Economics is All About Redistribution

And new economies need new methods of redistribution.

"Redistributionist" is a dirty word for the right, like gun-grabber, bleeding heart, tree hugger, and statist. Yet we are currently treated to the spectacle of a Republican congress redistributing income, foregone taxes, and wealth to the tune of trillions, upwards towards the wealthy and well-connected. What does repealing the estate tax have to do with putting manufacturing workers back to work, or solving the opioid crisis? Nothing, naturally.

In a state of nature, everyone has a job, which is to wrest bare sustenance from a rich, but complex and mystifying world. No one is "employed", since everyone is self-employed. And if you or the small family you rely on fail in that task, the end comes relentlessly. This represents the primitive "job guarantee". Everyone has a job, and failure to do that job is penalized harshly.

A developed economy has a different relation to work. Most people still live by their labor and wits, but there is so much wealth and technological prowess that most people's work is completely dispensible. Whether we have lawyers, rock bands, and toothpaste is a matter of significant, but not existential, importance. Even the food production system is so broadly based that no single person's work is existentially important to anyone, even themselves, given a modest safety net. And this system can support large numbers of people with no jobs at all, with ease. Yet income remains tied to work, despite the fact that we are moving to a future where the ratio of work needed to labor available is plunging, taking the labor market and incomes with it.

Who runs this system? Whom does it serve?

The trajectory of all this is quite clear. Those with wealth receive the benefits of industrial productivity, which is increasingly capital-based rather than labor-based. Those with only labor to offer, even of a specialized and educated nature, get increasingly locked out of the income / redistribution system. Whether this will lead to a Keynesian crisis of lack of overall income and spending is not clear. The rich spend much less than their income, as witnessed in the recent revelations of overseas tax shelters holding trillions. But so far, the Fed and other institutions (here federal deficits play a critical role) are working mightily to keep the system churning, despite the extensive replacement of good jobs with bad jobs, and consequent declining worker pay (relative to productivity). The system is no longer working- labor is no longer an effective way to keep everyone employed and paid in a manner that befits an advanced society as productive as ours.

This is what the current class war is all about. Republicans are shamelessly doubling down against the very voters who thought they were supporting a better deal on jobs and a restoration of the middle class. Rather, this administration is pulling every available lever to entrench the rich/capital and pull the rug out from under workers, leaving them even more powerless and destitute than before. Who would have thought?

What should we be doing instead? Some propose a basic income, whereby every citizen gets a small income, merely for existing. This neatly cuts the connection between labor and income, but has many problems. First, it is not a decent income, but extremely minimal. So it ends up being miserable welfare, at best, for the poor, and an unnecessary gift to the rich. Second, it does not provide the reciprocal benefits to society, or the individual, that work does. To let so much personal energy go to waste, paying people to do nothing, presents both a moral hazard an an enormous social loss. We can do much better.

Social Security could be cited as an example of a very successful basic income, given to all. But it is explicitly tied to previous work, and serves a specific social function of supporting those who can not work any more. Public services like roads, public buildings, scientific research, and the like are also good examples of implicit income given to all, and surely health care should come under the same universal service category. But income for working-age people represents something quite different- it is the source of their freedom, and represents their service to the larger society. We need to find a way to preserve and enhance those relations while gradually disentangling it from the semi-feudal work-as-labor model in capitalism.

Basically, people should be paid for a wider range of activities. For example, voting could be paid. Serving on juries could be paid, far better than currently. Sending children to school could be paid. Positive social activities should be paid for, not just classed as volunteer activities or duties. Perhaps the biggest opportunity is in the non-profit sector. If the government funded non-profits on a broad basis, while enforcing governance, management, and mission rules, we could end up with endless opportunities for public service and fairly paid work.

Where would the money for all this come from? The main actor in the economic system is, to be frank, the government, not the private sector. The government prints the money, runs the central bank, and has first rights to production such as defense spending, police functions, and other necessities (which becomes particularly clear in war-time). The fact that capitalist enterprise and competition has been a beneficial and innovative way to organize the private economy to provide the bulk of most people's needs does not mean this will always be the case or needs to be the sole form of work and income. As mentioned above, capital is concentrating and the need for labor is gradually uncoupling from the need to produce goods. But it shouldn't be uncoupled from doing social good. Indeed, the capitalist system has led to enormous social harm, and seems to have led to an appalling revolution in values, putting the greediest and most predatory people in the most successful positions.

Thanks to mind-boggling political and intellectual corruption by which they have gained power through a supposedly populist political movement, these arch-capitalists are right now trying to entrench their feudal powers over workers by relieving themselves of taxes, by empowering corporations to rule more of our lives, enhancing the legal immunities of corporations and relieving them of any public purpose (especially in the case of media companies), by weakening our democracy and the state, and by keeping the labor market weak and workers dependent on the private sector for income. It is the last gasp of a system that will either turn towards an even uglier feudalism, or be turned back and regulated into a progressively smaller share of our economic, social, and political lives.

• Paradise papers and the so-called rule of law.
• But why shelter your riches from taxes when you've got a congressman in your pocket?
• And for that matter, why not appoint a tax evasion expert to head the IRS?
• "The United States, he noted, currently has one of the highest levels of inequality in the history of the world."
• Which Republicans want to make hereditary.

How Did I Get Here? (From the Primordial Soup)

Review of recent speculations about the origins of protein translation.

DNA may be the biological master code, but proteins are the soul of the machine- the shakers and makers that do everything, or almost everything, around a cell. Given how different these chemicals are in their roles and nature, how did they arise in evolution, and come to the indirect but essential relationship they have today? That is the story of translation and the origin of life. One of the exceptions to the current ubiquity of proteins in active roles is the ribosome- seat of protein synthesis- whose catalytic core is RNA throughout. Indeed the only molecule that can do it all- code for information, survive for reasonable lengths of time, (at least under acidic conditions), and do catalytic reactions, is RNA. This has led to a rough consensus that the very beginnings of chemical reproduction and life-ish chemistry began with an "RNA world". This does not exclude other chemicals, like amino acids and membrane-like lipids participating, but they would not be active in the central reproductive and coding operations that characterize life.

Envisioning the addition of DNA is easy. DNA is similar enough to RNA that there are only a couple of alterations needed to make this far more durable form. Copying is also similar enough to whatever mechanism RNA had to copy itself that the transition between the two is relatively straightforward to envision. And of course, RNA remains the universal carrier of transitory codes- between the durable DNA store and the translation system.

