Big Data: the new Waiting for Godot

In Samuel Beckett's cryptic play, Waiting for Godot, two men spend the entire play anticipating the arrival of someone, Godot, at which point presumably something will happen--one can say, perhaps, that the wait will have been for some achieved objective.  But what?  Could it simply mean that they can then go somewhere else?  Or, perhaps, there will be no end because Godot will never, in fact, arrive.

www.mckellen.com

A good discussion of all of this is on the BBC Radio 4 The Forum podcast.  Apparently, Beckett insisted that any such answers were in the play itself--he didn't imply that there was some external meaning, such as that Godot was God, or that the play was an allegory for the Cold War--which is one reason the play is so enigmatic.

Was the play written intentionally to be a joke, or a hoax?  Of course, since the author refused to answer or perhaps even to recognize the legitimacy of the question, we'll never know.  Or perhaps that in itself, is the tipoff that it really is a hoax.  Or maybe (I think more likely) that because it was written in France in 1949, it's an existentialist era statement of the angst that comes from the recognition that the important questions in life don't have answers.

Waiting for the biomedical Promised Land
That was then, but today we are witnessing real-life versions of the play: things just as cleverly open-ended, with the 'What happens then?' question only having a vague, deferred answer, as in Beckett's title.  And, as in the play, it is not clear how self-aware even some of the perpetrators are of what they are about.

I refer to the possibility that we are witnessing various Big Data endeavors, unknowingly imitative but as cleverly and cryptically open-ended as the implied resolution that will happen when Godot arrives.  Big Data 'omics is a current, perhaps all too convenient, scientific version of the play, that we might call Waiting for God'omics.  The arrival of the objective--indeed, not really stated, but just generically promised as, for example, 'precision genomic medicine' for 'All of Us'--is absolutely as slyly vague as what Vladimir and Estragon were presumably waiting for.  The genomic Godot will never arrive!

This view is largely but not entirely cynical, for reasons that are at least a bit subtle themselves.

Reaching the oasis, the end of the rainbow, or the Promised Land is bad for business
One might note that if the 'omics Godot were ever to arrive, it would be the end of the Big Data (or should one say Big Gravy?) train, so obviously our Drs Vladimirs and Estragons must ensure that such a tragedy, arrival at the promised land, the elimination of all diseases in everyone, or whatever, never happens in real life.  Is there any sense that anyone seriously thinks we would reach resolution of the cause of disease, with precision for all of us, say, and be able (that is, willing) to close down the Big Budget nature of our proliferating 'omictical me-too world?

We have entrenched the search for Godot, a goal so vague as to be unattainable.  Even the proper use of the term 'precision' implies an asymptote, a truth that one never reaches but can get ever closer to.  If we could get there, as is implied, we should have been promised 'exact' genomic medicine. And wouldn't this imply that then, finally, we'll divert the resources towards cures and prevention?

However, even if the perpetrators of the Big Promises never think or aren't aware of it, we must note that the goal cannot be reached even with the best and most honorable of intentions.  Because of births and deaths, and environmental changes, and mutations and recombination, there truly never is the palm-draped oasis at which our venture could cease.  There will never be an 'all' of us, and genetic causation is ever-changing (in part because of the similarly dynamic environment), meaning that there are no such things as risks to be approached with 'precision'.  Risks are changeable and not stable, and indeed not fixed numerical values.  At best, they are collective population (or sample) averages.  So there is never a 'there' there, anywhere.  There is only a different one everywhere.

But awareness of these facts doesn't seem to be part of the 'omicsalyptic promises with which we are inundated.  They seem, by contrast, rote promises that are little if any different from political, economic, or religious promises--if only we do this, we'd get to a Promised Land.  But such a land does not exist.

If we had, say, a real national health system, it would be properly and avowedly open-ended without anyone honorable objecting (if it were done well).  And epidemiologically, of course, there will always be new mutations, recombinations, environments and the like to try to understand--disease with, or without strong genotype-phenotype causation.  There will always be a need for health research (and basic science).  But science, of all fields of human endeavor, should be honest. It should not hold out the promise that Godot will arrive, but in a sense, openly acknowledge that that can never happen.

But this doesn't let those off the guilty hook who are hawking today's implicit Big Data, big open-ended budget promise that by goosing up research now we'll soon eliminate genetic disease (I recall that Francis Collins did indeed, not all that long ago, promise that this Paradise would come soon--um, I think his date was something like 2010!)  It's irresponsible, self-interested promising, of course.  And those in genomics who are intelligent enough to deserve to be in genomics do, or should, know that very well.

