Saturday, December 15, 2018

Screwy Locomotion: the Spirochete

How do spirochete bacteria move?

Getting around isn't easy. Some of our greatest technological advancements have been in locomotion. Taming, then riding, horses; railroads, automobiles, airplanes. Microorganisms have been around for a long time, and while flying may be easy for them, getting through thicker media is not, nor is steering. The classic form of bacterial motion is with an outboard motor- the flagellum. The prototypical bacterium E. coli has several flagella sprinkled around its surface. Each flagellum is slightly helical, thus forming a languid sort of propeller, which if turned along its helical axis, (at roughly 6,000 rpm), can propel the bacterium through watery media. Turning multiple flagella in this same direction (counter-clockwise) encourages them all to entangle coherently and unite into a bundle. It turns out, however, that bacteria can easily switch their motors to the opposite direction, which causes the flagella to separate, and also to flail about, (since for a left-handed helix, this is the "wrong" direction), sending the cell in random directions.

A typical bacterium with multiple flagella, which will cooperate in forming a bundle when all turned in the same direction, consonant with their helicity (i.e. counter-clockwise).

These are the two steering options for most bacteria- forward or flop about. And this choice is made all the time by typical bacteria, which can sense good things in front (keep swimming forward), or sense bad things in front / good things elsewhere (flail about for a second, before resuming swimming). The flagellar base, where the motor resides, uses both ATP and the proton motive force (i.e. protons that were pumped out by cellular respiration, or the breakdown of food). The protons drive the motor, and ATP drives the construction of the flagellum, which is itself a very complicated dance of self-organization, built on the foundation of an extrusion/injection system also used by pathogenic bacteria to inject things into their targets.

Animated video describing how the flagellum and its base are constructed.

But sometimes a bacterium really needs to get somewhere badly, and is faced with viscous fluids, perhaps inside other organisms, or put out by them to defend themselves. One human defense mechanism is a DNA net thrown out by neutrophils, a type of white blood cell. Spirochetes have come up with an ingenious (by evolution, anyway!) solution- the inboard motor. This is not a motor sticking out of the bottom, but a motor fully enclosed within the cell wall of the bacterium.

Choice of directions (small forward or back arrows) that are dictated by the rotation of the flagella (blue). One set of flagella originate at the rear, and a second set originates at the front. Only if they turn in opposite directions (top two panels) does the spirochete swim coherently, either forward or back. 

How can that work? It is an interesting story. Spirochetes, as their name implies, are corkscrews in shape. In mutants lacking flagella, they instead relax to a normal bacterial rod shape. So they have flagella, but these are positioned inside the cell wall, in the periplasmic space. Indeed they form the central axis around which the corkscrew rotates, with one set of (approximately ten) flagella coming from the rear and another set from the front, each ending up around the middle. If each set rotates as hard as it can, they drive their respective ends to counter-rotate, in reaction. If the front motors (of which there are several) turn their flagella counterclockwise, as viewed from the back, they will, in reaction, drive (and bend) the nose into a clockwise orientation. If the back set of motors run clockwise, driving their flagella counterclockwise (also as seen from the back), then the rear part of the bacterium counter-rotates in clockwise fashion, and the coordinate action drives spiral bending and an overall drilling motion forward.

Video of a non-spirochete bacterium with its flagellum stick to the slide, causing the tail to wag the dog.

Video of spirochete bacteria in motion.

On the other hand, if the motors on the opposite ends of the bacterium go in the same direction, then the flagella induce opposite, instead of coordinate, counter-rotations, and the bacterium doesn't tumble randomly, as normal bacteria do, but contorts and flexes in the middle, with a similar re-orienting effect. This ability incidentally shows the remarkable toughness of these bacteria, considering the lipid bilayer nature of their key protective membranes. These bacteria can also easily reverse direction, by sending both sets of motors in reverse, operating very much like little drills. How this exquisite coordination works has not yet been worked out, however.

Reconstruction, drawn from electron microscopy, of one end of a spirochete, showing the motor orientations, the sharp hook/base of the flagellum, the membrane and cell wall structure, and one of the signaling proteins (MCP), which transmits  a sensory signal to dictate the direction of motor rotation.

One thing that is known, however, is that spirochete motors are massive- almost twice the size of E. coli motors, with special outside hooks to propagate power through the tight turn inside the periplasmic space. It is interesting that these motors can be scaled up in size, with more subunits, and more proton ports for power, as if they were just getting more cylinders in a (fossil fuel-burning) car engine.

Structure of the Borrelia flagellar motor, showing the stator (blue), which is attached to the membrane and stabilized against rotation; the rotor (yellow spokes and teal C-ring), and the gateway ATPase complex which unfolds and transmits the structural components (proteins) into the central channel from which they build the machine.

All this is in service of getting through messy, gelatinous material. The model for most of this work is the spirochete responsible for Lyme disease. The characteristic red ring seen in that infection is thought to track the progress of the spirochete outward and away from the original tick bite site, in relation to the immune system catching up via inflammation. But such viscous environments are quite common in the organic muck of the biosphere, including biofilms established by other bacteria. So the evolutionary rationale for the superpowers of spirochetes is probably quite ancient.

  • EPI has a comprehensive solution for righting the inequality ship.
  • John Dingle also has a solution.
  • "Entitlements" are OK- on the importance of social insurance. Remember, the military is always insolvent, from a budgetary perspective.
  • Sleazebags to the end.
  • On the types of epilepsy.
  • A persistent cycle of resource extraction, incumbent interests, regressive politics, and non-development. Let's not go there ourselves.
  • A lesson in jazz.

Saturday, December 8, 2018

Psychodrama of the Reformation

Luther's personal demons drove the split of European Christendom. A second post from "Fatal Discord", a double biography of Luther and Erasmus, by Michael Massing.

It is hard to believe, but Martin Luther was ridden with self-doubt. That is what drove him to become a monk, to confess his sins for hours a day, and to search for a way out through the scriptures and other theological writings. When he came across Augustine, he underwent a sort of conversion experience which seems to have led to a decade-long burst of energy, rebelling against the Catholic church and pouring out a prodigious flow of theses, tracts, and books on his new evangelical theology, including a full German translation of the Bible. (It is worth noting parenthetically that in these early days of printing, the pamphlets and books brought out by Luther and his adversaries were easily as intransigent, abusive, and uncivil as our current twitterverse, an atmosphere that may have had something to do with the brutal wars that ensued.)

"Now, in reading Augustine himself, Luther found nothing about free will, good works, or doing one's best. Instead, he found stern pronouncements about human wickedness, divine majesty, and undeserved grace. If Augustine was correct, the selfish urges and prideful thoughts that were continually welling up in him represented not simply his own personal failings, but ingrained features of human nature. As forbidding as Augustine's theology might seem to others, Luther took great comfort in the idea that his fate was not in his own hands."