The modern flow of biological information: DNA->RNA->protein.

But getting from the RNA world to the protein world of today remains very hard to envision. There has been quite a bit of recent speculation on the matter, presenting several divergent stories for how this key transition came about. It is an interesting time to take a look at the field, even though it is possible that we may never have a definitive, or even consensus, answer.

The first interesting point to make is that copying RNA is intrinsically a perilous and questionable practice. We naturally think of nucleic acid copying with the model of DNA in mind: making the reverse complement by zipper-like Watson-Crick base pairing. This is the strongest form of nucleic acid interaction, and it takes helicases or other energy typically to pry the resulting duplex nucleic acid pair apart. The product of this reaction is also only a reverse complement, not a precise copy of the original. To copy a functional ribozyme, a second reverse complement would be needed to come up with a true copy of the original. This leads several authors to speculate about "direct" RNA copying systems, where the reverse complement is avoided, thereby sparing the system from these two perils, the first of which is actually the more serious. Reverse complementary sequences form a black hole of stable pairing, from which their originators would have a very difficult time extricating themselves under pre-biotic conditions.

One author (Taylor) proposes an obscure set of base pairing bonds, less strong than the Watson-Crick base pairs, that might form a basis for direct instead of reverse copying. This is highly speculative, and such effective pairing is not shown explicitly in the model, or elsewhere to my knowledge. Thankfully, this property plays no role in his model, which goes on to draw on tRNAs as models for an RNA-based adapter that might have originally brought their nucleotide ends to a ribozyme to carry out this parallel replication into direct RNA copies. This naturally leads to an evolution into carrying amino acids, and the replicative ribozyme transforms into a ribosome.

Proposal from Noller for a double-bridging system for RNA replication that uses a minimal system of adapter RNAs, which are then pre-adapted for later use in ribosomal protein synthesis. 

Another author (Noller) later proposed a similar RNA replication mechanism that produces direct copies at the cost of a similarly non-direct mechanism. In this theory, two identical tRNA-like structures serve as the intermediate bridge between the template and product RNAs in an early RNA replicase, cleverly using short (and normal Watson-Crick) base-pairing interactions to build the copied product RNA, triplet by triplet. Again, the proposal of an indirect (not zippering basepair-mediated) mechanism solves the problems of making reverse complement copies and two-stage copying, at the cost of substantial complexity. But it also obviously lays the foundation of the future ribosome, which uses a similarly indirect (tRNA) means to bring amino acids together bit by bit as directed by a coding RNA template.

Not so fast, claims another group (Harish and Caetano-Anolles). They do an exhaustive analysis of the phylogenetic history of all the RNA and protein components of the ribosome, and come to the somewhat startling conclusion that proteins were there from the very start, co-evolving with the ribosomal core and playing roles in the origin of translation. They allude to non-ribosomal peptide synthesis as a possible source for the early portions of this partnership, which seems under-developed. Phylogenetic analysis is notoriously murky at these early times, especially using RNA sequences, and can be confused with conserved functionality. Perhaps most pursuasive, however, is their specific set of findings that various protein and RNA portions of the ribosome each have, as one would expect, a variety of different ages, and that the oldest protein portion is in contact with the oldest RNA portion, at the mRNA decoding and ratcheting region. This implies not only that proteins were very early partners in whatever this ribozyme was at the time, but also that the peptidyl transfer center, previously thought to be the most ancient heart of the ribosome, only came later. They suggest that this complex was at the time an RNA replicase, but avoid saying much about it.

This raises more insistent questions about how useful, large, and ultimately conserved proteins could be devised at a time before the ribosome arrived, and also, if proteins were present, why weren't their superior catalytic capabilities used to engineer the (later-arriving) peptidyl transferase site, instead of the RNA-based mechanism that still exists?

Lastly, a fourth proposal (Ma) takes another approach to the bridging RNA system, proposing that small RNAs were capable of binding amino acids from very early times, and could have been used for a primitive form of templated protein synthesis. Indeed, they may have started out as RNA-bound co-factors for special ribozyme reactions, rather than as units for peptide synthesis at all. But the amino acid carriers then became standardized, and once they exposed an anticodon, could be harnessed into templated protein synthesis, given some energy, perhaps from the "charged" state by which their amino acids were attached. This theory is a tRNA-first class of theory, and leaves a great deal unsaid and unaccounted for, yet has the virtue of simplicity, plus the recognition that amino acids were common in the prebiotic soup, and likely played some kind of important role from early times.

As one can tell, this field is in ferment, with very interesting ideas deployed to explain a momentous transition of which we can see (and feel and experience) the consequences, but have only the most speculative view of its ingredients, key problems, and context. Origin of life research is a little like string theory in that respect, with little hope of experimental validation, premised on a faith that drawing out the consequences of what is known about the world must, (with a little guessing about what is not known), clarify a world that is at its heart remorselessly logical.

• Corrupt cronyism, against CNN.
• Elite blind spots- the Wykehamist fallacy.
• Charity is not going to rebuild the Caribbean.
• Conservative media- think of them as the brownshirts.
• Economic graph of the week. Labor force composition by age- the kids are not alright.

Travels up the Cilium, and Back Down Again

Cilia are far more than wavy arms.  They are key sensory organs for most cells and have complex internal dynamics.

Cilia are the fuzz of Paramecia, and the sweepers of our respiratory system. They can be flagella, but are structurally unrelated to bacterial flagella. They are yet another eukaryotic innovation, bound by a membrane and composed of a microtubule bundle with complex boundary and transport mechanisms to construct themselves and provide unique functions. While some cells have lots of cilia, virtually all eukaryotic cells have at least one, and that one is called the primary cilium. It arises from the microtubule organizing center left over after cell division, which then migrates to the cell surface (via a vesicle intermediate) and grows a new bundle of microtubules pointed outside to create a key sensory organ. Indeed, primary cilia are the eyes, ears and noses of many eukaryotic cells.

Comb jellies move using cilia.

The cilium membrane is kept distinct from the bulk membrane of the cell via a collar or "necklace" of proteins around the base, implying special transport mechanisms for membrane components as well as for the many internal components needed to build and maintain cilia. This allows various signaling molecules to specialize to the cilium, forming a concentrated and specialized sensory platform.

For example, the photoreceptors in our retinas sit inside modified primary cilia, elaborated and evolved from the more primitive sensory system common to all eukaryotic cells. Fat cells have a primary cilium that displays G-protein coupled signal receptors that receive status updates from the body, and are defective in at least one genetic syndrome of obesity. Other genetic syndromes of ciliary function result in developmental defects, kidney disease, diabetes, and cancer.

