Communism 2.0

An attempt to get at the kernel of communism, and what we might make of it today.

"In the individual expression of my life I would have directly created your expression of your life, and therefore in my individual activity I would have directly confirmed and realised my true nature, my human nature, my communal nature." - Marx, on free production

After studying the biography of Leon Trotsky, one question remained- what on earth actuated such sustained and apparently blind devotion? What was the motivating core of communism that could move so many to such sacrifice, even accepting that there were many opportunists who saw in this new religion (as is ever the case) a means to power?

An off-hand comment by Trotsky, mentioning the ruins of the slave civilization of ancient Greece, struck me as illuminating the whole question of what was going through their minds. Marx was calling his time to a new consciousness of iniquity, which we have yet to fully appreciate, as we still live within the tenets of the capitalism.

Slavery in antiquity was accepted as the natural course of affairs. If one's gods failed to keep the city, if one's army turned and fled, if one's debts rose over one's head, or if fate was otherwise unkind, slavery was one of the natural (and remorselessly Darwinian) consequences. Slavery was not individually an unalterable condition, as occasional slaves bought their way back out of slavery, or rose to high office and respect. But no one thought it was an unnecessary or optional institution. Even the Christians who took in slaves as fellow worshippers had no special animus towards the institution- because they didn't see it as an institution, but as part of the normal course of affairs, now and forever.

This tendency to take for granted the system one lives in is natural enough, and comes to mind now, after free-market-ism, Republican jingo-ism, and capitalist / managerial greed-ism has come under a cloud. Now that the various communisms of the twentieth century have definitively all imploded or petered out, perhaps we are freer to look around without fear at the warts of capitalism and consider whether there is a better way to live than this one we take as natural.

Communism in its original incarnation was a direct comment on the new slavery of Marx's time- the Dickensian horrors of early/middle capitalism, much like what China is experiencing right now, ironically enough. Marx decried the dehumanization, the regimentation, and the rank oppression of his day, and thought that the new concentration of labor engineered by capitalism was propitious for political and social action against that system.

Such action, whether taking revolutionary color, or the modest shape of labor unions, struck fear into the hearts of capital, prompting counter-revolutionary propaganda that continues to this day, celebrating the US as the home of freedom, contented capitalism, God, and apple pie. It led to substantial progress in working conditions and in wages, especially from the New Deal through mid-century; progress that is eroding continually.

That much is obvious. So where are we today? Is capitalism the natural and default condition, or is there there something better that we can imagine?

At this point, I was going to present a model of an equal-wage economy, where everyone was paid the same, eliminating much of the alienation and competitiveness, leading to greater workplace and cultural cohesion. Unfortunately, there are serious defects with such a model, especially in combining it with free buyer markets, capital mobility, and other freedoms, which is in some part what the Soviet Union found as well (though in a radically different context). Such a blanket form of egalitarianism, while an interesting thought experiment, has to be approached in a more gradual fashion, much as we have in the US through tax-based redistribution, and as the quasi-socialist economies of Scandanavia have come close to achieving.

The point, of course, is that salary pricing in the labor market is both grossly inefficient, (witness prices paid to spectacularly incompetent managers as a matter of course), fundamentally dehumanizing / devaluing, and also largely unnecessary, since positive human motivation arises mostly from other factors such as status, personal relations, and intellectual interest, not money. Places like Japan manage to have prosperous economies and civic cultures with far less monetary inequality. Indeed, in my ideal world, the people with the worst jobs (maids, garbage men, farmers) would be paid the most, and those with the most satisfying jobs (CEOs, academics) would be paid the least, while the labor market would be far more transparent and active than it is now, based on interest and working conditions, not pay.

In this way, wage slavery would be ameliorated and human values propagated, while preserving the many other freedoms essential to civic and economic prosperity. Such a broad program would be more interesting and effective than the labor movement, since labor routinely descends into simple greed of its own, whether it is the featherbedding of longshoremen who hold our ports hostage, or the staggering pension debt (estimated at a half-trillion dollars unfunded for California alone) of public employees unions extorted by their political clout. While they did "bring us the weekend", those days of general civic benefit are long gone.

So I see the true legacy of communism as living on in the gradual democracy-to-socialism spectrum of Western political systems, which have substantially corrected many of the deficiencies of early capitalism, (though not in the West Virginian coal mines, apparently), but still have a long way to go to reach a fully humane social system- one which allows people to express their talents and productive motivations in a truly free way.

• Not to mention that prosperity and freedom promote atheism.
• Regulatory postmodernism and Schrödinger banks. (My understanding is that the decline of Rome was far more gradual than portrayed here, indeed almost imperceptible to its subjects. Still, an interesting post.)
• Relink on Krugman and the climate- absolutely imperative reading (and doing). With all the economic analysis, the even more important and deeper reason for resolving climate change is moral- to leave future humans (and other biosphereans) the kind of healthy planet that was left to us. 
• Humans have removed 90% of large fish from the oceans. That is not decimation, it is extermination.
• And the current sea level rise predictions.
• Funny discussion of our energy future.
• Feynman on the ultimate answers.
• Republicans show their colors.
• Still a long road in Afghanistan.
• Bill Mitchell quote of the week:

"One could also argue that the introduction of a tax in the first place is oppressive. It all depends on how you define oppression. It is oppressive to have red lights at intersections and fine people who disobey them. But the benefits of safety and relative certainty on the roads easily offsets this invasion of our liberties. It is all about judgements we make about the “efficiency” of living together."

...

"I have seen no credible research that suggests that private rates of return in nations that have larger public sectors are lower than otherwise. But I have seen a lot of credible research that shows that reduced inequality in income distributions is a positive fillip to economic growth rather than the other way round. Nations that impoverish vast masses of their population waste the greatest potential they have – the capacity to work and achieve."

• And another outstanding Mitchell blog takes the long view on financialization and intergenerational policy.

"The crisis has it origins back in the 1970s when the OPEC oil price shocks led to a change in the dominant macroeconomic paradigm from Keynesian to Monetarist (which has morphed into other schools of thought just as evil). In this broadly neo-liberal era, the fundamental changes to the distributional system – via the attacks on unions and the redistribution of national income to profits was a fundamental building block of the current crisis. For it presented the capitalist system with a realisation problem.

If you are going to cut workers wages and entitlements and keep real wages subdued while productivity growth was strong then how were the goods and services being produced going to be purchased and consumed? Answer: bring in the financial engineers who loaded the workers up with debt."

The curious case of Japan

According to the deficit terrorists, Japan should be going down the drain.

After a Republican administration where "deficits don't matter", as Dick Cheney put it, we are back in familiar territory with a Democratic administration hounded by the deficit terrorists for "profligate" spending and a "burgeoning" public debt that is "unsustainable", "out of control", with debt clocks counting down (or up) and warnings of armagaddon. Which is it, and why all the drama?

The drama, as one can imagine, is almost entirely political. But before we get to that, one needs to understand the substance of national debt. In this analysis I am following the Modern monetary theory school of William Mitchell et al., whose blog rewards close study. This perspective was also recently put very well by James K. Galbraith.

In the modern state system, nations issue fiat currency that has no intrinsic value- it isn't based on gold, conch shells, or anything else. Its value derives from the state's power to coerce all citizens to settle their taxes to and payments from the government with this symbolic tender, and the promise that the government will maintain that tender at stable value through its monetary policy actions. It also floats vs the currencies of other countries, adjusting relative value continuously in response to trade balances and related currency trading.

Other systems, where nations have pegged their currency to some external value, are not uncommon (the Euro nations have notional sovereignty individually while not having sovereign currencies, and China has effectively pegged its currency to the dollar). But they have an entirely different set of problems, are not the focus of this theory, and are not relevant to the US monetary system. Gold, thankfully, is no longer used anywhere as a currency base.

