Chromosomes Blown to Smithereens

Where do cancers and cancer relapses come from?

DNA is a treasure trove that keeps on giving. The human genome sequence was a milestone that may not have been self-interpreting, but has provided grist for leaps of technical advancement and knowledge. Ancestry studies are one example, but disease studies are of more immediate interest. Cancer is now understood to be a molecular disease where the DNA suffers mutations that release various brakes on cell proliferation. One of the most influential types of mutations are gene fusions, where one gene that has roles in proliferation is broken from its normal regulatory controls, either within its coding sequence (such as a repressing protein domain) or its upstream expression controls, and hooked up with some other gene that drives its expression in new places and high levels. A recent paper studied several cancers in detail, sequencing samples from various time points and locations, coming up with very interesting findings about the origins of these mutations and the nature of metastasis.

One example of a genome blow-up, called "chromoplexy". A few regions of the genome got caught in some kind of spindle, and came out with several breaks which then were repaired to form re-joined fusions. In this diagram (right) of one resulting fusion, of genes BCLAF1 and GRM1, the chromosome 6 parts on the outside have rejoined, while the broken parts between the rejoined ends have fused to each other and then to chromosome 16, with one small bit unassigned and perhaps ending up somewhere else. The diagram seems to indicate that GRM1 ends up upstream of BCLAF1, (these are divergently transcribed in the native chromosome), which I think is an error.

Chromoplexy is one form of a genome blowup, one that is restricted in scope (at least compared with the even more destructive chromothripsis). The best theory about its origin posits that the affected portion of the genome (typically an early-replicating and transcriptionally active region) gets caught outside the normal nucleus, forming a temporary mini-nucleus which is cut off from normal controls, causing the trapped DNA to break up. The cell has strong controls against free DNA ends, and uses end-joining DNA repair to patch things up, pasting ends together essentially at random. This is obviously quite dangerous, and leads to unexpected gene fusions, of which hundreds of different examples are now known that drive various cancers. One such fusion, diagrammed above, is between genes BCLAF1 (upstream) and GRM1 (downstream).  GRM1 is a receptor for glutamate, the most prevalent excitatory neurotransmitter. While most highly expressed in the brain, glutamate receptors act throughout the body, and malfunctions are connected with a variety of diseases. Increased expression and activation can drive cell proliferation. The other fusion partner, BCLAF1, is a promoter of cell suicide, or apoptosis. That function will be lost in the fusion, which might have some importance to the disease (though a second copy presumably remains intact elsewhere). The important part is that it is very widely expressed, especially in bone marrow. An earlier paper describing this fusion states:

"The GRM1 coding region remains intact, and 18 of 20 CMFs (90%) showed a more than 100-fold and up to 1,400-fold increase in GRM1 expression levels compared to control tissues. Our findings unequivocally demonstrate that direct targeting of GRM1 is a necessary and highly specific driver event for CMF [bone tumor chondromyxoid fibroma] development."

This pattern of mutation, and the specific fusions that resulted, became apparent due to the deep sequencing the researchers did, taking samples from the patient's tumors and from normal tissues. An important concept here is of mutational signatures. Each mechanism of mutation has its characteristic pattern of mutations left in the genome. Exposure to UV light, which causes C->T mutations, will leave a much different pattern in the genome than the localized chromoplexy blowup mentioned above. So a forensic analysis of the patient's DNA can tell what happened, in some mechanistic detail. For example, the various fusions seen in these samples were not part of extensive copy number variations- reduplications that are common in cancerous cells, which indicated that this blowup took place once as a discrete event, not repeatedly or slowly over a long period of time.

It can also tell when it happened, and here we get to a particularly interesting message from this paper. When they sequenced primary and relapsed tumors, (with comparisons to normal tissue), such tumors shared some key mutations, those which drove the overall cancer. But they failed to share many others. Indeed, the metastatic tumors carried none of several mutations that were uniformly present in the primary tumor. This says that metastases or relapse cancers, (this part of the study was specific only to Ewing's sarcoma, a bone cancer typically arising around ages 1-20), typically do not develop from the primary tumor, but from cells that carry the same driver mutation, but diverged before primary tumor formation. They are independent events, and metastatic prognosis has little to do with the fate of the primary tumor.

The author's proposed time course of Ewing's sarcoma evolution, placing the origin of metastatic and relapsing tumors well before and outside of the primary tumor at the time of diagnosis.

Whether this observation about metastisis applies to other tumors is naturally important to follow up. It would alter significantly how we deal with primary tumors, and informs the kind of conservative treatments (lump-ectomies, for instance) that are becoming more common. As sequencing becomes cheaper and more common for all kinds of tumors, the particular drivers, from whatever mutational source, can be identified and used to direct specific, (buzzword: "precision") treatments. GRM1 can be targeted by direct or indirect means. But if one has Ewing's sarcoma, typically associated with a fusion of EWSR1-FLI1, where FLI1 is a transcription factor that drives growth factor production and hence cell proliferation, a different set of therapies would be indicated.

• The Green dream is on.
• Our cold war with China.
• AIPAC is the NRA of foreign policy.
• Bill Mitchell on economics education, especially macro.
• Election crisis.. no problem.
• Give to the rich, take from the poor.
• Notes on experts.

Truth, Justice, and the American Way

Stephen Walt's critique of our overextended, idealist, militarized, and not very bright foreign policy: The Hell of Good Intentions.

Americans have gotten rather used to running the world. Whenever news arrives about some horror or injustice, action is expected. No matter how distant the crisis, we now have interests, and assets, close-by. It is a mindset we inherited from the Greatest Generation, who build a post-war order out of constant vigilence and activity- first to reform the perpetrators of the war, and then to forestall the spread of communism. After the Soviet Union imploded, we were left free, with a vast whirring mechanism of diplomatic and military machinery. For those raised on Lone Ranger episodes and Superman comics, which may describe a good portion of the foreign policy community over the last few decades, the answer was obvious- do good.

Stephen Walt takes direct aim at this mindset, which in his telling is borne as much from laziness and stupidity as from good intentions and US interests. We have committed terrible blunders in our rush to save people from predatory states- the prime examples being Vietnam and Iraq, which cost roughly 1.3 million and 0.5 million lives respectively, though the latter remains open-ended, due to our responsibility for creating ISIS. The people responsible for these comprehensive, mind-boggling disasters should have been tried as war criminals. But instead, our system barely batted an eye, and most of the architects of both horrors went on to continued participation in the US foreign policy commmunity, often at high levels.

