Saturday, December 28, 2019

On the Origin of Facts

Bruno Latour tours the Salk Institute, finds science taking place, and has a hard time deconstructing it.

There is a production process in science, by which the educational background, institutional setting, funding decisions, social accidents, and happenstances that form directions of research, hunches, hypotheses, and insights are stripped away, intentionally and systematically, to produce "facts" in a form ready for publication. This de- / re-contextualization serves to obfuscate the process and shamanize the practitioners, but more importantly it serves to generalize the resulting fact and put it into its scientific rather than social context. And it is the scientific context- the fact's objective existence- not the social context, that makes it powerful and useful for further construction of other facts. The social context forms part of the essential background / input, but the produced facts and insights are not by nature social, nor should they be received as such.

Experiments are instrumental in this transformation process, which goes from a hunch, to a collegial suggestion, to an hypothesis, to a testable hypothesis, to the hunt for alternative hypotheses and thus for experiments designed to exclude them and to support the main hypothesis, (if true), followed by group presentations and critique, outside peer review that adduces more alternative hypotheses and possible experiments, and finally to publication and collegial acceptance (or rejection and refutation). When all this is done, the murky origins of the hunch necessarily fall away and become trivially unimportant, (other than in memoirs and reminiscences), and the fact stands alone as supported with all the armament that science can bring to bear, both in its technical testing capabilities and its social structure of critique. It thence, if lucky, becomes a sentence in a textbook. In Bruno Latour's words, it is "freed from the circumstances of its production"

The above was a recounting of the conventional (and scientist's) perspective on the evolution of scientific facts. Whether this is the case is contested by social constructivism, a movement in philosophy that adheres to antirealism, which is to say that all of what we regard as outside "reality" is socially constructed, and thus science is likewise a social institution that generates conventions that by its social power it is able to foist onto a naive public, who in turn, like sheep, contribute their taxes to keep the scientific community wallowing in money and social power, cranking out yet more obscure and artificial "facts". Indeed, the very status of truth that is given to facts is fundamentally a social construct made up of a community of believing people, whatever their reasons and supposed evidence.

A few of Latour's works over the years. He declines to be post-modern, because he disagrees with the whole frame of modernity, as being somehow different from or non-continuous with the rest of history. And this attitude comes back to his dismissive attitude towards science and the enlightenment as being a break in kind from prior ways of understanding the world. It has just been fetishes all the way down.

Bruno Latour (along with his co-writer Steve Woolgar) waded into this controversy back in the 1970s with a French philosophical and anthropological background, to investigate what really goes on in a laboratory. He embedded himself into a leading laboratory and learned how it operated, informally and formally. This is recounted in the book "Laboratory Life" (1979; recent review), which, as usual for continental philosophers, is challenging to make sense of. The authors tend to straddle the two perspectives, both respecting and recounting the normal scientific activities and perspectives, (if rather laboriously), and then also persistently suggesting their contrary viewpoint and program that they bring to the project.
"Despite the fact that our scientists held the belief that the inscriptions could be representations or indicators of some entity with an independent existence 'out there', we have argued that such entities were constituted solely through the use of these inscriptions. ... By contrast, we do not conceive of scientists using various strategies as pulling back the curtain on pregiven, but hitherto concealed, truths. Rather, objects (in this case substances) are constituted through the artful creativity of scientists. Interestingly, attempts to avoid the use of terminology which implies the preexistence of objects subsequently revealed by scientists has led us into certain sylistic difficulties. This, we suggest, is precisely because of the prevalence of a certain form of discourse in the description of process. We have therefore found it extremely difficult to formulate descriptions of scientific activity which do not yield to the misleading impression that science is about discovery (rather than creativity and construction). It is not just that a change of emphasis is required; rather, the formulations which characterize historical descriptions of scientific practice require exorcism before the nature of this practice can best be understood."

Exorcism indeed! One might posit a simpler explanation- that science is, in fact, in the business of discovery, though with the caveat that what is to be dis-covered is never fully known beforehand, sometimes not even suspected, and thus there is a great deal of intutition, creativity, variation, and social construction involved in the process, and uneven and unpredictable results coming out. While the status of the resulting fact is never perfectly secure, and is supported by another social process of conventional agreement, that agreement is routinely granted once the preceeding critical hoops have been surmounted and leads generally to the vast pool of factual and "objective" information that finds its home in the academic literature, textbooks, college instruction, Wikipedia, etc. A pool that is further confirmed routinely by succeeding work and technical developments that depend on its objective factuality.

