On attentiveness and names.

On attentiveness and names.

When a scientist first discovers a function for a gene, that scientist gets to name it.  Sometimes these names seem reasonable enough: I worked with a hematologist who did a study to identify proteins involved in apoptosis, which means roughly “programmed cell death” or “cellular suicide,” and so each gene wound up named “Requiem 3”, “Requiem 4,” etc.

Fruit fly geneticists tend to give their discoveries more creative names than other scientists.  There’s the gene “cheap date” – if a fruit fly is missing that gene, it will – ha ha – be unable to process ethanol and  so quickly passes out.  Another genetic mutation produced male flies that would court either males or females, and so this was known for over a decade as “fruity,” until another scientist decided that universal courtship could be less offensively described by the term “fruitless,” because clearly any mating-like activity that does not lead to progeny is a waste of time.

Yup, some gene names were bad.  One person’s idea of a joke might seem to somebody else like a mean-spirited reference to the wider world’s power dynamics.

Other gene names were bad not out of malice, but because humor at the expense of a fruit fly doesn’t make as many people laugh when a human child is dying. 

A gene that produces a somewhat spiky-shaped protein was named after Sonic Hedgehog.  It seemed funny at the time!  See?  The protein is spiky, the video game character has spiky hair, and … get it?  You get it, right?

 Okay, so this Sonic Hedgehog protein doesn’t look all that much like Sonic the Hedgehog.  But spend enough time staring at something like protein crystal structures and you’ll experience pareidolia, like seeing animal shapes in irregularly dappled plaster ceilings, or anthropomorphic gods amongst the twinklings of the stars.

Well, the Sonic Hedgehog protein establishes a concentration gradient that allows cells to recognize their spatial position in a developing body.  If a human fetus comes to term despite having a mutation in the Sonic Hedgehog gene (genetic abnormalities will often result in a miscarriage, but not always), the resulting child will have severe brain defects.

And then a doctor has to explain, “Your baby is suffering because of a Sonic Hedgehog mutation.”

And so, in 2006, geneticists capitulated to medical doctors. No more fanciful names for genes that might lie at the root of human health problems … which, because humans and fruit flies are actually pretty similar, means most genes.  Patients would now be told about a mutation in the SHH gene instead of Sonic Hedgehog, or a mutation in the LFNG gene instead of Lunatic Fringe.

Words have power, after all.


Some people are more attentive to their environments than others.  During evolutionary time, this trait was obviously good for humanity.  If your tribe is traveling through a hostile environment, it helps to have somebody around who is paying attention to the world.  A friend who’s primed to notice encroaching threats like a hungry lion about to leap out and attack.  Maybe we should take a different path.  Which, yeah, that sounds like a good idea.

Other people are particularly inattentive to their surroundings, so it’s easy for them to ignore the world and focus instead on one single problem.  During evolutionary time, this trait was surely good for humanity, too.  It’s helpful to have somebody on the lookout for threats that might eat you, obviously.  But it’s also helpful to have somebody who might discover a way of using dried grass to weave baskets.  A way of cooking mud into pottery that could carry or store water.

Image by Herb Roe on Wikimedia Commons.

Neurodiversity is a virtue in and of itself.  Over the millennia, the world has offered our species many challenges.  Populations that were sufficiently diverse that some members were good at each of a variety of tasks were most likely to flourish.  A cooperative species like termites or Homo sapiens benefits from specialization among its members.

Left to our their own devices, people would naturally fall asleep and wake up at different times.  Some brains are primed to work best in the early morning; others work best late at night.  And that’s good.  It reduces the amount of time that a tribe would be susceptible to attack, everyone asleep.

But in the modern world, we occasionally forget to feel grateful for the diversity that allowed our species to thrive.  The high school students whose brains are primed for late-night thinking drag themselves through morning classes like zombies.  They’ll be midway through first period before the sun rises.  Their teachers glance derisively at their slumped and scruffy forms and call them lazy.


Eventually, humans invented language.  Much later, we invented writing.  Much, much later, we invented the printing press, and then written words became so widely accessible that most humans could benefit from learning how to read.

Of course, reading is easier for people who are inattentive to their environment.

If I had been born earlier in human evolution, I totally would have been lion bait.  When I’m reading a book, or am deep in thought, the rest of the world melts away.  When I’m typing at home, K or the kids sometimes shout my name several times before I even realize that I’m being spoken to. 

People like me, or this kid at a library, totally would’ve been lion bait.

Luckily for me, I wasn’t born way back then.  Instead I was born into a world where inattentive people – the people best able to block out the world and instead focus on their own thoughts – are the most likely to find academic success.  People like me become medical doctors.  Then we get to name the world’s various conditions and maladies.

And so, when it came time to categorize the sort of person who is especially attentive to the world, people like me (who obviously thought that our way of being is the best way to be) referred to those others as having an attention deficit disorder.

Identifying those people’s awareness of their environs might sound like a virtue; instead, we castigated those people’s difficulty at ignoring the world.

I’ve never read the Percy Jackson books, but I’m glad that they exist, if only for passages like this (from The Lightning Thief):

“And the ADHD – you’re impulsive, can’t sit still in the classroom.  That’s your battlefield reflexes.  In a real fight, they’d keep you alive.  As for the attention problems, that’s because you see too much, Percy, not too little.”


Childhood trauma can cause symptoms that medical doctors term “attention deficit disorder.”  Which makes sense – if you’ve gone through an experience where your environs were threatening, you should learn to be more aware of your environment.  It should become more difficult to ignore a world that has proven itself to be dangerous.