This is because foreign policy is a strongly political field, at least as practiced in the US. Who would have hired Jared Kushner to run US Middle East policy? No one in their right minds, that's who. But the rot runs much deeper. Foreign policy is not science, and is difficult to evaluate, especially considering our problems with prophecy. So standards are virtually absent, replaced with a go-along-get-along ethic within a tight zone of conventional ideas. A big change since the Reagan era has been the intrusion of neoconservatives into this community, via right-wing administrations and their partisan think tanks like the Cato institute, American Enterprise Insitute, and Heritage Foundation. These were the minions who pushed the Iraq war, and they keep pushing the zone of mainstream thought rightward. Their current project is to demonize Iran. Which is odd, because Iran is a more functional democracy than Saudi Arabia, and intellectually far richer and more dynamic as well. The motivation for all this comes mostly from Israel, which has tacitly allied itself with Saudi Arabia and Egypt in a new cynical status quo ... just so long as no one says anything about the Palestinians.

The checkered career of Elliott Abrams is if anything more disturbing for those who believe that officials should be accountalbe and advancement should be based on merit. Abrams pleaded guilty to withholding information from Congress in the 1980's, after giving flase testimony about the infamous Iran-Contra affair. He received a pardon from President George H. W. Bush in December 1992, and his earlier misconduct did not stop George W. Bush from appointing him to a senior position on the National Security Council, focusing on the Middle East. 

Then, after failing to anticipate Hamas's victory in the Palestinian legislative elections in 2006, Abrams helped foment an abortive armed coup in Gaza by Mohammed Dahlan, a member of the rival Palestinian faction Fatah. This harebrained ploy backfired completely: Hamas soon learned of the scheme and struck first, easily routing Dahlan's forces and expelling Fatah from Gaza. INsted of crippling Hamas, Abrams's machinations left it in full control of the area. 

Despite this dubious resume, Abrams subsequently landed a plum job as a senior fellow at the Council on Foreign Relations, where his questional conduct continues. In 2013, he tried to derail the appointment of the decorated Vienam veteran and former senator Chuch Hagel as secretary of defense by declaring that Hagel had "some kind of problem with Jews". This baseless smear led the CFR president Richard Haass to distance the council from Abrams's action, but Haass took no other steps to reprimand him. Yet, apparently, the only thing that stopped the neophyter secretary of state Rex Tillerson from appointing Abrams as deputy secretary of state in 2017 was President Donald Trump's irritation at some critica comments Abrams had voiced during the 2016 campaign.

Naturally, Abrams has recently been appointed as the Trump Administration's envoy for the crisis in Venezuela, which should inspire confidence. The most that the mainstream press can manage as a description is that he is "controversial".

What is worse, not only are egregious blunderers and arguable criminals never held to account, (Bush, Cheney, Kissinger), but truth-tellers and whistle-blowers are routinely side-lined. Remember Eric Shinseki? He was quickly sidelined from the military in the Bush administration, after giving an accurate estimate of the number of troops needed to stabilize Iraq. He was later rescued from exile by Barack Obama, but did he re-enter the military? No, he was put in charge of the VA, safely out of the way, and in an impossible job to boot.

In September 2002, for example, thirty-three international security scholars paid for a quarter-page advertisement in the New York Times' op-ed page, declaring 'War with Iraq Is Not in the U.S. National Interest.' Published at a moment when most of the inside-the-Beltway establishment strongly favored warm the ad warned that invading Iraq would divert resources from defeating Al Qaeda and pointed out that the Unites States had no plausible exit strategy and might be stuck in Iraq for years. In the sixteen-pus years since the ad was printed, none of its signatories have been asked to serve in government or advise a presidential campaign. None are members of elite foreign policy groups such as the Aspen Strategy Group, and none have spoken at the annual meetings of the Council on Foreign Relations or the Aspen Security Forum. Many of these individuals hold prominent academic positions and continue to participate in public discourse on international affairs, but their prescience in 2002 went largely unnoticed.

One interesting point that Walt makes along the way is that one capability that has atrophed due to all this dysfunction is true diplomacy. The Iran nuclear deal was one of the few recent episodes where we actually sat down with friends and enemies and hammered out a peaceful deal, agreed to by all sides. It is far more frequent these days to make big pronoucements, whether bland or insulting, then threaten punitive action like sanctions or drone strikes. Granted, the Al Qaedas and ISISs of the world are not likely to come to any Geneva tea parties, but there is a lot of good we could be doing by diplomacy, such as in Latin America and Africa, which is being left on the table. Instead, we have very secretive military activities in about 20 African countries. Militarization has colored our foreign policy to an excessive degree. And how has our "Peace Process" been going in the Middle East? This one was not a casualty of militarization, but of Israelization. Because of our failure to bring sufficient pressure to get to a Palestinian state solution, Israel continues to be an Apartheid state, and our reputation in the region is a shambles, shown to be the lapdog of Israeli interests.

The Lone Ranger brings in the bad guy to close a successful episode.

Walt's solution to these dysfunctions is to reel back our ambitions, from what he describes currently as a policy of "liberal hegemony" to one of "off-shore balancing". Liberal hegemony is the idea, which is sort of a hat-tip to Karl Marx, really, that liberal prosperous democracy is the desirable endpoint for all peoples everywhere, so we should not mind giving history a shove every now and then to get everyone there faster. The benefit for the US is clear as well- the more democracies there are, especially as encouraged by us, the more friends we have and the more stable the world in general.

Off-shore balancing, in contrast, is more hands-off, and regards US interests involved only where some region of the world is being taken over by a large hegemon, (like China), which could create such a global imbalance that we in the Western Hemisphere may be threatened. The Middle East should be left to its devices, especially as long as the Iran and Saudi axes are reasonably closely matched. Likewise, Europe is not a problem, even with Russia glowering from the east, since power is heavily diffused, and Europe even without US help is well able to take care of itself. While seemingly cynical and isolationist, this is really a very traditional approach to foreign policy, steeped in centuries of experience with Metternich-ian balance-of-power practices in Europe.

While Walt offers some very accurate and telling critiques of the state of the US foreign policy establishment, I think the prescription does not quite fit the problem and he tends to soft-pedal its implications. While the Middle East would obviously be better off with a little less US meddling, would it be better off with more Russian meddling? I have previously advocated for prompt, decisive involvement in Syria, which might have led to a better outcome than what is happening now, for both the people of Syria, and our own strategic position. But it may have been just another costly fiasco- that is what makes this field so treacherous. (Incidentally, Walt mentions the US Holocaust Museum's extensive research on Syria, especially on the prospects of US involvement. It casts a rather dubious light overall, but does suggest that early intervention can be far more effective than late intervention.) Turning to China, Walt does not mention the fate of Taiwan, of the South China sea, of the Philippines, or Japan. Would keeping Australia out of Chinese domination be a vital interest of the US? How many interests would he be willing to give up before things get truly serious?

