Darwin the Newtonian. Part III. In what sense does genetic drift 'exist'?

It has been about 50 years since Motoo Kimora and King and Jukes proposed that a substantial fraction of genetic variation can be selectively neutral, meaning that the frequency of such an allele (sequence variant) in a population or among species changes by chance--genetic drift--and, furthermore, that selectively 'neutral' variation and its dynamics are a widespread characteristic of evolution (see Wikipedia: Neutral theory of molecular evolution). Because Darwin had been so influential with his Newtonian-like deterministic theory of natural selection, natural evolution was and still is referred to as 'non-Darwinian' evolution. That's somewhat misleading, if convenient as a catch-phrase, and often used to denigrate the idea of neutral evolution, because even Darwin knew there were changes in life that were not due to selection (e.g., gradual loss of traits no longer useful, chance events affecting fitness).

First, of course, is the 'blind watchmaker' argument.  How else can one explain the highly organized functionally intricate traits of organisms, from the smallest microbe to the largest animals and plants?  No one can argue that such traits could plausibly just arise 'by chance'!

But beyond that, the reasoning basically coincides with what Darwin asserted.  It takes a basically thermodynamic belief and applies it to life.  Mother Nature can detect even the smallest difference between bearers of alternative genotypes, and in her Newtonian force-like way, will proffer better success on the better genotype.  If we're material scientists, not religious or other mystics, then it is almost axiomatic that since a mutation changes the nature of the molecule, if for no other reason that it requires the use of a different nucleotide and hence the use and or production of at least slightly different molecules and at least slightly different amounts of energy.

The difference might be very tiny in a given cell, but an organism has countless cells--many many billions in a human, and what about a whale or tree! Every nonessential nucleotide has to be provided for each of the billions of cells, renewed each time any cell divides.  A mutation that deleted something with no important function would make the bearer more economical in terms of its need for food and energy. The difference might be small, but those who then don't waste energy on something nonessential must on average do better: they'll have to find less food, for example, meaning spend less time out scouting and hence exposed to predators, etc.  In short, even such a trivial change will confer at least a tiny advantage, and as Darwin said many times to describe natural selection, nature detects the smallest grain in the balance (scale) of the struggle for life.  So even if there is no direct 'function,' every nucleotide functions in the sense of needing to be maintained in every cell, creating a thermodynamic or energy demand.  In this Newtonian view, which some evolutionary biologists hold or invoke quite strongly, there simply cannot be true selective neutrality--no genetic drift!

The relative success of any two genotypes in a population sample will almost never be exactly the same, and how could one ever claim that there is no functional reason for this difference?  Just because a statistical test doesn't find 'significant' differences in the probabilistic sense that it's not particularly unusual if nothing is going on, tiny differences nonetheless obviously can be real.  For example, a die that's biased in favor of 6 can, by chance, come up 3 or some other number more often in an experiment of just a few rolls. Significance cutoff values are, after all, nothing more than subjective criteria that we have chosen as conventions for making pragmatic decisions (the reason for dice being this way is interesting, but beyond our point here).

But what about the lightning strikes?  They are fortuitous events that, obviously, work randomly against individuals in a population in a way unrelated to their genotypes, thus adding some 'noise' to their relative reproductive success and hence of allele (genetic variant) frequencies in the population over time.  That noise would also be a form of true genetic drift, because it would be due to a cause unrelated to any function of the affected variants, whose frequencies would change, at least to some extent, by chance alone. A common, and not unreasonable selectionist response to that is to acknowledge that, OK! there's a minor role for chance, but nonetheless, on average, over time, the more efficient version must still win out in the end: 'must', for purely physical/chemical energetics if no other reasons.  That is, there can be no such thing as genetic drift on average, over the long haul.  Of course, 'overall' and 'in the end' have many unstated assumptions.  Among the most problematic is that sample sizes will eventually be sufficiently great for the underlying physical, deterministic truth to win out over the functionally unrelated lightning-strike types of factors.

On the other hand, the neutralists argue in essence that such minuscule energetic and many other differences are simply too weak to be detected by natural selection--that is, to affect the fitness of their bearers.  Our survival and reproduction are so heavily affected by those genotypes that really do affect them, that the remaining variants simply are not detectable by selection in life's real, finite daily hurly-burly competition. Their frequencies will evolve just by chance, even if the physical and energetic facts are real in molecular terms.

But to say that variants that are chemically or physically different do not affect fitness is actually a rather strong assertion! It is at best a very vague 'theory', and a very strong assumption of Newtonian (classical physics) deterministic principles. It is by no means obvious how one could ever prove that two variants have no effect.

So we have two contending viewpoints.  Everyone accepts that there is a chance component in survival and reproduction, but the selectionist view sees that component as trivial in the face of basic physical facts that two things that are different really are different and hence must be detectable by selection, and the other view that true equivalence is not only possible but widespread in life.

When you think about it, both views are so vague and dogmatic that they become largely philosophical rather than actual scientific views.  That's not good, if we fancy that we are actually trying to understand the real world.  What is the problem with these assertions?

Can drift be proved?

