The maelstrom of science publishing: once you've read it, when should you shred it?

There is so much being published in the science literature--a veritable tsunami of results.  New journals are being started almost monthly, it seems, and mainly or only by for-profit companies.  There seems to be a Malthusian growth of the number of scientists, which has certainly produced a genuine explosion of research and knowledge, but the intense pressure on scientists to publish has perhaps changed the relative value of every paper.

And as I look at the ancient papers (that is, ones from 2016-17) that I've saved in my Must-Read folder, I see all sorts of things that, if they had actually been widely read, much less heeded, would mean that many papers being published today might not seem so original.  At least, new work might better reflect what we already know--or should know if we cared about or read that ancient literature.

At least I think that, satire aside, in the rush to publish what's truly new, as well as for professional score-counting and so on, and with the proliferating plethora of journals, the past is no longer prologue (sorry, Shakespeare!) as it once was and, one can argue should still be.  The past is just the past; it doesn't seem to pay to recognize, much less to heed it, except for strategic citation-in-passing reasons and because bibliography software can be used to winnow out citable papers so that reviewers of papers or grant applications won't be negative because their work wasn't cited.  You can judge for yourself whether this is being realistic or too cynical (perhaps both)!

The flux of science publishing is enormous for many reasons.  Not least is the expansion in the number of scientists.  But this is exacerbated by careerist score-counting criteria that have been growing like the proverbial Topsy in recent decades: the drive to get grants, big and bigger, long and longer.  Often in biomedical sciences, at least, grants must include investigator salaries, so there is massive self-interest in enumerable 'productivity'.  The journals proliferate to fill this market, and of course to fill the coffers of the publishers' self-interest.  Too cynical?

Over the years, in part to deflate Old Boy networks, 'objective' criteria have come to include, besides grants garnered, a faculty member's number of papers, ranking of the journals they're in, citation counts, and other 'impact factor' measures.  This grew in some ways also to feed the growing marketeering by vendors, even who provide score-counting tools, and university bureaucracies.  More generally, it reflects the way middle-class life, the life most of us now lead, has become--attempts to earn status, praise, wealth, and so on by something measurable and therefore ostensibly objective.  Too cynical?  

Indeed, it is now common for graduate students--or even undergrads--to attend careerism seminars.  Instruction in how to get published, how to get funded, how to work the System.  This may be good in a sense, or at least realistic, even if it was not so when, long ago, I was a graduate student.  It does, however, put strategizing rather than science up front, a first-year learning priority.  One wonders how much time is lost that, in those bad old days, was spent thinking and learning about the science itself.  We were, for example, to spend our 2-year Master's program learning our field, only then to get into a lab and do original work, which was what a PhD was about.  It is fair to ask whether this is just a change in our means of being and doing, without effect on the science itself, or whether careerism is displacing or even replacing really creative science?  When is objection to change nothing more than nostalgic cynicism?

Is science more seriously 'productive' than it used to be?
Science journals have always been characterized largely by the minutiae they publish, because (besides old boy-ism) real, meaty, important results are hard to come by.  Most observation in the past, and experiment these days, yields little more than curios.  You can see this by browsing decades-old volumes even of the major science journals.  The reports may be factually correct, but of minimal import.  Even though science has become a big industry rather than the idle rich's curiosity, most science publishing now, as in the past, might more or less still be vanity publishing.  Yet, as science has become more of a profession, there are important advances, so it is not clear whether science is now more splash than substance than it was in the past.

So, even if science has become an institutionalized, established, middle-class industry, and most of us will go down and out, basically unknown in the history of our fields, that has probably always been the case.  Any other view probably is mainly retrospective selective bias: we read biographies of our forebears, making them seem few and far between, and all substantial heroes; but what we are reading is about those forebears who really did make a difference.  The odd beetle collector is lost to history (except maybe to historians, who themselves may be making their livings on arcane minutiae).  So if that's just reality, there is no need to sneer cynically at it.

