On gene duplication and oppression, a reprise.

On gene duplication and oppression, a reprise.

Evolution depends upon the unnecessary.

Evolution is a process in which those organisms best suited to their environments – either because they persist longer than others or produce more progeny – become more abundant.  For a lineage to become better suited to an environment over time, the organisms have to change in a heritable way.

DNA polymerases aren’t perfect.  Whenever enzymes copy our genetic material, they make mistakes.  To be honest, these mistakes are rarely beneficial.  Sometimes they cause other enzymes to stop working.  Sometimes they turn a cell into cancer.  But that same imperfection – which changes genetic information from one generation to the next – gives rise to evolution.

The evolution of a particular species of bacteria has been carefully documented in biologist Richard Lenski’s laboratory.  These were allowed to compete inside a precisely-controlled environment over hundreds of thousands of generations, and some of the bacteria were frozen after every few hundred generations to keep track of all the genetic changes.

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Zachary Blount and Richard Lenski horsing around with some of the Petri dishes from Blount’s work on the evolution of citrate utilization in one . Image from Wikimedia.

In this experiment, a single subpopulation gained the ability to metabolize a new nutrient, which gave it a huge competitive advantage and allowed it to conquer its tiny world.  But how?  After all, most of a bacteria’s genes are already important for something, and, when mutations occur, the most common outcome is for functions to be lost.  If you give a radio and a screwdriver to a toddler, you probably shouldn’t expect crisper reception come evening.  Chances are that your radio won’t work at all.

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Gene duplication, as depicted by the National Human Genome Research Institute on Wikimedia Commons.

As it happens, a very rare event happened before this bacterial subpopulation “learned” to use the new energy source.  When the experiment was re-started with various frozen samples, most lineages never acquired this ability.  But in one set, there had been a “gene duplication event.”  During cell division, the enzyme that copies DNA had stuttered and accidentally included two copies of a gene that bacteria only need one copy of.  And these bacteria, recipients of that unnecessary second copy, would almost always gain the new metabolic function and swamp out the others.

Once there were two copies of the gene, the second copy was free to change.  A mutation in that copy wouldn’t cause the bacteria to grow weak or die, because they still had a fully-functional copy of the enzyme.  And eventually, through the rare happenstance of random error, bacteria would accumulate enough mutations in that second copy that it gained a new function.

In the beginning, this new function was pretty weak.  But once there was a faint glimmer, natural selection could refine it.  Without an unnecessary second copy of that gene, though, the bacteria never would’ve gained the new metabolic pathway.

You can look at human culture in a similar way.  Which isn’t to say that one culture is intrinsically better than another, and certainly doesn’t imply that we’re progressing toward some teleological goal.  Evolution is just a matter of statistics, after all.  The things that are, now, were probably descended from things that were good at being and producing.

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An image from a 1902 engineering textbook from Wikimedia Commons.

For instance, cars make human life easier.  And so the traits that allow a culture to have cars, like a basic understanding of mathematics and a willingness to follow rules on roadways, seem to spread pretty easily.  Car cultures have swamped out non-car cultures all over the planet.  Walking is pretty great, and so are bikes, but any culture that has access to mechanical engineering textbooks seems to have a pretty huge advantage over those that don’t.

But if you’d dropped a mechanical engineering textbook into the lap of a Paleolithic hunter-gatherer, it’d seem pretty useless.

It took a lot of waste to reach a state when the textbook could matter.  Over many generations, there was excess and dead weight.  Many centuries of an oppressor class stealing from the mouths of the poor, really.

Somebody who is struggling every day to procure food doesn’t have the luxury to fiddle with mathematics.  That’s why so many of the early European scientists were members of the aristocracy.  They didn’t need to work to eat because they had serfs to steal food from, levying taxes for the use of land that was “theirs” because their ancestors had done a bang-up job of murdering other people’s ancestors.

In the generations after humans developed agriculture, the average quality of life plummeted.  If you were told to pick any year and your soul would be suddenly re-incarnated (pre-incarnated?) into a randomly-chosen Homo sapiens alive at that time, you’d probably be happier 20,000 years ago than at most times during the last few millennia.  20,000 years ago, nobody lived terribly well – there was scant medicine and a constant risk of famine – but the suffering and servitude experienced by the majority of humans later on was worse.

After farming, people worked harder, for more hours a day, to produce a less varied, less healthful diet than the hunter-gatherers had eaten.  They had even less access to medicine, and still endured the constant risk of famine.  Oh, and envy.  Because farmers, who had to live in place, could be conquered.