Maybe the simplest thing in an empirical setting would just be to rule out genetic drift, and show that even if the differences between two genotypes are small in terms of fitness there is always at least some difference.  But it might be easier to take the opposite approach, and prove that genetic drift exists.  To that, one must compare carriers of the different genotypes and show that in a real population context (because that's where evolution occurs) there is no, that is zero difference in their fitness. But to prove that something has a value of exactly zero is essentially impossible!

Is each outcome equally likely?  How to tell?

Again to a dice-rolling analogy, a truly unbiased die can still come up 6 a different number of times than 1/6th of the number of rolls: try any number of rolls not divisible by 6!  In the absence of any true theory of causation, or perhaps to contravene the pure thermodynamic consideration that different things really are different, we have to rely on statistical comparisons among samples of individuals with the different competing genotypes.  Since there is the lightning-strike source of at least some irrelevant chance effects and no way to know all the possible ways the genotypes' effects might differ truly but only slightly, we are stuck making comparisons of the realized fitness (e.g., number of surviving offspring) of the two groups.  That is what evolution does, after all.  But for us to make inferences we must apply some sort of statistical criteria, like a significance cut-off value ('p-value') to decide. We may judge the result to be 'not different from chance', but that is an arbitrary and subjective criterion.  Indeed, in the context of these contending views, it is also an emotional criterion.  Really proving that a fitness difference is exactly zero without any real external theory to guide us, is essentially impossible.

All we can really hope to do without better biological theory (if such were to exist) is to show that the fitness difference is very small.  But if there is even a small difference, if it is systematic it is the very definition of natural selection!  Showing that the difference is 'systematic' is easier to say than do, because there is no limit to the causal ideas we might hypothesize.  We cannot repeat the study exactly, and statistical tests relate to repeatable events.

There's another element making a test of real neutrality almost impossible.  We cannot sample groups of individuals who have this or that variant and who do not differ in anything else.  Every organism is different, and so are the details of their environment and lifestyle experiences.  So we really cannot ever prove that specific variants have no selective effect, except by this sort of weak statistical test averaging over non-replicable other effects that we assume are randomly distributed in our sample.  There are so many ways that selection might operate, that one cannot itemize them in a study and rule out all such things.  Again, selectionists can simply smile and be happy that their view is in a sense irrefutable.

A neutralist riposte to this smugness would be to say that, while it's literally true that we can't prove a variant to confer exactly zero effect, we can say that it has a trivially small effect--that it is effectively neutral.  But there is trouble with that argument, besides its subjectivity, which is the idea that the variant in question may in other times and genomic or environmental contexts have some stronger effect, and not be effectively neutral.

A related problem comes from the neutralists' own idea that by far most sequence variants seem to have no statistically discernible function or effect.  That is not the same as no effect.  Genomes are loaded with nearly or essentially neutral variants by the usual sampling strategies used in bioinformatic computing, such as that neutral sites have greater variation in populations or between species than is found in clearly functional elements.  But this in no way rules out the possibility that combinations of these do-almost-nothings might together have a substantial or even predominant effect on a trait and the carriers' fitness.

After all, is not that just what have countless very large-scale GWAS studies shown? Such studies repeatedly, and with great fanfare, report that there are tens, hundreds, or even thousands of genome sites that have very small but statistically identifiable individual effects but that even these together still account for only a minority of the heritability, the estimate of the overall amount of contribution that genetic variation makes to the trait's variation.  That is, it is likely that many variants that individually are not detectably different from being neutral may contribute to the trait, and thus potentially to its fitness value, in a functional sense.

This is one of the serious and I think deeply misperceived implications of the very high levels of complexity that are clearly and consistently observed, which raises questions about whether the concept of neutrality makes any empirical sense, and remains rather a metaphysical or philosophical idea.  This is related to the concepts of phenogenetic drift that we discussed in Part II of this series, in which the same phenotype with its particular fitness can be produced by a multitude of different genotypes--the underlying alleles being exchangeable.  So are they neutral or not?

In the end, we must acknowledge that selective neutrality cannot be proved, and that there can always be some, even if slight, selective difference at work.  Drift is apparently a mythical or even mystical, or at least metaphoric concept.  We live in a selection-driven world, just as Darwin said more than a century ago.  Or do we?  Tune in tomorrow.

Darwin the Newtonian. Part II. Is life really 'Newtonian'?

In yesterday's post I suggested that Darwin had a Newtonian view of the world, that is, he repeatedly and clearly described the organisms and diversity of life as the product of evolution, due to natural selection viewed as a force, which in an implicit way he likened to gravity.  At the same time, he knew that there was widespread evidence of various kinds for long-term evolutionary stasis, which a prominent geologist has recently called  "Darwin's null hypothesis of evolution," the idea that evolution does not occur if the environment stays the same.

That suggests that a changing environment leads to a changing mix of organisms that live in the environment, including of their genotypes.  It makes evolutionary sense, of course, because environments screen organisms for 'fitness'.  However, its negative--no change in the environment implies no evolution-- doesn't make sense and badly misrepresents what is widely assumed that we know about evolution. Even if we define evolution, as often done in textbooks, as 'change in gene frequencies' such change clearly occurs even in stable environments.  Mutations always arise, and selectively neutral variants, that is, that don't affect the fitness of their bearers, change in frequency by chance alone, not by natural selection, which means that at the genomic level evolution still occurs. It's curious that not only can organisms stay very similar in what seem like static environments, but also can be similar even in changing environments.

