Science Says ...

What are facts, and how can we respect them?

The recent and prevalent locution of "science says ..." is grating to everyone- scientists, civilians, red, and blue. We get the shorthand meaning, but it has unpleasant, domineering overtones. Yet, sadly, something needs to be said, if facts can not make themselves heard. The "science says ..." mantra means that not only is something a fact, but it is widely, perhaps unanimously, recognized as a fact by experts who know where such facts come from and what they mean. Lately this usage has been in flood due to the pandemic, a way for data-driven people to criticize their more negligent neighbors.

The problem is that facts are not always totally clear or secure. So we have to fall back on arguments from authority, to support what we believe are important actions, based on other values. Masks were originally denigrated - by scientists! - as not very useful for protection against viruses that were small enough to easily pass right through typical cloth. But as more data came in, it became clear - to scientists - that even partial filtering and simple dispersion of infectious aerosols was quite helpful, not only for others facing a possible asymptomatic carrier of SARS-COV2, but to mask wearers themselves, by reducing the infecting dose. This is especially true in a setting with decent ventillation. Evidence piled up from epidemiological studies as well as mechanistic studies of mask wearing, that even lax masking is better than none. Now a shorthand for all that is "science says...". 

But the evidence is hardly 100%. Small studies and suggestive trends in disease data from well and poorly-masked populations make for important public health recommendations, but not quite facts. More detail and mechanism will be helpful, including the relative amounts of virus capture and dispersion by masks, and the role of the infectious dose in the severity of disease- the race that is run between viral replication and immune defense. Few people are themselves directly conversant with all this work, which means that most have to appeal to the authority of those that are. But then any blogger can claim to be an authority, and declaim a different set of conclusions and thus facts. 

We seem to have mostly settled down about these facts, tentative as they are, when it comes to the coronavirus, even though actually respecting them and changing habits comes hard to some. But climate change has been a different matter, being so economically important and implicated in everyone's current way of life. One's conservatism is directly related to resistance to changing one's way of life, which necessarily implies denying and disbelieving the once-subtle, now overwhelming evidence that "science says" assigns blame for accelerating climate change to us and our production of heat-trapping gasses.

Facts? What facts?

This is where the "science says ..." mantra becomes politically fraught and adversarial. If reality is knocking on your door and telling you to repent, confess your sins, and change your ways, experience tells us that is has to knock extremely hard. Addicts tend to change only after they have hit rock bottom, and see death in the eye. Listening to a bunch of pointy-heads and libtards go on about the biosphere, arctic ice, and obscure species is just not compelling. Quite the opposite- it is often taken as offensive and completely out of touch with a fossil fuel addict's immediate struggles and attachment to basic habits and ways of being.

And who cares about facts anyhow? Not the modern Republican party, not our president. Whether "science says" those facts or their own eyes behold them, the social facts of political control in grossly unfair setting of US power structures, and continuing support from the morally unmoored rich and their corporations, are far more significant than any global risks that all will bear with increasing pain over the coming decades. The social facts of the right wing media's blizzard of propaganda are likewise shaping a totally different world, in both values and truths and facts, than what scientists are perceiving. The mantra of "science says" then comes to mean a set of values rather than just facts, that we should perhaps attend to non-human species and ecosystems instead of worrying about a war on Christmas; that expertise is more valuable than con-jobbery and lying propaganda; that worrying about the vastly excessive human population on Earth might be more important than saving every fertilized egg for the patriarchy. For science is a value system, both in its methods and its objects. It is largely and generously funded by society, but naturally has its own agenda, which seems far-sighted and logical enough to its practitioners, but is, in the end, a set of values, which themselves will be judged by society as worthy of propagation, or not.

• An example of how the science has to be parsed pretty carefully, by expert observers. Masks, planes, and time.
• Our degraded country.
• That tired Taliban, ready to take over all of Afghanistan.
• Medicare advantage, or disadvantage?
• Are we great again, or what?
• Climate action and inaction.. still highly insufficient.

An American Economic History, Through Farming

From plantations to free soil, and back to plantations.

