Saturday, December 26, 2009

A beneficial mutation

In pursuit of that mythical beast, the beneficial mutation.

I was in a brief discussion with another blogger recently about the possibility of human evolution, in light of the vanishingly small rate of beneficial mutation. Given the few million years involved, and the small population sizes, wouldn't it be simply impossible for apes to have accumulated beneficial mutations at the requisite rate to evolve into humans, which required roughly 170,000 such alterations, by one estimate? I will leave the details of that discussion there, but much turned on the probability of beneficial mutations, which I rated much higher than my friend did.

So, an interesting study popped up in Science recently that touches on this problem, and illustrates some of the concrete issues related to mutations in a natural setting.

Ciclid (sounds like "seek-lid") fish are famous in evolutionary biology for their rapid adaptation to new lakes and their diversification within existing habitats. This paper discusses a single mutation occuring in several species in Lake Malawi which borders Malawi, Mozambique, and Tanzania. The OB (orange blotch) mutation occurs in the gene Pax7, not affecting the protein sequence of the Pax7 protein product, but occuring in its control region and increasing its expression, though the authors do not give a detailed analysis of where and when this expression takes place. This increased expression allows the OB allele to be dominant over the wild-type BB allele.

Cichlids of Lake Malawi, female (left), or male (right); wild-type (top), or carrying the OB allele of Pax7 (bottom).

Pax7 is known to regulate the development of pigment cells in fish, (its human counterpart also has developmental roles, though slightly different effects). Incidentally, its cousin Pax6 is famous for an evolutionarily conserved role in eye development. So this mutation makes a great deal of sense in view of the phenotype, which is that fish get a mottled coat (bottom) due to fewer but bigger melanophores, where before they had a relatively uniform coat (top).

For females of these species, the mottling is beneficial by being quite a bit more effective camouflage than their wild-type uniform dark color, in relatively light-colored, rocky settings. For males, however, the mottling is a catastrophe, destroying their day-glo coloring and beautiful striping. They go from disco kings to blotchy wallflowers. Much of the paper is devoted to figuring out the odd genetic system which reduces the number of affected males dramatically in these species (about 20 species share this mutation), while maintaining the OB females in high proportion (though the authors don't give population numbers).

But something needs to be said about the basic mutation- it affects a gene which has dramatic effects on development, without deranging that development completely. It is almost as though the developmental genetics of this organism (as is true for many others) is pre-positioned for evolvability, involving a lot of controlling genes with complex regulation, which can be tweeked by relatively minor mutations to alter some features of the organism while the rest of the program goes on with little detriment.

This illustrates (anecdotally, at least) how beneficial mutations may be reasonably frequent. Variation exists in all populations, and living conditions are changing all the time. So while most changes are detrimental versus the optimized mean of the ecological landscape, conditions favor change in many edge cases and novel conditions, creating room for novel phenotypes to take advantage. Ecological landscapes are also a great deal more ragged and chaotic than the smooth abstract surfaces often used to illustrate them. I see this frequently in daily life, where some disruption to my well-honed routine first makes me upset, but then reveals a new way of doing things that I adopt as a new routine. A beneficial mutation has occurred and been selected for, which happens with some regularity.

Getting back to the fish, our males were left with a serious problem- how to minimize their embarrassment while providing the females with these beneficial OB blotches? The evolutionary solution turns out to be to link the Pax7 OB allele with the female version of a novel sex determining locus (W), so that the mutation is tightly linked to the female W, and thus happens only in female fish. Remember that not all species use the X/Y chromosome system of sex determination, indeed there are a dizzying array of such systems.

Thus not only was the OB mutation beneficial, but it was beneficial enough to overcome the harm it does to males, and to induce the resolution of that harm by linking OB with the female W determiner- a gene which the authors claim is yet another beneficial mutation (or transposition, or novel gene) that arose after the OB mutation, over-riding the locus that determines gender in other species of cichlids in the region and resides on another chromosome. Indeed, it might be beneficial enough to switch the sex chromosomes of the species (or incipient species) with OB from the previous #5 chromosome to this new location, #3, illustrating how sex determination mechanisms can shift over time.

Such hugely beneficial mutations will be rare, but based on these observations of genomic, developmental, and ecologic plasticity, I'd suggest that beneficial mutations of more modest effect are more common than the vanishingly small rates that were assumed in the analysis cited above.

Saturday, December 19, 2009

Deficit terrorism

An interesting blog makes the case for liberal economics

Second only to theoretical physicists, economists carry a professional mystique of abstruse knowledge in the service of vast power. Vaults full of gold, trillions on "balance sheets", jargon swirling, and schools like the Chicagoans, Austrians, and Keynesians at each other's throats. Those employed at the central bank can create money ex nihilo, with god-like powers! The current crisis has made us painfully aware that while economists may use mathematics (and hopefully arithmetic) for pedestrian activities, the heart of their profession is a kind of psychoanalysis, along with a bit of conjuring. Who will ever forget Gerald Ford's Whip Inflation Now program?

Understanding is a precious commodity, and for all the critique raining down on the current administration, very difficult to come by. We can take it as given that the Republican talking points are, as usual, self-serving idiocy. Yet even discounting that, the situation is murky. I've recently gotten interested in a blog by a liberal economist who takes even Paul Krugman to task for basic blunders of macroeconomics! Not an easy thing to do with a nobel prize winner, but as I said, economics ain't physics.

I am no expert, (as usual), so bear with me (if you like) while I work out below what is going on in our economy, with the guidance of Bill Mitchell (interview), of Australia's University of Newcastle. His blog is something of a firehose of solid economics, indifferent spelling, and tart sarcasm directed at the leading lights of the profession, particularly conservatives who have suddenly found deficit religion, after eight years when "deficits don't matter". Thus Mitchell refers to the "deficit terrorists" of the present day who are prolonging the agony of this economic ... repression? decession? You make the call.

Let's start at the beginning, when the government prints money. Sovereign governments that print their own money and demand that legal tender back for taxes and the like are in a quite special position, relative to those sad-sack organizations like households, businesses, and states, that have to balance their books. Governments can print more money to cover their spending, and indeed have to do so as the economy they are responsible for grows and demands more money at stable value.

The current crisis was a bit of an error by the banks, which have another role in printing money. They make loans on the basis of small reserves, (the fractional reserve system), creating money out of thin air when they make a loan, and destroying that money again when it is paid back, while keeping the interest. Normally, the central bank keeps close tabs on the reserves underlying bank activities, so that this creation is held in check, tracking economic growth. In normal times, (again), tweeks to the interest rate charged to banks for this reserve money controls interest rates throughout the economy, thus lending activity, and thus money creation, and thus inflation.

But a funny thing happened on the way to the current unpleasantness, which was that banks, non-banks, and quasi-banks got into a low-reserve (i.e. overleveraged) lending game through esoteric "instruments" (we wouldn't want to call them loans- loans have standards!). The Federal Reserve completely lost control of the fractional reserve lending system, and the various lending "innovators" blew up when the markets they were overleveraged into began to decline.

Why wasn't this inflation of the bubble accompanied by monetary inflation? Ungodly trillions were being minted by the "banking" system, causing an asset bubble, not money-value inflation. This is perhaps where the psychoanalysis part comes in. Those of us buying houses during this period would call it inflation pure and simple, and of a particularly painful kind. But the CPI was not paying attention, since rental rates were not going up in lock step (one sign of housing market imbalance, incidentally). Most of the economy also had spare capacity for production, and offshoring/importing kept wages low. So as long as most indicators were stable, few businesses were raising prices, and the Fed, keeping its eye on the CPI, wasn't raising rates, and all were happy, except for one or two corners of the economy that were going absolutely bonkers.

