MRGA

Make Russia Great Again: Conservative, white, Christian, low levels of immigration, despotic ... what's not to love about Russia?

It would be unbelievable if it weren't true. The Republican party, which conducted the Red Scare of the 50's, and stood up for democracy, political conservatism, apple pie, patriotism, and militarism around the world, now stands for something quite different. A combination of hatreds- for Democrats, for immigrants, and, seemingly, for personal freedom- seems to have sent the Trumpy ecosystem into a very weird place, where Russia is good, autocracy is strength, and American democracy is weakness. What are real patriots to do?

Republicans in congress sure look like they are selling out Ukraine. After linking aid to southern border fixes, they realized that the fixes were going to be politically beneficial to Democrats, as would the Ukraine aid, so both were scuttled. The newest proposal appears to cut Ukraine aid, and not accept the Senate bill, but that is also stalled. We are, at best, in for a long negotiation, all furthering the interests of making Russia great again. And Trump himself was not shy about putting it all in words, declaring Putin's invasion of Ukraine "smart", and inviting invasion of more NATO countries.

This policy is, in essence, throwing away the whole post-war order and rationale for American power, stretching across our innumerable alliances from Europe to Japan. It is unimaginable to any serious student of American power and the last hundred years. But here we are, serving the interests of our enemies in the most blatant ways. Russia, needless to say, is not our friend. Could have been our friend, in the post-Cold War period, but Russia ended up under the thumb of Putin, whose hatred of the West appears foundational to his political success, and even more, to his KGB heart. 

What is the deeper thread behind this craziness? I think it goes back to the culture war. Republicans have decisively lost the overall culture war in America. Gay marriage is here to stay, diversity is mainstream, and even abortion is, after the overturning of Roe, a huge loser for Republicans. They are souring on America in a fundamental way, and looking elsewhere for inspiration. Like Nazi Germany, Hungary, and Russia. At least that is the way it looks and the way they, and especially Trump, talk. And with enough money and propaganda behind them, Republicans can to some extent buck the math and the good will of contemporary American democracy. The question is- how far? The last presidential election was razor-thin, but still, not a great indication that this strategy is going to be broadly popular, and recent elections have shown even worse results. 

In addition to straining to help Russia, this movement is doing anything but making America great again. Our friendships around the world are in tatters, with everyone nervously eyeing the next election. Republicans stand firmly behind making a sociopathic dolt president, for a second time. And their Supreme Court is authoring a new epoch of medieval jurisprudence. This is how empires crumble, when powerful factions decide that their hold on power is more important than the law, more important than petty democracy, more important than peace and stability, more important than truth, and that a little insurrection or civil war might not be such a bad way to force their views down everyone else's throats. When backed by oodles of money, shamelessness, and a relentless propaganda bullhorn, it is, needless to say, highly combustible.

• When people feel powerless.
• Oh, those innocent days.
• Platitude.
• Want to die in the arms of a corporation?
• Hunter Biden Hunter Biden Hunter Biden.
• Plastic is trash.
• Economic effects of the war in Russia.

A New Form of Life is Discovered

An extremely short RNA is infectious and prevalent in the human microbiome.

While the last century might be called the DNA century, at least for molecular biology, the current century might be called that of RNA. A blizzard of new RNA types and potentials have been discovered in the normal eukaryotic milieu, including miRNA, eRNA, lincRNA. An RNA virus caused a pandemic, which was remedied by an RNA vaccine. Nobel prizes have been handed out in these fields, and we are also increasingly aware that RNA lies at the origin of life itself, as the first genetic and catalytic mechanism.

One of these Nobel prize winners recently undertook a hunt for small RNAs that might be lurking in the human microbiome- the soup of bacteria, fungi, and all the combined products that cover our surfaces, inside and out. What they found was astonishing- an RNA of merely 1164 nucleotides, which folds up into a rigid, linear rod, which they call "obelisks". This is not a product of the host genome, nor of any other known organism, but is rather some kind of extremely minimal pathogen that, like a transposon or self-splicing intron, is entirely nucleic-acid based. And the more they hunted, the more they found, ultimately finding thousands of obelisk-like entities hidden in the many databases of the world drawn from various environmental and microbiome samples. There is some precedent for this kind of structure, in the form of hepatitis D. This "viroid" of only 1682 nucleotides is a parasite of hepatitis B virus, depending on that virus for key replication functions. While normal viruses (like hepatitis B) encode many key functions of their own, like envelope proteins, genome packaging proteins, and replication enzymes, viroids tend to not encode anything, though hepatitis D does encode one antigenic protein, which exacerbates hepatitis B infections.

The obelisk RNA viroid-like species appear to encode one or two proteins, and possibly a ribozyme as well. The functions of all these are as yet unknown, but necessarily the RNAs rely entirely some host cell (currently unknown) functions to do their thing, such as the RNA polymerase to create copies of itself. Unknown also is whether they are dependent on other viruses, or only on cells for their propagation. Being just discovered, the researchers can do a great deal of bioinformatics, such as predicting the structure of the encoded protein, and the structure of the RNA genome. But key biology, like how they interact with host cells, what functions the host provides, and how they replicate, not to mention possible pathogenic consequences, remain unknown.

The highly self-complementary structure of one obelisk RNA sequence, leading to its identification and naming. In green is one reading frame, which codes for the main protein, of unknown function.

The curious thing about these new obelisk viroid-like RNAs is that, while common in human microbiomes, both oral and gut-derived, they are found only in 5-10% of them, not in all samples. This sort of suggests that they may account for some of the variability traceable to microbiomes, such as autoimmune issues, chronic ailments, nutritional variations, even effects on mood, etc.

Once a lot of databases were searched, obelisk RNAs turn up everywhere, even in some bacteria.

This work was done entirely in silico. Not a single wet-lab experiment was performed. It is a testament to the power of having alot of genomes at our disposal, and of modern computational firepower. This lab just had the idea that novel small viroid-like RNAs might exhibit certain types of (circular, self-complementary) structure, which led to this discovery of a novel form of "life". Are these RNAs alive? Certainly not. They are mere molecules and parasites that feed off, and transport themselves between, more fully functional cells. But they are part of the tapestry of life, which itself is wholly molecular, with many amazing emergent properties. Whether these obelisks turn out to have any medical or ecological significance, they are one more example of the lengths (and shorts) to which Darwinian selection has gone in the struggle for existence. 

• Want to become a rabbi?
• Hey, what happened to reading?
• Is hell other people?

How the Supreme Court Should Rule in the Colorado Ballot Case

There is one path forward that can salvage the court's standing.

The US Supreme Court is sinking to unusual depths of corruption and illegitimacy. Bush v. Gore was a step down in its ability to manage the rules of our political and legal system, where it made a hasty and, it claimed, one-time-only carve-out for its favored candidate, leading to almost a decade of tragically bad policy and poor government. Then came Citizens United, another step downward, opening firehoses of secret money from the wealthy, using the fig leaf of "free speech" to cover the corruption of politics with money. Then came the overturning of Roe, deeming women unworthy of rights that are far more basic and intimate than those enumerated in the Bill of Rights. And most recently have come the drumbeat of reports of corruption among the right-wing justices, who appear to regard themselves as too dignified to abide by the laws and norms they hold others to.

