Atheism, or Archetype?

Religion is built on a series of inborn archetypes and intuitions. Does that mean it is inevitable?

Religion is natural, but is it right? Increasing numbers of people in the US are giving up the practice and belief, if polls are to be believed. Hellfire and damnation is sure to follow, according to those left in the pews, at least those of the farthest evangelical congregations. As a student of Carl Jung, I appreciate the psychology of religion, seeing its processes as deeply reflective of our individual and communal psychologies, as well as the consequence of a complex evolutionary process whose aim has been as much social solidarity and reproduction as much, or more than, philosophical truth. At base, we are not rational beings, and follow a variety of themes and images, termed archetypes in the Jungian system, which persistently guide our dreams,  motivations, and cultures. We are not just economic units driven by profit and loss, but have richer dramatic lives and needs.

Father

What could be more obvious? We grow up in households with father figures who are unimaginably powerful. Food just appears, housing, furniture, love, care, and power and discipline. It is no wonder that, once we grow up, there is a father-shaped hole in our view of the world. In the usual patriarchial culture, the father stands alone, at the top, as both creator and moral disciplinarian, in an archetype that is expressed over and over again in cultures throughout the world, from Zeus to Allah, as it is in our political systems naturally as well. But the mother archetype is also in play, especially in Catholic and Hindu cultures, in the Marys and various powerful devas. Is it possible to see the world without using these instinctive lenses? That is what the scientific revolution and enlightenment attempted, in a cognitive revolution that remains, evidently, incomplete. Take prayer. In the form of requesting something from the father in the sky, it is pathetically immature and retrograde, however understandable in primitive conditions of complete existential mystery. On the other hand, some meditation, joy, and gratitude for the wonders of existence are surely healthy and consistent with mature knowledge of where we stand in the universe. Involvement with this archetype reflects quite directly how far one has gotten along the developmental road from childhood to maturity.

Heaven

The afterlife used to be a rather drab, depressing affair, in the classical Greek and Jewish systems. Then it was progressively gussied up into a lottery jackpot, in the Islamic and Christian systems. Buddhists and Hindus also find life after death, in the form of reincarnation, to be absolutely central to their philosophies. The magic of consciousness is incredibly hard to give up, and hard to get rational perspective on. It takes stringent dedication to naturalism and the evident facts of the world to accept, deep down, that death is really going to be the end- of everything. One need only think about animals- they are obviously conscious, and there are levels of consciousness all the way down the scale of evolution, to infinitesimal, then finally to nothing at all. How does that work, other than in direct proportion to their physical, brain-based endowments? What could be more clear, and in stark contravention of our intuitive and (weirdly) hopeful dream of life after death?

Tribe

We are not just endowed with intellect, but with a social nature, which focuses our striving and loyalty on the tribe. Our tribe is right and good, theirs is bad and wrong. Tribalism founds and plagues every new religious sect or philosophical school, which strains to show how it is right and its predecessors wrong. Jung vs Freud, Analytical vs Continental, Shiite vs Sunni, in endless profusion. Religions lack even the veneer of factual basis which characterize other divides like political polarizations or academic disputes. Doctrine, orthodoxy, and heresy are freely defined by whoever has social power. If one's village is Evangelical, woe to Catholics. If one's family is Seventh-Day Adventist, mere contact with outsiders is forbidden. Tribes have totemic symbols and artistic traditions as part of their identification / bonding apparatus, tokens of the archetypal processes at work.

Magical or zodiacal symbols in an Islamic Book of Wonders, circa 1400. 

Magic

Living in an enchanted word is natural, and wonderful. We all start there in childhood and treasure the dramatic, humanistic power of seeing the world through archetypal lenses- in animals with special totemic powers, crystals that heal, trees that listen. This is truly where traffic with archetypes is most fluid and explicit- bringing dreams to narrative life. Religious superstition raises this drama to existential levels, putting the magic on a celestial level of god(s), all-powerful father figures, and alternatives of eternal hell-fire or bliss. The chances of all this actually describing any kind of reality is nil- we are talking total fantasy. But its evident grip on billions of people shows just how powerful magical thinking is and how far we are from being rational.

Truth

All claim truth, but few prove it. Religions are notorious for splitting into sects, each possessing the final truth, the real story. Interestingly, atheists do not splinter in this way. There is plenty of bickering, about what humanism entails or is, how liberal humanists should be, etc., but there are no Seventh-Day atheists, or Twelver atheists, or other miscelleneous schools. Communism was atheistic, but was in truth a quasi-religious, authoritarian cult all its own. Once one has discarded attachment to these archetypes and the theologies they underpin, and to the need for truth as a matter of self-identification, why then it is easier to agree on what is actually true, as well as on the many areas where we just don't know, without the need to make up stories. This need, a dire need, for answers, especially to "big" questions, is a tipoff that we are dealing with archetypal energies, not with a rational level of thought.

