Saturday, June 27, 2015

Christians Have All The Morals

Review of "Terrorism and Civilization", by Shadia Drury

Some weeks ago, I discussed, somewhat tongue-in-cheek, how atheists have no morals. This time we turn the other cheek to consider Christian morals in some detail. Shadia Drury published a response to the 9/11 attacks in the form of a frontal assault on religious morality and Christian morality in particular, a book that should have risen to the top of the Atheist cannon, but didn't, perhaps due to her obscurity, her gender, and the book's high price.

Her case is relentless as it is remorseful, about the opportunities lost in the West due to the twisted, irrational and inhumane doctrines that originate from the New Testament. At least the Old Testament god was understandable, if a little hot-tempered. The New one is positively terroristic. Nor does Jesus (assuming for the monent that he was a real person and that the scriptures about him are at least partly true) get off in this thorough indictment, for he brings us this new system which features carelessness about this world and its people, thought crime, eschetological selfishness, orignal sin, and eternal damnation.

Hell is, of course, one focus. Jews didn't have hell, really. That was Jesus's invention, though obviously stolen from the Zoroastrians. His doctrine is that mere belief in him is the main thing.. everything else is secondary, in any practical, moral, and eschatological sense. However, many are called and few are chosen, which is to say that even if you fulfill his need for faith, you could still end up in hell, which is painted in the most fiery colors, as endless suffering and eternal. This is pure psychological terror, obviously, and was stunningly effective against the other religions of the day, which were all more reasonable.

Jesus also introduced thought crime, since belief in him was the main criterion of salvation. He also deemed immoral thoughts as bad as immoral actions. Adultury in one's mind as bad as in the flesh, etc. So where was one to go for relief from such a regime? There is nowhere to hide. Many serious believers have been agonized by this, for example John Bunyan in Pilgrim's Progress, a despairing work full of terrors and sin.

The reason for the horrors of Bunyan's epic travellogue are that humans, in Jesus's system, are fallen and evil. They are sinners who have no right to salvation, who are saved (if at all) by grace granted in return for slavish faith. Drury makes the acute observation that Freud, that ostensible iconoclast and atheist, follows the Christian system in virtually every psychological particular, from the innate sinfulnes of man (the id), and the need for terror (repression) to keep the inner beast under control, to the therapeutic salve of confession (the couch, in place of the booth).

Nietzsche too comes in for a drubbing, in an even more profound way. The Christian morality is one of blind obedience, of faith in the unbelievable, and terrorism inner and outer. All for our own good, naturally. If one fails to reframe the basic parameters of this model of humanity, then revolt against this edifice of lies might take an ugly turn, to immorality and perverse delight in reversing every dictum of the reigning moral order, so as to return to one's "true" nature, which though sinful, is at least honest and alive. Thus the bathos about Dionysus and the amoral Ɯbermensch.

This accepts a frame that is far from true, however. Humans are many bad things, but they are not fundamentally bad beings. We are basically good beings with complex and often conflicting needs and ideals. We are pro-social. We love and seek love in return. We are fiercely moral. Drury points out that it is our civilization and our highest ideals that are what is in some ways most dangerous about us- our ability to organize huge groups, spout ideological rhetoric about utopian ideals, not to mention creating modern technology, for warfare and totalitarianism on unimaginable scales. It is the beast within that required nurturing, and our better natures that required the most advanced instruments of repression, when one thinks of the rankest horrors of the twentieth century.

So it is time to relax. The work of civilizing ourselves remains great, and constant cultivation is certainly desirable. But it does not require terrors of religion, nor theories about how damnable we are. Nor should we leap to the other Rousseau-ian end of spectrum, where everything natural, native, and naive is all that is good. As the religiously and ideologically burned-out countries of Europe are showing, there is peace, prosperity, happiness, and not least, highly sensistive morality, in a post-Christian, moderate, and humane culture.

  • Kansas is just fine ... steal from the poor, give to the rich is a winning, sustainable strategy, especially considering how damnable we are.
  • The Devil and Mr. Scalia. At least one justice is a fossilized relic, and has either lost his marbles, or enjoys trolling interviewers.
  • Over 100 jihadist training camps, thousands of trainees ... this is not a fringe phenomenon.
  • California's sclerotic housing mess. Incumbent owners always win when new housing / zoning is killed. Especially with prop 13.
  • Grexit is coming.
  • Whom we feel for... white police edition.
  • Another 1%. Or is it the same one?
  • Enriching the 1% makes everyone poorer.

Saturday, June 20, 2015

Plowing Through a Fork

DNA polymerase and DNA helicase help each other out at the replication fork.

