Thursday, May 5, 2016

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 KnellerWikipedia

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.

Wednesday, May 4, 2016

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:



Tuesday, May 3, 2016

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. 

Tuesday, April 26, 2016

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.

Thursday, April 14, 2016

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.

Tuesday, March 29, 2016

Statistical Reform.....or Safe-harbor Treadmill Science?

We have recently commented on the flap in statistics circles about the misleading use of significance test results (p-values) rather than a more complete and forthright presentation of the nature of the results and their importance (three posts, starting here).  There has been a lot of criticism of what boils down to misrepresentative headlines publicizing what are in essence very minor results.  The American Statistical Association recently published a statement about this, urging clearer presentation of results.  But one may ask about this and the practice in general. Our recent set of posts discussed the science.  But what about the science politics in all of this?

The ASA is a trade organization whose job it is, in essence, to advance the cause and use of statistical approaches in science.  The statistics industry is not a trivial one.  There are many companies who make and market statistical analytic software.  Then there are the statisticians themselves and their departments and jobs.  So one has to ask is the ASA statement and the other hand-wringing sincere and profound or, or to what extent, is this a vested interest protecting its interests?  Is it a matter of finding a safe harbor in a storm?

Statistical analysis can be very appropriate and sophisticated in science, but it is also easily mis- or over-applied.  Without it, it's fair to say that many academic and applied fields would be in deep trouble; sociopolitical sciences and many biomedical sciences as well fall into this category.  Without statistical methods to compare and contrast sampled groups, these areas rest on rather weak theory.  Statistical 'significance' can be used to mask what is really low level informativeness or low importance under a patina of very high quantitative sophistication.  Causation is the object of science, but statistical methods too often do little more than describe some particular sample.

When a problem arises, as here, there are several possible reactions.  One is to stop and realize that it's time for deeper thinking: that current theory, methods, or approaches are not adequately addressing the questions that are being asked.  Another reaction is to do public hand-wringing and say that what this shows is that our samples have been too small, or our presentations not clear enough, and we'll now reform.  

But if the effects being found are, as is the case in this controversy, typically very weak and hence not very important to society, then the enterprise and the promised reform seem rather hollow. The reform statements have had almost no component that suggests that re-thinking is what's in order. In that sense, what's going on is a stalling tactic, a circling of wagons, or perhaps worse, a manufactured excuse to demand even larger budgets and longer-term studies, that is to demand more--much more--of the same.

The treadmill problem

If that is what happens, it will keep scientists and software outfits and so on, on the same treadmill they've been on, that has led to the problem.  It will also be contrary to good science.  Good science should be forced by its 'negative' results, to re-think its questions. This is, in general, how major discoveries and theoretical transformations have occurred.  But with the corporatization of academic professions, both commercial and in the sense of trade-unions, we have an inertial factor that may actually impede real progress.  Of course, those dependent on the business will vigorously resist or resent such a suggestion. That's normal and can be expected, but it won't help unless a spirited attack on the problems at hand goes beyond more-of-the-same.




Is it going to simulate real new thinking, or mainly just strategized thinking for grants and so on?

So is the public worrying about this a holding action or a strategy? Or will we see real rather than just symbolic, pro forma, reform? The likelihood is not, based on the way things work these days.

There is a real bind here. Everyone depends on the treadmill and keeping it in operation. The labs need their funding and publication treadmills, because staff need jobs and professors need tenure and nice salaries. But if by far most findings in this arena are weak at best, then what journals will want to publish them? They have to publish something and keep their treadmill going. What news media will want to trumpet them, to feed their treadmill? How will professors keep their jobs or research-gear outfits sell their wares?

There is fault here, but it's widespread, a kind of silent conspiracy and not everyone is even aware of it. It's been built up gradually over the past few decades, like the frog in slowly heating water who does't realize he's about to be boiled alive. We wear the chains we've forged in our careers. It's not just a costly matter, and one of understandable careerism. It's a threat to the integrity of the enterprise itself.
We have known many researchers who have said they have to be committed to a genetic point of view because that's what you have to do to get funded, to keep your lab going, to get papers in the major journals or have a prominent influential career. One person applying for a gene mapping study to find even lesser genomic factors than the few that were already well-established said, when it was suggested that rather than find still more genes, perhaps the known genes might now be investigated instead, "But, mapping is what I do!".  Many a conversation I've heard is a quiet boasting about applying for funding for work that's already been done, so one can try something else (that's not being proposed for reviewers to judge).

If this sort of 'soft' dishonesty is part of the game (and if you think it's 'soft'), and yet science depends centrally on honesty, why do we think we can trust what's in the journals?  How many seriously negating details are not reported, or buried in huge 'supplemental' files, or not visible because of intricate data manipulation? Gaming the system undermines the very core of science: its integrity.  Laughing about gaming the system adds insult to injury.  But gaming the system is being taught to graduate students early in their careers (it's called 'grantsmanship').