Latour does not, in the end, adhere to the hard program of social construction, for the simple fact that the object of the scientific story he recounts, the thyrotropin releasing hormone (TRF), was found, was found to be a specific and real substance, and went on to a respected place in medical practice and the textbooks, not to mention later earning a Nobel prize. There is real comedy in the attempt, however, as the anthropologist takes on the scientists at their own game, analyzing and plumbing their depths for structures and paradigms that they themselves hardly suspect, complete with diagrams of the laboratory, pictures of the roof and other apparatus, graphs of publication trends, and verbatim interviews with protagonists, underlings, etc. It is a sort of depth-psychology of one laboratory.
"But it would be incorrect to conclude that the TRF story only exhibits the partial influence of sociological features. instead, we claim that TRF is a thoroughly social construction. By maintaining the sense in which we use social, we hope to be able to pursue the strong programme at a level apparently beyond traditional sociological grasp. In Knorr's terms, we want to demonstrate the idiosyncratic, local, heteregeneous, contextual, and multifaceted character of scientific practices. We suggest that the apparently logical character of reasoning is only part of a much more complex phenomenon that Auge calls 'practices of interpretation' and which comprises local, tacit negotiation, constantly changing evaluations, and unconscious or institutionalized gestures. ... In short, we observe how difference between the logic of scientific and non-scientific practices of interpretation are created and sustained within the laboratory."

Granted, most of this is overwrought, but the true worth of this work was that these observers came into an eminent lab and paid minute attention to what was going on, and emphasized that what comes out of the sausage machine in publication and other products is far different than the materials that go in. While the conventional approach would emphasize the preceeding scientific observations and technical developments that led the leader of this lab to even contemplate that the purification of TRF from millions of dissected brains was possible and desirable, Latour emphasizes instead, and with some success, the social contingencies that surrounded the original uncertainties, the slow progress, the false leads and constantly discarded "bad results", the huge amount of money and effort required, and other nitty-gritty that forms the day-today of laboratory life. The latter emphasis is useful in accounting for how science gets done, but discards other crucial inputs, and is ultimately not at all convincing as a general theory of what science accomplishes or is.

I think the confusion arises fundamentally (apart from professional jealousy) from the fact that social constructivism is perfectly valid for some areas of our lives, such as arts, fashion, religion, morality, and to some extent, politics. Many problems do not have an objective criterion, and are socially constructed on an ongoing basis with criteria that boil down to what and who is thought good, whether for the individual, family, collective, etc. And the insistant denial of the total social construction of one's own field- as is understandably routine among scientists- is particularly vehement (and unfounded) in the case of religion and has lent the latter bizarre and extraordinary power through the centuries, which the deconstructivist project is entirely appropriate and well-prepared to investigate. And it should be said that many forms of primitive and pseudo-science partake of this form as well, if not of outright fraud. So the line is hardly stable or absolute. But when it comes to science as practiced in the enlightnement tradition, with a variety of safeguards and institutional practices that feature competition, peer review at multiple levels, and final public transparency, the approach falls flat.

  • A contemporary accounting of this scientific race, last of a 3-part series.
  • TRF is one of a series of "releasing hormones", operating between the hypothalamus and pituitary. Or should the word "is" be put in quotes?
  • A critique of the critique.
  • Mankiw takes on MMT, and obsesses about inflation, along mainstream lines.
  • MMT replies.
  • Limited liberty at Liberty University.
  • Notes from the Taliban.
  • Birds: who cares?
  • A cult is exposed.

Saturday, December 21, 2019

We Are All Special

A study in yeast finds that rare mutations have outsize influence on traits.

The word "mutation" is frowned upon in these politically correct days. While we may have a human reference genome sequence derived from some guy from Buffalo, New York, all genomes are equal, and thus differences between them and the reference are now termed "variations" rather than mutations.