While DNA may not have been the first molecule at the origin of life, it now forms the heart of our replicative and molecular existence, its iconic and elegant stairway storing the digital data that has taken over the world as our wonderful biosphere. Its replication is a complicated process, but has to be done rapidly, since for one of our cells to divide, three billion bases need to be gotten through. A recent paper discussed how that happens, for the DNA polymerase itself can not open up the parental DNA strand fast enough through its own locomotion. It needs a DNA helicase to help unwind the oncoming DNA, whose strands are not only glued together by their basepairs, but can be festooned with histones and all sorts of other bound proteins that need to be cleared away.

In this cartoon of DNA replication, (going right to left), the synthesis of the leading strand (top) is so undramatic that its DNA polymerase is left out altogether. But note that a helicase rides at the fork where DNA melts. In this system (from E. coli), DNA polymerase III (pink) is the major polymerase that carries out leading strand and the major part of lagging strand synthesis, while DNA polymerase I is a fill-in enzyme that fills in gaps that are left at the end of every run of DNA polymerase III. The last step on the lagging strand is sealing by DNA ligase of the DNA polymerase I run, which goes right up to the next unit of lagging strand, made previously. Unlike in the diagram, there would be no nucleotides missing when/where this ligase acts. An RNA primer for the lagging strand polymerase III synthesis is shown in green.

To digress slightly, one of the most critical complications in DNA replication is that of the lagging strand. DNA comes in two strands, but all polymerases operate only in one direction (5' to 3'). So replicating the leading strand, which runs 5' to 3', is a piece of cake, even if it requires a helicase for assistance. The other strand is called the lagging strand, and has to be made piecemeal, with the polymerase running "backward" from the replication fork, primed each time by a special RNA-synthesizing priming polymerase. So this process is intrinsically assymetrical and messy.

Anyhow, the researchers use the classic model system of polymerase and helicase from the T7 phage, which infects E. coli bacteria and comes with its own (encoded) stripped-down and efficient DNA replication machinery, for late stages of infection when it needs to pump out full viral genomes at high speed. It is known that the helicase is essential. The polymerase by itself can work, but only slowly, and is particularly retarded by GC-rich regions, the GC nucleotide pair having three hydrogen bonds compared to the AT pair's two bonds. The question for these researchers was.. how closely do the helicase and polymerase work? Are they distant partners, or cheek-by-jowl?

One could imagine that the helicase could proceed some distance ahead of the polymerase. But it is also known that the helicase doesn't work that quickly by itself either. The helicase looks like a lifesaver ring that forms around a single strand of DNA, and consumes dTTP as an energy source to tug on it, pulling it away from the duplex fork which the helicase is trying to melt. Neither activity alone explains the total high rate of DNA replication, suggesting that they work closely to help each other along. The current work put them through their paces either apart or together, and controlled by various concentrations of their inputs, dTTP in the case of the helicase, or all four deoxy-nucleotides in the case of the polymerase.

On a single strand of DNA where it doesn't need to do any helicase-ing, the T7 helicase moves along at a nice 65 nucleotides (nt)/second pace. Likewise, the polymerase, when given plenty of nucleotides and single stranded DNA, chuggs along at 200 nt/second. The final rate of the complex on duplex DNA is about 200 nt/second also, so what needs to be explained is how the polymerase regains that rate when facing duplex DNA and perhaps non-ideal concentrations of reactants, plus other obstacles. For the helicase, how and why does it go faster when yoked to the polymerase than it does on clear single-stranded DNA on its own?

Performance of DNA polymerase alone, on GC-rich DNA. It is slowed down substantially, but much less when given an excess of its substrates, the deoxynuceotide triphosphates (dNTPs).

Key computed parameters of the polymerase alone. With higher GC content in the DNA, the polymerase maximum rate (k-cat) doesn't slow down much, but its responsiveness to substrate concentration( Km) rises substantially.

One way to manipulate the system is to present the enzymes with double-stranded GC-rich DNA in comparison to AT-rich DNA, and ask what other ingredients, such as more nucleotides, do to their speed. The comparison is rather subtle, and depends on decomposing the reaction into two components, a measure of the first part of the reaction, enzyme + nucleotide binding (Km), and a measure of the second part- how fast the enzyme is at maximum if it has plenty of inputs (kcat). As shown in the first graph, the DNA polymerase is significantly slowed down by GC-rich DNA duplex. But that effect is substantially alleviated by high concentrations of nucleotides, indicating that the polymerase has problems opening the duplex DNA for lack of enough new nucleotides to stuff into the template position as the fork sporadically melts. The polymerase is not good at holding on to temporarily melted nucleotides.
Performance of helicase alone on GC-rich templates. The rate is hugely slowed down no matter what the dTTP (energy substrate) concentration.

