Iran and Saudi Arabia

Modern propaganda and ancient hate.

Frontline has an excellent three-hour series on the conflict between Iran and Saudi-Arabia. They come off like minuature versions of the US and the Soviet Union- superpowers of the Muslim world enmeshed in an ideological and tribal battle that is fought through proxy forces throughout the Middle East, making a hash of smaller countries and making strange bedfellows with the likes of Israel.

The Shia-Sunni split was always an undercurrent in the Islamic world, but was sharpened by the advent of modern fundamentalism. While the Saudis have always been fundamentalist in theory and corrupt in fact, Iran plunged into total fundamentalism with the revolution of 1979. The documentary discusses how sharply this changed the dynamics in the Muslim world, with Iran suddenly vaulted into the vanguard of the fundamentalist movement. This perennial "back-to-basics" feature of religion became a deeply ideological and psychological response to the muddled end of colonialism and the general failure of modernity in the Muslim world. We hear mostly of its Sunni / Salafist incarnation, as ISIS, Al Qaeda, the Muslim Brotherhood, etc. But for the Shia, it had an extra edge of tribal revolt against Sunni oppression.

Shia make up roughly 1/3 of Muslims in the Middle East, with populations in each country. They are a majority in Bahrain, though they have no role in the government. That was the situation in Iraq as well until recently. Iran's fundmentalism is sectarian, not pan-Muslim. Thus, despite ethnic divisions, it has been an instrument to unite Shia populations across the region, such as the Hezbolla party in Lebanon and the now-ruling parties in Iraq. Iran's reach is obviously limited by this sectarian character, but they have been willing to arm their friends to the hilt and send their minions into battle for the most dubious causes, especially the Assad government in Syria, which is composed of another Shia sect.

Saudi Arabia is petrified by all this, partly because they have their own Shia population, but more because their own power projection has been so bungled in comparison. They have assiduously funded fundamentalist madrassas and terrorists, and what do they have to show for it? Hatred from the West, yes, but also quite a lot of hatred from their own spawn, such as Osama Bin Laden, whose disgust with the top-heavy, spoiled, corrupt Saudi institutions was emblematic. Their best friend, the US, conquered Iraq and not only botched the whole project disastrously, but left the country in Shia hands. And in Pakistan, one of their most successful test beds of miseducation, does all the fundamentalism add up to a strong state or a good friend? No, it has led to chaos, double-dealing, and misery.

One of the themes going through this story is propaganda. No one in Iran gets Lebanese Hezbolla fighters to die in Syria for Assad without a very heavy dose of propaganda. A bunch of Saudis do not fly into the World Trade Center without lengthy indoctrination. Fundamentalism in general is the triumph of poorly thought-through ideals and archetypal images over reason and basic decency. The Palestinian cause, now in its twilight, was one long piece of performance art- of grievance and rage as policy and, occasionally, power. And the long Saudi / Wahhabi campaign of Jesuit-style fundamentalist eduction has only furthered the weakness and backwardness of the Muslim world in general, not to mention its violence, particularly against women. The record is appalling, but the mechanism teaches universal lessons- that people can be led in disastrous directions by well-crafted propaganda, based on supposedly profound fantasies.

It is something we are learning in the US as well, to our peril. Does free speech mean that private broadcast networks can spew the most pleasing, and scurrilous, falsehoods? Just how much bilge can the internet contain, and not blow up? Conflicts like the one above, between Iran and Saudi Arabia, are made possible by propaganda, which moves people to extraordinary emotion and effort. World War 2 remains a textbook example, with Germany and Italy transformed by deeply emotional, false, and effective, propaganda. We are in the US at a tipping point, with half the population feeling themselves part of the Republican team, whose life support comes from propaganda that seems, at least to this biassed observer, unworthy of any political discourse or intellectual respect, headed by a President who lies so casually and habitually that we now take it as absolutely normal. How can reason and empathy penetrate this jungle of mean self-righteousness?

