Friday, August 23, 2019

Worse than The Bridge at San Luis Rey!

Thornton Wilder's 1938 book The Bridge of San Luis Rey is a classic with a lesson for today that too many know but are in denial about.  Wilder's book follows the lives of 5 different, generally unrelated people, who for a variety of reasons all end up at a rope bridge over a huge gully in the mountains of Peru.  Unbeknownst to them, they will be on the bridge when it fails, dropping them to their deaths.

Why were they there, a monk asks?  Was there some inevitability about their paths?  Were they connected by some unknown factors?  What, if anything, is the message of, or the lesson from their fates?  Even investigating the possibility of fateful forces cost the monk his life in the dour Church of his time.

But what about our time?  Are we, in a symbolic sense, headed for doom at a bridge that will fail, but to which we seem inevitably driven?  There are reasons to think this could be the case.....

Ecological self-made disaster
The world's natural resources are fragile, destructible, and limited.  In particular, good arable land and other similar resources can be exhausted or destroyed by over-use and mistreatment.  And these factors can be brought on by the demands of an ever-growing population.  Furthermore, human short-term selfish thinking makes it difficult if not impossible for us to restrain ourselves.

In this case, the problem is global warming because of our relentless burning of fossil fuels.  This is made worse by our unconstrained destruction of the Amazon forest and so on, that are the 'lungs' of the earth in this regard.  We pollute the seas, over-fish, and have agricultural habits that destroy the long-term viability of the soils.

Glaciers melt, seas rise, and this inevitably will drive people away from major population centers that, historically, were located by transport media--seas, rivers, and lakes.  If these overflow their banks, massive numbers of people will head inland....but 'inland' is already densely occupied!  And these climate-related changes are well under way and, given the nature of things, their momentum is perhaps unstoppable.

Careless resource consumption and culpable over-population are responsible.  The warning signs have been around for decades (e.g., the widely read book The Population Bomb by Paul Ehrlich in 1968--now 51 years ago).  We have climate-change warners now commonly going around trying to tell people of the dangers (I'll note that even these authors fly all over, contributing needlessly to the problem, to give talks at meetings, autograph their books at booksellers, and so on, though Greta Thunberg is a notable exception).  The hypocrisy, or lack of taking the problem seriously even by those who know better, is rather striking.  Or is it 'frightening' a better word: we simply can't seem to restrain our individual greed and short-term pleasures, even when faced with an impending catastrophe.

To me, this is like passengers enjoying a leisurely, fancy meal, with fine wine, in the dining car of a train that is speeding towards a bridge that's out--as in San Lus Rey.  But unlike the book's characters, we know what the story is.  Yet, even so, we cannot seem to impose the obviously required consumption self-restraint on ourselves.  It's due not only to relentlessly selfish insatiable commercialism or capitalism, but to our own individual, short-term selfishness as well, that we just seem unable to restrain.  Maybe our economic system makes that hard or impossible.  But it doesn't make it not a problem!  We know the issues, but can't seem to react properly.

Can we do anything about it--in time?  Will we?
Your guess is as good as mine.....and perhaps you're more optimistic, less a student of history, and you'll be right.  But based on human history, the odds are against that.  Disastrous societal strain seems inevitable.

Are we fated to meet at San Luis Rey, and plummet together into the rocky abyss?  Wilder's book is worth reading.....and thinking about.  But in our case, the chasm we're headed so rapidly to won't just take out 5 unlucky travelers: it will destroy billions of lives!  And it will do that with slow trauma: famines, wars, displacement, and other disasters as an essential aspect of the process.

Of course, if it pares back the human population to some few million worldwide, the rest of Nature will rejoice, because it will, once again, have a chance to evolve in a more properly orderly way.

Thursday, August 22, 2019

Beauty is bad for physics---and a blemish on life sciences, too!

