In praise of anthropomorphism

Animals have emotions, despite all our efforts to deny it.

Anthropomorphism has traditionally been held to be a prime scientific sin, forsaking objectivity for blubbery empathy and purple descriptions of the humanity of animals. Incidentally, the term applies to inanimate objects as well, like ascribing emotions to wind and lightning, usually as part of a theistic, or at least animistic, bout of story-telling. But animals are a different matter. They really have emotions and consciousness, and we would be better off accepting and studying them than ignoring them.

Descartes famously declared that animals have no souls, are entirely mechanistic, and thus have no emotions either. Convenient for pulling the legs off frogs, no? It was an advance of sorts, since he recognized the human body was mostly mechanistic as well, with a crowning dab of immaterial soul on top. He thus contributed to the decline of vitalism in biology over the next two centuries. But his line of thought also sanctioned casual violence toward animals.

Are emotions special to humans? That could hardly be true, considering how we regard emotions as such "base" remnants of our evolutionary inheritance. If they are so unshakable, whereas reason is so easily "lost", it hardly stands to reason that they would be absent from our animal forebears and relatives. Indeed, despite animals typically being less demonstrative and vocal about them (due mostly to our obliviousness), we should assume that they have every bit as intense emotions as we do.

Likewise, one can argue from human childhood development, which is characterized by a painfully gradual mastering of our overwhelming and demanding early emotions. Do children and infants feel less than adults? Hardly. They feel more keenly, stocking up on feelings with which they love (or hate, or resent) their relatives for a lifetime. Surely, following the thread backwards, it would be impossible to imagine that animals fail to have similar emotions. Our attachment to pets is of course another expression of this highly trafficked two-way street of emotions.

Behaviorism in the 20th century eshewed any recognition of animal emotions, figuring it could observe inputs and outputs, and not bother with any kind of inner life or complicated modeling of the black box of the mind. (Odd that this movement took place simultaneously with depth psychologies like psychoanalysis and the like. Perhaps this was some kind of intellectual mirroring.) But this soon became totally insupportable, since the most complex element in the equation is the brain, hosting an inner life largely hidden to observers. It takes careful observation of external behavior to appreciate what this main actor- the mind- is up to, as pioneered by ethologists like Nico Tinbergen, Konrad Lorentz, and Jane Goodall.

But really, one only has to look in one's back yard to be struck by animal consciousness and emotion. We have squirrels, blue jays, flocks of finches, nesting titmice in the spring, towhees, hummingbirds, cats and numerous nighttime denizens. They interact with clear emotional content, from taking painstaking care of their young and playing tag to fighting with each other in ever-shifting coalitions. To see a bird switch from solicitously feeding its young and coaxing them out of the nest, to ferociously fending off a marauding jay or squirrel is to know that they feel immediately and intensely the precariousness of their fate.

Chickadees even have a reasonably complicated language of threat levels and locations, which other birds, and now humans, understand. What really brought this to mind recently was a newspaper story in the sports section about a local fisherman who brought up a thresher shark by the tail in San Francisco Bay. A delightful fight was had by all, and the shark ended up dead, either from its exertions or drowned from being dragged backwards to the boat. The proud fisherman displayed his catch, and was congratulated profusely.

But how would he have felt being hooked on the leg and dragged through the bay to his death? We used to do that kind of thing to each other, dragging enemies to their deaths through the streets, but have more recently thought better of it. Another recent bit of media was a couple of reviews of the book "Do fish feel pain"? Obviously they do, though scientists apparently only brought themselves to consider the question in the last decade or so.

One would think the simplest application of the golden rule would imply that torture of animals would not be regarded as a "sport", but rather addressed as psychopathic behavior. Which doesn't mean that meat-eating is necessarily immoral, but that inhumane treatment of animals is. The mechanized farm system is a horror of animal mistreatment, despite some occasional amelioration (see Temple Grandin). This is where we need to raise awareness and apply our moral resources.

A further question is to ask how far back in phylogeny such feelings and consciousness go. I would say that bare emotions go back right to the beginnings of any nervous system. The only point to have such a nervous system, after all, is to search out those things that afford pleasure and avoid pain, as encoded in our emotions. They are what e-motivate us to do those things that keep us and our progeny alive, and what could be more basic than that?

• Our conflicted relationships with animals.
• LSD and psychotherapy.
• Conservative economists and reason ... not related.
• More on income inequality.
• Fraud at the heart of Kabul. No wonder the Taliban gets some credit for better government!
• The Rev. Hearty on the power of words.
• Price, on Jung and blasphemy.
• Bill Mitchell quote of the week:

"I think the best thing a non-sovereign government can do in terms of advancing the interests of its people is to move towards sovereignty as soon as possible. That might involve jettisoning a currency arrangement/peg (such as in Latvia, for example).

It might require exiting a monetary union that has taken the currency-issuing monopoly away (such as the EMU nations). In this instance, that might necessitate a formal default on all debt that was incurred in the currency that the nation is exiting (such as Greece at present).

The reality is that a sovereign government holds all the cards in this situation. Please read my blog – Why pander to financial markets – for more discussion on this point.

There would be short-term costs but by re-establishing the currency sovereignty the nation will always be able to advance the best interests of its domestic economy.

This doesn’t mean that a nation that is short of real resources etc will be able to establish a high material standard of living by moving to sovereignty. The real standard of living is always determined by the access a nation has to real resources. Fiscal policy does not create these resources but can ensure they are more fully utilised and thus more effectively deployed. A poor nation will not become rich just because it is sovereign."

Why work?

In honor of labor day, some thoughts on the importance of work.

People without work are destroyed, slowly but surely. One of the primary objects of our collective enterprise is to provide gainful and meaningful employment, as well as providing for each other's basic needs and wants. Under prehistoric conditions, we had plenty of work that was clearly meaningful- sustenance, close community support of various kinds, warfare.

I think that the US (and other advanced economies to a lesser extent) have lost sight of this important psychological point. Jobs really are primary, and economic productivity is secondary. Our agricultural system produces everything we truly need with 3% of the population. What does everyone else do? They basically serve each other with luxuries of various sorts and keep each other employed in the many projects of civilization, however ephemeral.

Would an economy be good where only half of those who wanted to work got jobs, even if it produced everything everyone needed? No, it wouldn't. It wouldn't be "fair", given our inborn sense that everyone else needs to earn their keep in some way. It wouldn't be psychologically sound, given our equally inborn sense that we ourselves exist to serve the common good in some way, however small. And, given the system of home economics we live in, where expenditure requires income, it would be devastating in the absence of huge income redistribution, repugnant to both recipients and providers.

Here is an interesting quote from a passe psychologist...

"... the proletariat demands the obsession of work in order to keep from going crazy. I used to wonder how people could stand the really demonic activity of working behind those hellish ranges in hotel kitchens, the frantic whirl of waiting on a dozen tables at one time, the madness of the travel agent's office at the height of the tourist season, or the torture of working with a jack-hammer all day on a hot summer street. The answer is so simple that it eludes us:the craziness of these activities is exactly that of the human condition. They are "right" for us because the alternative is natural desperation. The daily madness of these jobs is a repeated vaccination against the madness of the asylum. Look at the joy and eagerness with which workers return from vacation to their compulsive routines. They plunge into their work with equanimity and lightheartedness because it drowns out something more ominous. Men have to be protected from reality. All of which poses another gigantic problem to a sophisticated Marxism, namely: What is the nature of the obsessive denials of reality that a utopian society will provide to keep men from going mad?"  -Ernest Becker, 1974, p. 186, The Denial of Death

We need work, though we also need to be fairly paid (valued) for it. Marx certainly understood this in his theory of alienation, though his now-defunct utopia didn't follow the thread out properly. The point of life is not to escape work, though shallow people may think so. No, the point is to do work you love, and if that is not possible, at least to do work that is socially valued, so that you feel a part of the larger society- to feel needed.