Like Vladimir and Estragon, we'll always be told that we're waiting for Godot, and that he'll be coming soon.


NOTE:  One might observe that Godoism is a firmly entrenched strategy elsewhere in our society, for examples, in regard to  theoretical physics, where there will never be a collider big enough to answer the questions about fundamental particles: coming to closure would be as fiscally threatening to physics as it is to life sciences.  Science is not alone in this, but our society does not pay it nearly enough skeptical heed.

Traffic jams ---> Trophic jams

We live in State College, PA, a small university town.  Well, it isn't nearly as small as it was when we moved here in 1985; Penn State enrollment has gone from around 30,000 when we got here to something like 50,000, and the town has grown to keep up.

How did that happen?  In essence, by sacrificing farm fields, turning them into condo centers, fine suburban-style cardboard 'mansions' with big grassy lots, 2-3 car garages (so everyone could drive a few miles to the nearest grocery), and so on. Even in this fairly small town, during the day, there are cars going through most intersections most of the time, even in the residential tracts.

To get from here to anywhere you need to get on I-80 or I-95, or some other throughway, where there is an endless chain of nearly stationary cars and trucks, hour after hour, mile after mile after mile.  Even when not obstructed by an accident or construction, the traffic is so heavy that it's not at all unusual for very slow, or creeping, or stopped traffic jams  tolitter the route.

The global traffic jam....
This same situation is happening all over the country, all over Europe, all over Japan and much of India and China.  It is even happening in parts of Africa and Australia.  This is 24/7.  The endless rivers of steel, rubber, and petrochemicals is like a river, and as Heraclitus said you can't step into it twice:  in no two moments is this same stream actually the same.  The cars and people and their arrangement are different--and, of course, we are never using the same gasoline twice: once used, it is burped into the atmosphere.

When you've been around more than a few decades, you'll start to realize that the current situation isn't 'normal'.  In a decade or two, or three, you'll think today was good and you were used to it, but that what has become normal, the jam of all jams, is what's really intolerable.

The traffic jam is, of course, due to the unconstrained growth of population, and its per capita consumption.  And this traffic jam, in turn, will have its longterm side effects in terms of the resources it uses up.  And that is going to lead to another kind of jam.

The global trophic jam
As we pave and build condos and shopping malls over what has for  millions of years been millions of acres of fertile land, we reduce the potential food production for us and other creatures, plant or animal.  Our sewage and waste claims more in water and land areas.  And we seem unable to prevent there always being more of us.  That means more paving, more building, and altered climate.  This means less fertile land for growing food--a trophic jam.

Climate is changing, and at least some of this is due to human-induced global warming.  Ostrich-like deniers, note: Climate change is happening regardless of why!  This will moisten some arid lands, and even more it will dry out currently fertile lands, in large amounts.  It will raise water levels on coasts and in rivers.  Since before the industrial age, settlements--now cities--were built on waterways for trade and so on, many or even most major cities will be threatened by water rise.  This will drive people inland, to cover over even more arable land.  Those living inland should realize that they will not be able to keep this inrush out.

Some areas, like Northern Canada perhaps, will become wetter.  But hardly anybody lives there.  Other areas, the rich farmlands, will become drier and likely many will become arid.  Nations that rely on food for their people or for trade, will have to look elsewhere--and if all of human history is any guide, this trophic jam will inevitably lead to attempts at military conquest.  If the breadbasket has shifted, say, from the US to Canada, and there's real food pressure, does anyone doubt that military expeditions won't head northward?

Our relentless, unconstrained traffic jams are irritating, especially to the impatient (like me) or those who want to spend time with their families, or bowling, rather than sitting in traffic.  But these headaches may be dooming us to stomach aches--the kind one gets when there isn't enough food.

One can be a climate denying ostrich, or a rosy believer in science and engineering, but if what we here and many others who know much more than we do are making these warnings, they are not all Chicken Littles.  Yet, like the swarm of lemmings, we are headed for the cliffs.

Apparently, today at least, we can't tell, or don't care to tell, the connections between traffic and trophic jams.