Returning to the topic, the current administration's support for Saudi Arabia and hatred for Iran is not easy to understand, on the face of it. Saudi Arabia is at least as destabilizing a force in the world and in the Middle East. Both are explicitly fundamentalist, and both seek to export their ideologies abroad. Both are sources of oil, though the Saudis have far more and play the lead role in world oil prices. We do not care that much on our own behalf anymore, but have strong interests in keeping the oil infrastructure (political, military, and physical) of the Middle East intact on behalf of the developed world, for much of which (Europe, Japan) we have explicit defense responsibilities. So sure, we want to be friendly with Saudi Arabia and continue to have military bases in the area. But we have interest in friendship with Iran as well, which has far greater human and intellectual potential. Both countries have a fraught relationship with Israel, though Saudi Arabia has of late been much more accommodating, in its cynical and conservative/authoritarian way. But Iran's problems with Israel seem similarly superficial, just a way to gain credibility with the Palestinians and other disaffected Muslims. And our own difficult history with Iran, and their vitriolic propagada against us, is hardly reason to fall in line with Saudi Arabia's sectarian program. It would be better to turn the other cheek, as the Obama administration started to do.

If the struggle for supremacy in the Middle East were prompting a flowering of cultural, scholarly, and scientific advances, that would be one thing. But the reality is far more tawdry, where the Saudis just buy more arms from the US to dump on Yemen, and Iran coopts and arms Shia communities in the neighborhood, destroying Lebanon in the process, and bidding to do the same in Iraq, Syria, and Yemen. The collision of irrational ideologies, served by up-to-the-minute propaganda methods, run by governing structures ranging from dysfunctional to medieval, is a toxic brew not likely to enhance the culture or living conditions of those in the region any time soon.

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Science is not the Answer

Bryan Appleyard has some complaints about the new priesthood and its corrosive effects on the old verities, in "Understanding the Present: Science and the soul of modern man".

This is a genuinely exciting book (dating from 1993) about modernity- our age where science in all its facets has not only transformed practical existence, but also our spiritual lives, de-mystifying nature and tossing religions, one after the next, onto the scrap heap. Appleyard is not happy about it, however- far from. He is tortured by it, and while he can not stomach going back to religious orthodoxy, whether of fundamentalist or mildly liberal varieties, nor can he accept the new regime, which he views, somewhat mistakenly, as scientism. That is the belief, fostered (in Appleyard's view) by the gushing popularizers like Carl Sagan, Jacob Bronowski, and Richard Dawkins, that science can not only solve all our questions of knowledge, but forms a new technocratic morality of reasonable-ness and tolerance which, if properly worshipped, could resolve our social, political, and spiritual problems as well.

The first half of the book is far better than the second. Setting up the problems of modern spirituality is far easier than solving them. In broad strokes, humanity used to be at home in heavily archetypal religious realities. While actual reality did intrude from time to time, the fables of Christianity, to take the main example in the West, were (and for some, still are) magical tales which gave us hope of a benevolent meta-reality and a pleasant afterlife. But intellectuals kept trying to make sense of them, until they "sensed" them completely out of existence. Appleyard cites Thomas Aquinas as perhaps the finest of these intellectuals in the theological tradition. His main work was to reconcile Aristotle, the pre-eminent scientist of antiquity, with Christian orthodoxy. This was taken as the height of theology, not to mention truth in general. But it planted the seed of modernization and logic- if something is logically or empirically true, it must necessarily be consonant with the Catholic religion, which is by definition true. Thence downwards through the enlightenment, Newton, the  industrial revolution, existentialism, liberal theology, to the plague of atheists we see today. The Catholic church tried to draw the line with Galileo and the heliocentric model, but that did not go well, and a few hundred years down the road, they gave up and said they were sorry.

"Science was the lethally dispassionate search for truth in the world whatever its meaning might be; religion was the passionate search for meaning whatever the truth might be."

All religious pretensions to scientific truth have been exploded, and the only choices left, as Appleyard sees it, are regression into fundamentalism, continuation to the endpoint of modernist anomie where humans are morally worthless or even negative destroyers of pristine nature, an acceptance of science itself as humanity's triumphalist project, which through its powers and gifts can give us all meaning, ... or something else. Appleyard spends much of the second half of the book on the fourth option, discussing quantum weirdness, chaos theory, computational incompleteness theories, and related fields which put the lie to the determinist dreams of nineteenth century science. Science does not know everything, and can not know everything, thus there is some gap for us as humans to be free of its insidious, deadening influence- a humanist space.

There are many things wrong with Appleyard's take on all this, some of which are contained in his own arguments and writing. Science has long held to the fact/value distinction, as he discusses at length. Even such a solidly scientistic enterprise as Star Trek recognizes regularly that Spock can neither supply all our values, nor even on his own terms operates without idiosyncratic values and meaning. The world of Star Trek is morally progressive and rational, but its motivations and meaning come from our human impulses, not from an algorithm. Exploration, skimpy uniforms, and great fight scenes are who we are.

