worth asking carefully whether what's really being looked for are individual differences, or group differences.  Why 'we' (those in power) 'need' (that is, want) to know which of 'their' behaviors are built-in, is unclear, but seems frequently to justify acting in discriminatory ways, favoring some and neglecting others.  In other words, of course intelligence is the result of gene action, but the argument is really about variation rather than mechanism.

But before we address these issues, it is worth providing a quick description of the core of the 'scientific' basis of the argument, which typically rests on a measure called 'heritability' (denoted here by H but typically written h-squared).

Heritability: simple-sounding word, but a slippery measure
When the genetics of intelligence, or most other behavioral traits for that matter, is considered, the proof that they are genetic is usually that their heritability is high.  Heritability has been known for decades to be a rough indirect indicator of genetic mechanistic cause, but it's a very elusive measure. The usual measure of H is basically the ratio of the amount of variation in genes (G) divided by the amount of variation in genes + variation in environment, G/(G+E), all within a particular sample at a particular time.  This is estimated typically by comparing the trait measure in relatives, since close relatives share specifiable fractions of their respective genetic variants.

This figure schematically shows the scatter of genetic similarities, each dot being values of the measure in an offspring compared to the average of its mother and father.  The figure shows the difference in such correlations if environmental effects are great and genetic variation accounts for only 10% of the similarity (left panel), or small where the environments contribute only 10% (right).

From Wikimedia images, taken from Nature

H in itself measures no specific genes or gene-variants, nor any specific environmental variants.  To avoid some confounding or confusing contributors to the trait, various additional types of sample are often studied or comparisons made, such as between adoptees vs biological children, or dizygous vs monozygous twins. Heritability studies also often try to remove correlations among relatives that are due to shared family environments that could, in the computation, falsely appear as genetic.  While these strategies are not useless, they are well-known to be imperfect.

Since the measure H is a ratio that depends on the particular conditions in your particular sample, if one of the terms (G or E) were to change, even within that same sample, the H value would also change. In other words, let the same population (the exact same set of genotypes) experience changed environments, and H will change. In that sense H is not an absolute measure of how genetic a trait is, but of how relatively important it is.  Let us repeat that--heritability is not a definitive measure of the genetic contribution to a trait.  It is about its context in a particular sample.

Every study of traits like IQ test scores, used as hopeful stand-ins for 'intelligence', shows that there is substantial heritability, though usually far below 1.0.  That means that environmental effects are important, usually predominant, even if genetic variation is contributing as well.  That's about all that H measures show.  'Environment' in this sense tells us nothing in itself about what the specific individual contributing factors might be, because they don't behave the way genetic factors do, thanks to the rules of genetic transmission from parent to offspring; environmental factors don't have theoretically specifiable patterns of clustering among people or even among relatives. The apparent environmental component estimated in H studies can also include things like chance, testing inadequacy, measurement error and so on.

The undeniable bottom line is that variation in traits like intelligence test performance is certainly affected by genetic variation because the trait itself is mechanistically affected by genes. But that is a crude and almost useless fact because the genetic component is generally polygenic, meaning that it is affected by large numbers of varying genomic elements, each making very small individual contributions. Here, we conveniently ignore whether current fad factors such as microbiomic or epigenetic effects are relevant, because each of them is variable, in each population or sample, and over time--even in each individual over time--and could in principle be inherited and hence appear in families as being 'genetic'.

What this means is that even each individual's inborn genetic component will be very different, that is, each of us will have different combinations of variants at tens or hundreds (or more) of contributing gene regions.  The predictability of achieved results from genomes, much less individual variants, will be correspondingly small, practically useless, as we've clearly seen for so many other complex traits (GWAS results, for example, even of IQ test scores). If we could measure environments the way we can measure genomic variation, they would be similarly complex with many individual factors involved, most with individually weak effects.  As with genotypes, the complexity of these environmental factors would mean each person is unique and predictions are weak, and that changing circumstances and imprecision in the risk estimates would have a large potential effect on each person's achieved results.  We've discussed these limitations (and the overselling) of genetic association studies many times here.