The primary cilium is a product of the centriole or MTOC previously used in cell division.

A recent paper (review) investigated the intgernal dynamics that makes all this possible, a train system of cargo carriers that travel up and down the microtubule bundles of cilia. The microtubules are oriented in a single direction, minus at the base to plus at the tip. Two classes of motor proteins go in opposite directions, kinesins going up towards the plus end, or anterograde, and dyneins going in opposite fashion, towards the base, or retrograde. How cargoes attach themselves to these motors, and how their transport is regulated, makes up a very interesting field of study.

This paper observed the transit time of transport carrier complexes (IFT) at the tip, before heading back down to the cilium base.

These researchers used a fluorescent technique to look at individual cargoes as they were making this trip. If cargoes are made fluorescent, and then most of them are bleached out by overexposure, then a few remaining ones can be tracked. Their questions were mainly about how long these materials spent at the tip, and how the decision was made to reverse course. The operative acronym here is IFT, for intra-flagellar transport. Multiple cargoes seem to gang up into literal trains, which seems to depend a special coupling mechanism. For example, the authors labeled one of these dedicated transport proteins, called intraflagellar transport 27, or IFT27. They found that it takes about three seconds for this protein to hold up at the tip before being re-organized into a retrograde train. One of the cargoes being carried up the cilium is dynein, the motor required for all the return trips.

Experimental image set, showing time slices (going down). The fluorescent train comes up the cilium (towards the right) a first, then waits around for a couple of seconds at the tip, before dissociated fluorescent components start their return trips (on two different train sets, here) going back towards the left.

On the other hand, kinesin, which powers the trip up the cilium, does not get actively carried back down, but diffuses back, which is ten times slower. The authors suggest that this may be the rate limiting step restricting cilium length, since as the cilium grows, more of the kinesin is clogging its length, and less is available at the base to serve new anterograde trains. but since kinesin is expressed cytoplasm-wide, this is not an entirely compelling speculation.

In contrast to the train protein tracked above, fluorescently labeled kinesin powers its way up the cilium, but then dilly-dallies about, diffusing slowly back down without joining any powered trains.

What regulates all this? The motors and train proteins are nucleotide binders of various sorts, powered by ATP or GTP, so there is ample precedent for fine regulation using such systems. Perhaps just coming to the (+) end of a microtubule fiber sets switches in the kinesin and train proteins, priming them for the return conformation. What turns the dyneins on at the right time, and what regulates cargo attachment/detachment is still a mystery, however. As for cargo proteins like signaling receptors, some are known to have special targeting sequences which let them bind to the vicinity of the ciliary base, where they are transferred to the IFT train system. Others are sent to the primary cilium via the golgi protein sorting and vesicle generation system. If the targeting is high enough in affinity, such receptors can be essentially vacuumed from the rest of the cell and localized entirely to the cilium, thereby explaining the extreme localization/specialization of some signaling pathways and receptors to the primary cilium.

• Can our voting system get any worse?
• Too toxic for Trump, but not for Liberty University.
• Final gambit for fossil fuels in the US- sell public lands at a loss.
• CO2 not only going up, but going up ever faster.

The Sierra Club as a Religious Organization

Yes, and a good one, too.

The divides in the US have many dimensions, but a significant one is religious. Conservatives crow about their traditional religion- Christianity- and then, bizarrely, vote for Trump. What they really seem to be for is patriarchy and its traditional society-wide hierarchy (based on male-ness, but also on its accessory patriarchal religion and on race). Their model in the South shows that a bare-majority or even minority race can maintain power for decades in an ostensibly democratic society if enough levers of social, political, overt, violent, as well as covert power are used consistently. The movement against Confederate monuments is a watershed in consciousness of the thoroughgoing way the social gestalt of the South has been shaped by its treasonous and revanchist elite.

As far as rural and Southern America are concerned, the bicoastal elite live in another country entirely. In that country, we tend to think we have no narrative, no gestalt at all, but purely a functional this-is-the-way-it-is approach to reality and truth. A committment to reason, science, innovation, good public policy, social justice, etc. But of course, that can not be true. We have a narrative as well, and nothing illustrates it better than the Sierra Club.

This is the home of the shamans of environmentalism- the tree-huggers, whale watchers, and activists, inhabiting a completely different narrative from that of traditional Christianity and patriarchial conservatism. Its roots go deep into paganism and the natural reverence humans have for nature. It is a nature religion, but not animistic. There are no anthropomorphic deities or weird powers. We are the gods, but are fallen, now that we have inherited this awe-ful responsibility of taking care of a world that we have so hopelessly befouled. There is no bearded or other male figure behind the curtain. The Sierra Club conducts pilgrimiges, has its saints, sacred places and its version of the end-times, preaches to its believers, and expounds at every opportunity an ideology of love of and care for nature. It has its fetishes for untrammeled, unspoiled locations, its secret misanthropy, its revelations of human insignificance. And even jihad, if you count GreenPeace in the same sect.

A recent article by Gary Kamiya in the Sierra Club organ makes its religious nature particularly clear:

... Which takes us back to the wilderness within. No matter how refined we may think ourselves, at some level we are all still wild creatures, made up of the same materials as the mountains, the deserts, the oceans, the distant stars. "Wilderness" carries a connotation of chaos and anarchy, but that's misleading. Our inner wilderness is no more disorderly than the world itself is. A wild mind is a balanced mind. The wild world may be deeper and more heterogeneous than the city world, but the difference is only a matter of degree. The sense of wilderness is our birthright, and we can experience it anywhere. "The wilderness as a temple is only a beginning," Snyder writes. "One should not dwell in the specialness of the extraordinary experience . . . to enter a perpetual state of heightened insight." The real goal, he says, is to see all the land around us, whether in the country or in the city, as "part of the same territory—never totally ruined, never completely unnatural." 

Of course there is still absolutely nothing like a face-to-face encounter with deep wilderness. Once at Buck Lake, I was awakened by the screaming call of a pack of coyotes racing unseen through the 3 A.M. darkness, the shrill sound moving fast along the mighty granite ridge across from my campsite, then fading into the distance. That sound still rings in my memory, a quicksilver affirmation of the strangeness and holiness of the world.