"The key to the struggle, it cannot be said too often, is the way in which science forces us to separate out values from our knowledge of the world. Thanks to Newton we can not discover goodness in the mechanics of the heavens, thanks to Darwin we cannot find it in the phenomenon of life and thanks to Freud we cannot find it in ourselves. The struggle is to find a new basis for goodness, purpose, and meaning."

But then Appleyard frequently decries the new scientistic regime as having destroyed morals in general.

"... all moral issues in a liberal society are intrinsically unresolvable and all such issues will progressively  tend to be decided on the basis of a scientific version of the world and of values. In other words they will cease to be moral issues, they will become problems to be solved. The very idea of morality will be marginalized and, finally, destroyed."

This makes no sense, as he himself concludes by the end of the book. It seems to be a matter of looking for morals and meaning in all the wrong places. After a long excursion through the death of scientific determinism, he consoles us that science doesn't, and can't know everything. Thus we can go about our lives with our own values, desires, and dreams without paying much mind to any moral teachings from the scientific priesthood, which didn't exist anyhow. Whew! Determinism is a complete red herring here. Science studies all of reality, whether complicated or simple. If broad swathes can be subsumed into the master equation of gravity, that is wonderful- empowering on practical and psychological levels. But sometimes the result of all this study is a large database of genes and their properties, whose complicated interactions preclude easy prediction or codification (harkening back to the cataloguing of Aristotle and Linnaeus). Or sometimes it is a prediction system for weather which, despite our best efforts, can only see a limited distance into the future, due to inherent limitations to any model of a chaotic reality. That is OK too. Such pursuits are not "not science", and nor does such ignorance furnish us with free will- that comes from adaptability. The results of our studies of reality do not imply much about our meaning and values in any case, even as they defang the oddly materialistic superstitions and totems of yore. Our powers of understanding may be amazing, and fetishized by the educational system and science popularizers, but are not the foundation of our moral humanity.

Scientific studies of ourselves have, however, been enlightening, uncovering the unconscious, Darwinian designs, ancient urges, and a great diversity of ways of being. They have also clarified the damage we are doing to our environment via the wonders of modern life. This has informed our self-image and hopefully our values, but hardly determined them. Humility is the overall lesson, as it has been from all the better religious traditions. Appleyard decries relativism, the liberal tendency towards excessive humility- suspicion of one's own culture, and excessive regard for those of others. But isn't that merely a slight overshoot / correction from the madness of colonialism, slavery, genocide, rampant technology, greed, and war that has been the Western history over the last couple of centuries? Isn't it a spiritually healthy step back? In any case, it is an example of human values at work, perhaps more influenced by our prosperous condition than by any dictates from science.

Appleyard's fundamental complaint is against the new priesthood that has taken over management of the wonders of creation, but has at the same time failed to address our human needs for solace and meaning. Indeed, some of its high theologians delight in telling us that the universe, and ourselves, are utterly meaningless. Appleyard constantly weaves god into the discussion, while taking no exlicit pro-god position. He can not bring himself to bite that bullet, but rather is content to complain about being thrown out of Eden for the sin of too much knowledge. Well, it was always a cheap trick to read our fate in the stars or in goat entrails, and to read our meaning in ancient wonder-tales. These methods were merely externalizing values that came from within. The patriarchial systems of theology express most clearly the interests and desires of the men who run them. So we are, in the modern dispensation, merely reduced to a state of honesty about stating what we want, without the false veils of magic, authority, and supposed moral objectivity. And that change seems, at least to me, beneficial for our moral situation, overall.

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• Who cares about truth anymore?
• Our common economic statistics are not cutting it.
• Japan is doing very well, thank you.

On Vacation

Just a few links for this week:

• Let's protect marine life.
• Notes on experts.
• Altruism, for me!
• Making China great again.
• Religion as a disease.
• What on earth has happened to freedom of speech?

Arthur Kornberg

Notes on a great biochemist.

One thing that has made America great is our biomedical research establishment. Over the second half of the 20th century, the US created a uniquely effective set of funding institutions, and grew a large cadre of scientists who have led the world in the adventure of figuring out what makes us tick. Biology, at the molecular level, is an alien technology, based on chemistry, yes, but otherwise utterly unlike to any technology we have developed or been previously familiar with. It has taken decades to get to our current incomplete level of knowledge, and it will take decades more to unravel such complex processes as the detailed genetics of early development, or of schizophrenia, or the nature of consciousness.