Now it is faced with a case that tests the very core of the court's abitlity to do its job. What does the constitution mean? Does the fourteenth amendment mean what it says, and if so, should it be enforced? A great deal of commentary suggests, probably correctly, that this court is desperately looking for a way out of this legal conundrum that allows it to do nothing and avoid overturning any apple carts. That would not, however, be a wise course. 

To recap, the Colorado case was brought by voters who sought to bar Donald Trump from the Colorado primary and general election ballots, due to his participation in the insurrection of January 6, 2021. The fourteenth amendment to the federal constitution bars such participants from federal and state offices. The Colorado Supreme Court ultimately agreed, sending the case to the US Supreme Court. The congressional report on the January 6 events makes the record of those events quite clear. It uses the word "insurrection" several times, as do many of its sources, and it is crystal clear about the participation by and culpability of Donald Trump in those events. 

The question is really about how the Constitutional provision should be brought into execution, being worded without a lot of explicit legal structure. One thing it does say is that congress can relieve its prohibition in individual cases by two-thirds votes of each house. But it leaves unsaid who should adjudicate the question of fitness for office, as is also the case for the more basic qualifications such as age and citizenship. Trump had previously, and ironically, dabbled in these same legal waters by casting doubt on the citizenship of Barack Obama. But since no one with half a brain took him seriously, the issue never entered the legal sphere.

Well, the worst course would be to let the clear language of the constitution lay inert and find some technicality by which to do nothing. What I would suggest instead is that the court recognize that there needs to be a national adjudicating power to decide this question in the case of candidates for national office (and indeed for any office whose qualifications are mentioned in the constitution). And that power should be itself, the US Supreme Court. The court might invite the legislative branch to provide more regular methods of fact-finding, (or even a clarifying amendment to the constitution), but given the constitutional clear intent, history, and logic, (not to mention the general Article III clauses putting all questions arising from the constitution in its hands), the court should take upon itself the power to say that the buck stops at its door. And naturally, in consequence, that Trump merits disqualification, on the facts of the January 6 events as found by the lower courts, and on his position as an officer, indeed the paramount officer, of the United States.

This solution would neatly take over from the states the responsibility of saying that any national candidate meets or does not meet the various qualifications set forth in the constitution. Such cases could begin in state courts, as this one did, but would need to go to the US Supreme Court for final decision. This solution would hold Trump to account for his actions, a principle that Republicans have, at least  traditionally, cherished. This solution would also go some way to removing the stain of the Bush v Gore decision, and establish a new and clear element of constitutional jurisprudence, in setting forth who adjudicates the qualifications of national political candidates. In fact, this function can be tied to the practice of having the chief justice of the United States administer the oath of office to the incoming president. It would be proper for the court to be the institution that decides on the basic fitness tests, and thus who in general may take the oath, while the people decide the political outcome of the election, among fit candidates.

I am no legal scholar, but the merits of this solution seem pretty clear. On an earlier occasion, the court summarily took on the task of determining the constitutionality of laws. This role was not explicitly set out in the text, but was a logical consequence of the structure that the constitution set up. Here likewise, the logic of the constitution indicates strongly that the final word on the fitness of candidates for national office must rest with, not the voters, not the states, and not the legislative or, heaven forbid, the executive branch, but with the federal judicial branch, of which the US Supreme Court is the head.

An alternative, and perhaps more likely, solution, is for this court to state all the principles above, but then hold that in its judgement, Donald Trump is fit for office after all. Maybe it will deem the insurrection just a little insurrection, and not the kind of big insurrection that would turn a jurist's head (despite the over thousand charges filed, and hundreds of federal convictions so far). Or maybe it will deem Trump insufficiently involved in the insurrection to merit disqualification. What it can not do is deem him not an officer of the federal government- that would be beyond belief. The pusilanimous, partisan sophistry of this alternative would not go over well, needless to say. Many would ask whether Clarence Thomas, himself virtually a participant in the insurrection at one remove, should have recused himself. Minds would be blown, but few would be surprised, since for this court, expectations could hardly be lower. Going against its partisan grain would, on the other hand, be a signal and heartening achievement.

This second approach would at least resolve the legal questions, but at the cost of further erosion of the court's legitimacy, given that the events of January 6 are so well documented, and the constitutional peril that Trump poses so obvious. For the whole point of having a Supreme Court which takes on tough issues and plugs logical holes in our constitution is that it also takes some care to plug them well, and preserve our democracy in the process.

• What happens when the Supreme Court gives in to politics?
• One state, one system.
• A solar energy insurrection in Puerto Rico.
• Democratic inequality is related to wealth inequality.
• More on the court case- ballots vs office holding.

Spiritual Resources for the Religiously Abstemious

Nones are now a plurality in the US. What are we supposed to do?

The Pew research institute recently came out with polling that shows a significantly changed religious landscape in the US. Over the last couple of decades, while the religious right has been climbing the greasy pole of political power, gaining seats on the Supreme Court, and agitating for a return to patriarchy, their pews have been emptying. The religiously unaffiliated, or "nones", comprise 28% of the US population now, almost double the level two decades ago.

One has only to see the rabid support evangelicals give their orange-haired messiah to understand what has been turning people off. Or glance over the appalling chronicle of sexual abuse unearthed in the Catholic church. Maybe the horsemen of the Atheist apocalypse have had something to do with it. Russia under Putin is strenuously demonstrating that the same system can be just as cruel with or without religion. But these patterns of gross institutional, moral, and intellectual failure, and their ensuing critiques, are hardly new. Luther made a bit of hay out of the abuses of the Catholic church, Voltaire, among many other thinkers, ridiculed the whole religious enterprise, and Hitler was a forerunner of Trump in leaning on religion, at least early in his career, despite being a rather token Christian himself (other than in the antisemitism, of course). What is new now?

A dramatic rise in numbers of people with no religious affiliation and little interest, from Pew polling.

I am not sure, frankly. Europe has certainly been leading the way, showing that declining religion is quite compatible with prosperous and humane culture. But perhaps this phenomenon is part of the general isolation and atomization of US culture, and thus not such a good thing. It used to be that a community was unthinkable without a church (or several) to serve as the central hub. Churches served to validate the good and preach to the bad. They sponsored scout troops, weddings, charitable events and dinners, and committees and therapeutic encounters of all sorts. They were socially essential, whether one believed or not. That leaders of society also led the churches knit the whole circle together, making it easy to believe that something there was indeed worth believing, whether it made sense or not.

