Native Americans and Genetics

A fraught story.

The recent profusion of DNA studies of human lineages have clarified a lot about human history- where we came from and where we have travelled over the millennia. All this depends on samples from native populations- the ones we came from. It is only apparent that we came out of Africa if there are stable African populations that constitute the source and retain the vast diversity of our oldest homeland. But what if the natives do not want to be sampled? What if they are woke to the colonialist and genocidal legacy of the science / scientists doing the sampling, and want no part of it?

That is what happened, in part, in the recent flap over Elizabeth Warren's announcement of Native American heritage. Native South or Central American, that is. As told by a couple of experts, the lab that performed the analysis could not get permission to use North American samples, so used DNA from populations elsewhere in the Americas. Since Warren is herself from North America, indeed Oklahoma, and since the history of native peoples throughout the Americas is known to be relatively recent, expanding over last 15,000 years at the outside, the method is clearly valid in inferring, indirectly, some North American native ancestry for Warren.

So why the guff she caught from the Native American community? It was quite puzzling to hear their representatives trying their hardest to pour cold water on her claim, as though they were getting talking points from the FOX propaganda channel. Despite her not claiming to be a tribal member or wanting to be, they trotted out their arcane rules for membership, which certainly wouldn't accept anything so white as DNA testing. But lo and behold the tribe- the Cherokee in this case- use fractional blood relations determined from a list compiled by white people of the US government back in 1902. There are no good answers here, after half a millenium of disposession, destruction and abuse, but denying the obvious is not one of them.

The deeper issue is the appropriation and objectification of Native Americans and their culture by others, from here to Germany and beyond. Playing cowboys and indians, putting on Karl May dramas, naming sports franchises ... we have a very fraught relationship of romanticization and trivialization, little of which has anything to do with real Native Americans, particularly those living today who wish to be custodians of their own culture even while still suffering under the various debilities of their treatment by the dominant culture. I was part of this myself, in the Boy Scouts, which still play at being Indians, mortifyingly enough. Then the history of eugenics, and the plundering of native treasures, archeology, and burials, etc. has put so-called scientists in a particularly bad light.

This forms the backdrop of the notorious fate of the Kennewick man, an archeological find that led to bitter, drawn-out controversy. The almost complete skeleton, found in Washington state at the Columbia river, was 9,000 years old, and by morphology was more similar to other peoples such as the Jomon aboriginal people of Japan than native Americans. Ironically, it was DNA testing that confirmed affinity with Native Americans after all, after which the remains were given to the local Native American nations, including the Umatilla, which buried them at an unpublished location. From the native perspective, this fed into the narrative that their history is eternal and static, meaning that any pre-Columbian artifacts or remains found on what is currently their land is associated with their culture in some way, despite the thousands of years that may have passed and migrations that may have happened, and thus presents the right of possession and cultural use. One gets the distinct impression that Native Americans do not really want to know their own deep history, preferring a religious narrative of having been forever in the Americas, instead of having wandered in a few thousand years before the Europeans did.

From a scientific perspective, the episode was a travesty of political correctness, as a 9,000 year old skeleton could have no imaginable cultural connection to the current inhabitants of the area, while being an inestimably rich source of knowlege about this early post-glacial time of North American settlement. This antiscience attitude is perhaps a fair harvest for all the harms and hurts inflicted over the last few centuries, science being one of the most domineering and distinctive expressions of Western culture. Still, the loss to general knowledge rankles.

One Cherokee representative spoke of how irritating it is to repeatedly meet people who claimed to be part Cherokee, expecting some positive pat on the head. But those people wouldn't dream of moving back to the reservation, or taking part in Cherokee culture, as is undoubtedly true of Elizabeth Warren as well. It is a "heritage" without practice and of dubious significance. Nor may they be alive to the sense of loss and injury this represents, as such blood mixing may not have been voluntary, but the result of rape and rapine of various sorts.