But, if one is determined to pry into everyone's inherent worth, here's how to do it properly:
Here's an idea: Let society decide that we want to know the real genetic truth about behaviors, not just the mechanisms but the effect of variation among individuals.  To do that, we must pass legislation to ensure that all environmental factors that contribute to behavior--all of them!--are exactly the same for everyone, from conception onward.  Once that is done, variation in test performance will be entirely due to genes, since the environmental variance, E, would be zero, so that H would be 1.0.  Now we can see how strongly genes in general, or individual genetic variants, determined results.  However, we assert with confidence that the result of individual genetic prediction would still be hopelessly complex in most cases (excepting, for example, clearly pathogenic genetic variants, which we know to be rare, and even they are usually not simple).

But this is of course a fantasy: making environmental effects uniform for everyone is obviously impossible, for at least two reasons.  First, we can't make the climate in Maine like that in Florida or California.  We can't have identical schools everywhere, or the same number of books in every home, or the same number of words spoken to each infant at each developmental stage.  And so on.  So maybe a more realistic idea would be to make the environmental variation the same everywhere, so that in a sense it was a kind of uniformly distributed 'error' term in measuring genetic effects.  Of course that can't be done either, for the same sorts of reason.

Secondly, genes don't work on their own, but interact with 'environments' in almost every imaginable way, and certainly in the development of the brain.  That means that separating G and E (as in G+E) is clearly an oversimplification of something very poorly understood.  Even fixing the same environment everywhere would not have the same effect on every genotype.

The bottom line, in reality, is that arguments, usually by those in privilege, that behaviors (and hence their societal value) are inherent, are almost inevitably working some other form of self-advantaging agenda.  Racism is right beneath the surface in much of this, but so are xenophobia and class differences.  So are hopes of producing babies with some desired property.  That's clear from the history of the subject.

Since it's impossible to think that society could make environments uniform for everyone so all that's left is genetic variation, the next most salubrious thing a society could do would be to provide the best environmental conditions for all of its members to thrive in, not expecting everyone to achieve the same but at least to have safe, satisfactory lives.  More socioeconomic equity by the elimination of poverty and privilege would be a solution if such equity were the real objective. Of course since the beginning of history this has been the stated goal of those who bemoan the unfairness of society (though less so of others who say we're inherently unequal and we ought to reward the privileged).  We gain little by peering into individual genomic 'souls' and condemning those found genetically wanting to fates that we, in the elite, decide is best for them (inevitably making sure we stay at the top).

This doesn't seem too cynical a view of the subject: If what those who assert the deep importance of genetics of behavior really want is for society to be fair, the first thing is to understand the environmental effects that obviously are the predominant causes of behavioral variation, and rectify the inequities.  Let society ensure that everyone has the same conditions: no upper class advantages in schools, ballet lessons, Kaplan prep courses for SATs to get them into Princeton, no jobs to get through family or parents' contacts, same number of books in every house, no corner drug dealers nor rats in the hallways in poor neighborhoods......  Or, how about broader 'intelligence' testing ideas, to include smarts like the ability to read defenses in basketball while flying through the air, or work a fork-lift efficiently, or fix one of today's complicated cars....

is a complex factor that is misused as much as it is used, because there are too many reasons to interpret its computational subtleties in ways that conveniently favor one's own social agenda. Not everyone interprets these issues in this way, but behaviors like intelligence are too juicy for those with such intentions to resist.  But, yes, let's be scientific, and commit to a concerted effort to make H approach 1.0, so that we can really understand the genetic contributions--that is, to make test-score differences really 'genetic'!  Then we could make sense of 'genetic' causes.  But, would any serious thinker believe it would be very useful?

Tuesday, December 15, 2015

Christmas lights and/or lights out?

Wikimedia commons

Maybe you're too young or have just forgotten the early 1970s Arab oil embargo, but there's a sobering, if not depressing lesson to be had by recalling it.  At that time, oil supplies were limited as a way of forcing up the price.  People waited in long lines to fill up their gas tanks.

And then responded by lowering the speed limit to improve gas mileage, and by restricting the amount of gas that could be bought.