We naturally like tidy answers to our more fundamental, or even troubling, questions about Nature and existence.  In genetics we want to find the genes 'for' important traits so we can engineer the nasties away--even if we know some other nasty will arise, even if later in life.  We want the cosmos to follow neat, universal rules--to make a universe, after all, that makes sense.  Tidy.  Understandable.

One thoughtful physicist (who now describes herself as 'ex-physicist) is Sabine Hossenfelder, author of a very good book called Lost in Math, and many good articles.  Here is one from a recent online magazine issue.  In this she asks whether the universe is 'beautiful', or whether physicists should expect it to be that way.  She basically says 'no', the universe is the way the universe is, and as scientists we should try to understand it that way--on its own terms, not those of our wishful thinking.  It need not be 'beautiful', as she puts it.

In the life sciences, we are enamored of projects, like physicists' colliders, that are too big and expensive to stop once they have been started--good for the science business, whether or not really as good and efficient a way of investing in science itself.  And, like physicists, we want the solutions to be neat mathematical and useful for predicting--indeed as orderly and 'beautiful' (and universal) as physics sometimes claims to be.  In the human life-science case, we are promised that our DNA sequences can predict disease or other traits, including intelligence and so on.  We want or believe that these traits are somehow built into our genomes, as unfolding (evolving) inevitabilities during our lifetimes, and hence predictable with 'precision' genomics.

It sounds like religious promises of eternal life, does it not?  Indeed, that we know the promises are patently false, at best inaccurate to an unknowable extent since every individual is genomically as well as environmentally unique, doesn't seem to slow down the juggernaut of vested interests exploiting that point of view, which if you think of it closely resembles the threats some churches make when passing the plate to those wanting their souls saved for eternal bliss.

Evolution is in a sense and by its nature very non-beautiful: local, sloppy, inconsistent, and so on.  It has to be that way.  It can't be too predictable.  It depends for its progress on mistakes and flukes--we can think of them as beauty marks some of the time.  But mostly they aren't.  Nonetheless, that is, ironically, the beauty of it all.  That is how complex organisms can evolve in complex environments, and those successes include us!

What beauty!  A Remarkable Unbroken Path
The lack of general predictability of disorders, especially late in life, that we know largely depend on living conditions as well as inherited (and somatically mutating) DNA, is what makes life what it is.  That we must come to an end is not a cheery thought, but were it not for that we'd have had no beginning!

And, if you think of it correctly, we--you, I, and all whom we know--are the so-far eternal descendants of the very origin of life.  There is, for each of us visiting the earth today, an unbroken path back to the origin of life.  What could be more beautiful than that?

So there is a place for beauty.  It is, literally, in the eye of the living beholder, not in a test tube.

Wednesday, August 21, 2019

Locality: life's Newtonian equivalent of 'universality'

In, 1687, in his groundbreaking Principia, Isaac Newton made a fundamental assertion--a fundamental assumption--about reality.  It is that whatever you observe in some location, such as your lab, will apply everywhere else in the cosmos.  He was talking about the nature of the physical universe, following similar views of Galileo, who quipped that the laws of nature were written in the language of mathematics.

Paperback Philosophiae Naturalis Principia Mathematica Book

If the universe was God's creation, its vastness would be of a kind, similar everywhere.  That notion is what stands behind the idea of universal 'laws' of Nature.  The 'laws' were not passed by an Angelic Congress, but are simply God's way of organizing physical existence--all of it!

These laws, discovered by classical physics, are deterministic and universal, not probabilistic, not haphazard.  I don't recall anything about what Newton thought of probabilities other than a debate with Pepys about gambling, but that was not central to his cosmic worldview, which was essentially deterministic--which is what you might expect from an all-knowing God.

But subsequent science has revealed at least two key additions.  First, some of Nature seems inherently probabilistic.  Here we are not restricted to measurement issues, because probabilities seem inherent in quantum-level phenomena.   Secondly,  probabilism means that conditions are at least to some extent contingent on what did happen, relative to what might have happened.  This means that predictions can only be probabilistic at some scale; whether that means the cosmos' states and future are unknowable or not is not for someone like me to opine about!  Whether the probability values are, somehow, fixed, and if so how that is, are interesting and, I think, important questions.