Today, farming is a small part of our economy. But it remains existentially important, and politically and culturally significant far beyond its share of GDP. The family farm evokes the heartland, the honest toiler, the communal and salt-of-the-earth values of rural life. The United States was founded on the promise of land- ever more land taken from Native Americans for ever more white people to till. Land was the original job guarantee. Anyone disgruntled with their current condition could go West. Some created vast plantations or ranches, while most founded family farms. When some of the last arable land on the frontier became available in Oklahoma, it resulted in the notorious land rush of 1889, typified by "Sooners" who jumped the gun into this so-called unassigned territory. A generation or two on, they authored the dust bowl by their enthusiasm and negligence.

The late 1800's were a pivotal period. The frontier was closing, industrialization was changing the workforce and mechanizing farming. It was perhaps the high point of the family farm, as so movingly portrayed in its perils, pride, and community, in the film version of The Wizard of Oz. One underappreciated cause and purpose of the Civil War was to preserve free soil and free labor as the guiding principle in new territories and states. The plantation system of labor was the alternative, just as firmly rooted in American soil as the small family farm, and just as greedy for new frontiers. Plantations were the original corporate agriculture, driving an army of employees (i.e. slaves) over vast acreages of market-crop monocultures, typically cotton, tobacco, and, in the Carribean, sugar cane.

But, despite winning the Civil War for free labor, and adapting to progressively greater levels of mechanization, the family farm is dying, and has been dying for decades. A recent piece in the New Yorker describes the situation in Wisconsin, which has seen a steep decline in family dairy farms, driven out of business by the inexorable efficiencies and amorality of corporate farming. Capitalism is the remorseless agent, setting up new plantations on rebooted principles of cheap labor and enormous scale. Instead of slaves, the labor is now an unending flood of poor and undocumented hispanics, ready to work for less, and under poorer conditions, than "free" labor.

Is this the kind of capitalism we want more of? Is the kind of rural America we look forward to? It is more than a little ironic that rural America voted overwhelmingly for the Republicans, who offered nostalgic nostrums while being the foremost purveyors of capitalist fundamentalism, cheap oppressed labor, and rural decline. Thus some might say, they deserve what they are reaping. But that is merely spite speaking, not policy. It is clear that government policy has had a great deal to do with this evolution of farming, from lax labor policy to trade policy and growing regulatory and bureaucratic complexities, and explicit farm support systems that support corporate farms foremost.

So, we have been divided from the outset, between a corporate, plantation model of farming, and a small-holder, family model of farming. The memorialized plantations of Mount Vernon and Monticello are fascinating examples of the former, each originally worked by an army of slaves to create in this new land a rich, even refined existence for the lords of the manor. It was Jefferson's dream that America would be overspread by small family farms, even as he himself ran a brutalizing corporate operation. It was just one more of his romantic dreams, along with a discomfort with slavery that did not extend to emancipating his own slaves. But the US did indeed make his dream real across the Midwest by eradicating slavery and accepting floods of immigrants to run their own farms and found rural communities. 

The silo-inspired Emerald City. Was it a storage and processing cooperative?

It is clear that it will take deep changes in policy to preserve family farming, and humane and ecologically sound farming. Not just cash payments to farmers, as the current administration is attempting to save its political position, but a much more thorough rethinking of how rural America should operate. We need far stiffer rules for labor and ecological practices on large farms, so that the playing field is leveled. We need better support for cooperative processors, buyers, bankers, equipment supply, transporters, and extension systems so that small farms have the long-term support they need to survive. We need to edge away from stark capitalism towards a mixed model, for instance maintaining some price supports with intelligent government planning, so that farmers are not whipsawed by lethal market forces. And making those price supports graduated against farm size, to recognize the unique value, and unique challenges, of the small farm.

• "There can be no permanent disfranchised peasantry in the United States."- from the inaugural address of James Garfield, 1881.
• The biosphere is going downhill.
• Everyone has hope.
• Toadies in the swamp.
• A lack of innovative thinking in the medical community.
• The Taliban will soon be running things.

Genetics and the Shahnameh

We have very archetypal ideas about genetics.