But the deeper issue is one of stupidity. Doing less will not make us smarter. Walt gives some very positive reviews to the various anti-establishment views of Donald Trump and the demographic that he connected with in winning the presidency. Trump was all about throwing the bums out, and retrenching US foreign policy with fewer entanglements and a more modest approach. How has that turned out? Walt decries what is quite evident- our policy, which seemingly couldn't get any worse, now has gotten much worse, with a dotard and his various short-lived protectors and yes-men running things. US interests and influence throughout the world are shriveling by the hour.

A second observation is that the Iraq was not brought to us by idealism. It originated in the psychology of unfinished business on the part of Bush, Cheney, and their extended right-wing establishment. Their idealism was, as anyone could see, paper-thin pablum, matched by their total disinterest in the actual country, its people, and what was to become of them in the aftermath. Stupidity reigned supreme, and hundreds of thousands were killed, and countless more lives destroyed and ravaged for that stupidity.

The case of Vietnam was different. We had recently half-won the Korean war, and saved its Southern half from bondage- a fate that becomes more shocking every year as we view what goes on in Chinese-backed North Korea. Due to our loss of the Vietnam war, all of Vietnam remains a totalitarian state- the South would have been much better off had we/they won the war. Our involvement there was heavily idealistic. But it was stupid. The smart people knew the lay of the land, knew the experience of the French, and knew that it was a civil war that the North had a huge head start on, in comparison with the corrupt, illigitimate Southern government. It was a triumph of hope over experience.

So what we need is more experience and smarts. The US needs a better foreign policy system, not different ideals. We need to rigorously insulate our intelligence and analysis system, of which the State Department is a prominent part, from politics. That means stopping the revolving doors of personnel coming from think tanks, lobbying organizations, corporations, and political appointments. Country and region experts need to have long-term relations with their areas, not short posts. Analyses need to be given something like five-year reviews, with promotion dependent on success. Those let go should never be let back in. Accountability needs to replace hackery, corruption, and amateurism. This community needs to be de-militarized as well, which has been a rising problem for decades. These analyses should have public and secret components, with as much as possible made public so that the country can see the work that is being done, and learn what the basis of our foreign policy is. Like militarization, excessive secrecy has also degraded discourse and accountability.

Lastly, we need a more mature media discourse about foreign policy, less reactive to the news of the day, (let lone the twitter-minute), and more analytic and historically aware. Off-shore balancing is a very credible view in this discussion, but so are more idealistic approaches. Helping abused populations in foreign lands is a good thing, if it succeeds. The point is to succeeed rather than fail in our foreign policy projects, which requires deep experience, accountability, good information, and mature discussion. Perhaps we will find out that we should be doing less, once we filter out the bad ideas. Or perhaps we will find out that to do the things we might want to do (think of the second Iraq war) would be, if done properly, unrealistically expensive and unfeasible for that reason.

• Faux-ocracies are a rising challenge.
• The Taliban is weary of gaining ground in Afghanistan.
• New Taliban, same as the old Taliban.
• Yes, we are dealing with a fascist.
• Medical insurance should be left to the private sector?
• We need a wealth tax.
• And a bigger inheritance tax.

The Power of Prophecy

What makes prophecy such a compelling narrative device in fantasy and myth, and a psychological fixation?

Humans have been obsessed, from the beginning, with the future. As the only animal conscious of the future, its inscrutibility quickly became a frustrating obsession. One wikipedia page lists 372 forms of divination. Some of the earliest far Eastern writing we have is from divination using bones with wishes or questions written on them. How natural is it, then, to imagine that there is someone on the other end to tell us the answers, or some people gifted intrinsically or through some divine possession or shamanic training to foretell the future? My newspaper still publishes the daily horoscope, a sadly watered-down echo of these most fervent longings to peer into the unknowable.

It has been a fixation in drama, from Oedipus to Harry Potter. The Greeks went to Delphi and received dramatically cryptic answers, which could be famously misinterpreted. Oedipus fell into this trap, fulfilling precisely what he had strained every nerve to prevent. When used in fiction, prophecies are relentlessly fulfilled, since otherwise, why bring them up? Like for the more generic foreshadowing technique, the magic only works when the portents are true, and the characters, while twisting every which way to evade or fulfill them, find in the end that fate has spoken with one voice out of the timeless dimension.

The Harry Potter series makes generous use of prophecy, both in its main plot lines, where Harry is marked in advance in various ways for his extraordinary fate, including the special symbol tattooed on his face, and in one particular episode, where the characters fight it out in a hall of phophetic orbs, climax of the fifth book. The bible, of course would hardly be the book it is without a flood of prophecies. The new testament was in large part composed around the supposed fulfillment of various prophecies made in the old, with some squeezing and patching required. The king of the Jews who came to save the world  bears hardly any resemblence to what the old prophets were expecting! Yet, mysteriously and gloriously, the fulfillment came about in the least expected way, etc... Then the New Testament closes with another round of even more feverish prophecies, in the form of revelations where the mundane world will finally receive its just deserts and be swept away in favor of a new and perfect dispensation.

Stonehenge, in part an astronomical prediction machine.

Obviously, it is empowering to feel even a little in control of fate, a little gifted with insight into the future. Why else are countless people betting on sporting events? Why else make such a fetish of astronomy and the prediction of what can minimally be predicted- the steady progress of the days and seasons? It is endlessly maddening to know that the future is coming, but know so little about it. But the tide has turned a bit over the last few centuries as a new mode of thought came to the fore- science. The successful analysis and prediction of Halley's comet showed on a poplular level the power of Newton's system and its ability to predict the future. Now we can predict the weather with startling accuracy, at least a week or so in advance, and can likewise predict the climate decades into the future, somewhat to our horror. Yet there is so much that still eludes prediction. Even in the physical world, earthquakes remain a frustrating challenge, apparently fundamentally unpredictable. And despite the "end of history", human affairs remain not just unpredictable, but irrational, as our current political regime so amply demonstrates.

In its humbler incarnations, prophecy is merely evidence of intelligence- a keen imagination or intuition that is able to discern where things are going sooner than the next person. This is where sports betting and stock picking get their acolytes. But beyond that it is clearly a fictional device- one that we love in its fateful foreshadowings and tragic struggles, but one that has never risen above that level to divine inspiration, reading the mind of god. Naturally, that is because such a thing does not exist. We are trapped within the plodding arrow of time, as we are under the spatial light-speed limit, as we are under our own mastery of fate, such as it is, having no other to turn to.

• Like we need more billionaires running things, and preaching about the national debt.
• Wealth is the problem, far more than income.
• And we have the candidates to solve it.
• George Will does something good.
• Protect your and your country's health- leave facebook.
• Treason and corruption, continued.
• Income tax rates have no effect on economic growth.
• But what do economists know, anyway?