Life is part of the universe, but its fundamental laws are of locality, not universality
Life is a chemical and hence physical phenomenon.  But life in the deeper sense is about how these molecules are organized, and this seems fundamentally different from the kind of molecular evolution seen in stars.  Each star seems, from what one reads, to be similar at the chemical or atomic/subatomic level.

But life evolves by local conditions.  Mutations arise locally and are filtered by selection and chance locally.  Successful mutations and genotypes spread by migration from their source, but are then always subject to genetic and environmental conditions in their new localities.

Locality also is the central fact or organismal organ and system diversity.  In this case, it is local conditions determining gene activation and expression.

But, in a sense prisoners of 19th century physics success, the long shadow of Newton and Galileo, we seem to hunger for laws of life that apply, as the slogan goes, to 'All of us' and that leads to genomic medicine that we are told can be known with some kind of presumably universal 'precision'.  These are, to me, irresponsible misrepresentations made by Francis Collins and NIH, perhaps as their strategy to pry mega-bucks from Congress--because they are naive relative to the biology they promise to understand.

But if we overlook the truth and live in slogans, does this undermine the very science we want to nurture?  The assumption of universality, to me, is fundamentally misleading about how life works and how our genotypes got here.  Whether or how we can use this understanding to develop appropriate medications and so on, is a separate set of very important questions, about which I'm not capable of making judgments....

Tuesday, August 13, 2019

Big Data, Big 'omics-everything....and the sorry state of biomedical research support

People on the federal grant take often speak of 'Big Data' with a nearly lascivious joy.  Big Data is code for biomedical research projects that once begun are too large and costly to terminate, whether or not they did, or do, deliver seriously important truths--truths worthy of their cost.

But when careers depend on it, Big Data and the associated Everything-'omics are as much a fad and ploy for job security for medical school researchers as they have anything to do with science.  Huge open-ended projects need claim nothing that can be rigorously tested, and such fishing expeditions are likely to find at least something that can be blared to the public as major discoveries.  We see it every day, it seems.

One can criticize the Big Hunger for Big Data projects, but they are survival tactics for biomedical researchers, many of whom only get their salaries from external funds, and for those without any actual ideas or means to actually find something profoundly new.  Those 'means' should include freedom from regular bottom-line accountability: hard problems can't be solved on some material-based schedule.  That is because the biological world is complex!

There is, as a rule, not one gene, or even a consistent few genes, that 'cause' traits we care to understand.  Environment--a complex and vague term--interacts with organisms to yield their traits. This is how, via evolutionary processes, we got here in the first place.  Interactions, redundancies, and other complexities have been built into our biology for countless millions of years. Indeed, complexity is protection against vulnerability for survival, and organisms have obviously evolved complexity for that among other reasons (including that redundancy and complexity make room for new innovations to evolve without lethally threatening current systems).  So we should be surprised when we don't find complex redundancy--indeed we have clearly been documenting its universality. And we should stop promising that we'll find the 'genes for' complex traits, like heart disease or obesity etc.

But complexity is not good for the research system
The current research funding system started roughly after WWII, when funds were plentiful and the army of investigators and their staffs and administrators was far smaller.  This is an historical, sociological fact rather than one about the causative nature of the world that we want to understand.

Research used to be much more about solving scientific questions by forming and testing hypotheses, experiment, and so on, than it was about salaries, overhead, and the status of having a Big research group.  But many biological problems are complex--really complex not just as a self-promoting adjective, and to address them should involve patience as well as funding that is stable and doesn't rest on rushing stories to the news media and other means of hyping findings.  Careerism as we see it today is not compatible with this, and the currently gross waste on the fads for Big Fishing Expeditions shows this.