Nevertheless, it would seem advisable for Native Americans to get off their metaphorical high horses and be more welcoming to the diversity that exists in the US. Even if the pride that Warren feels in her minuscule Native American ancestry is somewhat false, romaticized, and lacking in practice/practical effect, it is still pride, unmistakably, rather than its opposite. Citizens of the US generally take pride in vibrant Native American cultures and take steps through the government to help them, via direct aid, educational assistance, gambling concessions, and other benefits, after and in compensation for, the deeper history of genocide, reservation confinement, ethnic cleansing, and cultural extermination. The relationship is surely a difficult, guilty one. No one wants to alter the definitions that American Indian nations have developed for their formal membership. But their wider membership of genetic descendants is also a positive asset, in pursuit, not of assimilation, but of friendly relations with the wider, shared culture.

• Stiglitz on inequality.
• Meanwhile, the Taliban may not be popular, but they are persistent.
• Class action? Good luck.
• What are you if you enjoy lying? 
• Homelessness is a growing crisis of inequality and government sclerosis.
• Now for some nice piano.
• And some nice paintings.

Caught in a Lie

Why does our political system spend decades stuck in states of denial?

I am enjoying an infinitely long podcast about the Civil War. One of its lessons, and of that period in history generally, is that incredibly large numbers of people can, for decades, believe convenient or politically motivated falsehoods. The gulf between the Declaration of Independence and the reality of slavery was there for all to see, particularly in the South. But it took a century for the issue equality to come to a head in the war, and then another century for it to come to a head again in the civil rights movement. And we are far from done with it now.

Decades were spent explaining away the obvious with justifications ranging from the nakedly instinctive and economic to the scientific and religious, that people are not after all created (legally, politically) equal, and even if they were, to the victor belong the slaves. It took a national movement of abolition, and particularly the book Uncle Tom's Cabin, to rub people's noses in the fundamental contradiction and injustice. And even then, half the country, full of perfectly respectable and intelligent people, fought a bitter war to escape the truth of the matter. It is appalling to look back at the time spent, and the lives wasted and lost, in this process of slow awakening.

"You can fool all the people some of the time and some of the people all the time, but you cannot fool all the people all the time." - attributed to Abraham Lincoln, but of uncertain provenance.

Smoking is another, smaller, example. The tobacco companies didn't really need to work very hard to convince people that smoking was safe, since most of the country was addicted to nicotine and didn't want to know the truth. But a concerted campaign of disinformation and unconscious conditioning, through floods of advertising and copious product placements lulled the addicts to somnolence, while continuing to draw in new generations of "rebellious" young customers.

Now our politics seem to be in another decades-long process of denial and division. The racial issue still lives as part of the divide, as does resurgent economic inequality, but more important is the environmental issue. The earth is in peril, and it is our own greed and ignorance that put it there. Half of our political system is dedicated to denial, which is getting more flagrant with each election. Perhaps, like the period before the Civil War, the more endangered one's comfortable lies are, the more vociferously, even militantly, they are defended. At this point we have a chief executive who lies maliciously about everything, as a matter of habit, and we hardly bat an eye. Particularly telling is his advice to men accused of sexual assault - "You have to deny everything"- advocating perjury.

Interestingly, the parties (though not the regions) responsible for these epochs of lying and denial have switched dramatically. The Republican party brought us the clarity of abolition, union, and Lincoln. The exodus of Democrats from congress during the Civil War allowed a fresh wind of progressive legislation, such as fiat money, income tax, and the land grant education system. Now, Republicans are the party of the South and of vested priviledge- racial, economic, and patriarchial. It is for all these fossilized interests that Republicans maintain a policy of denial, shamelessly serving the wealthy and the industries they run, like the Koch conglomerate, and the coal and oil companies. Lies serve as a defense against rational policy and democracy. They serve as a screen against understanding and care for the future by the electorate- especially the vaunted "base", of which it is difficult to say whether it is predominated by ignorance, cynicism, meanness, or worse.