The idea of dual environmental-genetic stasis is an inference made from species that seem to stay similar for long time periods in environments that also appear similar--but how similar are they really?

Indeed, there are several problems with the widely if often implicitly assumed 'null hypothesis':

  1.  It is a very narrow assumption of the meaning of 'evolution', implicitly implying that it refers only to functionally important traits or their underlying genotypes. As we will see, there are ways for genetic change (and even trait change) to occur even in static environments, so that an unchanging environment doesn't imply no biological change.
  2.  It implies that 'the environment' actually stays the same, although 'environment' is hard to define.
  3.  It implies a tight essentially one-to-one fit between genotype and adaptive traits, so that in unchanging environments there will not be any functional genomic change.

All of these assumptions are wrong.  In essence, there cannot be 'the', or even 'a' null hypothesis for evolution.   Sexual reproduction, horizontal transfer, and recombination occur even without new sequence mutation.  To ignore that along with assuming a stationary environment, and adopt a null hypothesis that had anything like mathematical or Aristotelian rigor would be to reduce evolution's basis to something like this not-very-profound tautology:  Everything stays the same, if everything stays the same.

So let's look at this a little more closely
From the fossil record, we infer that some species stay the 'same' for eons, sometimes millions of years.  Then they change.  Gould and Eldridge called this 'punctuated equilibrium' and it was taken as a kind of up-dated version of Darwinism--mistakenly, because Darwin recognized it very clearly at least by the 6th edition of his Origin.  And while some aspects of animals and plants can hardly change in appearance for long time periods, close inspection shows that only some aspects of what can be preserved in fossils stays similar; other aspects typically change.  Also, speciation events occur and some descendants of an early form do change in form, even if the older species seems not to change. So we should be very careful even to suggest that environments or species really are not changing.

But mutations certainly occur and that means that even for a set of fossils that look the same, the genomes of the individuals would have varied, at least in non-functional sequence elements.  That itself is 'evolution', and it is misleading to restrict the term only to visible functional change.  But genetic drift is just the tip of the molecular evolution iceberg.  It is now very clear that there are many ways for an organism to produce what appears to be the same trait--and this is true both at the molecular and morphological levels.  That is, even a trait that 'looks' the same can be produced by different genotypes.  I wrote about this long ago in a rather simple vein, calling it phenogenetic drift, and Andreas Wagner in particular has written extensively about it, with sophisticated technical detail, in his book The Origin of Evolutionary Innovation, and this paper.  (The images are of my general paper and Wagner's book given just to break up the monotony of long text! ; he has written a more popular-level book as well called Arrival of the Fittest, which is a very good introduction to these ideas).

Recent exploration, with great detail

A modest statement of principl

Wagner explores this in many ways and among his views is that the ability of organisms to evolve innovative traits is based on the huge number of overlapping, essentially similar ways it can carry out its various functions, which allows mutations to add new function without jeopardizing the current one. Redundancy is protective against environmental changes as well as enabling new traits to arise.

This is in a sense no news at all. It was implicit in the very foundational concept of 'polygenic' control-- the determination of a trait by independent, or semi-independent of many different genes.  The way complex traits are thus constructed was clear to various biologists more than a century ago, even if the specific genes could not be identified (and the nature of a 'gene' was unknown).  A fundamental implication of the idea for our current purposes is that each individual with a given trait value (say, two people with the same height or blood pressure) can have its own underlying multi-locus genotype, which can vary among them.  Genotypes may predict phenotypes, but a phenotype does not accurately predict the underlying genotype (a deep lesson that many who promote simplistic models of causation in biomedical contexts should have learned in school).

And of course that does not even consider environmental effects, even though we know very well that for most characters of interest, normal or pathological, 'genetic' factors account only for a modest fraction of their variation. And, of course, if it's hard to identify contributing genetic variants, it's at least as difficult to identify the complex environmental contributors who make inference of phenotype from genotype so problematic. That is, neither does genotype reliably predict phenotype, nor does phenotype reliably predict genotype and the idea that they do so with 'precision' (to use todays' fashionable branding phrase) is very misleading.

In turn, these considerations imply that even if we accepted the idea of natural selection as a Newtonian deterministic force, it works at the level of the achieved trait, and can ignore (actually, is blinded to) the underlying causal genetic mechanism.  There can be extensive variation within populations in the latter, and change over time.  Just because two individuals now or in the past have a similar trait does not imply they have the same underlying genotype and hence does not imply there's been no 'evolution' even in that stable trait!

In this sense, evolution could be Newtonian, driven by force-like selection, and still not be genetically static.  But there's more.  How can there actually be stasis in a local environment?  If organisms adapt to conditions, then that in itself changes those conditions.  Even within a species, as more and more of its members take on some adaptive response to the environment, they change their own relative fitness by changing the mix of genotypes in their population, and that in turn will affect their predators and prey, their mate selection, and the various ways that the mix of resources are used in the local ecology.  If, say, the members of a species become bigger, or faster, or better at smelling prey, then the distribution of energy and species size must also change.  That is, the 'environment' cannot really remain the same.  That ecosystems are fundamentally dynamic has long been a core aspect of population ecology.