640px-Maler_der_Grabkammer_des_Sennudem_001Those conquered farmers could be taxed, charged rent, etc., with the proceeds used to feed an idle class.  Most of the idlers produced nothing of value.  They ate others’ food and lived in un-earned luxury (although their “luxury” would seem pretty shabby to us).  But a few of them – a very few – produced the cultural innovations (like mathematics, medicine, poetry, astronomy) that gave us the modern world.

It feels more than a little disconcerting that a gruesome history of violence and oppression allows me to type this essay on a laptop computer.

In the past, though, oppression was the only way for our world to have “excess” people, those who could be free to devote their time and energy toward changing things.  Now, however, food production (and many other things) has been heavily automated.  We could have a much larger excess population, which could increase the rate of cultural evolution.  A luxurious lifestyle could be had by all using the essential (food- and shelter-producing) efforts of a smaller number of people than ever before.

With a guaranteed basic income – which could be funded by taxing wealth at a very low rate, maybe a percent or two – nearly all people could effectively become aristocracy.  People could follow their passions and curiosities.  Most, as ever, wouldn’t change the world. That’s how evolution works.  Chaotic tinkering with things that are pretty good rarely improves things.  But with billions of tinkerers, the odds that something works out are better.

It’s easily within reach.  Instead we’ve stuck with the same system of celebrating historical violence that was used to oppress people before.  Maybe it was necessary, all that cruelty, to get from our past to here.  But it certainly isn’t needed now.

Featured image: DNA duplication diagram by Madeline Price Ball on Wikipedia.

On naked mole-rats.

On naked mole-rats.

When Radiohead first toured, their audiences just wanted to hear “Creep.”  They were invited to play a show in Israel – everyone just wanted to hear “Creep.”  They were invited to tour America – everyone just wanted to hear “Creep.”  At festivals, people walked away after they played it.  By then the song was several years old.  The dudes in Radiohead were sick of it.

To be fair, Pablo Honey was a pretty weak album.  “You” is a fine song, but the proffered singles – “Anyone Can Play Guitar” (more ironic in retrospect than it was at the time) and “Stop Whispering” – aren’t very compelling.  At the time, nobody knew their new material.

Now, of course, Radiohead is many people’s favorite band – mine too (tied with The Marshall Cloud and anything else my brother makes).

The essayist Eliot Weinberger has also toured on the strength of a hit single.  From Christopher Byrd’s 2016 profile in The New Yorker:

EliotWeinbergerBW350In person, Weinberger is genial and self-contained; he smiles frequently and is prone to wisecracks.  When I asked him about the essay [“Naked Mole-Rats,” from his 2001 collection, Karmic Traces], he said “In Germany, I’m sort of like one of those bands that had one hit record, and so I give readings and people ask me to read ‘Nacktmull,’ which is the naked mole-rat.  It’s their favorite one.  This pretty girl said, ‘Last night, I was in bed reading it to my boyfriend.’  And I said, ‘Don’t you have anything better to read?’”

Yet, like Radiohead, Weinberger has released new work every few years – he seems to have been writing constantly ever since he dropped out of college circa 1970 and began translating the poetry of Octavio Paz – and much of it is better than the hit everybody knows.  Over the past two months, I’ve had the pleasure of reading all his books – many are stunning.  The Ghosts of Birds discuses Adam & Eve, the dreams of ancient Chinese poets, and the authorial voice of George W. Bush’s “autobiography.”  I’ve written previously about What Happened Here, a collection of Weinberger’s essays about the Bush years.  And Weinberger has written extensively about the political value of poetry.  From “The T’ang” (in Oranges and Peanuts for Sale):

…[I]n the last years of the dynasty, warlords ravished the country.  One of them, Huang Ch’ao, a salt merchant who had failed the civil service exams, captured Ch’ang-an in 881.  A satiric poem was posted on the wall of a government building, criticizing the new regime.  (As, eleven hundred years later, the Democracy Movement would begin with the poems that Bei Dao and other young poets glued to the walls in their capital, Beijing.)  Huang Ch’ao issued orders that everyone capable of writing such a poem be put to death.  Three thousand were killed.

When dudes ask what we’re doing teaching a poetry class in jail, it’s great to have stories like this to relate … or to toss out a quote from Norman Dubie, my co-teacher’s advisor, who says, “If Stalin feared poetry, so should you.

And yet, I have to admit: Weinberger’s “Naked Mole-Rats” really is a lovely essay.

