On scrutiny.

On scrutiny.

We can be attentive to only a small sliver of the world.

We’re constantly surrounded by so much noise, so many smells, so many different colors, textures, tastes.  The amount of sensory information that we’re bombarded with every moment would be overwhelming if we weren’t so good at ignoring our environment.

Consider smells.  Chemicals waft through the air, bind to olfactory receptors in our nose, and cause a signal to ping our brain: there’s the floral scent of an ethyl acetate here …  But, if we stay near the source of that chemical, our brain will keep receiving that signal.  Thankfully, this information is discarded by our subconscious minds.  As long as the types of smells in a space aren’t changing, we soon notice nothing.

If our clothes feel the same against our skin from one moment to the next, all the tactile information being sent from the surface of our body is similarly ignored.  But the information is still there.  If we focus your attention on your shirt, you can feel it.

The-Pearl-294878In The Pearl, John Steinbeck reveals how this glut of information can cause us to be hoodwinked.  A poor diver becomes suddenly wealthy when he finds a giant pearl.  The diver’s infant child was stung by a scorpion and has begun to recover … but a greedy doctor would rather the child receive an expensive cure.  The doctor knows that he can fool the diver by drawing his attention to details that never seemed important before.

It is as I thought,” [the doctor] said.  “The poison has gone inward and it will strike soon.  Come look!”  He held the eyelid down.  “See – it is blue.”  And Kino, [the diver], looking anxiously, saw that indeed it was a little blue.  And he didn’t know whether or not it was always a little blue.  But the trap was set.  He couldn’t take the chance.

If we scrutinize the world, we can always find something that looks strange.

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When I was in high school, I had to get a medical physical each year.  Those cost $5 – a school nurse would measure my blood pressure, listen to my heart, and look at the curvature of my spine.  I felt healthy enough when I signed up for these physicals, and the nurses invariably agreed.  Even repeatedly-concussed football and soccer players were given a clean bill of health.

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This $5 exam was insufficient to find anything wrong with us.  But if we’d been subjected to a $25,000 battery of diagnostic scrutiny instead, I’m sure we’d have seemed flawed.

Indeed, in a recently-published study designed to shill the new $25,000 physical from a company called “Health Nucleus” in California – which includes DNA sequencing, metabolite analysis, full-body MRI, two weeks of heart monitoring, and more – 40% of their seemingly-healthy study participants were diagnosed with “something seriously wrong.”  In several study participants, doctors found clusters of aberrant cells: pre-cancer.

In sexually-reproducing multicellular organisms, most cells carry DNA instructions to sacrifice themselves for the sake of the whole.  Some of these instructions code for contact inhibition, which means that cells stop growing when their edges bump into neighbors.  Other DNA sequences code for apoptosis, which means that cells commit suicide once they’re no longer needed.

But the mechanism for transmitting these instructions is imperfect.  DNA is copied again and again by jiggling protein machines called polymerases, and these make about 60 mistakes each time they copy our genomes.  Worse, DNA is copied from copies, so the mistakes pile up over time.  Like classroom handouts that have been photocopied from photocopies so many times that the words blur into static, DNA sequences that instruct our cells to cooperate can become unreadable.  At which point a cell is cancerous.

4.0.4Cancer cells continue growing without regard for the neighbors they’re crowding.  They carry on dividing – spewing forth copies of themselves – long after a team-player would’ve snuffed itself.

Most human adults harbor cancer cells.  All the time, they lurk in us.  And our immune systems destroy them.  Chemotherapy drugs do not kill cancerous cells – they slow the growth of all cells, giving a patient’s own immune system time to fight the menace.

So it’s unsurprising that doctors found pre-cancer in some of the study participants who underwent this $25,000 physical.  Study participants were as old as 98.  Their average age was 55.  After so much time alive, of course some of their cells had gone bad.

Early detection of cancer does boost a patient’s chance of survival, but sometimes in a trivial way.  Healthy patients whose immune systems would have destroyed a population of aberrant cells without any intervention … who might never have realized that anything was ever wrong … are counted as “cancer survivors.”  Extremely sensitive diagnosis can identify cancers early enough to be cured, but has the drawback of mis-labeling healthy people as diseased.

Every diagnosis of disease leads to harm – from worry, from the risks inherent in all medical treatment – and so has to be balanced against the expected outcome from doing nothing.  With some conditions, doing nothing would be deadly.  But by scrutinizing healthy people, you can always find something that looks strange.  Of course you’ll find “evidence of age-related chronic disease or risk factors” when you subject older people to a $25,000 battery of medical tests.  If you aggressively treat all of these, you’ll cause more harm than good.

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Because overdiagnosis can cause so much harm, the search for pre-cancer reminds me of the search for pre-criminals.  We can always find something wrong when we look hard enough.

I assume the researchers investigating children to find “pre-criminals” mean well.  I can imagine a world in which at-risk children are given more resources.  If it’s true, for instance, that a brief assessment of 3-year-olds or surveys filed by the teachers of 6-year-olds can predict future criminal behavior, we should cut spending on prisons and law enforcement to fund childhood nutrition, education, and enrichment instead.

Instead, we respond to intimations of future disobedience by watching people more closely.

Adorable Preschooler Playing with Colorful Dough

Our predictions of criminality become self-fulfilling: lifelong mistrust makes people criminals.  The racial injustice of mass incarceration is caused in part by unequal enforcement.  As far as we know, U.S. citizens of all ethnicities break laws equivalently often, but police scrutinize minority neighborhoods more closely, so that’s where they find crimes.

Similarly, when an elementary teacher decides that a student is trouble, that student gets scrutinized.  Equivalent misbehavior reaps unequal discipline.  In the U.S., children in preschool are targeted for school suspension based on the color of their skin.  A suspension disrupts education, pushing students further behind.  When a teacher decides that a student won’t learn, that student is prevented from learning.

And researchers have developed an automated image analysis that predicts the likelihood that someone is a criminal just from a photograph of his clean-shaven face.  Which isn’t as evil as it sounds.  Or, rather, it is evil, but not because a computer is doing it – the computer algorithm is simply revealing and quantifying the evil way we humans judge people by their appearances.

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Genetics differences are real, and they do make a substantial contribution to people’s proclivities.  But human brains are so plastic that the way we’re treated matters more: if you’re curious, you might want to check out this inadvertent identical twin study.

With a glance, we form strong opinions about people’s characters.  Some children we brand “pre-criminals.”  Is it shocking that, after decades of mistreatment and scrutiny, these children become the lawbreakers we always expected them to be?

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.