Yes, it has led to biotechnology and growing prospects for improved medicine. But the historical significance of this epoch lies in the knowledge gained, of finding and exploring a vast and ancient new world. One of the leading scientists of the early days of enzymology and molecular biology was Arthur Kornberg, whom I learned from through his textbook on DNA replication. It was a model of clarity and focus, filled with apt illustrations. It was the rare textbook that didn't try to cover everything, and thus could treat its proper subject with loving care and detail.

The cover depicts a micrograph of replicating viral DNA, the new duplex forming in a loop in the middle, and much of the DNA covered with proteins that help the process along.

Kornberg was the subject of both an autobiography and a biography / hagiography. The latter was written by a fellow scientist, but steers only gingerly into the science, sticking mostly to the story of Kornberg's life, times, and relationships. And what science there is is rather biased. For example, several years after the Watson-Crick model of DNA came out, Kornberg's lab developed a compositional assay for their short snippets of replicated DNA made in the test tube, and deduced that replication was anti-parallel. That is, one DNA strand of the duplex runs in one direction, chemically speaking, while the other strand runs in the opposite direction. This is portrayed as a discovery, for which Crick was very grateful in correspondence. But the Watson-Crick model had already posited the anti-parallel nature of DNA as an intrinsic property, and the model had been richly supported by that point, so Kornberg's work was at best confirmatory. Crick was just being polite.

An interesting side-light is that this epoch in biochemistry and molecular biology was substantially enabled by the scientific and technological breakthroughs of the Manhattan project and nuclear physics. It was isotopes like phosphorous-32 and sulphur-35 that allowed far more sensitive assays for nucleic acids than ever before, allowing tiny amounts of enzyme to be tracked down. DNA sequencing began with ladders of size-selected nucleic acids digested chemically from longer molecules and visualized by X-ray film thanks to radioactive P-32 enzymatically attached to the ends.

Early days, Arthur (right) and his wife Sylvie, who played a central, though unheralded, role in his laboratory and work.

One irony of the story is that Kornberg was so stuck in his system that he was resistant to the new fields it gave birth to, i.e. molecular biology. In his prime, he ran a factory of a lab, indeed a whole department, (first at Washington University, St Louis, then at Stanford), devoted to finding and characterizing the enzymes of nucleic acid synthesis and particularly DNA replication. These groups purified enzymes on a massive scale from E. coli cells, which were broken open, filtered, and then passed over various charge-selective and size-selective media, in extensive multi-step protocols to come out at the end with more or less pure single proteins or complexes of proteins. Some of these enzymes turned out to be extremely useful in biotechnology, for the cutting, copying, ligating, repairing of DNA, etc. As time went on, scientists realized that enzymology, while an important part of understanding how things work in cells, is usefully supplemented by the many methods of genetics and cell biology, which resulted in a hybrid field called molecular biology.

For example, Kornberg's Nobel prize was won, and name was made, on DNA polymerase I from E. coli. This enzyme replicates DNA, but not very well. It tends to fall off a lot. Some years later, another lab created a mutant E. coli strain that lacked the gene encoding this enzyme. And lo and behold, the cells were fine. They reproduced and replicated their DNA. It turned out that E. coli encodes five DNA polymerases, of which DNA polymerase I is among the least important- a repair enzyme that finishes gaps and other problems in the duplex, leaving the bulk of replication to other, far more ornate enzyme complexes. It was genetics that provided the critical clues in this story, showing how an integrated and diverse approach to research questions provides more productive answers.

Master of his realm, in later years, with fruit-themed computer.

Kornberg ran a family-style system in his departments. He had drawn most of its members (at Stanford) from among his own post-docs and students. It had communistic, but also authoritarian, elements. Space was shared, reagents were shared, even funding was shared- something unheard of today. At the same time, Kornberg had the last word on everything and was a ferocious micromanager. Researchers who wanted to make a name for themselves and build their own empires had to leave. But Kornberg picked well, and many of his colleagues had very influential careers, especially Paul Berg, a pioneer of recombinant DNA methods. Kornberg's strong dedication to his field and his system- his sense of meaning and purpose- was a precondition of success, communicating itself to all around him and fostering an unquestioned work ethic and community ethic. The Stanford department was legendary in its day, and inspired many other researchers to become enzymologists and use the laborious methods of protein purification to get their hands on the very gears and cogs of life.