Another aspect of work is self-expression. Even if it is something as small as cooking a meal for an appreciative customer, we are expressing our love and care for others. To do so, one typically has to plug into an organization which leverages individual effort into a useful function, whether a manufacturing plant or a hotel kitchen. Part of that integration is gaining specialized skills. Like learning to play a musical instrument, learning a variety of work-related skills provides a person with new avenues to express themselves- it gives them tools, and makes them more human.

In a full-employment environment, employers take on the responsibility of expanding their worker's skills, because employees are valuable and new skills easier to create by education than to find on the open market. In a high unemployment environment, employers slack off training, since skilled workers knock on their doors every day.

This is one of the more insidious problems of the chronically high-unemployment environment that the US has experienced over the last few decades. Employers have sharply curtailed the implicit contract with workers on all fronts, including reducing education and training. Workers are expected to come fully skilled from the school system or other experience gained on their own, including hopping between employers. Training is a dead letter, other than on strictly job-related terms. This doesn't work nearly as well as a more balanced system where workers are exposed to continuing education and don't have to go back to school (or quit their jobs) to gain new skills. The culture at large also loses out when employers treat their employees as mushrooms rather than as flexible learners.

So, while alienation from work is rampant, it doesn't have to be, and one of the most important ways to make work more humane, as well as better-paid, is to even the macro-economic playing field between workers and employers by pursuing policies that lead to full employment. Needless to say, this is not what is happening in Washington right now.

• Reich on work.
• Krugman on work, giving some notable numbers.
• Workers vs the financial system, in the contemporary class war.
• Work, at the movies.
• Price on piety and pietism.
• Bill Mitchell quote of the week:

"The rise in acceptance of Monetarism and its new classical counterpart was not based on an empirical rejection of the Keynesian orthodoxy, but was instead, according to Blinder, “a triumph of a priori theorising over empiricism, of intellectual aesthetics over observation and, in some measure, of conservative ideology over liberalism. It was not, in a word, a Kuhnian scientific revolution”."

An Obama report card

In the midst of media crazy, I offer a time-out to evaluate our helmsman.

As Republicans and their media lackeys demonstrate an ability to lower our political debate to unforseeen depths, out of range of reality force fields, I reluctantly wade into politics on this otherwise wider-ranging blog and try to make sense of the first half of Barack Obama's administration.


Grade: A

I give Obama a solid A. He has shown steadfastness and moral fortitude in the face of enormous challenges and maddening political headwinds, not to mention large piles of garbage left on the premises by his predecessor. He has also shown great intelligence in his policy and political actions. Do I wish for more? We all do. But Clark Kent he ain't. And the system he heads has serious problems translating even the best intentions and wisdom into practice.

What is going on, then, with the mood of the country and the polls, which show Obama and the Democrats slipping? Some of it is rational, since every leader's position degrades once he or she gets into the weeds of actual policy, unseemly legislative compromises, and the inevitable scandals of a far-flung bureaucracy. Also, the economy is bad and getting worse, much to everyone's chagrin. Republicans are polling worse even than Democrats, however, so we seem to remain with what is apparently only one responsible, if unloved, governing party.

But some is also not rational, as the "ground zero" mosque flap has shown. Republicans know the erogenous zones of their base, if not the electorate at large. So while Obama keeps appealing to our better angels, the party of crazy appeals to our demons, whether Muslim, Mexican, or fiscal. While Obama puts together centrist, even Republican-flavored policies, Republicans cry "No, No, NO", and somehow their base comes to believe that this is the way politics should work. Well, it isn't, not unless you are a Bolshevik bomb-thrower.

But enough of the happy talk. I'm a critic, so herewith we'll get into the deficiencies of the Obama administration.


Economics: Not enough spending

The reason that we are in a rut, with a double-dip looming, is that the Federal government hasn't spent enough money to restore the loss of aggregate demand from private sources. Simple as that, and as Keynes explained, this shortfall can become chronic, even downward-spiralling, if the Federal government doesn't use its powers properly. The Fed has done all it can. Wall Street has been tended to with fond solicitude and gobs of money. Banks have been flooded with reserves and liquidity. But they still aren't lending because of the above drop-off in economic activity, as well as their near-death experience with bad loans (a death experience for many smaller banks without political pull or systemic bigness).

Politically, Obama got as much as he could get from Congress in the first stimulus, so it is hard to fault him. The political culture is economically illiterate, which is not his fault either (but see below). The current Republican mania against deficits and spending is an alliance of the crazy and the greedy, using short-term demagoguery (not to say hypocrisy) to pursue class warfare and take the country to the cleaners. It is shameful that US citizens can be so easily bamboozled by false analogies between federal and private debts, not to mention amnesia with regard to Republican fiscal and political intentions.

Not enough has been done to bring order to the financial system either, especially instituting fundamental reforms like charging a tax on every transaction, which would serve to put an important brake on the whirlwind of financialization our economy has been through in recent decades. The proposed systemic risk panel will do nothing when the next risk looms over the horizon, since every crisis is caused by blindness on the part of the major actors. This is well-covered by Hyman Minsky's theory of the financial cycle.

On other fronts, like putting the car industry through bankruptcy and funding new energy initiatives, the administration has done an excellent job. In areas within its power, aside from excessive solicitude to Goldman Sachs, it has put forward-thinking policy into practice. But without congressional support, a president can only work around the edges.


Justice: Lamentable perpetuation of executive privilege on intelligence matters

We all thought the new administration would be a breath of fresh air for civil liberties, NSA snooping, wiretap laws, perhaps even airport security theatrics. But virtually nothing has changed from the Bush administration. As covered extensively by Salon's Glenn Greenwald and NPR's On the Media radio program, the Obama justice department has perpetuated the cases and attitudes of the Bush administration, keeping the burgeoning intelligence establishment in clover and giving short shrift to transparency and civil liberties.

I don't fault the administration for failing to close Guantanamo prison on time. That remains a legal nightmare, not to say quagmire. But it would be helpful if the administration worked with Congress on a better legal framework for non-POW prisoners in general, so that coining new names (enemy combatant) doesn't give the executive carte blanche within a legal black hole. The long-term nature of these conflicts, and the non-state nature of the enemy, needs to be faced and addressed humanely and effectively for the long term. The same goes for enemies before they become prisoners, since the battlefield has become world-wide and other countries deserve some transparency on what framework we use to assassinate their citizens.


Foreign policy:  Good intentions beset by some inconsistency

While Obama got off to a good start by capitalizing on his election to mend relations with the Muslim world and most remarkably with Russia, other areas have been less productive. Iran policy and Israeli policy have been captive to the Jewish lobby and stuck pretty much where they were in the Bush administration. The biggest enemy of Israel is its own moral decline, as it dehumanizes the Palestinians and loses its legitimacy inch by inch to the orthodox and others of its own leaders trapped in the past, whether the Arab-Israeli war past, or the Biblical and Roman past.

Iran is not the enemy, but is just gathering street cred/making hay with the Sunni world by its flamboyant hatred of Israel. It is a veneer over the more fundamental Sunni-Shia divide. Iran remembers well its war with Sunni Iraq, and for all its professed craziness would not bring another such war on its head. Pakistan is Islamic too and has a nuclear bomb. Is Pakistan any more of a strategic threat to anyone with the bomb than without it? No- it has made no practical difference, except domestically in national pride and some sense of security. The same low-level wars, terrorism, and foreign policy go on with or without such bombs.

More deeply, the Obama administation has failed to fully put its principles into practice. We should say to Iran, for instance, that we don't accept its government as legitimate and look forward to true democracy instead of the theocracy / autocracy they have now. While sanctions have limited, and sometimes counterproductive effects, our words and actions have great effect, and should with all countries side consistently with the people and with progressive elements over autocratic governments. This goes for friendly countries as well. In Afghanistan, we can work with the government while deploring the election fraud and corruption that makes it such a wretched partner and servant of its own people. More principled consistency, while sometimes costly in the short run (viz our various military agreements & bases with Central Asian autocracies), is critical to our long-term legitimacy in a world where our leadership only goes as far as other people's perceptions and allegiances.