Unlike the polymerase, the kinetics of the helicase are changed by difficult-to-open GC content mostly in the k-cat, or maximum rate, with little or negative effect in the Km or substrate (dTTP) sensitivity.

Conversely, the helicase has another problem. No matter how much nucleotide (more precisely, deoxy-nucleotide triphosphate), you give it, it maxes out at pretty slow rates on GC-rich DNA. This suggests that it just isn't a terribly good helicase by itself, but if given a push...

Rate of the combined enzymes on 50% GC template is quite fast. The nucleotide concentration for the polymerase (dVTPs, which stands for a mix of dATP, dGTP, dCTP, while the dTTP is provided for the helicase) is kept extremely low. But the combined system makes a much higher rate (~70 nt/second) than the polymerase alone did at the minuscule concentration of 5 micromolar dNTPs (I estimate perhaps 10 nt/second from the graph above). This is reflected in the combined Km for nucleotides in the combined case (top, in red) vs the polymerase alone case (bottom, red).

The reason for all this is structural, that the helicase is better at grabbing on to the single strand coming out of the fork, but doesn't have much oomph behind it to plow forward continuously. The polymerase, in contrast, has a good engine, but doesn't grab onto the incoming single strand DNA well, letting it slip back into the duplex with high frequency. The complementary relationship makes sense, since you really do not want the helicase travelling off by itself unwinding the cell's DNA, but rather want it coupled to where it is really needed- right ahead of the DNA polymerase, as a kind of cow-catcher and rail splitter.

The red nucleotide pictured is fluorescent, and its melting changes the fluorescence signal as measured on the Y-axis of the graphs. Melting in the absence of any dNTP substrate is only substantial when both helicase and polymerase are present.

Lastly, with some more intricate fluorescence assays, (on which this whole work is based), the authors look at the two or three nucleotides of the fork itself, and which of them are grabbed by the two enzymes in single-stranded form. This is done without giving them any nucleotide triphosphates as energy source or substrate, so it is looking at initial binding. Polymerase or helicase alone bind to the fork, but are pretty ineffective at melting any of the first three nucleotides of the duplex (darker bars). But the two enzymes together melt them quite well (light blue bars). So it is not just the engine of the polymerase behind, but a physically cooperative binding mechanism at the fork that gets the DNA melted in advance of replication.

The authors come up with a highly schematic vision of what this might look like, with some wildly stretched DNA going into the helicase- the green rung of the non-template (right) strand. The helicase then hangs on tightly to each nucleotide that it captures, as the polymerase is busy doing its thing of synthesizing the new DNA strand.

Model of the polymerase (beige) and helicase (pink) collaborating at the replication fork.

  • ISIS deploys foreigners to kill themselves. Clever! 
  • More guns in church is the answer, plus let's blame the victim, says NRA.
  • Employers pay only what they can get away with. "The minuscule gains that households have made have largely come because women have increasingly entered the workforce—meaning families are working longer hours, as they run faster and faster to stay in place." ... "Median incomes for male workers now in their thirties are about 12 percent lower than the income was for their fathers’ generation at the same age."
  • Is German labor through being squeezed?
  • Cringely on IT feudalism: "H-1B has always been unnecessary."
  • Pluses and minuses of Dodd-Frank.
  • Just like his crony brother ... Jeb! raked in money sitting on the board of a criminal organization. One more argument, incidentally, for the completely merited pay and corresponding utility of business executives.
  • Some modest suggestions on financial literacy and better retirement planning.
  • Ethical grifters.. er drifters .. in finance.
  • Greek drama: "What that means is that the involvement of European governments has not helped Greece at all. ... The additional money provided by the European authorities has been used to pay off Greece’s creditors ..." Default & grexit should have been the first resort, not the last.
  • MMT making dramatic inroads into the policy central plexus.
  • Dawkins, Hunt, completely bonkers.
  • Thanks, Warriors, for a golden moment.
  • Economic graph of the week. We are far from full employment.

Saturday, June 13, 2015


Society affects gene expression and development, and genes contribute to social traits and behavior.

Is it any news that we are biological beings? That all aspects of our being, from toenails to theology, are biologically based? That was the premise of sociobiology, the science of the behavior and evolution of social organisms. Of which we are one. Unfortunately, the smell of eugenics was still too strong in the political atmosphere to allow thinking about how our genes affect our behavior, so that splash by E.O. Wilson died down and the science went on by other names.