So the government creates currency and spends it, transferring it to the private economy, and then demands some of it back as taxes. The government is free to produce as much currency as it likes, but if it goes on a bender, (as in Zimbabwe), then its people find that their currency has become worthless, since an excess of paper notes are chasing a limited number of real goods. Note that the Zimbabwe situation is due both to excess currency production, and also to a death-spiral decline of real goods production.

The next step of a currency-issuing government is to allow banking to take place. Banks take deposits of currency in return for promises of interest payments and safekeeping, and likewise extend loans for (higher) interest in return for promises of repayment. This system has the ability to create money as well, in the form of loans which the bank credits as deposits to the account of the debtor. There is no intrinsic need to have deposit money on hand to cover the loan created, and indeed according to MMT, there isn't really even a fractional necessity for some reserve amount to support lending- a point that Ben Bernanke has recently underlined by suggesting that the US scrap fractional reserve requirements entirely for banks. "The Federal Reserve believes it is possible that, ultimately, its operating framework will allow the elimination of minimum reserve requirements, which impose costs and distortions on the banking system."

Allowing banking is quite dangerous, since this money created by banks (called endogenous, as balanced debt and asset accounts in the private economy) and can implode in crises like we have recently experienced. Banks call in and extinguish loans, refrain from making new loans, and debtors walk away from their remaining balances, which are then written off. This is in addition to the market-based paper wealth lost in such a crisis, also in large amounts. The government tries to control this money by regulation, like centrally controlled interest rates, capital requirements, and sound lending practices. We learned recently what can happen when these controls go by the board.

Part of the mechanism by which the government controls interest rates and inflation are Treasury bills, notes, and bonds, created to exchange money out of the private system in return for more ornately printed pieces of paper which function as longer-term money, with maturities set from one month to thirty years.

If the government offers a bond at a selected interest rate, and finds buyers, this sets the national interest rate at that maturity level, since private bankers, with their higher risk and need for a spread, would never offer loans for lower interest, nor deposits for much higher interest. They get their liquid money from this bond system and related instruments, after all. The government can (print up) and buy and sell massive amounts of such bonds in its market operations in order to achieve the interest rate structure it desires.

The key question is- why is money available to buy these bonds? Isn't everyone busy buying and selling real goods, and also squeezing their last farthing to pay taxes? No- some people restrict their consumption in order to save for the future. Much of this saving constitutes the private debt/asset balances of investment and bank operations, and as such keeps churning around the private economy. But if the government offers a perfectly safe way to save and pays a modest level of interest as well, why not take advantage of it?

This saving is foregone consumption for the private sector as a whole, and the government gathers up this net saving as its inflow of bonds, amounting to the national debt, denominated in its own currency, which means that it can pay any interest required by again printing money as needed. All this foregone consumption doesn't contribute to inflation, which is a function of consumption, so neither does the bond and debt position of the government.

What we have here, then, is a grand cycle of money creation and storage, where money issued by the government is collected back from the private sector in taxes and bonds, then spent again (or burned, or stored on an electronic account) by the government, as it deems best to keep the value of the currency stable. If government spends too much without collecting commensurate amounts of money back in taxes or bonds, (or seeing it disappear into the hands of foreigners by way of the balances of trade), inflation results. Conversely, if it collects too much, or issues too little, then deflation results, barring the effects of private money creation.

You can see from all this that the absolute level of government debt is immaterial. It is the flows that are important, and these flows tend to be self-correcting as the system evolves, with excess spending and public debt in low points of the business cycle where private savings flee to the safety of government bonds just as the government has greater spending needs for unemployment and other cyclical costs, (or more hopefully, for anticyclical fiscal intervention), and conversely at high times of the business cycle, high appetite for private investment risk (rather than government bonds) and lower government spending.

When well managed, these flows keep the currency value stable even as they counteract problems that private economy creates through the business cycle, and also provide a savings vehicle that institutions and citizens take advantage of (now that, through the wonder of capitalism, they typically have no pensions and may still be thinking about retirement). Low inflation can be as compatible with high debt as with low debt, since the absolute amount of debt has no direct effect on inflation. Nor does it have effects on anything else, other than an obligation for the government to, minimally, keep printing the money required to service the debt and to redeem it or roll it over, as it desires for its macroeconomic policy settings.

---

At last, we now get to Japan, whose population of champion savers has generated a government debt of 200% of GDP, the second highest in the world (second to Zimbabwe, indeed). That is 2.5 times the level of ours, which stands at 80% of GDP. With all the hue and cry about our public debt, you would think that Japan is a bananna republic, already twirling down the proverbial drain. The ratings agencies think so, having downgraded Japan's soverign debt a few times.

But they don't know anything. (Big surprise!) Japan can keep on printing whatever money is needed to cover the interest as well as further fiscal stimulus, since it has been facing deflation, not inflation, for nearly twenty years. The meaning of this is that Japan, as a currency system, has been underconsuming for many years, preferring to save vast amounts of money in their state-run postal / banking system: the money that the people owe to themselves. Additionally, Japan's large export surpluses mean that, unlike the US, Japan is not devoting any of its public money creation or fiscal spending to the accumulation of foreign Yen balances. So the system stands out as unusual, but also quite innocuous- a stable and prosperous nation which happens to have a super-high amount of debt (i.e. savings) owed to itself in a great big government piggy bank.

What does the future hold? Could everyone in Japan take a year off of work and consume out of savings? That wouldn't work, since there would then be nothing produced and nothing to buy. Inflation would quickly result. But a little of that would't hurt, since deflation has been ongoing for over a decade.

Savings rates are declining in Japan, and its pension funds have become net sellers of government bonds. This means that the government will find it more difficult to sell bonds at its chosen interest rate of near zero. This won't be a problem in the least. Japan does not need to sell bonds to "finance" its public spending (nor does any fiat currency-issuing government). They can just print it. Indeed, perhaps at that point, without mitigating bond sales, their fiscal stimulus will finally have the positive effect of reversing the deflation that has been dogging the economy so long.

The debt will decline as the demographic transition works out, and the real claims this debt represents will be drawn as consumption, returning Japan to a more normal state of economic affairs, perhaps even importing more goods from the US, and devoting more of its saving to business investment after a long period of investment decline. Japan's public debt may well remain relatively high, however- a healthy safety blanket for a security-minded, saving-oriented culture.

---

Incidentally, why all the political posturing on public debt here in the US? Some fears are honest, but inapplicable. Others are purely opportunistic. Debt denominated in a currency you don't administer is indeed highly dangerous, as Greece found out this year. They are in the same situation as any household- having to balance income with outgo, and make up the difference with temporary borrowing on the private bond markets. No printing Euros for them! Debt to others is risky indeed. But public debt in our own currency is not, even if that currency is lying in Chinese bank vaults (whose spending would cause devaluation of the dollar vs the RMB, exactly what China so staunchly resists).

One might also compare all this for a moment to private debt, like sub-prime mortgages or over-leveraged credit default swaps. Such debts are unstable, since they are not backed by a fiat currency- issuing government, (supposedly, at least). Such a government may make an error in its inflation settings, but has no reason to ever default on its own-currency debt. Private debts are subject to loss of confidence of repayment or outright default, such as in the Lehman situation, when the ability to make payments is interrupted, if only temporarily in a great game of musical credit chairs. Such catastrophic loss of confidence is impossible for public debt in financial terms. Only in political terms, through revolution or other complete breakdown, could such confidence be put in question.

Much confusion arises since the word "debt" is used, and the analogy of government debt to household debt is so very tempting. But they are not the same at all, and shouldn't be confused. Public debt could just as well be called public savings, (much like the chimerical Social Security trust fund), though either way it only represents redistributed claims on future real production, not actual saved-up production or loss.