Senate policy: Obama's kowtowing to the Senate has been disgraceful

We need the "nuclear" (or "constitutional") option, and  we need it yesterday. No decent policy can be made with such a sclerotic and corrupt institution. Answer? Warfare, all-out. A recent New Yorker article has described the dysfunction of this institution in some detail.

The basic dynamic is that senators as a body have given themselves powers (holds, filibusters, other procedural roadblocks) that are not in the constitution, but leverage off the constitutional necessity of the Senate to make of each Senator a little Prince of No. Combine that with rampant corruption / influence peddling, and the originally unrepresentative Senate has turned into a place where all decent legislation either dies outright or by a thousand cuts. America can not long survive with such a moribund institution standing in the way of true representation and rational policy. Nor does the trend towards an imperial presidency, which has continued under Obama, get better when oversight from Congress is absent, due to its own institutional sclerosis.

Obviously, the modern 60 vote requirement has protected some liberal causes when the Senate was in Republican hands. So there are dangers to eliminating it. But its flagrant abuse in Republican hands has created total gridlock, and the time has come to end it. More generally, such super-majority requirements sap the institution itself. In California, we have a similar problem, where all budgets require a 2/3 majority. Any minority can hold up a budget, the legislature becomes gridlocked, and its role in state government diminishes (at least any positive role it might have). One can say that the empowerment of individual legislators directly disempowers their institution as a whole. So we need to get back to the original design of majority rule, to strengthen legislative institutions, restoring their responsibility and effectiveness.

Incidentally, Obama needs to use a few sticks when dealing with the Senate. He has been far too deferential to its dysfunctions and prima donnas. It has been all carrots and no sticks. And as the battle lines have hardened and senators have learned that there is little cost to opposing the president, compromise has become more chimerical. I don't know details of how LBJ ran the Senate, but I suspect there was some hardball involved.


Climate policy: Little gains, big loss

I am sympathetic with Obama's basic decision to deal with health care and economic issues with the limited attention span available from the Senate. The House has passed a good climate / energy bill, but the dysfunctional Senate has completely betrayed its putative role as the far-seeing, responsible institution of US government. Indeed, the Senate has betrayed our common future for a few pieces of silver- the corrupt contributions they get from the fossil fuel industry.

So here we are, with the most important issue of our time lying moribund on the operating table, a victim of its very scale, of its long-term and global nature, and of criminal disinformation campaigns by our society's malefactors of incumbant wealth. As I said at the outset, Obama is a superhero, but he can't do everything. The administration has taken bold steps in its stimulus composition, in new vehicle standards, in EPA regulation of CO2, and more. But the overall policy needed to address the true costs of our fossil fuel addiction had a heart attack in the Senate over the summer, and it is not clear whether our political system will ever deal with the issue effectively.


Pulpit policy: For all Obama's speeches, he has failed in critical educational missions

Obama has been very good as a consistent and thoughtful exponent of his administration. The stentorian tone can sometimes grate, but he is clearly engaged and expresses good policy. At a deeper level, however, there has been a failure to educate the electorate about critical realities that all his policy depends on. The president is not just a manager but a leader, who must go beyond expressing what he wants Congress to pass and how he is running his administration, to bringing a sometimes reluctant electorate with him to new views of the metanarrative- how the world works. Granted, with a firehose of hate and misinformation spewing from FOX and related media, he has his work cut out for him. But I believe he could do more.

For example, the current economic debate is shameful in its superficiality. The national debt is "high". How high is "too high"? How high is bad? Media answers to this question have been a Rorschach test of one's politics, having nothing to do with economics. In fairness, Obama's own advisors seem confused on the matter, showing how deep the rot has progressed within the economics profession. But ideally, Obama would come out and say that the US presents zero credit risk of any kind. Investors, far from running scared, are stocking up private savings and buying US debt despite historically low interest rates. And whether they did or didn't wouldn't make any difference to the government's ability to spend the currency it prints as needed to restore economic activity and more importantly, jobs. When times are better, investors will be less interested in buying government debt, will withdraw their savings, and the situation will naturally reverse itself.

These are very simple facts, and go right to the heart of economic theory that was so painfully learned through the Great Depression. Economics seems to be controlled by ideologs opposed to these views, who claim that (Democratic) government is "bad", and that government "meddling" is bad, and that banks will lend when they have less regulations, and any number of other fairy tales. What is needed is a presidential education campaign in serious economics to forestall the floundering inaction that is sending us into further depression/recession.

In all the above issues, (the Senate, foreign policy, economics, climate change), the president needs to develop deeper intellectual knowledge, more fundamental critiques of our current dysfunctions, and clearer rhetoric so that he can lead more effectively from a position of greater authority, cutting through the clouds of chaff thrown up by incumbent interests. Trimming corners works much of the time, and pious hopes make easy speeches. But someone as talented as our current president can do better, and I hope he does.

• Charles Blow on Jews turning Republican. No wonder, as Israel loses the moral high ground and plumps for attacks and a new world war. That sounds Republican to me.
• Economics of the depression, here we come!
• Krugman really, really gets it. In fact, he gets it before it happens.
• Bernanke to Earth ...
• A little more on the real attitude of Pakistan, to the Taliban and Afghanistan.
• Some excellent reflections on the establishment and foreign policy.
• David Yost tells of himself.
• Bill Mitchell: No quote- rather, some ragged clips from his 80's Aussie reggae band.

Design-o-zymes

Interesting progress is afoot in designing enzymes from scratch.

While the vain, egomaniacal self-sequencing Craig Ventner has grabbed headlines for "creating life", more interesting and useful projects are afoot. While his employees have inserted a replica of a natural genome into an existing cell and gotten it to propagate, that was never an interesting problem. We have altered the DNA of organisms for decades through recombinant DNA technology. Whether replacing large amounts or small amounts, the true intellectual difficulty is not whether copied DNA can work in a host cell, it is how to design such DNA to do new things- making novel genes and gene networks that inform us about their biology, synthesize new chemicals, cure diseases, create truly new life forms, etc.

So I was far more impressed by a recent pair of papers in science about new successes in designing enzymes, in one case more or less from scratch and by computational means (accompanied by a review). It is the protein that is the main actor in cells and in life. Anything that needs doing in biology, from digesting food to lifting weights, is done by proteins. The only thing they don't do is store information for their own synthesis, and all the informational and catalytic tasks done by RNA.

Proteins are also dauntingly complex- little dynamic chemical packages that fold into intricate shapes and sometimes harness advanced quantum mechanics, (advanced for us, that is), like in the photosynthetic reaction center), to do magical feats of chemical transmutation. No wonder that it has been extremely difficult for scientists to consider themselves capable of designing new proteins- evolution has set the bar very high. Even understanding how existing proteins work has been hugely challenging. X-ray crystallography has allowed scientists to gain detailed pictures of protein structures, but these are static images. Much of the magic of protein action lies in their dynamics, where complex electronic surfaces and structural rearragements take place on a routine basis.

A classic example is myosin, which uses ATP to bend its head against actin to power our muscles, in a power cycle that has only recently been elucidated. But changes in shape are common, occuring also, for example, in hemoglobin as it picks up oxygen and then dumps it out in the peripheral tissues. These dynamic aspects, along with electronic and even quantum mechanical elements, have made proteins quite difficult to understand, and thus also to model and design for our own purposes.

Nevertheless, Siegel et al. decided to design a novel enzyme for a reaction that, as far as known, is not carried out by any biological enzyme- the joining of two separate molecules into one ring structure in a Diels-Alder reaction. Step one was to imagine the ideal transition state for the reaction- the structure of the reactants just as they cross the energetic divide between being unjoined and being joined. In organic chemistry, this state is typically promoted by using high pressure and exotic catalysts like niobium pentachloride. Enzymes do utilize a wide variety of metals, (like iron to bind oxygen in hemoglobin), but these workers wanted to start simple and begin with just protein-based building blocks. This involved using quantum mechanics and organic chemistry to model that state in terms of both its shape, the electronic fields that would stablize it, and some key hydrogen bond acceptors and donors that could help the reaction along.

Image of one designed catalytic active site (left) with the substrates in color.
At right, the scaffold's structure in green (right), and the designed changes shown in red.