The issue was free will. If god creates everything, rules all, and sees all time, then how much power do humans have? None, obviously. It was John Calvin who took Luther's position to its full extent, arguing for full pre-destination of everyone's fate, with a decided minority pre-destined (elected) to enter heaven, and all others going to hell. The Catholic church, despite Augustine's influence, took the more practical route of claiming some free will, such that prayer, putting money in the collection plate, feeding the poor, and even buying indulgences, would all be put on the sinner's tab when they got to the pearly gates.

Opening page of Matthew from the Luther Bible, 1534.

It is difficult to run a society without rewards for good behavior, so while the Catholic church did not go the whole way to Pelagianism, it did run a middle course, rewarding (in the next world, at least!) good works, while also holding god to be super-powerful, just not all-powerful. Luther's epiphany that faith alone saves, and that good works count for nothing, solved his personal dilemma, and fueled his world-shaking rebellion. But it also left his parishoners with little incentive to do good works, or even to attend church. Luther was faced with continuing apathy through his later years in Wittenberg, reduced to berating his dwindling flock for its moral and religious laxity.

It was in the peasant's rebellion, starting about seven years after his electrifying theses, that the problems of Luther's theology really became apparent, causing self-doubt and confusion to creep back in, gradually sapping Luther's confidence, productivity, and influence. The peasant's revolt was driven by a new crop of preachers more extreme than Luther. If rebellion against the Catholic church for its worldly excesses and oppression was permissible, why not rebellion against the landowners and lords whose oppression was even worse, and whose theological support far weaker? And if all believers are priests, and all can read and interpret the bible, then why listen to the doctors of theology from Wittenberg? Luther was aghast at what he had unleashed, and turned completely around to support the nobility in this bitter and ugly fight, full of unspeakable tortures and massacres.

Luther continued to collaborate closely with the temporal authorities for the rest of his career, and the Lutheran church became a state-affiliated chuch, ridden with many of the same compromises and theological perplexities that characterize the Catholic church, and which Luther had originally thought he had escaped. The energy of the reformation would re-emerge in the Calvinists, Puritans, Methodists, Quakers, and countless other sects of which there are now many thousands. Purity is always energizing, but neither practical nor defensible in what is, in reality, a godless and complicated world. In the end, the attentive tolerance of humanism regularly turns out to be the better solution.

Saturday, December 1, 2018

The Peregrinations of Humanism

What happened to the project of Erasmus? What used to be solidly Catholic turned into atheism, aka "secular humanism".

Have there ever been non-secular humanists? Yes, virtually all were Catholic back when humanism was truly in flower, in the 1400's and 1500's. There have even been humanist popes! Humanism was a big theme of the Renaissance when Western intellectuals turned their attention to the languages and authors of antiquity with new vigor. The preceeding movement of scholasticism had built on an earlier encounter with Aristotle and Neoplatonism, which led to the founding of many universities and reached its peak in the output of Thomas Aquinas. But scholasticism was more concerned with conforming Aristotle to Catholicism and making a show of reasoned logic / dialog, (dialectic), rather than truly plumbing the depths of Aristotle's profound corpus and methods. They knew he was the intellectual giant of antiquity and far beyond their own achievements. Only with humanism was Europe ready to deal more deeply with the ancients.

This was a time when scholars started hunting in earnest for manuscripts hidden in cloister libraries, and encountered both manuscripts and scholars fleeing the now-defunct Byzantine empire. These scholars improved their Latin based on a wider familiarity with these sources, and started learning Greek and even Hebrew. Erasmus of Rotterdam was one of the greatest of these hunters and scholars, and turned his learning into (among many, many other projects) a newly corrected edition of the Bible, with Greek facing the Latin, the first time the Latin Bible had been (intentionally) revised in over a millennium. This story is told in the outstanding book, Fatal Discord- a parallel biography of Erasmus and Martin Luther.


Luther obviously runs away with the show, and the book, by fomenting a fundmental revolution in Western culture. Author Michael Massing suggests that Europe faced divergent paths, Erasmus representing the more liberal, reformist, and moderate course, which could have saved everyone a lot of trouble. Luther read Erasmus's new bible and other writings, was also inspired to learn Hebrew, and based much of his revolution on Erasmus's ideas. But Erasmus never renounced the Catholic church, and hated warfare above all other forms of waste and injustice. He was in this a humanist to the core. Luther was more of a fundamentalist, standing on Sola Scriptura- of his interpretation, naturally- come hell, high water, or martyrdom.

So what is humanism, after all? In a theological sense, it is attention to and learning from diverse aspects of the current and past world, in contrast to assuming that one's scripture contains all knowledge. If the world, humans, and human reason are all made by god, then this wider field of inquiry is not only permissible, but essential, to fully appreciate her work. On a pedagogical level, humanism became the program that Erasmus set up based on his thrilling scholarship- the learning of Latin foremost, from the great classical authors, and then Greek as well, along with rhetoric, grammar, and some logic- the Latin trivium, in short. While revolutionary in the fields of biblical studies, higher criticism, and philology generally, this program eventually fossilized into the "liberal" education in the classics that was standard through the 19th century, plaguing young minds with dead languages, long after Latin had lost its role as the universal intellectual language of Europe.

And on an ethical level, humanism is the sense that truth and scholarship must be beneficial, over their opposites, and that, in line with the rest of renaissance sensibility, human achievements and flourishing are the measure of social and theological systems. While the neoplatonists where quite consonant with the abstract, ethereal concerns of the Catholic church, other authors and ideas from antiquity were much less so, and the humanists, Erasmus as a prime example, turned into a somewhat skeptical if not critical community within the church, urging reform from the bloated, corrupt, militaristic, and intellectually lazy institution it had become.

This breakdown became evident in the confrontation with Luther. In response to his copious tracts, books, and theses detailing the problems of the church, its response was simply to assert that he was wrong, and that any opposition to the pope and tradition was inadmissible. The Catholic church failed to make a serious intellectual case, and it would take decades, if not centuries for it to do so. Book burnings were the first response, followed by the Index of banned books, which featured not only those of Luther, but those of Erasmus as well. This spelled the inevitable end of humanism in the Catholic church, since skepticism and intellectualism are incompatible with hierarchy and fealty.


Humanism had a much longer career in Protestant lands, with their greater freedom and diversity. Charles Darwin came within a hair's breadth of becoming an Anglican minister, and mostly viewed his naturalist interests in the positive light of god's work on earth. But they inevitably parted ways even here, as the mechanisms of nature gradually revealed themselves to be anything but divine. Now one hardly hears about religious humanism, as humanism has become synonymous with thorough theological skepticism and this-world ethics. What would Erasmus say? The EU has named its internal student exchange program after him, in honor of his pioneering role in promoting pan-European projects and intellectual community. He would have been appalled at the way the Protestant reformation bled Europe and led to ceaseless division. But I am sure he would still be in the intellectual, cosmopolitan vanguard, which remains humanist today.