Doubtless there is more to the story, but that is as much as I understand. When all that money from "innovative" banking was extinguished out of the system, we were in great danger of spiralling deflation, which prompted the Fed to flood the banking system with extra reserve money, buy up hundreds of billions of questionable assets, and reduce interest rates to zero. The extra reserve money made the banks more secure, (except those saddled with the most toxic leveraged garbage who couldn't cop a bailout from the Goldman, er, Treasury overseers), but it didn't induce them to lend. Lending depends on the customer's future prospects, and prospects suddently turned rather sour, even while businesses were pounding on the doors for money to tide them over this difficult time.

This is where the government comes back into the picture, printing and spending money. Mitchell's basic point is that government occupies a free position versus the private economy, with outflows:

- Direct spending (fiscal)
- Loans of reserve funds to banks (monetary)
- Purchase of bonds, notes, etc. on the open market with printed money (monetary)

And inflows:

- Taxes
- Debt, which is money collected from the private economy in return for IOUs
- Banking reserves called in and liquidated.

What the government does with its money is entirely immaterial. It could burn all the money that comes in the door by way of taxes and debt issues, and print new money for whatever it wishes to spend. The only stricture is that, as the manager of the monetary system of the private sector, the government (encompassing the Fed, Treasury and all the rest) wants to provide net money to the system such that inflation stays low- i.e. the value of the issued money remains stable. One could adopt the motto- "real macroeconomists care about inflation, not debt".

(Incidentally, due to this fundamental connection between the fiscal and monetary arms of government, Mitchell advocates combining central banks into government treasuries, so that they can act in unitary fashion, as they did in the US in this crisis anyhow.)

As a liberal-left economist, Mitchell adds the extra monetary policy aim of generating full employment, which used to be front and center in the US, but has receeded with the ascendence of Reagan and Friedman. Are these aims at odds? That is a critical question, especially now. Mainstream economists believe in something called the NRU, or the natural rate of unemployment, where the economy is producing as many jobs as could be expected without generating excess inflation, considering the number of malingerers and others reporting to be interested in work, but not really worthy of private sector employment.

As you can tell, this is something of of moral, even theological, concept. Leftists tend to think of NRU as zero, since everyone willing to work should get a job, if only a state-supported minimum wage job. The mid-century in the US stands as a sort of golden age in this respect, where for a long period anyone who wanted to work could find a job, during the huge post-war economic expansion. Rightists tend to think, in contrast, that people need to be "motivated" by the specter (indeed, the reality) of joblessness to be in a properly craven postion vis-a-vis business.

But one point is not really in dispute- however one celebrates the "creative destruction" of capitalism, the destruction of families, life savings, and human capital is no one's ideal. The current bubble-destruction cycle has been deeply damaging, especially to those still desperate for work. Their labor is being wasted- flushed down the toilet due to business, government, and monetary policy mismanagement. And their spirits are being crushed.

So far, the Fed has staved off deflation with its trillions of monetary support. But can the Fed, and the government in general, do more? Here we come up against the deficit terrorists, who say that the government is already in hock up to its ears and simply can't do any more. Hogwash! say liberal-left economists such as Mitchell. Is inflation a threat? No- deflation remains the current threat. So not only should the government be spending more money to replace mismanaged and dried-up labor demand, it doesn't even have to issue more debt to do so, but should just spend outright, leaving inflation management as a bridge to cross when we get to it.

Indeed, with inflation in negative territory, the policy goal is to increase inflation, (the customary goal being ~2%), which would best be accomplished by net government spending, either by sending money into the long-term bond markets, (analysis mentioned below), or directly into jobs programs, especially for our crumbling infrastructure and alternative energy needs. As everyone points out, the Great Depression was finally fixed by the biggest and most spectacularly wasteful direct jobs program in history- World War 2.

Issuing debt into the private economy to "finance" government spending simply takes money out of one pocket of the private economy (the rich who buy bonds) to put it into another (fiscal spending by the administration and congress). In normal times, that is a useful tool for monetary stability and for facilitating saving by the private economy , but right now, a great deal of extra money needs to be added- to stave off deflation, to spur economic activity in general, and to reduce the existing loan burden through modest inflation.

The financial bubble, despite creating vast amounts of money through Alice-in-Wonderland mechanisms, created only pockets of inflation, not general inflation. The subsequent implosion was so severe that much more money needs to be pumped in- about two trillion more, by one analysis which recommends that the Fed buy that amount of debt from the Treasury, effectively printing that amount of money and putting into the bond market, lowering long-term rates. The point is not to resume the over-inflated ways of the top of the bubble, but to provide the right amount to counteract the whipsaw of private lending contraction, allow the resumption of normal economic activity, and ameliorate unemployment.

[ed.note- Deeper reading of Mitchell's blog informs me that the above prescription, of the Fed buying $2 trillion of treasuries on the open market, would not actually constitute printing money, since the bonds bought would represent private liquid assets that would be extinguished. The result of all this buying would actually be to slightly lower long interest rates, which may be helpful in an indirect way, though already-low rates are not a big spur to lending. Buying this debt from the Treasury would likewise not have any effect unless the Treasury turned around and spent that money fiscally into the economy, like on infrastructure, alt. energy, etc. programs, or through a tax holiday.]

The ~1.5 trillion dollar gap of GDP, due to wasted labor and other resources.

So, do deficits matter? Yes, but mostly from a monetary perspective. The government doesn't need to "finance" its spending with debt. If the monetary system is stable, such financing (or alternately, taxation) is advisable, to keep the net money flows between the government and the private economy stable. (It also may be forced to do so if it has formally separated the central bank from its fiscal adminstration, as we have, even if the central bank then turns around and purchases those debts with created money.)

But it doesn't have to, especially when deflation is the present danger. It can (and should) spend freely without corresponding taxation or debt issuance in a deflationary situation, when the private economy lacks enough money, whether due to trade imbalances, government running net surpluses, or a credit implosion. Interest payments on government debt are certainly an encumbrance on future government spending, and some countries have reneged on such obligations (though never the US). Today's low interest rates are, however, a signal that such debt is, in concrete terms, not a problem now.

Overall, the response of the Fed and the government in general has been better to this implosion/decession than it was to the Great Depression. But the unemployment rate (much higher when one includes the underemployed, discouraged, etc.) says empirically that not enough has been done. That the financial industry should lose jobs after its overexpansion goes without saying, as is true to some extent for the housing industry as well. But the rest of the economy (so-called Main Street) is innocent in this cataclysm, and its suffering is a mark of failure in monetary and fiscal policy. In the future, one can imagine that were this kind of financial implosion to happen again, (heaven forfend!), the government should take even more rapid and forceful steps to replace credit, money stocks, and economic demand so that citizens would not be facing such terrible disruption and chaos.

  • One unemployed person.
  • All that said, who is mostly responsible for our current debt?
  • Frank Rich has a great column on the not-so-great Bernanke.
  • Survivor, for those of you looking for morals.
  • Santa and god- closer than you might imagine.
  • Mr. platitude raises his game.
  • The psychology of denial.
  • Amazing maddening story of abortion in war.
  • A great airline columnist keeps making the case against TSA.
  • Religious zealots run amok in the middle east.

Saturday, December 12, 2009

Who turned out the lights on the Dark Ages?

Review of Glubb's The Empire of the Arabs

A few weeks ago, I reviewed the first book of this pair, The Great Arab Conquests, by General and Sir John Glubb (1963). This week I conclude with its sequel (1966), which takes the story from the 680's, (the origin of Shiism in the Karballa massacre), 48 years after the death of Muhammed, to the mid-800's, covering both the Umayyad and early Abbasid dynasties of the early Muslim Empire.