On Montaigne's cat

The person who, in a sense, invented the blog way back in 1580 in the form of his meandering Essays, was Michel de Montaigne.  He rambled across much of the territory of human thought, opining, suggesting, hinting, retreating and, well, just musing often rather incoherently.  Isn't that how most all modern blogs--this one included--are?!

Sadly for him, Montaigne couldn't Tweet his frequent 'posts', but he did Meow one.  In a famous oft-quoted part of his 'An Apology for Raymond Sebond', Montaigne muses about the arrogantly vain and presumptuous way that we judge our own uniqueness, in particular relative to other species.  In a famous passage, he writes:

"When I play with my cat, how do I know that she is not passing time with me rather than I with her"

  "Am I not a 'me'?"  Our own Mu (drawing by Anne Buchanan)

Humans routinely, conveniently, ignore the thought.  It is not in our self-interest.  Indeed, by now our cultural legacy is from the often obscure writing of Rene Descartes who, at least about himself recognized "I think, therefore I am."  But, apparently, a cat doesn't, so isn't.  By turning other creatures into automatons, mere machines, in the period that laid the foundation for modern science, Descartes' objectifying dogma opened not only justification for raising or hunting animals for our tables with a clear conscience, but also for the diverse experimentation that we do on uncountably many laboratory animals (indeed, the story with plants and their sense of self-awareness is becoming more complex, but that is too disturbing to think about).

Mea culpa!
I am personally heavily burdened by the thought of what I did over decades of research to countless mice.  Wholly innocent of any offense, they suffered the ultimate mortal penalty, so we could see what genes were expressed in their unborn young's teeth, or model effects on their craniofacial development or even, unforgivably perhaps, determine when they grew too old and their lives were no longer (to us) worth living and 'sacrificed' them.  No Viagra relief, retirement centers, hearing aids, etc. for them!

We were once forced to 'euthanize' (gas to death) a large number of laboratory mice, males, females, and young.  This was done in the usual 'humane' and research-ethics-approved say.  Deep in their sacrificial tank, as the hissing N2O began and the mice sensed the lack of air, they grouped tightly together in a terrified death huddle, young pressed against their mothers, that as I watched reminded me of images of Hitler's death-showers.  I will never forget that, though it was entirely within the standard accepted IRB protocols by which 'we' manage and manipulate 'them'.  They're just things after all.....aren't they?  Of course, if so, why do we bother with any sort of 'humane' treatment?  Or, if they're like us, why are we allowed to manipulate them, often to their terror and suffering?

We smugly let chimpanzees retire comfortably to senior centers (e.g., Chimp Haven, in Louisiana).  Why?  Because they are like us!  But other animals, even rhesus monkeys, are merely them.  Their lives are disposable.

Fortunately, for doubters at least, there is no after-world in which justice will be served to us, or where we might ask Him (She? It? Them?) why life was created as a food chain in which each depends on one or another form of this sort of savagery just for survival.

The science question
All of this is confession in the side booth, but it does raise the important question that bemused Montaigne: what is the 'me' of a cat like, compared to my own 'me'?  Can we ever know?  Scholars have long mused over what the nature of consciousness might be and how we could ever know it.  When the detached, mechanistic Descartes said, metaphorically, 'I think therefore I am", in the realm of consciousness he was 'thinking' in an exclusive way.

Frans de Waal, a prominent primate-watcher, has argued in a convincing way that 'thought' as we would casually use the term, doesn't really require language--doesn't have to be just the way you, right now, are doing it, to exist in every meaningful sense.

Of course, consciousness and its causative or even phenomenological nature has always been, and still is, essentially elusive.  I think and I am....but how?  How does wiring among a huge bunch of neurons lead to the meta-phenomenon of self-awareness?  Or since clearly cats and even bugs are self-aware in some senses, and many if not all animals have similar genomes and neural structures and wiring, why don't they, too, have the same sense.  Is there such thing as a lesser sense of 'me'?  How could we know, and  more importantly on what basis can we assert that they don't really have It?

Many have opined that science is the specifically objective endeavor by which we, operating from the inside (of our own heads), assess the way the outside world works.  If so, then science can't be expected to look inside the inside, from the inside, so to speak; perhaps consciousness is a literally subjective phenomenon that we experience but cannot examine by what we call 'science'.  Further, we assume that it--whatever it is--is also experienced by (at least some of our more decent) human fellows.