The language and sentiments are clearly religious. But there is no theology, no theos at all. It suits the "spiritual-but-not-religious" mindset, whose sprituality is affective and natural, not burdened by over-thought (yet underbaked) theology and relic supernaturalism. Science isn't a problem here, but another way to appreciate the glory of what we love on so many levels- our world and biosphere.

Is all this good? People are naturally religious, creating and needing frames of meaning beyond mere subsistence and reproduction. The Republican Party and current administration shows what can happen when such a frame becomes completely moribund, paying lip service to Catholic and generally Christian dogmas while throwing any semblence of actual moral principle to the wind and practicing shameless greed. It is a revolting spectacle on every level. True religion fosters empathy and puts us in touch with our core values and commonality, not just among males, or with fellow countrymen, or even with humans, but with all beings.

• Silent holocaust.
• More lies.
• Are human desires endless, and therefore work endless? Only if money is distributed equitably.
• Does all our productivity get channelled to the top, or to those doing the work?
• How to design drugs with knowledge and computers.

Not the Last Dark Age- the One Before That

Review of 1177 B.C., by Eric Cline, about the decline and fall of the Bronze age around the Eastern Mediterranean

In this time of cultural and political decline, it is useful to contemplate previous cultural cataclysms. While "the Dark Ages" typically denotes the roughly five hundred year hiatus between the fall of Rome and the resurgence of wider cultural ties and development in Western Europe, that was hardly the only extended collapse of high level civilization. A previous Dark Age had followed the collapse of the Bronze Age circa 1200 BCE, leading to the several historically empty centuries before we hear about the classical Greek civilization rising from the ashes in the 700s BCE.

The Greeks cherished their dramatic sagas dating from that prior, heroic epoch, much as the English later looked backwards romantically via the Arthurian saga, going do far as to send Arthur to defeat the Romans in battle. But the battle of Troy was no fantasy- it really happened. The only question is whether it was part of the destruction of the Bronze age, or part of its normal, competitive, affairs.

In fact, it is astonishing what we do know about this age, given its distance from us and the ensuing civilizations. Eric Cline has assembled an excellent guide to this period, the late Bronze age, dredging up a great deal of scholarship old and new on the many civilizations clustered around the Eastern Mediterranean from Italy to Egypt. We owe particular debts to the writing developed earlier in this age, both the hieroglyphic style in Egypt, and the cuneiform style from Babylon, which was adopted by the Hittites and others. The clay tablets so amenable to preservation (especially after fires) have been a gold mine of knowledge about the affairs and attitudes of the time.

Hittite writing from about 3300 years ago, using cuneiform script.

We have correspondence between kings as well as more mundane accounts. We have in some cases both sides of a diplomatic exchange, even a momentous peace treaty between Egypt and the Hittite empire. It is quite amazing. These unearthed records paint a picture of extensive contacts and trade between the states of Cyprus (Minoans), the Mycenaeans of mainland Greece, the Hittites of Anatolia, the Assyrians, the Ugaritic state in what is now the northern Syrian coast, the Canaanites, and Egypt. It is easy to get carried away with globalization analogies and complexity theory. But unfortunately, we have very little to go on when it comes to what ended this period. The Egyptians record enormous battles with "the Sea Peoples", which seems to have been a coalition of several enemies. But they also say they won this war, and the pharoah, Ramses III, was laid to rest in high style, though murdered in an internecine plot. Cline goes through a large amount of archealogical evidence, which shows earthquakes, drought and climate change, internal revolt as well as external invasions during these times. It is, in sum, hard to finger any single cause for the eventual decline of all these cultures into several hundred years of relative silence and decreptitude, (not to mention tomb-robbing), though there may have been a combination.

It was once fashionable to cite the Sea People as the instigators, in an orgy of rapine and destruction, as is related in the Iliad, and the Egyptian annals. It is not clear who the Sea Peoples were, however. They may have been Myceneans, but evidently encompassed other groups as well, maybe even free-booting pirates. And the various destroyed cities of this age were not all invaded, let alone by these groups. The Hittites were sacked by other enemies.

Ramses III mortuary relief showing prisoners from battles with the "Sea Peoples". Note the diverse head-dresses.

Cline resorts to the decline of trade, and complexity theory in his speculations. But a problem is that, despite the excitement of finding trade relations between these states, and royal correspondence, it is highly unlikely that a state like Egypt was substantially dependent on outside trade or other assistance. Such relations were icing on the cake, but hardly fundamental to its perpetuation. The cause has to be found elsewhere, either in general theories of cultural sclerosis and decline, or perhaps in disease or technological innovation. Also, if invasions or revolts were at issue, why did some other state not take advantage of them? The preceding centuries had seen a constant tug-of war between Egypt and the Hittites for control up the Levant, indicating that, were one weakened, others would rush to take up the slack. Yet both went into decline, and the Hittites vanished completely. It may indeed just be a coincidence that many cultures had reached a high level simultaneously, and then at similar times were overcome by ruder powers less inclined to leave historical traces.

The stage of the Bronze age was originally set by the migration of Indoeuropean peoples into the Middle East, founding the Mycenean and Hittite cultures, among others. Their earlier spread was enabled by a suite of decisive technological innovations like horse riding, wheeled carts and chariots, mobile warfare, and herding, which enabled mobility and military success. By the late Bronze age, these were no longer novel and had diffused all over the region. But perhaps some other innovation, like improved and larger ships or nascent iron working, may have tipped a critical balance. Secondly, herding and livestock domestication generated a variety of new diseases, which eventually played such a large role in the destruction of the native peoples of the New World. Perhaps one of these diseases had yet to burn its way through the late Bronze age Mediterranean. It must be said, however, that such an event would probably show up in the Egyptian annals, and also that other cultures managed to recover within a generation or two from devastating plagues, such as the black plague.

Lastly, cultural decline might be inevitable after a long period of stability. Stability breeds complacency and a cultural dynamic where the powerful stay powerful, with ever less merit and justification as time goes on. Their corruption, combined with the resentment of the powerless, can lead morons into power, a bad sign in any age and a sure path to decline, for all their protestations of greatness.

• Conservative "thought".. puts the conservative before the thought.
• But perhaps the thought is better than the action.
• Big data is not the same as understanding.
• 24 hours hate.
• Markets reflect human psychology.
• Xi Jinping and the rise of China.

What Adulthood Looks Like in the Brain

A gene expression turning point in the mid-20's correlates with onset of schizophrenia, among other things.

Are brains magic? No. They may be magic-al in how they bring us the world in living color, but it is mechanism all the way down, as can be seen from the countless ailments that attack the brain and its functions, such as the dramatic degradation that happens in boxers and football players who have been through excessive trauma. All that amazing function relies on highly complex mechanisms, but we are only beginning to understand them.