Again, I can not praise Glubb's history highly enough. He writes with sweeping knowledge, genuine sympathy, and prenetrating insight, and with some verve as well. His main flaw is that as a thoroughly military product of the late British empire, he naturally concentrates on military affairs and high strategy, writing in a very traditional historical mode. Here is his reflection on the concept of political freedom:
The citizens of Britain and the United States claim today to be free men and to live in free countries, but their freedom is only relative. In practice they have agreed to a compromise. They have consented to surrender their freedom to a vague entity known as the majority, which can make laws which others must obey. In other words, men who live in settled communities are not personally free. In order to enjoy a limited amount of freedom under such circumstances, they agree to surrender the remainder.

The fact that, under this system, we still claim to be free, makes us fail to comprehend what freedom meant to a nomadic Arab. He knew nothing of the majority. He claimed the right to do as he wished, even if every other man on earth disapproved of such action. The nomad really was free, and the key to his perfect freedom was mobility. As soon as these men came to live in cities and acquired immovable property, they lost their mobility and therefore their perfect freedom. But they did not of course think the matter out in this manner. Personal freedom had become to them an instinct. Although living now in houses and in cities, they were not prepared to take anyone's orders. Those who were trying to organize and rule an empire with such subjects soon found the task impossible. p. 208

Westerners are typically unacquainted with the basics of the Muslim empire (I certainly wasn't, only learning the barest bones of Greek and Roman history in school). Yet the Muslim empire was larger than the Roman empire at its height, had a brilliant, if somewhat shorter, run, and is more of a living presence in our own world, as many of its former subjects still yearn (or even take up arms) for its re-establishment. No one wants to re-establish Rome, except in the most loosely metaphorical sense!

Before getting to Glubb's insights on the middle ages, I'll touch on a few themes from the rest of the book. The original impetus for Muslim imperialism was religious, uniting an age-old warrior raiding tradition and pan-Arab peace inspired by Muhammed's charisma and theology into a duty to spread the faith outwards by jihad. Almost on a lark, the newly minted Muslims, earlier content to harry each other and the empires on their frontiers while making a living conveying trade goods from the orient, marched on the Byzantine empire in the Levant, the Persian empire in Iraq, the Byzantine empire in Egypt, and the core of the Persian empire in Persia, in quick succession.

As luck would have it, these adversaries had exhausted themselves in prior wars with each other, leaving the way virtually open. The same situation repeated itself as the Muslims entered North Africa in the 690's to 700's, and Spain in the 710's. Only the Berbers in North Africa put up continuing resistance, ironically after adopting Islam, but then finding that the promise of social and political equality in Islam failed to materialize. It was an Arab aristocracy, as it remains today in the deep feud between Saudi Arabia and the Sunnis (dressed in white, in Umayyad tradition), and Shiite Iran (dressed in black, in Abbasid tradition, or green, in Shiite tradition).

The tenor of government gradually devolved, from the popular acclamation of the first two caliphs after Muhammed (who also followed the religious and ascetic traditions of early Islam), to the nepotism installed by the Umayyads (family of the Umaiya, who were ironically descended from Muhammed's bitterest opponents in Mecca) whose capitol was in Demascus, to the more Eastern-themed despotism of the Abbasids (family of Abbas, more closely related to Muhammed, but not descended from him). The Abbasids rose on the back of rebellion from Persia, using the name Ali to rally the Shia partisans against the family that killed both Muhammed's son-in-law Ali and his son Hussain, of Karbala fame. They also had engineered their rebellion through messianic propaganda, charismatic organizers, intrigue, and secret cells- techniques that would be familiar to any Bolshevik.

Imagine the disappointment when the "Ali" meant by the Abbasids turned out to be quite different from the Ali of Shia veneration. Related, yes, but it was a bait and switch, with the truth coming out only after the Abbasids had authored a Mafia-style bloodbath and seated themselves firmly in power. This remains as one example of the much abused messianism of Iranian muslims, who had thought (mistakenly) that a reign of peace, justice, and light would follow the Umayyad overthrow.

Another aspect of the decline from Muhammed's original vision was the increasing violation of his commandment that Muslims were not to kill each other. The first civil war, involving Ali and the Umayyads, produced profound shock among those familiar with the original traditions. But as the decades passed, the empire descended into a welter of civil wars, and the energies once devoted to expansion (which effectively ended by 715) turned inward. Glubb seems to get a rise out of punctiliously reporting the various severed heads transported great distances through the empire, usually to inform the caliph of some great news, whether good or ill. Few chapters pass without such a scene. One can almost sympathize with the recent extremists in Iraq who expressed their nostalgia for the long-lost caliphate with such beheadings.


Now let me focus on the most fascinating chapter of the book, about the European dark ages (entitled "The End of Mare Nostrum"). Glubb digresses to argue that Muslim sea power in the Mediterannean accounts for the sudden autarky of Europe after the long centuries of Roman rule and commerce. The Arabs were far from natural mariners, at first keeping from naval engagements entirely, then gingerly hiring Egyptian and Lebanese ships and crews and using them as platforms to engage hand-to-hand with the enemy. But after several more decades, the Muslims gained regular fleets and control of the Mediterranean, which was the highway of the Roman Empire, early and late. The Byzantine empire was essentially confined to Greece and the Adriatic by ~700.

Glubb observes in one example that papyrus by the boatload was used throughout Europe to keep records, such as at the Merovingian court in France. But that ground to a halt abruptly with the Muslim defeat of Egypt, and Europe was forced to use parchment instead. One can imagine how devastating this was to government, commerce, and learning in general. The Arabs eventually learned the art of paper making from the Chinese, and relayed this to Europe centuries later. In the mean time, the Muslim empire cut Europe off from virtually every trade route of the ancient world- to Africa, to Egypt, to India, and to China and points east. Only Russia, the Baltics, and Byzantium remained in contact, and the latter only tenuously, through a sea lane that made Venice so wealthy.

Likewise with gold:
In the same manner, the supply of gold was cut off. The Merovingians at first alloyed their gold coins with an increasing admixture of silver, but eventually even this became impossible. In Charlemagne's time, only silver coins were in use. When Charlemagne became the ruler of France and Germany in 771, he found himself at the head of an inland state with no external commerce. p. 143
This, despite the Muslim empire virtually swimming in gold and other fruits of their industry and trade with the orient in the days of the Abbasid dynasty.

The question Glubb fails to pose is why- why didn't the Muslim empire continue the trade that was so profitable previously? Why did the Muslim control of the Mediterranean take the form of piracy (up to the US's defeat of the Barbary pirates in 1815, indeed!). Long-distance trade lay at the heart of traditional Arab life, so this is quite puzzling. But traditional Arab life meant raiding and plunder as well, on a freelance basis, so perhaps the net result was anarchy on the sea lanes. Also, once the Muslim empire moved inland from Damascus to Baghdad and became more Persian-oriented during the Abbasid period, its interest in the Mediterranean declined. Much later in the book, he does offer this paragraph:
There was little or no trade between the Arab Empire and Europe, owing to the unending hostility between Islam and Christendom. The Mediterranean, in Roman times the greatest highway of trade in the world, had become a no-man's-land and only war fleets or pirates sailed on its blue waters. A commercial trickle passed from the Arab countries by the Black Sea to Byzantium, chiefly through the hands of the Khazars of the lower Volga.