More time and energy are taken up playing today's game than was the case, or was necessary, in the past--at least I think that is pretty clear, if impossible to prove.  Even in the chaff-cloud, lasting knowledge does seem to be much more per year than it used to be.  That seems real, but it reveals another reality.  We can only deal with so much.  With countless papers published weekly, indeed many of them reviews (so we don't have to bother reading the primary papers), overload is quick and can be overwhelming.

That may be cynical, but it's also a reality.  My Must-Read folder on my computer is simply over-stuffed, with perhaps a hundred or more papers that I 'Saved' every year.  When I went to try to clean my directory this morning, I was overwhelmed: what papers before, say, 2015 are still trustworthy, as reports or even as reviews of then-recent work?  Can one even take reviews seriously, or cite them or past primary papers without revealing one's out-of-dateness?  New work obviously can obsolesce prior reviews. Yet reviews make the flood of prior work at least partially manageable.  But would it be safer just to Google the subject if it might affect one's work today?  It is, at least, not just cynicism to ask.

Maybe to be safe, given this situation, there would be two solutions:

1.  Just Google the subject and get the most recent papers and reviews; 

2.  There should be software that detects and automatically shreds papers in a Science Download directory, that haven't had any measurable impact in, say, 5 or (to be generous) 10 years.  We already have sites like Reddit, whose contents may not have a doomsday eraser.  But in science, to have mercy on our minds and our hard discs, what we need is Shred-it!

Germline gene therapy: Frankenstein or Frankincense?

Science, like any other human enterprise, is largely reactionary.  People in established positions of influence like to have their own way but perhaps even more, like their ways to stay basically the same: change is threatening.  For that general reason, new ideas that promise to be transformative are often faced with reactionary opposition.

A few decades ago we had the recombinant DNA revolution.  Changing DNA in bacteria for experimental reasons was seen as a potential global threat: if recombinant bacteria escaped the lab, they could become a global pandemic disaster that would make malaria or the bubonic plague seem trivial by comparison.  Of course, those excited about the potential of the new method, for legitimate as well as venal reasons, pushed hard to be allowed to proceed.  After careful examination, various protections were imposed (like working with experimental strains of E. coli that could not really live outside of test tubes), but these were loosened or abandoned over time, as the threats never materialized.

There are still some rumblings about this, as for example, the recent controversy over labs refusing to desist from engineering dangerous flu viruses to see what changes were needed to enable them to transfer from person to person more easily (they originate now in animals).  The rationale is to anticipate such occurrences and develop preventive measures or vaccines etc.  This work is on-again-off-again, in response to governmental and other dictates, and then pressure from investigators to do this no matter what, and then back again, as the issues are batted back and forth, unresolved.

A few years ago there was the reaction to cloning, when it was done to make Dolly, the sheep in a lab in Scotland.  There are many issues about this process, both the sci-fi horrors of cloning armies of humans who are genetically unable to experience fear, and the fact that cloning from an adult's cell would make newborns more vulnerable to age-related diseases.  Human cloning is not allowed as yet, though there are some rather similar things going on in the in vitro fertilization world to select embryos without known disease-related genetic variants.  As we understand it, various types of cloning are widespread in agricultural animals.

Another example is the reaction to genetically modified organisms (GMOs) and their potential to make proteins that would turn out to be allergenic or in other ways harmful, or to damage ecosystems by altering pests infestations as well as inadvertently destroying insect pollinators, the enabling of large-scale monocropping, and so on.  This debate is ongoing, and widely publicized.  It has stimulated 'natural' foods, non-GMO containing foods, local sustainable agriculture, etc.  Some of the resistance was, in essence, not about personal health but about the way GMOs threaten local farmers around the world, deplete natural variability, threaten bees and other pollinators, and more.