One way to look at the brain is through its components, the proteins expressed from our genomes. Those proteins run everything, from the structural building program to the brain's metabolism and exquisitely tuned ion balances. Current technology in molecular biology allows researchers to tabulate the expression of all genes in any tissue, such as the brain or parts thereof. This is sort of like getting a quantitative parts list for all the vehicles active in one city at a particular time. It might tell you a little about the balance between mass transit and personal cars, and perhaps about brand preferences and wealth in the city, but it would be hard to conclude much about detailed activity patterns or traffic issues, much less the trajectories or motivations of the individual cars- why they are going where they are going.

So, while very high-tech and big-data, this kind of view is still crude. A recent paper deployed these methods to look at gene expression in the brain over time, in humans and mice, to find global patterns of change with age, and attempt to correlate them with diseases that are known to have striking age-related characteristics, like schizophrenia.

They duly found changes of gene expression over time, and tried to concentrate on genes that exhibit dramatic changes, reversing course over time, or plateauing at times that they call turning points. Below are a few genes that show a dramatic decline in mice, from youth to adolescence.

Expression of selected proteins in frontal cortex of mice, with age, showing turning points in early adulthood, which is about five months here in mice. These genes each have variants or other known associations with schizophrenia.

Perhaps the most interesting result was that, if they tabulate all the cases of turning points, most seem to occur at early adulthood. The graphs below show rates of genes with turning points at various age points. One can see that by about age 30 and certainly 40, (about age 7 months in mice), the brain is set in stone, gene-wise. There is little further change in gene expression.

Number of genes by age when their expression shifts direction, either up, down, or plateauing.

In contrast, age 15 to 30 is a very active time, with the most genes changing direction, and the largest changes of expression peaking about age 28. Given the many genes and complex patterns available, the authors reasoned that they could do some reverse engineering, predicting a sample's age from its expression pattern. And using only 100 genes, they show that they can reliably estimate the age of the source, within about 5 years. Secondly, they broke the gene sets down by the cell type where they are expressed, and found distinct patterns, like genes typical of endothelial cells attaining peaks of expression very early, before 10 years of age, as physical growth of the brain is maximal, while genes typical of pyramidal neurons, one of the most important and complex types of neurons, reach their inflection points much later, in the mid-twenties.

Types of genes and their rough times of expression shift, by age. Most key neuronal genes seem to settle into unchanging patterns in early adulthood. PSD is post-synaptic density, typical of synapses where learning takes place.

Particularly interesting to the authors are genes associated with post-synaptic density, part of the learning and plasticity system where connections between neurons are managed. These genes were especially enriched with turning points in early adulthood, and also feature a disproportionate number of genes implicated in schizophrenia, whose onset occurs around this time. The genes tended to be turned down at this time, in neurons. While these observations correlate with the age-specific nature of schizophrenia, they do not go much farther, unless it could be shown that the genetic variants that confer susceptibility are perhaps mal-regulated and more active than they are supposed to be, or some other mechanism that makes the connection between the defect (all of which so far which have very weak effects), and the outcome. For example, one such variation was found to increase expression of its gene, which is present and functional in the post-synaptic densities.

It is interesting to see the developmental program of our brains portrayed in this new way, but it is only a glimpse into issues that require far more detailed investigation.

• Bob Cringely loses his house.
• Inherit the wind... or at least track it.
• Money + Stupidity + Democracy = Power

Vegas

A brief post.

Since no ideological, political, or religious motive has yet emerged for the massacre in Vegas, I would tend to interpret it as a terminal case of gun nuttery. We have long heard how violent video games and movies were supposed to be damaging our brains. Well, I think gun fetishization is an even stronger deranging influence. One can read it in the gun blogs, where a discourse of fear and power, of tactical preparedness and no retreat turn into a machismo echo chamber. And actually owning guns seems to have similar effects, turning owners minds to the power they wield, somehow generating the need for more and more, and more elaborate fantasies of what to do with them. Apparently 3% of gun owners own half the guns in the US. It is a disease, is culpable, and should be in the DSM.

• How to be a good parent.
• The 2009 infrastructure spending program turned instead into a fiscal lifeline for the states.

Father Dearest

Toxicities, perversions and archetypes around the father role. Based on Raised Right by Jeffrey Dudas, and Toxic Parents, by Susan Forward.

The father archetype looms large over our personal and collective lives. Fathers are inescapable, for better or worse, in their shaping of our identity, meaning, and purpose. Most cultures, including all those of Indo-European descent, are patriarchial. Father figures are central to our political lives and mythology. God is a father.

Our current political divide is steeped in the father archetype. Democrats are the mommy party, Republicans the daddy party. Never has that been clearer than with the current occupant of the White House, who seems to think that his orange patriarchial aura should suffice to get the entire country to fall in line behind every tweeted emission. But it is nothing to make light of- the psychology of these polar tendencies is fundamental to humanity and probably many other beings. Perpetual contrasts exist between competition and cooperation, risk and security, discipline and forgiveness, war and love, yang and yin.

A recent book about icons of the right argues that father mythology pervades the personal and political conceptions of the right. Fathers only have authority in the family if the state moderates its nanny-ish tendencies. CEOs only have proper authority if the state does not meddle in their companies. And the country is properly run only when a father figure lays down the law on standards of morality and behavior, however much that conflicts with the first two aims. Many prominent figures on the right have frought, to say the least, relations with their own fathers. Newt Gingrich comes to mind, but the author Jeffrey Dudas profiles William Buckley (absent, though overbearing, father), Ronald Reagan (drunk, weak father), and Clarence Thomas (deserted father, replaced by totalitarian grandfather). Each found a personal and political mythology in constructing a new image of the father figure, mostly drawn on the founding fathers.

It is the usual authoritarian / patriarchal story- what ails the world (read- the self, or the early self) is lack of discipline, and masculine modeling, which is supplied by the authoritarian leader who will restore order, law, and the scope for other elements of the patriarchy down the line (corporate, police-state, and family) to do likewise, will heal the society. This resolves the chaos resulting from lack of boundaries and discipline, and lack of social hierarchy. All this is claimed in the name of freedom- the true freedom of the orderly citizen, not that of the malcontent and rabble-rouser. Reagan provided an especially clear vision of this condition of the state, set in contrast to the hippie protesters on whom he cut his teeth as governor of California. And he justified it in terms of the American dream of freedom and equal opportunity for all- all virtuous and deserving citizens, that is.