Saturday, November 24, 2018

The Problem With Atheism

Bernard Mandeville and the impossibility of getting along without lying.

We live in a little cloud of lies. From the simplest white lie and social protocol for hiding unpleasantness, to the universal belief that one's own family, city, country are better than the other ones, untruth is pervasive, and also essential. Vanity, optimism, a standard set of cognitive biases.. are opposed to the reality principle. The economic commonplaces which are, as Keynes noted, unknowningly derived from some defunct economist. Our unconscious is resolutely irrational. Euphemism, humor and swearing are ways to refer to truths that are difficult to bring up in straightforward fashion. But more serious truths are the more deeply hidden. Such as death, the final stop on everyone's trip. Full-on honesty and truth? No one wants that, or could live with it.


Many thinkers have plumbed these depths, from Machiavelli to Freud. Bernard Mandeville was one, profiled in a recent BBC podcast. His most enduring (and brief) work was the Fable of the Bees, which portrays a society much like Britain's, rife with greed, ambition, corruption, and crime. Due to moralist complaints, god decides to make this hive moral and good, upon which everything promptly goes to pot. The economy, previously held up by a love of luxury, collapses. Courts and lawyers have nothing to do, clothing fashions fail to change. The traders leave the seas for lack of demand, and the military succumbs for lack of population. The hive ends up resembling one truly composed of bees, and goes to live a hollow tree, never to be heard from again.
"Those, that were in the Wrong, stood mute,
And dropt the patch'd vexatious Suit.
On which, since nothing less can thrive,
Than Lawyers in an honest Hive."
... 
"Do we not owe the Growth of Wine
To the dry, crooked, shabby Vine?
Which, whist its shutes neglected stood,
Choak'd other Plants, and ran to Wood;
But blest us with his Noble Fruit;
As soon as it was tied, and cut:
So Vice is beneficial found,
When it's by Justice lopt and bound;"

His point, naturally, was that vice is both natural and to a some extent the underpinning of national greatness and economic vitality (given some beneficial management). Greed is good, as is irrational optimism and ambition. Mandeville was also a famous anticlericalist in his day, but that is another story. It was a classic contrarian point, that what we fight tooth and nail to vanquish or hide has, in reality, a role to play in the national character and success, for all its embarrassment. And that we routinely lie, to ourselves above all, to hide the truth of reality so that we can go on our way from one day to the next.
"My aim is to make Men penetrate into their Consciences, and be searching without Flattery into the true Motives of their Actions, learn to know themselves."
- Bernard Mandeville, in Free Thoughts on Religion, the Church, and National Happiness.

What is our most florid and communal lie, but religion? This is the salve of social togetherness, moral self righteousness, and imaginary immortality. It is the finely tuned instrument that addresses alike our private fears and social needs. And atheists know it is completely, utterly wrong! But what is the point of saying so? Religions have been corrupt, abusive, greedy and murderous from time immemorial- they have many faults. But untruth is not a flaw.. it is the reigning feature of this imaginative confection, providing the credulous a full belief system to support a positive and hopeful self-image, (not to mention conventional authority!), so important to happiness, providing the more skeptical an endless labyrinth of theological puzzles, while providing even the most skeptical or apathetic a social institution to call home.

So why go around ripping the clothes from believers, crying that their cherished narratives of meaning are senseless- that they should go forth theologically naked? It is a serious question for atheists, going to the heart of our project. For Freud, after all, repression had a positive function, and was not to be comprehensively cleared away, root and branch, only pruned judiciously. Lying is indeed integral to mature social functioning. Clearly, untruth is not, by itself, an unacceptable portion of the human condition. This implies that atheists need to be generally gentle in approach, and selective in what they address directly- the most significant outrages and injustices perpetrated by religions, of which there is no shortage. When religions invade the territory of science, making bone-headed proclamations about biology and geology, that clearly crosses such a line. And likewise when religions insinuate themselves into governmental institutions, bent on seeking power to foist their beliefs and neuroses on others.

The so-called arrogance of atheists consists of their opposing / exposing the cherished verities of others as false. Such arrogance is of course not unknown among religious believers and zealots either, and for much more modest cause. The secular state settlement of the West has forced religions to forego armed conflict and state violence in the pursuit of their truths and enemies. Atheists should take a page from this success to lead by example and humor, rather than frontal assault, even rhetorically.


  • BBC to continue spouting religion.
  • Silicon valley has its religion as well- a sort of Stockholm syndrome.
  • But lies in politics.. is there no limit?
  • Hate is in the textbooks, in Saudi Arabia.
  • Euro countries are not independent.
  • 5G to rule them all.
  • Heredity counts for a lot.. more than parenting.
  • The labor market could run much, much better.

Sunday, November 18, 2018

Three Rings to Rule Them All

Condensins, cohesins, and SMC5/6: a family of ring-shaped protein complexes that keep chromatin organized, compacted, and generally under control.

Each of our cells contains a meter of DNA, scrunched up to microscopic proportions. This DNA is particularly visible during mitosis, when it is neatly condensed into chromosome brushes, which get pulled and segregated in the remarkable ballet of cell division. We also know that topoisomerases, which can cut this DNA, either nicking on one strand to allow unwinding, or on both strands to allow strand passage (to uncatenate or untangle as needed), are central players in keeping this mess under control, at least in a passive sense. But obviously, to make neat chromosomes, and for countless other tasks, some of which will be described below, more than topoisomerases are required. Another class of proteins called SMC (structural maintenance of chromosomes) supplies some of the lariats, knots, and other rope tricks that are needed to keep our nuclear DNA going in the right direction, and has been the focus of quite a bit of recent progress.

Bacteria generally have one SMC protein, but we have six, paired into three functional ring-shaped complexes: condensin, cohesin, and SMC5/6  (no clever name, unfortunately). They were originally found to function, respectively, in the condensation of mitotic chromosomes, in the cohesion of sister chromatids, and in DNA repair. The SMC proteins pair up to form large rings, of about 50 nm, have an ATPase activity which has been recently found to function as a motor along DNA, and associate with a bunch of other proteins to regulate their activities. It is generally believed that the rings they form can encircle one or two strands of DNA, to provide the pairing and looping functions to be described.

Cartoon of how cohesin encircles both daughter strands of replicated DNA, to keep them paired until the critical separation point in mitosis.

For example, cohesins glue together daughter strands after DNA synthesis, so they do not float apart, but can be carried along as pairs into mitosis, and then separated at the right time (anaphase) with a dose of protease which cleaves the cohesin ring. Mutant cohesins cause DNA tangling and loss of proper segregation at cell division, leading to mutations and thence to death, cancer, etc. But having sister DNAs close together is convenient for other reasons as well. If one gets a mutation, homologous repair can use one strand of the good copy to directly invade the bad one, and after excising the bad portion, encode the repair. In fact, the various SMC complexes have somewhat overlapping functions, so some can fill in for defects in the others.