Rational rationing response (Wikimedia images)
Rational realities  (Wikimedia images)
How short is our memory!  At that time, Toyota and a few others (like a more honest VW then) made cars that were inexpensive, very easy to fix (as even I could do!), reliable, with much better fuel economy than most cars get today. We suddenly realized that we'd been living too high on the hog, and that it was time to tighten our belts--for everyone's collective good.  And we did not like being dependent on somebody else for our lives. Saving, economy, restraint, and self-sufficiency were actually popular, even here in the US.  'More' was not the only word in our vocabulary; small was beautiful as a widespread slogan of the '70s had it.  Of course, as soon as the embargo ended, auto-makers started puffing up their cars.

How times have changed!  Today's immediate news is all about the urgent need for stalling climate change.  Those who want to feel virtuous are using LED light bulbs and driving (expensive) hybrid cars.  Note the word 'driving', because our way of life still supports burgeoning suburbs that require driving (your Prius) many miles a day, even just to get a bottle of milk.  Pump prices are low--and Wall Street is bleating!  All the car makers, including Toyota, have been making, marketing, and selling road hog cars way bigger than most people have any need for.  Hardly anyone is complaining.  It's not even clear if the feel-gooders buying hybrids are actually saving much if any fossil fuels, given the environmental and cost issues of the batteries, and so on.  Even so, the total usage is up.

Not only were speed limits reduced to what were fuel-efficient speeds, street lights were turned out at night. And, then-President Jimmy Carter did things like put solar panels on the roof of the White House, use a wood stove for heat, and (though a Baptist, or perhaps because he had a sincere faith) requested that people not use Christmas lights in 1979 and 1980.  They might have been nice to look at, but they used energy that we realized we should save.

But...but we're now saving the earth!!!
The news media are currently blaring self-satisfied stories about how the Paris conference (that is, the countless delegates who flew there, and ate lots of meals requiring imported food) actually came to an agreement about possibly, maybe, we'll see, restrictions of fossil fuel usage.  Hopefully, they'll at least do the limited things they say.  So, brush your hands off in gratitude, and believe that we'll really 'save the earth'!

Has saving the earth sunk in?  From Wikimmedia images

However as the above picture shows, the depth of understanding is, one could say, rather shallow. Unlike the '70s, within living memory, the idea of real curtailing of our energy wastage is long forgotten in today's post-conference feel-good moments.

Yes, gaudy holiday lights (even imported by ship from very far away) don't individually use up much energy.  And, I mean, shouldn't we be able to show off our piety to our neighbors, even out-do them in that respect?  We don't need to save the earth that much, surely!

Symbolic restraint like LED light bulbs and (relatively) fuel-efficient cars show that the issues in reality have hardly sunk in.  The idea that we might actually realize what restraint in lifestyle would mean, if we were to take equity and posterity seriously, seems far-fetched.  Symbolic gestures -- like squiggly light bulbs -- that still allow us to keep up what we've been doing all along make us feel good.  But without a serious self-imposed embargo on our behavior, all the news stories and hand-wringing about climate change is false piety.  But that's nothing new, a delusion not all that different from religion.

But, of course, it must all be OK, because now we're finally saving the earth!

Ah, well, it might seem unseemly, in this Holiday season, but I can't help but wonder how many people in our world could be fed and have a decent life if we did even a little bit less driving and flying, and turned off these beautiful lights.

Monday, December 14, 2015

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.


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?  

Monday, November 30, 2015

Quantum spookiness is nothing compared to biology's mysteries!

The news is properly filled these days with reports of studies documenting various very mysterious aspects of the cosmos, on scales large and small.  News media feed on stories of outer space's inner secrets.  We have dark matter and dark energy that, if models of gravitational effects and other phenomena are correct, comprise the majority of the cosmos's contents. We have relativity, that shows that space and even time itself are curved.  We have ideas that there may be infinitely many universes (there are various versions of this, some called the multiverse).  We have quantum uncertainty by which a particle or wave or whatever can be everywhere at once and have multiple superposed states that are characterized in part only when we observe it.  We have space itself inflating (maybe faster than the speed of light).  And then there's entanglement, by which there seem to be instant correlated actions at unlimited distances.  And there is some idea that everything is just a manifestation of many-dimensional vibrations ('strings').