Now, the leadership of society has moved on. We are mesmerized by technology, by entertainment, and sports, perhaps to a degree that is new. The capitalist system has found ways to provide many of the services we used to go to churches for, to network, to get psychotherapy, to gossip, and most of all, to be entertained. Community itself is less significant in the modern, suburban, cocooned world. Successful churches meet this new world by emphasizing their social offerings in a mega-church community, with a dash of charismatic, but not overly intellectually taxing, preaching. Unfortunately, megachurches regularly go through their own crises of hypocrisy and leadership, showing that the caliber of religious leaders, whatever their marketing skills, has been declining steadily.

The "nones" are more apathetic than atheistic, but either way, they are not great material for making churches or tightly knit communities. Skeptical, critical, or uninterested, they are some of the least likely social "glues". Because, frankly, it takes some gullibility and attraction to the core human archetypes and drama to make a church, and it takes a lot of positive thinking to foster a community. I would promote libraries, arts institutions, non-profits, and universities as core cultural hubs that can do some of this work, fostering a learning and empathetic culture. But we need more.

As AI takes over work of every sort, and more people have more time on their hands, we are facing a fundamental reshaping of society. One future is that a few rich people rake off all the money, and the bulk of the population descends into poverty and joblessness, unneeded in a society where capitalism has become terminally capital-intensive, with little labor required. Another future is where new forms of redistribution are developed, either by bringing true competition to bear on AI-intensive industries so that they can not take excess profits, or by thorough regulation for the public good, including basic income schemes, public goods, and other ways to spread wealth broadly. 

Such a latter system would free resources for wider use, so that a continuing middle class economy could thrive, based on exchanges that are now only luxuries, like music, personal services, teaching, sports, counseling. The destruction of the music recording industry by collusion of music labels and Spotify stands as a stark lesson in how new technology and short-sighted capitalism can damage our collective culture, and the livelihood of a profession that is perhaps the avatar of what an ideal future would look like, culturally and economically.

All this is to say that we face a future where we should, hopefully, have more resources and time, which would in principle be conducive to community formation and a life-long culture of learning, arts, and personal enrichment, without the incessant driver of work. The new AI-driven world will have opportunities for very high level work and management, but the regular hamburger flippers, baristas, cabbies, and truck drivers will be a thing of the past. This is going to put a premium on community hubs and new forms of social interaction. The "nones" are likely to favor (if not build) a wide range of such institutions, while leaving the church behind. It is a mixed prospect, really, since we will still be lacking a core institution that engages with the whole person in an archetypal, dream-like fantasy of hope and affirmation. Can opera do that work? I doubt it. Can Hollywood? I doubt that as well, at least as it applies to a local community level that weaves such attractions together with service and personal connection.

• Those very highly moral religious people.
• Molecular medicine is here.
• Why do women have far more autoimmune syndromes?
• What to do about Iran.
• "As we’ll see, good old-fashioned immortality has advantages that digital immorality cannot hope to rival." ... I am not making this up!

Evolutionary Elaboration of mRNA Splicing

An RNA helicase scoots through the spliceosome to advance the process of mRNA splicing. And some other tricks.

In our cells, virtually all mRNAs transcribed from DNA have to go through an editing process to cut out intervening junk called introns. This process is called splicing, and its evolutionary origin, later elaborations, and current mechanism are all quite interesting. Life didn't start with introns, and only eukaryotes have them as a regular feature of their genomes. They appear to have arrived with the bacterium that became our mitochondria, which come from a lineage that has (relatively few of) what are called group II self-splicing introns. These are RNA segments that behave a bit like transposons, being able to jump into DNA, and then reverse-transcribe that segment into a copy of itself in genomic DNA. 

The ur-eukaryote seems to have had an incredibly prolific infection, which left its host genome riddled with these bits of DNA. A key point is that, in group II introns, their splicing out of a transcribed RNA message is auto-catalytic- entirely mediated by their own RNA structure. They are self-propagating parasites, which have, over time in eukaryotes, been tamed to become fertile aspects of our own gene regulation and evolution. For example, introns often fall between protein domains, allowing these relatively compact modules of protein structure to be replicated, moved, and plugged, via rare mutational events, into new settings to contribute new functions to existing or novel proteins.

A map of a group II self-splicing intron. In red are the ends of the host RNA (or DNA) which are to be either jumped into or excised out of. The rest is the structure of the intron, which carries its own catalytic ability to do these reactions. This kind of thing is what appears to have turned into our own splicing and intron/exon systems, since the core catalytic mechanisms, such as the use of lariats and branch points and RNA catalysis, are the same.

Representation of the core spliceosomal reactions in eukaryotes, which result in a free lariat form of the excised intron, and the joined exons, which go off to code for their protein. "SS" stands for splice site. The sequences in red characterize introns.

The mechanism of intron excision in our cells is, at its core, still RNA-based, even though there are now also hundreds of proteins involved in the rather massive machinery of what is now called the spliceosome. It is clear that over evolutionary time, what was originally an unwelcome and shocking invasion of proto-mitochondrial introns into the proto-nuclear host genome has been regulated, speeded up, accessorized, and integrated into our normal method of gene expression. The spliceosome is the result- a huge and dynamic complex that uses key bits descended from the original RNA catalytic components to guide and catalyze the splicing reaction.

Representation of the core splicing reactions, with the key small RNAs added in (U1, U2, U4, U5, U6). These both guide (by direct RNA-RNA hybrid formation) and perform catalysis at the two chemical bond-breaking/reforming steps.

There are three key locations seized upon by the spliceosome. First is the 5 prime splice site- the end of the coding exon and beginning of the intron, typically a "G" nucleoside at the start of the intron. Second is the branch point, an "A" near the end of the intron, which is where the chemistry of splicing begins. And third is the 3 prime splice site- the end of the intron, with another "G" nucleoside, next to the beginning of the next coding exon. While the first two sites are specifically recognized by RNA components of the spliceosome, (U1 at the 5 prime splice site and U2 at the branch site), the 3 prime splice site is simply recognized by scanning for the first "AG" downstream of the branch site.

The first reaction is to bring the branch site and the 5 prime splice site in proximity, such that the branch site A covalently invades the G at that site and displaces it, releasing the exon end and forming a loop (called a lariat, in red above) in the intronic RNA. The second reaction is to bring the 5 prime exon end over to the 3 prime exon end, and similarly prompt and invasion that links them, displacing the intron entirely.

So simple to describe, but not so easy to do. Accuracy is paramount, since the three-codon reading frame of mRNA would be destroyed by even a 1 nucleoside error in splicing. Splicing now gates the export of mRNA from the nucleus, so that only fully and accurately spliced transcripts get out to the ribosomes in the cytoplasm for translation to protein. This gating has been considered by some the very reason that the nucleus exists at all- a way to solve some of the knotty problems that arose in very early eukaryotic evolution when all these introns invaded. 

Another reaction scheme of splicing, showing the key RNA and some other proteins along the way, principally the key helicases that help drive things forward. Note where PRP2/ATP comes into the picture, just as the complex is preparing for the first catalytic step.