So Dick Cheney was right. Debt doesn't matter, other than how the Treasury and central bank handle its flows in their pursuit of stable monetary value. Real macro-economists worry about inflation and unemployment, not public debt.

However, much of the confusion and vitriol is not honest at all, but part of a longstanding conservative agenda to hobble government, to prevent policy action by Democrats, to keep the private sector in the driver's seat of (volatile) money creation, and, most perniciously, to prevent the use of fiscal tools to improve the position of labor.

The original mandate of the Federal Reserve was to keep the money stable and to maintain full employment. Conservative ideology has chipped away at the latter bit by bit, until today that part of the Fed's mandate is all but forgotten, in favor of the first. High unemployment (as much as low inflation) is in capital's interest, decreasing labor costs in a hyper-competitive labor market. Proper use of Keynesian policy with fiscal support at ebbs of the business cycle can keep employment high with minimal impact on inflation, however, as it did in the 50's and 60's.

Certainly in this cycle, the amount of fiscal stimulus in the US has been insufficient, and been inefficiently applied. Unemployment remains shockingly high. Debt terrorism is explicitly dedicated to preventing any more stimulus from being created, even as we still face more deflation than inflation pressure, and more importantly, devastating unemployment. From a macroeconomic perspective, this makes no sense, since we have such glaring infrastructure and other needs (green energy) which could be so productively matched with unemployed labor. But no! Nothing further should be done- we must await the spiritual stirrings of our bankers who, doing God's work, may, in the fullness of time, once again deign to lend to worthy capitalist projects.

• Some more data on Japan, with a conventionally alarmist view of debt.
• Excellent counterpoint.
• Some more details on the Fed... accountability might be better than independence.
• Newsletter of Fed data, with graph showing the direct relation of private saving with government debt (I believe BOCA refers to the leakage due to trade deficits, to be added to private saving).

• Debt terrorism, cont... not that a smaller union among a few northern European nations wouldn't make more sense than the broad euro zone, but that there is any "possibility of a catastrophic plunge in faith in the dollar" from "which global investors could flee".
• Legalize it (the poppies) ...
• Then replace the Afghan government.
• And then my wife said: "What's an atheist at his funeral? .. All dressed up, and nowhere to go."
• Manipulation of morality in the brain.
• Goodbye to coal.
• Bill Mitchell quote of the week:

"It is now forgotten but the ECB also took advantage of hundreds of billions of US dollars provided by the Federal Reserve via swap lines which helped prevent an entire collapse of the European banking system.

...

Further, the only sustained fiscal response to the crisis by the EMU has been to pressure member governments to employ pro-cyclical policies to get back within the “rules” even though the rise in the budget deficits was driven significantly by the automatic stabilisers. Pro-cyclical fiscal policy is the exemplar of bad policy practice and defies the concept of sustainable fiscal intervention."

Driven to speciate- meiosis and PRDM9

Many crossover sites in meiosis are selected by the protein PRDM9, which has been evolving extraordinarily rapidly, contributing to the speciation of humans. (Warning... this post is unusually technical.)


Analysis of the human genome is picking up speed. A recent issue of Science provided two examples, one paper describing dramatic advances in the search for human genes with variants whose prevalence in the population has risen recently due to strong selection. Another set of papers each found the same gene, PRDM9, to act in crossover hotspot selection, converging from two separate mouse genetics studies and one computational study which I will focus on.

One of the more subtle processes of reproduction among sexual organisms is chromosome crossing-over at meiosis. Typically each chromosome arm, as it goes through the meiotic division that reduces the diploid genome inherited from the two parents into one haploid genome found in gametes, ends up not as a pure copy of either parent's chromosome, but as a patchwork, with some portions from one parent and the rest from the other. Sort of a contra dance, with a choreographed do-si-do of DNA recombination.

Getting there requires one or more crossover events per chromosome whose core is direct recombination between DNA from the two parents somewhere along the chromosome arm, and involves complicated chromosomal dynamics which can also influence cell division. To whit, if any single chromosome fails to have such a connecting crossover, it also fails to align at the center of the cell during metaphase I and floats off in the cytoplasm, stopping cell division at a point called the pachytene checkpoint, usually fatally. You don't want those gametes!

One might imagine that these crossovers occur randomly across the genome, but they don't. They occur primarily at what are called "hotspots", distributed unevenly over each chromosome. Hotspot locations change dramatically from species to species. We have almost completely different ones from chimpanzees, even though most of our DNA is the same. Why is that?

The reason seems to be an even more subtle process called "biased gene conversion", which is the engine behind all the phenomena of this article, causing in this case something called "meiotic drive". Crossover events begin with breaks in the DNA: double-stand breaks that are repaired using the information from the undamaged, homologous strand of DNA. The sound DNA physically invades the duplex of the damaged DNA, allowing both duplexes to be filled out by polymerases, i.e. repaired, (as diagrammed below) based on the sequence of the undamaged DNA.

Diagram of gene conversion- the repair of one homolog suffering a break with information from the other DNA/chromosome homolog.

But some of the time, this repair resolves not a clean invasion and retreat of the "good" DNA, (which process is called gene conversion), rather it resolves by the crossed DNA getting cut the other way, one DNA strand of the "good" chromosome staying with the opposite arm/strand of the damaged chromosome. In the diagram, this takes place after the "New DNA Synthesis" stage, where, if you just swing the arms around and cut the products a little differently (up and down, in line with the gray arrows), you end up with a crossover rather than two cleanly repaired original chromosomes. These crossover events are the ones that meiosis relies on (and regulates) to end up with properly inter-joined homologous chromosomes in meiosis I, where one homolog comes from each parent. However meiosis involves plenty of gene conversion as well- only a minority of induced double strand breaks end up as cross-overs.

If an organism has a mechanism to cause double-strand breaks during meosis, (as they do), and that mechanism relies on signals on the local DNA as targets of these breaks, (as it does- those are the hotspots), then it follows that the activating signal will tend to get erased when it is heterozygous and attracts repair by undamaged DNA lacking that particular local hotspot sequence. This process of eliminating the very markers that start the events of DNA repair / gene conversion / crossing over represents a bias, since one sequence variant tends to lose out over time and get erased- not just from the gametes, but from the population as a whole. Thus the term "biased gene conversion". Thus also the term "meiotic drive", since it is an example of selection based on the peculiarities of the molecular system, which "drives" the genetic composition of the population in a non-random direction.

In this paper (with review), the hotspot of interest contains the sequence CCTCCCTNNCCAC, where N stands for any nucleotide. They claim that this sequence is at the core of 40% of human meiotic recombination hotspots, while not being involved in chimpanzee hotspots at all. While other papers in the issue arrive at the protein that binds this sequence from painstaking genetic mapping of loci that affect hotspot usage in mice, the current paper gets there from computational analysis of zinc finger proteins.

Humans have about 691 zinc-finger proteins, which typically bind DNA with their zinc-finger domains, and do something else with the rest of the protein, like regulate transcription, or as in this case, direct the double-strand break apparatus. One reason the family is so large is that its members have a modular design where each finger, which is a protein loop that coordinates one zinc ion inside while its outward-facing amino acid residues touch the DNA, touches about four nucleotides in the major groove. Zinc-finger proteins typically have multiple fingers, up to thirty in some cases, enabling them to recognize lengthy and specific sequences. This modularity allows them evolve easily by shuffling around pieces of their genes. They are also interesting from a biotech standpoint, in the quest to develop technical ways to regulate arbitrary DNA sequences with injectable or gene therapeutic agents.

The modularity is also a boon to bioinformaticists, who, as this paper demonstrates, can predict from a target sequence what zinc-finger protein might bind to it. Given the target sequence mentioned above (which is set within an additional 30 base pairs of influential context), these authors estimated that the binding protein had about 12 fingers, and could also estimate what the key residues of these fingers probably were. Scanning the human genome data, they came up with one protein that closely fit the bill- PRDM9. Below is their diagram of the critical fingers/residues of this protein, aligned along the human target DNA sequence to which it binds, also aligned with its homologs from other species.