The general explanations are that these things make no 'sense' in terms of normal human experience, using just our built in sensory systems (eyes, ears, touch-sense, smell, etc.) but that mathematically observable data fit the above sorts of explanations to a huge degree of accuracy.  You cannot understand these phenomena in any real natural way but only by accustoming yourself to accept the mathematical results, the read-outs of instrumentation, and their interpretation.  Even the most thoughtful physicists routinely tell us this.

These kinds of ideas rightfully make the news, and biologists (perhaps not wanting to be left out, especially those in human-related areas) are thus led to concocting other-worldly ideas of their own, making promises of miracle precision and more or less health immortality, based on genes and the like.  There is a difference, however: unlike physicists, biologists reduce things to concepts like individual genes and their enumerable effects, treating them as basically simple, primary and independent causes.

In physics, if we could enumerate the properties of all the molecules in an object, like a baseball, comet, or a specified set of such objects, we (physicists, that is!) could write formal equations to describe their interactions with great precision.  Some of the factors might be probabilistic if we wanted to go beyond gravity and momentum and so on, to describe quantum-scale properties, but everything would follow the same set of rules for contributing to every interaction.  Physics is to a great, and perhaps ultimate extent, about replicable complexity.  A region of space or an object may be made of countless individual bits, but each bit is the same (in terms of things like gravity per unit mass and so on).  Each pair, say, of interactions of similar particles etc. follows the same rules. Every electron is alike as far as is known.  That is why physics can be expressed confidently as a manifestation of laws of nature, laws that seem to hold true everywhere in our detectable cosmos.

Of cats and Schroedinger's cat
Biology is very different.  We're clearly made of molecules and use energy just as inanimate objects do, and the laws of chemistry and physics apply 100% of the time at the molecular and physics levels. But the nature of life is essentially the product of non-replicable complexity, of uniquely interacting interactions.  Life is composed strictly of identifiable elements and forces etc at the molecular level. Yet the essence of life is descent with modification from a common origin, Darwin's key phrase, and this is all about differences.  Differences are essential when it comes to the adaptation of organisms, whether by natural selection, genetic drift, or whatever, because adaptation means change.  Without life's constituent units being different, there would be no evolution beyond purely mechanical changes like the formation of crystals.  Even if life is, in a sense the assembling of molecular structures, it is the difference in their makeups that makes us different from crystals.

Evolution and its genetic basis are often described in assertively simple terms, as if we understood them in a profound ultimate sense.  But that is a great exaggeration: the fact that some simple molecules interacted 4 billion years ago, in ways that captured energy and enabled the accretion of molecular complexity to generate today's magnificent biosphere, is every bit as mysterious, in the subjective sense of the term at least, as anything quantum mechanics or relativity can throw at us. Indeed, the essential nature of life itself is equally as non-intuitive. And that's just a start.

The evolution of complex organisms, like cats, built through developmental interactions of awe-inspiring complexity, leading to units made up of associated organ systems that communicate internally in some molecular ways (physiology) and externally in basically different (sensory) ways is as easy to say as "it's genetic!", but again as mysterious as quantum entanglement.  Organisms are the self-assembly of an assemblage of traits with interlocking function, that can be achieved in countless ways (because the genomes and environments of every individual are at least slightly different).  An important difference is that quantum entanglement may simply happen, but we--evolved bags of molecular reactions--can discover that it happens!

The poor cat in the box.  Source: "Schrödinger cat" by File:Kamee01.jpg: Martin Bahmann, Wilimedia Commons

This self-assembly is wondrous, even more so than the dual existence of Schroedinger's famous cat in a box.  That cat is alive and dead at the same time depending on whether a probilistic event has happened inside the box (see this interesting discussion), until you open the box, in which case the cat is alive or dead. This humorous illustration of quantum superposition garnered a lot of attention, though not that much by Schroedinger himself for which it was just a whimsical way to make the point about quantum strangeness.