Electron micrographs of purified condensin, showing the structure of a ring with large blobs (containing ATPase and other accessory proteins) at one end (customarily the bottom) and a smaller blob on the other side where the two SMC proteins also dimerize (called the "hinge" region). Bar is 100 nm.

Condensin is the main driver of chromosome compaction, looping, and transcriptional domain establishment. Ultrastructural studies of mitotic chromosomes have long shown that mitotic chromosomes are composed of loops- variably sized and perhaps of multiple levels. Condensin has perhaps been the best studied of the SMC family, with beautiful recent work (also here) showing that it forms loops by pumping DNA through its ring structure. In the experiment shown below, a single molecule of DNA, fluorescently labeled, was attached to a surface at both ends. Then a flow was set up in the ambient fluid, towards the top right. When cohesin protein (purified from yeast cells) was added, along with ATP, it selected a site on the DNA, then started forming a collar and pumping out the free portion of the DNA, forming a little loop. At the end of the experiment, several minutes down the line, this cohesin complex spontaneously let go, allowing the DNA back into its original state, waving freely in the flow.

A single DNA molecule in a fluid flow cell, anchored at two points (red circles), shown through time as it is bound by one codensin molecule, which forms a little pumped loop within a few seconds.

Such looping is not only relevant for mitotic chromosome structure, but also for transcription. Genes are driven by regulatory protein binding sites, "enhancers", that can be very far from the core coding portion of the gene- often tens of thousands of base pairs away. How does such an enhancer know which gene it is supposed to enhance? It has gradually become clear that genes are surrounded by a zone of isolation with "insulator" DNA sites on the boundaries. Cohesins have recently been shown to be key creators of these zones, binding to the boundary sites and pumping out the intervening DNA, isolating one loop from its neighbors, at least with respect to processively scanning searches by DNA binding proteins, and also with respect to mega-complex fomation by the enhancers of each zone.

The SMC5/6 complex is proposed to facilitate replication by keeping the daughter strands close so that that topoisomerase II can come in and relieve topological tangles.

The SMC5/6 proteins perform yet another function, of facilitating replication. Like cohesins, this complex forms rings around recently replicated DNA. The replication fork is itself enormously complex, but as it works, (probably stationary, being fed in sewing machine fashion), the DNA going in and coming out is continuously writhing about to accommodate its helical twist. Imagine a sewing machine working on fabric with an intense twist of one full turn per ten stitches- it would be quite a challenge to operate. Most of the stress can be accommodated on both sides, incoming and outgoing, by continuously nicking and relaxing by topoisomerase I. Yet it is thought be helpful to keep the two daughter strands in close proximity, to allow stand-passing topoisomerase II to undo more serious tangles, and also to prepare for the long-term use of cohesin which keeps the daughter strands together through interphase and into mitosis.


What is known about how the SMC proteins actually operate? That is still a work in progress. In order for condensin to form DNA loops, it needs at least two functions- an anchor to hold on to one region of DNA, and an ATP-using pump that scrunches the neighboring DNA and feeds it through its ring structure. The anchor is quite well characterized. It needs to be relatively agnostic about the sequence it binds to, but once attached, it must stay put while the rest of the molecule does its work. This is accomplished with a special knotting portion of one of the accessory proteins attached near the ATPase portion of the complex. These proteins form a positive charged groove, ready to bind DNA. Once bound, there is also an unstructured extension of one of these proteins (in green below) that comes down to lock the DNA in place, prompting the authors to call it a "safety belt". This structural shift does not require ATP, but is required before the ATPase nearby can become active.


Structural cartoon of two accessory proteins of condensing (yellow and beige), which form the anchor. This binds DNA non-specifically, and once bound, gets locked in place by a unstructured protein extension and also licenses the ATPase to begin operating to pull neighboring DNA through the ring. The topology of the shown DNA/chromatin is likely wrong.

What is the ATPase doing? It has just recently been shown that it really is a DNA translocase, (partly as shown above), after some years of doubt. It is also remarkably efficient, traversing at a rate of ~70 basepairs per second, and only using two ATP per second, thus covering about 35 bp per ATP. It must be using the length of its ring to make jumps of some kind- a mechanism more reminiscent of actin or kinesin than of typical DNA/RNA translocating enzymes. Researchers working in this field have proposed a couple of models. One is that the ring separates at the base (right, below) to allow the two ATPases of the paired SMC protein complexes to "walk" alternately along the DNA, taking long strides of up to 50 nm. This obviously risks losing whatever is being enclosed in the ring, so is problematic. The second idea (left, below), is that the extended, coiled portions of the SMC proteins somehow fold and unfold in response to ATP hydrolysis at the end, allowing the complex to take half-steps while rigorously keeping the ring closed. It would be difficult to envision how this mechanism works in detail. It may be that more than one ring cooperate, to resolve some of these coordination issues.

Rings composed of two SMC proteins (red, blue) are proposed to walk along DNA using their ATPase activity by two alternative mechnisms. Note that the SMC molecules with blobs on the ends are not symmetrical. The ATPase and other significant accessory proteins and activities of the complex are all on the lower (striped) blob of each SMC protein, while the other blob represents a much simpler "hinge" region of the proteins which dimerize but have no other known functions.

  • Capitalism vs community.
  • What is wrong with the EU.
  • Learning and flexibility as the red/blue divide.
  • One electric utility keeps causing devastating fires in California.
  • Canada helps parents keep working.

Saturday, November 10, 2018

Fight For the Biosphere

The Story of the Earth Liberation Front: If a tree falls.

What is sacred? No one lives without deep values, whether conscious or unconscious. When I recently travelled to a small midwestern town, I was struck by its devotion to its institutions of reproduction- the high school, the church, the football game, the picket fences. Small town American is under perpetual siege from the outside, from the Amazons, Wallmarts, cheap drugs, bombarding media, and changing values. From capitalism in general, though no one would put it that way. Getting young people to stay instead of heading out to the big city or the coast is one challenge. Another is facing a flow of poorer immigrants who do want to come, but who drop the bottom out of the local labor market and are difficult to assimilate. The FOX and Sinclair propaganda channels harp constantly on "traditional values", as though applying a magic incantation against change (even as they and the right end of the political spectrum work to remove what fetters are left on capitalism, and to destroy the public goods & institutions that these communities rely on). No wonder Trump found a fearful and responsive electorate.