In a nutshell, it must be true that if genotypes change, that changes the local environment because my genotype is part of everybody else's 'environment'. In that sense, only if no mutations are possible can there be no 'evolution'. Even if one wants to argue that all mutations that arise are purged in order to keep the species the 'same', there will still be a dynamic mix of mutational variants over time and place.

One could even assert that an essence of Darwinism, literally interpreted, is that environments cannot be the same because the adaptation of one species affects others, even were new mutations not arising, because it affects the fitness of others. That is what his idea of the relentless struggle for existence among species meant, so stasis did cause him a bit of a problem, which he recognized in the later edition of the Origin.

I think that in essence Darwin viewed natural selection as being basically a deterministic force, like gravity, corresponding to Newton's second law of motion. And the idea of stasis corresponds to Newton's first law, of inertia. Today even many knowledgeable biologists seem to think in that way (for example, invoking drift only as a minor source of 'noise' in otherwise force-like adaptive evolution). Selective explanations are offered routinely as true, and the word 'force' routinely is used to explain how traits got here.
But there are deep problems even if we accept this view as correct.  Among other things, even if natural selection is really force-like, or if genetic drift exists as a moderating factor, then these factors should have some properties that we could test, at least in principle.  But as we'll see next time, it's not at all clear that that is the case.

Darwin the Newtonian. Part I. The Darwinian worldview

History shows that, even in science, things that everyone has long taken for granted may not be true.  Thinking in ways more carefully constructed to be restrained by what we actually know is often difficult, and the temptation is to believe what we want to believe. There are many normal, human, not to mention professional reasons for this.  But it's not good for science.  What may appear to be clear-cut 'objective' concepts about the material world can verge on the abstract or even philosophical, based on subjective opinion more than fact.  As we've discussed before, in a sense this is due to our need in evolutionary biology to rely on statistical tests based on internal comparisons, rather than to use statistical methods to test hypothesized, externally derived laws of nature (see this series and earlier--search on 'statistics' or 'p-value').

In 1859, Charles Darwin's Origin of Species culminated what considerable contemporary rumination had been suggesting, with his assertion that life today is the result of a material, historical process, by which current organisms have arisen by divergence from a common ancestry.  His synthesizing insight transformed biology in many ways.  Before that biology had largely been a descriptive science.  Before Darwin, with a few very speculative exceptions, the best causal explanations for the diversity and adaptations of organisms had been that God created them on an ad hoc basis.  Darwin saw otherwise, but his thinking was embedded in his era's general views about science.

Thanks to developments in the European Enlightenment period, by Darwin's time causation in nature was being viewed, by scientific thinkers at least, as based upon natural laws.  The Newtonian view of the cosmos was the prevalent one and, in keeping with this, Darwin adopted an implicitly quantitative, law-like view of biology.  As far as I know, Darwin was not a diligent student except in relation to areas like geology and botany, and he certainly was not mathematical (he himself said so).  However, he must have known at least something about Isaac Newton (a rather famous Cambridge predecessor).

Isaac Newton; 1689 by Godfrey Kneller, Wikipedia

Still, whatever he formally knew of Newton's laws of motion Darwin essentially accepted some of Newton's basic laws of motion, which we can state as follows:
1.  An object at rest remains at rest (law of inertia)
2.  Objects move or change motion only when force-like acceleration is applied, (and the greater the mass of the object the greater the force needed to change its motion)
3. Every action involves an equal and opposite reaction (when pushed, an object pushes back)

There are, I think, important analogs in Darwin's thinking, and there is still today widespread uncritical application of Newtonian-like thinking to Darwin's ideas.  The other day, I heard a deservedly famous and prominent geologist say that Darwin's 'Null hypothesis of evolution' was that unless the environment changes, no evolution will occur. This is analogous to the law of inertia, and I think it's actually fundamentally quite wrong, but we will see why it seems tempting and plausible.

The classical idea, still asserted without much if any questioning, is that organisms are fitted to their environment.  Analogous to the Newtonian law of inertia, if the environment doesn't change, neither will the organisms.  Darwin was, to my knowledge, not wholly explicit about this, but it was at the very least implicit in his view as expressed in The Origin of Species.  At least, by the 6th edition he recognized that there can be long time periods when organisms seemed not to change.

However, and this is analogous to Newton's second law, if the environment changes, then in a force-like way it screens the varying genomes of organisms, favoring those that are suited to the new conditions.  The force Darwin called natural selection.  I'm mixing bits of new and Darwin-time terminology here, but the gist of Darwin's view is that natural selection is a deterministic force, which he likened to the force of gravity in his law-like, deterministic worldview in regarding to 'motion' (change) in organisms.  Indeed, he many times asserted that the smallest difference among organisms would be detected and screened by selection.

After this has gone on for a while, the selective 'acceleration' ceases because the organisms are now adapted to their surroundings.  At that stage, the law of inertia takes over. His theory of inheritance was fundamentally wrong, but the Darwinian idea expressed in modern genetic terms is that the organisms in a population at any time and place vary genetically, and when the environment changes, those whose genotypes are best suited to the new environment will reproduce more prolifically, and will increase in frequency, driving inferior genotypes out of the population.