Be that as it may, it is clear that the originally RNA-only mechanism changed over time by accreting proteins that each decided they had something useful to add to the process. At the same time, the RNA got separated into several pieces (on independent genes) that could then be carried and precisely manipulated by these helping proteins. The spliceosome now involves five distinct small RNAs and over 200 proteins, which engage in a complex ballet of sequential steps. A special class of these proteins, the helicases, are the subject of a recent paper that provides new structural information. Helicases are proteins that can use the power of ATP to unwind DNA or RNA, or just chug along it. At least eight such proteins participate in splicing. 

Structures from a recent paper, showing how PRP2 (at bottom, in violet) chugs its way along the mRNA intron (blue) into the very heart of the spliceosome complex, partially evicting the SF3B1 protein (green), among others, and prompting many other changes. At top is shown the 19 nucleoside stretch of the mRNA that was traversed, getting close to the branch site "A" in red. 

The paper makes the interesting observation that, structurally, most of the helicases reside on the periphery of the spliceosomal complexes, while the catalytic and guiding RNA are, naturally, at the center. They use a mutant form of one of them, Aquarius, to freeze spliceosomes in a key conformation just before the branch site and 5 prime splice sites are brought together. In combination with a bunch of other structural work by others in this and other labs, they show that one dynamic event is the tracking by a second helicase, PRP2 (violet, above), that brings it from its peripheral position (b, at bottom) along the intronic mRNA (blue strand) into the core of the splicesome near the U2 RNA (c; U2 is not shown here). They show that PRP2 traverses 19 nucleosides (top, a), a rather remarkable trip that forms part of the sequence of events that brings the branch site and 5 prime splice site close to each other.

Further structures, focusing on the catalytic site and RNAs. Note how the branch site (red, "BS-A") is, after the action of the Aquarius helicase, (third panel), brought in tightly close to the 5 prime splice site (green, "5'SS) in the C, or catalytic, complex. The U2 and U6 RNAs then have an easy job of bond-exchanging catalysis.

So it turns out that these helicases appear sometimes to be used as ratchets, that start on the outside of the complex. Once activated by some prior trigger, they pull on a thread in a way that helps to overall process forward. The progression of PRP2 into the spliceosome core evicts a bunch of other proteins and activates the other helicase Aquarius. That protein is likewise positioned perpipherally but is hanging onto another thread of the intronic RNA and helps to further push the branch and 5 prime splice sites together, in a way that finally leads to the desired reaction. Note in the image above that it is the RNAs that occupy the central reaction site- the intron in blue (green), and the U6 and U2 RNAs, which catalyze this first key reaction of splicing.

RNAs are not great catalysts, so it is understandable that, as in the case of translation by the ribosome, a bunch of proteins shoehorned their way into the process (over evolutionary time) in ways that evidently made splicing more accurate and more rapid. Indeed, yeast cells get along without the Aquarius protein at all, though they otherwise have a very similar splicing apparatus, showing that the accretion of proteins on the spliceosome did not end in very early stages of eukaryotic evolution, but continued through the origin of metazoans, and may still be continuing. The added proteins did this through using their talents for precise spatial positioning, and for the use of energy (from ATP) to drive things ahead, if only by intricate conformational ballet rather than direct catalysis.

• "Ron DeSantis should be forced to carry his presidential campaign to term."
• Nones are not nuns.
• Medical errors and AI.
• The worse the better... GOP edition.
• Two minutes hate.

The Tragedy of Daniel Boone

Pathfinding and hunting his way through the paradise the Indians had built.

Daniel Boone is (or used to be) one of the most iconic / archetypal figures in US history and popular consciousness. His remains have been fought over, his life mythologized and serialized, and his legacy cherished as heroic and exemplary. It all began with his trusty rifle, with which he was the surest shot. He was a pathfinder, never lost in the vast wilderness he explored and helped settle. And he was a steadfast leader of men, rescuer of damsels in distress, and killer of Indians. What's not to admire? His definitive biography, by John Faragher, paints a more ambivalent picture, however.

Boone loved the woods- loved hunting, loved nature, and loved solitude. Given those talents and tendencies, he naturally strayed from the borderlands of North Carolina into the mountains, becoming a full time hunter and trapper. In a couple of early forays into what we now know as Kentucky, he hunted on a commercial basis, wasting the animals to pile up hundreds of pelts, which his employees / colleagues processed in camp. 

The biography emphasizes that what Boone found in Kentucky was a paradise- lush and full of game. The region, believe it or not, was full of not just deer and beaver, but bear and buffalo. It is the kind of eden that had been encountered by Europeans many times over in the "New World". Fisheries of unimaginable richness, skies full of birds, forests as far as the eye could see. Kentucky was not an uninhabited eden, however- it was the cherished hunting ground of native Cherokee and Shawnee, among others, who saw exactly what Boone saw, but responded to it differently. Not with plunder and destruction, but with care and stewardship.

Boone blindly shot away, and then followed his cultural programming further by leading his family and many others across the mountains to found Boonesborough, building a fort and defending it against numerous Indian attacks. The biography notes that Boone's parents had ten children, and he had ten children, and his children had similar sized families. One can imagine where that kind of reproduction leads, to desperate expansion and heedless use of resources. While acknowledged as the pioneer of Kentucky settlement, Boone was no businessman, and all his grasping for land in the speculative rush that developed in his wake came to naught. He was sloppy in his paperwork and was outlawyered and out-cheated at every turn. One may see the personality type of his adversary in the current senior senator from Kentucky, Mitch McConnell. Boone was all too honest and simple, having been raised a Quaker.

Portrayal of the siege of a stockade, not unlike that of Boonesborough, as Native Americans try to drive off the cloud of locusts denuding their land.

The game had been hunted out, the people had become unfriendly and dense underfoot, and Boone's property and business schemes had all fallen apart. In despair over what he had wrought in Kentucky, Boone pulled up stakes and moved out to the next frontier, near St. Louis. An extremely late hunting trip has him heading through what is now Yellowstone park, reliving for the last time the kind of eden that Native Americans had nurtured with their respect for the value and cycles of nature, and even more, with their light footprint as small populations.

European culture and immigrants have accomplished wonderful things in America. But decimating its natural wonders, resources, and native peoples is not one of them. Daniel Boone was caught up in the economics of inexorable population growth and the need to make a "business model" out of hunting and trapping. Well, what comes of that is not pretty, and not at all sustainable of what had brought him into the woods to start with.

• Networked businesses are a free-market nightmare.
• White Jesus.
• Earworm of the week: a lovely rendition of Joni Mitchell's Both Sides Now.

Why Does Wyoming Emit 57 Times as Much CO2 per Capita as California?

Diversity is not always a good thing. States are in very different places when it comes to the carbon intensity of electricity generation.