But everyone has their god- communists worshipped the sacred revolution, into whose maw millions were fed. And into the bargain had their trinity of Marx, Engels, and Lenin. To others, capitalism is a glowing, sacred value, and to some extent for good reason. The adoption of capitalism in China has brought about the most massive and rapid transition out of poverty, ever. (Even though the means to get there has been ecocidal technology.)

But these major ideologies and religions are weakening in our time. People are becoming disaffiliated with the cultural structures and institutions that used to cultivate sacred values, whether those of explicit religion or of its various modern ideological substitutes. The balance is often made up, on a personal level, by "nature". This is our instinctive and "natural" religion- the groves of the pagans, the auspicious birds and other animal spirits, the awesome scale and impurturbability of the surrounding vista, not to mention our own mystifying biology.

A fairy ring in a wooded grove.

The dedication to conservatism that pervades small town America is deeply in conflict with respect to this deeper set of values, as well as being counter-historical. A mere six or seven generations back, these lands were peopled by Native Americans, before being invaded by pioneers. These pioneers found, in their westward expansion, an undreamt-of natural abundance of game, fertile soil, and plant and wildlife of all sorts, which they promptly set about chopping down, shooting, poisoning, and generally extirpating. The illusion of stasis upon which rural Americans are so intent on staking their politics belies tectonic shifts to their natural surroundings and supporting ecosystem.

For the world is on fire. It is not just the loss of wolves, and the invasion of exotic species, and the relentless spread of pesticides, and countless other piecemeal assults that are degrading what we imagine to be perennial nature. It is global warming that is making nature itself a shadow of her former self. California has been literally on fire the last couple of years. Seasons are palpably shifting. Droughts are spreading. The Arctic sea ice is dwindling. Corals are dying en masse all over the world. Wildlife has been halved over the last half-century. Forests continue to be burned and clear-cut.

Those who see the sacred in nature are deeply appalled and affronted by all this. In the late 90's and early 00's, the Earth Liberation Front formed to take direct action against this desecration, not just by protesting, but by attacking those responsible for the clear-cutting, especially of old growth forests. The Northwest is full of roads that have a thin screen of trees to shield the innocent driver from vast clearcuts hidden behind. What are called "National forests" are in reality more tree farms than forests.

El Dorado "national forest"

The documentary "If a Tree Falls" is a moving story of a fight in defense of sacred values, against the modern Maloch of the timber industry. Whether this fight is noble or not is one of the themes of the piece. But the timber cutters have another set of values, more in line with the conventional property and rapine program of American capitalism, and get to brand the ELF activists as "terrorists".

The irony of the ELF actions is sadly unmistakable, using fossil fuels like diesel oil to burn down the buildings of the forest destruction complex, (i.e. the forest service and the timber companies), which will be immediately rebuilt using yet more timber. The bulk of the film profiles one of the last holdouts from Federal investigation and prosecution, Daniel McGowan. A pudgy, unprepossessing terrorist indeed, he gradually comes into focus as unshakable in his deep sense of sacred values which are in total opposition to the established order. Likewise, the prosecutors and investigators are profiled at some length, embodying their dedication to the values of law and order under the existing system. Yet they are visibly uncomfortable with what those values ultimately stand for and accomplish in this case.

Capitalism is fundamentally amoral, and exists to serve whatever we as private people want to have. It is a tool, not a value system. If we want houses made of wood, it supplies that wood, no matter the incidental cost to public lands and the animals and plants that live there. If we want electrical power, it will burn the coal to supply that power, and transmit it over fragile lines that regularly cause devastating conflagrations in high winds, abetted by global climate heating. We can not blindly trust capitalism to safeguard our long-term interests, let alone our sacred values, from our short-term needs. That is the work of government. And the last people to whom we can entrust that government are those who own and benefit from the capitalist system.

  • Conservation vs conservatives.
  • Pakistan shows who its friends are.. the Taliban.
  • "Free speech" in Europe is a little different than in the US.
  • The media is not so great in Britain, either.
  • Facebook remains a cesspool. 
  • Burn it up. The destruction of social trust favors Republicans.
  • Fellow sleaze, in a completely illegal appointment.
  • The US excels in diagnosing and treating rare diseases.
  • Economic graph of the week... Left cities are economically more equitable, which is perhaps not saying much.
Economic mobility in various cities, vs overall employment growth.

Saturday, November 3, 2018

Inequality Spelled the End of Rome

Historian Michael Grant pins the blame for the decline and fall of Rome on economic and social inequality.

We have never had a government by the rich, and for the rich, quite like today. How this could come to pass as a response to one of the most severe financial panics in our history, to financial mass malpractice, and to the Occupy movement, is quite curious. It is perhaps a testament to the innate temperamental conservatism, coupled with the extraordinary power of money in our media and political system. Where are we headed? One way to think about it is to look to history.

Fabulous relief from a late Empire sarcophagus. Rome was about power.

Rome ruled the Mediterranean for roughly five hundred years, from its scrappy beginnings assimilating neighboring city states on the Italian peninsula to its wimpering end at the hands of successive Germanic armies. Some of its greatest gifts were for politics- running a durable, elitist political system with extremely complicated rules, operating a likewise complex legal system, and treating foreign and allied powers with harshness, but also substantial generosity. Throughout its time, inequality was the rule, including slavery at the very bottom. The system was run by and for those at the top- the senators, landowners, and slaveholders. But at the beginning, there was a great deal of civic virtue- it was a republic, and ambition for the public good / growth of the empire often coincided with personal ambition. But defending a static or contracting multi-continent empire is not as much fun. Increasingly, the rich relieved themselves of taxes and public responsibilities, and the burden of supporting the enormous empire fell on the lower classes, in the form of tax-farming.

This is briefly outlined by Michael Grant in his book "A Social History of Greece and Rome". He stresses at some length that the lower classes- the slaves, the ex-slave freedmen, the poor and middling classes- lived quite miserably, and were treated miserably by the system. But they had no political organization or power, and no consciousness of themselves as a class. They were inert, apart from a few riots and revolts which were always local affairs, driven by desperation rather than principle or organization. This has been true through history. Democracy and other revolutions from below are generally not led from below, but by a faction of the rich, engaged in their customary occupation of competing for power at the top. Our founding fathers were not Scots-Irish hillbillies, but colonial aristocrats disaffected from their fellow lords and peers back in Britain.