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During the 1970s, evolutionary biologist Richard Alexander gave a series of lectures describing conditions that might spawn eusocial vertebrates.  Alexander was a bug guy – the term “eusocial” refers to bees, ants, and termites, where individuals are extremely self-sacrificing for the good of the colony, including an abundance of non-breeding members helping with childcare.

Alexander proposed that a eusocial species of mammal could evolve if they lived in relatively safe underground burrows that could be expanded easily and defended by a small percentage of the colony.  The animals would need to be small compared to their food sources, so that a stroke of good luck by one worker could feed many.

thebioofnakedAn audience member at one of Alexander’s lectures mentioned that this “hypothetical eusocial mammal” sounded a lot like the naked mole-rat and connected Alexander with Jennifer Jarvis, who’d studied the biology of these critters but hadn’t yet investigated their their social structure.  The collaboration between Alexander and Jarvis led to the textbook The Biology of the Naked Mole-Rat.

Eliot Weinberger combed through this 500-plus page textbook to produce his 3-page essay.  In Weinberger’s words:

As many as three hundred inhabit a colony, moving a ton of dirt every month.  They have a caste system

The medium sized are the warriors, who try to fend off the rufous-beaked snaked, the file snakes, the white-lipped snakes, and the sand boas that sometimes find their way in.When, by chance, two colonies of naked mole-rats tunnel into each other, their warriors fight to the death.

Interbred for so long, they are virtually clones.  One dead-end branch of the tunnel is their toilet: they wallow there in the soaked earth so that all will smell alike.  They are nearly always touching each other, rubbing noses, pawing, nuzzling.

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Like us, naked mole-rats are both good and bad.  They are cooperative.  They are affectionate.  They are always touching.  Encountering outsiders, they fight to the death.  When a breeding female dies, many other females regain fertility and the colony erupts into civil war.

Naked mole-rats care for others.  Naked mole-rats are callous toward others.

[The breeding female, of which each colony has only one] has four or five litters a year of a dozen pups.  The babies have transparent skin through which their internal organs are clearly visible.  Only a few survive, and they live long lives, twenty years or more.  The dead babies are eaten, except for their heads.  At times the live ones are eaten too.

These details are drawn from innumerable experimental observations.  We humans have spent decades investigating the naked mole-rats.  But Weinberger ends his essay with the reverse.  Naked mole-rats observe us, too:

Sometimes a naked mole-rat will suddenly stop, stand on its hind-legs, and remain motionless, its head pressed against the roof of the tunnel.  Above its head is the civil war in Somalia.  Their hearing is acute.

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Naked mole-rats “are continually cruel in small ways.”  But they are outdone by naked apes.  After all, the cruelty of naked mole-rats is invariably directed to others of their own kind.  Our cruelty embraces ourselves as well as them.

For a research paper published in 2008, Park et al. discovered that being pinched by tweezers causes naked mole-rats pain, but the injection of caustic acid does not:

We tested naked mole-rats in standard behavioral models of acute pain including tests for mechanical (pinch), thermal, and chemical pain.  We found that for noxious pinch and heat, the mole-rats responded similarly to mice.

In contrast to the results using mechanical and thermal stimuli, there was a striking difference in responses to strong chemical irritants known to excite nociceptors [these are sensory receptors that detect noxious inputs, like pain].  Indeed, the two chemicals used – capsaicin and low-pH saline solution – normally evoke very intense pain in humans and other animals.  Injection of either irritant into the skin rapidly evoked intense licking and guarding behaviors in mice.

(In case you’re worried that acid-resistant naked mole-rats might conquer the world: a form of kryptonite exists.  Injection of an 11-amino-acid signaling peptide allows acid to hurt naked mole-rats just as much as it hurts mice.  Half a dozen animals were subjected to each treatment.)

So, naked mole-rats are selectively resistant to pain.  This has inspired some envy in human researchers – after all, chronic pain is miserable, and most of our strategies to dampen pain have a few unwanted side-effects.

But what really gets us humans jealous is that naked mole-rats seem not to age.

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Naked mole-rats almost never develop cancer.  They should get cancer.  After all, their cells, like ours, copy themselves.  Over time, each copy is a copy of a copy of a copy… any errors are compounded.  And some errors are particularly deadly.  Our cells are supposed to stop growing when they touch each other, and they are supposed to commit suicide when their usefulness has run its course.  But the instructions telling our cells when and how to kill themselves can be lost, just like any other information.  Too many rounds of cell division is like making photocopies of photocopies… eventually the letters melt into static and become unreadable.