"In silico prediction of the binding consensus for PRDM9 ... Below the text is the sequence of four predicted DNA-contacting amino acids for the 13 successive human PRDM9 zinc fingers (one oval per finger, differing colors for differing fingers, and the separated finger is gapped N-terminal from others) and their predicted base contacts within the motif. (C) Sequence of four predicted DNA-contacting amino acids for the PRDM9 zinc fingers in seven mammalian species, presented as in (B). Distinct fingers are given different colors; fingers present in at least two species have a black border."

Note that the same protein in different species has almost completely different DNA-binding residues and thus target specificity. This rate of change far surpasses that in the rest of the genome, where very little change typically separates us from any of these other mammalian species, and  most of that change is random. This data (combined with other work that confirms the connection between PRDM9 and crossover hotspots) accounts for why hotspot locations differ so dramatically between humans and chimpanzees, at least those that are directed by this protein.

So here we have it- an inexorable genetic process by which the targets of meiotic recombination continually change under the pressure of biased gene conversion, matched with a targeting protein which seems to evolve rapidly in response, as though the actual sequence it binds to is of minor significance, just as long as it has something to bind to as the rug is continually pulled out from under it.

How does this relate to speciation? Speciation depends on mating/fertility barriers between populations, either geographic, behavioral, biological, etc. A typical example is hybrid infertility- the inability of individuals from different protospecies to mate and have offspring, or the infertility of those offspring. Mules come to mind, for instance.

Problems in meiosis result in infertility. Specifically, reduction of meiotic crossovers below the one-per chromosome level is fatal to the resulting gametes, as outlined above. As the PRDM9 gene races to keep up with gene conversion that erases its targets, it will diverge between populations, leading to changes in hotspot locations and sequence. The arrival of two incompatible parental genomes, one of which lacks the ability to recognize the crossover hotspots of the other, is a recipe for catastrophe- specifically, for meiosis I non-synapsis. This indeed is how one of the other papers in this issue found PRDM9- by locating a genetic variant in mice directly responsible for the hybrid infertility between Mus domesticus and Mus musculus.

These findings advance considerably knowledge and theory about speciation in animals whose genetic variation can be quite low (on average), whose generation times may be quite long, and whose populations can be quite small. It is very exciting to be able to synthesize, using the modern toolchest especially including the human genome, these strands of cell, molecular, and evolutionary biology.

• Another discussion of the PRDM9 gene, authored before its molecular function was understood, and focusing on its role in speciation.
• On girls, real girls, and equality.
• Great news from Iraq.
• Nice quote from Gregor.

"We have lost touch with the hurdles faced by our not-too-distant forbears who, in a world of wood and coal, found waterway transport a kind of miracle. What kind of a nut, for example, would blast through all that granite in upstate NY to build a canal? A nut who did not have oil, that’s who."

• Nope, no objective morals. Sorry.
• Ditto from the CBC, on "And The Moral Of The Story is ...".
• Somehow, Australians remain free while still having public health care.
• Bill Mitchel quote of the week...

"This insight allows us to see another dimension of taxation which is lost in orthodox analysis. Given that the non-government sector requires fiat currency to pay its taxation liabilities, in the first instance, the imposition of taxes (without a concomitant injection of spending) by design creates unemployment (people seeking paid work) in the non-government sector. The unemployed or idle non-government resources can then be utilised through demand injections via government spending which amounts to a transfer of real goods and services from the non-government to the government sector.

...

So it is now possible to see why mass unemployment arises. It is the introduction of State Money (which we define as government taxing and spending) into a non-monetary economics that raises the spectre of involuntary unemployment."

I am a program

On programming and being

As a programmer by trade and a biologist by training, I am afforded an endlessly fascinating perspective on the question of being, since organisms turn out to be (via the magic of DNA) enormously complicated learning and self-reproducing programs.

Now that we are all dependent on computers and comfortable with various analogies between computation and biology, (memory, viruses, language, bugs(!)), it might seem unproblematic to see ourselves as programs, instantiated in messy wetware and programmed with glacially slow evolutionary optimization. But of course there is a great deal of resistance, since one of the features of our program is that we see outwards, not inwards, and thus customarily don't have the faintest appreciation of our psychological or bodily inner workings. Indeed, our program creates a brain that militantly resists thinking of itself as a program, enjoying instead an illusion of sovereign freedom and a sovereign view over its flowing experience, as though its own basis were immaterial.

While some nerds revel in the computational analogy, and hope that they may shortly "download" their brain contents into immortal mechanical devices, it is fair to say that most people resist the analogy, whether instinctively or behind the smokescreen of elaborated theology. Unfortunately, science has relentlessly chipped away at these superstitious defenses, starting at the outer perimeter of humanity's geographical place in the cosmos, proceeding to kill the knights of vitalism through biochemistry, then breaching the sanctum of our mental sovereignty through Freud and the later work of psychology.

Really, there is nothing sensible left of the idea that subjectivity is as it naively seems- an immaterial soul with intuitive powers to communicate with the foundations/founders of the universe. But then, a final mechanistic account of subjectivity is not at hand either. At least the problem of consciousness is on the research program in earnest, at last, but solving it will take a few more years- decades at most.

On the silicon side, programs have become behemoths of complexity, though remaining well short of "artificial intelligence". Language translation on the web has become a great example of mini-intelligence, however. What is the barrier to true intellegence? It is learning. Humans are voracious learning machines, pulling in and storing vast amounts of information, but more importantly, interlinking it all organically in our neural nets, so that connections between near and far facts and ideas arise instantly as the need (or "inspiration") arises via related ideas, creating an integrated "world" for us to inhabit.

Despite all the databases, no computer yet inhabits this kind of world. Current programs are nowhere near learning at this high level and structure. It is a bit like the "total information awareness" project of John Poindexter, which was supposed to bring Big Brother to life across the federal government. Which was killed not because it worked, but because the concept itself was so disturbing.

But these capabilities will develop. That is the basis for Kurzweil's "singularity"- a point when machines can really learn and inhabit general conceptual worlds effectively, to the point of driving technological development faster than humans can (not to mention reproducing themselves!). Of course, there is the countervailing trend of diminishing returns to technology as the real limits of science and sustainability are reached. But at any rate, just as we have relegated half our minds to Google already, we may relegate the rest at some point in the future, and just enjoy life.

On the philosophical level, silicon is more benign and interesting. When I am looking for a so-called "bug" and puzzling over a program's mystifying behavior, the temptation to pray to unseen beings glimmers across the screen. But one thing you learn is that there is always, always, a definable cause. It may be a single character out of place in an enormous program, a well-hidden bug in infrastructure you have relied on for years, or a machine physically melting down. In philosophy, this is called the principle of sufficient reason (PSR), (in physics, it is Newton's third law, or many other conservation laws), and to come up against it day after day, on a relentless basis, can be most sobering.

Biology has similar moments, science being predicated on the PSR as well- the observation and assumption that causes can be found for any phenomenon. But cells and organisms are complicated systems, often more persistent in their inscrutiblility than we are in unlocking their secrets. Thus the triumph when the gene is found that causes a dramatic phenotype or syndrome, or the virus that causes a disease.

The science of genetics, and especially the discovery of DNA with its endless transmission through the generations, creating discardable somatic bodies as it goes along, brought the subject of biology down to a matter of programming, in the sense of heredity and evolution. How is the program propagated, preserved against accidents, read to create bodies, and divided to mate with partner DNAs? Most critically, how does this DNA make a brain and mind?