But nobody seems to give a thought beyond sympathy for the poor cat!  That's too bad, because what's really amazing is the cat itself.  That feline construct makes most of physics pale by comparison.  A cat is not just a thing, but a massively well-organized entity, a phenomenon of interactions, thanks to the incredible dance of embryonic development.  Yet even development and the lives that plants and animals (and, indeed, single-celled organisms) live, impressively elaborate as they are, pale by comparison with various aspects these organisms have of awareness, self-awareness, and consciousness.

This is worth thinking about (so to speak) when inundated by the fully justified media blitz that weird physics evokes, but then you should ask whether anything in the incomprehensibly grand physics and cosmology worlds are even close to the elusiveness and amazing reality of these properties of life and how these properties could possibly come about, how they evolved and how they develop in each individual--as particular traits, not just the result of some generic evolutionary process.

And there's even more:  If flies or cats are not 'conscious' in the way that we are, then it is perhaps as amazing that their behavior, which so seems to have aspects of those traits, could be achieved without conscious awareness.  But if that be so, then the mystery of the nature of consciousness having evolved, and the nature of its nature, are only augmented many-fold, and even farther from our intuition than quantum entanglement.

Caveat emptor
Of course, we may have evolved to perceive the world just the way the world really is (extending our native senses with sensitive instruments to do so).  Maybe what seems strange or weird is just our own misunderstanding or willingness to jump on strangeness bandwagons.  Here from Aeon Magazine is a recent and thoughtful expression of reservations about such concepts as dark matter and energy.

If quantum entanglement and superposition, or relativity's time dilation and length contraction, are inscrutable, and stump our intuition, then surely consciousness trumps those stumps.  Will anyone reading this blog live to see even a comparable level of understanding in biology to what we have in physics?

Wednesday, November 25, 2015

Epigenetics: what is it and what isn't it? Part II: How far can it take us?

Some people are heralding discoveries in epigenetics as a vindication of Lamarck's idea of the inheritance of acquired characteristics.  As we said yesterday, and in our previous posts on Lamarck, in a technical sense this may be so, if multigenerational transmission of epigenetic marking can be clearly demonstrated.  This is a big 'if' but in subtle ways.  DNA usage can be inherited, as epigenetic research shows.
Lamarck.  Any serious connection to epigenetics? Source: wikimedia commons
Let's assume it can be transgenerational--that is, not erased in the formation of sperm or egg cells so that a given gene's epigenetic marking can be transmitted across many generations.  In a way, this would subvert the adaptability of organisms by pre-programming, as if they had already been exposed to whatever environmental factor leads to the epigenetic marking.  That would be anti-evolutionary in the sense that organisms have, by and large, evolved to adapt to environments, not to predict them, so it would be better to re-set the genome so it doesn't express genes that it doesn't need to express, etc.

But let's assume current findings are basically supported by research that shows transgenerational inheritance.  This would be Lamarckian inheritance--the inheritance of acquired characteristics--but is it Lamarckian evolution?  That's a more subtle question.  If it is, say, useful to respond to some nutrient X, then passing a hyper-responsive gene usage pattern would be adaptive.  It would be based on experience and inherited, Lamarckian.

What sorts of traits are we talking about here?  We need to be careful in several ways.  First, the epigenetic effects that have been identified affect gene regulation (gene expression or not, expression levels), but not the structure of genes or their regulatory DNA sequences.  In itself, that's no big deal, as regulation is a part of function and hence evolution.  ln fact, if individuals who do better because they mark certain genes for (say) increased expression, and that is inherited, and if the modification increases survival, that's good--it's adaptive!  If then at some later time a DNA sequence change, a mutation, makes the cell respond in the same way without requiring the more temporary epigenetic marking, then the new cellular responsiveness would become built into the genome itself.  That has long been known as a potential evolutionary phenomenon (called either the 'Baldwin effect' or 'genetic assimilation').  It presents no challenge to evolutionary thinking and is still basically Darwinian.  It would mean that while evolution can occur by epigenetic means, it eventually goes the usual genome-based way of 20th century evolutionary theory.  No problem.  It can be called Lamarckian, but we shouldn't give Lamarck too much credit, because he had no knowledge of any of these mechanisms, and was (like Darwin after him) largely guessing about how to fit what is observed to some persuasive theory.