The Darwinian analogue to Newton's third law of motion is that changes in the nature of one organism in a local area improves its use of, and thereby alters, its local ecology.  The faster foxes catch the rabbits and proliferate. But this in turn makes the rabbits hoppier.  This then sets up a new force--in the local organisms--that Darwin referred to as the relentless 'struggle for existence.'

There are some issues in this view that are not well enough appreciated.  Darwin's endless struggle for existence suggests a continuing maelstrom of change, and yet it has been noticed that some species, based, for example, on ancient fossils.  Likewise, widely dispersed species that seemed similar across their areas of habitation implied that they had long had been static--because it takes a long time to spread over vast geographic areas.   In the case of some dinosaurs, a hundred or more million years, and based on some bacterial fossils, several billion.

Stromatolite (bacterial fossil); Western Australia, By Didier Descouens 

The idea this suggests is one of evolutionary stasis. This was recognized by Darwin, at least by the 6th edition of the Origin, and he mused over how periods of stasis would lead eventually to evolutionary change.   This idea, often now called 'punctuated equilibrium,' was claimed by Gould
in his final tome to be his own life's main discovery and contribution.  Perhaps he had not read Darwin closely enough?

An important point here is to recognize what Darwin was trying to account for.  Either selection is a relentless force-like aspect of nature, or there can be a static period when no force is being applied. How can both be true?

One answer is that there is no way for genotypes to be static, because mutations always arise.  Even if some are purged by selection's force, many will be selectively neutral and genomic evolution will always be occurring.  However, what we can see in fossils is only some aspects of morphology.  This means that while genomes are evolving, at least neutral parts, some aspects of traits persist, for adaptive or whatever other reason.

The idea of an evolutionary 'Null hypothesis' is hence elusive.  In one sense, some trait may not change unless the selective environment changes.  In another sense, selection can maintain functionally adaptive traits, while other traits and neutral DNA sequences change.  The traits may not 'evolve', but the sequence does.

Such ideas go against even Darwin's idea of life as an endless universal struggle, and perhaps why he had to do some rationalizing to account for apparent stasis.

Even this account for stasis of a single species would seem incompatible with the view of a relentless struggle among species that drives all of them in the endless rat-race of adaptation.  In that reality every part of an ecosystem affects every other part, so how can there be stasis?

We will think about some of these issues in the next three posts.  First, we'll ask whether life really can be viewed as 'Newtonian,' as Darwin did.  Then, we'll ask whether natural selection and genetic drift actually exist as they are universally characterized to be.  We'll see that our theories and our methods of inference, leave major issues open even about these fundamental aspects of the theory of life.

They were all my future specimens. And they died.

Without skeletal collections we'd struggle to do much evolutionary biology, especially when it comes to studying fossils.

We'd hate to let all those specimens go to waste, just languishing there in museum drawers. Sciencing them brings honor to their death. (Thanks for the new verb, Andy Weir.) But while we're learning from skeletons we can never forget that they're dead.

So although many of our samples are animals that were hunted by President Theodore Roosevelt (thanks Smithsonian!) or Major Powell-Cotton (thanks Powell-Cotton museum!), many of them, especially when it comes to human skeletons, are ones that died of "natural" causes.

You're thinking, well, duh. Well, yeah. Duh. But sometimes what's obvious still isn't so obviously important until someone goes to the trouble to very carefully consider it.

If the "osteological paradox" has already come to mind, that's probably because you're familiar with the classic paper "The Osteological Paradox" co-authored by a certain Mermaid and other former graduate school professors of mine.  Although the paper discusses issues that are more complicated and more specific than we need to hash out here, "osteological paradox" is a great term for the conundrum that scientists face when reconstructing things like health, fitness, and adaptation in past populations from the remains of the individuals who died.

Naturally, if you've been raised on "osteological paradox" thinking, it's one of the first things that comes to mind when you see a visually stunning study by my colleagues that analyzes pelvic morphology of dead individuals to reveal differing adaptive morphologies in the pelves of males vs. females.

Sexual dimorphism in the human pelvis has been known for quite some time, and it's already well-understood that the differences are largely located in the dimensions of a woman's birth canal. But this new study shows that differences are observable from birth and that women at post-reproductive ages do not retain the obstetrically-beneficial dimensions that younger women do during their fertile years. One of the arguments this new paper makes is that human female pelves are adapted to be most accommodating for childbirth during the child-bearing years. And that very well may be the case. However, these claims for adaptation, like most based on human skeletal samples, were based on women who were dead and, thus, not adapted.

In this context, the concluding paragraph of "The Osteological Paradox" is worth quoting:

"...choosing among competing interpretations of the osteological evidence requires tight control over cultural context as well as a deeper understanding of the biology of frailty and death. These problems deserve far more attention than they have received to date if we are to make sense of the biomedical consequences of the major social and environmental changes that have occurred during the course of cultural evolution."

And that could be extended to "biological evolution" as well. Maybe it has been in a later paper.

Anyway, when we're looking at dead humans with an evolutionary mindset, it's probably good to ask whether we can know if selective pressures were the same across the timespan covered by the sample. It's also probably good to ask whether environmental conditions were the same across the timespan covered by the sample. It's also probably good to sing this to ourselves as we design our evolutionary study of the human skeleton:

On shouting, "SEED MY BABY WITH MY VAGINAL MICROBES!"