Obviously, DNA does not program the brain in the same explicit way that Microsoft programs Windows. The programming is indirect, generating and regulating complex proteins that have small lives of their own, which in turn generate dynamic metabolic, regulatory, and developmental processes, (an example in neuronal patterning), which in turn generate complex structures like brains. It's a messy process, built on a haphazard basis. It relies on many forms of homeostasis- feedback regulation- to maintain "normal" operations in the face of genetic and environmental variability, as well as to leverage normal obstacles and challenges into learning and development.

It's a bit like the Sims/SimCity game. There are discrete units of basic structure- people with various roles, furniture, urban fixtures, needs to fulfill. Once everything is working together, and combined with other players, you may end up with a city that behaves in complex ways, built out of relatively simple reproducible parts. Most theories of brain development rely on similar self-organizational behaviors to do much of the heavy lifting, for instance Edelman proposes massive neuron growth followed by function-induced testing/weeding/death to come up with properly structured networks, once the basic anatomy is in place.

Finally, there is the being of a program, rather than the making of programs (playing god, in a way) and the analysis of biologically given programs. Through the amazing alchemy of DNA, development, and neural brainwave patterns, we are the program, feeling the programmed instincts to learn, to live, to reproduce. We also feel the programmed need to imbue it all with inspirational meaning that is worth living for, and worth dying for, chosen freely with no influence from the programming.

• But we aren't a program!
• Excellent interview on consciousness issues, with Thomas Metzinger.
• Howell Raines, calling the storm troopers and brownshirts what they are.
• Interesting interview with a solar entrepreneur.
• Martin Wolf on "Chermany" as the black hole of global aggregate demand.
• The wasabi receptor- found!
• Wall street selects for psychopaths.
• Cary Tennis meets his death panel.
• Bill Mitchell quote of the week:

"But an economic system should be about enhancing the prospects for the people. What other reason would there be to organise production and work in the way we do? That is actually the nub of all this ideological debate. The mainstream is not about people – the people are just “factors of production” (as they are referred to in the mainstream microeconomics textbooks) and are there to create profits."

Mr. Toad's wild ride

An evolutionary reconstruction of the world-wide radiation of toads speaks to the process of speciation.

What makes toads so successful? They arose sixty million years ago in South America from frogs that had existed for 200 million years before, and had spread all over the world by twenty million years ago. In our day, cane toads have become pests in Australia, arriving from Hawaii and showing their awesome evolutionary fitness.

A recent paper in Science (with comment) attempts to classify traits among toads and deduce which traits were present in those lineages that spread most rapidly, arriving at a suite of traits that promoted both radiation and speciation.

The distinction between toads and frogs is a bit hard to define. Proper toads are a phylogenetic lineage (Bufonidae). But many frogs which convergently evolved similar dry-tolerance traits are commonly called toads, while some rainforest toads (harlequin frogs) are called frogs. This paper sticks to the lineage-based definition, however.

Traits allowing toads to spread rapidly over the terrestrial globe are relatively obvious, involving independence from water- to live in drier areas outside rain forests; fat storage and large size- also for portability; secretion of toxins for protection; and high fecundity- large numbers of small eggs, with larvae that feed themselves rather than living off egg reserves.

The authors deduce these traits from current conditions- traits common in the most widely-distributed toads, relative to those toads with smaller geographic distribution. The authors then take this method back in time, creating a DNA-based family tree (phylogeny) of toads, aligning it with paleontological data for time estimates, and deducing which toads had which traits at which times in the past.

They use paleontological data and various statistics to estimate which toads had which traits back in the day. For instance, poison glands appear in toads shortly before their entrance into North America ~47 milion years ago- no toads from lineages branching prior to this point have them.

Their key conclusion is that those lineages that spread to new areas (entering North America, for instance, or Asia) shared a high number of these portability traits. Thereafter, these lineages generated a radiation of species, many of which were more specialized again and restricted in range. The figure shows what they are talking about, with color codes indicating the proportion of portability traits at each divergence.

Phylogenetic tree of toads, color coded with inferred range-expansion traits (click for larger size).

The authors conclude that toads have repeatedly evolved both range-expanding and range-restricting traits, and it is the range-expanding traits that led not only to range expansion (obviously) but also to speciation, since arriving in new continents and climates generates speciation (sometimes called range-edge speciation).

An important corollary is that lineage representatives at the range edge tend to both colonize new areas and to generate new species. "We hypothesize that these reciprocal effects [of range expansion, leading to better adaptation to diverse habitats] have caused the rapid global colonization of bufonids and produced the enhanced genetic drift at the expanding frontier, with consequent high levels of population differentiation and speciation."

Something similar happened in the human lineage. Absolute genetic diversity is highest in the ancestral homeland of Africa, hosting lineages far more ancient than those that migrated to other parts of the world. Yet migration to range edges and distant continents led to new traits and population differentiation, and may have involved range expansion traits as well. What have been traditionally been viewed as "races" would have become incipient species, had hundreds of thousands more years elapsed with sufficient isolation (as apparently was true for past hominid lineages, which ramify as more fossils are unearthed).

Perhaps our instinctive xenophobia is a related mechanism of speciation by which miniscule differences between virtually identical populations is psychologically enforced, preserving whatever small advantage or peculiarity a successful population embodies. This would operate in delicate tension with our other strong tendency to seek novel experiences, resources, and marriage partners in other lands.

• Galbraith gets it- and writes an excellent primer on government spending and deficits.
• Great pair of articles on Afghanistan in TNR. I'd reiterate that the Afghan people would probably welcome NATO replacement of Karzai and a guarantee of 10 years of federal administration.
• Interesting notes on Jung and antisemitism.
• A small reminder of what Republicans do with power.
• Moral sentiments and morals.
• Bill Mitchel quote of the week:

"But on more substantive matters, today I have been thinking about how much momentum the conservative lobby has at present and that history is being continually re-written to give these characters the oxygen they need to warp public opinion. We are now in danger of an even greater shift to the right in the coming years than was represented by the “neo-liberal” era. It is an ugly thought. But the macroeconomics is clear – if these ideas really take over the policy making process – then we will be facing a lengthy period of economic malaise."

Parallels between Trotsky and Paul

Yes, I am reading the final volume of Isaac Deutscher's excellent biography of Leon Trotsky, and it is inspiring me to utter things like "Proletarians, to horse!", and "death to the imperialist capitalist running dogs!", and "all hail the international revolutionary vanguard".

It also reminded me strongly of the biography of the semi-apostle Paul, oddly enough!

Both sent epistles far and wide to cult members urging loyalty, good behavior, settling squabbles, and urging a world-wide revolution (Trotsky during his final decade of exile, which this book covers).

Both proselytized on behalf of prophets from two generations before, who had been beaten down and ignored in their own time.

Both were outsiders to the power centers of their cult (the Jerusalem church in the case of Paul, the Soviet Union under Stalin in the case of Trotsky). In response, both took their message to an international audience.

Both believed in a second coming of their ideology- changing the world through revolutionary means towards a glittering future of righteous harmony.

Both are recognized as animating spirits and organizers of what ultimately became totalitarian institutions that lived on long after them- eighty years in the case of the USSR, and 1300 years in the case of Catholic hegemony in the West. Institutions that, incidentally, spent generous portions of their energies spinning "orthodox" doctrines and hounding and killing heretics.

Both were ultimately executed for their pains- by, or with the connivance of, their own cult leaders.

And, of course, both believed unshakeably in an ideology that makes no sense whatsoever in the rational light of day. One remarkable aspect of Deutscher's work, for instance, is his  constant valorization of struggle. His hero is in constant political struggle, hurling thunderbolts of epistolatory brilliance, dashing off books, pamphlets, and articles. The proletarian revolution is always on a knife's edge, whether from its enemies like Hitler, or from its friends, like Stalin. He had fought a civil war to defend the revolution, and now from exile fought on to the end to preserve its principles, amidst ever fewer followers and dwindling interest from the larger world.