If the notion that in reality consciousness is the internal experience that is out of bounds for the essentially external purview of science, then we may relate our own and describe it as each of us sees it in others, from the outside, but we can't really understand it objectively.  If so it would simply be out of bounds by being inappropriate for science.  Many dabblers have tried to get around these obvious limitations, and they document all sorts of externally observed 'neural correlates', and in the same sense that a bullet through the head ends the phenomenon, these observations may reflect much about its objective nature.  But since consciousness is inherently about the experience, whatever the wiring, these correlates are, so far at least, just that--correlates.

Then how can we pronounce about other species?
Given this, what justifies the Cartesian convenience by which we blithely judge that they, not even cats, don't have 'it'?  Or is it just a more profound kind of convenience, namely, that we want them--other species--to be 'things' so that we, with our self-declared special powers, can control their lives and even eat them?  Is that different from the view wasps and tigers must essentially have of their prey?  Or is there such a thing as 'partial' or 'lesser' consciousness, compared to ours--as opposed simply to a different kind of consciousness, for example, not based on symbolic language as ours is?

Mammals, like our cat and dog friends, and even birds, have very similar genotypes to ours.  They have very similar cellular and anatomical structures, and neural wiring, to ours.  Their behaviors are very similar to ours.  They communicate in ways quite similar to ours except, perhaps, that it is more by stereotypical signaling than abstract symbols.  But we presume to dismiss their particular internal experiences as being mechanical, that is, fundamentally different from ours.

Is our declaration that they are just machines, or at least don't really have 'it', more than our particular convenient, self-interested rationale for doing what we like to them?

In its fashion that we would completely recognize were we to experience it, does a cow in the slaughterhouse queue ever ask:  'Whats this? Why me?', or a cat wonder 'What is it like to be a human?'  I ask what is it like, what does it seem and feel like, to be a laboratory mouse enjailed in a tiny cage?  Or to be gassed to death, at our convenience?  Montaigne's question is as cogent today as it ever was:

"When I play with my cat, how do I know that she is not passing time with me rather than I with her"

Our  cats (and chipmunk).
Drawings by Anne Buchanan.  For more of her fantastic artwork, see http://www.annevbuchanan.com/

                                           Left, center: are they not 'me's?  Right: aren't cat and chipmunk 'me's?

Thinking about science upon entering the field. IV. Finale

Here is the fourth and final of a four-part series of posts by Tristan Cofer, a graduate student in chemical ecology here at Penn State.  He has been thinking about the profession he is being trained for, and the broader setting in which it is taking place, and into which he will have a place:

For my final entry in this series, I would like to revisit some ideas from my earlier posts, as they pertain to a book that I recently finished, called ‘What is Real?’ (Basic Books, 2018) by Adam Becker. The book recounts quantum theory’s formative years during the early twentieth century, focusing as much on the personalities that were involved in the theory’s development as on the science itself.

Becker devotes much of the book to the 1927 Solvay Conference, which gathered twenty-nine of the world’s leading physicists to discuss the newly formulated theory. Attendees at the conference were divided into two ideologically distinct groups. In the majority, were Werner Heisenberg, Max Born, and others who had adopted Danish physicist Niels Bohr’s ‘Copenhagen interpretation’.

Influenced by Heisenberg’s ‘uncertainty principle’, Bohr claimed that subatomic entities had ‘complementary’ properties that could never be measured at the same time. Electrons, for example, behaved like ‘particles’ or ‘waves’ depending on the experiment. To Bohr, this implied that electrons, photons, and other subatomic entities only had probabilities until they were measured. ‘Reality’ simply did not exist in the quantum world. It was therefore pointless to talk about what was happening on the quantum level, since quantum theory could not describe the way the world ‘is’.

On the other side of the aisle were Louis de Broglie, Erwin Schrödinger, and Albert Einstein who were adamant that physical systems were ‘real’ whether we acknowledged them or not. Led by Einstein, this group argued that although considerable advances had been made in developing quantum theory, it was hardly complete. Rather than do away with reality at the quantum level, Einstein et al. suggested that hidden processes, such as de Broglie’s ‘pilot waves’, could explain apparent contradictions such as wave–particle duality.

In the end, Bohr’s instrumentalist view won the day over Einstein’s realist one. Quantum mechanics was a closed theory that was no longer susceptible to change. Einstein and his supporters were largely ignored, and Einstein himself was painted as an out-of-touch curmudgeon who simply would not accept the new theory. At least that is how the story has been told over the past several decades. Becker, however, gives a slightly different account. He argues that the Copenhagen interpretation’s popularity had less to do with its epistemological value than with the cult of personality surrounding its architect, Niels Bohr.