Step two was then to attempt to design a protein which would supply a "pocket" that could fit that transition shape while allowing the reactants access and giving them extra assistance with properly shaped electric fields and hydrogen bond donors, etc. This was done using protein design software based on the relevant chemical principles. The hard part was then next to translate this small "pocket" design into a protein that could provide the backbone and folding to bring such a pocket together.

For this, they consulted a library of known small protein shapes, (which they called scaffolds), and chose 84 candidates for synthesis into proteins. This means that they read out the protein scaffold sequence, then superimposed their designed active site onto that sequence, substituting amino acids as needed in key places, (involving 13 mutations in one case), and lastly back-translated it all (conceptually) into the DNA of a gene they could synthesize on a machine. This DNA was then linked to a promoter that would drive its synthesis and inserted into the genome of a bacterium. They then grew up a bunch of these cells, popped them open and purified out the translated (actual) protein, and tested it for its ability to carry out the new Diels-Alder reaction.

What did they find? Only two designs had detectable, though paltry, enzymatic activity, with turnover of about 4 reactions per minute. Then they went back in, looked under the hood with their modelling programs, and made a few additional mutations on one of these candidates that then increased this catalytic rate a hundred fold. Not too shabby!

Schematic of the reaction and its transition state which was designed around.

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What these experimenters do not go on to do is harness the power of evolution to optimize their design. That is doubtless because they do not have a selective test for their reaction- i.e. a way for cells to depend on successfully carrying out this reaction which is not biologically significant. That could doubtless be arranged, but to show something of the sort, another paper in the same issue takes over the story.

In this case, industrial biochemists with a small biotech (Codexis) and partner Merck wanted a better way to perform a pharmaceutical synthesis previously catalyzed by rhodium under harsh conditions, by doing it with an enzyme. They were able to find an existing enzyme that performs a similar reaction (transamination) and used a bit of design, and a lot of mutagenesis and quasi-evolutionary selection to optimize it to industrially useful levels. A bonus of such a switch is that the new process is more stereo-specific, (as enzymes typically are), creating precisely the correct product, suffers from no rhodium contamination of the products, and can be done under mild conditions, rather than the 250 psi previously used. This is a good example of "green" chemistry.

In brief, these workers slightly opened the binding pocket of their candidate enzyme (from a soil bacterium) using molecular design software to allow it to have some activity on their chosen (unnatural) substrates. They then mutated the active site with abandon to find improved variants, and then finally unleashed the enzyme in more general mutagenesis + selection system to accommodate several other parameters needed for large-scale synthesis. This was done by creating libraries of mutated variants, (35,000 in all), and using industrial-scale screening to test each for its activity individually. They also optimized for performance in their chosen conditions of high substrate concentration and a high level of organic solvents- conditions that a natural enzyme would never see.

The result? An enzyme that is industrially usable, tens of thousands-fold faster than the original semi-designed natural enzyme, giving 100% correct product in 50% DMSO solvent at 40ºC with no heavy metal contamination and less waste and cost all around. While these researchers didn't use a true evolutionary system to optimize their enzyme, (it was not done in cells using an endogenous replication system), there are numerous ways to do this kind of thing, and the principle is the same- make lots of mutations, test them, then take the best candidates and repeat the process.

So, if you are after truly novel functions rather than vanity projects, focus on proteins- the workhorses of life- to do new and useful things. The ability to design truly novel molecular functions opens enormous vistas in both biotechnology and in the more heady project of tinkering with life itself.

• Krugman keeps getting it.
• A song for our times- Pieces of a man, by Gil Scott-Heron.
• How much does consciousness owe to language?
• The "ground zero" mosque debate: cynically divisive and unnecessary, except for Neanderthals.
• Bill Mitchell quote of the week, regarding public surpluses and supposed public saving schemes like Social Security:

"Thus the concept of a fiat-issuing Government saving in its own currency has no meaning. Governments may use their net spending to purchase stored assets (spending the surpluses for instance on gold or in sovereign funds) but that is not the same as saying when governments run surpluses (taxes in excess of spending) the funds are stored and can be spent in the future. This concept is erroneous. Please read my blog – The Futures Fund scandal – for more discussion on this point."

The policy is crazy

Pakistan literally has a policy of crazy, repelling everyone around it.

After being bamboozled for decades, the US is beginning to face up to the fundamental challenge of Pakistan. From its founding, Pakistan has employed its "tribals" to harrass, first India, and now Afghanistan. The policy is habitual and deeply intwined with its religious and political roots. Mohammad Ali Jinnah first created Pakistan as an extortion demand, saying in essence "Give us a rich slice of India, or you will have a civil war". Well, India still got an ugly civil war at partition as well as several wars with Pakistan since.

Why? Why all this crazy? The Mughal empire at 1700 ruled almost all of what is now India, Pakistan, Bangladesh, and Afghanistan. Empires in decline tend to have feelings of entitlement that can lead to lashing out. Muslims see themselves as a martial culture, (rightly so), and thus destined to rule over the vegetarian acolytes of the cow. At independence, Muslims couldn't psychologically deal with the prospect of no longer being in charge .. not even being used by the British as their cat's paws and administrators, but rather being swamped to insignificance in a democratic and majority Hindu country. The irony, of course, is that Pakistan has been perpetually politically dysfunctional; not capable of ruling itself, let alone anyone else, while India has become more stable with more durable democratic institutions.

Thus the rump Mughal mini-empire of Pakistan was born, founded as an Islamic state, a tenet of which is to wage Jihad, and not just the internal, meditative kind. Immediately, an irritant presented itself in the form of Jammu and Kashmir, provinces of the newly minted India that were majority Muslim (67%), but whose Sikh Maharaja, already under attack from Pakistan, decided to join India. The blatant insult of a possible province not seeking to join the already militaristic and dysfunctional new state of Pakistan was too much to bear, and Pakistan has continually thereafter trained, funded and made it a matter of official policy to destabilize and terrorize Jammu and Kashmir as best it can.

Why do its own people put up with this craziness? And more to the point, why do individual insurgents put their lives on the line for such a hopeless and frankly evil policy? Here we get to the true evils of religion, which can plant such certainty, such social solidarity, and such aggressive doctrine into the hearts of its adherents that they are usable for suicide bombing.

Fast-forward to the 1980's, and the interests of Pakistan and the US aligned fatally with the Soviet takeover of Afghanistan. Pakistan had the network of crazies, the US had the money and arms. A match made in heaven, at least as far as waging Jihad against the Russians. The US essentially endorsed what had become standard Pakistani policy for giving itself a feeling of security on each of its borders- behave like a nest of killer bees, ready to be stirred up at the least provocation and able to project force via the conveniently "ungovernable" terrain all about.

Friends? Who needs friends when you have terror on your side? Yet there was one thing Pakistan did need, which was money and military toys to keep its political elite in clover. The US was thus diddled along with promises of "cracking down" on terrorists, non-proliferation,  and being a strategic partner against the Soviets. Which was something of a live issue back when India had pro-Soviet sympathies and Afghanistan had been overrun, but no longer in 90's and after.

Once used to the taste of governing another country, (or at least de-governing one), via its Taliban friends and other networks of Jihadis, Pakistan was never going to give up willingly after the Taliban's fall and let the flowers of democracy bloom. All and sundry, including Bin Laden, Zawahiri, and Mullah Omar were taken in and nurtured in Pakistan, with a wink and nod. Selected individuals of US interest from Al Qaida were captured, but the infrastructure of the Taliban was never touched, and was even allowed to take over whole provinces in the northwest. What one might charitably call provincial autonomy in the tribal areas was studiously used as cover for a continuing policy of stabilizing the Taliban and destabilizing Afghanistan.

The sad part is that these countries had all the makings of great friends. Closely tied by culture, religion, geography, even blood and tribe, they could have been like the US and Canada, one the slightly more rural and nice version of the other. But no! Closeness can engender blood feuds and condescension as well. And, not to put too fine a point on it, the militarism of Pakistan means that its political elite sees its political stability built on outside threats and domestic fear, not on friendship and commercial progress. (Is this reminiscent of a recent US administration?)