The only "neutrals" between Islam and Christendom were the Jews, who were permitted to live and trade in the countries of both "blocs". They had the entry alike to France, Spain, Constantinople, Egypt, Syria, and India. Individual Jewish merchants even travelled from France to Suez and thence to India and back.
Such widespread commerce naturally required corresponding financial arrangements, and a system of banking, making use of letters of credit and cheques, was available to merchants. Indeed our English word cheque is derived from the Arabic sek. p. 324

While the decline of Rome is mostly due to endogenous economic factors (such as vast inequality of wealth, with few land-owners and many landless workers), the final blow to the old Roman commercial system was its maritime disappearance at the hands of the Muslims, plunging Europe into isolation, feudalism, and darkness. The Muslim empire would also decline from its heights in the early Abbasid era, and face its own dark age at the hands of the Tatars and Mongols, just in time to send some of its fleeing intellectuals to a re-awakening Europe.

But this kind of thing also didn't help, as noted on page 124:
The Goths who conquered Spain were few in number and constituted merely an aristocratic ruling class, who lorded it over the slaves and serfs, as their Roman predecessors had done. In 587, Reccared, King of the Goths, was converted to the Catholic faith, and in 616 began to persecute the Jews, who were extremely numerous and prosperous in Spain.

  • An interesting analysis of oil price/efficiency sensitivity, arguing that we need to get to $300/barrel to approximate the efficiency incentives of the 70's oil shock.
  • Could we have our masculinity back, pleeeez?
  • PhD thesis on evangelical creationism.. you just can't make this up.
  • The women will save us, continued ...
  • What if the Victorians had had computers?
  • Rick Warren hates in the nicest possible way.
  • Dobzhansky's classic essay on evolution.

Saturday, December 5, 2009

Truth is overrated

"Convictions are greater enemies of truth than lies" -Nietzsche

As the car talk guys say, do you want to be right, or do you want to be happy?

As an exponent of the new atheism, I was intrigued by a recent piece by the pro-religion reporter at NPR, Barbara Hagarty, describing a "schism" in the atheist community (nudge nudge, wink wink). Apparently atheists are divided on how strident to be- whether to tell believers in religion, psychic phenomena, and all spiritualisms conventional and unconventional that they are wrong, wrong, wrong, or perhaps rather to stay in the closet, or else to suggest ecumenically that everyone has some "truth" to contribute to the "conversation".

I tend to be on the strident side, concluding after long exposure to religious claims, dabbling in various traditions, and scientific training, that, well, however well-meaning, it is all a load of bunk. But whether to tell everyone this good news is a matter of temperament, of political expediency, and also of basic philosophy- how valuable is truth, anyhow? Aren't lies sometimes better?

As a scientific type, I value truth above all things, by temperament and training. Yet how reasonable is that? Truth serves many useful functions, helping us survive, helping us know ourselves, others, and the world. But truth changes over time, and every person has his or her own version of it, sometimes diametrically opposed to that of others. In religion, this problem is particularly acute, with evangelicals as sure of their truth as atheists are of theirs. If each of us value only truth, then all will immolate each other in proselytizing fervor, particularly if the true message happens to include a dollop of evangelism, whether by insistently spreading the "good news" or by the sword as in Islam.

Another value has to take precedence, and that value is love, or at least communal regard for our fellow humans, however deluded. Truth has its place, but surely, no atheist wants to follow the example of the church in burning heretics for their own good in the hereafter, or Muslims in their early practice of killing infidels for sport and plunder, otherwise known as jihad. Nor do contemporary religionists in our fair land, excepting perhaps the far-out Major Hassans and left-behinders.