But what Lamarck was talking about were 'real' adaptations, like flight in bats, or whales in the sea, or the complex organs by which mammals execute special function, or the evolution of eyes. These are the 'real' adaptive changes that he, and Darwin and many others, were trying to account for in natural rather than theological terms.

Modification of expression levels of insulin or some metabolic trait, or even some skin pigment based on life-experience would seem so trivial relative to more complex 'real' adaptations, that we seemingly can keep Darwin on his pedestal of honor, and Lamarck in the laughing gallery.  Or can we?

Different sorts of 'adaptation'
The epigenetic examples that have been studied so far concern the usage of genes, that is their regulation.  They do not affect the structure of the genes themselves (that is, the protein or functional RNA that they code for).  In that sense, the standard anti-Lamarckian view of epigenetics would be that it doesn't really introduce anything new, but just adjusts what is already there.  Yet Darwin and even Lamarck were concerned with  how new traits arise.

We all know of the ridicule levied at Lamarck for arguing that giraffe ancestors became modern giraffes by striving to eat high leaves, which in essence stretched their necks and that change was then inherited.  Lamarck didn't require random mutation and natural selection, and in fact he only mentioned giraffes once in his book. There he noted that legs and other structures, not just necks, had to change in their evolution.  Laughter notwithstanding, Darwin would say that mutations variously giving longer necks and differently structured limbs etc., led their bearers to bear more baby giraffes and long-neck adaptation occurred that way.  But could such complex structures have evolved by epigenetic means, by quantitative changes in development later genetically assimilated?

Giraffes by epigenetic evolution?  Source: wikimedia images
Regulatory modification doesn't seem able to produce new things, does it?  Is it possible to produce new structures by changing the expression patterns of currently existing structures?  If there is anything seriously 'Lamarckian' about epigenetics, perhaps this is where any really interesting issues arise (and, keep in mind that Lamarck's kinds of explanations were the sort of thing one might conjecture with what was known at the time, so one can, at most, use his name reservedly, as is the case with Darwin).

Mutations can occur in regulatory regions and affect the binding efficacy of regulatory proteins.  So changes in DNA sequence of these regions can affect the expression of genes they control.  In that sense mutations can in principle arise that do what epigenetic modification does: change gene expression.  If this occurs in situations where environmentally induced expression changes occur, then genetic assimilation can introduce expression changes more permanently in the genome.  There's no problem here.

Still, epigenetic changes don't directly change the structure of proteins, so can the latter be related to epigenetic responses to the environment?  In principle, certainly they can!  Gene structure clearly affects the dynamics of the protein's actions.  Mutations in the structure of a cell-surface receptor that responds to some environmental factor can affect its efficiency, and in that sense mimic the effect of epigenetic change that raises or lowers the sensitivity of genomic response to that same factor. Similarly, making more of something (say, collagen in skin and bone) could be similar in effect to making less but stronger material.  In that sense, genetic assimilation of structural changes can, in principle, mimic or be equivalent to epigenetic effects (here, by the way, we're ignoring whatever it is that enables a particular environmental factor to affect gene-specific epigenetic change--a major and highly relevant issue!).

In fact, it is not so trivial to ask what is a 'new' trait rather than a modification of something existing, especially if one thinks in terms of how development works.  Giraffe necks are complex structures, but are longer necks new or just quantitative changes in all the tissues involved?  If you think carefully, the very fact of evolutionary continuity--descent with modification to use Darwin's own phrase for it--raises the question as to what's actually new rather than quantitatively different from what came before.  The answer in our context here is not at all obvious.

In sum, one issue is that if gene structure changes can have similar effects to gene regulatory changes, then epigenetic mechanisms, that is, traits acquired by experience, can be related to adaptive evolution in the usual Darwinian sense of adaptive traits.  But this is not at all the same as the adaptive evolution of complex traits.  Could they, too, evolve via epigenetic mechanisms?