Now the US and Pakistan have settled into a dysfunctional relationship, with the US never able to tell whether Pakistan's latest promises of virginity are any truer than its last. Would its behavior improve more if we cut the cord, sending Pakistan into a nuclear-armed renewed bitterness, or if we held Pakistan closer with "assistance" by which it is enabled into a quasi-stable and quasi-cooperative relationship?

The answer is obviously that the latter has not worked and will not work. On the street, Pakistanis are virulently anti-US. Pakistan continues to have a policy of destabilizing Afghanistan- indeed much more actively than Iran has dared to do in Iraq or Afghanistan. Pakistan continues its internal dysfunction, with a highly militarized political culture replete with corruption and callous disregard of its own population (especially its various ethnic minorities and "tribals"). Pakistanis routinely claim that they have borne the brunt of Islamist violence, and that is true. But it is only true because they have been playing with fire since their founding. Whether it is the fault of Islam itself, or its embittered historical legacy, Pakistan has brought that problem entirely on itself. Our role should be to contain it as much as possible and support its progressive institutions, but to not financially- let alone militarily- abet their militarism and their tragically short-sighted policies.

An interesting fact in the mix is that there is no formal border between Afghanistan and Pakistan. Pakistan's military rulers have found it convenient to keep the area porous and putatively uncontrolled, while Afghans have in principle opposed dividing the Pashtun people. It may be time to turn this state of affairs to advantage by breaching the Drurand line, taking some of this territory for Afghanistan and uniting the Pashtuns, while at the same time bringing these tribal areas under better (Afghan) government. As things stand, these border areas of Pakistan (the Federally Administered Tribal Areas, or FATA) have been put explicity under Taliban rule via active Pakistani policy. Obviously, this is untenable for both Afghan, US, and global interests, not to mention the locals who have been either cowed or executed. Taking the fight to the FATA in person, rather than solely via drones, would be a logical step in light of the perpetual duplicity, not to say hostility, of Pakistan (and might be quite a morale builder for Afghanistan besides). Then Pakistan could decide whether it really wants a war against a country with which it could have very friendly relations, or will accede to better administration.

My prescription would thus be to double down on Afghanistan, strengthen ties with India and Russia, and treat  Pakistan as it has asked to be treated- with some hostility. We should cut our aid and assistance (certainly military) while offering the prospect of better relations when Pakistan's political elite decides to grow up. Would we lose what help Pakistan now gives us? Probably yes- all our shipping-based supplies to Afghanistan go through Karachi/Quetta, and we have various secret military bases in the country, as well as implicit drone attack rights and some intelligence assistance against Al Qaida. So this would not be a minor loss. But what does it help us to get logistical support from Pakistan if we are fighting Pakistan at the same time?

Might Pakistan be driven into the arms of, say, Iran or China, to form a new axis of the disgruntled and misunderstood, not to mention the Jihadi? That would be a likely outcome, seen in formal terms. Our policy towards Iran and Pakistan should really be similar- friendly to their people and their progressive sectors, but awaiting maturity and reciprocity instead of giving gratuitous aid to their retrograde leaders. Pakistan would need a friend somewhere to fend off encirclement by the many powers who just "don't understand". But at some point, one wonders whether they might find it within their power to take a look within and do the hard work of psychotherapy/demilitarization/de-Islamization ... and realize that the enemy was never outside to start with.

Here is a quote from a recent Pakistani newspaper commentary, showing typical narcissistic victimhood, not to mention a unique brand of English:

"Besides the physical threats to security of Pakistan emanating from multiple directions, Pakistan has to contend with never-ending vicious propaganda campaign launched by Indo-US-western-Israeli-Afghan nexus to demean Pakistan and its premier institutions."

• The Pakistani-India border dance, complete with coxcombs.
• A fine book on the topic excoriates all concerned, especially the US, as if we were supposed to save the "region" from its own immaturity and dysfunction.
• In the meantime, Pakistan needs some help!
• Banking with squids.
• Class war could hardly be more obvious, could it?
• The "Discovery" institute seems incapable of learning, ironically.
• Sphagnum  moss ejects its spores at 32,000Xg.
• A fascinating graduation address.
• Bill Mitchell quote of the week:

"But the US political scene is even more moribund than ours if that is possible. Even the progressives are claiming there is a fiscal crisis. The facts speak otherwise."...

"So the only “deep hole” I can see in the US is the gaping real GDP gap and the resulting and shocking labour underutilisation data. Which sophisticated nation thinks it is acceptable to have 16.5 per cent of your willing labour force idle in some way or another? Answer: None. Only a nation operating under the destructive spell of neoliberalism would envisage making such a situation worse by cutting back the very thing that is maintaining growth at present."

Petr Kropotkin: biologist, anarchist

Petr Kropotkin takes on Darwin, Huxley, Spencer, Victorian anthropology, and the state, in his humanist tour de force- "Mutual Aid".

As the long night of Boshevism set in, one of the last free acts of the Russian people was the mass public funeral of Petr Kropotkin, beloved anarchist and biologist, in 1921. In 1920 he had sent a prophetic letter to Lenin:

"I have read in today's Pravda an official communique from the Council of the People's Commissars, according to which it has been decided to keep as hostages several officers of Wrangel's army. I cannot believe there is no single man about you to tell you that such decisions recall the darkest Middle Ages, the period of the Crusades. Vladimir Ilyich, your concrete actions are completely unworthy of the ideas you pretend to hold. ... If you admit such methods, one can foresee that one day you will use torture as was done in the Middle Ages."

And this was only one small incident, out of the many (including setting up the Cheka) by which Lenin betrayed the idealism of anarchists and others across the political spectrum to create the system that flowered so fully under Stalin. Kropotkin himself had worked towards liberal democracy in Russia, and had been offered a government position by socialist revolutionary Alexander Kerensky during the ill-fated 1917 interregenum.

When one thinks of anarchism, one usually thinks of obscure bomb-wielding cells and loners bent on nothing but destruction. Something like Ted Kaczynski, perhaps. A bizarre utopianism blind to the need for common refuge in law and state. Advocates of chaos rather than order. One wonders, then, how they could have been so influential at the turn of the last century- why anarchists were one of the prime parties in the Russian revolution and in the Spanish revolution and the fight against Franco, actually governing some regions, such as Barcelona, as narrated by George Orwell.

Part of a collection of posters from the Spanish civil war.  The text announces that the poster was produced by the anarcho-syndicalist trade union Confederación Nacional del Trabajo (CNT) in conjunction with the international anarchist organization Asociación Internacional de los Trabajadores (AIT).

The activating impulse of anarchism was of course far more subtle and interesting, and it is laid out in fascinating detail in "Mutual Aid". Petr Kropotkin, raised in a loving home at the highest levels of the Russian nobility, was a biologist and geologist first, and later took up anarchism. His many field trips through Siberia taught him about both the animal and human landscape, convincing him that in the battle for survival, banding together was one of most important resources for any species.

Kropotkin (engaging in what he calls an "embryology of human institutions") insistently points out the degree to which animals including humans are naturally communal and sympathetic, ranging from societies of ants to self-organized guilds of medieval craftsman and even to the nagging consciences of the super-rich who are moved to feats of philanthropy. He is careful to not dispute Darwin directly, respecting the fundamental principles and observations put forth in Darwin's works (which is itself remarkable, since Darwinism was subject to a great deal of scientific and popular derision in his era and the ensuing several decades). But he emphasizes non-antagonistic aspects of biology, and excoriates Darwin's followers, especially Thomas Huxley and Herbert Spencer, who, using mantras like "nature, red in tooth and claw", carried water for the political and racial elites of their day.

The Victorian era, both in Europe and in the US, saw a frenzy of self-justifying theories of white superiority, and a glorification, nay a need, to defeat "inferior" races and nations supposedly in fulfillment of Darwin's theories. Needless to say, Darwin himself would have taken a dim view of all this, since, horrifying as natural selection was on the grand scale, it was never conceived as a normative project for human morals, but as a description of biological reality. Humanity's job, the more enlightened Victorians thought, would be to get as far away from these "natural" morals as we possibly could, with the aid of stern moral training and plenty of psychological repression.