So I don’t quite understand why naked mole-rats don’t get cancer … but, in my defense, no one else does either.  Tian et al. found that naked mole-rats fill the space between their cells with a particular sugar that acts as an anti-clumping agent.  This contributes to their cancer resistance, because cells that can’t clump can’t form tumors… but, although many types of deadly human cancers form tumors, others, like leukemia, do not.

Lung_cancer_cell_during_cell_division-NIH.jpgOf course, “cancer” cells – mutant versions of ourselves that would kill us if they could – appear all the time.  Usually, our immune system destroys them.  Most chemotherapy agents do not kill cancer.  Chemotherapy involves pumping the body full of general poisons that stop all cells from reproducing, with the hope being that, if the spread of cancer can be slowed, a patient’s immune system will sop up the bad cells already there.

In addition to anti-clumping sugars, naked mole-rats must have other (currently unknown) virtues that enable their remarkable tenacity.

And, although the little critters seem not to age – they have “no age-related increase in mortality” and remain fertile until death – they do die.  The oldest naked mole-rat lived for 27 years in captivity, and seems to have been at least a year old when first captured, based on his size.

He was rutting and eating normally until April, 2002… but then, seemingly without cause, he died.  Writing for Scientific American shortly after this duder’s death, David Stipp described him (and naked mole-rats in general) as “a little buck-toothed burrower [who] ages like a demigod.”

But it’s worth noting that he had aged.  He had accumulated extensive oxidative damage in his lipids, proteins, and, presumably, his DNA… which is to say, his cells were noticeably rusted and falling apart.  He just didn’t let it slow him down.  Not until he keeled over.

They live with gusto, the naked mole-rats.

For as long as they energy, that is.  Several researchers have proposed that naked mole-rats have all these powers because they starve often in the wild.

Caloric restriction – which means, roughly, intentional starvation – is known to extend lifespan in a wide variety of species.  It’s been tested in monkeys, mice, flies, and worms.  Between two- and ten-fold increases in lifespan have been observed.  There are some unpleasant side effects.  Hunger, for instance.  Caloric-restricted mice spend a lot of time staring at their empty food bowls.

Many humans who attempt caloric restriction on their own find it difficult.  Hunger hurts, especially when there’s food nearby.  Plus, it’s a rare diet that provides adequate nutrition while still limiting calories.  Malnutrition makes people die younger, which defeats the point… unless your goal is simply to make God uncomfortable.  Maybe you’ll get a wish!

But naked mole-rats have no choice.  Workers tunnel outward, searching for tuberous roots.  When they find one, they’ll gnaw it carefully, attempting to keep the plant alive as long as possible, but the colony invariably consumes roots faster than a plant can grow.  Although naked mole-rats try to be good stewards of their environment – they are compulsive recyclers, eating their own excrement to make sure no nutrients are lost – their colonies plunge repeatedly into famine.

And they sleep in mounds, hundreds of bodies respiring underground.  Anyone sleeping near the center probably runs out of oxygen.

But they survive.

We would not.  Most mammals, deprived of oxygen, can no longer fuel their brains.  Our brains are expensive.  Even at rest our brains demand a constant influx of energy or else the neurons “depolarize” – we fall apart.  This is apparently an unpleasant experience.  It’s brief, though.  At Stanford, my desk was adjacent to a well-trafficked gas chamber.  A mouse, or a Chinese-food takeout container with several mice, was dropped in; a valve for carbon dioxide was opened; within seconds, the mice inside lost consciousness; they shat; they died.

A naked mole-rat would live.  Unless a very determined researcher left the carbon dioxide flowing for half an hour.  Or so found Park et al. – a graph from their recent Science paper is shown below.  Somewhere between three and twelve animals were used for every time point; all the mice would’ve been dead within a minute, but perhaps as few as three naked mole-rats died in this experiment.

survival curves

Human brains are like hummingbirds – our brains drink up sugar and give us nothing but a fleeting bit of beauty in return.  And our brains are very persnickety in their taste for sugar.  We are fueled exclusively by glucose.

Naked mole-rats are less fussy than we are – their minds will slurp fructose to keep from dying.

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Naked mole-rats: the most cooperative of all mammals.  Resistant to cancer.  Unperturbed by acid.  Aging with the libidinous gracelessness of Hugh Hefner.  Able to withstand the horrors of a gas chamber.

And yet, for all those superpowers, quite easily tormented by human researchers.