On the study of naked mole-rats.

On the study of naked mole-rats.

This is a riff on an essay from several years ago.

In 1974, evolutionary biologist Richard Alexander gave a lecture describing the conditions that might spawn eusocial vertebrates. 

Alexander was a bug guy – “eusocial” refers to extremely cooperative animals like bees, ants, and termites. Individuals sacrifice themselves for others.  Non-breeders help with childcare.  The colony seems more intelligent than its members.

Alexander proposed that a eusocial mammal could evolve if the animals were small compared to their food sources, and if they lived in underground burrows that could be expanded easily and defended by a small percentage of the colony.

After the lecture, an audience member mentioned that this “hypothetical eusocial mammal” sounded a lot like the naked mole-rat.  Alexander was introduced to Jennifer Jarvis, who had studied individual naked mole-rats but not their social lives.  Alexander and Jarvis collaborated to write The Biology of the Naked Mole-Rat.

Eliot Weinberger condensed this 500-page textbook into his 3-page essay, “Naked Mole-Rats.”

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

Weinberger wrote that naked mole-rats “are continually cruel in small ways.”  But they are outdone by naked apes. 

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For a research paper published in 2008, Thomas Park and colleagues found that being pinched by tweezers causes naked mole-rats pain, but injection with caustic acid does not.

“We tested naked mole-rats in standard behavioral models of acute pain including tests for mechanical, thermal, and chemical pain.  We found that after noxious pinch or 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.  Two chemicals were used – capsaicin from hot peppers and hydrochloric acid – which normally evoke very intense pain in humans and other animals.  Injection of either rapidly evoked intense licking and guarding behaviors in mice.”

“In contrast, naked mole-rats showed virtually no response.”

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Perhaps you worry that acid-resistant naked mole-rats could conquer the world.  Fear not.  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.  Or us.

Half a dozen animals were subjected to each treatment.

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Naked mole-rats don’t die from cancer. 

They should.  Their cells, like ours, are copied from copies of copies.  Errors compound.

Some errors are particularly deadly.  Our cells are supposed to stop growing when they touch.  They are supposed to commit suicide when old.  But the instructions telling a cell when and how to kill itself can be lost, just like any other information.

This is cancer.

In cancer, a single cell proliferates at the expense of others.  A cancer cell claims more than its fair share of space.  It commandeers nutrients.  This cell, and its progeny, and its progeny’s progeny, will flourish. 

Then the scaffolding creature dies.  Then the cancer cells die, too. 

But every cell that isn’t an egg or sperm is terminal anyway.  In the colony of our body, most cells are non-breeding members.  From a cancer cell’s perspective, it has nothing to lose.

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We develop cancer often.  With each passing day, we produce about 100 billion new cells.  Each time we produce a new cell, all 3 billion letters of our genome must be copied. 

The enzymes that copy our genome make one mistake every billion letters.  Each cell division: three new mutations.  Each day: three hundred billion new mutations.

Some mutants are trouble. 

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Our bodies kill cancer.  Your immune system – the same mess of mucous, inflammation, and goo that goes haywire during the flu – seeks and destroys renegade cells.  Your body is a fascist enterprise; white blood cells, its militarized police.

Chemotherapy does not kill cancer.  Chemotherapy means flooding the body with poisons that stop all cells from reproducing.  With luck, if the spread of cancer is slowed, your immune system can kill it before it kills you.

In naked mole-rats, cancers always grow as slowly as if the rodents were receiving chemo, allowing their immune systems to squelch cancers at a leisurely pace.  Their cancers are slowed by a heavy sugar called “hyaluronan,” which is packed so tightly into the space between cells that there is no room to grow.

In 2013, biologist Xiao Tian and colleagues wrote that “naked mole-rats may have evolved a higher concentration of hyaluronan to provide the skin elasticity needed for life in underground tunnels.  This trait may have then been co-opted to provide cancer resistance and longevity.”

They became impervious to cancer almost by mistake.

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The record lifespan for a naked mole-rat in captivity is 28 years, 4 months.  The record-holder was nicknamed James Bond.  He was senior consort to his queen and continued rutting – and siring pups – up until the day he died.

Bond was dissected.  His cells showed extensive oxidative damage in their lipids, proteins, and DNA.  Bond should have been hobbled by age.  But time did not slow him down.

Science writer David Stipp described him as “a little buck-toothed burrower who ages like a demigod.”