Kropotkin's project is to show that even this view is off the mark. Humans have formed societies spontaneously from time immemorial, and help each other the more heroically the more dire their circumstances. The natural setting of humans is the tribe or clan of 50 to 150 individuals, not the nuclear family of today, and certainly not the war of all against all. His point is that evolution has fitted all advanced social species with powerful pro-social inclinations (and concomitant high intelligence) by which they naturally engage in mutual aid, whether it is birds anxiously alerting each other to danger, chimpanzees tenderly taking care of each other's grooming, or humans taking in orphans after another family's catastrophe. "In the great struggle for life .. natural selection continually seeks our the ways precisely for avoiding competition as much as possible."

The importance of this message becomes clear when one hears anthropologists routinely describe people living in what we regard as primitive tribal societies as the happiest people on earth. I have previously blogged about the Amazonian Pirahã who exemplify this state. Their life seems to take us (well, them, really) back to the garden of eden- a time of deep contentment when the tribe was everyone's focus, sharing was the theme of adult and child life, and the serpent of greed was kept at bay. No state or bureaucracy is required to maintain this society- it is spontaneous and eternal, though capable of being poisoned by modern encroachment, as well as subject its own endogenous, though rare, wars.

Kropotkin makes it clear that this ideal is what he as an anarchist has in mind- the spontaneous organization of tribes, villages, neighborhoods, guilds, clubs .. all the most fulfilling parts of the human condition are his goal, while the state (more or less totalitarian in his European experience) is the enemy, with its overbearing destruction of competing social organizations, its promotion of social atomization. This atomization, where we typically find ourselves living in nuclear families (or even alone) in the modern world, is just as much a target of anarchists as the state. They are two sides of the same coin, expressing the same alienation from our true social and psychological inheritance.

"Unbridled individualism is a modern growth, but it is not characteristic of primitive mankind."

The greatest example of biological mutualism was only fully understood after Kropotkin's time. That is the banding together of individual cells to form animals. From extremely modest beginnings, this form of mutual aid society, extending eventually to the routine suicide of individual cells during organismal development and self-defense and whole bodies slaughed off after reproduction, now rules the world, having opened vistas of ecological possibility unimaginable to our witless single-celled forebears.

And that is the real secret of mutual aid- that helping each other not only helps each individual weather difficult times and thus gain fitness, but also opens new niches and ecological possibilities unavailable to individuals. It clearly supports the concept of group selection, which is a very large topic in itself. Mutual defense is particularly powerful against threats from outside the group, whether from other groups in the same species, from other species, or from the elements at large. Conversely, a war of all against all leads quickly to one of those Shakespearean plays where everyone ends up dead on stage. Not a very successful outcome, if maybe an effective piece of moral instruction, so vital in our greedy age.

"In short, neither the crushing powers of the centralized State, nor the teachings of mutual hatred and pitiless struggle which came, adorned with the attributes of science, from obliging philosophers and sociologists, could weed out the feeling of human solidarity, deeply lodged in men's understanding and heart, because it has been nurtured by all our preceding evolution."

In biology, Kropotkin was a visionary, as altruistic aspects of our social nature and that of other organisms are still regarded as pathbreaking areas of research (as I have blogged about previously). Only now is the evolutionary community coming to a better realization that altruism is not foisted on us by god or indoctrination, but is built deeply into our software, and has been forever. While Kropotkin focuses entirely on the positive, in order to reply to the Victorian triumphial tide of "Social Darwinism", it is important to allow that our situation is conflicted, as reflected in the recently coined term "frenemy", which signifies that we have both competitive and mutualistic impulses, perpetually intertwined.

"As to the intellectual faculty, while every Darwinist will agree with Darwin that it is the most powerful arm in the struggle for life, and the most powerful factor of further evolution, he also will admit that intelligence is an eminently social faculty. Language, imitation, and accumulated experience are so many elements of growing intelligence of which the unsocial animal is deprived. Therefore we find, at the top of each class of animals, the ants, the parrots, and the monkeys, all combining the greatest sociability with the highest development of intelligence."

Taking all this up to the current era, Kropotkin devotes several chapters to the wonders of the medieval guild system, the free merchant city, and their relentless destruction by centralized states, royals, and religious empires. From a military perspective, royal and non-royal states were not defensive-minded social clubs like the guild-based civic militas, but were predatory and eager to make war on others, usually destroying the many benefits piled up in peaceful times by the mutual aid societies of day-to-day life.

An Amsterdam civic militia, by Frans Hals.

Kropotkin was incidentally visionary in his view of history as well, remarking that while historians concentrate on the dramatic bloodbaths of past conflicts, they would do well to pay closer attention to the intervening times of peace which are more reflective of core human values as well as creating the wealth that those headlining battles tussle over.

Speaking of the loving craft that medieval guilds devoted to their cities, Kropotkin quotes: "'No works must be begun by the commune but such as are conceived in response to the grand heart of the commune, composed of the hearts of all citizens, united in one common will' - such were the words of the Council of Florence;" 

He then transitions to the labor struggles of his time and the debasement of human values in capitalism. While a great deal of amelioration has since taken place in the developed world, with milder democratic states becoming the rule, his point still holds. It is well-illustrated by BP executives paying each other millions of pounds while patronizing the "small people" on the US Gulf. Modern capitalism relies completely on the natural inclination of its workers to be "team players" while at the same time systematically underpaying them and callously discarding them when convenient in our system of "at will" employment. Managments and boards routinely betray their fiduciary, not to mention ethical, responsibilities by essentially embezzling the riches that they were hired to tend.

This situation is frankly feudal, and it is time to reconsider whether we can make more of human potential by taking a page from the book of human nature. That is, by organizing companies as true "teams" where all members share and share alike, starting with being paid the same, having open books, and having democratic governance.

Lest this be considered starry-eyed liberalism, the anarchic impulse cuts across today's political spectrum. While Democrats labor to make of the state a more supportive, equitable, and sharing institution, Republicans aim to shrink the central government, in hopes of reinvigorating community-level institutions. Thus their mantra of state's rights, local charity, and private initiative. We can argue about which approach is more fair and effective, not to mention beset by ulterior and lesser motives, but it seems as though each party has an implicit vision of improved mutual aid, (i.e. the common good), that drives its ideology. Ironically, the mantra all politicians agree on- that the families are the bedrock of America- is one that is somewhat suspect from Kropotkin's perspective, however, since it really does take a village, not just a family.

Lastly, to bring this discussion full circle, these concepts have some application to Afghanistan, whose clan-based social structure is closer to our evolutionary origins than it is to modernity. Modernity is sure to extinguish the Afghan's age-old freedoms, traditions, and insularity, justifying their deep fears. Freedom to oppress women, freedom to engage in blood feuds and impromptu wars, freedom to run their valleys and villages as theocracies, freedom to terrorize the entire world if they so desire. Well- perhaps there are limits to my & Kropotkin's valorization of the primitive tribal state. Or perhaps Islam promotes an ugly trough of medievalism situated between the high points of true edenic tribalism and modern democracy.

At any rate, traditional social systems have many virtues, and we should not aim simply to blow them up. Better to adapt our aims, while creating a better form of modernity that might be more naturally attractive. To be specific, Afghan provinces and localities need more autonomy, so that they can, for instance, elect their own governors. Strong central government is neither operationally practical, nor theoretically desirable in this setting, beyond the red lines of preventing civil war and Talibanization. Governance, as always, should come from the bottom up.

"New economical and social institutions, in so far as they were a creation of the masses, new ethical systems, and new religions, all have originated from the same source, and the ethical progress of our race, viewed in its broad lines, appears as a gradual extension of the mutual-aid principles from the tribe to always larger and larger agglomerations, so as to finally embrace one day the whole of mankind, without respect to its divers creeds, languages, and races."