After the first human genome was cranked out, the natural question was- How do we differ, and what do those differences say about our medical futures and our evolutionary past? This led to the 1000 genomes project, and much more, to the point that whole genome sequencing is creeping into normal medical practice, along with even more common panels of a smattering of genes analyzed for specific issues, principally cancers. Well, we differ a lot, and this data has been richly rewarding, especially in forensic and evolutionary terms, but only somewhat in medical terms. The ambition for medical studies has been extremely high- to interpret from our code why exactly we are the way we are, and what our medical fate will be. And this ambition remains unfulfilled. It will take decades to get there, and our code is far from controlling everything- even complete knowledge of our sequences and their impact on our development and medical issues will leave a great deal to accidents of fate.

The first approach to mining the new genomic information, especially variations among humans, for medically useful information was the GWAS study. These put the 1000 genomes (or some other laboriously accumulated set of sequences, which came tagged with medical information) into a blender and asked which variations between people's sequences correlated with variations in their diseases. Did diabetes correlate with particular genes being defective or altered? Despite huge resources and high hopes, these studies yielded very little.

The reason was that the notion of variation (or mutation) and especially the intricate field of evolutionary population genetics, was, among these researchers, in a somewhat primitive state. They only accepted variations that occurred a few times, so that they could be sure they were not just random sequencing mistakes. In a population of, say, 1000, any variation that occurs a few times has a particular nature, which is to say that it must be somewhat stable in the population and have a long history, to allow it to rise to such a (modest, but significant) level of prevalence. This in turn means that it can not have a severe effect, in evolutionary terms, which would otherwise have cut its history in the population rather short. So it turned out that these researchers were studying the variations least likely to have any effect, and for all the powerful statistics they brought to bear, little fruit turned up. It was a very frustrating experience for all concerned.

A recent paper recapitulated some of these arguments in the setting of yeast genetics. The topic remains difficult to approach in humans, because rare variations are, by definition, rare, and hard to link to diseases or traits. Doing so in a clinical study requires statistical power, which arises from the number of times the linkage is seen- a catch-22 unless one can find an obscure family pedigree or a Turkish village where such a trait is rampant. In yeast, one can generate lineages of infinite size at will, and the sequencing is a breeze, with a genome 1/250 the size of ours. The only problem is that the phenotypic range of yeast is slightly impoverished compared to ours(!) Yet what variety they can display is often quantifiable, via growth assays. The researchers used 16 yeast strains from diverse backgrounds as parents, (presumably containing a wide variety of distinctive variations), generated and sequenced 28,000 progeny, and subjected them to 38 growth conditions to elicit various phenotypes.

The major result, graphing the frequency of variations against their phenotypic effect. The effect goes up quite strongly as the frequency goes down.

These researchers claim that they can account for 73% of phenotypic variation from their genetic studies- far higher the rate seen for any complex human trait. They see on average 120 loci affecting each trait across the study, and 12 loci affecting each trait in any one mating. Based on past work with libraries of yeast strains, they could also classify the mutations, er, variations they saw coming from these diverse parents as either common (similar to what was analyzed in the classic GWAS experiments in humans, occurring at 1% or more) or rare. Sure enough, the rarer the allele, the bigger its effect on phenotype, as shown below. In rough terms, the rare variants accounted for half the phenotypic variation, despite comprising only a quarter of the genetic variation.

In an additional analysis, they compared all these variants to their relatives in a close relative of this yeast species, in order to judge which allele (variant / mutant or the reference / normal version) was ancestral, i.e. older. As expected, the rare variations that led to phenotypic effects were mostly of recent origin, and more so the stronger their effect.
"Strikingly, no ancient variant decreased fitness by more than 0.5 SD units, whereas 41 recent variants did."

The upshot is that to learn about the connection between genotype and phenotype, one needs significant (and typically deleterious) mutations, as geneticists have known since the time of Mendel and Morgan. Thus the use of common variants (with small effects) to analyze human syndromes and diseases has yielded very little, either medically or scientifically, while the study of rare variants has been a gold mine. And we all have numerous rare variants- they come up all the time, and are likewise selected out of existence all the time, due to their significant effects.