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Humans typically cease breeding long before we die.  From an evolutionary perspective, as soon as we stop having children, our fitness drops to zero.

And yet, we have long lifespans.  The dominant theory is an offshoot of “the grandmother hypothesis” – because we often care for grandchildren, there may have been evolutionary pressure to maintain good health until our grandchildren also reach reproductive age. 

With twenty-year generations, there’d be an incentive to survive until our sixties.

After that, perhaps our ancestors were no longer helpful.  And so we’ve inherited a propensity to decay.  Expensive medical interventions can preserve us longer, but once we pass our natural lifespans, brains and bodies weaken.

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When scientists starve animals in the lab, it’s called “caloric restriction.”  This protocol extends lifespan in a wide variety of species.  Monkeys, mice, flies, and worms.  Ten-fold increases in lifespan have been observed.

Caloric restriction should extend the lives of humans, too.

There are unpleasant side effects.  Caloric-restricted mice spend their time staring at empty food bowls.  They are listless: barely moving, barely sleeping.  They live longer, but worse – and if they are fed slightly less, they die of malnutrition.

Frequent starvation in the wild may have caused naked mole-rats to evolve their prodigious longevity.

Naked mole-rats expand their colonies outward, searching for edible roots.  When they find a good root, they gnaw it carefully, attempting to keep the plant alive as long as possible.  But a colony of naked mole-rats eats faster than any plant can grow.  When the plant dies, the colony plunges into famine. 

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Most eusocial animals carefully ventilate their homes.  Termites build giant pylons in the desert.  Although temperatures outside careen from 35 degrees at night to over 100 during the day, the interior of the mound remains a constant 87 degrees.  And the termites do not asphyxiate.  Their exhalations are swept away by circulating air.

Naked mole-rats burrow with less care.  They sleep in piles, hundreds of bodies lumped together underground.  Those near the center soon run out of oxygen.

We would die.

Most animals, deprived of oxygen, can’t fuel their brains.  Thoughts are expensive.  Even at rest, our brains demand a constant influx of energy or else the neurons “depolarize” – we fall apart.

Since the death penalty was reintroduced in the United States in 1976, we have killed eleven prisoners in gas chambers.  During the 1983 execution of Jimmy Lee Gray in Mississippi, officials cleared the observation room after eight minutes.  Gray was still alive, gasping for breath.  His attorney said, “Jimmy Lee Gray died banging his head against a steel pole in the gas chamber while reporters counted his moans.”

Gas chambers are pumped full of cyanide gas, carbon monoxide, or carbon dioxide.  Carbon dioxide is cheapest. 

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With each breath, we inhale oxygen, burn sugar, and exhale carbon dioxide.  When we drive, our cars intake oxygen, burn gasoline, and exhaust carbon dioxide. 

In small amounts, carbon dioxide is beneficial.  Carbon dioxide allows plants to grow.  But when you put too much inside a chamber, somebody dies.  Put too much in the air worldwide and we all die.

The planet Venus was habitable, once.  Humans could have lived there.  Venus had a deep ocean and mild weather.

Through some fluke, Venus experienced a temporary bump in the amount of carbon dioxide in the air.  Carbon dioxide traps heat, which caused water to evaporate.  Clouds formed, which trapped more heat.  The cycle continued. 

Venus is now a fiery inferno.  The ground is bare rock.  Sulfuric acid rains from the sky.

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Lab mice die in gas chambers.  Sometimes one mouse is set inside the plexiglass box; sometimes several mice inside a Chinese-food takeout container are gassed together.  A valve for carbon dioxide is opened; the mice lose consciousness; they shit; they die.

A naked mole-rat would live.  Unless a very determined researcher left the gas flowing for half an hour.  Or so found Thomas Park and colleagues – the same team that discovered that naked mole-rats dislike being pinched.  As they reported in 2017:

Human brains drink sugar.  We are like hummingbirds that way.  And our brains are very fussy eaters.  We are fueled exclusively by glucose.

Naked mole-rats are less particular.  Their minds slurp fructose to keep from dying.

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Naked mole-rats are the most cooperative of mammals.  They are resistant to cancer.  Unperturbed by acid.  They age with the libidinous gracelessness of Hugh Hefner. 

They are able to withstand the horrors of a gas chamber.

And yet, for all these talents, naked mole-rats are easily tormented by human scientists.

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Featured image from Wikimedia Commons.

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.