• Incidentally, a book on Kropotkin's era has recently appeared.
• Please fight lead poisoning of humans and wildlife.
• Krugman keeps getting it. Does anyone listen?
• America's climate shame just keeps on going.
• "There is now only one bluefin left for every fifty that were swimming in the Atlantic in 1940."
• Are you getting married?
• Bill Mitchell takes on the Japan problem, which looks like where we are headed.
• Bill Mitchell quote of the week:

"One of the major agendas of the neo-liberal era has been to disabuse us of this care for others ....

In effect, the austerity push is based on ideology – on the view that private markets will self-correct and if charity is required it will come from private citizens. The anathema to the austerians is public welfare and fiscal support for the disadvantaged ....

There is a long lineage to these ideas. Greenspan’s blind faith in the market was inspired by his mentor Ayn Rand. Would Greenspan care about the unemployment now? I doubt it.

[quoting Ayn Rand:]

'As to altruism — it has never been alive. It is the poison of death in the blood of Western civilization, and men survived it only to the extent to which they neither believed nor practiced it. But it has caught up with them — and that is the killer which they now have to face and to defeat. That is the basic choice they have to make. If any civilization is to survive, it is the morality of altruism that men have to reject …

Make no mistake about it — and tell it to your Republican friends: capitalism and altruism cannot coexist in the same man or in the same society.

Tell it to anyone who attempts to justify capitalism on the ground of the “public good” or the “general welfare” or “service to society” or the benefit it brings to the poor. All these things are true, but they are the by-products, the secondary consequences of capitalism — not its goal, purpose or moral justification. The moral justification of capitalism is man’s right to exist for his own sake, neither sacrificing himself to others nor sacrificing others to himself; it is the recognition that man — every man — is an end in himself, not a means to the ends of others, not a sacrificial animal serving anyone’s need.' "

And, as if to prove the point, Greenspan has just come out with an austerian rationale for canceling the Bush tax cuts. One doesn't know whether to laugh or cry.

Watching the evolution knobs spin

Evolution really happens at the dials controlling genes, more than in protein sequences those genes encode.

The shock of humans having only ~23,000 genes has yet to fully sink in. Fewer genes than soybeans? Than the potato? Additionally, the depth to which some of these genes are conserved is also astonishing, with a promoter of eye development working quite well when transplanted into fruit flies. What, then, makes us different? What has evolution been doing all this time?

A recent paper in science adds evidence that far more variation goes on in the promoters of genes than in their coding sequences. The authors tracked the sites of action (i.e. DNA binding) of two liver-specific transcription regulatory proteins in chickens, opossum, mice, dogs, and humans, and found that few  were recognizably conserved. Most sites disappeared, reappeared, altered, and mutated with considerable abandon.

The regulators themselves (CEBPA, and HNF4A) were very well conserved, meaning that as proteins, they had virtually the same sequence in each organism. And more critically, their preferred binding site on DNA stayed the same as well. That tends to be hard to change if their binding to thousands of different sites (~20,000 is the estimate given for each protein) is important for an organism's liver and other organs. Putting it in technical terms, such binding specificities tend to be subject to strong purifying selection.

On the other hand, the individual sites are much less constrained by evolution, since changes affect only that individual target gene. Some genes that have been studied as targets of CEBPA include metabolic enzymes, detoxifying enzymes like cytochromes P450, EPHX1, and SULT2A1, several insulin-regulated genes, growth factors, the gene for albumin, coagulation factor VIII, and other transcriptional regulators in liver development and function.

The current authors use some high-tech wizardry to isolate all the DNA bound to these regulatory proteins from each species of interest, and sequence around each site to see where it maps in the respective species' genome. This gives them the dataset of sites that they then mine to ask whether the sites have stayed consistent over evolutionary time. The answer is no: "For these two liver-specific TFs, binding events appear to be shared 10 to 22% of the time between mammals from any two of the three placental lineages we profiled, separated by approximately 80 million years of evolution (figs. S6 and S7). This result reveals a rapid rate of evolution in transcriptional regulation among closely related vertebrates."

For example, they show the binding of CEBPA to one region around the gene for PCK in liver. Phosphoenolpyruvate carboxykinase is a metabolic enzyme which helps synthesize glucose.

The coding exons of the PCK1 gene are shown at the lower right. kb = kilo basepairs. Hsap = human, Mmus= mouse, Cfam = dog, Mdom = short tailed opossum, and Ggal = chicken.

The pattern in chicken is quite simple. More sites appear in the mammals, with novel and significant sites appearing in dogs and humans. The scoring of these sites is somewhat unclear, in terms of how minor a site could be and still score, not to mention that they had no functional tests of which sites actually affected local gene transcription.

A key and well-occupied site right at the start of the PKC1 gene is well-conserved, however, and probably has a dominant regulatory role. What role the other sites might have is not clear, and might be minimal. So their  conclusion needs to be taken with a bit of salt, as they indicate that most of the highly conserved DNA binding sites are at this kind of most-influential position near genes that rely heavily on regulation by the bound regulator.

Nevertheless, the reason for flexibility in regulator binding is not hard to find, since binding sites are often composed of only six or eight nucleotides, with sloppy allowances for binding to sites with some mutations as well. New sites can appear easily, and old sites can be destroyed just as easily. So these regulatory proteins bind all over the genome and these sites change frequently, allowing regulatory variation to happen easily by mutation. The authors conclude "Taken together, the steady accumulation of small changes in the genetic sequence appears to rapidly remodel thousands of TF binding sites in mammals." [TF refers to transcription factor, another word for DNA binding regulator].

Given the complexity of biology, the network is the real locus of evolution, with the pieces (proteins encoded by genes) being shuffled around by regulatory experiments over time. Indeed, another recent paper compared the multicellular organism Volvox with its single-celled relative Chlamydomonas, and found that they had almost exactly the same number of genes, and few gene differences overall. They conclude: "This is consistent with previous observations indicating co-option of ancestral genes into new developmental processes without changes in copy number or function." And one of the most important mechanisms of such co-option is placing the given gene under novel regulation. This process is slightly reminiscent of the human economy, which is being driven increasingly as a "knowledge economy", shuffling around financing, software, and organization while the basic commodities of existence remain far more constant.

• Free will, explained. (Only in part, however.. it leaves out our moral responsiveness to others.)
• A judicious analysis of the wikileaks doc dump.
• The Taliban is getting desperate and may be in decline.
• MMT economics in a nutshell.
• Walter Mead pens an uncharacteristically idiotic screed against the greens. As if "prohibition" were being proposed by anyone, anywhere. Note the mash note to fellow anti-green Andrew Revkin.
• Meanwhile, yet another CO2 related apocalypse rears its head.
• Bill Mitchell quote of the week, speaking of Minsky's model of financial cycles, requiring broad anti-cyclical policy as well as (right now) government stimulus:

"Through phases of recession, recovery, tranquility, and euphoria, the economy endogenously moves from robust to fragile financial structures. The fragile structure characterised by high levels of speculative and Ponzi finance becomes vulnerable to a multitude of shocks, any of which, in isolation or concert, can alter perceptions of future income flows needed to validate the debt structure and drive the economy into crisis."

Mind of matter

I propose a tentative model of qualia and consciousness.

A rich thread of comments over at another blog motivated me to tackle the problem of consciousness with as much specificity as evidence currently allows, including the voluminous evidence for its material basis. So here I try to lay out a plausible model of fully brain-based consciousness, to address the dualist, who typically says that he or she can not imagine any material basis to consciousness, and even claims that there is some kind of philosophical necessity that the "hard problem" of consciousness is beyond scientific analysis entirely. (I have previously written about the neurobiology of consciousness, which remains unresolved.)

As a philosophical naturalist, I would predict that no new physics will be required to resolve the consciousness problem (such as 5th dimensions, quantum consciousness in microtubules, etc.). It is pretty clear that the brain is a messy product of evolution and works by electrochemical / molecular mechanisms. It is encoded by DNA, bounded by physical space (the head), and is affected at all levels by known lesions, chemicals and other effects. Nothing more esoteric is likely to show up in its study, other than incredibly intricate organization, which we still have great difficulty analyzing as a purely technical matter.