One could compare atheism to the concept of nirvana in Buddhism and Hinduism- the release from the cycle of rebirth, from attachment to the archetypes, and escape to a level of intellectual / emotional freedom. Escape from rebirth is implicit, since the atheist doesn't believe in rebirth, heaven or afterlife at all. It focuses attention on this life, this moment, and compassion here rather than later. But to escape the causes of suffering, (especially the infliction of suffering upon others!), by regarding the archetypes intellectually and skeptically, and by distancing one's self from them, is far more important. To leave behind the seductive entanglements of archetypal belief and the often-abusive social relations they entail is personally momentous, and a healing balm for a planet full to the brim with faithful dogmatists.

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The Extermination of Tibet

China is culturally cleansing Tibet. "Seven Years in Tibet", by Heinrich Harrer, and "My Land and My People", by the Dalai Lama.

It may be falling off the world's radar screen, but Tibet remains a tragically oppressed land, well worth our remembrance and sympathy. Two books, "Seven Years in Tibet", and "My Land and My People" describe the heartbreaking slide from a happy, innocent, and isolated region to the Orwellian horrors that succeeded and continue today. One of the first significant acts of the new communist government of China, fresh from its civil war against the government that actually faught the Japanese, was to fulfill not any orthodox communist aims or development for its people, but the most rapacious and ancient ambition of Chinese governments, to subjugate its neighbor to the West, Tibet. Amid a blizzard of lies, China invaded the virtually defenseless state, oppressing Tibetans from the start in an ever-escalating war of cultural extermination. After almost ten years of trying to get along with the overlords and calm the waters, amid general rioting, the Dalai Lama fled in a dramatic escape from occupation, to welcome refuge in India, where he and the Tibetan exile community remain today.

Tibet was, frankly, a medieval culture, with economic relations ranging from nomadic to feudal. But medieval in the best sense, of a people thoroughly engaged in a set of archetypes that yielded a richly nourishing, dramatic life experience as well as a durable social structure. Tibetan Buddhism is very demanding, taking a fair fraction of men and resources into monasteries where they live off the rest of population and devote themselves to philo/theological hairsplitting. But they also devote themselves to various traditional arts, and most of all to the cultivation of peace and compassion- the touchstones of Buddha's solution to the suffering of this world. After a long and martial history, Tibet eventually put itself under the control of its most respected leaders, the Lamas, creating a system that was peaceful and benevolent, if also hidebound and conservative.

Take the story of how the current Dalai Lama was found and put in power. It is a veritable fairy tale of portents, dreams, signs and wonders. It has a sort of Wizard of Oz quality, which obviously resonanates, not only with us as a romantic tale, but with Tibetans as a great origin myth. And one can make a case on a practical level that choosing a humble and obviously bright peasant child to rule one's land may be a superior method to one which relies on the most ambitious people to sell themselves in some way to various institutions of power, and to the populace every four years. How often do we fantasize that any halfway intelligent person could do as good a job as the current office holder? Especially if that person were from early on steadfastly dedicated to the cultivation of peace and compassion in him or herself and others?

Likewise, the Dalai Lama's secret and arduous escape from Tibet was again the stuff of legend, binding him to his own people, and endearing him to people around the world. The Tibetan system values spiritual attainment, expressed in the extremely pacifist ideology of Buddhism, combined with a great deal of pre-buddhist folk religion and symbology. The culture was thus temperate and peaceful, perhaps too peaceful for its own good, but surely a model to emulate in our spiritually unbalanced times. The Chinese, in contrast, brought rapacious domination, racism, and cruelty. They were and remain atheist. But it seems that their compassionless spiritual vacuity (which is quite a different thing) was more important, leading them (especially through the cultural revolution) to despoil the cultural treasures, institutions, and people of Tibet.

We may wonder whether China is more culpable in all this than the US was in its virtual extermination of Native Americans and their many cultures. The answer is clearly yes. The gulf between the American cultures was far wider, and the state of historical consciousness lower. Native Americans had no continent-wide governments of centuries standing, no meticulously recorded written histories and philosophical traditions, and little basis for common ground or negotiation with the colonists and their successors. We have belatedly granted Native Americans limited sovereignity in their institutions and barren territories, while China keeps pouring more Han Chinese into Tibet and keeps 100% social control. The world had just fought a war to end all wars, and to liberate peoples from totalitarian military oppression, including those of South Korea. But Tibet was a bridge too far- we could not lift a finger in China's back yard, and now hardly say a peep.