Science today has become pretty much a self-sustaining System, from bureaucrats at all levels to investigators who must sing (i.e., claim Big Results) for their supper.  It sows dishonor and misrepresentation (as well as the occasional desperate scientific fraud).  We all know this but somehow seem powerless to redress things and restore research to the realm of science, where the science is the substance not the window-dressing for fiscal needs as it so often today.  When the system is hyper-competitive, who can afford to confront it?

Things can be changed--even if won't be easy
Reform is never easy, as established conditions are very inertial.  Vested interests, like grant-dependent salaries, must be faded out or even, sometimes, uprooted.  But over recent decades we've clearly allowed those conditions and empires to be built, indeed we often were part of their being built.  But it is time for deep, difficult reform.  We need to fund Big Ideas, Big Efforts at Hard Problems, not just facile sloganized Big Data or 'omics-everything.

But is there the will--and the bravery--for reform?  Where is it, or where can it be nurtured?  The unrest must be stirred to action.

Sunday, August 11, 2019

Who, me?? Why did I clog my 'widow maker'? [on medical cause and effect...and how we know, if we know]

So, having just returned from and now recuperating from coronary bypass surgery, I have to ask the 'complexity' question--a very personal one in this case: Why me? I've lived a physically and physiologically vigorous life.  My diet may not have always been the very best for cardio health (though, for reasons we've discussed here many times over the years, it's not completely clear what that diet should actually be), but it wasn't particularly bad, given what's thought these days to be a "healthy" diet.  

The surgeon who remodeled me at Penn State's fine medical complex in Hershey, said he knows the risk factors in a population but couldn't know why any given individual developed clogged coronary arteries, nor which artery would be affected.  His job was to replace, not explain them, one might say.  So, he didn't even attempt to tell me why I was now in need of bypass surgery.  

As he said, there are five known major risk factors: obesity, unhealthy diet, high cholesterol, genetic predisposition, and smoking. Yes, having diabetes and high blood pressure are risk factors as well, but correlated enough with obesity that perhaps he considers these two conditions to be side effects of obesity.  In any case, these risk factors have been determined by looking at associations between possible causal variables and heart disease in populations.  Resulting statistics describe the population, not identifying specific high-risk individuals within it.  Indeed, some people with heart disease have all the risk factors, some have a combination of a few, and some have none.  And even then, it's not possible to say which was the cause of the disease in most individual cases.   

I have none of these risk factors -- though, I could make up a story.  I smoked when I was young, my father had a pacemaker when he was old, but he lived to 99.  Still, I have done vigorous exercise my whole life, thinking that was my "get cancer program" since it meant, I thought, that I would go not out with a coronary.  What caused my artery to clog?  Indeed, why in my case was the clog in an unstentable artery location, and hence required major surgery? 

This brings up, again, the question of whether one's individual risk can even be known with any sort of 'precision'. Or is that an illusion? Is it a culpably false promise made by the calculating Dr Collins at NIH, to get NIH funding, rather than to give the public a realistic understanding of what we know and what we can hope to know based on research investment of the type he favors?

How, based on current methods of science, can it really be individual? What kind of information would that require, just considering actual, i.e., past effects, assuming they could really be ascertained to any reasonable measurement standard?  What would you need to consider?  Diet, exercise, personality (temperament, for example).  Climate?  Profession? The effects of war, drought, epidemic?  Genes, even?

Of course, the gross and inexcusable BS of promising 'precision genomic medicine' based on very costly, open-ended genomic (and other 'omic) data collection enterprises is culpable.  It is an often openly acknowledged way of getting, and keeping, mega-funding without having any real ideas (and understandable since medical schools culpably don't pay faculty salaries or basic research costs as part of their jobs).  Focused science has chances of finding things out; blind data enumeration, far less so--and what we've done of that so far shows this quite clearly.