Frankenplant

40% more efficient plants? Done!

What is the most common protein in the biosphere? It occurs in plants, right? Right- it is RuBisCO, the enzyme that fixes carbon dioxide from the atmosphere, is the workhorse of agriculture, and hero of the fight against global warming, should we choose to grow more plants instead of burning them down. Its full name is ribulose-1,5-bisphosphate carboxylase-oxygenase, meaning that its substrate is a five carbon sugar (ribulose) that has two phosphates attached, and the enzyme attaches a carboxyl group from CO2, but can also attach an oxygen instead (the oxygenase part). And therein lies the problem. RuBisCO is phenomenally inefficient (maybe ten reactions per second) and error-prone (using oxygen [O2] instead of CO2 roughly a quarter of the time), which is why it is made in such prodigious quantities, amounting to half the protein complement of leaves.

Plant researchers have been casting about for a long time for ways to make this core reaction more efficient. But have had no success. Indeed, an interesting paper came out a few years ago arguing that as far as this enzyme is concerned, the shape and chemical similarity between CO2 and O2 are so close that RuBisCO is perfectly optimized, exchanging speed for what specificity is possible given its substrates. It varies quite a bit in this tradeoff, depending on the specific environment, arguing that the optimization is quite dynamic over evolutionary time. One of the few innovative solutions that plants have developed is not a tweek to the enzyme, but a physiological compartment present in C4 plants (like corn), which concentrates CO2 and excludes O2, thus resolving the competitive constraint for some of their chloroplasts. Their RuBisCO enzymes are adapted to have a slightly more relaxed attitude- slightly less specific for CO2, while also almost 2-fold faster, gaining an significant advantage.

The error pathway, fixing oxygen instead of CO2, is called photorespiration, since it uses up oxygen like regular respiration, but now in a completely wasteful way. The product is phospho-glycolate instead of 3-phospho-glycerate, and the glycolate is both inhibitory to photosynthesis and difficult to dispose of. It is typically exported from the chloroplast, and bounced around between the peroxisome and mitochondrion in its way to being turned into the amino acid glycine, all at the cost of roughly twelve ATP. It is hard to believe that this waste goes on day in and day out across the biosphere, but it seems to be the case. One might note that this yet another case of the steep price of success, since RuBisCO evolved in a high CO2 environment. It was the success of the photosynthetic process that covered the earth with green and filled the atmosphere with what was to all existing life forms a poison- oxygen.

Now, a team of researchers have engineered a way around this conundrum, at least reducing the cost of glycolate recycling, if not resolving the fundamental problems of RuBisCO. They describe the import of a set of genes from other species- one from pumpkin, one from the alga Chlamydomonas, and five from the bacterium E. coli, plus a genetic suppressor of glycolate export from the chloroplast, all resulting in a far less costly recycling system for the waste product glycolate.

New pathways (red, blue) inserted into tobacco plants, plus inhibition of the glycolate transporter PLGG1. Some of the wild-type pathway for diposing of glycolate is sketched out on the right.

Firstly, glycolate export was suppressed by expressing a tiny RNA that uses the miRNA system to target and repress the gene (PLGG1) encoding the main glycolate transporter. Secondly, the researchers imported a whole metabolic system from E. coli (red part at top of diagram) that efficiently processes glycolate to glycerate, which, with a phosphorylation (one ATP) can be taken right up by the RuBisCO cycle. Lastly, they backstopped the bacterial enzymes with another pair that oxidize glycolate to glyoxylate (glycolate oxidase), and then (malate synthetase) combine two of them into malate, a normal intermediate in cellular metabolism. This was all done in tobacco plants, which, sadly, are one of the leading systems for molecular biology in plants.

Wild-type plant is on the far left, and a sample plant with all the engineered bells and whistles (AP3) is on the far right, showing noticeably more robust growth.

Combining all these technologies, they come up with plants that show biomass productivitiy 40% higher than the parent plants, as well as reducing plant stress under high light conditions. After 3 billion years of plant evolution, this is a shocking and impressive accomplishment, and can be extended to all sorts of C3 plants, like wheat and other grains (that is, non-C4 plants). Due to the number of genes involved, unintentional spread to other plants, such as weeds, is unlikely. But given the urgency of our CO2 waste problem, one wonders whether we might welcome such escapes into the wild.

• Some notes on Sweden.
• MMT is coming into the mainstream, despite kicking and screaming.
• Complete regulatory capture of the consumer financial protection bureau. Now protecting predatory lenders.
• For some countries, history is circular.
• The tribulations of absolute pitch.

Ice Cream is True

Many philosophers seem to think that what we like and want may also be true. Critique of "On Truth", by Simon Blackburn

Hardly any academic field is subject to such divergent opinions as philosophy. While most people ignore philosophy and especially what philosophers say, with complete indifference, if not mockery, philosophers see themselves as grappling with the most enormous questions that lie at the very heart of our society and humanity. They are the ones asking the deepest questions of what is good, what is true, what is meaning, and what is being. Why, oh why are they marooned in ivory towers writing tedious monographs that no one reads or cares about? Specialization is particularly pernicious in this field, transforming what might be a pleasant conversational raconteur and dorm room bullshitter into an academic mired in most arcane and pointless hairsplitting, in emulation of fields of actual research, employed solely because university students must, after all, have philosophy courses.

Still, hope springs eternal that the mental firepower so evident in the written work of these fields could come down off the mountain and briefly enlighten the masses about what is true. Such is the project of Simon Blackburn, eminent atheist philosopher retired from Cambridge and other institutions. His book is modeled on that great work of Harry Frankfurt, On Bullshit. Bullshit happens when the speaker doesn't care about truth at all, whether for it (truth) , or against it (lying). Our current president puts out a lot of bullshit, but mostly he is a pathological liar with a genius for coming up with the most mendacious and divisive lie in any situation. That is why speaking with Muller was deemed by everyone around him to be a "perjury trap". Going further, the new politics we inhabit seems to have left rational discourse behind. The right decries political correctness, which cruelly enforces reason and decency. The solution is to create an emotional discourse full of tribal identifiers but otherwise senseless, making of our politics a simple blue/green contest, ending up, ironically enough, in identity politics.

Blackburn also takes some political shots, which, since he is British, aim mostly at the egregious lying prevalent in the pro-Brexit campaign. But the book is largely a survey / critique of philosophical attitudes towards truth. The starting point, naturally, is the correspondence theory of truth. While called a theory, is it more a definition- that truth consists of mental models that correspond with reality. Heliocentrism is more true than geocentrism, Thucidides is more true than Herodotus, NPR news is more true than FOX news. Blackburn takes those outré philosophers (postmodernists particularly) to task for disputing such basic conceptions.