That work has found, among other things, many connections between our psychology and our physiology. It should be no surprise that we are profoundly affected, to the point of suicide and other forms of death, by information that first arrives to our brains. Our immune systems are sensitive to social state, as are digestion, mood, activity, etc. Hypertension is one of many long-term consequences of stress, for example. This close relationship leads to to idea that we might be able to judge happiness by objective measures, rather than exclusively by self-report. And that would open up new vistas in morality, particularly morality vis-a-vis other species.

But it goes the other way as well, as our social capacities are based on biology. Psychological traits of great complexity can run in families, and scientists are only starting to gain glimpses of genetic alterations that cause such traits and their variation. The very ability to be flexible, to learn and adapt, is itself obviously of genetic origin. The question, typically, is how much people differ in significant social traits and how much we should care about that. We pride ourselves on meritocratic systems of education, business, and government that weed, select, and reward those who are gifted, who also align with and master the social system. But are we just rewarding something that the persons themselves had little to do with, just as criminals typically have little responsibility for their genetic or social deprivations, or actors for their looks? We may be, but reward we must, as a sociological necessity, if we want societies to benefit from good rather than bad talents.

Is it also an evolutionary necessity? Should those who succeed in the existing social system be rewarded with more reproduction? Typically we do not and should not have sufficient confidence in the universality or durability of our social system to make that case in its most brutal, eugenic sense. However, we should not be blind to the genetic underpinnings of social success and all its consequences. For example, the trend toward intellectual atheism that is so fervently touted in other areas of this blog fights a rate-dependent battle against the higher reproductive success as well as intellectual insularity of religious populations. What is the deconversion rate compared to the biological and ideological reproduction rate? Is religiosity a positive trait for humans? How much to we care about our evolutionary trajectory, a path we are on whether we are conscious of it or not?

Anyhow, as an example of the genetic implications of sociality, a recent paper described a gross increase in genetic complexity that accompanied the social evolution of bees. They found a measurable correlation between social complexity and gene regulatory complexity, which is a step in addressing the question of the interrelation of genes and behavior, in general.

Bees come in many social levels, from solitary to "eusocial", a term the E. O. Wilson made up to describe animals that are not  just polite and social as we and many other animals are, but behave as super-organisms, with genetically determined castes with division of labor, and restriction of reproduction to a small subset of those castes. The members of such a collective have no independent existence, die when the hive dies, and are seen by evolution as a group that has group-level traits that are extensively selected for.
Phylogenetic tree of the species considered. Solitary bees are marked in blue, simple sociality in green, more advanced sociality in yellow, and full-blown eusociality on red. 

The researchers basically lined up lot of genomes, from various levels of social organization among the bees, and looked especially at promoter regions, where the primary control over gene expression happens. They found a striking increase in complexity, which is to say number of binding sites for regulatory proteins, all over the genomes of the more social species. Indeed there was a 10-to-1 bias of genes that gained promoter binding sites over those that lost sites in the more social species. This is a dramatic effect, and makes sense in terms of the "mode-switches" required on a genetic level to create castes with separate developmental and behavioral traits out of one ancestral species.

Bias found among orthologous bee genes (that is, the same between each species) between those that gained promoter regulatory sites in more social species (blue) and those that lost them (red). The X axis is not genes, but the individual regulatory proteins whose DNA-binding sites were identified.

They also found, interestingly, that the particular genes involved in these increases were not the same in different social insect lineages. They took different genetic / evolutionary routes to eusociality in detail, even though they ended up with similar properties. So this is a kind of convergent evolution that shows that group selection and the sociality it selects for did not just arise multiple times in life's history out of some kind of molecular happenstance, but is an optimal ecological solution that attracts quite a bit of selection, as we can tell by the dominance of social species, both in the insect world and in our own.

Overlap among the various social lineages of which genes showed rapid, positive evolutionary selection. The result is that there is very little overlap, indicating that there are many ways to skin the social cat.

  • Termites, same story is pending.
  • Sociological reflections on WD Hamilton.
  • Review of Churchland, on the brain and morality.
  • More on body-mind interconnections.
  • What the Y chromosome says about out of Africa models.
  • Do voters understand economics, from today's ideological, corporate media?
  • Global warming doesn't mean more plants, it means more desert.
  • Breaking up big SDI banks would be "un-American".
  • Notes on currency manipulation.
  • Notes on division of labor, and why technology is probably more important to the organizational structure.
  • NIH talk on depression- current research status and promising developments.

Sunday, June 7, 2015

Bacteria Form Communities Too

Moral issues among the tiniest life forms.