Bohr was a ‘physicists’ physicist’ and the preeminent scientist of his time. In contrast to Einstein (who described himself as a ‘one-horse cart’), Bohr collaborated with other physicists throughout his career and mentored many others at his institute in Copenhagen, where he enjoyed considerable financial support from the Danish government. According to Becker, Bohr’s social influence, together with the convoluted and sometimes confusing way that he expressed himself, led many to revere him as a near mythical figure. Indeed, in one particularly telling passage, Becker quotes Bohr’s former student John Archibald Wheeler, who compared Bohr to ‘Confucius and Buddha, Jesus and Pericles, Erasmus and Lincoln’.

‘What is Real?’ serves as an important cautionary tale. While we want to believe that science advances only through its devotion to empirical fact, many ‘facts’ are decided upon not by what they say, but by who says them. We each belong to a ‘thought collective’ with fixed ideas that prevent us from seeing things objectively. Competing ideologies are quickly swept under the rug and forgotten. Indeed, in my experience, I have found that students are rarely exposed to the histories and philosophies that have shaped their respective disciplines. Do we all have our own ‘Copenhagen interpretation’, firmly enshrined in a scaffolding of tradition and convenience? I suspect that we do. To borrow a line from Daniel C. Dennett’s, ‘Darwin’s Dangerous Idea’: ‘There is no such thing as philosophy-free science; there is only science whose philosophical baggage is taken on board without examination’.

The problems are in physics, too!

We write in MT mainly about genetics and how it is used, misused, perceived, and applied these days.  That has been our own profession, and we've hoped to make cogent critiques that (if anybody paid any attention) might lead to improvement.  At least, we hope that changes could lead to far less greed, costly herd-like me-too research, and false public promises (e.g., 'precision genomic medicine')--and hence to much greater progress.

But if biology had problems, perhaps physics, with its solid mathematical foundation for testing theory, might help us see ways to more adequate understanding.  Yes, we had physics-envy!  Surely, unlike biology, the physical sciences are at least mathematically rigorous.  Unlike biology, things in the physical cosmos are, as Newton said in his famous Principia Mathematica, replicable: make an observation in a local area, like your lab, and it would apply everywhere.  So, if the cosmos has the Newtonian property of replicability, and the Galilean property of laws written in the language of mathematics, properties that were at the heart of the Enlightenment-period's foundation of modern science, then of course biologists (including even the innumerate Darwin) have had implicit physics envy.  And for more than a century we've thus borrowed concepts and methods in the hopes of regularizing and explaining biology in the same way that the physical world is described.  Not the least of the implications of this is a rather deterministic view of evolution (e.g., of force-like natural selection) and of genetic causation.

This history has we think often reflected a poverty of better fundamental ideas specific to biology.  Quarks, planets, and galaxies don't fight back against their conditions, the way organisms do!  Evolution, and hence life, are, after all, at the relevant level of resolution, fundamentally based on local variation and its non-replicability.  Even Darwin was far more deterministic in a physics-influenced way, than a careful consideration of evolution and variation warrants--and the idea of 'precision genomic medicine', so widely parroted by people who should know better (or who are fadishly chasing funds), flies in the face of what we actually know about life and evolution, and the fundamental differences between physics and biology.

Or so we thought!
Well, a fine new book by Sabine Hossenfelder, called Lost in Math, has given us a reality check if ever there was one.

In what is surely our culpable over-simplification, we would say that Hossenfelder shows that at the current level of frontier science, even physics is not so unambiguously mathematically rigorous as its reputation would have us believe.  Indeed, we'd say that she shows that physicists sometimes--often? routinely?--favor elegant mathematics over what is actually known.  That sounds rather similar to the way we favor simple, often deterministic ideas about life and disease and their evolution, based on statistical methods that assume away the messiness that is biology.  Maybe both sciences are too wedded to selling their trade to the public?  Or are there deeper issues about existence itself?