We often say 'family history', and clinically this may be the most useful piece of predictive information, but what does that actually explain?  Did Dad or Uncle Jane have the same trait because of genes, or because of their shared family habits and lifestyles?  How could you really tell?  A surgeon need not care, as their job is to fix the clogged pipes, and if heart disease runs in a family the physician will treat his or her patient as high risk.  Still, to prevent this sort of thing, we need to know what causes it. 

This is a central biomedical question!  It is hard enough to know, much less accurately measure, all factors in life that might in this or that way be a 'risk' factor for a given disease, like clogged coronary plumbing.  Is it a delusion to think we could identify, much less measure all the factors?  If, as seems obvious, there isn't just a single factor, and probably everyone's exposure set is different (and their effects need not be 'additive'), how on earth can we even know how well we are measuring, or ascertaining, such factors?

And, if we can do this, it only applies directly to current cases and their past lifestyle exposures.  But what we would like to do, for individuals and for public health, is to predict the future to lower risks.  However, there is no way, not even in principle, no reasonable chance of knowing what future exposures will be, not even for populations.  Diets and lifestyles change in ways we cannot predict, nor can we predict major future events--climate, war, pestilence, food types and availability, etc., that would be highly relevant.

So what should we do with our understanding of these unpredictable factors?  Perhaps just level with patients and the public, and stop using the public to endow a particular, and particularly costly, part of the university research empire.  Maybe a return to focused, hypothesis--based research--actual science--in my view.

Friday, August 9, 2019

Laura! Laura! Please don't do this!

I was, for the first time ever, a hospital inpatient a couple of weeks ago.  As it turned out, because I knew what angina pectoris is, I went to the docs, and they sent me to the hospital where, to make a long story short, I had bypass surgery.  It's not been easy, but at least I had not waited too long!

I seem to be doing fine, given all that.  I hope so; but not everyone in the hospital is as lucky.

In one part of my odyssey, I shared a room with an older man, annoyingly having Fox "News" at loud volume, though he was relatively insensate and not at all watching that bigoted claptrap.  He moaned a lot, and, in his confusion, repeatedly called for his daughter  "Laura!  Laura!  Don't do this!  Please, oh, please, don't do this!"

In my time sharing that room, I overheard the doctor telling the man's relatives, quietly, that his leukemia was not responding to treatment.  The man himself clearly was not being told this, and/or was far beyond comprehension.  At one point, the ashen old man was wheeled out by a nurse, to another room to leave me some peace and quiet (I think the nurses realized the impact of his relentless moaning on me).  Then, a few hours later, I was off to my own adventures--heart bypass surgery.

These kinds of experiences are, I guess, in store for most of us, as we meander through the savage realities of aging, even if it is because of the medical care system, our well-off lifestyles, hospitals and treatments that we can have those experiences at all.  It is not easy to think about, especially when one's self is involved, not just relatives or neighbors or somebody else, or newspaper stories or science-journal statistics.

I am not sure what to write about in this context.  One wants treatments, and hospitals are fine locations where the treatments can be obtained.  Does one also want to know the whole truth about what the doctors find?  Who should be told?  Who should just be given various sorts of comforting (even when or if false) words?  Who decides?

I hope that, this time at least, I am on the road to some sort of comfort and success, even though at my age (late 70s), it is obvious that the future can't only hold good experiences.  In the hospital, one is forced to see the future, and the approaching end.  This is not a new thought, and we all know life, indeed, life on earth and even the earth itself, are temporary.  But it is a thought to keep in mind, today, and each day.

And the lesson, or my message, for readers of this post is: value today, value those you care about and who care about you.  All are precious!  All are temporary.....

Thursday, July 11, 2019

Human races are not like dog breeds

If you googled for information comparing race in humans to dog breeds, we wrote this open access, peer-reviewed article specifically for you. There is even a glossary at the end of the main text, and some of the sources we cite are also open access. Thanks for reading.

Are human races like dog breeds? No.
Are human races the same as dog breeds? No.
Are human races just like dog breeds? No.
Are human races basically dog breeds? No.