That is the essence of our cosmopolitan civilization- that while philosophy (love of truth) is an abiding pursuit and jewel of cultivation, the most important object of cultivation is our regard and love for each other, without which quests for truth can't happen. Thus cosmopolitanism (citizenship in the cosmos) seems a worthy successor to a long line of ethical traditions: Tribalism, Eye-for-an-eye-ism, Christianity, humanism, eco-ism et al.

~~~~~ Bonus post! ~~~~~~

"Freedom and not servitude is the cure of anarchy; as religion, and not atheism, is the true remedy for superstition." - Edmund Burke

I was deeply intrigued by this quote, and thought it might make a brief blog topic. Burke seems to be appealing to the golden mean, where too much freedom is anarchy, too little is servitude. All of which was so starkly demonstrated to him in the dramatic course of the French Revolution. In similar manner, religion is a little superstition, while atheism is none. This connects with other quotes of his, that "Superstition is the religion of feeble minds.", and conversely, "Man is by his constitution a religious animal; atheism is against not only our reason, but our instincts."

The context of the top quote, in a speech about those upstart colonies across the Atlantic, is all about governance, not religion. So the simile of religion was a throwaway comparison in this instance. Yet it is surely a very common sentiment across all cultures. Catholicism, Islam, and other organized religions serve to domesticate and civilize the basic human superstitious impulses which suspect hidden powers at work behind every manifestation. Likewise, much of the horror of colonialization across the Americas and elsewhere involved the destruction of indiginous spiritual traditions, some of which declined to such sad depths as ghost dancing or drowning in a sea of alcoholism.

From an atheist perspective, indeed from most perspectives, superstition is not a good thing, no matter whether in small or large amounts, so Burke's basic comparison is not quite right. The golden mean between anarchy and totalitarianism surely is institutionalized self-government as exampled by the English parliamentary institutions. Whether that can be called "freedom" is another matter, but it seems the best practical approximation, affording as much freedom as possible, in addition to the necessity of well-regulated government.

On the other hand, where is the golden mean between superstition and no superstition? If man is indeed a religious, superstitous animal, then some accomodation may have to be a made, much as we accommodate our many other frailties, without holding them up as ideals. Eating is necessary, but we don't make it a matter of philosophical hairsplitting or organized belief with truth claims about its wonderfulness, sanctity, and relations with a divine gourmand.

That, perhaps, is the crux of the response to atheism, that it turns a supercilious eye on one of our most personal, unrepentant, and inexcusable weaknesses, which makes those under its gaze decry atheists for meanness, inability to experience great things and deep emotions, and the like.

  • Topical interview with Frank Schaeffer on truth vs comity (towards the end).
  • Wonderful article on the genetics, potentials, and risks of gifted children.
  • Hot show on KCRW
  • Nice meditation on being and seeking goodness. No need for theology at all, really, just an appreciation and cultivation of our better natures.
  • But we don't want our brains to fall out, do we, Mr. Huckabee?
  • Blog I am starting to follow.. on cranky, er, stimulating, contrarian, and liberal economics.

Saturday, November 28, 2009

The gene for ... ?

Just how do they pack a human into 23,000 genes?

An interesting aspect of biology in this "post-genomic" age is how it has frustrated many researchers. Here we had expected genes "for" alcoholism, schizophrenia, autism, and all the other ills that ail us, but the road to find them has been rocky, tortuous, and has, in many cases, petered out to nothing. It turns out that genomes are complicated and don't come with user manuals. They didn't develop over evolutionary time in tidy ways that generate bodies and behaviors linearly from the DNA. Fruit flies have 15,000 genes, yeast cells have 6,000, and bacteria have 3,000. Most human genes are shared with bananas (i.e. the encoded proteins would function interchangeably). 99% of our DNA is shared with chimpanzees. So what makes us different, and oh-so-much better?

For every condition like eye color that can be attributed to simple mendelian variation in one or a couple of genes, there are a multitude of other conditions whose origin is not simple, but arises from the network of interaction of many genes. Coat types in dogs is another example of simple genetics, outlined in a very nice paper recently, where three genes suffice to explain most of the variation in dog hair types, from short/smooth (the wild-type) to curly, long, wavy, and wiry:

Combinations of novel alleles at three genes (FGF5, RSPO2, and KRT71) create seven different coat phenotypes: (A) short hair; (B) wire hair; (C) "curly-wire" hair; (D) long hair; (E) long, soft hair with furnishings; (F) long, curly hair; and (G) long, curly hair with furnishings.

But most aspects of biology are not so simple. Autism is the example I will focus on most, though similar observations apply to cancer, schizophrenia, personality/temperament, and on down the list of interesting and important conditions/traits.

Genes function in complex networks of regulation, both from the upstream direction of receiving regulatory signals, and downstream in the gene product's (a protein, usually) modification by other systems like phosphorylation and degradation, to eventual roles in combination with other gene products. It's all a big mess of interacting effects. What we see as the ultimate phenotype is the end result of complex mechanisms and lengthy development. Just as a cello has only four strings but an infinitude of musical expression, so genes can be played in different tissues, at different times, and in different volumes to accomplish many tasks.

For example, one set of genes, BMP1 to 20, (bone morphogenic protein), is an evolutionarily related (i.e. duplicated and diverged multiple times) family encoding small proteins that induce developmental events, like formation of cartilage and bone, when secreted by nearby cells. BMP4 is used repeatedly through development to induce notochord formation, eye formation, bone, and tooth formation, and pituitary formation, among others. To quote from one resource:
"Defects in BMP4 are the cause of microphthalmia syndromic type 6 (MCOPS6) also known as microphthalmia and pituitary anomalies or microphthalmia with brain and digit developmental anomalies. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS6 is characterized by microphthalmia/anophthalmia associated with facial, genital, skeletal, neurologic and endocrine anomalies."
Not a simple story, is it? BMP4 is used, reused, and reused again for similar purposes all over the body. A drug that inhibits its action would have devastating effects, though if that drug could closely control the timing and place of its effects, it might be very useful. That is one of the many challenges of drug development today.

Conversely, a single trait can be composed of the work of many genes. Down syndrome results from the duplication of an entire chromosome- many genes with slight increments in amount of product produced seems to cause a wide spectrum of altered traits. Autism seems similarly be be the consequence of the action of many genes, defects in any one of which can have similar effects. Autism spectrum disorder (ASD) has strong heritability (70% to 90% estimated), yet searches for the responsible genes have come up with not one, but scores of genes. I'll focus on one study that contributes to this story: "Efforts to map disease genes using linkage analysis have found evidence for autism loci on 20 different chromosomes." That is quite a statement, considering that we only have 24 chromosomes [a reader helpfully points out we have only 23!].

This paper used high-tech genomics to look for tiny deletions and other genetic variations throughout the genomes of families afflicted with ASD. Out of 195 autism patients and 196 controls, they found variants in 14 patients versus 2 in the control set. All the variants were heterozygous, indicating that, like in Downs, small increments or decrements in gene function may be responsible, with one normal gene copy remaining in each case. Some of the genes were expressed in the brain, while others were known to participate in retardation disorders, and others have little known about them.

Two other observations stand out. First is that most of these small genomic duplications or deletions are novel- they happened recently, and being deleterious, will die out rapidly as well. Autism "runs" in some families, but most cases result from spontaneous defects in a wide variety of genes. Second is the large number of genes estimated to be in this pool of possible ASD causers- at least 29 found so far between this and other studies, with more to come as more families are analyzed with ever more comprehensive methods. This is relevant to the rate of occurrence of this disorder, which is very high for genetic disorders, and possibly rising. It is known that autism rates go up dramatically for children of older parents.

So ASD seems to be the result of rare defects in any of numerous genes, many known to be involved in synapse formation and activity. It might be that an over-arching pathway of early brain development channels many genetic problems into the same syndrome, much as many problems with cars result in the common syndrome of "it won't start". Thus to think of genes "for" such diseases is problematic, given the complicated relations. There appears to be a developmental process that generates the syndrome, driven by many genes and susceptible to many distinct defects. And the case of ASD doesn't even touch on the separate issue of genetic variants that individually have tiny phenotypic effects on a trait, (such as height, for instance), but combine with many others to determine the overall trait quantitatively.

More deeply, for the genome at large, it isn't size that matters. Soybeans have almost three times the number of genes we have (though one-third the overall amount of DNA). It is how you use what you've got, in complex networks of regulation, combination, and reuse that makes a brain out of a bunch of cells. As the old Sun slogan had it, the network is the computer.

  • A relevant review of genome-wide association studies of "disease genes."
  • Climate disasters, a tad overdrawn.
  • The casually callous and obtuse David Brooks does in health care.
  • Does the Economist know economics?

Saturday, November 21, 2009

Treating patent addiction

Is the pharmaceutical patent system working for us, or against us?

An interesting web-book by Dean Baker makes the case that our government is socialist- but for the benefit of the rich rather than the poor. The general case has quite a bit going for it, with several trenchant points, though others are pretty weak, such as Baker's discussion of the role of the Federal Reserve.