Co-authored by Emily Pereira, Anthropology major, University of Rhode Island

When I was pregnant, the human microbiome was hot. And news about the microbiomes of newborns was even hotter, at least to my eyes and ears because I was on the verge of having one.

This was in 2014. Studies were starting to find that babies born via c-section have different microbiomes than babies born vaginally. These findings were being interpretively linked to health problems down the road. 

Here’s a write-up of one study of a few 4-month-olds that I came across while pregnant: “Infant gut microbiota influenced by cesarean section and breastfeeding practices; may impact long-term health”

And today studies continue to pop-up that find differences in baby microbial composition and then suggest those differences may be linked to future health problems. For example, here’s a recent one from 2016 in JAMA Pediatrics: 

“CONCLUSIONS AND RELEVANCE The infant intestinal microbiome at approximately 6 weeks of age is significantly associated with both delivery mode and feeding method, and the supplementation of breast milk feeding with formula is associated with a microbiome composition that resembles that of infants who are exclusively formula fed. These results may inform feeding choices and shed light on the mechanisms behind the lifelong health consequences of delivery and infant feeding modalities.”

These discoveries about c-sections seem important because microbes are now famous for being linked to all kinds of health troubles. 

According to the American Microbiome Institute... 

“studies are finding that our bacteria (or lack thereof) can be linked to or associated with: obesity, malnutrition, heart disease, diabetes, celiac disease, eczema, asthma, multiple sclerosis, colitis, some cancers, and even autism.”

And of course many of those same things have been epidemiologically traced back to birth by c-section. Here’s a report on one study, “published in the British Medical Journal, [that] found that newborns delivered by C-section are more likely to develop obesity, asthma, and type 1 diabetes when they get older.”

Another found that, “people born by C-section, more often suffer from chronic disorders such as asthma, rheumatism, allergies, bowel disorders, and leukaemia than people born naturally."

One can’t help but assume it’s all connected. If microbes are to blame for this list of problems and if c-sections are too and if c-sections are causing babies to have different microbiomes, then the following conclusion seems like a no-brainer: we need to be wiping c-sected babies with their mother’s vaginal juices.

So although I did basically nothing to prepare for a c-section (d’oh!), I imagined that if my childbirth came to surgery, that it would be really easy to avoid the risks to my baby's health by simply wiping him down with something soaked in my lady fluids.

I had even caught wind of a trial of this procedure, written-up somewhere, and so I mentioned it to my OB at a prenatal visit. She said she’d heard of it and that there was a term for it but the term escaped her. The idea excited her, but it wasn’t even remotely close to being part of regular clinical practice yet. Remember, this was summer 2014. Sensing it was too soon and out of reach, I changed the subject of conversation. Yet, I continued to believe that someone would just help me out with the whole vaginal swabbing thing if need be. It seemed simple enough. No biggie.

At the time, I didn’t Google around for tips or instructions so I don’t know what the Internet was offering up to would-be mothers/vaginal-microbe believers like me. But today it’s quite easy to find encouragement to D-I-Y transform your kid’s c-sected microbiome into a naturally-born one.

Here, let Mama Seeds explain:

“In the event of a c-section, be proactive. Mamas, we know this recommendation is not without its “icky-factor," but WOW it makes perfect sense when you think about it, and some believe it will be a standard recommendation in the future. Here goes: if your baby is born via c-section, consider taking a swab of your vaginal secretions and rubbing it on your baby’s skin and in her/his mouth. I know, ick. But when babies traverse the birth canal, they are coated in and swallowing those secretions/bacteria in a health-promoting way, so all you’re doing is mimicking that exposure. Don’t be afraid to ask your midwife or OB to help you collect the vaginal swabs—or do it yourself, if you’re comfortable. You have all the available evidence on your side.” - Michelle Bennett, MD is a full-time pediatrician, a Fellow of the American Academy of Pediatrics, a mother of two, and a founder of Mama Seeds.

Like I said, I didn’t have Mama Seeds. But I didn’t need Mama Seeds. While I was being wheeled into emergency cesarean surgery, I still shouted “SEED MY BABY WITH MY VAGINAL MICROBES!”

The reaction from the hospital staff? There was no reaction and, surprise surprise, there was no artificial seeding of my baby’s microbiome.

And that’s good. That’s how it should have gone down because my request was not based on scientific thinking. I hope you'll forgive me. I was pregnant. I wasn’t myself.

Slowly I’m becoming myself again, though, and thanks to a keen student, Emma Pereira, this post’s co-author, I’ve learned quite a bit about the science behind whether I should have seeded my newborn with my vaginal microbes. And the answer to anyone who’s wondering is a resounding NO. At least for now.

Here’s why.