"At the end of the twentieth century the intellectual fashion known as postmodernism took an ironical stance towards science, regarding it in an anthropological spirit as simply the ideology of a particular tribe of self-selecting people calling themselves physicists, chemists, engineers, and biologists. The standpoint seemed to many to be a sophisticated response to science's claims to authority. It was tough-minded and knowing, and its proponents could flatter themselves as having seen through and exploded spurious claims to authority, as relativists and skeptics typically do. It was all very exciting- until one saw the same sophisticates using iPhones and GPS devices, relying detergents and paints and aeroplanes, vaccinating their children, and doing all the other things that the progress of science has enabled us to do. And then its glamour disappears, and instead it looks more than a little bonkers."

But there have been other, less dismissive approaches to defining truth- the coherence theory and pragmatism. Both take a step back from the correspondence definition, in light of our practical difficulties in knowing when we have gotten to that glorious state of correspondence. Coherence substitutes an agreement among authorities, such as a convergence among physicists of the late 1800's that everything of importance had already been found, and it was only left to work out the details. Global warming supplies another example- if 99% of relevant experts assign it to human causes, then perhaps it is, for all practical purposes, true. Pragmatism takes a similarly indirect approach relying on practical effects for validation of a truth. If planes fly, then much of the aeronautical theory underlying them is likely, again, to be true. I think it is useful to class coherence and pragamatism as methods of ascertaining or approximating truth, not as definitions. The point of truth remains getting us in sync with reality. If we were gods, then no pragmatism or coherence among authorities of lines of evidence would be needed- we would just know what the truth is, but it would still be a matter of correspondence between reality and our sovereign mind.

From there, things really start going downhill. Blackburn makes a diversion into deflationism, which claims that the correspondence theory is not so much a theory as a tautology, therefore meaningless. The problem here is a reliance on absurd linguistics. The word truth is generally not needed in truth claims, like "grass is green", as opposed to "the thought that grass is green corresponds with the facts", or "it is true that grass is green". It should be obvious that in the first phrase, the word "is" does a lot of work, setting out the truth claim quite clearly. It is hardly meaningless, or not a truth claim, thus it is little surprise that adding extra "truthy" qualifiers hardly add anything.

From there, the discussion descends into aesthetics, morality, and religion. Blackburn seems to have a hard time making sense of these fields, virtually giving up critique, and laying out lots of philosophical history and attitudes, which end up putting quite a bit of value on truth talk in these fields. For example, if we all agree that killing babies is bad, then it is true that killing babies is bad. Or, if ice cream is good, then it is true as well. There is a lengthy discussion of the formation of tastes, such that experts with deep knowledge of some art form can educate others to have more refined tastes, which all seems to form an argument for the truth of the tastes and the authority of the experts.

"But if we have been careful and imaginative and profited from the best opinion of others in the common pursuit, we can be reasonably confident that we have done justice to the topic [of some case of artistic evaluation]. We can advance our opinions, which also means we can judge them, perhaps provisionally and in cognisance of our own fallibility, as true."

But here I have to differ fundamentally. Philosophy deals with what is true and what is good. These are not the same things. Just because everyone agrees on something being good ... does not make it true. The criterion is radically different, being our judgement of goodness for human existence, whether for us personally, or for larger social structures such as our family, country or global society. Even if that judgement is putatively objective, such as population growth in response to "good"  policies or virtues, the value of that criterion remains subjective, as it is we who value population growth and flourishing, not perhaps the other animals who may die as a result. So one might claim it to be true that something is good, given expert justification or widespread agreement, but calling things true because they are good, or very good, in some aesthetic, moral, or other subjective sense, is bad philosophy as well as bad language. Whether Blackburn really intends this claim is unclear due to the murky nature of the discussion, unfortunately. At any rate, it is the age-old gambit of religions, to cast what they wish and like as truth. For philosophy to confusedly retain this atavism in its approach to morality and other goods would be deeply mistaken.

• Lawyers and truth.
• Facebook is evil.

UBI: Creeping Communism or Libertarian Liberation?

Review of "Give People Money", advocating for Universal Basic Income, by Annie Lowrey. Subititled "How a universal basic income would end poverty, revolutionize work, and remake the world".

This is a good book if one wants to read a litany of complaints about late capitalism- inequality, crummy work, appalling poverty in the midst of plenty, gender inequality and unpaid work, misdirected foreign aid. One might indeed say that never have so many reasons been adduced for a policy with which they are so tenuously connected. To put the argument briefly, if we were to give everyone in the US a monthly income of, say, $1,000, no questions asked, it would by definition end poverty, set an effective minimum wage of roughly $6.25 (full time), and cost about $3.8 trillion, roughly doubling the federal budget.

What are the various problems that the UBI is thought to address? First is of course poverty. While $6.25 is even below the current minimum wage, it is enough for a bare existence. Lowrey cites several experiments in poor third world countries that show that this kind of income is generally put to good use- much better use than aid that comes in the form of second-hand clothes, bed nets, shoes, or any of the other myriad do-good schemes that first world donors cook up. But there is a crucial difference- these experiments are conducted among a functional population generally at par for their society, whose only problem is that they, as are everyone else around them, poor, relative to more developed economies, whose goods and technologies are available for a price.

The poverty-stricken in the US are, by contrast and almost definition, dysfunctional, with health problems, drug problems, intellectual problems, and other issues that money alone is unlikely to fix, and may well make worse. San Francisco has had, for example, a long-term program to switch from money to in-kind and supportive care. If the problem is merely lack of money, then yes, cash assistance is an ideal solution. But UBI is, for this problem, a nuclear bomb, spewing money to everyone regardless of need, and possibly to the detriment of those in the most need of more structured help. There are better policies, as there are for virtually every problem that UBI putatively addresses.

Day laborers wait for work. Would UBI help?

Another problem dwelt on in the book is crummy jobs and inequality in its many dimensions, from a slipping middle class to persistent gender and racial discrimination and lack of wealth accumulation. Needless to say, the pittance represented by UBI is going to address none of these issues. The best that might be said is that it gives something, which is more than nothing, to those out of the workforce who are caring for children, the elderly, on a love-instead-of-money basis. And since the poor are disproportionately female and minority, they would also benefit the most from UBI, at least in subjective / relative terms. But again, it is a pittance, and since everyone gets the UBI, it does a poor job addressing inequality, particularly if its funding comes from a regressive source like a carbon tax, though better if it comes from an income or financial transaction tax. It does not even raise the minimum wage, given its extremely low level.