All is well with this nuclear family, enjoying its driverless car in 1957.  Each person's role is well-defined and secure.

The problem is that, while the patriarchial virtues certainly have merit, they are hardly the only virtues. Worse, they tend to paper over a great deal of presumption about the fairness of the current starting conditions, and the ability of its stated virtues to afford the promised success, not to mention the sterling virtues and talents of those currently at the top of the heap. That is why Horatio Alger stories are such a staple of the right. If Clarence Thomas can make it, or Steve Jobs, or Jack Kemp, or .. fill in the blank... then anyone can, with enough gumption.

That is, however, a sucker's game, as likely to raise up the masses as is the local Indian Casino. Not only should success or even a decent life not depend on such extraordinary efforts and talents, but it clearly does not for the well-to-do, who bequeath countless social, material, and political advantages on their offspring, resulting in the remarkable lack of social and wealth mobility that we see in the US today. The starting blocks are starkly different for different people, and it is absurd to preach individual morality tales when material and other forms of inequality are so tragically and obviously responsible for the lack of freedom and prosperity for most citizens. Where are the reparations for slavery, for example? Also missing is any model or justification for communal, public goods. Life becomes a competition of atomized individuals, with family structure and discipline separating the wheat from the chaff, but without a rationale for wider social cooperation and institutions, such as public schools or anti-corruption mechanisms in government, or business regulation, that render the level playing field which the patriarchial myth assumes and depends on, but refuses to address.

Which is not to say that personal virtues, just saying no, stick-to-it-ive-ness, discipline, and the like, are not good things. The wise and benevolent father figure is also a very good thing. Yet, as Susan Forward points out, toxic, abusive, and even incestuous, parents are all too common. One in ten families, by her estimation, experience incest. It is shocking and horrifying, yet preaching from on high is not going to help, particularly as the perpetrators are often the very ones, through the magically empowering nature of the archetype, doing the hypocritical preaching.

Indeed, it is the damaged children who seem to end up on the right, latching on to the one certainty they have learned, that their own efforts avail them something in the rough-and-tumble of life. Desperate for good parenting, they seek father figures and a father mythology that will heal. And one is naturally ready to hand, in the patriarchy, the founding fathers, orginalism. Virtually every religion furnishes the same tale- a father who is both loving and strict, giving commandments and boundaries with one hand, while providing hope of temporal and supernatural power with the other. Most people don't take it too seriously, but if the need is intense enough, if the child within is damaged enough, this patriarchal solution seems to become a template for everything- how to live one's own life, and how the nation should be run as well.

As Dudas writes:

"Not exclusive to modern American conservatism, this longing for stability, for an end to what Willam Connolly calls the 'homesickness' of the human condition, is a hallmark of modern living. Modern times, Connolly argues, are defined by the widespread loss of belief in transcendent purpose (in 'myth') and, accordingly, by an eruption of nihilism. But this nihilism, and the felt loss of meaning that accompanies it, (of Kristeva's 'melancholia'), is so upsetting that it has been the subject of an astonishing range of ameliorative attempts. Hence the feverish devotion to those human projects that attempt to establish the sorts of 'antimyths' that Fitzpatrick locates at the heart of modernity: projects of science, reason, and the state, for example, with which human life might be organized and infused with the noncontingent foundations that existed before (to paraphrase Nietzsche) humans killed off God.
...
But as with all other modern attempts to forestall nihilism, it turns out that the melancholic's desire is 'impossible'. ... The desire for the stable object is impossible and magical because the object (Father) is oversaturated with meaning; it is itself a floating signifier that is purposed and repurposed according to the endless demands of desire rather than to the rigors of logic or intellectual coherence."

Our current president is a damaged child, from a totalitarian father, who reproduces the same parenting style with his own children, and now towards the rest of us as well. Add in desperate narcissim, and the result appears to be pathological lying and manipulativeness, as well as complete blindness to the perspectives of those not on his favorite cable news channels. We have all become victims of bad parenting, and need to redouble our efforts to break the cycle.

• Back when the government ran finance, not Wall Street.
• Too many old savers leads to persistent low interest rates and inflation.
• The market is quite high.
• North Korea has very effective deterrence.
• The rich are still getting richer.
• Getting a PhD is not so great for your job prospects.
• Annals of feudalism, cont... workers are about to be stripped of legal recourse for abuse.
• Economic graph of the week. Robbing the poor to give to the rich, under the proposed tax "plan".

Who pays what under the new plan?

Profiles in Greed

Ulysses S Grant, Carl Icahn, and the character of capitalism.

Listening to a long podcast series about the Civil War, I was struck once again by the unusual character of our 18th president. Every one who knew him agreed that he had no sense for business. Yet he led the US army to a series of strategic victories, and wrote one of the great military autobiographies, and clearly did not lack intelligence. What makes the difference?

To contrast, a recent profile of Carl Icahn, paragon of US business and hero of Donald Trump, paints a character of quite a different color. Highly intelligent, yes, but with the added characteristics of intense greed and minimal scruples- apparently a modern-day Ebenezer Scrooge.

Grant was a forthright person, in love and war. Indeed, the archtypal story of his childhood was about a negotiation for a horse where he told the seller straight out what he was willing to offer, which thus became what he paid. Grant was very good with horses, possibly a mark of a character with less guile than normal. People, with their less scrupulous machinations, were more difficult, which clearly led to many of the disasters of his presidency. Does warfare require guile? On some, very strategic level, yes. But generally, clarity, consistency, attention to detail, and courage are more significant virtues. I don't think his Civil War campaigns were marked by strategic cleverness or deceit, but more by sound military reasoning, siezing strong points, deploying overwhelming numbers, fighting doggedly, and pursuing advantages opportunistically.

Ulysses Grant, colorized

Many of these virtues are relevant to business, but evidently one needs something more to succeed. The profile of Icahn describes in detail how he tried to use his influence with the president and his position as a semi-official economic adviser for personal gain- to rescind a rule requiring oil refiners, one of which Icahn owns, to blend ethanol or else buy offsets on a special market. His refiner could not blend ethanol, so was subject to a quite volatile market in RIN offsets. While unsuccessful, the effort was flagrantly unethical and illustrated Ichan's intense greed, his great skill in manipulating others, and his consistent practice of skirting the law whenever possible and advantageous. What a contrast to Grant! And something of a contrast to our current president as well, who isn't smart enough to be in the same league, and looks up to Icahn as a hero who sits on a far larger pile of money.