California has been working hard to become a more sustainable place, from an energy and emissions perspective. Compared to the baseline of 2000, population has risen 15%, electricity production has held steady, and emissions are down 15%. We have a very long way to go, but are diligently chipping away at the sustainability problem. Look across the country, however, and it is quite a different picture. A remarkable map shows each state's per capita emissions just for electrical power production.

Map of the US showing per capita CO2 emissions from electricity generation alone.

It turns out that most states emit multiple, some many multiple, times the atmospheric and climate pollution of states like California. It is clear that there is very weak regulation on the federal level, and that we have hardly progressed from the laissez-faire mine and drill policies of the last century. Aside from hydropower concentrations in the Northeast (Vermont, Maine) and Northwest (Washington, Idaho), no state has lower emissions than California, and as noted in the title, Wyoming puts out a whopping 57 times more carbon per person per year solely in the electrical sector.

Part of the problem is simple chemistry. Coal was the traditionally cheapest source of energy, but has high carbon emissions (not to mention sulfur, nitrogen, ash, and other noxious pollutants and waste). Its general formula is CH, with a roughly 1:1 ratio of carbon and hydrogen. In contrast, methane is CH4, with four hydrogens per carbon. Each of those bonds (whether carbon-carbon or carbon-hydrogen) yields the same amount of energy. So per unit of energy released, methane emits roughly half the CO2. On top of that come the costs of scrubbing out the sulfur dioxide and nitrogen compounds that have been the target of decades of policy against acid rain, which further decrease the efficiency of coal. Imagine on top of that the huge (about 1/3 of total yield) energy cost of scrubbing out the CO2 from coal smokestack emissions, compressing, and sequestering it underground, and one can appreciate what a pipe dream this "solution" is, to keep coal combustion a viable energy source.

Coal combustion is not, indeed, viable at all, if one gives any thought to the atmosphere or the rest of the environment. And it isn't even economically viable any more against renewable wind and solar energy. But there is so much sunk investment in the power plants and mines, that change is hard to motivate. In addition, there are the hidden costs of wind and solar, being the batteries, grids, and other backup power sources needed to cover their intermittent nature. Those are real concerns. But one of the biggest issues is simply the nature of regulation in various states. California has set up complex rules to make utilities sensitive to the cleanlines of their power mix, and their cost structure. Other states have simpler regulatory systems that give utilities markups for all capital expenditures and investments, allowing them to pass through such white elephants as wildly over-budget nuclear power plants. And also continue paying for coal that is costing more than renewable, competitive sources of energy.

More broadly, we need to keep raising the costs of pollution on a wide, federal basis, to a level that forces recalcitrant states to advance global climate goals with clean energy. The US still gets almost a quarter of its power from coal. Much of this is generated and exported from Wyoming, either as electricity or as coal trains. This needs to stop. Many of the most emitting states lie in the midwest and Rockies, which have outstanding wind energy resources. The energy is there for the taking, but it has become a political issue, with red states now dedicated to thumbing their noses at the libtard environmentalists, even if it means spiting their own faces in terms of total electricity costs, pervasive pollution, and appalling jobs.

Trends of fuel sources for electricity generation in the US. Coal has decreased steadily, but still comprises roughly a quarter of generation.

While renewable energy has made astonishing strides in efficiency and cost, it is clear (as we have learned in California) that carrots alone will not make the energy transition happen and save the environment. The government predicts, under current and foreseeable policies, that emissions from the electricity power sector will remain the same out to 2050. That is unacceptable. Sticks have to be used as well, to internalize the enormous and ever-growing costs of atmospheric pollution onto the sources of that pollution- the diverse and sometimes egregiously dirty fuels that feed our insatiable appetite for power.

• The logic of Russia.
• Reality- so unfair to religion!
• Statistics is a difficult field and widely misunderstood: "... it feels paradoxical to discover that >80% of research is potentially “wasted.” Two independent estimates from the fields of medicine and ecology confirm that this is the case."
• That provocative flag of democracy.
• The humble barcode.
• Going deeper into life, not shallower.
• Beyond apps: the next step in AI and phones.

Damned if You do, Damned if You Don't

The Cherokee trail of tears, and the Palestinian conundrum.

History is a long and sad tale of conflict, interspersed with better times when people can put their animosities aside. Just as economics deals in scarcity and its various solutions, history likewise turns on our inevitable drive towards overpopulation, with resulting scarcity and conflict. Occasionally, special technological, spiritual, organizational achievements- or catastrophes- may allow periods of free population growth with its attendant bouyant mood of generosity. But more commonly, groups of people covet each other's resources and plot ways to get them. This was one of the lessons of Malthus and Darwin, who addressed the deeper causes of what we see as historical events.

The "New World" provided Europeans with an unprecedented release for their excess populations, especially the malcontented, the desperate, and the ambitious. They rhapsodized about the "virgin" lands that lay open, generally dismissing the numerous and well-organized natives present all over these lands, as "savages", occupying a lower technological and theological level of existence. There were plenty of rationalizations put forth, like Christianizing the natives, or "civilizing" them. But the hypocrisy of these formulations becomes clear when you consider the fate of the Cherokees, one of the "five civilized tribes". 

By the early 1800's, a couple of centuries of contact had already gone under the bridge, (as narrated by Pekka Hämäläinen in "Indigenous continent"), and native Americans were all integrated to various degrees in trading networks that brought them European goods like guns, pots, knives, and novel practices like horse riding. The Cherokees, occupying the lower Appalachians and piedmont between what is now Georgia and Alabama, were more integrated than most, adopting European farming, living, schooling, and governing practices. They even owned African American slaves, and wrote themselves a US-modeled constitution in 1827, in the script devised the scholar Sequoya.

Did this "progress" toward assimilation with the European culture help them? Far from! Their excellence in farming, literacy, and government raised fears of competition in the white colonists, and the Georgia state government lobbied relentlessly for their removal. Andrew Jackson finally obliged. He pressured the Cherokees to re-open their status as a settled nation, devised a removal treaty with a minority party, and then sent all the Cherokees in the region (about 16,000) off on the Trail of Tears, to the barren lands of Oklahoma. These Cherokees lost roughly a quarter of their population along the way, in a brutal winter. Compare this with the partition of India, where about twelve percent of the refugees are thought to have perished, out of roughly 16 million total.

A small part of the annals of ethnic cleansing, US edition. Needless to say, the "Indian territory" ended up a lot smaller than originally promised.

 

Georgia was thus ethnically cleansed, and does not seem to experience a great deal of regret about it. The logic of power is quite simple- the winner gets the land and spoils. The loser is lucky to not be killed. That the Europeans were significantly more powerful than their native antagonists doesn't change the logic, though it might appeal to our empathy and nostalgia in retrospect. The Cherokees and other Native Americans might have been accepted into US society. They might have been given one or two states for their sovereign governments, as the Mormons managed. There were a lot of possibilities that might have made us a more interesting and diverse nation. But at the same time, most Native Americans participated fully in the politics of power, terrorizing each other, making slaves of each other, and killing each other. They were not innocents. So the fact that they came up against a stronger power was hardly a novelty, though in this case that power was blundering and cruel, shared very few of their cultural coordinates, and was highly hypocritical about its own.