Could classical complex adaptive traits evolve through epigenetic means?
We now have extensive direct knowledge to show that tens, hundreds, or (typically) thousands of different genes are employed even in simple phenomena like the formation of basic tissue layers and lineages in embryos. The same is true for bones, eyes, organs and so on.  These causal elements all vary in and among individuals and species so that, within limits, many different combinations of genes and (importantly) the timing of their expression affects the traits that develop.  The differences are related to regulatory as well as structural sequence.  Genomewide mapping shows similarly complex causation of traits like behavior, or diseases like cancers, diabetes, and so on.

Similarly, we know that most of the traits we discuss in regard to adaptive evolution (and that were the objects of Darwin's and Lamarck's interest), evolved gradually, usually over countless thousands or even millions of generations.  That's hard to keep in mind, but to understand evolution properly we must try to do so.

An important fact is that the function of most genes is to affect the expression of other genes through various sorts of signaling or processing, indirectly as well as directly.  Signals, receptors, regulators, modifiers, and so on all are about quantitative effects, and an embryo is the result of a cascade of quantitative interactions, that end in physical structures and processes (like metabolism).  Even if final properties of adaptive traits are purely structural, they are the result of regulatory interactions.

A central question, perhaps the central question, has to do with the fact that for the above scenario to be plausible, epigenetic effects based on life-experience in the environment must affect relevant gene usage, and it is far from automatic that all of these factors involved in complex adaptive traits could be induced in that way. It's a lot easier to account for minor metabolic effects like this than for other traits, even bit by bit.  Still, some of them might, and they all would, in principle, be legitimate subjects for an epigenetic evolutionary role.  This will likely be an important area of investigation.

Could major adaptations such as Lamarck and Darwin were mainly concerned with evolve through epigenetic stages?  Clearly, with such hypercomplex systems as we're made of, and their very gradual evolution, there is no way to argue that epigenetic changes, aided by various forms of genetic assimilation, could not account for the evolution of complex adaptive traits.  At least some of organisms' life experience exposures (what Lamarck called habits or striving) can affect their gene usage and, ultimately over such incomprehensibly complex genetic and temporal landscapes, lead to the origin and evolution of complex adaptive traits.

Could some lifestyle activities in Africa have led for whatever reason to growth changes in giraffe-ancestors' necks, slowly and bit by bit, that led them to notice and eat higher leaves, which then led to genetic assimilation (which is a form of natural selection)?

Could doesn't mean did, obviously, nor even if these ideas applied to some traits there's no reason they would have to apply to all traits.  We know evolution takes many paths.  But the discovery of environmentally induced regulatory changes by epigenetic marking could in principle lead to complex trait evolution.  Even at best the onion-like multilayering of how an environmental experience comes to affect the expression of only some specifically relevant genes in the first place, will have to be understood.

Evolution, and evolutionary theory, carry on
Even if all of this epigenetic driving of aspects of evolution were found to occur, that would not be a threat to the general notion of adaptive Darwinian evolution--it just adds another aspect of the mechanisms involved, which often would involve a component of natural selection.  And indeed Darwinian concepts, especially of strong natural selection, are themselves very oversimplified relative to a far more nuanced reality.

If epigenetics turns out to be more broadly and evolutionarily important than we currently know from solid facts, Lamarck would in that limited sense be right, but it would not be for anything other than the idea that adaptive traits can appear to have evolved through gradually accumulated life experience.  Lamarck was quite aware of the complexity and, importantly, slowness of evolution. But he can't be credited with more than that.  He had no specific information about mechanism and in that sense no anticipatory insight.  In essence the same was true of Darwin: he was observing variation in life and accounting for its arrival via natural historical rather than theological or other non-material means. On present understanding, Darwin's ideas, flawed or incomplete (or pure guesswork) though they often were, seem closer to the mark of our current understanding in many ways, epigenetics notwithstanding, than Lamarck's (not to mention various others who at the same general time speculated about evolution).

Truly transgenerational phenotypic effects may be real or even widespread.  They may be built into genomes or might, in principle, last indefinitely many generations.  They could be more flexible relative to changing environments, via epigenetic routes than having to be hard-wired in the genome. But even if so, this would mainly add details to the generally understood means of evolution of traits, simple or complex.  Every such discovery, if true, would improve our understanding of life.  The jury is clearly still out in this case, and jurors are still properly doubtful, about whether or not it is a fact.