The more convincing, and libertarian, argument for a UBI is its simplicity and possible role in replacing other poverty programs. Aid like food stamps, housing assistance, and work training are all rather paternalistic and ridden with absurd paperwork, dehumanizing conditions, and arcane regulations. While some of these burdens come from simple bureaucratic evolution, most come from intentional policy built up to discourage people from becoming poor by penalizing and controlling them in various ways, resulting usually from right-wing and Southern racist politics. Replacing much of this with cash is very attractive, even if much of the new income will be wasted or if its amount fails to cover actual needs like housing in expensive areas. However, as mentioned above, many of the poor are dysfunctional, and got to where they are due precisely to their inability to handle money. To make cash assistance work, the responsible sheep would need to be separated from the goats who will end up on the street even with a UBI. This would inevitably bring back the caseworkers, rules, and other periphernalia of the welfare state.

The next level of the libertarian argument is that robots are going to take all our jobs, to which UBI is a solution. It pains me to have to say this, but this makes little sense. First, automation has been with us since the invention of the spear. Lowrey herself quotes Bill Gates: "What the world wants is to take this opportunity to make all the goods and services we have today, and free up labor let us do a better job of reaching out to the elderly, having smaller class sizes, helping kids with special needs. You know, all of those are things where human empathy and understanding are still very, very unique. And we still deal with an immense shortage of people to help out there." Clumsily put, but you get the idea- taking care of each other is the core of what we as people want to do, and should be doing. Making widgets is only one baroque byway on the true path of our life's work. Lowrey closes by mentioning the Star Trek economy- where no one needs money, all fundamantal needs are fulfilled, yet there are still jobs and ambition- a competition for status directly, not via the accumulation of money, but through the medium of work and service.

But this is probably not what libertarians have in mind. Their idea is more that the eggheads and Hank Reardons of Silicon Valley can keep on working their interesting, highly paid jobs, and not worry about stepping over homeless people, or being responsible employers in the new app-disintermediated gig economy, or facing the pitchforks of a vast and growing proletariat, all by feeding them crumbs of UBI. It is hardly an attractive future. On the other hand, one can view UBI as the first phase of future communism, where everyone shares in a basic level of decency, regardless of contribution. The UBI might be programmed to increase with time, in proportion to economic productivity or technological displacement. I can not regard this as an attractive future either, really, given the fundmantal importance of work in our personal and communal lives, and the impossibility of seeing an end to work, or having some principle to tell us what the best level of UBI should really be. Having ever-growing numbers of parasites living off the fat of the robots is reminiscent of ancient Rome, where maybe one fifth of the city population was on the dole, supported by the vast resources of the empire and armies of slaves. While this system was durable, lasting over five centuries, it does not look to me like one worthy of emulation.

Lastly, there are the children. Lowrey does not go into in detail since its ramifications may be so perverse, but supposing that UBI is granted from birth, the accumulation of children would likewise accumulate a sizeable income. Such an excessively pro-child policy would encourage more children among those most poor and most dependent on UBI, a social and plantery disaster.

---

What is an alternative to all this? A job guarantee has many positive characteristics, which I have mentioned previously.

• It gives money to those in need, not to everyone.
• It provides a decent standard of living, not a pittance, perhaps $25,000 per year, plus benefits.
• It automatically sets a substantial floor for wages, working conditions, and benefits for the private economy.
• It is automatically and strongly counter-cyclical, increasing when the private economy goes into recession.
• It naturally replaces much of the current poverty infrastructure.
• It provides services, insofar as the job holders are doing something productive.
• One could imagine a central job board, used internally by government projects and prospective employees, but also by private employers to make better offers to those employed in the program.

I would envision the job guarantee system as offering a full range of government-run work, from NASA engineering to street sweeping. Employees could be fired at will, demoted from better jobs to worse jobs, (or promoted), as their talents, behavior, and willingness to move merit. If they crash out of the simplest jobs, like litter pickup and invasive plant clearing, they could be offered a basic income for no work (at the UBI level of $12,000 per year- plus health insurance, which would be universal anyway). The conditions would be that they stay out of jail, off the streets, and out of drug and mental facilities. If they crash out of that, they would be faced with more paternalistic options of case worker intervention, food vouchers, group home living, having their finances handled by a trustee, etc. At this level, work requirements would not exist anymore, or lifetime caps, etc.

One of the most positive aspects of communism was its guarantee of work. The work may not have been efficient, but it gave everyone a place in society, and a paycheck, and benefits. It is one of the few aspects of communism worth emulating, if it can be made to work alongside a higher-paying, innovative, and well-regulated private economy.

Combining a job guarantee, cash benefits, and more controlled programs, a spectrum of appropriate options would be available at all levels of society to lift everyone out of poverty, to intervene where needed, to provide maximal freedom, and to use public money efficiently. Whether job guarantee holders actually accomplish anything is secondary- the major benefits occur regardless. Yet as noted above, there is a great, indeed infinite need, for work. For example, child care up to school age, and elder care (given some certification of disability and need for care) could qualify for one job guarantee position, regardless of the status of other people in the household. This would help families cope with services that are so important to society at large.

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Not a crisis

Not a crisis

To Re-engineer a Bacterium

Computational modeling of E. coli regulatory circuitry suggests that some bloat has crept in over the years.

Are we at the point of redesigning life? So far, studies of biology have relied on observation, and on mutations, generally for the worse. We have also tinkered around the edges by introducing new modular functions to some species, most notoriously pesticide and herbicide resistance in crop plants, and antibiotic resistance in bacteria. But what about redesigning whole organisms? A paper from a few years back (2012) took a stab at redesigning the genome of the model bacterium, E. coli, for simplicity. The quest was pretty elementary- ask whether the genes of the organism could be re-organized to function as well as the wild-type genome, but in fewer operons, with simpler regulation. Operons are sets of protein-coding genes lined up like a multi-car train, all induced transcriptionally by one promoter at the upstream end. The more similar functions one can stuff into one operon, the simpler the overall regulatory system can be. On the other hand, the joined genes are harnessed together in mRNA/transcription terms, so any regulatory flexibility that might be useful at that level is lost.

A schematic operon, with a promoter and other regulatory sites, which drive transcription of a set of coding genes, which are transcribed into one mRNA message, which is then translated into a series of distinct proteins. What is gained from chaining many related genes into one operon?

It was, admittedly, a rather academic exercise, with limited criteria for "normal function" of the genome: that its genome should produce all the products of the wild-type organism under ~100 different environmenal conditions. And it was all computational, done by iterative, computer-based evolution but never translated into a lab test of actual organisms (though synthesizing a bacterial genome based on this data is probably quite practical at this point). What they did have was a set of differential equations expressing key regulatory activities of a normal cell, concerning its metabolism, environmental inducers, transcriptional regulators, and genome targets. This is not a full cell simulation, leaving out protein translational controls, degradation, cellular structure and other modes of regulation, but still covers a lot of territory.