So Rome was always nervous about its poor and its slaves, but never faced an organized revolution, let alone a Marxist intellectual critique. This allowed progressively worse treatment as time went on, to the point that free Romans chose to become virtual serfs under large landowners rather than face the tax collectors and military recruiters on their own, leading right into the conditions of the medieval period. A state rests on the allegiance and service of its members. If the rich couldn't be bothered to fund its needs, and the poor were hounded to the point of desperation, of what is such a state made?
"Christian writers, too, support the poor, sometimes with passion, but the effect was one again, in practice, non-existent. The destitute had to be content with the assurance that their plight would stand them in good stead in the next life. Christianity, like to many other institutions, has been blamed for its contribution to the fall of the western Roman empire- because it perpetuated the internal social rifts. And there may be something in this, although the main contribution of faith was to establish a focus of loyalty which was not the imperial court, and was not, in fact, of this world. But the fall of the empire was complex. External pressures played a major part. Internally, the main cause was not Christianity, but the gulf between the rich and the poor whom the rich exploited." - Michael Grant, in A Social History of Greece and Rome

What Americans think inequality of wealth should be like, compared with what they think it is, compared (top) with what it actually is. In fact, the top 1% owns over 40% of the wealth and gets one fifth of all income.

While we in the US have only had such antique social extremes in the slave-holding South, the current level of inequality is, in quantitative terms, astonishing and alarming. The trend of our current administration of giving gargantuan tax breaks to the rich, along with countless other gifts of relief from public good regulations, worker rights, and criminal enforcement, means that we are headed not just back through the New Deal into another gilded age, but possibly well beyond. It is hardly the land of the free if so many are economic slaves to others, with homeless beggars on every corner. As Rome evolved from an aristocratic Republic into a more frankly royal Empire, we seem headed in a similar direction, under a new Octavian who has no patience for the weak, the losers, civil society, democracy, or civility. The state exists for winners. Why anyone (who is not rich) follows him is beyond me, but then the lessons of history are usually learned only by those who don't need them.

Saturday, October 27, 2018

Native Americans and Genetics

A fraught story.

The recent profusion of DNA studies of human lineages have clarified a lot about human history- where we came from and where we have travelled over the millennia. All this depends on samples from native populations- the ones we came from. It is only apparent that we came out of Africa if there are stable African populations that constitute the source and retain the vast diversity of our oldest homeland. But what if the natives do not want to be sampled? What if they are woke to the colonialist and genocidal legacy of the science / scientists doing the sampling, and want no part of it?

That is what happened, in part, in the recent flap over Elizabeth Warren's announcement of Native American heritage. Native South or Central American, that is. As told by a couple of experts, the lab that performed the analysis could not get permission to use North American samples, so used DNA from populations elsewhere in the Americas. Since Warren is herself from North America, indeed Oklahoma, and since the history of native peoples throughout the Americas is known to be relatively recent, expanding over last 15,000 years at the outside, the method is clearly valid in inferring, indirectly, some North American native ancestry for Warren.


So why the guff she caught from the Native American community? It was quite puzzling to hear their representatives trying their hardest to pour cold water on her claim, as though they were getting talking points from the FOX propaganda channel. Despite her not claiming to be a tribal member or wanting to be, they trotted out their arcane rules for membership, which certainly wouldn't accept anything so white as DNA testing. But lo and behold the tribe- the Cherokee in this case- use fractional blood relations determined from a list compiled by white people of the US government back in 1902. There are no good answers here, after half a millenium of disposession, destruction and abuse, but denying the obvious is not one of them.

The deeper issue is the appropriation and objectification of Native Americans and their culture by others, from here to Germany and beyond. Playing cowboys and indians, putting on Karl May dramas, naming sports franchises ... we have a very fraught relationship of romanticization and trivialization, little of which has anything to do with real Native Americans, particularly those living today who wish to be custodians of their own culture even while still suffering under the various debilities of their treatment by the dominant culture. I was part of this myself, in the Boy Scouts, which still play at being Indians, mortifyingly enough. Then the history of eugenics, and the plundering of native treasures, archeology, and burials, etc. has put so-called scientists in a particularly bad light.

This forms the backdrop of the notorious fate of the Kennewick man, an archeological find that led to bitter, drawn-out controversy. The almost complete skeleton, found in Washington state at the Columbia river, was 9,000 years old, and by morphology was more similar to other peoples such as the Jomon aboriginal people of Japan than native Americans. Ironically, it was DNA testing that confirmed affinity with Native Americans after all, after which the remains were given to the local Native American nations, including the Umatilla, which buried them at an unpublished location. From the native perspective, this fed into the narrative that their history is eternal and static, meaning that any pre-Columbian artifacts or remains found on what is currently their land is associated with their culture in some way, despite the thousands of years that may have passed and migrations that may have happened, and thus presents the right of possession and cultural use. One gets the distinct impression that Native Americans do not really want to know their own deep history, preferring a religious narrative of having been forever in the Americas, instead of having wandered in a few thousand years before the Europeans did.

From a scientific perspective, the episode was a travesty of political correctness, as a 9,000 year old skeleton could have no imaginable cultural connection to the current inhabitants of the area, while being an inestimably rich source of knowlege about this early post-glacial time of North American settlement. This antiscience attitude is perhaps a fair harvest for all the harms and hurts inflicted over the last few centuries, science being one of the most domineering and distinctive expressions of Western culture. Still, the loss to general knowledge rankles.

One Cherokee representative spoke of how irritating it is to repeatedly meet people who claimed to be part Cherokee, expecting some positive pat on the head. But those people wouldn't dream of moving back to the reservation, or taking part in Cherokee culture, as is undoubtedly true of Elizabeth Warren as well. It is a "heritage" without practice and of dubious significance. Nor may they be alive to the sense of loss and injury this represents, as such blood mixing may not have been voluntary, but the result of rape and rapine of various sorts.

Nevertheless, it would seem advisable for Native Americans to get off their metaphorical high horses and be more welcoming to the diversity that exists in the US. Even if the pride that Warren feels in her minuscule Native American ancestry is somewhat false, romaticized, and lacking in practice/practical effect, it is still pride, unmistakably, rather than its opposite. Citizens of the US generally take pride in vibrant Native American cultures and take steps through the government to help them, via direct aid, educational assistance, gambling concessions, and other benefits, after and in compensation for, the deeper history of genocide, reservation confinement, ethnic cleansing, and cultural extermination. The relationship is surely a difficult, guilty one. No one wants to alter the definitions that American Indian nations have developed for their formal membership. But their wider membership of genetic descendants is also a positive asset, in pursuit, not of assimilation, but of friendly relations with the wider, shared culture.

Saturday, October 20, 2018

Caught in a Lie

Why does our political system spend decades stuck in states of denial?

I am enjoying an infinitely long podcast about the Civil War. One of its lessons, and of that period in history generally, is that incredibly large numbers of people can, for decades, believe convenient or politically motivated falsehoods. The gulf between the Declaration of Independence and the reality of slavery was there for all to see, particularly in the South. But it took a century for the issue equality to come to a head in the war, and then another century for it to come to a head again in the civil rights movement. And we are far from done with it now.