Reading a recent translation of the Persian Epic, the Shahnameh, I was impressed with two things, among all the formulaic focus on war and kingship. First was what it did not say, and second was its attitude, which is shared with all sorts of traditional societies, towards blood, nobility, and what we now understand as genetics. This epic, which transitions from wholly myth in the first half to quasi-history in the second, stops abruptly at the Arab conquest. Not a word is uttered past the overthrow of the last Persian pre-Islamic ruler. Not a word about Islam, not a word about the well over three hundred years of history of Persia under the Arab yoke by the time this was written circa 1000 AD. That says a lot about what the author, Abolqasem Ferdowsi, regarded as the significant boundaries of Persian history. Not that he was opposed to narrations of decline and suffering. The final era of the Sassanian Empire was one of chaos and decline, with regicides and civil war. But apparently, that history was still Persian, while the Arab epoch was something else entirely- something that Iran is still grappling with.

The epic is full of physical descriptions- kings are always tall as cypresses and brave as lions, women are always thin as cypresses, their faces like full moons and their hair musky. True kings radiate farr- glowing splendor that they show from a young age, which marks them as destined rulers. But farr can also be lost, if they turn to the dark side and loose popular support. The Chinese have a similar concept in the mandate of heaven, which, however, is not portrayed as a sort of physical charisma or halo. Children are generally assumed to take after their parents, for good or ill. The concept of the bad seed comes up in the Shahnameh, especially in the saga of Afrasyab, king of Turan and long-time antagonist of Persian kings and their champion, Rostam. Persian king Kavus has fathered a great (and handsome) champion, Sayavash. Through several plot twists, Sayavash must leave Persia and is adopted by Afrasyab, even marrying his daughter. But then the drama turns again and Afrasyab kills Sayavash. Thankfully, Sayavash had already fathered a future king of Persia, whom the Persians suspect of bad lineage, due to his descent from Afrasyab- a suspicion that they are slow to overcome.

"By the time the boy was seven years old, his lineage began to show. He fashioned a bow from a branch and strung it with gut; then he made a featherless arrow and went off to the plains to hunt. When we was ten he was a fierce fighter and confronted bears, wild boar, and wolves. ... Seeing the boy's noble stature, he dismounted and kissed his hand. Then he gazed at him, taking in the signs of kingly glory in his face."

Ancient peoples have generally taken nobility and bloodlines very seriously, for several reasons. First, obviously, is that children do take after their parents, for good and ill, just as ethnic groups similarly have some distinctive characteristics. Second is that, for practical as well as psychological reasons, people always seek good rulers and stable ruling systems, which in the aristocratic, patriarchial setting means an orderly transition from king to prince. The fairy tale (archetypal) ending is that the prince and princess take over the kingdom, and everyone lives happily ever after. Third, is that hierarchy of some sort seems to be part of our cultural DNA. Someone or group is always up, others down. Whatever the group or organization and whatever its professed principles, hierarchy re-asserts itself. Those on top want naturally to stay on top, and bequeath that position to their future replicas, i.e. their offspring. To do that they will generate all the practical advantages they can, and into the bargain foster a mythos of just distinction, based on their glorious bloodline, if not outright divine sanction from god. Thus genealogical trees, heraldry, etc.

The Shah is not like you or me...

The ruling houses of Europe over the whole post-Roman Era were infested with these archetypes and mythologies. Marrying "up" or "down" was a vast game carried out across the continent. And what has it gotten us? Prince Charles. It is obvious that something went awry in this genetic exercise of assortive mating, as it did ultimately in the tragedies of the Shahnameh as well. The behavior of royals generally fails to select for all the positive traits that are ultimately needed. Their training fails frequently as well to expose those good traits that do exist. But most of all, genetics is far more of a crapshoot than the archetypes allow. 

Children do take after their parents, but there are stringent and interesting limits. A child gets only half of each parent's genes, and those genes may be from either copy in each parent. That copy might have been totally silent- recessive vs the other dominant allele. Two brown-eyed parents can have a blue-eyed child, if they are heterozygous for eye color. Multiply this over thousands of loci, and the possibilities are endless. This is why traits of the grandparents sometimes are thought to come up unexpectedly, or novel traits entirely. The genetic mixing that takes place on the way to new life is carefully engineered to replicate, but with wide variation on the theme, such that any child is as much a child of its wider lineage and environment as of its particular parents. Genetic defects remix during this process as well, concentrating in some children, and leaving others fortunately free to realize greater potentials. The obsessive concentration of lineages that characterize royalty systems, such as was taken to an incestuous extreme in Egypt, leads to inbreeding, which means the exposure of defective alleles due to excessive homozygosity. We all have defective gene alleles, which are typically recessive, and thus get exposed only when they pair up with an equally defective partner. Thus an extreme focus on lineage and purity leads to its own destruction.