1.   We don’t know if it’s necessary. Despite the increasing numbers of studies, no one to our knowledge has looked longitudinally at the microbiomes of humans born via c-section to find out if the changes detected (in very small samples) early on in these studies actually last, let alone if they can be causally linked to differences in health. It seems like the money and the technology is there to identify (via genetic sequencing) myriad microbial species, but the time and energy just isn’t there to do much else. So, although there is a growing literature, the dots aren’t connected yet. A graphic may help explain what we've learned: 

2.  You could actually harm your baby. Because there is currently no known good to come of seeding one’s c-sected baby with one’s vaginal microbes, there can only be bad. Yes, authors of this study published recently in Nature Medicine took a bunch of gauze that had been sitting in the mother’s vagina for an hour and swabbed 4 babies for a duration of about 15 seconds right after their birth by c-section and then found a significant difference in their microbiome at 30 days-old compared to babies who weren’t treated.  The microbiome wasn’t identical to vaginally born babies, but at least it wasn’t identical to those poor c-sected controls who didn’t get swabbed, right? Well, maybe wrong. First, please revisit number 1. And, second, maybe causing a baby to have a c-sected microbiome is not worse than seeding a baby with genital herpes, which is a very real possibility in practice, outside of these early, highly controlled pilot studies. As reported in Should C-section babies get wiped down with vagina microbes?, “the procedure could unknowingly expose newborns to dangerous bugs, pathogens that babies born by C-section usually avoid. Group B streptococcus, which is carried by about 30 percent of women, can trigger meningitis and fatal septicemia... Herpes simplex virus can lead to death and disability in newborns. And chlamydia and gonorrhea can cause severe eye infections.”

So, again, as of right now, there is no reason to seed one's c-sected baby with one's vaginal microbes. And there are very good reasons not to! 

We think that the temptation to blame the rise of numerous complex health problems to something as simple (and easily knowable) as the way we’re born is similar to the temptation to reduce these very same complexities to what’s coded in the genome. For some people, maybe even many, it may turn out to be this simple! But we’re far from knowing whether that’s true. 

Spare your baby from meddling with his microbes until the evidence is there. 

On this day in 1986

Lost in an African Jungle*

It all began in L.A. California when I had to go to Africa on safari, to hunt the Wild Weirdo Snake. Because I was a scientist and had to study one. So I went to Africa to the big bush (the grassy swamp land). I was there but suddenly I got lost. Luckily, I brought a map. But it started to rain and my map got soaked. So I couldn't use that. But then, in the midst of the jungle, I heard what sounded like Indians. So, I ran, but they were coming from all directions. They came and got me. They had a Wild Weirdo Snake for a pet. So they wrapped it around me. I died. So they ate me. And for the rest of my life my head hangs from a stick.

The End

Is this the Wild Weirdo Snake? (source)

*Thanks to my mother for saving this.

The last orang standing (no place to swing): why do we care?

Every time we see documentation of threats to the existence of particular species, the issue arises as to whether human activities are responsible.  And if so, there's usually a plea to stop the devastation. Recent examples that led me to think about what this means include the April 5 NY Times story about devastation being experienced by the orangutans in Indonesia, whose range is becoming ever more limited.  Here is an image from that story:

All alone in a devastated habitat.  NYTimes story 4/5/2016

The pathos of the image is evocative, and even heart wrenching, but fortunately this particular animal was rescued.  Here is a heart-warming image from the same story:

Rescue!  From the same Times story

And there was a recent, truly uplifting story, from Al Jazeera, about a conservationist who has spent decades carefully and patiently enabling orangs to return to the forest.

Orangutans are in trouble, and at least some people seem to care.  Indeed, the pathos is about much more than individual orangs orphaned to a cruel fate.  It is about the endangerment of their species itself. There are similar concerns about other species, such as the likely impending doom of other great apes (besides ourselves): chimps and gorillas, in particular.  But, in fact, why are we concerned?

Why the concern?
It may seem obvious.  After all, every individual dies--humans, ants, birds, our pets, our children, ourselves--and orangs.  We don't want to die or suffer, so maybe it's natural in some way for us to empathize with those who are dying or suffering.  Knowing we ourselves will die some day, we don't like to see other individuals die, and in a collective sense, we extend the same feelings of empathy rather automatically to whole species.

But while it may be uncomfortable to think about it, 'we care' doesn't apply to everyone and it's at least worth thinking a bit about why anyone would care.  Every species becomes extinct.  There will always be a last one standing (or, if there are still trees around, swinging).  And it, too, will go.  Even if we except those lineages of life that continue to produce offspring which some day we would dub with a new species name, many if not by far most species eventually disappear without issue.  Extinction is a permanent loss (even if some geneticists occasionally resuscitate a dodo, mammoth or Neanderthal from DNA), but so is every death.

Orangutans and chimpanzees may be cute fellows we can relate to, but there have been quite a few other ape species over the past few million years.  Each was presumably just as cute and cuddly and person-like in its own way, as the orangs, and chimps are today (not to mention those lumbering gorillas, and gibbons, those acrobatic swingers).  But something did each of them in, except for the one lineage that led to us--and it may have been that one--our ancestors--who did the others in at the time!  They didn't set up nature reserves for the other, unlucky, apes.

Extinction is a normal part of life.  So I again think it's fair to ask why our empathy is so poignant when we can document fates such as those of the orangs, or the many other endangered species, that we can see in the flesh.

The daily obituaries and the vanishing orangs are instances of business-as-usual, that happen to be taking place in our own particular time. It may well be that the specific forces at work today are uniquely due to the predominance of humans on the earth, but from a more distanced view, that is just one of many more or less unique eons or events during earth history.  We've been changing things very rapidly, but perhaps not particularly more dramatically than major cataclysmic meteor strikes or volcanic eruptions that have, or may have, quickly changed global climates and led to mass extinctions.