Sometimes it takes a village, even for bacteria. Famous for being mindless, pitiless, evolutionarily-honed automatons, it turns out that bacteria have need of community and have ways to detect and signal that a community is ready for action. Not only that, they have ways to punish cheaters who do not pull their weight for the collective, tiny as it might be.

A recent computational biology paper developed game theory models based on bacterial dynamics to explore what signals are needed for group cooperation and how they evolve. Suppose that some bacteria face a food source (say a piece of wood) that requires acidic pH to digest. One bacterium isn't going to make much headway by itself. But if a thousand gather and crank out some protons in unison, they could make themselves a feast. Then what if one of them decides to loaf around, eating its fill but not producing any acid to help digestion?

This presents a series of problems. First, each bacterium needs to be able to tell whether there are enough colleagues about to make a collective / individual effort worthwhile. Second, it needs to know whether such a decision is shared by the others, so that they act in unison. And third, of course, they need to devise some way to punish or mitigate cheating and loafing.

Incidentally, these authors refer routinely to a personified "Nature", as in "We shall assume that Nature may choose between two different states ...". This is somewhat off-putting, and doubtless a consequence of being computationally oriented, making them wish to make it clear when they are speaking of natural cases, versus in silico, modelled cases. This should, however, not create any presumption of a theology of some shadowy entity behind the curtain or pan-consciousness, etc.

The authors simulated basic game theory conditions where individuals either signal or do not signal, with varying costs, and either cooperate or do not, responding or not responding to the majority signal around them. The idea was to vary the costs and benefits, and introduce mutants that employ other strategies, to ask what conditions lead to stable conditions, especially those resembling the world we actually see, where cooperation is, among bacteria, reasonably common.

In fairness, they asked themselves quite limited questions, focussing on whether signalling systems routinely evolve under conditions where cooperation is beneficial. Obviously, the answer to this is going to be yes, under any state where the conditions vary and are not adverse, requiring cooperation, all the time. The strategies they entertained were brutally simple- either signal or don't, and either cooperate or don't. So there was little subtlety.

Bright / beige areas show where most of the simulated populations reside under various conditions, while practicing the cooperative, signalling responsive strategy. The Y axis is cost of signalling. Very high costs (as a proportion of the benefit gained) do inhibit signalling, but this is biologically not very realistic. The various graphs then show: 1. selection pressure for the cooperative benefit, which strongly stablizes cooperation, as well as signaling  2. As the cost of cooperation rises, populations are OK with higher signalling costs, given a relatively high selective constraint for cooperation, (gamma š›¾ is set at 5). 3. If the rate of bad conditions rises to high levels, it makes no sense to signal that fact, really, and populations cooperate, either without signaling at all (i.e. all the time) or in response to a lack of signal.

One further problem is that the authors have given themselves the simplification that only one mutant form can exist at a time, either invading and taking over the whole population, or dying out before the next mutant strategy comes onto the scene. That means that a shirker strategy of benefitting from the cooperation of others may briefly invade a more cooperative population, but can never realistically take over the population when the benefits of cooperation (i.e. selective pressure for cooperation) are set high.

Thus the main question that we would realistically have about cooperative strategies, which is about the stable rate of shirking in otherwise cooperative populations, and the evolution of counter-strategies of detection and punishment, never come up in this analysis.

Thankfully, there is other work in the field that has established punishment strategies, though not yet any active surveillance and detection strategies, which might be beyond bacteria's cognitive capacity. In one example, the human pathogen Pseudomonal aeruginosa secretes small amount of cyanide, which the cooperators are resistent to, but the cheaters are not.

Small as they are, bacteria face basic dilemmas of survival and group action. They have the glimmerings of moral needs and one can readily see how increased capabilities led to increasingly complex behaviors of evasion, deception, and group control that we express in our moral systems.

  • Another paper on the collective propensities of bacteria.
  • Some notes on the origin of the Origin.
  • Hello, eco-pod.
  • Some questions are lies. Many of them, actually.
  • MMT at the BOE.
  • Obscene spending by the rich. But honestly, the real problem is that they don't spend enough.
  • Workers need more power. Freedom for companies does not equal free markets.
  • The case for vacation.
  • A private company committing fraud? We are shocked!
  • Fiscal policy would have been very effective. Paying people more would likewise be very effective.
  • All you can really fault the Fed, in policy terms, is for not pushing for more fiscal policy. This paper also makes the important point that higher unemployment equals higher inequality.
  • Organized crime is dead.. long live finance.
  • Bill Mitchell on the full employment period and policies, vs our feudal age.
  • Walmart hires according to pure managerial and business merit, reinforcing the idea that CEOs deserve extraordinary pay and power on a marginal utility & productivity basis.