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 immortality.

Ravana_Statue

In my last essay, I mentioned Ravana’s boon.  Immunity to harm from gods.  But that wasn’t what he wanted.  Here’s another quotation from the Uttara-kanda, this time from the Robert Biggs translation (it’s less literal than the Dutt translation, which means fewer bizarre sentences.  Less poetic, though.  But I definitely appreciate that he did all that work and then posted it online, free of charge):

“[Ravana]* fasted for ten thousand years, and at the end of each thousand years he offered one of his heads into a sacrificial fire.  In this way he passed nine thousand years and offered nine of his heads into the sacrificial fire.  At the end of ten thousand years when he was about to cut off his tenth head, Lord Brahma appeared before him.  Very satisfied by [Ravana]’s austerities, Lord Brahma stood there accompanied by other demigods.  Then he said: ‘O [Ravana], I am so pleased with you.  Quickly choose the boon you desire, O knower of what is right.  What desire should I now fulfill.  Your effort should not go in vain.’  Then, with an overjoyed heart [Ravana] bowed his head and replied in a faltering voice: ‘O lord, the greatest fear for living beings is death.  I choose immortality.’  When requested in that way, Lord Brahma replied: ‘You cannot have complete immortality, therefore ask me for some other boon.’

*The name used for Ravana throughout that passage is Dashagriva, which means “Ten-necked one.”  I substituted it throughout.  And, right, maybe it’s worth quoting just the final lines of the Dutt translation of that passage, cause it’s rather more abrupt in its denial: “Thus accosted, Brahma spoke to the Ten-necked one, ‘You can not be immortal.  Do you therefore ask of me some other boon.’ ”

So, the dude did all that meditating; once he was getting offered gifts, he wanted eternal life.  And Brahma, like most gods, was not thrilled at the request.  Jehovah was equally ticked at the prospect of his newly-enlightened playthings gaining immortality: here’s a passage from the King James Bible:

“And the Lord God said, Behold, the man is become as one of us, to know good and evil: and now, lest he put forth his hand, and take also of the tree of life, and eat, and live for ever:

Therefore the Lord God sent him forth from the garden of Eden, to till the ground from whence he was taken.

So he drove out the man; and he placed at the east of the garden of Eden Cherubims, and a flaming sword which turned every way, to keep the way of the tree of life.”

So, people want to live forever, and gods aren’t going to help them do it.  That sounds like a job for science!  Indeed, many laboratories are researching ways to extend lifespan.  I don’t think any bioscientists imagine their efforts will ever result in immortality — that’s more a computer science aim than a bioscience one at the moment; here’s a reasonable introductory review into the study of human connectomes — but it seems pretty clear that they’re hoping their work can aid human longevity.  Which I get, obviously, despite my penchant for Malthusian pessimism (“Assuming then my postulata as granted, I say, that the power of population is indefinitely greater than the power in the earth to produce subsistence for man.  Population, when unchecked, increases in a geometrical ratio.  Subsistence increases only in an arithmetical ratio.  A slight acquaintance with numbers will shew the immensity of the first power in comparison with the second.”Thomas Malthus, a legendary curmudgeon).

CaptureLike there’s my graduate school baymate (the way our labs were set up was pairs of desks tucked into long alcoves of bench space, so there always wound up being one person who you talked to and collaborated with most), who planned to study lobsters after getting his doctorate: lobsters have limited senescence.  That is, they show fewer signs of aging than humans do; if we were more like lobsters, perhaps nursing homes would be rowdier places.  Of course, they’d needed to widen the hallways, reinforce the floors, etc., but I’m sure that’d seem like a fair trade for a little bit more vivacity.  Currently my buddy isn’t actually working on lobsters – he’s pursuing research more likely to help people in the near term – but someday maybe he’ll get back to it.

But the research into lobsters is focused on figuring out why they live a long time.  And there are similar studies focused on the secrets of other long-lived creatures; the most recent one I caught was a paper on whales.  The authors analyzed the bowhead whale genome and found that there might be extra copies of some DNA repair enzymes, and less of certain metabolic proteins (like a premature stop codon in a protein named UCP1 that generates heat).  About what you might expect: if you want to live a long time, DNA repair is good, metabolism is bad.  And it’s interesting, sure, but, again, unlikely to extend lifespan in the near future.  Good-lookin’ droids, but not the droids Ravana was looking for… anything that comes from that work will help other people a long time from now.  And that’s no good.  Honestly, interrogate any Malthusian and eventually they’ll tell you: the problem with longevity is that everyone else might attain it too.  If there were an a magic plant to provide immortality to just me, right here and now, then that’d be fine.  Unless a serpent happened by and stole it.  Then I’d probably be sad and start to weep.

But in the meantime, we’ve got some strategies for life extension to discuss!  Things that you could try today.  Like perfusion with hydrogen sulfide.  That’s right – inhale a horrible toxin in order to live!

(Don’t actually try this, by the way.  Hydrogen sulfide isn’t good for you.)

The first study using hydrogen sulfide to lower metabolic rate was done in Mark Roth’s lab: they were gorking mice with it, the idea being that a low metabolic rate, low oxygen consumption, etc., might make you more likely to survive massive blood loss or nasty surgery without physiological damage ... if you’re not in a suspended animation-like state and you experience hypoxia, bad things happen to your brain.