The differences between ethnicities are far less than those between families. Human lineages may have some strongly selected and differentiated traits, such as skin color, but such traits are exceedingly rare. Otherwise, our genetics are a cloud of variation that crosses all ethnic lines. Humans were a single lineage only a few hundred thousand years ago, or less, so broadly speaking, we are all the same. Indeed compared to most species, such as chimpanzees, we have much less genetic variation overall, and are virtually clones, due to the relatively recent bottlenecks of extremely low population that reduced genetic diversity. Our current population size relative to those of the other great apes certainly does not reflect conditions in the past!

Education was another ingredient in the traditional systems of nobility and aristocracy. Only the rich could afford an education, so only the upper crust were educated, thus gaining one more credential in addition to their genetic credentials, over the middle and lower classes. Such notions of aristocracy died perhaps hardest in military circles, where officers were long an aristocratic class, selected for their connections, not their ability. It was one of the great American innovations to establish a national military college to which admission was distributed liberally to deserving candidates, (at the same time as similar academy was set up in revolutionary France by Napoleon). It is obvious that the capacity for education was far more widespread than originally conceived, and we benefit today from the very active diffusion of education for everyone. Yet not all are college material. Some children are bright, some less so. Genetics and early development still count for a great deal- but good (and bad) genes can come up anywhere. That means that in the end, the American system of meritocracy, for all its defects, of which there are many, and despite its significantly unfulfilled promise to many, is a huge advance over the hidebound traditions, archetypes, and injustice, of aristocracy.

But back to genetics- what are we finally to make of genetics, eugenics, and noble bloodlines? It is clear that humans can be selectively bred, just like any other animal. Twins and twin studies make it abundantly clear that all sorts of traits- physical and mental- are gene-based and heritable, to striking extents. It is also clear that historical attempts at eugenics have not turned out well, whether through systems of nobility or more modern episodes of eugenics. The former were largely self-indulgent and self-serving ideologies designed to keep power and status among an elite, within which poor choices in mates and inbreeding consistently led to genetic doom. The latter were ideological exercises in frank racism, no more anchored in positive values, genetic or otherwise, than the aristocracies of yore. There have been occasional successful genetic experiments in human breeding, such as the Bach family, Yao Ming, and Stephen Curry, which show what can be done when one puts one's mind to it! (The Trump brood may also be cited as another, if negative, example.)

But generally, selective breeding implies a single set of values that constitute its goal. Our values, as a society, are, however, diverse in the extreme. We celebrate some people more than others at a political or social level, but have been heading in the direction, since our country's founding, of recognizing the dignity and worth of every person without exception, along with their freedom to form and express their own values. We can neither agree on a society-wide set of specific values that would shape any form of selective eugenics, nor allow individuals to go beyond the bounds of normal mate selection to plunge into cloning, genetic alterations, and the like, to inordinately expand their genetic influence on succeeding generations. All that would strike at the heart of the social project that is America- to foster individual opportunity and merit, while at the same time respecting the rights and worth of each individual- indeed, each way of life. It is likely that, given the technology, we might come to a general consensus to eradicate certain genetic diseases and syndromes. But beyond that lies a frontier of genetic engineering that the US is particularly poorly suited to cross, at least until we have made America great again, so to speak, and become another society entirely.

• Some calming piano.
•  Oh, yeah- remember the tax cut? That went to the rich.
• Some people are prepping for war.
• Maybe low-dose infection is one way to approach Covid-19.
• International fisheries are not just environmental disasters, but human rights disasters.
• The difference between being a con man and being a president.
• Some possible futures for Earth. RCP 8.5 takes us (in a matter of 80 years) to conditions last seen 40 million years ago.
• Followup quote from Frederick Douglass:

"Color prejudice is not the only prejudice against which a Republic like ours should guard. The spirit of caste is malignant and dangerous everywhere. There is the prejudice of the rich against the poor, the pride and prejudice of the idle dandy against the  hard-handed workingman. There is, worst of all, religious prejudice, a prejudice which has stained whole continents with blood. It is, in fact, a spirit infernal, against which every enlightened man should wage perpetual war."

Why Are Cells So Small?

Or, why are they one size, and not another?