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Coronavirus Testing Update

A review of how testing is done, and where we are at.

We in the US are flying blind through the current epidemic, with cases popping up all over, testing done on very few people, and the rest ranging between nervousness and panic. What is the death rate? We still do not know. Did China contain its outbreak by draconian measures, or by wide-spread infection and natural burnout? How about South Korea, or Taiwan? Everyone claims the former, but it far from certain what actually happened. We need more testing, and particularly scientifically sampled population testing, and post-infection exposure testing. The basics of epidemiology, in other words.

SARS-CoV-2 is the virus, and COVID-19 is the disease. Most people do not seem to have mortality risk from infection, other than the elderly and infirm. In these respects, and in its great infectiousness, this disease resembles influenza. Testing from patient samples is done by RT-PCR, which stands for reverse-transcription polymerase chain reaction. The reverse transcription part employs specialized enzymes to copy the viral genomes, which are RNA, from the patient sample, into DNA, the more stable molecule that can be used in PCR. And PCR is the revolutionary method that won a Nobel prize in 1993, which uses a DNA polymerizing enzyme, and short segments of DNA (primers), to repetitively (and exponentially) replicate a chosen stretch of DNA. In this way, a minuscule amount of a pathogen can be processed to an easily detectable amount of DNA. The FDA mandates using three target regions of the new Coronavirus N protein encoding gene for its tests, but will accept one target, if the test is otherwise properly validated. They point test makers to the NAID resource that provides positive control material- RNA genomes from SARS-CoV-2.

 Just the primers, Ma'am. These tubes contained dried DNA- the short primers with specific sequences needed to amplify specific portions of the SARS-CoV-2 viral genome. Using these requires quite of bit of other laboratory equipment and expertise.

Schematic of PCR, the exponential amplification of small amounts of DNA to huge amounts. Primers are in green, nucleotides are light blue, and the target template is dark blue.

So far, so good. But there are a range of test technologies and ways to do this testing, from the bare-bones set of primers, to a roboticized, fully automated system, each appropriate to different institutions and settings. To use the basic primer set, the lab would have to have RNA extraction kits or methods to purify the viral genomes from patient samples, then a reverse transcription kit or method, then a PCR machine and the other materials (nucleotides, high-temperature DNA polymerase, purified water and other proper solution ingredients). The PCR machine is basically a heater that cycles rapidly between the low temperature required for polymerizing and primer annealing, and the higher temperature required to melt all the DNA strands apart so that another round of primer annealing can take place. And all this needs to happen in very clean conditions, since PCR is exceedingly sensitive (of course) to small amounts of contamination. Lastly, the DNA product is typically detected by trace fluorescent markers that light up only double-stranded DNA, and can generally be detected right in the tube, with an advanced PCR machine.

Automated sample handling machines are used in clinical labs.

Virtually all of this can be mustered by any competent molecular biology lab. Results would take a few days, due to the work involved in all the setup steps. The PCR itself and analysis of its results would take a few hours. But such labs do not operate at the requisite scale, or for this purpose. That is the province of clinical testing labs, which come in various sizes, from a small hospital in-house operation to a multinational behemoth. The latter run these tests on a vast, mechanized scale. They might manufacture the DNA primers themselves, or buy them in bulk, and have the proper logistical structures to do these tests from scratch in a reproducible way, to a high standard. Providers at these scales need different kinds of materials for their testing. A small provider may need a turn-key solution that comes with pre-packaged cassettes that just need the sample added before plugging into the machine, while a larger provider would save costs by using bulk reagents and massively robotized sample handling and PCR machines.

A one-hour test in a turn-key package. But at relatively high cost.

So who are the players and what is the status? The CDC did not, for some reason, use the WHO test, or tests already developed in China, whose capacity for such manufacturing and testing is prodigious. The CDC at first didn't allow anyone else to run the tests, and when they did, they did not work correctly. It has been a bad scene and much valuable time has been lost- time that resulted in the US losing any chance of containment. Now, the FDA is authorizing others to run these tests, with detailed instructions about sampling, extraction, and machinery to be used, and is slowly granting authorization to selected manufacturers and kit makers for more kinds of tests.