Hossenfelder eloquently makes many points about relevant ways to improve physics, and many are in the category of the sociology or 'political economics' of science--the money, hierarchies, power, vested interests and so on.  These are points we have harped on here and elsewhere, in regard to the biomedical research establishment.  She doesn't even stress them enough, perhaps, in regard to physics.  But when careers including faculty salaries themselves depend on grants, and publication counts, and when research costs (and the 'overhead' they generate) are large and feed the bureaucracy, one can't be surprised at the problems, nor that as a result science itself, the context for these socioeconomic factors, suffers.  Physics may require grand scale expenses (huge colliders, etc.) but genetics has been playing copy-cat for decades now, in that respect, entrenching open-ended Big Data projects.  One can debate--we do debate--whether this is paying off in actual progress.

Science is a human endeavor, of course, and we're all vain and needy.  Hossenfelder characterizes these aspects of the physics world, but we see strikingly similar issues in genomics and related 'omics areas.  We're sure, too, that physicists are like geneticists in the way that we behave like sheep relative to fads, while only some few are truly insightful.  Perhaps we can't entirely rid ourselves of the practical, often fiscal distractions from proper research.  But the problems have been getting systematically and palpably worse in recent decades, as we have directly experienced.  This has set the precedent and pattern for strategizing science, to grab long-term big-cost support, and so on.  Hossenfelder documents the same sorts of things in the physics world.

Adrift in Genetics
In genetics, we do not generally have deterministic forces or causation.  Genotypes are seen as determining probabilities of disease or other traits of interest.  It is not entirely clear why we have reached this state of affairs.  For example, in Mendel's foundational theory, alleles at genes (as we now call them) were transmitted with regular probabilities, but once inherited their causative effects were deterministic.  The discovery of the genetics of sexual reproduction, one chromosome set inherited from each parent, and one set transmitted to each offspring, showed why this could be the case.  The idea of independent, atomic units of causation made sense, and was consistent with the developing sciences of physics and chemistry in Mendel's time as he knew from lectures he attended in Vienna.

However, Mendel carefully selected clearly segregating traits to study, and knew not all traits behaved this way.  So an 'atomic' theory of biological causation was in a sense following 19th century science advances (or fads), and was in that sense forced onto selective data.  It was later used to rationalize non-segregating traits by the 'modern evolutionary synthesis' of the early 1900s.  But it was a theory that, in a sense, 'atomized' genetic causation in a physics-like way, with essentially the number of alleles being responsible for the quantitative value of a trait in the organism.  This was very scientific in the sense of science at the time.

Today, by contrast, the GWAS approach treats even genetic causation itself, not just its transmission, as somehow probabilistic.  The reasons for this are badly under-studied and often rationalized, but might in reality be at the core of what would be a proper theory of genetic causation.  One can, after the fact, rationalize genotype-based trait 'probabilities', but this is in deep ways wrong: it borrows from  physics the idea of replicability, and then equates retrospective induction (the results in a sample of individuals with or without a disease, for example), with prospective risks.  That is, it tacitly assumes a kind of causally gene-by-gene deterministic probability.  One deep fallacy in this is that a gene's effects can be isolated, but genes are in themselves inert: only by interacting do DNA segments 'do' anything.  Far worse, one may say epistemologically worse if not fatal, is that we know that future conditions in life, unlike those in the cosmos, are not continuous, deterministic, or predictable.

That is, extending induction to deduction is tacitly assumed in genomics, but is an unjustified convenience.  Indeed, we know the prevalence of traits like stature or disease changes with time, and along with literally unpredictable future lifestyle exposures and mutations.  So assuming a law-like extensibility from induction to deduction is neither theoretically or practically justifiable.

But to an extent we found quite surprising, being naive about physics, what we do in crude ways in genetics much resembles how physics rationalizes its various post hoc models to explain the phenomena outlined in Hossenfelder's book.  Our behavior seems strikingly similar to what Lost in Math shows about physics, but perhaps with a profound difference.

Lost in statistics
Genetic risk is expressed statistically (see polygenic risk scores, e.g.).  Somehow, genotypes affect not the inevitability but the probability that the bearer will have a given trait or disease.  Those are not really probabilities, however, but retrospective averages estimated by induction (i.e., from present-day samples that reflect past-experience).  Only by equating induction with deduction, and averages with inherent parameters, indeed, that take the form of probabilities, can we turn mapping results into 'precision' genomic predictions (which seems to assume, rather nonsensically, that the probability is a parameter that can be measured with asymptotic precision).

For example, if a fraction p of people with a given genotype in our study, have disease x, there is no reason to think that they were all at the same 'risk', much less that in some future sample the fraction will be same.  So, in what sense, in biology at least, is a probability an inherent parameter?  If it isn't, what is the basis of equating induction with deduction even probabilistically?