So even if the details of human agency are specific, the phenomena of change are generic.  The comings and goings of individual plants and animals, of species and ecosystems have always been specific to a given time and place.  That is the essence of evolution as we know it.  One could even say that, as biologists, we should be glad that we can see the theoretically hypothesized, inferred process of extinction in action in diverse ways.

It is also interesting to me that while we may rue the passing of a few orangs in a jungle, that means we are being unsympathetic with the people who need (or want) more rice fields or timber, or to make a living by selling ivory.  Indeed, in many ways we often seem less concerned about the many individuals of our own species who are daily subjected to marginal or lethal living circumstances, or who are bombed out of existence, also by humans. There are far, far more such victims--each of them individuals--than there are living orangs who could be subjected to such forlorn fates as are seen in these recent news stories.  So in some ways the 'we' who are so empathetic are sitting in protected privilege, and isn't that empathy a kind of self-flattering feeling?

Vegetarians have various reasons for following their diets, one of them being that they don't want to be the cause of death or suffering of animals.  This may be similar to sentiments about displaced orangs.  And of course, most people who can do eat meat, even if we want to save the orangs, and are antagonistic to poachers or encroaching farmers.  It may seem less existential because we can, after all, always make more chickens or cows.  And if salmon become endangered, we try to stop catching them (for a while).  That is rather selfish even if there might be a twinge of compassion involved.

It is rather similar with climate change, I think.  We know very well that not even continents are forever.  Islands and shores come and they go. We owe today's gorgeous mountain ranges, and spectacles like the Grand Canyon, to yesterday's destruction of what was before.  Why do we care about climate change when, in essence, climates have always changed and the major effects of this epoch will occur decades or a century or more from now, when neither we nor even our children, will be here to see them?  Yes, humans may be the immediate cause of this cycle, but if we stopped driving and flying today, biogeography will change anyway, in its own ways and on its own times.

In every objective sense, climate change and the conflicts and dislocation that will be associated with it, will just be another part of the earth's long and dynamic history, an evolutionary history, not always pleasant, in which every today is left behind to become a yesterday to its tomorrow.

The meaning of 'life' is local
Obviously the key is what 'in every objective sense' means, or doesn't, to these feelings.  Perhaps the fact is that this is not a phenomenon in any objective sense.  Instead, it is personal and emotional. Is it a form of sappy nostalgia, or some strange empathy that we extend to a few furry friends if not always even to members of our own kind?  Is it deeper and more self-referential, an extension of the empathy for our children and close kin, that evolution has programmed in our particular species? Do we shed tears for the hapless orangs because we know our own similar fate awaits us?  Is our empathy for orangs and other endangered species a way of pretending, somehow, that by 'saving the planet' we are saving ourselves--a need to feel important, or a desire to avoid facing the fact that it will be me sometime soon, too?

To many people this sort of empathy gives life its 'meaning', a vague term that refers to values we choose to hold.  These values are subjective, and we know that such 'meaning' is just for our own personal, temporary lives.  Some deeply religious people believe God gave us the earth to exploit, yet other equally religious people believe we must cherish it and keep it as pristine as God made it. Indeed, the atheists I know are at least as empathetic to these values for reasons they might not even think need explaining: it's just how they feel about the cosmos.

Personal value systems are in essence how we choose to live and what to value in the time we happen to have here, even when we also know they make little difference to long-term nature.  It isn't nice to do so, but I think it's appropriate to note that even this kindly view is not so innocent: What people value is also what they so often seem to feel they must force others to value as well, which is more or less how we behave about sociopolitics generally.  We sympathize with the orangs and elephants but demonize the farmers who are clearing the forest, or the ivory hunters.

To me personally, at least, if we want to try to be objective about the cosmos, and we accept that evolution, with its emphasis on reproduction and survival and thats pretty much it, explains how we got here, i't's unclear why we should particularly care about anything other than what affects us directly, or perhaps indirectly in the sense of our children, and even that seems to be purely from survival instinct.  Maybe it just pleases us to see orang-rescue stories.  But I still find it curious that we care or even wish to prevent what we know very well has always happened, and is indeed the basis of the evolutionary processes that made us possible.  In some ways, we act as if extinction were some new phenomenon, newly ominous in the world.

So what if, in our time, it happens to be a few apes or coral or whatever that disappear?  The 'so what?' would have to be either that we are oblivious to the realities of evolutionary existence or that we know those realities but choose to hold some values that give us a sense of existential value or purpose, in our own lives, even if they are individually fleeting.

I myself like attempts to preserve what seems good in the world.  I am warmed by the fact that some lucky orangs will be given a chance at life, because somebody cares to do that for them.  I feel that way even if I know that their eventual death, out there in cruel Nature, is likely to be very unpleasant. In fact, it may be a blessing, because the last orang standing, or swinging, will be very lonely.  And I love our three cats!

I personally agree with sustainability people in thinking that we should cut down--way down--on our consumption and pollution, and on causing major ecological changes.  But I also realize that my feelings are just my own, probably rather egotistical, way of making it through the temporary maze.

There will be a last hurrah for the orangs.  It is likely to be soon.  But, despite all I've just said, I don't want to see it, because while it may be naive vanity, I too care.