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Figure 2A, Miller and Roth (2007).

Or course, that’s all for acute episodes dosed with hydrogen sulfide.  The Roth lab also did a study where they raised worms with or without 50 parts per million hydrogen sulfide in the atmosphere, and the worms with hydrogen sulfide lived longer (see Figure 2A for a nifty graph).

The next strategy is to supplement your diet with glucosamine.  This is an inhibitor of glycolysis: roughly speaking, the process by which your cells turn food into energy.  Work done in Michael Ristow’s lab showed that when mice were fed glucosamine every day for the bulk of their lives, they lived a little longer (see Figure 3C for the nifty graph).   And they presented significance testing for whether or not lifespan was increased… but didn’t mention a percentage for how much longer the mice lived.  Glancing at it, I’d say not much.  But some!  A little bit more time!

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Figure 3C, Weimer et al. (2014).

Or there’s caloric restriction.  Caloric restriction is something that’d be more reasonable for you to try at home than the whole huffing hydrogen sulfide thing, although I still wouldn’t recommend it.  Even though there’ve been very promising results in a variety of species… even in humans, so if you happened to decide today that this is something you’d want to do, the evidence is on your side.  Massively reduce the amount you eat and you might live longer.  Or not.  Caloric restriction also sounds a lot like anorexia, which causes horrible health problems.  Good job, photoshop!  And it’s apparently tricky to balance caloric restriction to be exactly right to promote lifespan without succumbing to all those anorexia-related health problems.

But in summary, it seems to be metabolism that kills you.  Oxygen eventually destroys cells.  And mitosis, which has to occur to replace your cells, involves doubling your DNA, which can never be 100% error-free.  So once you live enough, you’ll die.

The current strategies used to extend life – hydrogen sulfide, glucosamine, caloric restriction – seem primarily to slow metabolism.  So I don’t really think you’d be getting much more life.  You would persist in the world for more time, but would you be having more fun?  Would the integral of your fun vs. time graph over your entire lifespan even match that of someone living faster and less healthily?

I mean, I know my answer.  Not that I’m particularly unhealthy, but I volunteer as an assistant coach for the high school long distance runners, which means I go out and run with them a couple times a week, which means my metabolism works pretty hard.  I’m using up my heartbeats young; I won’t live forever.  But I still like doing it; I like running and I like running with them, talking with kids on the team, trying to make their time in high school a little less horrible than mine was.

img466psAnd as a last salvo for this essay, it might be worth quoting at one more curmudgeonly writer who’s pointed out some of the flaws in the whole “help everyone live longer” scheme: good old Jack Vance, whose debut novel “To Live Forever” is the best allegory for pursuing a tenure-track academic career I’ve ever read.  Seriously, if that’s your gig, you should check it out.  Yes, Jack Vance wrote pulp, but he was still a great stylist (it’s taking a great deal of restraint on my part not to quote a passage from his “Eyes of the Overworld” here… maybe I’ll try to find a way to work it in to a later, shorter essay) and the world he describes in “To Live Forever” feels eerily familiar to me, despite Vance having never taken part in it.  Here, I’ll quote a few passages from the beginning of that book: as you read, perhaps you’ll want to imagine modern terms like “impact factor” or “citation tracker” where he wrote “slope.”

At this time the word “slope” was charged with special meaning.  Slope was a measure of a man’s rise through the phyle; it traced the shape of his past, foretold the time of his passing.  By the strictest definition, slope was the angle of a man’s life line, the derivative of his achievements with respect to his age.

The Fair-Play Act carefully defined the conditions of advance.  A child was born without phyle identification.  At any time after the age of sixteen he might register in the Brood, thus submitting to the provisions of the Fair-Play Act.

If he chose not to register, he suffered no penalty and lived a natural life without benefit of the Grand-Union treatments, to an average age of 82.  These persons were the “glarks,” and commanded only small social status.

The Fair-Play Act established the life span of the Brood equal to the average life span of a non-participator–roughly 82 years.  Attaining Wedge, a man underwent the Grand-Union process halting bodily degeneration, and was allowed an added ten years of life.  Reaching Third, he won sixteen more years; Verge, another twenty years.  Breaking through into Amaranth brought the ultimate reward.

To apply this formula to the record of each individual, an enormous calculating machine called the Actuarian was constructed.  Besides calculating and recording, the Actuarian printed individual life charts on demand, revealing to the applicant the slope of his lifeline, its proximity either to the horizontal boundary of the next phyle, or the vertical terminator.

If the lifeline crossed the terminator, the Emigration Officer and his assassins carried out the grim duties required of them by the Act.  It was ruthless, but it was orderly–and starkly necessary.

The system was not without its shortcomings.  Creative thinkers tended to work in proved fields, to shun areas which might prove barren of career-points.  The arts became dominated by academic standards; nonconformity, fantasy and nonsense were produced only by the glarks–also much that was macabre and morose.

So, as soon as humans learned how to live forever — Jack Vance postulates an uploading methodology similar to the connectome-based schemes I linked to earlier — there had to be a way of determining which humans would live.  And it’s at that point that many of the most promising candidates would resort to conservative behavior; better to inch toward success than swing with all your might and maybe miss.  Better to propose a project that you know will yield something than to throw all your effort into a grand scheme and maybe come up with nothing. No publication, no grants, no tenure.