All this comes to mind when viewing the Israeli-Palestinian conflict. Israel won the major Middle East wars that so dramatically emasculated the Palestinians, first in the civil war that left Jordan and Egypt in charge of the Palestinian areas, then in the 1967 war that left all these areas in Israeli hands. But what to do with them? On founding, Israel was a liberal, New Testament kind of country, with humanist values and lefty kibbutzim. The then-recent Holocaust also caused a bit of hesitance when it came to either killing or exiling the losing Palestinians. Indeed, given that its neighbors Jordan and Egypt lost these wars, it would have made some sense at that time to deport all the Palestinians, of which there were about one to two million. But rather than do that, or make a firm border, Israel immediately started encroaching into Palestinian territory with security areas and "settlements", and has set up an ever more elaborate, though selectively porous and self-serving, security and boundary system.

Both sides have a schizophrenic reaction to the other. On the Palestinian side, the psychology of losing has meant quietism and acquiescence by some, but resentment and militantcy by others. Both lead to a spiral of worse treatment, the weakness of the former inviting abuse, and the desperate depredations of the latter inciting revenge, "security" measures, and tighter occupation. The provocations by each side are unendurable, and thus the situation deteriorates. Yet, in the end, Israel has all the power and the responsibility to come up with a long term solution. Over the decades, Israel has morphed from its founding ethos into something much more conservative and Old Testament, less beholden to the humanisitic ideals of the post-WW2 period. The wanton killing, starvation, and collective punishment of Gaza makes visible this moral breakdown.

The Palestinians can't win either way, either through Hamas's implacable hatred and impotent attacks, nor through the acquiescence of the Palestinian National Authority, which, in thanks for its good behavior, has received the creeping expansion of Israeli "settlements" on its land. These now take up, according to a detailed map, about 1/3 to 1/2 of the land of the West Bank. Overall, the options are: 1) to expel the Palestinians outright, which appears to be, for Gaza at least, where Israeli policy is heading, (made more ironic by the realization by historians that the Biblical Exodus never actually took place), or 2) to continue to muddle along in a torturous occupation with creeping dispossession, or 3) to grant Palestine some kind of autonomy and statehood. Assimilation, (4), long dreamt of by some, seems impossible for a state that is fundamentally an ethnic (or theological) state, and whose whole raison d'etre is ethnic separation, not to even mention the preferences of the Palestinians. Though perhaps assimiliation without voting rights, in sort of semi-slavery or apartheid, is something the Israelies would be attracted to? Perhaps insignia will need to be worn by all Palestinians, sewn to their clothing?

Map of the West Bank of the Jordan, color coded by Palestinian marginal control in brown, and settler/Israeli control in red.

What should happen? Indigenous Americans were infected, decimated, hunted down, translocated, re-educated, and confined to a small and very remote system of reservations. Hopefully we have have progressed a little since then, as a largely European civilization, which is putatively shared by Israel. Thus the only way forward, as is recognized by everyone outside Israel, is the two-state solution, including a re-organization of the Palestinian territories into a final, clearly demarked, and contiguous state. Israel's current political system will never get there. But we can help the process along in a few ways.

First, it is disappointing to see our current administration shipping arms to Israel at a furious pace, only to see them used to kill thousands of innocent, if highly resentful, civilians. Israel has plenty of its own money to buy whatever it needs elsewhere. We need to put some limitations on our military and other aid relationships, to motivate change. (Though that raises the question of Israel's increasingly cozy relationship with Russia). Second, we should recognize Palestine as a state, and bring forward its integration into the international system. This will not resolve its borders or myriad security and territory issues viz Israel, but it would helpfully motivate things in that direction. Israel has constantly cried wolf about the lack of a credible partner to negotiate with, but that is irrelevant. Israel is perfectly capable of building the walls it needs to keep Palestinians at bay. But then it wants pliant workers as well, and a peaceful neighbor, security viz Jordan and Egypt, territorial encroachments, and many other things that are either destructive, or need to be negotiated. 

By far the most constructive thing that could be done is to freeze and re-organize the Jewish settlements and other periphernalia that have metastasized all over the West Bank. There is no future without a decent and fair solution in territory, which is the third big thing we need to press- our own detailed territorial plan for Palestine. For one thing, Israel could easily vacate the whole corridor / valley facing Jordan. That would give a consolidated Palestine a working border with a country that is now peaceful, quite well run, and friendly to both sides. There are countless possible maps. We just need to decide on one that is reasonably fair and force it on both sides, which are each, still after all these years, apparently unwilling to imagine a true peace. This means principally forcing it on Israel, which has been the dominant and recalcitrant party the entire time.

The Cherokees are now one of the largest indigenous populations in the US, at roughly a quarter million, with their own territory of about seven thousand square miles in Oklahoma. They have internal and partial sovereignty, which means that they deal with their own affairs on a somewhat independent basis, but otherwise are largely subject to most laws of the enclosing governments. The Cherokees could easily have been assimilated into the US. Only racism stood in the way, in a mindset that had long descended into a blind and adversarial disregard of all native Americans as "others", (the irony!), competitive with and less than, the newly arrived immigrants. We could have done much better, and one would like to think that, a hundred or a hundred and fifty years on, we would have.

In the end, the West (read as European civilization, as developed out of the ashes of World War 2) is either for or against wars of aggression, ethnic cleansing, apartheid, and human rights. Israel has won its wars, but never faced up to its responsibilities to the conquered Palestinians, and has tried to have it both ways, to be viewed by the world as a modern, enlightened state, even as it occupies and slowly strangles the people it defeated decades ago. 

• Slovenly strategic thinking. But really, visionless long-term politics.
• One Gazan speaks.
• Settler colonialism.
• Who's the victim?
• Shades of Scientology ... the murky networks of the deep evangelical state.
• In California, solar still makes sense.

Some Challenges of Biological Modeling

If modeling one small aspect of one cell is this difficult, how much more difficult is it to model whole cells and organisms?

While the biological literature is full of data / knowledge about how cells and organisms work, we remain far from true understanding- the kind of understanding that would allow computer modeling of their processes. This is both a problem of the kind of data, which is largely qualitative and descriptive, and also of amount- that countless processes and enzymes have never had their detailed characteristics evaluated. In the human genome, I would estimate that roughly half its genes have only been described (if at all) in the most rudimentary way, typically by loose analogy to similar ones. And the rest, when studied more closely, present all sorts of other interesting issues that deflect researchers from core data like their enzymatic rate constants and binding constants to other proteins, as might occur under a plethora of different modification, expression, and other regulatory conditions. 