That leaves us with either an identity position that dualists don't seem to understand, (that there exists some brain-based processes that are objective physical events and also constitute subjective consciousness at the same time), or an eliminativist position, which we all dislike (that consciousness doesn't really exist). The problem may go away, but surely not by claiming that we have no consciousness after all. Indeed, the fact that there are unconscious processes that include forms of perception, intuition, and many other computations means that there is some real distinction between things that are unconscious and those that enter consciousness, and thus that consciousness is not an epiphenomenon or semantic issue.

So I should explain the identity position a bit better, despite the admitted lack of a real scientific solution in place.

Everyone has heard about continuity in movies- the need to keep hairstyles constant, props in the same places, etc. even when a shoot of one scene goes over several days, so that the illusion of continuity is preserved. I think this is a big clue to consciousness, which could be thought of as consisting, in part, of a brief memory loop that keeps our experience continuous. The ability to associate a split-second ago with now gives us not only a sense of time, but of consciousness itself, since otherwise we would be bombarded by what seem random stimuli, uncontrolled, uncorrelated, and meaningless.

So that is part of the answer, which can be easily imagined to be embodied by the gamma wave system in the brain that is the humming in-phase communication of ever-changing coalitions of neurons from all over. This would be the perfect system to glue together percepts and mental contents while giving them limited continuity of a fraction of a second, some of which is then stored to short-term memory, which is so notoriously poor, (hippocampus), some of which is stored in turn to longer-term memory (frontal cortex). Recalling something from memory weakly re-creates the engram (gamma pattern) that was originally driven by the perceptual system, and engages the same consciousness system, though with much lower intensity and different feel. We need a prompt like a smell or madelaine to assemble the engram again more fully, though it is never again quite the same as the first time in any case.

But we still have not gotten to the heart of the issue- the redness of red. We know that lesions like strokes can cancel out perceptions very selectively. There was a recent New Yorker article on the inability to read words while having unimpaired vision- an amazingly specific stroke effect. But the funny thing is that the sufferers routinely have to deduce their deficits. If something is missing, even something like half the visual field, we are not notified. The consciousness system soldiers on as though nothing has happened, forming an impression of the world that feels complete out of all the remaining bits and pieces.

Thus consciousness is very grade-able, both among humans with various talents and deficits, and among animals with different senses and brain sizes, as well as within one person in different moods, states of sleep, Dilbertian meetings, etc. It is also the kind of system that presents whatever comes up and doesn't care about what is missing. This again fits the gamma wave system, which wouldn't join up nerves that were not firing, but would just assemble whatever forms a minimal coalition of activity. And lastly, I'll make a stop at synesthesia, where one sensory modality bleeds into another, for instance inducing people to perceive certain numbers as having particular colors wherever they appear. The cause seems to be a literal mixing of neurons in relevant areas of the brain, which has obvious selective implications, both for problems arising from extensive wrong-wiring, and for the possible creativity and special perceptual powers that might result from limited cross-wiring.

What is red? Remember that red is a complete fabrication- our brain's way of mapping qualia to what in physics are numerically different wavelengths of light. The brain can apparently make anything it likes of the stimuli coming in. We should not be surprised if bats see their sonar world in living color as well. The question is why red feels so immediate, and what transaction actually occurs between red and "our perception" of it. In other words, what is the difference between unconscious and conscious information processing?

The difference seems to lie in entry into a privileged process in the brain, such as perhaps the gamma wave system. Other areas of the brain may talk to each other and process information, but that does not enter consciousness. Whatever does enter consciousness comes from relatively high level areas of processing, by virtue of the brain's wiring, which mostly flows from inputs (signals from the eye) to higher levels of processing that are biased towards participating in these gamma wave coalitions (analyses of shape, object identity, face identity, motion, etc.). Some people such as artists may able to "see" a scene without a lot of computational processing and overlaid interpretation, but as it is at a more basic sensory level, implying that they have conscious access to unusual levels of processing.

So consciousness is a part of a unique level of processing, where interpretations are collected and cross-correlated and learned from. Why does that feel real as unconscious processing clearly does not? Incidentally, unconscious processing may be just as complex, as we learn from our social intuitions, which can be incredibly spot-on and discerning about situations we have given little conscious thought to. Dreams also point to enormous depth and richness to unconscious processes, so it may be a mistake to put all this in some kind of higher/lower hierarchy.

A sense of reality may in this theory be the product of pure associational power- the construction of a sufficiently complex and rapidly integrated virtual world becomes what we call consciousness. If everything we see instantly generates a map of spatial, social, artistic, analytical, and other associations, that alone gives the scene "reality", immediacy, and red-ness. Seeing red becomes conscious not through some magical or impossibly recurrent homunculus behind our eyes, but by its particularity in contrast to other sensations and its web of immediate associations with the vast arrays of implicit and explicit knowledge we carry around in the database of our heads.

Suppose you were to see a uniform field of red all the time, day in and day out. You would no longer be conscious of red at all. You would not only be seeing the world through rose-colored glasses, but be seeing only the rose colored glasses and nothing else. Had you no other senses, you would probably lose consciousness altogether, a sensory-deprived victim of extreme torture. But of course we have many other senses- sound, smell, touch, and several newly discovered ones, such as body and spatial sense and the like. We also have dreams- the ability to draw on our voluminous past sensory impressions and their plastic re-arrangements in imagination. So it is literally impossible to do this kind of experiment.

This theory can account for the graded-ness of consciousness, its natural development through evolution, its materiality, and in addition provides a program for the instantiation of such experiences in artificial systems. It informs the common observation that high-level consciousness is dependent on knowledge, such that the study of art history gives us new eyes in museums, and the study of biology gives us new eyes in nature. It also provides a program for the study of consciousness, since its physical correlate should be quite discrete and find-able (by the identity theory mentioned above). It is in the correlation of subjective consciousness to this postulated physical correlate that the test will be found, either confirming detailed correspondence, and driving other theories to extinction, or not.

Lastly is the issue of emotion and pain. The above theory deals with cognitive consciousness, like *appreciating what red is in an immediate way. Emotions are simpler, not necessarily association-based. They are prior to high-level cognition. Past pain is certainly a strong spur to current aversion by association, but how did past pain happen? How was it perceived? There is something elemental and not associative about raw emotions like pain, which form perhaps our first and most traumatic form of consciousness.

Pain can function without consciousness at all. We typically notice that we have pulled our hand from the fire after the deed is done, and wonder at the reflex. But pain can also flood consciousness, issuing its imperative command to fix whatever is wrong. Similarly, other emotions typically operate below consciousness, to the point that our partners are often more familiar with our tics, mannerisms, and broadcast emotions than we ourselves are. As above, the cognitive contents of emotions can be characterized as associative, (what hurts, who did it to us, what is causing pleasure, etc.), but emotions carry extra contents injected alongside as the valence of the pleasure or pain- the command by other systems of the brain that this is something to be done again, or never again.

So it is no surprise that consciousness seems to be a complicated system, requiring rapid and  wide-spread associations to provide the brute contents and textured differentiation of cognition, as well as a brief memory loop that gives continuity to experience. Emotions are injected as extra cognitive contents and feelings, using specially responsive brain areas that date from early evolution and provide more than information: motivation.

I have tried to present a model that is plausible given current evidence, though obviously not very detailed. While there is plenty of circumstantial evidence that something material and eletrochemical in the brain is responsible, it will take a few decades yet to fill in those details.

• Theologians working at public universities find it getting hot under the collar.
• Can you lose your sense of smell? 
• A billion dollars here, a billion dollars there...
• One gets the impression that Hamid Karzai doesn't know much about power.
• Though his isn't the only government beset with unaccountable bloat and corruption.
• An interesting reflection on the worth of work:

".. while collecting salaries of between £500,000 and £10 million, leading City bankers destroy £7 of social value for every pound in value they generate." ... ".. for every £1 they are paid, childcare workers generate between £7 and £9.50 worth of benefits to society."

• The financial industry needs a transaction tax.
• Wear a Pink Sari and Carry a Big Stick.