One would think that the philosophical core of Marxism would take this heroism and constant struggle into account, as do, say, evolutionary biology and conventional economics. But no- the wiki page on communism sums it up as ...

"Pure communism" in the Marxian sense refers to a classless, stateless and oppression-free society where decisions on what to produce and what policies to pursue are made democratically, allowing every member of society to participate in the decision-making process in both the political and economic spheres of life.

It is hard to tell what relation this has to the titanic struggles, not to mention deception and force of arms, involved in establishing every actual communist state, or with the theory of the dictatorship of the proletariat, or to human nature at large. Democracy is a wonderful thing, when honestly implemented. But it is no way to run smaller and more personal affairs, where personal ownership and initiative are the more effective and natural principles. So the idea of extending democracy -writ large- to questions like how to run one's farm or office, is completely counter-productive, especially when the democracy in question is of Stalin's (or Trotsky's) ilk.

All this is richly reinforced by Trotsky's own career, since he gained power not through democratic means, but at the head of an armed worker's insurgency, had little use for democracy after gaining power, relied on (capitalist) royalties on his published works for income during exile, ran his household along conventional autocratic lines, and employed all means at his disposal- charisma, discipline, and intellect, for one aim, which was power. The true communist society was just as much a mirage as the second coming and last judgment of Jesus, now almost two thousand years overdue.

In theory, the communist ideal was predicated on an over-abundance of material goods, so that all would get according to need, and material competition would be a thing of the past. But this completely misreads human psychology. Not only are human material needs bottomless, (witness the ability of billionaires to spend their money endlessly and want still more), but in the end, material objects become symbolic of desires that lie closer to our hearts- status and power, with which Trotsky was so familiar. Society benefits from policies and structures that promote egalitarianism, but not from the erasure of all differences and distinctions, which requires oppression in very large doses.

Man does not live by bread alone. Indeed, the less plausible the ideal, the more devoted and fanatic the followers. In our time, it is Al Queda that carries the banner of world revolution, in hopes of a dream world of totalitarian Islam. Yesterday, it was Communism with its dictatorship of the proletariat. And the day before that it was Christianity with its messiah coming back from the dead to rule the earth and separate the believers from the damned. The pattern is clear, from these and many other movements- that millennial visions are humanity's deepest and most persistent danger, which needs to be perpetually opposed by cosmopolitanism and true democracy.

• Early warning gives a stunning climate report the once-over.
• Even honest right wing economists can figure out Keynesianism.
• But the Chicago school has no shame whatsoever, apparently.
• Track your electricity.
• Watch a minicooper being built, using lots of robots.
• Brave words from the NYT about economic recovery... 

"But those very overreactions may have set the stage for a recovery that will turn out to be stronger and faster than those after the two previous downturns."

I will put my understanding of macro-economics on the line and say that this isn't going to happen. Mr. Norris is simply guessing at trends, and not showing his data, other than saying that "order books are filling up", rather hopefully. Indeed, the statistics he charts indicate that we are at bottom, not that we will be going up any time soon.

Unless the US returns to the debt binge days of the mid-2000's, we are in for a protracted slump of high unemployment and capacity under-utilization. Commercial real estate has yet to bottom out, for instance. This is due to an overall demand implosion, driven by loss of wealth and higher savings desires, combined with a continuing strong dollar and trade balance deficits, combined with insufficient federal deficit spending to offset the first two. Many banks, including the largest, remain insolvent, rigging accounting rules to hide that fact. So another debt binge is hardly in the cards.

• Mitchell quote of the week, on the Russian default of 1998, after interest rates were raised to >100%, and the central bank had spent almost $30 billion defending the ruble's dollar peg against speculators.

"On September 2, 1998, the government floated the ruble.

First, this was not a bank crisis. It was the result of the currency peg and the massive exposure to foreign-denominated debt.

Second, at any time they wanted to they could have floated which would have stopped the need to hike interest rates and kill their economy.

Third, they never needed to default on domestic debt. That was the act of sheer stupidity and the poor advice they were getting. There was never a solvency risk in their own currency. The IMF were in there telling the Russian government that they had to implement an austerity plan and convincing them that they needed to “raise money” to fund the deficit – both erroneous propositions."

Down a black hole of accountability

The Justice Department says the buck stops.. nowhere.

The Obama Justice Department has now found that John Yoo and Jay Bybee did nothing wrong- not even enough to warrant referral to their State Bar associations for delicensing or other discipline. One might conclude that lawyers are routinely expected to do what they did- to recommend flat violations of law, humanity, and ethics at the behest of their employers. That this goes on in the interests of crime syndicates is not news. But as a matter of official US policy? The US is signatory to the UN convention against torture, just to name the first thing that comes to mind.

The decision scuttles the findings of the Justice Department's Office of Public Responsibility (OPR) report (large PDF), which highlighted:

"Much of the OPR report tries to show—at elaborate length—that the arguments in the torture memos are so bad and so tendentious that lawyers of this caliber could not have produced them in good faith."

"But the OPR report informs us that "most of Yoo's emails had been deleted and were not recoverable.""

We are left with a government that fails to be accountable to the law or to any notion of professional ethics. Those who torture are protected as following orders, those who order it are protected as following legal opinions given in good faith, and those giving the opinions are protected by a sort of freedom of speech or legal advice- that they offered merely opinions, dressed with legal reasoning, however spurious and mercenary. Where does this end, and what does this say about our imperial presidency, and about the accountability of our institutions?

It says that we are leaving the realm of lawful civilizations. When decent people are put in charge, the results may be acceptable. When not, then there is no telling what might happen, or what did happen. One striking aspect of the record of Abraham Lincoln, aside from his poetic and moving rhetoric, is his punctilious adherence to law, in both spirit and letter, even in the most dire moments of the Republic. He took extraordinary powers, but in a constitutionally justified, and, when possible, congressionally authorized, way (abetted by the secession of the Southern bloc in congress).

To read the decisions of that time puts ours in a rather unfavorable light. Lincoln got congressional approval for impositon of martial law throughout the US, after which the Supreme Court struck it down as overly broad, in light of the fact that in most places courts were in regular operation, making martial law unnecessary. Thus chastened, Lincoln continued the war with martial law restricted to areas actually at war. The war raised countless other constitutional issues, which show the quality of Lincoln's reasoning and attention to the law.

In our age, we receive a relative pinprick from a band of pathetic malcontents, and flee, panic-stricken, from our civil liberties and sense of ethics. We have been lulled into complacency, then infantilism, by our long reign as a super-power, and are shocked by the reality of mortality and of people who fail to share our interpretation of the American dream.

If the goal is American and global security, we are only shooting ourselves in the feet by scuttling the rule of law, especially international law. The US will not be the hegemonic superpower forever, so with an eye to the future, we should be paving the way to truly effective and humane international law, locking in place the ethics and processes that have succeeded so well in the West, at least to date.

• And this issue of legality and extra-legality is relevant elsewhere.
• Rev. Dr. Peter Hearty out-does himself.
• Glenn Greenwald nails the NYT.
• Honor where honor is due, IRS-wise.
• Have the banks won?
• Some more ominous signs on Afghanistan. As usual, the issue is whether the government is any good- is it better and less corrupt than the Taliban?
• Who knew that Rachmaninov wrote meltingly beautiful choral music?
• Bill Mitchell quote of the week: 

"No taxpayer will have to foot the bill for any of the government spending [i.e. debt]. He is talking about a government that is not financially constrained although he doesn’t realise that.

Taxes are paid and people don’t like paying them – that is clear. But what they don’t like is that the tax payments reduce their disposable income which means that taxation reduces the private command over real goods and services. There has to be “space” for public spending for a given real output capacity. Otherwise inflation becomes the threat."