Process of computational refinement of the target genome, making random variations, then assaying for modularity and transcriptional output, and then iterating again, many times. Top graph shows regulatory modularity, which increased almost monotonously due to the design of the genome manipulations. Bottom graph is the (computed/simulated) similarity of the transcriptional output vs the original genome, which takes a big hit at first, before climbing back to the original state.

They performed thousands of computerized steps of shuffling regulatory sites and genes around the imaginary genome, testing the result each time for its similarity to the wild-type case in terms of output, and for its modularity/simplicity. As one can see in the graph above, (bottom), the output was quite unlike the standard (wild-type) for a long time during this simulation, before regaining an approximation of the wild-type pattern later on. Clearly the first order of business was simplification, with accuracy of output secondary. The final results are impressive, given the limitations, reducing the total number of operon clusters to about 1/4 of the original.

Example loci from the work. After genome re-organization, several operons have many more genes (black arrows, text notes).

An example is given above. The arc operon is turned on in anerobic (low oxygen) conditions, and encodes factors that repress aerobic loci, such as those involved in oxidative phosphorylation- the use of oxygen to generate ATP efficiently. In the rewired cell, this promoter encodes not one, but 11 other genes as well, probably gaining time and parallel control for a lot of other functions that could benefit from coordinate regulation. But what is galS doing there? This is a key regulator that turns on galactose import, a function completely unconnected with anaerobic conditions. This is one instance (which the authors bring up themselves) where, due to the limited selective pressure these experimenters put on their models, they came up with an intuitively poor result. But overall, they document that, as expected, the functions of genes now coalesced into single operons are overwhelmingly similar as well.

This work, while abstract, and unlikely to have resulted in a bacterium as fit in the wild as its founding strain, is a very small example of computational cell and molecular modeling which has, like artificial intelligence, been the next big thing in biology for decades, but is becoming more powerful and may actually contribute something to biology and medicine in the coming decades.

• An analogous simplification experiment in yeast cells.
• A good diet is lots of activity.
• The Fed is wrong.
• It is hard for a fool not to look foolish.
• How European banks (and the Euro) fostered the financial crisis: “Six European banks were pumping out “private label MBS” from their “US … affiliates””.
• Libraries are civic institutions full of wonder.
• Just how dead is the Republican party?

Solar Power is Not as Easy as it Looks

Adding the first increment to the grid is far easier than adding the last, if we want to decarbonize electricity. Review of "Taming the Sun", by Varun Sivaram

Global warming is no longer a future problem, but a now problem, and getting rapidly worse. We need a total societal focus on extricating ourselves from fossil fuels. Putting aside the brain-dead / know-nothing ideology of the current administration, the world is broadly, if grudgingly, onboard with this program. What is lacking are the political will and technical means to get there. California now gets 29% of its electricity (including imports from other states) from renewables, of which 10% is photovoltaic (PV) solar power. The grid operator shows a pleasing daily graph of solar power taking over one-third of electricity demand around mid-day.

A typical day on California's power grid. at mid-day, and fair portion of the state's power comes from solar power (teal). But come sundown, many other plants need to ramp up to provide for peak demand.

 
Varun Sivaram's book is an earnest, somewhat repetitious though well-written and detailed look at why this picture is misleading, and what it will really take to go the rest of the way to decarbonization. Solar power has very bad characteristics for electrical grid power- the grid operator has no control over when it comes in, (it is not dispatchable), and it all tends to come in at the same time of day. While this time (mid-day) is typically one of heavy usage, it is not the peak of usage, which comes during the transition to cooking and evening activities, from 5 to 7 PM. This means that not only does the rest of the grid have to work around solar's intermittency, but the rest of the grid has to constitute a full fleet of power plants for peak needs- solar will not reduce the need for either baseline or peak power capacity.

This is extremely disappointing, and means that adding the first 10% of solar to the grid is relatively easy, but adding more becomes increasingly difficult, and offloads rising expenses to other parts of the system. We do not have the technical means to economically address these issues yet. Solutions come in two basic forms- energy storage, or alternative modes of non-CO2 emitting generation.

Storage technologies by current capacity and capability. Pumping water uphill into reservoirs is the only existing method of storing power in grid-scale amounts over long periods.

Storage is easy to understand. If we could only bottle all that solar electricity somehow, all would be well. Even if we can't save summer power for winter, but save it only for a few days, we could build enough solar generation capacity (at the current cheap and falling prices) to cover our needs at the lowest production time of year, and throw away the excess the rest of the year. This assumes that, over a suitably large geographic area, there will not be so much extended cloud cover that this could not be reasonably planned. But such storage technology simply does not exist yet. The diagram above mentions some of the major candidates. The best known are chemical batteries, like lithium ion. This is how off-grid and home backup systems manage the intermittency of solar power. But these are expensive, which is why it is cheaper to buy power from the local utility than to go off-grid, and also cheaper to build a grid-tied solar system than go off-grid. The most mature grid-scale storage technology is hydropower- pumping water back uphill into a reservoir. This is obviously not available in most places where storage is needed.

Where various storage technologies are in development.

Other methods like flywheels, raising and lowering rocks, etc. are all on the drawing board, but not yet in practical deployment at grid scale, or even demonstrated to be economic at that scale. Making fuels like hydrogen or hydrocarbons from solar energy is another prospect for storage, but again are not currently economical. Hydrogen has been touted as the all-around fuel of the future for many uses, but is so difficult to handle that, again, it is far from currently practical. Getting there will take money and effort. 2050 is when we need the power sector substantially decarbonized, world-wide (if not sooner!). It sounds far off, but it is only about 30 years- a very short time in power technology terms. The scale needed is also gargantuan, so we need these solutions to get off the drawing board as soon as possible- there is no time to waste.

The alternative methods of no-carbon generation are currently wind and nuclear, with CO2 storage (sequestration) from fossil fuel plants as a further option. Carbon sequestration is not a new technology, and is something that would be directly motivated by a carbon tax, though it is also phenomenally wasteful (as are many of our more adventurous methods of producing fossil fuels, like tar sands)- a fair fraction of the energy produced goes right back into compressing and pumping the CO2 back underground. Wind is also getting to be a mature technology, and shares with solar the problem of intermittency, so is not a solution for dispatchable or baseline power. Sivaram does note at length, however, that a helpful technology for both solar and wind is long-distance DC transmission, which would allow rich sources, like the plains states, or the Sahara, to be connected to heavy users.

The dream of the next generation of nuclear power, which has not been demonstrated at grid scale.

That leaves nuclear power as an important element in future power systems. Generation IV nuclear power promises cleaner, proliferation-proof, more efficient, and more sustainable nuclear power. China has several programs in development, as does the US. Again, as with all the other necessary technologies for a fully sustainable grid, these are not mature technologies, and need a great deal of research and development to come to fruition. I will not even delve into fusion power, which is not demonstrated terrestrially in principle, let alone development.