There was a brief period in the mid-20th century when business leaders were thought of as civic leaders as well. After the period of the robber barrons and Gilded Age, when the business community had been chastened by the great depression and the spectre of communism, (not to mention bitter union fights), and when the whole country had been brought together by the world wars. There was an ethic of fair dealing and paternalism towards workers, and of viewing the corporation as a public, civic entity, not just there to make money, but to play a supporting role in the American way of life. Perhaps I am looking back with rose colored glasses. At any rate, that period, however amicable, is long over. The captains of our current corporate landscape, especially those in finance, are poor models of any kind of ethics; scofflaws who are fined repeatedly, even in our attenuated enforcement landscape, providing models of greed, entitlement, and callousness.

How anyone could imagine that today's celebrity business leaders would make proper and positive civic leaders, particularly someone as twisted as our current president, is unimaginable (Michael Bloomberg excepted, perhaps). So now we are in an insult contest with North Korea, (among others), at an abysmal level of rhetoric which expresses perfectly the level of intellect and ethics our leader is bringing to the table, but which should surprise no one watching his business career or those of his colleages in the contemporary business world.

• I should be very unhappy right about now.
• Enemies bond groups.
• Francis Crick.
• State's rights, but only for crappy policy.
• Puerto Rico brings to mind.. guns and ammo, of course.

Bullets of Poison

Lead, condors, and the toxic legacy of right-wing politics.

Of the many ways we have ravaged our environment, some of the most heartbreaking are the silent killers- DDT, other insecticides, PCBs, trash, CFCs, CO2, PFOA, and lead. The same technologies that have conjured out of our environment the many wonders of modernity have also unlocked demons, like plutonium and other radioactive poisons, which we struggle to control and dispose of.

But our thoughtless dumping of pesticides and other poisons doesn't even rate that kind of drama. It took an especially gifted writer, Rachel Carson, to bring the ravages of DDT to light 50 years ago, and we have since slipped into an amnesia through which other poisons like the neonicotinoids have seeped into astonishingly widespread use, making arthropod wastelands of our most fertile country.

One of the more insidious poisons is lead. Through the Flint water crisis, we have learned once again that lead is pervasive, and an enormous health threat. Why have we tolerated it for so long? It has taken painstaking public efforts to get lead out of gasoline, out of paint, and out of new water pipes. Yet it is still common in old pipes, and in coal ash, killing and impairing Americans continuously. And it is common in firearm ammunition.

Poisoning oneself and one's family by hunting with lead is one thing, and tragic enough. But it turns out that other animals can be even more strongly affected, particularly the California Condor. This magnificent bird, North America's largest, is, naturally, attracted to carcasses and viscera left by hunters, and is not a picky eater when it comes to lead. But even if they were, it would be impossible to avoid lead from such carcasses, since lead bullets leave a wide swath of fragments and contamination in the victim. Condors also have particularly strong digestive juices that mobilize more of the lead they ingest than do those of other predators and scavangers, making lead the leading cause of death among the painstakingly re-established and tiny wild population. Indeed, that population can not grow until lead is eliminated from its food supply.

California has, with great political effort, established a ban on hunting with lead ammunition, to take effect within a couple of years. The Obama administration likewise set up a ban on use of lead ammunition in federal wildlife refuges. But the new administration, in line with the rest of its immoral and mindless policies, reinstated the use of lead ammunition. It is one more example of the sheer meanness and spitefulness that seems to pervade this sector of American politics- a segment of the elite and the electorate that could not care less about nature, about justice, and about the future in general. As long as they are "winning" over their perceived enemies, in a zero sum spiral of death, scientists, truth, justice, and the future of humanity, not to mention the biosphere, can be damned. Even the US Army has recognized that the costs of creating enormous toxic waste dumps out of their firing ranges and conflict zones (not to mention the manufacturing stream) is too high a price to pay, and has switched to unleaded ammunition. (Though uranium- that is a different story!).

A similar story has played out tragically in India, where an antibiotic used in cattle turned out to kill vultures, wiping out the population, and causing some very unpleasant ecological consequences in a country in dire need of efficient trash and carcass collection. While we should not stifle all progress with overly cautious regulation, once a tragic consequence from some technological innovation (or ancient practice) becomes apparent, we should recognize our own power in the role of the government to set rules for the good of our long-term collective interests- interests which surely include preservation of our own health and that of wild animals.

• Defenseless animals are next.
• Krugman: it isn't just science at stake, but civilization.
• The irony of Texas.
• Silencers- as American as apple pie.
• Bias in the biomedical literature.
• Incentives only go so far. Character counts for a lot as well- about half.
• Problems with the upcoming Vietnam War.

A Cosmos of Fear

Not Your Father's Star Trek Federation: Cixin Liu's dark vision in "The Dark Forest". (Warning: Spoiler alert)

After slacking off most of the book, Luo Ji gets down to the business of saving humanity in the last couple of chapters, even as he is spat upon by his beneficiaries as a false prophet. It has not been easy for the wallfacers project, which Earth developed after learning not only that there are extra-terrestrial aliens, but that they are intent on taking over Earth, and are also listening in to everything humans are doing. The idea was to nominate a few super-people to think and scheme in the privacy of their own minds, where the Trisolarians (aka Alpha Centurians), couldn't listen in. Sure, this involves a total lack of accountability. But on the other hand, it is humanity's only hope for secure strategic innovation. Sadly, Luo Ji's three colleagues have either committed suicide or disgraced themselves with schemes bordering on insanity.

Luo Ji's strategic insight is borne of a shockingly negative view of how intelligent civilizations would operate and relate in the greater cosmos. It incidentally offers a fascinating and neat hypothesis to the question of why we have never detected, let alone been visited by, aliens. The hypothesis is that natural selection operates in a particularly brutal way among rapidly developing, and far-distant civilizations. Communication is essentially impossible due to the distances involved. Yet the technological scope of civilizations that have a billion or two years on us is still remarkable, including missiles made of strong-force matter, vastly harder than regular matter, missiles capable of destroying whole stars, star-based amplification of messages that can easily be heard by the entire galaxy, and manipulation of sub-atomic / string theory dimensions to create protons with special computational and communication properties. The upshot is that a civilization can grow to highly threatening capability before others even know of its existence. All civilizations at some far level  of advancement are mortal threats, in principle, to others they know about, and given some with fewer scruples, some of them will simply extinguish any local threats they learn of, before asking too many questions.