...

"The progression in tax systems merely reflects the fact that you try to deprive those with the most purchasing power more than those with less – so-called equity ambitions. It is a way of more fairly sharing the burden of the price stability."

Left brain, right brain

A comment I made on another blog recently got me to thinking about reductionism and the fear religious people commonly express about it. The writer recommended a long article from a pontifical academy on the theology of Darwinism, which made a special point of denying the ability of reductionism / materialism to describe the essence or being-ness of humans. At the end of a comment, I said:

"Reductionism is not a reflection of the world, really, but of our mental capacity to understand it. We require abstracted models and systems, benefiting from breaking down and rebuilding in abstract fashion the complex entities of the world."

The world just is, whether we approach it with awe and mysticism, or with reductionism and analysis. The violence we do to holistic world views through dispassionate analysis is not violence we do to the world, but to the sensitivities of our fellows who have different perspectives. Conversely, theistic claims of sensitivity to holistic, indeed supernatural, phenomena, do violence to the understandings of anyone with an analytical bent, but again, not to reality itself.

Are the persepctives really so incompatible? I doubt it, and therein lies another approach to resolving the culture wars. Each side has a symbology or ideology by which it represents its perspective, each problematic in turn when taken too literally. These sides can be typified by the left-brain, right-brain divide, which is a bit of hyperbole, since we all partake of both sides, and differences tend to be minor. But still, people do seem to have slight preferences either for the left brain's analytical, concrete, reductive tendencies, or the right brain's holistic, intuitive and mystic tendencies.

On the analytical side, people often mistake description for understanding, and mistake understanding for participation and meaning. For all the detailed knowledge of physics, for instance, we still do not truly understand the fundaments of the universe- why matter and energy exist, and whence something as simple as gravity really arises (or the space-energy interaction on which it is based). Being able to describe in detail the workings of gravitational systems is a huge advance over our prior ignorance, in both practice and theory, but it is not yet full understanding. Such understanding may not be possible. But we shouldn't fool ourselves into thinking that labeling a lot of boxes with fancy words and gaining some operational and intellectual power over their relationships amounts to full understanding, or fulfillment of the human search for knowledge. (Which finds perennial expression in spiritual "seeking".)

These partial successes have given us great power over our environment, powers that continually reveal nasty side effects, but do they make us happier and better? Do they deepen our connection with the world- the participation mystique that forms one basis of happiness? They give us security against natural events, (acts of god, as it were), as they also alienate us from world-participation. Our involvement in nature becomes, at best, aesthetic and optional, rather than the Wagnerian life-and-death drama in which we were embedded primordially. Thus happiness has a frought relationship with what we in the modern left-brain West call knowledge and success.

On the other hand, the right-brain attitude of holism continually seeks greater significances and numinosities in the world, focusing not on how it is put together, but how it adds up to meaning. This syle of thought tends also to work with images and symbols rather than analytic ideas. Thus meanings are symbolized in religious imagery, starting from a plethora of spirits imbued into inanimate surroundings or sympathetic spirits experienced in hunted prey, and continuing on to civic deities and universal, patristic monotheisms apotheosizing increasingly complex social and philosphical concerns.

Obviously, these symbologies have their problems, not in their artistic expression and portrayal of psychological yearnings and dynamics, but in their morphing into matters of "fact" rather than matters of art or psychology. All too easily, left brain-types find themselves drawn into the vortex of imaginative religious ideas and feel a need to systematize, organize and regularize. And then to insist that not only are these ideas beautiful, but they are real. Indeed, real-er than real, with the prospect of greater lives after this one, higher worlds beyond this one, and deeper intelligences at work behind it all.

What is striking is that each style of thinking leaves such strong imprints on its content, doubtless because one can't avoid it. And that the cross-talk between styles of thinking can be so maddeningly fruitless, even destructive.

When taking this test on left-right tendencies, I come out right in the middle.

• Jung and Avatar, over at the oil analyst, of all places!
• Politics and physiology/temperament.
• Politics and mythology.
• Jewish orthodox cultism.
• The business card economy takes on China.
• Economic classic- Coase, on the nature of the firm.
• See-no-evil, hear-no-evil.
• Mitchell quote of the week, speaking of deficit terrorism in the context of the Federal budget:

"In general, the imposition of these restraints reflect ideological imperatives which typically reflect a disdain for public endeavour and a desire to maintain high unemployment to reduce the capacity of workers to enjoy their fair share of national production (income)."

Better psychoactive drugs

Careful choice of organisms yields faster drug screening

One of the lesser-appreciated aspects of biology is the momentous choice of research subject. Most biology is justified in medical terms, i.e., better understanding of ourselves as the target organism (I am speaking of molecular biology, mostly, not ecology and systematics). Yet that target is dauntingly difficult to work with. Generation times on the order of 25 years, enormous size, prone to high-maintenance living standards, and capable of organized political resistance to intrusive investigation, to say nothing of euthanization at the end of an experiment. No, something else needs to be done!

Fortunately, there have been plenty of questions amenable to biological investigation without resorting to inhumane methods. Many studies use cells isolated from humans, either taken recently and quickly amplified to large numbers, or developed from cancers which render those cells immortal for laboratory work. These unquestioning and docile research subjects are useful for cell-centric questions, like how the nucleus talks to the mitochondrion. But how brains work? That question is not going to answered in such a lab.

The unity of life allows us to go farther afield, however, and use other systems and organisms to answer significant questions. Bacteria and viruses were long the darlings of molecular biology, back when DNA was a novelty, and the most basic questions were being asked, like how any kind of living metabolism works, how proteins are strung together, how DNA controls protein production, and how simple cells orchestrate division. Bacteria are easy to grow, genetically simple, and a treasure trove of molecular information and tools- especially the many enzymes that have become standard in the field, like DNA polymerases, ligases, and cutting & trimming enzymes.

Yet with rising ambition, more complicated questions were asked, like how the golgi apparatus works, or the actin cytoskeleton. Bacteria don't have either of these internal structures, so other organisms were consulted- the simplest ones to have such (eukaryotic) structures but still be easy to work with. Baker's yeast fit this bill, leading to a rich research field that still is making great contributions to biology. And so it goes. Q: animal development, including simple brain development? A: fruit flies and nematode worms. Q: neuron, synapse, and reflex functions? A: The large sea-snail Aplysia. Q: plant-specific molecular biology and genetics? A: the mustard weed, Arabidopsis.

Lately, a small fish has become a popular- the zebrafish, Danio rerio. One of its benefits is that it is highly transparent, so its development is easy to watch. Also, as a vertebrate, it is much more closely related to the most important organism of all time (us) than are the other developmental models (fruit flies and nematode worms), while being much easier to grow and study than mice and rats. It represents a nice mean between ease of use and proximity to humans, for many questions.

One of those questions is how the vertebrate brain works, and how to efficiently isolate drugs that act on it. The current paper uses the moderate scale possible in zebrafish labs to screen for such psychoactive drugs, focusing on a relatively simple metric- activity measurements such as the sleep/wake cycle.

The general paradigm for creating psychoactive drugs has been hit-and-miss. Usually, someone happened across an interesting effect serendipitously while tasting/testing a drug for some other use in humans. (Prozac is an example, where the incidental antidepressant effect of some antihistamines led to this class of drugs. Another example is LSD, which was based on the known medically active compounds of ergot mold.)

Otherwise - and this is called the "rational" approach - a protein like a transporter for neurotransmitters is demonstrated to be important for brain function, and expressed in laboratory cells whose activity is then used to screen for drugs that alter the action of that protein/enzyme/transporter, after which that drug is tried on whole organisms, working up to humans if sufficiently promising. The only examples of this kind of drug would be those in already-established classes of chemicals, such as hunts for new SSRIs/Prozac, where, once the mechanism and target were understood, more drugs could be developed against the same target. I don't think any truly novel classes of psychoactive drugs have ever been developed in this way, since the theoretical connection between molecules and brain functions remains rather indirect at best. This method has been used with great success against HIV, however.