There is, we think, an even far deeper problem.  Statistics, the way we bandy the term about, is historically largely borrowed from the physical sciences, where sampling and measurement issues affect precision--and, we think profoundly, phenomena are believed to be truly replicable.  I'd like to ask Dr Hossenfelder about this, but we, at least, think that statistics developed in physics largely to deal with measurement issues when rigorous deterministic parameters were being estimated.  Even in quantum physics probabilities seem to be treated as true underlying parameters at least in the sense of being observational aspects of measuring deterministic phenomena (well, don't quote us on this!).

But these properties are [sic] precisely what we do not have in biology.  Biology is based on evolution which is inherently based on variation and its relation to local conditions over long time periods.  This does not even consider the vagaries of (sssh!) somatic mutation, which makes even 'constitutive' genotypes, the basic data of this field, an illusion of unknowable imprecision (e.g., it differs uniquely with individual, age, tissue, and environmental exposure).

In this sense, we're also Lost in Statistics.  Our borrowing of scientific notions from the history of physical sciences, including statistics and probability, is a sign that we really have not yet developed an adequate much less mature theory of biology.  Physics envy, even if physics was not Lost in Math, is the result of the course of science history, a pied piper for the evolutionary and genetic sciences.  It is made worse by the herd-like behavior of human activities, especially under the kinds of careerist pressures that have been built into the academic enterprise.  Yet the profession seems not even to recognize this, much less seriously to address it!

Taking what we know in biology seriously
The problems are real and while they'll never be entirely fixed, because we're only human, they are deeply in need of reform.  We've been making these points for a long time in relation to genetics, but perhaps naively didn't realize similar issues affected the fields of physics which appear, at least to the outsider, much more rigorous.

Nonetheless, we do think that the replicability aspects of physics, even with its frontier uncertainties, make it more mathematically--more parametrically--tractable compared to evolution and genetics, because the latter depend on non-replication.  This is fundamental, and we think suggests the need for really new concepts and methods, rather than ones essentially borrowed from physics.

At a higher and more profound, but sociological level, one can say that the research enterprise is lost in much more than math.  It will never be perfect; perhaps it can be perfected, but that may require much deeper thinking than even physics requires.

This is just our view: take a serious look at Hossenfelder's  assessment of physics, and think about it for yourself.

Thinking about science upon entering the field. Part III: Ethics and Responsibilities

Here is the third of a four-part series of posts by Tristan Cofer, a graduate student in chemical ecology here at Penn State.  He has been thinking about the profession he is being trained for, and the broader setting in which it is taking place, and into which he will have a place:

Growing up in a medical household, I remember being more than just a little impressed by, what seemed to me, to be the many responsibilities that physicians were expected to have towards their patients. Serving on call every third or fourth night, working weekends and holidays, and, not to mention, the years spent in school or as a resident and intern, seemed to me to go beyond the so–called Hippocratic imperative to ‘first, do no harm’, and instead to border on an ethical mandate that one should always strive to do the most good. I am no doubt, engaging in some hero worship here, and I concede that the extent to which this mandate actually informs a physician’s conduct (much less whether it really exists) is debatable. However, I would argue that for many people, myself included, ‘good medicine’, by and large, means medicine that does the most good.

This relationship between healthcare and ethical responsibility is perhaps unsurprising given the influence that physicians have over our, and our loved ones’, mental and physical wellbeing. Simply put, we want to know that the people that we trust with the things that are most important to us are indeed trustworthy. That being said, I find it somewhat curious that, by comparison, we in the scientific community are not held to a similar ethical standard. This, to me, begs the often-unconsidered, if not outwardly ignored, question: What are our social responsibilities as scientists?

Science, like medicine, is embedded in the culture(s) in which it is practiced. It is a humanistic enterprise in that we as humans undertake it, and like all everything we do, it comes with baggage that oftentimes remains unchecked. I wouldn’t claim here that scientists give no consideration to the social frameworks in which they work (that would be both unfair and untrue); only that, based on my own experiences thus far in graduate school, discussions about a scientist’s social responsibilities have been mostly self-interested, concerning internal matters such as research ethics and the like. These conversations are no doubt valuable, in that we need to know that our colleagues are doing work that we can trust and build on; however, they hardly encourage one to think beyond their rather limited responsibilities to our chosen profession.