We have personally encountered this sort of attitude, expressed only in private of course, again and again in the last couple of decades during which big studies and genetic studies have become the standard operating mode in universities, especially biomedical science (it's rife in other areas like space research, too, of course).  


There's no bitter personal axe being ground here.  I've retired, had plenty of funding through the laboratory years, our work was published and recognized.  The problem is of science not personal.  The challenge to understand genetics, development, causation and so forth is manifestly not an easy one, or these issues would not have arisen.  

It's only human, perhaps, given that the last couple of generations of scientists systematically built up an inflated research community, and the industries that serve it, much of which depends on research grant funding, largely at the public trough, with jobs and labs at stake.  The members of the profession know this, but are perhaps too deeply immersed to do anything major to change it, unless some sort of crisis forces that upon us. People well-heeled in the system don't like these thoughts being expressed, but all but the proverbial 1%-ers, cruising along just fine in elite schools with political clout and resources, know there's a problem and know they dare not say too much about it.


The statistical issues are not the cause.  The problem is a combination of the complexity of biological organisms as they have evolved, and the simplicity of human desires to understand (and not to get disease).  We are pressured not just to understand, but to translate that into dramatically better public and individual health.  Sometimes it works very well, but we naturally press the boundaries, as science should.  But in our current system we can't afford to be patient.  So, we're on a treadmill, but it's largely a treadmill of our own making.

Wednesday, March 23, 2016

Playing the Big Fiddle while Rome burns?

We've seemed to have forgotten the trust-busting era that was necessary to control monopolistic acquisition of resources.  That was over a century ago, and now we're again allowing already huge companies to merge and coalesce.  It's rationalized in various ways, naturally, by those on the gain.  It's the spirit and the power structure of our times, for whatever reason.  Maybe that explains why the same thing is happening in science as universities coo over their adoption of 'the business model'.

We're inundated in jargonized ways of advertising to co-opt research resources, with our  'omics' and 'Big Data' labeling.  Like it or not, this is how the system is working in our media and self-promotional age.  One is tempted to say that, as with old Nero, it may take a catastrophic fire to force us to change.  Unfortunately, that imagery is apparently quite wrong.  There were no fiddles in Nero's time, and if he did anything about the fire it was to help sponsor various relief efforts for those harmed by it.  But whatever imagery you want, our current obsession with scaling up to find more and more that explains less and less is obvious. Every generation has its resource competition games, always labeled as for some greater good, and this is how our particular game is played.  But there is a fire starting, and at least some have begun smelling the smoke.

Nero plucks away.  Sourcc: Wikipedia images, public domain
The smolder threatens to become an urgent fire, truly, and not just as a branding exercise.  It is a problem recognized not just by nay-saying cranks like us who object to how money is being burnt to support fiddling with more-of-the-same-not-much-new research.  It is an area where a major application of funds could have enormously positive impact on millions of people, and where causation seems to be quite tractable and understandable enough that you could even find it with a slide rule.

We refer to the serious, perhaps acute, problem with antibiotic resistance.  Different bugs are being discovered to be major threats, or to have evolved to become so, both for us and for the plants and animals who sacrifice their lives to feed us. Normal evolutionary dynamics, complemented with our agricultural practices, our population density and movement, and perhaps other aspects of our changing of local ecologies, is opening space for the spread of new or newly resistant pathogens.

This is a legitimate and perhaps imminent threat of a potentially catastrophic scale.  Such language is not an exercise in self-promotional rhetoric by those warning us of the problem. There is plenty of evidence that epidemic or even potentially pandemic shadows loom.  Ebola, zika, MRSA, persistent evolving malaria, and more should make the point and we have history to show that epidemic catastrophes can be very real indeed.

Addressing this problem rather than a lot of the wheel-spinning, money-burning activities now afoot in the medical sciences would be where properly constrained research warrants public investment.  The problem involves the ecology of the pathogens, our vulnerabilities as hosts, weaknesses in the current science, and problems in the economics of such things as antibacterial drugs or vaccinations.  These problems are tractable, with potentially huge benefit.

For a quick discussion, here is a link to a program by the statistical watchdog BBC Radio program MoreOrLess on antibiotic resistance  Of course there are many other papers and discussions as well.  We're caught between urgently increasing need, and the logistics, ecology, and economics that threaten to make the problem resistant to any easy fixes.

There's plenty of productive science that can be done that is targeted to individual causes that merit our attention, and for which technical solutions of the kind humans are so good at might be possible. We shouldn't wait to take antibiotic resistance seriously, but clearing away the logjam of resource commitments in genetic and epidemiological research to large weakly statistical efforts well into diminishing returns, or research based on rosy promises where we know there are few flowers, will not be easy...but we are in danger of fiddling around detecting risk factors with ever-decreasing effect sizes until the fire spreads to our doorsteps.