In the Civil War era, the purveyors of lies were mostly conservative social habits and structures that served the powerful- the dominance of the planter elite and the religions which supported them unstintingly. Power ruled nakedly, over slaves, but also over the social system more generally, including its media. Power is again, obviously, the problem today. It is those in power who do not want change, do not want to make the economic system more equal or sacrifice even a pittance for the future of the biosphere. The Supreme Court has pronounced money to be speech, which means the dominance of corporations and the rich. History is a litany of struggle for power between the rich and the poor, conducted by various mythologies and lies. The left has its problems with truth as well, particularly in its Marxist incarnation, which went so far as to claim itself as a science of history, economics, and social justice. Naturally, the lying reached an appalling crescendo when the Marxists gained maximum power under Stalin. Whatever the party, the powerful have the most to hide, and engage in the most habitual and cynical lying to keep it hidden, sometimes via blatant lying, but more often in plain sight via elaborate ideologies of other-denigration and self-justification.

But there are also technological issues. An internet that was supposed to spread truth and information is instead ridden with button-pushing trolls and corporate propaganda, while killing off the professionally edited media. Putin's Russia has refined disinformation to an alarmingly precise science, and Trump has been their most attentive student. Between them and the FOX propaganda channel, Rush Limbaugh and colleagues, independent thought hardly stands a chance. One characteristic of the lying is their loud claims of truth, such as the slogan "Fair and Balanced", and the reflexive denigration of any source of thoughtfully investigated and edited information as "fake news". Unbeknownst to the innocent, what were previously channels of information have transformed into fronts of warfare- class warfare.

"In science, if you stand up and say something you know is not true, that is a career-ending move. It used to be that way in politics." -Bill Foster, physicist and member of Congress 

• Tom Tomorrow on fake news.
• Ten commandments may need a minor update.
• Our system has a problem with minorities.
• Republican reminiscences.
• Weaponizing the dollar.. would be much more effective if we had friends.
• Defunding the IRS for complete impunity... of the powerful.
• "In 2014, an international team of biologists estimated that, in the past 35 years, the abundance of invertebrates such as beetles and bees had decreased by 45 percent."

Bounty Hunter, Protein Edition

CDC48 is an all-purpose protein extractor, bringing reluctant proteins in from far-flung parts of the cell, to be executed at the proteosome.

Every cell needs a recycling bin. While DNA lives forever, other molecules like membrane lipids, RNAs, and proteins do not. They are chemically less stable. They may also have functions that are sufficiently fleeting or conditional that they need to be turned off  quickly and specifically, one common method of which is to dispose of them entirely. For proteins, a vast infrastructure exists to identify and recycle them for these various reasons, involving hundreds of genes. A central character in this story is ubiquitin, a small protein that is, as its name implies, ubiquitous. It is used as a flag to mark proteins, usually for degradation, but also for other regulatory events. 

For example, one mechanism that sets protein lifespans is the N-end rule. A set of enzymes recognize the amino acid on the very N-terminus of each protein in the cell (if it is accessible). Different amino acids determine different life spans, from days (M, G, A, S, T, V, P), to a fleeting couple of minutes (R). These enzymes then ligate a ubiquitin to the protein, and leave it to be found by the next actor in the system, the bounty hunter of the cell, CDC48. Not all proteins need to be tracked down. Many diffuse on their own over to the proteosome, where they are willingly digested for the greater good. (Think Soylent Green, at risk of mixing metaphors) Some ubiquitin-flagged proteins are more reluctant, however. They may be stuck in one of many cellular membranes, or part of a big protein complex, or in a misfolded protein glob. Biology has become awfully complex in the last few billion years, and proteins find themselves in all sorts of tight spots.

The euthanasia processing center.

Most of the hundreds of genes devoted to this protein disposal process encode proteins (called E3 ligases) that attach ubiquitin to target proteins based on various rules such as the one above. Another recently described rule and protein (FBXL17) evaluates the quality of a particular family of protein dimers. If such a dimer is slightly misaligned or misfolded, a patch on its surface (called a degron) is exposed that interacts with this protein, which attaches a chain of ubiquitins, putting up the wanted poster that CDC48 and its colleagues later come around to collect.