Much of the opposition to these sorts of change is emotional and sociopolitical--but that is not a criticism, because people are emotional and sociopolitical.  And that applies to people on both sides of the debates: nobody can claim that the proponents of the new technologies are dispassionate and without self-interest and limited perspectives.

Human genetic engineering: a blessing like Frankincense?
There is now the beginning, or perhaps continuation, of a debate about human genetic engineering.  Should it be done?  What is it, exactly.  One recent discussion outlines the issues.  New technologies are being developed, one of which is called CRISPR, to engineer changes in specific genes in situ in cells.  This is being done in cell culture and experimental animals and plants, to see what the specifically transgenic effects on them are.  But the potential for genetic engineering to produce human babies that do not carry deleterious genes that there parent(s) may be known to carry hasn't been ignored--and, even better, the dangerous genes are removed from the population because when the babies themselves reproduce they only have the normal version to transmit to their children.

This is different from genetic engineering that tries to deliver therapy based on genetic methods to persons who are affected by genetically based diseases (like cystic fibrosis) or to deliver genetic changes to diseased tissues to counter the pathology.  Those approaches are struggling to live up to their widespread promise, but there is little opposition that we know of to their implementation.

The resistance to germ line gene therapy seems to be that engineering of specific heritable genetic changes could backfire and generate new pathologies, monsters, or other unexpected side effects if the methods, still yet unproven and undergoing testing in lab species, don't work as precisely as their proponents claim.

An old way wise men tried to bless the human future: Frankincense therapy

But the idea of germ-line and hence permanent fixes is not at all new.  It's a scientific analog, one might say, of the religious doctrine of the blessing conferred on humankind by the wise men one Christmas eve.  An effort to save our patrimony from much suffering.

Selective abortion, prenatal counseling, and even IVF are now used to prevent the birth of babies that carry known dangerous variants that one or both parents may be known to carry.  This has greatly reduced the incidence of thalassemia (a blood disease related to anemia) in Sardinia, and of Tay Sachs disease in Ashkenazi Jews, and there are likely many examples we just haven't heard about.  There are now two- and even recently three-parent IVF conceptions being constructed.

So this time, the reactionary response to a new idea does seem to be reactionary.  It isn't that there's no risk of horrible misadventures occurring if the new techniques fail, and it's fair enough to say this should be stopped cold until the techniques are reliable (or early enough tests available to do instantaneous aborting of dysgenic conceptuses).  But that is not the same as reacting to the idea of germ-line therapy in the first place as if it were new in concept.

To prevent Frankensteins?
There will, of course, be those who agree with all of this so far, but foresee the mis-use of the procedure by rogue elements or governments for example to create fearless soldiers, drones, slaves, and so on based on mass-scale genetic engineering of this type.  Or doing the same kind of thing to create super-plagues (e.g., to visit on enemies).  Rogue elements can be expected to arise here and there within governments (e.g., in intelligence services, military, or other agencies).

Blessing gone awry: Boris Karloff style

Dr Frankensteins would perhaps find willing employers in such places.  Some would be rogues. Some might offer their services to our enemies.  Some might engineer irresistible plague germs. Such elements always exist in society.  There is plenty of evidence to think that otherwise respectable scientists will be (or are) doing this covertly or will find ways, such as by leaving universities to set up companies, moving to more permissive countries, and so on, to do this and skirt regulations and restrictions.

It is also true that the same sorts of claims have been around for a long time. That the predicted disasters haven't occurred--yet--is no reason to relax vigilance.  After all, the Nazi 'scientists' and 'doctors' were among the leading professionals of their days.  And this sort of thing wasn't restricted to Germany in the 20th century: it was part of global eugenics thinking and actions taken against those deemed to be inherently (that is, genetically) inferior.  Only a newborn babe would be so naive as to think the same sort of mentality cannot be found among today's leading scientists.

But perhaps every blessing comes with a curse, and to gain the former we must guard against the latter.  While vigilance is never perfect, and risks always do exist, at least we should recognize the positive potential for removing dangerous genetic elements from human patrimony.