Then how do we get to usable models of cellular activities? Typically, a lot of guessing is involved, to make anything that approaches a computer model. A recent paper offered a novel way to go down this path, which was to ignore all the rate constants and even interactions, and just focus on the measurements we can make more conveniently- whole metabolome assessments. These are experiments where mass spectrometry is used to evaluate the level of all the smaller chemicals in a cell. If such levels are known, perhaps at a few different conditions, then, these authors argue, we can derive models of their mutual regulation- disregarding all the details and just establishing that some sort of feedback system among these metabolic chemicals must exist to keep them at the observed concentrations.

Their experimental subject is a relatively understandable, but by no means simple, system- the management of iron concentrations in yeast cells. Iron is quite toxic, so keeping it at controlled concentrations and in various carefully-constructed complexes is important for any cell. It is used to make heme, which functions not only in hemoglobin, but in several core respiratory enzymes of mitochondria. It also gets placed into iron-sulfur clusters, which are used even more widely, in respiratory enzymes, in the DNA replication, transcription, protein synthesis, and iron assimilation machineries. It is iron's strong and flexible redox chemistry (and its ancient abundance in the rocks and fluids life evolved with) that make it essential as well as dangerous.

Author's model for iron use and regulation in yeast cells. Outside is on left, cytoplasm is blue, vacuole is green, and mitochondrion is yellow. See text below for abbreviations and description. O2 stands for the oxygen  molecule. The various rate constants R refer to the transition between each state or location.

Iron is imported from outside and forms a pool of free iron in the cytoplasm (FC, in the diagram above). From there, it can be stored into membrane-bound vacuoles (F2, F3), or imported to the mitochondria (FM), where it is corporated into iron-sulfur clusters and heme (FS). Some of the mitochondrially assembled iron-sulfur clusters are exported back out to the cytoplasm to be integrated to a variety of proteins there (CIA). This is indeed one of the most essential roles of mitochondria- needed even if metabolic respiration is for some reason not needed (in hypoxic or anaerobic conditions). If there is a dramatic overload of iron, it can build up as rust particles in the mitochondria (MP). And finally, the iron-sulfur complexes contribute to respiration of oxygen in mitochondria, and thus influence the respiration rate of the whole cell.

The task these authors set themselves was to derive a regulatory scheme using only the elements shown above, in combination with known levels of all the metabolites, under the conditions of 1) normal levels of iron, 2) low iron, and 3) a mutant condition- a defect in the yeast gene YFG1, which binds iron inside mitochondria and participates in iron-sulfur cluster assembly. A slew of differential equations later, and selection through millions of possible regulatory circuits, and they come up with the one shown above, where the red lines/arrows indicate positive regulation, and the red lines ending with bars indicate repression. The latter is typically feedback repression, such as of the import of iron, repressed by the amount already in the cell, in the FC pool. 

They show that this model provides accurate control of iron levels at all the various points, with stable behavior, no singularities or wobbling, and the expected responses to the various conditions. In low iron, the vacuole is emptied of iron, and in the mutant case, iron nanoparticles (MP) accumulate in the mitochondrion, due in part to excess amounts of oxygen admitted to the mitochondrial matrix, which in turn is due to defects in metabolic respiration caused by a lack of iron-sulfur clusters. What seemed so simple at the outset does have quite a few wrinkles!

The authors present their best regulatory scheme, selected from among millions, which provides accurate metabolite control in simulation, as shown by key transitions between conditions as shown here, one line per molecular species. See text and image above for abbreviations.

But note that none of this is actually biological. There are no transcription regulators, such as the AFT1/2 proteins known to regulate a large set of iron assimilation genes. There are no enzymes explicitly cited, and no other regulatory mechanisms like protein modifications, protein disposal, etc. Nor does the cytosolic level of iron actually regulate the import machinery- that is done by the level of iron-sulfur clusters in the mitochondria, as sensed by the AFT regulators, among other mechanisms.

Thus it is not all clear what work like this has to offer. It takes the known concentrations of metabolites (which can be ascertained in bulk) to create a toy system that accurately reproduces a very restricted set of variations, limited to what the researchers could assess elsewhere, in lab experiments. It does not inform the biology of what is going on, since it is not based on the biology, and clearly even contravenes it. It does not inform diseases associated with iron metabolism- in this case Friedreich's ataxia which is caused in humans by a gene related to YFH1- because again it is not biologically based. Knowing where some regulatory events might occur in theory, as one could have done almost as well (if not quantitatively!) on a cocktail napkin, is of little help when drugs need to be made against actual enzymes and actual regulators. It is a classic case of looking under the streetlight- working with the data one has, rather than the data one needs to do something useful.

"Like most ODE (ordinary differential equation)-based biochemical models, sufficient kinetic information was unavailable to solve the system rigorously and uniquely, whereas substantial concentration data were available. Relying on concentrations of cellular components increasingly makes sense because such quantitative concentration determinations are becoming increasingly available due to mass-spectrometry-based proteomic and metabolomics studies. In contrast, determining kinetic parameters experimentally for individual biochemical reactions remain an arduous task." ...

"The actual biochemical mechanisms by which gene expression levels are controlled were either too complicated to be employed in autoregulation, or they were unknown. Thus, we decided to augment every regulatable reaction using soft Heaviside functions as surrogate regulatory systems." ...

"We caution that applying the same strategy for selecting viable autoregulatory mechanisms will become increasing difficult computationally as the complexity of models increases."

But the larger point that motivated a review of this paper is the challenge of modeling a system so small as to be almost infinitesimal in the larger scheme of biology. If dedicated modelers, as this laboratory is, dispair of getting the data they need for even such a modest system, (indeed, the mitochondrial iron and sulfur-containing signaling compound that mediates repression of the AFT regulators is still referred to in the literature as "X-S"), then things are bleak indeed for the prospect of modeling higher levels of biology, such as whole cells. Unknowns are unfortunately gaping all over the place. As has been mentioned a few times, molecular biologists tend to think in cartoons, simplifying the relations they deal with to the bare minimum. Getting beyond that is going to take another few quantum leaps in data- the vaunted "omics" revolutions. It will also take better interpolation methods (dare one invoke AI?) that use all the available scraps of biology, not just mathematics, in a Bayesian ratchet that provides iteratively better models. 

• Some technical advances in 2023.
• Stuttering is a problem, but it isn't a sign.
• How religions break down in political orientation.
• Goodbye 2023: Death Lemonade.

How Does Speciation Happen?

Niles Eldredge and the theory of punctuated equilibrium in evolution.

I have been enjoying "Eternal Ephemera", which is an end-of-career memoir/intellectual history from a leading theorist in paleontology and evolution, Niles Eldredge. In this genre, often of epic proportions and scope, the author takes stock of the historical setting of his or her work and tries to put it into the larger context of general intellectual progress, (yes, as pontifically as possible!), with maybe some gestures towards future developments. I wish more researchers would write such personal and deeply researched accounts, of which this one is a classic. It is a book that deserves to be in print and more widely read.