Decades were spent explaining away the obvious with justifications ranging from the nakedly instinctive and economic to the scientific and religious, that people are not after all created (legally, politically) equal, and even if they were, to the victor belong the slaves. It took a national movement of abolition, and particularly the book Uncle Tom's Cabin, to rub people's noses in the fundamental contradiction and injustice. And even then, half the country, full of perfectly respectable and intelligent people, fought a bitter war to escape the truth of the matter. It is appalling to look back at the time spent, and the lives wasted and lost, in this process of slow awakening.
"You can fool all the people some of the time and some of the people all the time, but you cannot fool all the people all the time." - attributed to Abraham Lincoln, but of uncertain provenance.

Smoking is another, smaller, example. The tobacco companies didn't really need to work very hard to convince people that smoking was safe, since most of the country was addicted to nicotine and didn't want to know the truth. But a concerted campaign of disinformation and unconscious conditioning, through floods of advertising and copious product placements lulled the addicts to somnolence, while continuing to draw in new generations of "rebellious" young customers.

Now our politics seem to be in another decades-long process of denial and division. The racial issue still lives as part of the divide, as does resurgent economic inequality, but more important is the environmental issue. The earth is in peril, and it is our own greed and ignorance that put it there. Half of our political system is dedicated to denial, which is getting more flagrant with each election. Perhaps, like the period before the Civil War, the more endangered one's comfortable lies are, the more vociferously, even militantly, they are defended. At this point we have a chief executive who lies maliciously about everything, as a matter of habit, and we hardly bat an eye. Particularly telling is his advice to men accused of sexual assault - "You have to deny everything"- advocating perjury.

Interestingly, the parties (though not the regions) responsible for these epochs of lying and denial have switched dramatically. The Republican party brought us the clarity of abolition, union, and Lincoln. The exodus of Democrats from congress during the Civil War allowed a fresh wind of progressive legislation, such as fiat money, income tax, and the land grant education system. Now, Republicans are the party of the South and of vested priviledge- racial, economic, and patriarchial. It is for all these fossilized interests that Republicans maintain a policy of denial, shamelessly serving the wealthy and the industries they run, like the Koch conglomerate, and the coal and oil companies. Lies serve as a defense against rational policy and democracy. They serve as a screen against understanding and care for the future by the electorate- especially the vaunted "base", of which it is difficult to say whether it is predominated by ignorance, cynicism, meanness, or worse.



In the Civil War era, the purveyors of lies were mostly conservative social habits and structures that served the powerful- the dominance of the planter elite and the religions which supported them unstintingly. Power ruled nakedly, over slaves, but also over the social system more generally, including its media. Power is again, obviously, the problem today. It is those in power who do not want change, do not want to make the economic system more equal or sacrifice even a pittance for the future of the biosphere. The Supreme Court has pronounced money to be speech, which means the dominance of corporations and the rich. History is a litany of struggle for power between the rich and the poor, conducted by various mythologies and lies. The left has its problems with truth as well, particularly in its Marxist incarnation, which went so far as to claim itself as a science of history, economics, and social justice. Naturally, the lying reached an appalling crescendo when the Marxists gained maximum power under Stalin. Whatever the party, the powerful have the most to hide, and engage in the most habitual and cynical lying to keep it hidden, sometimes via blatant lying, but more often in plain sight via elaborate ideologies of other-denigration and self-justification.

But there are also technological issues. An internet that was supposed to spread truth and information is instead ridden with button-pushing trolls and corporate propaganda, while killing off the professionally edited media. Putin's Russia has refined disinformation to an alarmingly precise science, and Trump has been their most attentive student. Between them and the FOX propaganda channel, Rush Limbaugh and colleagues, independent thought hardly stands a chance. One characteristic of the lying is their loud claims of truth, such as the slogan "Fair and Balanced", and the reflexive denigration of any source of thoughtfully investigated and edited information as "fake news". Unbeknownst to the innocent, what were previously channels of information have transformed into fronts of warfare- class warfare.
"In science, if you stand up and say something you know is not true, that is a career-ending move. It used to be that way in politics." -Bill Foster, physicist and member of Congress 

Saturday, October 13, 2018

Bounty Hunter, Protein Edition

CDC48 is an all-purpose protein extractor, bringing reluctant proteins in from far-flung parts of the cell, to be executed at the proteosome.

Every cell needs a recycling bin. While DNA lives forever, other molecules like membrane lipids, RNAs, and proteins do not. They are chemically less stable. They may also have functions that are sufficiently fleeting or conditional that they need to be turned off  quickly and specifically, one common method of which is to dispose of them entirely. For proteins, a vast infrastructure exists to identify and recycle them for these various reasons, involving hundreds of genes. A central character in this story is ubiquitin, a small protein that is, as its name implies, ubiquitous. It is used as a flag to mark proteins, usually for degradation, but also for other regulatory events. 

For example, one mechanism that sets protein lifespans is the N-end rule. A set of enzymes recognize the amino acid on the very N-terminus of each protein in the cell (if it is accessible). Different amino acids determine different life spans, from days (M, G, A, S, T, V, P), to a fleeting couple of minutes (R). These enzymes then ligate a ubiquitin to the protein, and leave it to be found by the next actor in the system, the bounty hunter of the cell, CDC48. Not all proteins need to be tracked down. Many diffuse on their own over to the proteosome, where they are willingly digested for the greater good. (Think Soylent Green, at risk of mixing metaphors) Some ubiquitin-flagged proteins are more reluctant, however. They may be stuck in one of many cellular membranes, or part of a big protein complex, or in a misfolded protein glob. Biology has become awfully complex in the last few billion years, and proteins find themselves in all sorts of tight spots.

The euthanasia processing center.

Most of the hundreds of genes devoted to this protein disposal process encode proteins (called E3 ligases) that attach ubiquitin to target proteins based on various rules such as the one above. Another recently described rule and protein (FBXL17) evaluates the quality of a particular family of protein dimers. If such a dimer is slightly misaligned or misfolded, a patch on its surface (called a degron) is exposed that interacts with this protein, which attaches a chain of ubiquitins, putting up the wanted poster that CDC48 and its colleagues later come around to collect.

CDC48 eventually arrives, as a special extractor of reluctant proteins, crow-barring them out of wherever they happen to be hiding so that they can be ferried over to the proteasome / recycling center. Its structure is a complex hexameric donut, and it has not one, but two ATPase activities, so one might say it comes equipped with two six-shooters. It collaborates with a large number of other proteins that help identify and track down squirrely proteins, as well as to help transfer them onwards. (CDC stands for cell division cycle, a famous series of mutants in yeast that won a Nobel prize in 2001 for their elucidation of the mechanics of cell division regulation. Many key cell division proteins have very short and closely regulated lifespans. The human version of CDC48 is named VCP and p97.)

Structure of CDC48 (green, blue, and purple portions) with a small inhibitor (red) jammed in that gums up its activity.