Large suppliers like Roche and ThermoFisher have just been approved to supply clinical labs with testing systems. Most significant is Roche, whose tests are pre-positioned and ready to go already at clinical labs around the country. The biggest clinical lab, ominously named LabCorp, offers a home-made test, but only "several thousand tests per day", which is not yet the capacity needed. So capacity for testing will rise very rapidly, and soon enable the diagnostic and surveillance testing that is so important, and has been missing to date.

• Notes on previous pandemics.

Post script:

An aspect I forgot to include is how to select the portions of the viral genome sequence to include in testing kits. Different institutions have clearly come up with primers to different genes, few as they are, and regions within those genes. For example, "The primers currently target the N1, N2, and RP genes of the virus, but these are subject to change."; "In particular, the test detects the presence of SARS-CoV-2’s E gene, which codes for the envelope that surrounds the viral shell, and the gene for the enzyme RNA-dependent RNA polymerase." There is a balance between finding regions and primer sites that are unique to the particular virus you are interested in, so cross-reaction to other viruses is 100% eliminated, and the problem of viral drift and mutation. Some regions of viral genomes mutate much more rapidly than others, but these viruses tend to mutate at pretty high rates overall, so keeping a test current from one year to the next can be challenging. That is also what our immune systems have to deal with, as cold and flu viruses change continually to evade our defenses. So the specific DNA primer targets of a test need to be relatively highly conserved, but not too highly conserved, to put it in evolutionary terms, and the regulating agencies have to keep a close eye on this issue as they approve various test versions, to find a proper balance of high specificity and long-term usability.

Post-Post script:
Yet more significant testing solutions have emerged by late March, including a rapid (~10 minute) system from Abbot, and rapid antigen testing kits that also render results in the ~10 minute range. This speed is enormously helpful, obviously, from the patient, provider, and health system perspectives. The Abbot system is based on something called isothermal PCR, which gets rid of the temperature cycling described above. It is run at an intermediate temperature (~60 degrees C) where the DNA is somewhat loose, and primers can invade duplex strands, and also used a DNA polymerase that can displace duplex DNA as it plows ahead. This plus some other clever tricks allows the DNA amplification process to happen continuously in the reaction tube, going to completion in the rapid time quoted for these tests. These tests also tend to be tough- relatively robust to junk in the samples, and variations in temperature and other conditions.

The antigen tests that are coming on line are particularly significant, since they can be used for wide-spread population surveillance, to figure out what proportion of the population has been exposed, even if no active infection is present. Due to what seems like a complete or virtually complete lack of contact tracing + quarantine, the current pandemic will only stop once most of the population has been exposed, providing herd immunity. Before that point, anytime we give up self-isolation, it will start over again, due to the relatively high rate of low- or asymptomatic cases, and their lengthy course. Health care workers that have been exposed and recovered will have a special role before then by being able to freely staff hospitals that otherwise may be in dire straights.

Actin's Other Life

How cell movement and migration are managed by internal actin structures.

We are familiar with actin in muscles, where actin filaments occur in almost crystalline arrays, interdigitated by structural proteins, myosin cables, and nerve / ionic regulators, causing the macroscopic flexing we rely on to get around. But how to individual cells get around? They use actin too, but very differently.

Most cells have actin and myosin inside, but they have many roles, forming a "cytoskeleton" that helps shape and move the cell, but also forming avenues of transport, where myosin attaches to actin on its motor end, and to other things like organelles or vesicles of proteins to be secreted on its other end. For cell movement, actin extends at the leading part of cells through its own polymerization, not by being pushed or pulled by myosin. Then, once the leading edge finds a place outside it that likes and adheres to, myosin acts on the actin network behind to drag the rest of the cell along.

A neuronal growth cone, with actin stained in red, microtubules in green. Actin polymerization is the motive force at the leading edge where cells figure out where they want to go.

Thus much of the story of cell movement, especially at the leading edge, as in neurons trying to find their way around to the right destination in the developing brain, comes down to the selective polymerization of actin, which is, naturally, a carefully regulated process. A recent paper discussed the role of actin-binding proteins in this regulation. It has long been known that cells have some proteins that encourage actin polymerization (profilin, Arp2, thymosin beta 4, formins), and others that inhibit polymerization, or even cleave existing filaments (CAPz, cofilin, gelsolin, severin), or medate crosslinking and branching (fascin, filamin). These proteins are all generally regulated by phosphorylation, so they can be quickly and reversibly controlled by the various signaling cascades that receive signals from the local cell surface and result in a variety of protein kinase (phosphorylation) activities. Thus the main research question is filling in the details of how actin management at the leading edge of cells is orchestrated. And this has been quite difficult, since the scales are very small in time and space, and the tuning quite subtle. Delete a gene, and it may have paradoxical effects, this being such a crude manipulation.