Baker hints that there are better ways of fighting inflation than raising interest rates. And he maintains that raised rates have their main effect in cutting employment, putting the poor out of work, insinuating that this is some nafarious soak-the-poor policy. I'm not so sure. Raised interest rates raise the price of money and restrict new loans, which are the primary motor of money creation (and of economic activity, in our fallen age) and seem to efficiently combat the core issues of inflation. That this disproportionately hurts those on the bottom rung of the ladder is an automatic consequence of the overall capitalist structure of the economy, not any special property of Fed action. Could the Fed collect dollar bills and burn them? I'm not so sure, for who would give them up without compensation? Baker doesn't actually lay out his alternative plan, (other than direct wage and price controls, which are a singularly wretched tool), probably with good reason.

At any rate, Baker does present one fascinating case study- of the drug industry- which I think is on much firmer ground. To summarize, the current major pharmaceutical industry makes its money from the 20 year patent. Once a compound is discovered and filed for a patent, the clock starts ticking on this government-granted license to sell the resulting drug for whatever the company wishes to charge. (This is typically a function purely of maximizing the product of price times sales into what they imagine the market will bear, rather than recouping actual costs of research and production, or competing against other producers). This system gives drug companies huge potential incentives to create important drugs that they hope become a standard of care, with high resulting market demand.

Drug companies say that they spend an average of $800 million to bring a new drug to market, so their standard of sovency has become the "blockbuster" drug with annual revenues over $1 billion. This system has served the US well in many respects, with leading-edge pharmaceutical research, a continuous flow of new drugs in the pipeline, and a vibrant generic industry to offer rapid price reductions once drugs go off patent.

On the other hand, the system is also riddled with inefficiencies and incentives contrary to the common good. The $800 million figure is, I believe, quite inflated, since much of the work of the drug industry is devoted to making drugs with modest beneficial effects- drugs that may slightly ameliorate chronic conditions like depression, diabetes, or Alzheimer's disease. These drugs are can be extremely difficult to test because their small effect size requires large populations for trials, followed by ornate, if not ambiguous, statistics. Consider penicillin- its ability to cure infections was immediately apparent, and did not require large trials with thousands of patients.

In comparison, consider a drug like donepezil for Alzheimer's disease. It improves cognition slightly for a few months, costs ~$220 per month (still under patent in the US). Numerous studies have been done, covering thousands of patients. (The Cochrane meta-analysis says "23 trials are included, involving 5272 participants"). They typically show just-detectable benefits, which, calculated in cost-of-care terms offers no discernable benefit (cost of drug vs cost of increased care of untreated Alzheimer's sufferers).

Not only that, but each other drug company that wants a part of the action makes a copy-cat drug with slightly different chemistry and similarly marginal benefits, requiring similarly exhaustive and expensive trials to gain FDA approval. And then the drug companies complain that that the FDA is too restrictive! But the fault, dear Brutus, lies not in our stars, or in our government bureaucracies, but in the quality of the drugs being created.

The drug industry has a big problem right now- its pipelines are drying up, despite the huge advances in molecular biology and genomics over the last few decades. As the technology of drug discovery is taking quantum leaps in efficiency and comprehensiveness, there seem to be fewer drugs coming out the other end. This might be due to a true shortage of targets- we only have 23,000 genes, after all, and many of their products have multiple functions, making drug-based inhibition a perilous business, frought with side-effects. There may just be a limited number of ways to use small molecules to interfere with human biology.

New drugs approved (blue- formulations and combinations,
red- underlying novel molecular entities)

On the other hand, the problem might also be institutional in the pharamaceutical industry. To make money, drug companies have to sell lots of drugs. That means large markets and common diseases, hopefully chronic. But not all diseases are chronic or common, or afflict people with ability to pay. Diseases of the third world are notoriously under-researched and so-called "orphan diseases" and infectious (i.e. acute) diseases are likewise underfunded. Rather than do innovative research in to basic disease mechanisms, drug companies spend much of their money making copy-cat drugs in popular categories (think cholesterol reduction, acid reflux, depression, erectile dysfunction). And, of course, drug companies also spend roughly twice as much money marketing drugs than in researching them.

I think both problems are serious and getting worse. Viagra offers an interesting example. This drug was discovered serendipitously when Pfizer researchers looking for drugs for angina and hypertension, (classic categories for profitable drug hunting), all based on publically funded research on NO2 signalling, discovered a completely unexpected effect of one candidate. Now several companies have created similar drugs and great happiness has been rendered to millions. But note that this drug was found by accident, and the condition was not even on the company's radar screen. A double-accident plus a lot of publically funded research brought us this new drug category, which has made drug companies three billion dollars annually for a decade.

Does society really have to pay these exorbitant prices for such modest effort and accidental benefits? Baker claims that the excess cost of the drug patenting system over making all drugs generic from the start is roughly $400 billion per year. Is that a fair price for the research and market motivation that the current system gives us? Remember that the entire NIH, upon whose basic research virtually all pharmaceutical innovations depend in whole or in part, only costs $30 billion annually, less than one-tenth the industry figure.

Baker makes a proposal that with a doubling of the NIH buget to replace the research and development functions of the pharmaceutical industry, including modest prize incentives for development successes, we could gain all the benefits of the current pharmaceutical industry and more (i.e. targeting diseases more equitably, and focusing on significant rather than on marginal effectiveness), for a small fraction of the societal cost. I can't but agree that this is a very reasonable idea.

Indeed, the NIH is already dipping its toes into this pool of drug development, setting up programs to develop drugs for neglected diseases, one sector where our current system is AWOL. If corporate neglect where purely a function of the prevalence and harm of each respective malady, this market structure might be defensible. But often it is a function of the prospective length of treatment, (hopefully forever), the depth of the prospective patient's pockets, and prospective prevalence as juiced by energetic "informational" campaigns for what may have been unknown or minor maladies.

The clamor for buying drugs in Canada has been a sorry commentary on the dysfunction of our patent and drug system. The domestic drug industry uses its corrupt political influence to induce the government to pay whatever the patent holders ask, even for such enormous government programs as Medicare. Canada, not beholden to these companies, and given to more rational social policy generally, does negotiate prices down, attracting the interest of US consumers saddled with uncontrolled costs. Then US politicians, frustrated with their own corruption, get on the bandwagon, either cynically to gain a few votes, or possibly as a way to indirectly pressure the domestic drug industry to moderate prices. It's an insane way to get to where we should be going, which is to rethink the whole rationale of the patented drug sector.

This sector is just one example of the inefficiencies in our sclerotic political-economic system that is saddled with enormous legacies of infrastructure and vested interests as we enter this new century and try to battle our way to a better future. Current Senate rules, for instance, allow Senators representing barely 12% of the population to block any action. Deliberation is one thing, gridlock is another.

  1. Kaufman M. Decline in new drugs raise concerns: FDA approvals are lowest in a decade. Wash Post. 2002; Nov 18:A1
  2. Pollack A. Despite billions for discoveries, pipeline of drugs is far from full. N Y Times. 2002; Apr 19:C1.
  3. Dyer G. Anaemic patient needs to take its medicine: investors have fallen out of love with an industry with fewer products in the pipeline. Financ Times. 2003; Apr 16:2.

  • Others have problems with the drug industry too.
  • Meanwhile, military health care remains abysmal.
  • Religion is natural, after all.
  • Gosh- another atheist dilemma.
  • Just how does Goldman mint its gold? (But also here.)
  • For the love of Islam!
  • Another interesting story on synaesthesia, a fascinating window into consciousness and yet another argument against souls, versus a rather fallible circuitry.

Saturday, November 14, 2009

The warrior religion

Brief review of Glubb's history of early Islam

I am glad to report finding yet another gem in the hoary stacks of the local Catholic library, this time a history of early Islam, The Great Arab Conquests, by Lietenant-General Sir John Bagot Glubb (string of British orders & honors omitted here), 1963. If Amazon is to be believed, this book is out of print, and not only that, but its title was swiped by another author in 2007. This is most unfortunate, since Glubb's work is fabulous- exceedingly well written, frank, pre-politically correct, yet full of sympathy for his subject. Glubb spent his career in the Middle East, serving in both world wars and running the Arab legion, later part of the Jordanian military. He takes particular pride in clearing up a few scholarly confusions using his intimate knowledge of the ground in the Middle East, and of its military uses.

The book focuses on the first fifty years of Islam, retelling the story of Muhammad's life, background, and call, then going on to detail the careers of the first five khalifs ("successors"). Glubb is a military man and focuses on the military aspects of the story, with excellent maps throughout. But as a long-time associate of Arabs, Bedouins, and people throughout the Middle East, he also evinces sensitivity and admiration for their cultures, some of which have persisted with little change from the seventh century. Military affairs were central to the early history of Islam, and to the mindset of Muslims of that time, so this focus is incisive as well as stimulating.