Nature or nurture? Tristram Shandy weighs in!

It is only because of our very casual and cursory attention to history that we credit Charles Darwin, in 1858, with showing us that every aspect of our natures is due, entirely and with infinite determinism, to natural selection fine-tuning our genomes.  We like heroes and because we're scientists, we want the heroes to be other scientists (so we can liken ourselves, and our own inherent brilliance, to those heroes).  We dismiss philosophers and historians of science as meddlers in our business if they do not cling to the mythologies we prefer about ourselves (and our inherent brilliance).  But if we're really scientists, and truly truth-seekers, we must bow to discoveries that undermine our self-flattering tales.  It hurts, it really hurts, if the discovery shows that the pioneers of our field were, in fact, religious or, worse, totally un-versed in the lore of science and the pursuit of objective fact.

But such is the sad reality about the fact of complete genetic determinism.

The opinions and discoveries of Laurence Sterne (as expressed by Tristram Shandy)
In 1761-3, the Rev. Laurence Sterne, published his study of environmental determinism, called The Life and Opinions of Tristram Shandy, Gentleman.

Laurence Sterne (1713-68); image from Google images

The book is written as a narrative of his life, by the title character.  Tristram notes that at the very moment of the act that led to his conception Mrs Shandy blurted out "Pray my Dear, have you not forgot to wind up the clock?"  About that question her husband, though a man of exceedingly regular habits, replied "Good G..!  Did ever woman, since the creation of the world, interrupt a man with such a silly question?"  The clock in question is shown in the background of this figure; in the foreground is a depiction of the use of forceps in deliveries (which crushed Tristram's nose during his birth).

The Shandy home (and the clock), from 1761 edition.  By Wm Hogarth, from Wikipedia images

Here is how Tristram describes the lifelong impact of his mother's ill-timed distraction:

I wish either my father or my mother, or indeed both of them, as they were in duty both equally bound to it, had minded what they were about when they begot me; had they duly consider'd how much depended upon what they were then doing;--that not only the production of a rational Being was concerned in it, but that possibly the happy formation and temperature of his body, perhaps his genius and the very cast of his mind;--and, for aught they knew to the contrary, even the fortunes of his whole house might take their turn from the humours and dispositions which were then uppermost;--Had they duly weighed and considered all this, and proceeded accordingly,--I am verily persuaded I should have made a quite different figure in the world, from that in which the reader is likely to see me.--Believe me, good folks, this is not so inconsiderable a thing as many of you may think it;--you have all, I dare say, heard of the animal spirits, as how they are transfused from father to son, & &--and a great deal to that purpose:--Well, you may take my word, that nine parts in ten of a man's sense or his nonsense, his successes and miscarriages in this world depend upon their motions and activity, and the different tracks and trains you put them into, so that when they are once set a-going, whether right or wrong, 'tis not a half-penny matter,--away they go cluttering like hey-go mad; and by treading the same steps over and over again, they presently make a road of it, as plain and as smooth as a garden-walk, which, when they are once used to, the Devil himself sometimes shall not be able to drive them off it.

. . . . .

--Then, let me tell you, Sir, it was a very unseasonable question at least,--because it scattered and dispersed the animal spirits, whose business it was to have escorted and gone hand in hand with the Homunculus, and conducted him safe to the place destined for his reception. . . . . Now, dear Sir, what if any accident had befallen him in his way alone!--or that through terror of it, natural to so young a traveller, my little Gentleman had got to his journey's end miserably spent;--his muscular strength and virility worn down to a thread;--his own animal spirits ruffled beyond description,--and that in this sad disorder'd state of nerves, he had lain down a prey to sudden starts, or a series of melancholy dreams and fancies, for nine long, long months together.--I tremble to think what a foundation had been laid for a thousand weaknesses both of body and mind, which no skill of the physician or the philosopher could ever afterwards have set thoroughly to rights.