One significant conundrum in biology is how cells know what size they are, and what size they are supposed to be. Bacteria are tiny, while eukaryotic cells are huge in comparison. And eukaryotic cells vary tremendously in size, from small yeast cells to peripheral nerves that span much of your body, even on to ostrich eggs. Outside of yeasts, not much is known about how these cells judge what size is right and when to divide. A recent paper proposed that the protein Rb plays an important role in setting cell size, at least for some eukaryotic cell types.

Rb is named for retinoblastoma, the form of cancer it is most directly responsible for, and is a well known gene. Many other cancers also have mutations in Rb, since it is what is called a "tumor suppressor gene". That is, it is the opposite of an oncogene. Rb interacts with hundreds of proteins in our cells, but its most important partner is transcription activator E2F1, an activator of cell cycle progression. Rb binds to and inhibits the activity of E2F1, (and a family of related proteins), halting cell division until some alteration takes place, like a regulatory phosphorylation that shuts Rb off, or an insufficient amount remaining in the cell.

The researchers took a clue from yeast, whose gene Whi5 accomplishes similar inhibition of the cell cycle as Rb, and is known to regulate the size of cells at division. So this work was not a big surprise. The interesting aspect is that Rb now has one more role, which logically integrates with its other known roles in the cell cycle. The authors used cells that over or under-express Rb to show that the copy number of Rb has a significant, if not overwhelming, effect on cell size. 

Amount of Rb correlates with the size of cell. The authors set up an inducible genetic construct to drive Rb expression, from zero to four times normal amounts.

So how do they imagine this mechanism working? Rb is a durable, stable protein, with a half-life almost twice as long (29 hours) as the cell division cycle in the conditions the experimenters used. Secondly, all Rb is pretty much in the nucleus, attached to DNA. So at cell division, roughly equal amounts necessarily partition to each daughter cell, even if their cell volumes are very different. Thereafter, each cell synthesizes Rb at a low rate, which does not keep up with cell growth, especially during the G1 phase of the cell cycle- that period prior to DNA replication and commitment to division. In fact, very little Rb is made in that period, allowing it to serve as a limiting factor through dilution as the cell grows. And when it is sufficiently dilute, it then contributes to the decision to have new cell cycle, by letting go of its repression of E2F1.

How several proteins accumulate during the cell cycle. Rb is shown in dark blue, and hardly accumulates at all in G1, the growth phase of the cell cycle before DNA replication (S phase) and division (M phase). For comparison, nuclear volume and a generic translation protein (EF1) rise monotonically with cell growth. Cdt1 is a key licensing factor for DNA replication. It accumulates during G1, and after the DNA replication origins fire, is destroyed by the end of S phase. Conversely, Geminin is a protein that binds to and represses Cdt1, preventing re-replication of DNA that has already replicated once. It accumulates during S phase and stays high until after division. After S phase, more Rb is made, partially catching up to the current cell size. 

That is the theory, at least, backed by pretty good evidence. But its effect is not proportional, and not uniform among cell types. There are clearly other controls over cell size in play- this is only one. Indeed, there are a couple of siblings of Rb (in a family termed "pocket proteins") which also regulate the cell cycle, and a vast network of other controls and stimuli that impinge on it. So finding even one regulator of this kind, and finding conditions where it has strong effects on cell size, is quite significant. As for the ultimate rationale of cell size in these or other instances, Rb regulation is only a mechanism that enforces logic that has been arrived at over evolutionary time, about the practical limits and ideal proportions of cells in, in this case, the human body, in response to various situations. Smaller cells have one virtue, that they are more easily disposable- such as the countless skin and gut epithelial cells that are sacrificed daily. Our long peripheral nerves are much more difficult to replace.

Conversely, Rb has many other roles in the cell, as suggested by the vast number of its interaction partners, diagrammed below by functional classification.

Functional classification of the many proteins that interact directly with Rb. It also has about 15 phosphorylation sites that can be regulated by various kinases.

• The Fed goes all MMT, behind the scenes. No more reserve requirements, no more market-based interest manipulation.
• We are increasingly at risk of civil war.
• Guess who recommends illegal voter fraud?
• Yet another effective Chinese vaccine.
• Bob Cringely on the pandemic loan program, and other misguided incentives.
• How the virus disarms and shuts down the host cell.