Thus the cosmos becomes a very dark place, where announcing your existence is tantamount to a death sentence, there being far, far more advanced civilizations always listening and on the lookout for either room to grow, or just threats to their own comfort and security. Nothing could be farther from the positive vision of Gene Roddenberry, which, admittedly, was developed out of a social agenda rather than a study of galactic sociology and biological imperatives.

What is one to think of all this? Firstly, much of the science underpinning this vision is fictional, such as star-killing technologies, and matter manipulation at theoretical or inconceivable scales. Secondly, insofar as the model is biological evolution, it takes far too dim a view of the possibilities and benefits of cooperation. Evolution has shown countless times that there is room for cooperation even amidst the struggle to survive, and that cooperation is the only way to gain truly vast benefits, such as from multicellularity, eukaryotic organelle specialization, and human sociality. Thirdly, we also know from our strategic games with existentially destructive weapons, such as is presently playing out with North Korea, that deterrence rather than offense becomes the principal goal among those having achieved such powers. Would deterrence work in cosmic game theory? It is a problem, since, given a star-killing capability that takes many years to travel to its target and presumably could not be detected at launch or perhaps even at close proximity, offense might happen with impunity. (The Milky Way is about 100,000 light years across.)

But perhaps the most persuasive argument is simple morality- that despite the cold logic Cixin Liu develops, intelligent beings of such vast sophistication are probably more likely to wish to learn about other civilizations than to destroy them, whether out of boredom or out of a Prime-Directive kind of respect and interest. It is sort of unimaginable, to me at least, that the explicit goal of any advanced civilization would be to sterilize its environment so completely, even if unadvanced human history does offer that as a common, blood-drenched, theme.

• Toles on the maelstrom.
• Noonan, defending the indefensible.
• Do we want open borders? Not if we want a welfare state and other public goods.

PIWI and Friends Fight Zombie DNA!

How tiny RNAs fight the good fight to keep mindless, selfish junk DNA from eating the rest of the genome.

Our genomes are full of junk. Only about 5 to 10% of it has any function at all. Not only is the rest junk, but over half of the genome is made up of transposable elements (also called transposons) in various states of mutational disrepair, mostly fossils and relics. These are selfish DNA "organisms" (about 6500 basepairs long) that when fully functional can reproduce by making copies which insert themselves elsewhere into the DNA. They are like zombies, mindless and simple, knowing nothing other than an implacable desire to reproduce by using the other machinery of the cell to attack the rest of genome with yet more copies of themselves, and continuing to do havoc even when partially diabled. This kind of thing can, naturally, be very damaging. That is why our germ cells have special protection through tiny RNAs called PIWI RNAs, or piRNAs.

piRNAs, at about 26 to 31 nucleotides in length, are even smaller than the transposable elements they defend against. In the typical case, they are encoded by one of thousands of clusters sprinkled around the genome. They are expressed mostly in the germ cells, where it is naturally of particular importance to keep transposons under control. After being processed to their mature size, they bind to partner proteins of the PIWI family forming a guided missile that finds the matching (i.e. complementary) sequence among other RNAs in the cell- those made by its target transposon- and destroys that RNA by chopping it up. We have tens of thousands of these piRNAs, and if their action is inactivated, transposons start jumping around at a hundred-fold the normal rate, and the sperm (this is usually studied in males) is infertile, because of all the damage, though also because of other roles piRNAs have in this process.

Where did this mechanism come from? It seems to be quite ancient, as is the race between parasitic DNA elements and cellular organisms. Sponges have them, and all eukaryotes even prior to animals all have the related miRNA systems which also act to cut up or down-regulate target RNA messages. How did we accumulate so much piRNA, on the order of 6,000 clusters encoding hundreds of thousands of individual units in our genome? That was doubtless driven by the promiscuous and persistent nature of the transposable elements they are fighting against, via natural selection. But do piRNA genes develop directly from transposons in some fashion? Otherwise, the cost from randomly mutating and hitting other parts of the genome by mistake could be quite high.

Indeed, there is something called a ping-pong mechanism that generates extra piRNAs from the remaining fragments of piRNA-cleaved transposon mRNAs. This helps finish the job of defense, but whether such piRNAs can somehow lead, even rarely, to extra units of genomic piRNA, via reverse transcription or other means, is yet unkown. What is known is that the clusters from which piRNAs are expressed are graveyards of old, defunct transposons. These regions seem to be specially marked in the chromosome, in ways again dependent on the piRNA system, so that they get transcribed and processed into piRNAs, rather than other things.

Basic cycle of piRNA production, action, and ping-pong propagation. After production and processing, short piRNAs (red), docked to their PIWI protein partners (Aub), direct the cleavage and destruction of transposable element RNA (blue). Some of the resulting pieces dock with another PIWI protein (Ago3), and get likewise processed to repeat the cycle on the complementary strand, which repeats again, etc. This makes the accuracy of the original targeting critically important, of course.

To do this, piRNAs have another role, which is to direct methylation of the DNA, setting up specialized chromatin zones. While all the other defensive operations of the piRNAs have been in the cytoplasm, this takes place in the nucleus, using different PIWI-related proteins. This process targets transposons as well as the related piRNA-generating clusters, and has a two-fold point. In the first place, it strongly represses normal transcription from transposons, another form of direct defense. Secondly, it seems to switch these regions into the piRNA mode of production, where altered transcription, which is not very well understood yet, generates the long piRNA precursors (rather than the transposon messages) and initiates their processing.

As if that were not all, piRNAs are sprinkled around the rest of the genome in normal genes, which they help to regulate. At later steps of sperm production, after the major role of defense against transposable elements has passed, this other class of piRNAs destroy most of the remaining cellular mRNA, to streamline the cell down to only the essentials. How this dramatic event is controlled and restricted to these times is not understood, however.

There is a great deal more to be said and investigated about this genomic quasi-immune system. However it is already clear that it is a critically important process that mobilizes massive resources, in a quiet arms race that we are running against persistent and ancient enemies that lurk within.

• Trains are the efficient way to travel.
• A history of parochialism in modern Egypt. Is the Brotherhood a nationalist model?
• "Unfortunately half of the violent crime in the United States goes unsolved."
• A nation of laws and justice, or of one race?
• The nation state remains the fulcrum of power, for better or worse.
• Krugman- Zoning in prosperous areas strangles construction and raises housing prices, not to mention fostering homelessness.
• The Russian view of history.
• The Afghan army is not very good.