The current authors decided to look into a relatively simple question- how is actin polymerization controlled by profilin, its most typical binding partner in the monomeric state, by its own ATP hydrolysis, and by formins, which are the main actors in speeding up actin polymerization? Actin all by itself polymerizes quite enthusiastically. Thus the cell keeps non-filamentous actin in dimers with various controlling partners such as profilin and thymosin beta 4, to keep a lid on excess polymerization. Profilin is the major partner, and binds actin very tightly. It strictly restricts actin addition to + ends of filamentous actin, not to the - ends, and not other actin monomer commplexes. It also impedes polymerization to a slight degree, even on + ends of actin filaments, due to its sticking a small finger into the interface where the next actin molecule would bind.

Structures of actin (teal and green) and profilin (pink) at the + end of a polymerizing filament (bottom). Profilin sticks a small structure into the cleft where the next actin monomer would add (zoom), slowing polymerization slightly.

The authors create a set of mutant profilin proteins, with altered binding strength to actin. The only useful ones were very subtle alterations. Binding too well inhibited actin polymerization completely, while poor binding rendered profilin entirely useless. But changes of about 5-fold in binding strength were telling in their effect.

The growth of actin filaments is strongly affected by the binding strength of profilin to actin. Profilin mutants that are weaker binders (pink) accelerate polymerization, while a stronger binder (purple) slows it down drastically.

The next step was to add in the effect of formin, a protein that binds to the actin-profilin dimer at the growing end of actin filaments in such a way as to encourage profilin to leave, and also encourage the next actin-profilin dimer to add on. Formin also induces a helical shape change in the actin filament that makes it more stable, resistant to the action of, for example, cofilin, which breaks it down. Thus addition of formins had dramatic effects, speeding up actin polymerization by several-fold, depending on which of a variety of formin versions was used. Not only that, but this system of formin + profilin managed actin monomers rendered the polymerization reaction almost entirely insensitive to the concentration of profilin / actin dimers and actin in general, as long as there was enough profilin to soak up all the free actin.

The growth of actin filaments is strongly accelerated by formin, a protein that binds to the profilin-actin complex at the growing ends of actin filaments, dissociating them to allow more units to add. DAAM1 is a weak formin, while mDia2 and mDia1 are progressively stronger formins, which show progressively faster acceleration of filament growth, in these direct microscopic assays. The arrow marks the growing actin filament end, and at bottom, graphs of actin growth, where the two dimensions above are reduced to one to give a time vs elongation graph.

This leads to the basic finding of the paper, which is that, assuming that free actin is immediately taken up into complexes of various kinds, either in new filaments or with profilin and other monomer binding proteins, the cell does not regulate actin growth by making more of it or altering the bulk amount of the actin:profilin dimers. There certainly isn't the time. Cells use the various specialized accessory proteins to orchestrate actin activities, and then regulate those in turn by the signal-driven phosphorylation events, which constitute an enormous field we won't get into here.

When formins and profilins are present at physiological concentrations vs actin, polymerization rates are insensitive to actin monomer concentrations, and instead depend on the identity of the formin, and presumably its post-translational regulation.

Yet one oddity remains- that actin is itself an ATP-ase. What is the role of this ornate property? The authors demonstrate quite conclusively that disabling the ATP-ase of actin does not alter the assembly and growth characteristics they are studying. Profilin still binds, heterodimers still polymerize, and formin still accelerates that polymerization. This is contrary to at least some old models, which rely on profilin being known to be an exchange factor for actin monomers, promoting the exchange of ADP for fresh ATP. Which was then thought to be essential for actin polymerization. Not at all - ATP does something else as part of actin, which seems to be to create a two-state system where actin with ATP is competent to for some functions, such as profilin binding, and stabilizing existing filaments, while actin with ADP is competent for other things, like release of actin from the other (-) ends of filaments. But the actual hydrolysis is immaterial to actin polymerization. All this was, sadly, already known over a decade ago, so it is not entirely clear why these observations were made in this article. At any rate, it is good that groups are still working on actin and applying ever more modern methods to quantitative studies of its function.

"Importantly, we found that ATPase-deficient actin was able to elongate actin filaments with nearly the same rates as wildtype actin at saturating profilin-actin concentrations. This clearly demonstrates that profilin release from the barbed end does not require cleavage of the β-γ phosphodiester bond of ATP in actin. More generally, the lack of assembly-related defects for ATPase deficient actin is consistent with the notion that ATP hydrolysis serves an essential function unrelated to filament assembly."

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