On power and species.

On power and species.

At track practice, a pair of high school runners were arguing.  Knowing that I’ve completed twenty-two years of schooling, they figured I could resolve their debate.

“Coach Brown, who would win in a fight, Superman or The Hulk?”

I stared at them blankly.  I knew a bit about Dr. Jekyll and Mr. Hyde, which helps to understand The Hulk, but I’d never read a Superman comic.  Superman didn’t sound like an interesting hero: he seemed too powerful.  Even The Hulk is more interesting within the context of a complex campaign, when he might become enraged and wreck his own plans, than in a single fight.

I failed to provide an answer, and the kids went back to arguing.  (“Superman could just turn back time to before The Hulk got enraged, then smash him!”) 

And I resolved to read a Superman book, to shore up this gap in my education.  Astounding, isn’t it, that Stanford would allow me to graduate without knowing anything about the paragon of the DC universe?

I chose Grant Morrison’s All-Star Superman.  And was pleasantly surprised – although Superman is indeed too powerful for the risk of danger to provide narrative tension, he’s still sad.  He doesn’t get the recognition that he feels he’s due; his powers leave him feeling isolated and alone; during the 24-hours when his girlfriend becomes his equal due to a magic serum, she spends her time flirting with other heroes. 

Doing great work can feel hollow if nobody appreciates it.

Midway through the series, Superman meets two other survivors from his native Krypton.  He expects that they’ll congratulate him on how well he’s kept his adopted planet safe.  Instead, they’re disgusted by his complacency.

Superman, in turn, feels disappointed by his brethren.  Within the world of comic books, characters who view their powers as conferring a responsibility are heroes; those who think that power gives them the right to do whatever they want are villains.

Homo sapiens are not as intelligent as the new arrivals from Krypton.  We are smaller, slower, and weaker.  Our tools are less technologically advanced.  If they chose to cull our kind, we could do nothing to resist.

#

I recently had the opportunity to read Luke Dittrich’s New York Times Magazine article on the Puerto Rican macaque colony that was traumatized by Hurricane Maria.  (I’ve written previously about Dittrich’s investigation into the history of “Patient H.M.” and unethical behavior among MIT memory researchers.)

This particular colony of macaques has been studied closely for years.  Researchers have voluminous observational data from both before and after the hurricane; they’ve stored many tissue samples as well.  The hope is that this dataset could unveil the biochemical consequences of trauma, and elucidate traits that allow some people to weather trauma more effectively than others.

With clear insights into the specific pathways affected by trauma, we might even be able to develop drugs that would allow humans to stave off PTSD.  Or cure it.

Macaques have long been used as subjects for medical research.  We’ve developed several vaccines that prevent AIDS in macaques, but unfortunately the differences between SIV (simian immunodeficiency virus) and HIV meant that some of these vaccines increased human susceptibility to the disease.  Whoops.

An image attributed to the Primate Research Laboratory at the University of Wisconsin – Madison and disseminated in 1992.

Macaques are highly intelligent, social animals with approximately 93% the same DNA sequences as us humans.  For immunology research, they’re kept in wire cages.  They can’t touch, don’t really get to move around.  But that’s not so bad compared to the nightmarish psychological studies that have been conducted on macaques in the past.  Dittrich’s article summarizes a few of Dr. Harry Harlow’s experiments.  Harlow named several pieces of his research equipment, such as “The Pit of Despair,” a small box devoid of light or sound in which children could be trapped for months on end, or “The Rape Rack,” which shouldn’t be described.

“[Harlow] found that the females who had endured the trauma of both the Pit of Despair and the Rape Rack tended to become neglectful or even severely abusive mothers.

#

We’ve conducted studies on humans who have been traumatized.  By surveying hurricane survivors, we’ve found that many suffer from PTSD.  But one drawback of these investigations, Dittrich writes, is that “the humans in these studies almost never become experimental subjects until after the traumatic events in question, which makes it hard to gauge how the events actually changed them.

If a researcher interested in how trauma affects individuals or societies were to dream up an ideal natural laboratory, she might imagine a discrete landmass populated by a multigenerational community that has been extensively and meticulously studied for many decades before the traumatizing event.  Even better, it would be a population to which researchers would have unfettered access – not only to their minds, but also to their bodies, and even their brains.”

We are to macaques as Superman is to us.  We are stronger, smarter, technologically superior.  We can fly into space; macaques have done so only at our whims.

In “St. Francis Visits the Research Macaques of Modern Science” by John-Michael Bloomquist, we eavesdrop on a conversation between the saint and Miss Able, the first primate to leave our planet.  St. Francis asks about her experience of the voyage; she tells him “The Gods did not let me see anything, the damn cone didn’t have a window.

The capsule and couch used by one of America’s first spacefarers, a rhesus monkey named Able, is displayed at the National Air and Space Museum. Able and a companion squirrel monkey named Miss Baker were placed inside a Jupiter missile nose cone and launched on a test flight in May 1959.

We are indeed like gods among macaques, but we have not elected to be heroes.  Instead, we’ve ravaged their ancestral lands.  We’ve wracked their children with twisted nightmares that they could not wake from. 