CDC48 eventually arrives, as a special extractor of reluctant proteins, crow-barring them out of wherever they happen to be hiding so that they can be ferried over to the proteasome / recycling center. Its structure is a complex hexameric donut, and it has not one, but two ATPase activities, so one might say it comes equipped with two six-shooters. It collaborates with a large number of other proteins that help identify and track down squirrely proteins, as well as to help transfer them onwards. (CDC stands for cell division cycle, a famous series of mutants in yeast that won a Nobel prize in 2001 for their elucidation of the mechanics of cell division regulation. Many key cell division proteins have very short and closely regulated lifespans. The human version of CDC48 is named VCP and p97.)

Structure of CDC48 (green, blue, and purple portions) with a small inhibitor (red) jammed in that gums up its activity.

As do many interesting protein complexes, CDC48 has a hole in the middle. This is where the tagged proteins get pulled through, yanking them right out of wherever they are, guns blazing. Which is to say, with plenty of ATP powering the process. The top part of the complex recognizes ubiquitin in the form of polyubiquitin chains, which is the typical degradation tag. The two rings, which are the meat of the CDC48 protein, each have an ATPase activity, and engage in a subtle hokey-pokey as they operate, (below) which is assumed to constitute the extraction process, pulling proteins bit by bit through the center. Since the target protein is covalently tagged with ubiquitin, it has been found that this central hole is big enough to accommodate two protein chains going through at the same time, either a hairpin shaped substrate following a leading ubiquitin chain, or ubiquitin and the target protein travelling alongside each other.

A very rough model of the structural changes of CDC48 as it burns ATP to pull protein chains through its inner ring, from top to bottom. 

"After interaction of the polyubiquitin chain with UN, [an accessory protein docked to the top of CDC48 that helps recognize the ubiquitin tag], Cdc48 uses ATP hydrolysis in the D2 domain to move and unfold the polypeptide substrate through its central pore. ATP hydrolysis in the D1 domain is involved in substrate release from Cdc48, a process that requires the cooperation of the ATPase with a DUB. The DUB trims the polyubiquitin chain, and the remaining oligoubiquitin chain is then also translocated through the pore."

When the protein gets to the other side, it is not quite clear what happens next. Most likely is that CDC48 waits till directly docked with a cytoplasmic proteasome before fully unfolding its captured culprit into the proteasome's maw. But there are likely to be partner proteins involved in this process as well, at least as helpers. This is an ancient and ubiquitous process, conserved from bacteria to humans. CDC48 makes up about one percent of proteins in a typical cell, a very prominent role in line with the minor, though critical, role, of bounty hunters in our legal and dramatic worlds.

• Stiglitz on the election.
• On the economic Nobels: " ... running out of resources is not a huge concern, but rather the exact opposite, that we will have access to and use too many polluting resources, should worry us. That is tremendous foresight for someone writing in 1974!"
• Also, inventors and innovators never get a break- their profits are small and fleeting. "I estimate that innovators were able to capture about 4 percent of the total social surplus from innovation."
• Do driverless cars want to avoid getting hurt?
• The Taliban may be winning ground, but hearts, not so much. For Pakistan, however, they are the ideal tool.
• Social dominance feeds on itself. Thus every family's quest to scrabble up the social tree.
• Ditto from Adam Smith.
• It remains odd to have a Russian operative in the White House.
• Is economics monotheistic?
• Dr. John McLaughlin.

The Quest For Meaning

We spend our lives searching for something that does not exist. And then realize that we have been fighting over it the whole time.

The meaning of life: 42? Or something more profound? Religions have been founded, and wars fought, over what by definition is most important to us, but on which no one seems able to agree. One advance in the philosophy of meaning was Maslow's hierarchy of values, which starts with basic sustenance, and rises through the more refined social values to self-actualization (possibly a dated concern!). If one does not have enough to eat, nothing else means much. But whether these form a true hierarchy is unclear, since many people have died for some of the more esoteric levels of this hierarchy, indicating that we are mixed-up beings, not always valuing life over some principle or ideology. It turns out that propaganda, social pressure, and decent odds, can make people kill and die for the most arcane propositions. Also, that winning means a lot to us.