Drug screening is a painful, laborious process, often starting with hundreds of thousands of miscellaneous compounds (derived either from obscure natural sources, or chemically synthesized in programs aiming at maximal diversity and appropriate-ness as drugs). Each is thrown at some cell or organism that has been engineered to test for a disease (cancer cells, for instance), or just watched carefully for interesting effects.

Here, the researchers looked for interesting effects of a battery of compounds on fish embryos grown in a large system of isolated wells, ten per drug treatment. They were able to screen 4,000 compounds (mostly already-recognized drugs) by computerized monitoring of each well, looking for sleep-wake behaviors. (Whether this approach can discover new hallucinogens is not at all clear!).

You can just barely see one fish in each of the square wells.

Graph of one drug's effect on sleeping (black bars) and waking activity (white bars) showing dramatic effects on waking activity, while much less on sleeping. Sounds rather unpleasant for the fish, actually. This drug binds to glutamate neurotransmitter receptors. The y-axis is measured activity- red, drug treatment; blue, controls with no drug.

What they found were new chemicals that affect sleep and wake cycles and general activity, inferring previously unknown pathways and perhaps leading to novel drugs- possibly a super-Ambien or super-amphetamine. They also show that this is an efficient way to characterize the mode of action of unknown chemicals, by comparing them through various assays with a panel of known drugs. If the patterns match, it is likely that the unknown drug works in the similar pathway, which may in turn tell us where its target protein fits biologically, if its role is unknown.

This group, based at Harvard, appears very well plugged into the pharmaceutical industry, indicating that this work is, in all probability, a demonstration of principle for a new biotech company that may use this set of methods to achieve a golden mean between rapid and broad drug screening, and screening for interesting properties that are medically relevant to us.

Graph showing that two chemical analogs of podocarpatriene-3-one (related to chemicals from the Neem tree used in ayurvedic practice) make the fish quite restless, taking far longer than control fish (DMSO) to quiet down after lights are turned off, which they term rest latency.

• Basics of modern monetary theory, from Mitchell, also here. Lengthy, but cogent. Includes the following quote from Abba Lerner, about the reticence of Keynesians:

"The scholars who understand it hesitate to speak out boldly for fear that the people will not understand. The people, who understand it quite easily, also fear to speak out while they wait for the scholars to speak out first. The difference between our present situation and that of the story is that it is not an emperor but the people who are periodically made to go naked and hungry and insecure and discontented – a ready prey to less timid organizers of discontent for the destruction of civilization."

• Some notes on the 'Hockey stick" climate warming controversy.
• People are happy to have best-of-science near-term weather reports, but long-term weather/climate reports? Not so much!
• William Mitchell quote of the week, speaking of government deficit terrorists and balanced budgetistas:

"... the use of the term “sound financial management” is an ideological construction which means at worst balanced budgets over the business cycles and maintaining a buffer of unemployed so that wage shares are low (profit shares are high) and inflation is low.

...

Meanwhile, the more important policy goal of full employment has been subjugated and unemployment used to further the free market ambitions which ultimately are designed to redistribute national income away from workers into the hands of capital. Along the way, the dominance of financial capital has somewhat usurped this process with deadly results as we are witnessing now."

Time for the Nuclear Option?

A simple step to make America more governable

Speaking from the dysfunctional state of California, it is disturbing to see similar dysfunction take hold of the federal system, where supermajority requirements are creeping into the legislative process. In California, our fate has been paved over by popular plebiscites for lower taxes and two-thirds majorities for budget passage, (prop 13), not to mention a gaggle of smaller budgetary set-asides and special deals, all enshrined in the state constitution. What the people pass in haste, they rue at leisure, and we are ruing now how any budget can be held hostage by any third of the legislature.

That most egregious proposition in the California consitution combined the budget passage requirement and the real estate tax freeze, which ended re-assessment of property values for taxation. Through this mechanism, families can pass property to their heirs in perpetuity at their original tax rates, forming in essence an aristocratic and parasitic class of property holders. What was originally framed as a way to keep senior citizens in their homes has become a black hole of local and state revenue, and a stunning social inequity.

The lesson from California is that representatives have a place in a democratic system, and that super-majorities are extremely corrosive (read: conservative, status-quo-ist) to the point of having a legislature at all. The California proposition system has done some good, but it also allowed greed and right-wing ideology to ensconce itself in the constitution, virtually permanently. My fellow citizens may eventually come to their senses. We may call a constitutional convention, or muster enough disgust to direct it at the right place (the rules) instead of the wrong place (the politicians) through further propositions. However all that seems unlikely, and it is more likely that we will continue to muddle along, succumbing to sclerosis and inertia imposed by our now-impossible rules, crumbling under 20% unemployment, made worse by the month as all levels of government within the state fire workers.

Something similar is happening in the US senate, where the 60-vote filibuster has gradually become the defacto bar to get anything accomplished, despite the text of the constitution. What was once a theatrical performance and last resort has become an anonymous routine applied to legislation or appointments with which any Senator disagrees. As in California, the Republican party has become a do-nothing rump gleefully empowered to see that nothing gets done.

As James Fallows relates in a recent Atlantic article, this is only a part of a larger pattern of institutional sclerosis, where over time interested parties grab special favors and economic shares of the state. Whether it is public employees getting featherbedded through their unions, or businesses asking for the umpteenth tax break, everyone wants their bit, until the state becomes tied, Gulliver-like, under a thousand threads of privilege and corruption.

Reform is thus a constant struggle against conservative instincts and entrenched interests. Incumbent interests can draw on incumbant money to preserve incumbant positions. The status quo may be virtually unshakeable without an occasional revolution, as Jefferson understood.

Nevertheless, there is one thing that can be done to get us out of this paticular rut, which is to blow up the Senatorial filibuster. I used to think differently, when such issues as radical judicial nominees and preservation of the Arctic wildlife refuge hung by a filibuster-sized thread. The inherently unrepresentative nature of the Senate, where a majority might represent less than 15% of the population, might lead us into terrible policy were the filibuster broken. And the filibuster was used rarely, for exceptional issues of deep principle.

But no more. The mores of the chamber and the political landscape have changed to such an extent that this rule has outlived its usefulness. Under current rules, the civil rights acts would not have passed when they did, among much, much other legislation. The check that filibusters used to provide has become a stranglehold when combined with such unwholesome developments as rabidly ideological media, the newly-decided corporate freedom to influence elections, and a heavily polarized electorate. One reason that most democracies the world over use the parliamentary system is that whoever is voted into power can then carry out their program, whatever it might be.

Our system needs to have that characteristic as well, which would be partly enabled by ending the filibuster. One might imagine exceptions for very long-term issues like Supreme Court appointments. But even this would be unwise, since all issues taken up by the Senate have long-term ramifications. On the whole, majority rule is the constitutional provision for a very good reason, which is that enabling minorities to block routine action is unconscionable if the state is to get anything done.

• Frank Rich gets it. Could some down and dirty arm-twisting could replace nuclear warfare? I have my doubts.
• Lessig on the other problem of shameless corruption.
• PR firm steps up to its personhood responsibilities and runs for congress.
• Meanwhile, government serves its master.
• If Obama wants jobs, he'd better do more than pray for them- make them.
• Even Krugman gets it on the deficit, at least partly.
• Video on thorium reactors.
• How to regulate banking.
• If I may toot my own horn, readers might find comments on another blogger's theological pointer entertaining.
• More sensory illusions and perceptual time-management by the brain.