One thing to note is that the quality of the khalifs was highly variable, from the high of Abu Bekr who directly followed Muhammad, to the pathetic impotence of Ali ibn abi Talib, who, along with three others of the first five, was assassinated. Glubb's portrait gives precious little evidence supporting the many partisans of Ali (Shia, or Shiatu Ali), vociferous as they are, since despite having high religious credentials and the closest personal connections with Muhammed, Ali was evidently passed over for the khalifate several times for what ultimately proved to be quite good reasons.

I won't try to retell the whole story, but just say that if you are interested in this history, you could hardly do better that this presentation, be it ever so hard to find! Glubb also wrote a sequel and several other books on the Arab cultures and his experiences.

Let me cite a few of the more striking passages, indicating Glubb's view of Islam and our relations to it.

Speaking of the first two khalifs,
We have already seen that almost the last act of Abu Bekr was to receive Muthanna ibn Haritha, who had ridden in hot haste from the Euphrates to beg for help on the neglected Persian front. The first act of Umar ibn al Khattab on assuming the Khalifate had been to dismiss Khalid ibn al Waleed from the supreme command in Syria. The second has been, as the dying Abu Bekr had ordered, ro raise a new levy for Iraq. Volunteers were at first slow in coming forward, for the Persians seem to have enjoyed the reputation of being more formidable than the Byzantines in war. As a result, recruiting proceeded by slowly, even though Muthanna himself made a speech in the mosque calling for assistance, and describing the immense plunder obtainable by those who followed the path of God and fought against the fire-worshippers. p. 160

In the book's conclusion...
The momentum of the great conquests had been so tremendous that they swept irresistibly forward without organization, without pay, without plans, and without orders. They constitute a perpetual warning to technically advanced nations who rely for their defense on scientific progress rather than the human spirit.
A cosmopolitan empire, with subjects professing different religions, could not constitute a devoted and homogeneous people of high morale, such as the Central Arabians had been twenty-five years earlier. p.359

Since the seventh century, many Muslim state have, at various times, established efficient legal systems and police forces, rendering private retaliation unnecessary, but the idea of revenge dies hard. In a wider sense, the right, and even the duty, of revenge has survived all modern reforms, for as a result of these early origins, it has become an accepted moral principle. This, it seems to be, is one of the directions in which Christianity differs most from Islam. Christians are never entitled to return evil for evil. In Islam, retaliation is a right, in some cases being even regarded as a moral duty. p. 367

Particularly is it noticeable that the idea of government by groups of men- cabinets, parliaments or committees- has no precedent at all in Arab history. Their idea of government is always one man. In theory he is chosen by the people. He must be humble, accessible, benevolent, pious and hospitable. Arrogant despots cannot be tolerated but nevertheless executive power must be vested in one man alone. All these traditions can be traced from the seventh century.

At various times since 1918, the Western Powers have painstakingly built up democratic, elective institutions in the countries of the Middle East. In every case, within a few years, these constitutions have collapsed and military dictators have assumed power. Perhaps this is not to be wondered at, for the military dictator is nearer the time-honoured Arab tradition than is Western Democracy. p.369

And this last parting shot:
This long-standing rivalry between Christians and Muslims has been due to political and geographical accident rather than to basic religious differences. Now that materialist atheism is challenging all spiritual values, the two religions might well make common cause against those who deny the existence of God altogether. There is, I believe, an immense field in which the two could co-operate. p. 371

One observation that struck me was the relation of Islam to power. Humans worship power- that is an unfortunate, but consistent, part of our nature (with obvious Darwinian origins). Power is an aphrodisiac to women, the source of male status, and the goal of youthful striving and careerist competition. Religion is little more than an expression of this emotion in over-wrought terms, since God is all-powerful, Jesus is Lord, and prayers and beseeching are our mode of intercession/intercourse with the imaginary beings.

Islam as refined this simple fact of human nature to the highest possible pitch, instituting and naming itself by universal submission to Allah who is great, while at the same time borrowing a bit of that greatness and demanding submission from all non-Muslims as a matter of right, whether the Dhimmi, (Christians and Jews), who are made second class citizens, or the outright infidels, who are offered conversion or death.

That is why terrorism works. The early Muslims used terror repeatedly, in quelling dissent in Medina under Muhammad, and in displaying power to quell resistance in the early conquests, when they didn't have the manpower to fully occupy the countryside (Glubb gives vivid examples in the conquest of Egypt). Terror cheaply communicates raw power and extreme dedication to one's cause, regardless of legitimacy or aims. And people respect, if not worship, power, combining a natural ability to tell which way the wind blows with a true respect for such dedication and will power. As Reagan said, "Nothing succeeds like success."

Saturday, November 7, 2009

Gray matter talks

New work on how the brain computes speech production.

A recent issue of Science had a few interesting articles on neuroscience, including one on how Broca's area in the brain processes language. But another article on functional brain imaging brought up a factoid that makes for an interesting introduction:
"Questions about functional segregation are constrained by the resolution of fMRI. For example, a voxel (volume element of several mm cubed) contains on average 5.5 million neurons, 10e10 synapses, 22 km of dendrites, and 220 km of axons."
Wow- I didn't know the brain was quite so dense. So why aren't we smarter? Honestly, one gets the impression that the brain is not very efficiently designed. No wonder vast regions of the brain can be destroyed in dementia before much of a deficit is noticed.

The current work (accompanied by a review) has its origin in rare people who have epilepsy and who get the unnerving procedure of having electrodes stuck into their brains. I have no idea why such an invasive test is done, but for Sahin et al., it was a godsend, allowing them to do the kind of electrophysiology normally restricted to other animals such as monkeys, rats, and cats. Such work has told us huge amounts about the visual system and other brain circuits, but cats can't talk, so such work can't tell us much about that human ability.

Image of Broca's area and fMRI activation by a speech task, in patient A.

Broca's area and a few others are well-known to be involved in speech production, by way of strokes and other lesions that specifically affect those abilities. But how does it work? Is processing sequential, like the visual system, where a hierarchy of processing takes signals from raw retinal input to various color, edge, motion, and shape detection, up to object recognition? Or is language different, capable of being processed in a more parallel fashion, with all elements (word choice, grammar, phoneme production) coming together at once?

Patient A, with the surface of Broca's area exposed and electrode paths indicated.

This paper supports the former model, finding sub-locations in Broca's area that activate during specific stages of speech production, indicating that, while the full region involved is far smaller than the huge areas devoted to visual scene interpretation, it is also hierarchically arranged, with computations happening sequentially.

Electrophysiology like this is still a pretty quaint and brutal way to look at the brain. Electrodes, resembling dipsticks, are stuck right into the grey matter, with the hope that not too many cells are killed, no blood vessels are blown, and that whatever neurons are near the active surfaces of the electrode give off enough electrical buzz for detection (called a local field potential). Each electrode has several channels (i.e. openings) along its length, so you can listen in to several discrete depths once it is inserted.

Illustration of probe location, with channels indicated in yellow.

The experiment was to cue the patient with a fill-in-the-blank sentence, such as "Yesterday, they ____" plus a generic word to fill in, such as "to walk", or "to think". The patient had the task of computing the right form of the verb (walked, thought) and speaking it silently. (How speaking silently actually works in these experiments is a little hard to understand.) The observation was that reading the cue sentence correlated with a small activation near the Broca area electrodes, while producing the requisite word correlated with much larger activations.

Mix of electrode traces from a few channels. The sentence with blank is presented at the cue time, and the word to be filled in is presented at the target time zero milliseconds (ms). The colored arrows point to the segments discussed below at 200, 320, and 450 ms.

The second observation was that the activations related to speech production were complex, taking place over roughly 600 milliseconds (ms), with distinct peaks and troughs at 200, 320, and 450 ms after presentation of the fill-in word, depending on the channel and electrode location. The point of the experiment was to vary the fill-in words such that more or less complex processing demands could be correlated with more or less complex electrophysiology during these periods of proccessing in Broca's area.

The strategy is much like trying to figure out how a computer works by holding a few electrodes to a computer chip while it is working- a ludicrously difficult and primitive approach to reverse engineering. But it is all we've got for the moment, until functional imaging and non-invasive EEG technologies reach higher resolution. The observations are thus correspondingly crude- that the processing of incipient speech can be broken down into sequential phases (three in this paper) of word identification, inflection processing, and phonology processing. Here is the variation they observe in word identification:

Here, the brown curve around 200 ms is higher for rare words (no examples given) than for common words (but not for short vs long, or multi-syllable vs monosyllable), indicating that this activity is related to word identification.