Even the Puerto Rican macaque colony that Dittrich writes about – some individuals are permitted to live out their days in relative peace, but this is a breeding center.  If you’re developing an HIV vaccine, your lab’s macaques will die; for a few thousand dollars each, this colony will furnish replacements.  According to their website, they maintain “an available pool of rhesus macaques in optimal condition for research.

We humans are like gods, but, unlike Superman, we’ve chosen to be villains.

On loneliness.

On loneliness.

Most laboratory animals live in bleak environs.  With mice, each cage typically contains a single animal.  There is bedding, food, and water.  There is very little space.

A lab mouse will be illuminated for many hours each day – sometimes twenty-four, sometimes slightly fewer – by fluorescent lights.  It will hear the constant thrum of ventilation fans and refrigerator compressors.  At least once a week, an apex predator – wafting stress-inducing smells, especially if it’s male – will reach into its home and grab it.

Chances are, it will see other mice.  A rotating cadre will fill adjacent cages during its tenure in the lab.  They will never touch.

Our cruelty makes for bad science, too.

When social animals are stored in isolation, their bodies and brains decay.  Neuron growth slows, which impedes learning.  Lifespan is curtailed.  Obesity rates increase.

Lab_animal_careIf we stop mistreating laboratory animals, though, new research might be inconsistent with past results.  When describing mice, scientists don’t say that deprivation stunts brain development.  Instead we write things like, “If a lab is studying the impact of stress on the growth of new neurons, for example, and then it lets mice exercise on a running wheel – which has been shown to spark neuron growth – the study could be jeopardized” (from David Grimm’s recent news article for Science magazine).

4117496025_8024f879d6_zWe give ourselves a very skewed view of neurology if we let ourselves think that a creature’s normal habits are stimulating neuron growth, rather than admitting that deprivation stops it.  For decades, most researchers thought that neuron growth ceased in adults.  Even in the 2005 paper demonstrating structural plasticity, the authors wrote that “such changes are only seen in response to external perturbation,” because brain development is sluggish in lab mice housed in normal conditions, i.e. those little cages.

Of course, some scientists do care about the well-being of their furry test tubes.  For instance, biologist Daniel Weary, who told Grimm “Our dream is that our animals live a better life with us than if they had never been born.”  Animals in Weary’s lab get to touch actual dirt.

Maybe not the highest bar, but the lives of most animals on our planet are worse than if they’d never been born.

Vivek_Murthy_nomination_hearing_February_4,_2014Most social animals – like mice, rabbits, and humans – aren’t going to be very happy when they’re housed in isolation.  Former U.S. Surgeon General Vivek Murthy considers loneliness to be a public health crisis, leading to health risks as bad as smoking or obesity.

Unfortunately, most biomedical research is done with research animals amongst whom pervasive loneliness is standard.  And our political system gives outsize influence to wealthy corporations that earn more money when people feel lonely.

We shunt humans into jail when we feel that their behaviors are unacceptable for the world at large.  Incarceration sends a message: don’t beat your family; don’t steal; don’t sell drugs; don’t take drugs; don’t be late for an appointment with your parole officer; don’t be too poor to pay your court fees.  To my mind, some of these offenses are worse than others.

The hope is that either the threat of incarceration deters people from these things, or that the experience of being incarceration cures them of the inclination.  (Or a third rationale – that seeing offenders punished will pacify others’ sense of fairness – which seems to encourage the evolution of cooperation, but, like many other evolved behaviors, seems unnecessarily vicious for the modern world.)

We’ve known for years that punishment doesn’t work well as a criminal deterrent.  And the experience of incarceration seems to make most people worse, not better.

Instead, we’re imposing loneliness on people who most need the help of friends and neighbors to turn their lives around.  Somebody screws up?  We store that person like a lab mouse.

10490113913_e3a697bdca_zI was recently chatting with somebody who’s done nine months so far for a parole violation – and is still waiting for his court date, which keeps being rescheduled.  (He’s already told the judge that he’ll plead guilty, and the prosecutor wanted to send him to rehab, but his PO nixed the deal.)

“It’s a lot better now, in J block.  Everybody said, you don’t wanna move from A block, you’ll get no bingo, you’ll get no … I don’t care about any of that.  We can look out the window, see people walking on the street.

“I spent almost an hour, the other day, watching this leaf blowing back and forth in the wind.  I was staring, thinking I’d say to the judge, ‘you can pile on whatever other charges you want, I’ll still plead guilty, I’ll plead guilty to all of it if you just let me out there to look at that leaf blowing around up close.  Just five minutes, just lemme see something!

“In D block, that was the worst.  All we could see was the parking garage.  On weekends, we’d see nothing, not even cars.  So I was starting fights every day.  I’d be like, hey, turn the TV to, I don’t know, some channel I don’t even like, just so I can start something with somebody.  Cause a fight would at least be something to do.”

John-Michael Bloomquist’s poem “The Prodigal’s Return,” about teaching poetry in jail, ends:

                                      Each day that I visit

the jail full of men, who hug me the way

their families cannot, write poems about childhoods

I couldn’t imagine, I feel the love of my father.

After nine months inside – un-touched, un-hugged, un-loved, under-slept – perhaps our man will finally be released.  Surely his time there will have cured him of his addiction!

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.

#

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.

6257373863_08b21a81b4_b

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.

#

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.

#

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.

#

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.