. . . . .

That I should neither think nor act like any other man's child:--But alas! continued he, shaking his head a second time, and wiping away a tear which was trickling down his cheeks, My Tristram's misfortunes began nine months before ever he came into the world.

The surprise is that more than two centuries ago at least some views were directly contrary to the predominant view these days, reflecting the way so much of our research resources are currently committed--that is, to the idea that genes rather than experience are what (also from the moment of conception) make us what we are.  But not everyone shared this view!

Things were debated even back then!
Last week we noted that in 1862, just after Darwin's Origin of Species, the novelist Wilkie Collins expressed the debate between Nurture advocates and their Nature foes as to which was responsible for our behavior. This was exactly a century after Sterne's Nature view just described.  Sterne had no notion of 'genes' and Tristram didn't attribute his nature to inheritance, which would put him in the Nurture category, even if at the extreme (being parentally distracted in flagrante delicto defined the imminent conceptus's entire future).

It wasn't long thereafter that the power of inheritance was debated, in little-remembered works, that applied to the same behavioral characteristics discussed in fiction.  Almost half-way between Sterne and Collins, in 1808, one M. Portal, a French professor of medicine, published the "Considerations on the Nature and Treatment of some hereditary or Family Diseases" (London Med. Phy. Journal, 21, 229–239, 281–296).  Members of the upper classes (at least) were concerned that they might sully their noble posterity by transmitting disease, especially mental disease, from parent to offspring.  Many traits were known to be transmitted (as Montaigne is quoted by Portal), "We find that not only are the marks of the body transmitted from father to son, but also a resemblance of temper, complexion, and inclinations of the mind."

A few years later, in 1814, a British physician named Joseph Adams took Portal's work to task, arguing that there were other ways that traits could cluster in families.  He, too, was speculating in that he hadn't the kinds of precision or systematic analytic methods we have today.  But he carefully pointed out that life-experience, infection, and other causes could account for such clustering.  Diseases present at birth, for example, were more likely to be hereditary than diseases that, even if similar among relatives, only appeared later.  He noted that inherited predisposition could lead to a disorder only after experiencing some environmental or life-style factor.  He was particularly interested to calm down those in the upper classes who were worried that behavioral traits ('madness') were inherited.  Additionally, Adams explicitly anticipated much of Darwin's ideas about evolution by natural selection, but that's unrelated to our topic today.  We've discussed Adams' book on MT before.

Joseph Adams' book, 1814

The bottom line is that, from these instances, ones that I just happened to know about, both literature and science reflect the fact that in the post-Enlightenment era we often think of as the Age of Science, western culture has long known of what appeared to be inherited traits, even if 'genes' per se weren't yet known of, and yet it was also clear that experience and living conditions could not only generate traits but generate family resemblance of traits.

But nobody knew the how, when, or why of the two kinds of cause, and without knowing units of causation in either life-experience or genetics, we had simply to guess or speculate about these things. The 20th century gave us Mendelian patterns to look for in families as signatures of genetic causation, but when we realized early on that many genes could generate similar traits it was known (to those who cared to recognize that fact) that Mendelian patterns were not needed even in 'genetic' traits.

We have almost the same level of confusion, mix, debate, and lack of clarity today, centuries later in our amped-up Age of Technical Science.  We now throw around terms like 'interaction' without, usually, having much direct sense of what we are actually referring to.  Sometimes, the contorted way we describe our ideas of causation seem not much different from the way Tristram Shandy did--only that was satire and we seem to be deadly serious!

Something's missing.


After-note:  If you haven't read Tristram Shandy, and are interested in more than just reading the flood of science articles in the journals that jam up your mail box every day, Sterne's book is a good, if wacky, romp through sense and nonsense.  Reading it takes patience, since it intentionally doesn't always flow in one direction, but it's no more contorted and obscure than those same science articles.