How much, for instance, should we expect our research to reflect the public’s values and interests? Because research is typically funded by tax-payer dollars, one might argue that, by extension, it is also carried out in their name. Is it, therefore, ethically reprehensible to conduct research that does not directly benefit the public in some way? Are we not also obligated to set research objectives with minority or special interests groups in mind? What happens when our interests conflict with the public’s? For example, can we defend using public funding to conduct research in evolutionary biology, knowing that some groups vehemently oppose teaching evolutionary theory?

Moreover, how should we deal with situations in which our internal responsibilities to ‘Science’ and our external responsibilities to the public are at odds with each other? Is it permissible to develop technologies that can quite literally change the world, without considering the people with whom we share it? Is this even possible? Are we even the best candidates to answer these questions, or should we consult ‘outsiders’ from the humanities and elsewhere in our discussions concerning the questions mentioned above? These discussions may seem like an unnecessary hindrance to scientific advancement, and perhaps they are. But maybe, that’s what we need.

Admittedly, I might be barking up the wrong tree here. Yes, Science has the potential to greatly benefit and harm the public, but so too do politics, business, and any other enterprise with deep pockets and a global reach. As a friend, much smarter than myself, once told me, maybe ‘Science is no more than a good way to keep smart people off the street’. At the end of the day, we all need to make a living, and conversations like these have the potential to make that harder to do. For better or worse, there is considerable pressure (both external and self-imposed) on scientists to do whatever they need to in order to bring in grants, publish to get tenure and advance their careers, and appease the powers-that-be to protect their self-interests. Most people either don’t want to, or can’t, risk rocking the proverbial boat—especially when there is little precedent to do so.

A new biomedical insight?

Here is a thoughtful and timely quote:

". . . . as no single disease can be fully understood in a living person; for every living person has his individual peculiarities and always has his own peculiar, new, complex complaints unknown to medicine—not a disease of the lungs, of the kidneys, of the skin, of the heart, and so on, as described in medical books, but a disease that consists of one out of the innumerable combinations of ailments of those organs. This simple reflection can never occur to doctors . . . . because it is the work of their life to undertake the cure of disease, because it is for that that they are paid, and on that they have wasted the best years of their life.  And what is more, that reflection could not occur to the doctors because they saw that they unquestionably were of use . . .  not because they made the patient swallow drugs, mostly injurious (the injury done by them was hardly perceptible because they were given in such small doses). They were of use, were needed, were indispensable in fact (for the same reason that there have always been, and always will be, reputed healers, witches, homœopaths and allopaths), because they satisfied the moral cravings of the patient . . . . They satisfied that eternal human need of hope for relief, that need for sympathetic action that is felt in the presence of suffering, that need that is shown in its simplest form in the little child, who must have the place rubbed when it has hurt itself. The child . . . . feels better for the kissing and rubbing. The child cannot believe that these stronger, cleverer creatures have not the power to relieve its pain. . . ."

The language seems a bit arcane, and this is a translation, but its cogency as a justification for today's Big Data feeding frenzy is clear.  People who are ill, or facing death, will naturally grasp at whatever straws may be offered them.  In one way or another, this has been written about even back to Hippocrates.

Of course, palliation or cure of what disorders can be eased or cured should be the first order and obligation of medicine.  Where nothing like that is clearly known, trials of possible treatments are surely in order, if the patient understands at least the basic nature of the research, for example, that some are being given placebos while others the treatment under investigation.  Science doesn't know everything, and we often must learn the hard way, by trial and error.

Given that, perhaps the most important job of responsible science is to temper its claims, and to offer doses of the reality that life is a temporary arrangement, and that we need to get the most out of that bit of it to which we are privileged to have.  So research investment should be focused on tractable, definable problems, not grandiose open-ended schemes.  But promises of the latter are nothing new to society (in medicine or other realms of life).

The problem with false promises, by preachers of any type, is that they mislead the gullible, and in many cases this is known by those making the promises--or could and should be known.  The role of false promise in religion is perhaps debatable, but its role in science, while understandable given human ego and the struggle for attention, careers, and funding, is toxic.  People suffering, of poverty, hardship, or disease, seek and deserve solace.  But science needs to be protected from the temptations of huckstering, so that it can do its very important business as objectively as is humanly possible. 

By the way, the quote is from about 150 years ago, from War and Peace, Tolstoy's 1869 masterpiece about the nature of causation in human affairs.