The point of all this, as made at some length by Sivaram, is that the key to getting to a decarbonized future (for electricity, the easiest energy sector to deal with) lies not simply in scaling up the PV present into a glorious future. Rather, it lies in further intensive research and development of a variety of complementary technologies. The next question naturally is: will the private sector get us there, even if there were a carbon tax? The answer is- unlikely. The Silicon Valley model of venture capital is not well-suited to the energy sector, where innovation comes in small increments, the regulatory weather is heavy, and the scale in time and capital to money-making deployment is huge. There needs to be continued, and vastly expanded, government direction of the research, along with much other public policy, to address this crisis.

• Fed still fighting the last war, or the one before that, or a class war. But good policy it is not.
• IRS heading towards total impunity.
• Justice is in peril.
• What a year...

World of Warlords

Why does the US keep funding warlords? And then wonder why "those people" are always fighing each other? Review of Ronan Farrow's "War on Peace".

What went wrong? We have asked ourselves that after countless foreign debacles, from Vietnam to Afghanistan and Iraq. Why does every intervention turn to ashes, and every good intention end in embarrassment and hatred? Ronan Farrow, celebrity diplomat and journalist, has an answer. Though he has been through a rough family life, Farrow is a smart cookie, and after starting with an absurdly puffy profile of Richard Holbrook, the book eventually settles down into sharp vignettes of American policy and institutions gone awry, and a case for rebuilding our diplomatic capabilities. Part of the war of the title is being waged on the State Department, conducted by the military and successive presidents ending up with our absurdly anti-State current executive. But it is facile to call that a "War on Peace", as though State is our Department of Peace. It is, rather, our reserve of strategic, long-range thought and professional experience in international affairs, and arm of American power, whether advancing that power dictates peace, war, or cold war.

"There are two types of military dispute, the one settled by negotiation and the other by force. Since the first is characteristic of human beings and the second of beasts, we must have recourse to the second only if we cannot exploit the first." -  Cicero, as quoted in the book. Which is incidentally ironic, given the relentlessly bloodthirsty culture and methods of Rome.

The Pax Americana of the post-war era has served us very well, not to mention most other countries. It has been a time of dramatically improving living conditions, rising population, and governance. It has been built on overwhelming conventional power, combined with formal alliances with countless partners and soft leadership by a system both prosperous and just (more or less) which others can aspire to. The outstanding example of this is China, which in its emulation of our mode of production has lifted itself out of dire poverty over the last four decades, and done so very peacefully.

On the other hand, we have made countless blunders when trying to force conditions to our favor more actively. Iraq is a shining example. We destroyed a country only to belatedly realize we had no idea how to run it or whom to hire to do the job. Then we skidaddled prematurely, leaving behind chaos. We have stuck more persistently with Afghanistan, (up to the present moment, at least), but remain in a quagmire of epic proportions with a government that is hopelessly corrupt, filled with warlords. This is where Farrow's book starts to come into the picture. Why so many warlords? Why all the corruption, and why is the facade of democracy so thin?

Afghan president Ghani, trapped in a power structure full of warlords, armed militias, and corrupt elements.

Going back to the start of the war in 2001, we used existing forces that were already arrayed against the Taliban, namely the warlords of the Northern Alliance. Integrated with a US air campaign, they quickly swept the field. But then, in the absence of other alternatives, we kept turning to them to run things, and kept arming them and turning to them again. The CIA and the military led the way, partnering with whoever could supposedly provide the goods- that is men and power, to use our guns and intelligence. But it was always a rotten deal, buying long-term dysfunction for short-term convenience. After World War 2, would we have turned to extremist militias to run Germany and Japan, just because they were most enthusiastic to kill their enemies? Funding and arming the most extreme elements of a society is certainly the best way to get those arms used, but not always the best way to rebuild that society.

Indeed much of our foreign policy over the last few decades has consisted of arming our motley friends. Pakistan is exemplary in this regard. We have been shipping them billions of dollars of military aid since 1955. And what do we have to show for it? A country that is one of the leading state sponsors of terrorism, which is in perpetual cold war if not armed conflict with both of its neighbors India and Afghanistan, whose clear policy is to destabilize Afghanistan, and which lies to us and the world without compunction. And which has blithely acquired nuclear weapons along the way, subjecting the whole world to the spectre of extreme Islamist takeover of a cataclysmic arsenal.

It has not been a very successful policy, whatever benefits the CIA may think it has gleaned over the years. The worst part is that all this aid has strengthened the military as the leading institution of Pakistan, leading to innumerable coups, overwhelming political power even when a general is not serving as president, as well as economic and media power, to the atrophy of civic life and democracy. The best that we could do at this point is to issue a heartfelt apology to the Pakistani people that we have contributed to the militarization of their society, cut all military aid, and focus on continuing constructive dialog with everyone in the region, especially India.

Similarly, in Central and South America, we have spent far too much time and money chasing leftist mirages with right-wing funding, helping to cause the chaos that is now driving so many migrants to our borders from El Salvador, Guatamala, and Honduras. Instead of dramatic stunts of cruelty at the border, we would be much better served setting up a region-wide peace and governance process to help these countries regain stability and democratic institutions. Where is that effort? Nowhere to be seen in this administration. Farrow describes a long-term trend by which the military and the intelligence/security complex in Washington has gained power and money, versus our organs of diplomacy and long-term intelligence, which have atrophied. Nation-building became a dirty word. So now we are now dealing with a series of unbuilt nations, several of which we have unbuilt ourselves. Fear has gained over reason, much to the detriment of our domestic institutions, not to mention our approach to world affairs.

One might even say that the US has become one of the greatest terrorist regimes in the world, engaging proxy wars and armies across the globe often to rather dubious ends and resulting in vast "collateral" damage. It is our lack of expertise and inability to understand other cultures and conditions that leads to the horrors/blunders of Vietnam and Iraq. And that can not be fixed with more know-nothing "strength" from dotards, or with ever higher military budgets and military "aid" packages to anyone willing to throw their own people under the bus of American interests. We are the policeman of the world, at least for the moment. The question is whether the model we pursue is one of SWAT-style military policing, or one of community policing. The former breeds problems on both the short and long terms, while the latter solves them.

And one can note that these practices and attitudes do not stay safely abroad, far from our own culture. The militarization and warlordism of our foreign policy sees its reflection in the growing domestic mania for guns, security, walls, and the installation of a would-be warlord in the White House. While the most grievous harms of this administration may be the diminishment of our network of international relationships and influence, US society is being corroded internally as well by the pessimistic, fearful, and ignorant tenor of the security state.

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