Eldredge's claim to fame is punctuated equilibrium, the theory (or, perhaps better, observation) that evolution occurs much more haltingly than in the majestic gradual progression that Darwin presented in "Origin of Species". This is an observation that comes straight out of the fossil record. And perhaps the major point of the book is that the earliest biologists, even before Darwin, but also including Darwin, knew about this aspect of the fossil record, and were thus led to concepts like catastrophism and "etagen". Only Lamarck had a steadfastly gradualist view of biological change, which Darwin eventually took up, while replacing Lamarck's mechanism of intentional/habitual change with that of natural selection. Eldridge unearths tantalizing and, to him, supremely frustrating, evidence that Darwin was fully aware of the static nature of most fossil series, and even recognized the probable mechanism behind it (speciation in remote, peripheral areas), only to discard it for what must have seemed a clearer, more sweeping theory. But along the way, the actual mechanism of speciation got somewhat lost on the shuffle.

Punctuated equilibrium observes that most species recognized in the fossil record do not gradually turn into their descendents, but are replaced by them. Eldredge's subject of choice is trilobites, which have a long and storied record for almost 300 million years, featuring replacement after replacement, with species averaging a few million years duration each. It is a simple fact, but one that is a bit hard to square with the traditional / Darwinian and even molecular account of evolution. DNA is supposed to act like a "clock", with constant mutational change through time. And natural selection likewise acts everywhere and always... so why the stasis exhibited by species, and why the apparently rapid evolution in between replacements? That is the conundrum of punctuated equilibrium.

There have been lot of trilobites. This comes from a paper about their origin during the Cambrian explosion, arguing that only about 20 million years was enough for their initial speciation (bottom of image).

The equilibrium part, also termed stasis, is seen in the current / recent world as well as in the fossil record. We see species such as horses, bison, and lions that are identical to those drawn in cave paintings. We see fossils of animals like wildebeest that are identical to those living, going back millions of years. And we see unusual species in recent fossils, like saber-toothed cats, that have gone extinct. We do not typically see animals that have transformed over recent geological history from one (morphological) species into another, or really, into anything very different at all. A million years ago, wildebeest seem to have split off a related species, the black wildebeest, and that is about it.

But this stasis is only apparent. Beneath the surface, mutations are constantly happening and piling up in the genome, and selection is relentlessly working to ... do something. But what? This is where the equilibrium part comes in, positing that wide-spread, successful species are so hemmed in by the diversity of ecologies they participate in that they occupy a very narrow adaptive peak, which selection works to keep the species on, resulting in apparent stasis. It is a very dynamic equilibrium. The constant gene flow among all parts of the population that keeps the species marching forward as one gene pool, despite the ecological variability, makes it impossible to adapt to new conditions that do not affect the whole range. Thus, paradoxically, the more successful the species, and the more prominent it is in the fossil record, the less change will be apparent in those fossils over time.

The punctuated part is that these static species in the fossil record eventually disappear and are replaced by other species that are typically similar, but not the same, and do not segue from the original in a gradual way that is visible in the fossil record. No, most species and locations show sudden replacement. How can this be so if evolution by natural selection is true? As above, wide-spread species are limited in what selection can do. Isolated populations, however, are more free to adapt to local conditions. And if one of those local conditions (such as arctic cold) happens to be what later happens to the whole range (such as an ice age), then it is more likely that a peripherally (pre-)adapted population will take over the whole range, than that the resident species adapts with sufficient speed to the new conditions. Range expansion, for the peripheral species, is easier and faster than adaptation, for the wide-ranging originating species.

The punctuated equilibrium proposition came out in the 1970's, and naturally followed theories of speciation by geographic separation that had previously come out (also resurrected from earlier ideas) in the 1930's to 1950's, but which had not made much impression (!) on paleontologists. Paleontologists are always grappling with the difficulties of the record, which is partial, and does not preserve a lot of what we would like to know, like behavior, ecological relationships, and mutational history. But they did come to agree that species stasis is a real thing, not just, as Darwin claimed, an artifact of the incomplete fossil record. Granted- if we had fossils of all the isolated and peripheral locations, which is where speciation would be taking place by this theory, we would see the gradual change and adaptation taking place. So there are gaps in the fossil record, in a way. But as long as we look at the dominant populations, we will rarely see speciation taking place before our eyes, in the fossils.

So what does a molecular biologist have to say about all this? As Darwin insisted early in "Origin", we can learn quite a bit from domesticated animals. It turns out that wild species have a great amount of mostly hidden genetic variation. This is apparent whenever one is domesticated and bred for desired traits. We have bred dogs, for example, to an astonishingly wide variety of traits. At the same time, we have bred them out to very low genetic diversity. Many breeds are saddled with genetic defects that can not be resolved without outbreeding. So we have in essence exchanged the vast hidden genetic diversity of a wild species for great visible diversity in the domesticated species, combined with low genetic diversity.

What this suggests is that wild species have great reservoirs of possible traits that can be selected for the purposes of adaptation under selective conditions. Which suggests that speciation in range edges and isolated environments can be very fast, as the punctuated part of punctuated equilibrium posits. And again, it reinforces the idea that during equilibrium with large populations and ranges, species have plenty of genetic resources to adapt and change, but spend those resources reinforcing / fine tuning their core ecological "franchise", as it were.

In population genetics, it is well known that mutations arise and fix (that is, spread to 100% of the population on both alleles) at the same rate no matter how large the population, in theory. That is to say- bigger populations generate more mutations, but correspondingly hide them better in recessive form (if deleterious) and for neutral mutations, take much longer to allow any individual mutation to drift to either extinction or fixation. Selection against deleterious mutations is more relentless in larger populations, while relaxed selection and higher drift can allow smaller populations to explore wider ranges of adaptive space, perhaps finding globally higher (fitness) peaks than the parent species could find.

Eldredge cites some molecular work that claims that at least twenty percent of sequence change in animal lineages is due specifically to punctuational events of speciation, and not to the gradual background accumulation of mutations. What could explain this? The actual mutation rate is not at issue, (though see here), but the numbers of mutations retained, perhaps due to relaxed purifying selection in small populations, and founder effects and positive selection during the speciation process. This kind of phenomenon also helps to explain why the DNA "clock" mentioned above is not at all regular, but quite variable, making an uneven guide to dating the past.

Humans are another good example. Our species is notoriously low in genetic diversity, compared to most wild species, including chimpanzees. It is evident that our extremely low population numbers (over prehistoric time) have facilitated speciation, (that is, the fixation of variants which might be swamped in bigger populations), which has resulted in a bewildering branching pattern of different hominid forms over the last few million years. That makes fossils hard to find, and speciation hard to pinpoint. But now that we have taken over the planet with a huge population, our bones will be found everywhere, and they will be largely static for the foreseeable future, as a successful, wide-spread species (barring engineered changes). 

I think this all adds up to a reasonably coherent theory that reconciles the rest of biology with the fossil record. However, it remains frustratingly abstract, given the nature of fossils that rarely yield up the branching events whose rich results they record.

• TV in China.
• How now at the Supreme Court?
• Tears are powerful.