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• MeToo and Kavanaugh. And perjury.

Striptease by HIV

How the virus disrobes is an important part of its life cycle, secrets of which are still being uncovered.

For such a tiny entity, HIV-1 has a very complicated life. Its study has generated numerous drugs that interfere with key life events, and have brought it under control in most developed areas of the world. But there is a lot left to learn. While its fusion with target cell membranes and eventual replication have received the most study, less is known about what happens in between.

The layers of HIV. Outside is a membrane, which features proteins like gp120 that binds to T-cell receptors.

The virus has several layers. On the outside is a membrane coat, designed to protect the virus in moist environments, but more imporantly to expose surface proteins that seek out T-cells specifically, and then to fuse with their membranes, thus entering them. Inside the lipid membrane and its supporting proteins is the capsid, a protein coat that protects the HIV genome from attack by internal T-cell defenses like RNases, helicases, RNA sensing proteins, interferons, and their various downstream effects. This capsid finally lets go if its cargo at the nucleus, where the viral genome, now transformed into double stranded DNA, integrates itself into the cell's genome.

Electron micrograph of HIV particles. The capsid sits inside the membrane coat, all of which is about 120 nm in diameter.

Innermost is the genome, composed of RNA, not DNA. Packaged alongside it are key enzymes integrase, RNase H, and reverse transcriptase. Once HIV enters the cell, and meets the rich mother-lode of ATP and other nucleotides, including deoxy-ribonucleotides that are the building blocks of DNA, the reverse transcriptase can begin its work. It copies the  genome in a complex sequence of starts within the linear RNA, hops to the other end of the RNA, continuation, and finally termination. All the while, the RNase digests the original RNA genome, in a remarkable process of self-transmutation. It is thought that synthesis of the complementary DNA strand only begins after the virus rides the cell's light rail system (microtubules) to the nucleus, where it leaves its capsid behind.

Some recent papers shed a bit of light on the nature of the HIV capsid, which is more interesting than previously understood. It was not previously clear whether the capsid uncoats at the membrane during original entry, or only at the nucleus, or even inside the nucleus. But one paper shows quite definitively that the capsid remains intact through the first strand of DNA synthesis, thus through most or all of the virus's trip from the outside membrane the nucleus. This work required rather difficult assays for capsid integrity, judged by the inclusion of fluorescent protein GFP into the viral genome. Most of this protein escaped during viral fusion with the membrane, since most of the free volume of the virus is outside the capsid. But a small portion remained visible as long as the capsid remained intact.

One hexamer of the capsid protein CA. At the center is pore, accommodating a very small molecule of ATP, in yellow/orange. The surrounding blue parts of the protein are positively charged, ideally suited to attract nucleotides and the IP6 stabilizing molecule.

Another paper took a closer look at the stability and composition of the capsid. It is known to be composed of roughly 1500 copies of the viral CA protein, in multimeric (hexameric and pentameric) rosettes. The structure above shows that at the center of these rosettes is a small pore, big enough to let in ATP- suggesting clearly that the deoxynucleotides needed for reverse transcription can enter even while the capsid is intact, providing the virus with the best of both worlds- protection from the cell's various specific antiviral defenses, but also food for its replication. In the lab, these capsids have been remarkably unstable, however, leading some to believe that the virus uncoats soon after it enters the cell. But these authors find that a chemical that is obscure, but common in cells, IP6, is shaped just right, and negatively charged just right, to sit in these rosette pores and stabilize the whole structure, extending the lifespan of capsids in the test tube to hours instead of minutes.

Two mysteries remain- first is how deoxyribonucleotides get in if IP6 is blocking the pores and stabilizing the structure. The likely answer is simply that these small molecules are not plugs. They have more stochastic behavior, jumping on and off frequently enough to allow other small molecules occasional access. The second question is what finally causes the capsid to unravel at the nucleus and release its now-DNA genome to join that of the cell. It is thought that these capsids are too large to go through the nuclear pore, so they may dock in some fashion and only transmit their contents, probably using special signals that mimick one of the many other proteins and molecules that are regularly imported into the nucleus. That process is currently unknown, and may be another avenue of viral inhibition and drug development.

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