The scale of the experiments done here in yeast allow high precision genetic mapping. Here, one trait (growth in caffeine) is mapped against correlating genomic variations. The correlations home in on variations in the TOR1 gene, a known target of caffeine and a master regulator of cell growth and metabolism.

  • Stiglitz on neoliberalism.
  • Thoughts about Britain's (and our) first past the post voting system.
  • Economists have no idea what they are talking about- Phillips curve edition.
  • Hayek and the veneration of prices.
  • Real trial or show trial?
  • The case for Justice Roberts.
  • Winning vs success.
  • Psychotic.
  • Lead from gasoline is being remobilized by wildfires.
  • Winter has been averted.

Saturday, December 14, 2019

Success is an Elixir

We are besotted by success. For very obvious evolutionary reasons, but with problematic consequences.

Why is the James Bond franchise so compelling? It got more cartoonish over the years, but the old Sean Connery embodied a heady archetype of the completely successful hero. A man as skilled in vetting wines as in flying planes, as debonair with the ladies as he was in fighting hand-to-hand, all while outwitting the most malevolent and brilliant criminal minds. Handsome, witty, and brutally effective in all he turned his hand to, there was little complexity, just relentless perfection, other than an inexplicable penchant for getting himself into dramatic situations, from which he then suavely extricated himself.

We worship success, for understandable reasons, but sometimes a little too much. As Reagan said, nothing succeeds like success. It is fundamental to our growth from childhood to adulthood, to demonstrate and be recognized for some kind of effectiveness- passing tests, graduating from school, becoming skilled in some art or profession, which is socially recognized as useful, maybe through the medium of money. The ancient rites of passage recognized this, by setting a key test, such as killing the bear, or withstanding some brutal austerity. Only through effectiveness in life can we justify that life to ourselves and to others. The role can take many forms- extroverts tend to focus on social power- the capability of bending others to their will, while introverts may focus more on other skills like making tools or interpreting the natural world.

The Darwinian case is clear enough- each life is a hero's quest to express one's inner gifts and capabilities, in order to succeed not only in thriving in the given environment, but in replicating, creating more successful versions of one's self which do so all over again. Women naturally fall for successful men, as James Bond so amply demonstrated, but as is seen in so many fields, from basketball to finance.


But all this creates some strong cognitive biases that have some influences that are not always positive. Junior high school is the most obvious realm where these play out. Children are getting used to the idea that life is not fair, and that they can communally form social standards and decisions about what constitutes success, which then victimize those on the losing end- what is cool, what is lame, who is a loser, etc. Popularity contests, like politics and the stock market, are notorious for following fashions that valorize what one generation may believe is success, only to have the next generation look back in horror and redefine success as something else. In these cases, success is little more than a commonly held opinion about success, which leads to the success of con men like our current president, who insists that everything he does is perfectly successful, and who inspires sufficient fear, or confidence, or suspension of disbelief, or is so ably assisted by the propaganda of his allies, that many take him seriously. Indeed, it is exactly the unaccountable support of his allies who surely know better that force others in the wider circles of the society to take seriously what no rational or decent person would believe for a second.

The status of minorities is typically a "loser" status, since by definition their beliefs and practices, and perhaps their very existence, are not popular. While this may be a mark of true Darwinian lack of success, it is far more likely to be an accident of, or an even less innocent consequence of, history. In any case, our worship of success frequently blinds us to the value of minorities and minority perspectives, and is a large reason why such enormous effort has been expended over millennia, on religious, legal, constitutional, and cultural planes, to remedy this bias and promote such things as democracy, diversity, due process, and respect for contrasting perspectives.

We are victimized in many other ways by our mania for success- by advertisers, by the gambling industry, by war mongers, among many others, who peddle easy success while causing incalculable damage. While it is hard to insulate ourselves from these social influences and judgements, which are, after all, the soul of evaluating success; as with any other cognitive bias, being in our guard is essential to avoiding cults, traps, and, ultimately, expensive failure.

Saturday, December 7, 2019

Links Only

Due to the press of business, only links this week.

  • Stiglitz on elites, neoliberalism, and the end of history.
  • Inspired by Ukraine.
  • Gaslighting on an epic scale.
  • Or maybe religion is the problem? It was always a factually challenged affair.
  • The gig workers of yesteryear- gyppo loggers in the Northwest.