As do many interesting protein complexes, CDC48 has a hole in the middle. This is where the tagged proteins get pulled through, yanking them right out of wherever they are, guns blazing. Which is to say, with plenty of ATP powering the process. The top part of the complex recognizes ubiquitin in the form of polyubiquitin chains, which is the typical degradation tag. The two rings, which are the meat of the CDC48 protein, each have an ATPase activity, and engage in a subtle hokey-pokey as they operate, (below) which is assumed to constitute the extraction process, pulling proteins bit by bit through the center. Since the target protein is covalently tagged with ubiquitin, it has been found that this central hole is big enough to accommodate two protein chains going through at the same time, either a hairpin shaped substrate following a leading ubiquitin chain, or ubiquitin and the target protein travelling alongside each other.

A very rough model of the structural changes of CDC48 as it burns ATP to pull protein chains through its inner ring, from top to bottom. 
"After interaction of the polyubiquitin chain with UN, [an accessory protein docked to the top of CDC48 that helps recognize the ubiquitin tag], Cdc48 uses ATP hydrolysis in the D2 domain to move and unfold the polypeptide substrate through its central pore. ATP hydrolysis in the D1 domain is involved in substrate release from Cdc48, a process that requires the cooperation of the ATPase with a DUB. The DUB trims the polyubiquitin chain, and the remaining oligoubiquitin chain is then also translocated through the pore."

When the protein gets to the other side, it is not quite clear what happens next. Most likely is that CDC48 waits till directly docked with a cytoplasmic proteasome before fully unfolding its captured culprit into the proteasome's maw. But there are likely to be partner proteins involved in this process as well, at least as helpers. This is an ancient and ubiquitous process, conserved from bacteria to humans. CDC48 makes up about one percent of proteins in a typical cell, a very prominent role in line with the minor, though critical, role, of bounty hunters in our legal and dramatic worlds.

  • Stiglitz on the election.
  • On the economic Nobels: " ... running out of resources is not a huge concern, but rather the exact opposite, that we will have access to and use too many polluting resources, should worry us. That is tremendous foresight for someone writing in 1974!"
  • Also, inventors and innovators never get a break- their profits are small and fleeting. "I estimate that innovators were able to capture about 4 percent of the total social surplus from innovation."
  • Do driverless cars want to avoid getting hurt?
  • The Taliban may be winning ground, but hearts, not so much. For Pakistan, however, they are the ideal tool.
  • Social dominance feeds on itself. Thus every family's quest to scrabble up the social tree.
  • Ditto from Adam Smith.
  • It remains odd to have a Russian operative in the White House.
  • Is economics monotheistic?
  • Dr. John McLaughlin.

Saturday, October 6, 2018

The Quest For Meaning

We spend our lives searching for something that does not exist. And then realize that we have been fighting over it the whole time.

The meaning of life: 42? Or something more profound? Religions have been founded, and wars fought, over what by definition is most important to us, but on which no one seems able to agree. One advance in the philosophy of meaning was Maslow's hierarchy of values, which starts with basic sustenance, and rises through the more refined social values to self-actualization (possibly a dated concern!). If one does not have enough to eat, nothing else means much. But whether these form a true hierarchy is unclear, since many people have died for some of the more esoteric levels of this hierarchy, indicating that we are mixed-up beings, not always valuing life over some principle or ideology. It turns out that propaganda, social pressure, and decent odds, can make people kill and die for the most arcane propositions. Also, that winning means a lot to us.

Meaning is not given or objective. There is no star or cloud telling us that we mean X, while people in the other tribe mean Y. Quite the other way around. I think we can safely say at this point that we have constructed religions (as one example of indoctrinating human institutions) as complex machinery to propagate meanings that we (or at least some) have devised, using gods as fronts for desirable social hierarchies, idle speculations, melodramatic ruminations, and elevated emotions. That these machineries are passed off as objective and profound is critical to their function, elevating their impressiveness (and oppressiveness). If your meaning and values can be dictated by me, who wins? If god says you should have a beard, how can you complain, and to whom? This is the quest of propaganda generally- to instill meanings into, and thus lead, masses of people.

So we have been fighting over meaning and values all along, through our social relations. There is nothing to seek, but rather a world to win, for as far as others share one's meaning, one gains power. For example, a recent post told the story of Arthur Kornberg, eminent biochemist. One of his leadership qualities was an absolute conviction of the importance of what he was doing. If his team members were not willing to be tied to the bench at all hours and have midnight phone calls for urgent updates, their tenure was short. How much of this was willing? That is hard to say, and is one of the mysteries of personal, charismatic, leadership- the diffusion of meaning to others. Parenting is the same story, naturally, as is politics. Parents promote respect for elders and the elderly as a core societal virtue ... and no wonder! Advertising is another big example in our culture. The alchemical transformation of a natural desire- for status, sex, safety- into a value and meaning structure that renders some product essential. We are far more what we buy than what we eat.


Meaning turns out to be more of a fight than a quest. Meanings are swirling all about us, and are up for grabs. There is no grail to find, but only a social contest between those who seek to tell other people what is most valuable and important, others who promote other, maybe contrasting, values, and innocents in the middle, caught in the cross-hairs of domineering social warfare. Even Buddhism, whose doctrine revolves around the illusory nature of existence, the non-self, and the dampening of one's attachments, seems eager to propagate those very doctrines, promoting the somewhat ironic meaning of meaninglessness.

Returning to Maslow's hierarchy, many of our meanings are objectively based. We need to eat, have room to live, and have the other necessities of our current technological status. Social status is another need, biologically based. Since most of these are subject to scarcity, we are immediately thrust into competition with our fellow humans. These objective necessities can be woven into much larger ideologies of competition and tribalism. On a theatrical basis, they are portrayed in sporting events, game shows, and reality TV. But they become more grounded in the business world- that merciless competition that ends in bankruptcy and homelessness. Which is in turn only a slight step above the level that characterizes the ultimate competitive test of meaning: warfare, massacre, and murder.

We are bombarded from earliest childhood with values and messages of meaning, many of which conflict. The confusion can be difficult to deal with, leading many into the arms of simple solutions- taking meaning from those who shout the loudest, or who simplify most audaciously. It is up to us to choose, though our basis is necessarily the choices we have made already and which have been made for us earlier on in our lives. Meanings build on each other. But they also have a rational aspect. If compassion is part of our value system and self-meaning, that will not sit well with projects of tribal pride and dehumanization. It is complexity that requires careful thought, which is why morality is not just a matter of feeling, but also of reason.

The meaning of life is not hard to find, but it is hard to decide on, from the myriad choices and influences surrounding us. That is why sticking with positive influences and avoiding cesspools like Facebook / Fox news is so important. It is also why "big question" discussions are often overblown, shills for the dissemination of some particular and parochial set of meanings.  The quest is not for some elusive single meaning, but for ways to chose among the vast numbers of them we meet along the way of life.