Meaning is not given or objective. There is no star or cloud telling us that we mean X, while people in the other tribe mean Y. Quite the other way around. I think we can safely say at this point that we have constructed religions (as one example of indoctrinating human institutions) as complex machinery to propagate meanings that we (or at least some) have devised, using gods as fronts for desirable social hierarchies, idle speculations, melodramatic ruminations, and elevated emotions. That these machineries are passed off as objective and profound is critical to their function, elevating their impressiveness (and oppressiveness). If your meaning and values can be dictated by me, who wins? If god says you should have a beard, how can you complain, and to whom? This is the quest of propaganda generally- to instill meanings into, and thus lead, masses of people.

So we have been fighting over meaning and values all along, through our social relations. There is nothing to seek, but rather a world to win, for as far as others share one's meaning, one gains power. For example, a recent post told the story of Arthur Kornberg, eminent biochemist. One of his leadership qualities was an absolute conviction of the importance of what he was doing. If his team members were not willing to be tied to the bench at all hours and have midnight phone calls for urgent updates, their tenure was short. How much of this was willing? That is hard to say, and is one of the mysteries of personal, charismatic, leadership- the diffusion of meaning to others. Parenting is the same story, naturally, as is politics. Parents promote respect for elders and the elderly as a core societal virtue ... and no wonder! Advertising is another big example in our culture. The alchemical transformation of a natural desire- for status, sex, safety- into a value and meaning structure that renders some product essential. We are far more what we buy than what we eat.

Meaning turns out to be more of a fight than a quest. Meanings are swirling all about us, and are up for grabs. There is no grail to find, but only a social contest between those who seek to tell other people what is most valuable and important, others who promote other, maybe contrasting, values, and innocents in the middle, caught in the cross-hairs of domineering social warfare. Even Buddhism, whose doctrine revolves around the illusory nature of existence, the non-self, and the dampening of one's attachments, seems eager to propagate those very doctrines, promoting the somewhat ironic meaning of meaninglessness.

Returning to Maslow's hierarchy, many of our meanings are objectively based. We need to eat, have room to live, and have the other necessities of our current technological status. Social status is another need, biologically based. Since most of these are subject to scarcity, we are immediately thrust into competition with our fellow humans. These objective necessities can be woven into much larger ideologies of competition and tribalism. On a theatrical basis, they are portrayed in sporting events, game shows, and reality TV. But they become more grounded in the business world- that merciless competition that ends in bankruptcy and homelessness. Which is in turn only a slight step above the level that characterizes the ultimate competitive test of meaning: warfare, massacre, and murder.

We are bombarded from earliest childhood with values and messages of meaning, many of which conflict. The confusion can be difficult to deal with, leading many into the arms of simple solutions- taking meaning from those who shout the loudest, or who simplify most audaciously. It is up to us to choose, though our basis is necessarily the choices we have made already and which have been made for us earlier on in our lives. Meanings build on each other. But they also have a rational aspect. If compassion is part of our value system and self-meaning, that will not sit well with projects of tribal pride and dehumanization. It is complexity that requires careful thought, which is why morality is not just a matter of feeling, but also of reason.

The meaning of life is not hard to find, but it is hard to decide on, from the myriad choices and influences surrounding us. That is why sticking with positive influences and avoiding cesspools like Facebook / Fox news is so important. It is also why "big question" discussions are often overblown, shills for the dissemination of some particular and parochial set of meanings.  The quest is not for some elusive single meaning, but for ways to chose among the vast numbers of them we meet along the way of life.

• Imagine ... if Trump ran Hollywood.
• We are in the middle of propaganda warfare.
• More lies.
• Automatons have long been used to fake the work of gods.