These curves at 320 ms indicate variation in response to verbal inflection processing- past tenses, irregular forms, etc. "Read" is the control, with no fill-in work. The patient just reads the sentence. "Null-inflect" is when a fill-in is asked for, but the proper form happens to be the same as what is cued, so there is no phonological processing, only implicit grammatical/inflection processing (Every day they ____ [walk]). And "overt" is when the fill-in demands both grammatical processing and changes to the word (suffix or change in form). (Yesterday they ____ [walk]). The experiments were run repeatedly, with flashed cards and randomized orders, with the curves reflecting averages, and curve differences given P-values of 0.01 or less.

Curves at 450 ms (note the different channel (depth) used) correlate with processing for sound construction- related to number of syllables, changes in word form, etc.

The author's conclusions are that they have dissected some aspects of speech production based on where their electrodes penetrated the patient's brains and the timing of observed electrical events, coupled with experimental variation of tasks given to the patients. While most of this was surely known indirectly, based on the many patients with known defects of Broca's and other areas from strokes and other ailments, seeing this activity and its variations in real time is certainly unprecedented, and will contribute to ongoing refinement of the functional mapping of the brain, which, as noted above, has so very far yet to go.

As a stutterer, this is fascinating, and I hope that far more is learned about the nature of speech construction, to the point that the miswiring involved in stuttering might be diagnosed (if not fixed). And of course it also indicates yet again that our behaviors are not magical products of souls, but are computational products of brains.

Saturday, October 31, 2009

Management, or feudalism?

How management captured the economy, and what we can do about it.

Americans are so cowed by this point that they hardly register a flicker of resentment when Wall Street executives give themselves billions in bonuses after flushing trillions down the drain and saying a begrudging "thank you" for more trillions in government life support. How did we come to this pass?

One of the great changes in the last 50 years has been the broadening of stock ownership. Out with the smoke filled rooms and blue-chip bespoke trading, in with mutual funds, etrade, and all-in dot-com stock investing. This has been great in many ways, putting more money to work in productive enterprises and earning regular people substantial gains (at times, at least).

But it also had the paradoxical effect of diluting ownership of corporations. When everyone owns a company, no one does. And management eventually learned what this meant- that they could run their companies as they wished, subject only to the whims of stock "analysts", but not to their true owners, who might have a longer-term interest. Boards of directors, previously direct representatives of the shareholders, now became hand-picked cronies of the management, ready to "motivate" management with lavish pay in an arms race of executive generosity.

The Reagan era helped generate the latest edition of this culture, claiming that America's greatness lay in its executives, and its economic prospects in trickle-down economics. Cultural progress emanated from the boardroom, not from the shop floor. Unions were there to be broken, not negotiated with. While the cult of entrepreneurialism remains a positive aspect of this culture, the cults of MBA-ism, management consulting, cronyism, and open corruption in boardrooms and in government lobbying has been anything but. And the bonuses and guaranteed stock options now being paid out of tottering or under-water balance sheets clarifies just what management meant by that "motivation" that was supposed to tie them to market "discipline".

It's a mess, and a recent article in the New Yorker article about a few corporate do-gooders who urge large stockholders (pension funds, mutual funds) to militate against a few of these excesses was nice, but far, far short of what is needed. We need a revolution in corporate governance that recognizes the limitations of the new corporate ownership model where some benefits are shared broadly, but many (sometimes most) are concentrated in the hands of a feudal management, which is left by the current owning, legal, and cultural regime to run its show unmolested, for its own benefit.

In the economics literature, this is called the agency problem, and pervades all sorts of interactions. We hire someone to do something for us, like build a wall. This requires supervision, but how can we comprehensively supervise the process without giving up and doing it ourselves? We can't. At some point, one has to either have faith that the person hired is honorable and will not make hidden errors, or one has to delay the payment so much that any errors become apparent prior to payment, perhaps postponing payment for 25 years or more. The latter is neither practical or palatable, so we put up with uncertainty in contractors, paying them before we really know the quality of their work.

With corporations, the agency problem is likewise enormous, and getting bigger all the time as ownership dilutes and legal protections, often legislated from the courts, expand. Specifically, the problem boils down to a few points:

1. Management is overly free of supervision by owners, leading to orgies of empire-building, vanity projects, short-term stock pumping, political freelancing, and other problems.

2. Management is paid in an undisciplined way, neither accounting for true long-term impact, nor being immediately subject to a coherent system of checks and balances. The "labor market" for executives is not just inefficient, but riddled with corruption.

3. Management meddles in government by lobbying, attaining disporportinate influence. The recent ruckus over the Chamber of Commerce only shines a brief and flitting light on this cancer in the body politic.

Corporations are creations of the state. They are not free associations of citizens in the classic sense, but are a special class of association (by charter) with several government sanctioned benefits, including limited liability, special tax structures, separate legal personality, regulatory services (not to mention bailout services), and more. Thus it is entirely reasonable, contra the supreme court, to restrict the free speech "rights" of corporations (i.e. their right to corrupt the political process by lobbying and political activism by management with corporate funds).

So we don't have to put up with corporate lobbying, corporate political donations, or corporate meddling in the political process. We don't need Wall Street bankers designing their own bailouts, and we don't need health "insurers" telling us whether we can or can not legislate health insurance reform.

Secondly, corporate governance needs to be reformed in a basic way. Pay must of course be reformed to reflect long-term incentives and the more prosaic recognition that management skill is neither as rare nor Empyrean as often portrayed by managers. But this will never happen while management appoints its own overseers. While ideally, corporate democracy would be re-established with true control by shareholders, this is impossible at the current levels of dilution, and at the level of apathy appropriate to the reciprocal form of dilution- which is to say that each individual investor in vehicles like pension funds and mutual funds has miniscule levels of any particular stock and thus miniscule interest in its governance. So some other mechanism is needed to guard the public good along with the shareholder interest.

I would recommend addition of a public board to all public corporations. This board would be legally superior to the private board constituted by current rules, able to fire that board and managment, run shareholder elections, and otherwise control the corporation in times of urgency. Such a board would in normal times represent the government and regulatory interests, keeping an eye on the company's affairs. Two of its members would attend private board meetings, and vice versa as well. Extra activity of this public board (beyond monitoring and regulation) would be decided by shareholders in a simple voting system, where rather than vote for specific people, (such as nominees of the management to a private board), votes would be for a level of confidence, perhaps from one to five.

In this way, shareholders would have a simple and direct way to register general concern with the enterprise, which in turn would tell this public board, appointed by the chartering government, (or the federal government for inter-state and international corporations), to either (#5) stay out of the affairs of the company, it is doing just fine, or (#1) take all actions necessary to correct a bad situation and right the affairs of a problematic management.

This idea recognizes that most corporations behave appropriately most of the time. It adds a check in cases of problems where a public board can be automatically activated at shareholder discretion, expressed in a straightforward way that gets around the difficulties of evaluating particular candidates and allows a general no-confidence attitude by shareholders to result in action to discipline management and resolve the situation. Such boards could also aid in the liquidation of businesses the government is otherwise reluctant to touch (see Lehman).

Naturally, there would need to be rules of various sorts to stipulate the kind of public boards that could be formed, insulated from political as well as corporate influence, perhaps diversified by origin in the civil service, academy, party affiliation and private sector. It would not be a board of expertise, but one of oversight, able to hire new executives and private board members in extreme circumstances, and to investigate the other actors. Members would be paid minimally, perhaps by the chartering institution or by general fees, similar to how the FDIC is funded.

There may be many other (and perhaps better) ways to approach this issue in corporate governance. The no-confidence vote system might directly remove a current board or management, instead of empowering a public board. It is a complicated issue, but the existence of the problem is not complicated at all- it is patent and in need of deep reform. It is eating at our politics, economic system, and culture, and we can only hope that capitalism is capable of undergoing further evolution for the common good.

PS- I have a special solution for the financial industry, whose gambling addiction appears to be more serious than previously suspected. Which is to levy a small tax on every transaction. Every share bought, sold, every derivitive conjured and sliced, would be taxed at a small rate, say 0.5% of value. This would have several beneficial effects- it would slow down financial transactions, of which there is far too much churning. It would enforce visibility of all such transactions, going into all relevant markets, whether currently regulated or not. It would raise huge amounts of revenue, which we could really use at this point (ahem!). And when applied to international currency speculation, it would lend some stability against being whipsawed by vast in/outflows of money. The recent program of super-fast trading by way of special computer networks by Goldman is exhibit A of trading that is simply contrary to the common good, and for which we need a systematic solution.