Even for somebody with my type of brain, it’s going to be easier to sit outside and read a book when there’s a squirrel nearby than if there’s a prowling grizzly fifteen meters away.

Some children have to learn early on that daddy’s sometimes a grizzly.  And if it can happen to him, why not other grown-ups, too?  Best to stay on high alert around the teacher.  She’s trying to get you absorbed in these number tables … but what if that’s a trap?


Certain drugs can narrow a person’s perception of the world.  They act like blinders, chemicals like nicotine, ritalin, and amphetamines, both un-methylated (sold under the trade name Adderall) and methylated (a CH3 group attached to the amine moiety of Adderall will slow its degradation by CYP2D6 enzymes in the liver, increasing the duration of its effects).

Note to non-chemists: the methylated analogue of Adderall goes by several names, including “ice,” “shard,” and “crystal meth.”  Perhaps you’ve heard of it — this compound played a key role in the television show Breaking Bad.  And it’s very similar to the stuff prescribed to eight year olds.  Feel free to glance at the chemical structures, below.

In poetry class last week, a man who has cycled in and out of jail several times during the few years I’ve taught there – who I’d said “hello” to on the outside just a few weeks earlier when he rode his bicycle past the high school runners and me – plonked himself down in the squeaky plastic hair next to mine.

I groaned.

“I know, I know,” he said.  “But I might be out on Monday.”

“What happened?”

“Failed a urine screen.  But I was doing good.  Out for six months, and they were screening me like all the time, I only failed three of them.”

“With … ?”

“Meth,” he said, nodding.  “But I wasn’t hitting it bad, this time.  I know I look like I lost some weight, dropped from 230 down to 205, but that’s just cause it was hard getting enough to eat.  Wasn’t like last time.  I don’t know if you remember, like, just how gaunt my whole face looked when they brought me in.  But, man, it’s just … as soon as I step outside this place, my anxiety shoots through the roof … “

This is apparently a common phenomenon.  When we incarcerate people, we carve away so much of their experience of the world.  Inside the jail, there is a set routine.  Somebody is often barking orders, telling people exactly what to do.  There aren’t even many colors to be distracted by, just the white-painted concrete walls, the faded orange of inmate scrubs, the dull tan CO shirts and dark brown pants.

The world in there is bleak, which means there are very few choices to make.  Will you sit and try to listen to the TV?  (The screen is visible from three or four of the twelve cells, but not from the others.)  Try, against all odds, to read a book?  Or add your shouting voice to the din, trying to have a conversation (there’s no weather, so instead the fall-back topic is speculating what’s going to be served for dinner)?

After spending time locked up, a person’s ability to navigate the wider world atrophies, the same as your leg would if you spent months with it bundled up in a cast.

And these are people whom we should be helping to learn how to navigate the world better.

“ … so I vape a lot, outside.  I step out of this place, that’s the first thing I do, suck down a cigarette.  And, every now and then … “

He feels physically pained, being so attentive to his surroundings.  And so he doses himself with chemicals that let him ignore the world as well as I can.

And, yes.  He grew up with an abusive stepfather.  This led to his acting squirrelly in school.  And so, at ten years old, medical doctors began dosing him with powerful stimulants.

Meanwhile, our man dutifully internalized the thought that he had a personal failing.  The doctors referred to his hyper-vigilance as an attention deficit disorder.


Words have power.

We can’t know now, after all the hurt we’ve piled on him, but think: where might our man be if he’d learned to think of his attentiveness as a virtue?

On prayer, diversity among deities, and ADHD.

On prayer, diversity among deities, and ADHD.

My new favorite computer game begins each round as a real-time strategy game like Starcraft.  You command your little empire to build temples and offer up various sorts of psalms – will you praise your deity’s ever-gathering hands, its watchful vigilance, its fiery vengeance?

After you feel that you’ve done enough to celebrate your deity, you can command your priests to summon it – at which point the gameplay switches to a third-person adventure mode vaguely reminiscent of the old arcade classic Rampage.  You must attempt to destroy opposing civilizations with your deity … but there’s a twist.  The attributes of your deity reflect the way it was prayed to.  With too much emphasis on its “ever-gathering hands,” your god’s hands become massive. Those unwieldy appendages drag behind you as you walk, plowing deep furrows into the ground.

In this phase of the game, the controls can seem laggy and loose.  It turns out that this is intentional; as in the game Octodad, an inability to control your creation is an essential part of the game.  Certain types of prayer might make your deity more powerful but also more difficult to manage.

John_Martin_-_The_Great_Day_of_His_Wrath_-_Google_Art_Project

Presumably you’d avoid this sort of self-destructive excess – like praising wrath to the extent that your god destroys your own kingdom promptly after being summoned – but opposing players can infiltrate your civilization with heretics, and the way they pray will affect your god as well.

Arturo Perez-Reverte’s The Club Dumas ends with the idea that “everyone gets the devil he deserves.”  This is the underlying concept of the game, but for gods instead of demons.

First Coming includes elements of both real-time strategy and arcade smash-em-up.  And the idea of human prayer sculpting physically-manifest deities is intriguing.  I’d go so far as to argue that it’s the greatest game, flawed only in that it doesn’t live up to the Ontological Argument for the existence of God.

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Bible_primer,_Old_Testament,_for_use_in_the_primary_department_of_Sunday_schools_(1919)_(14595468018)We live in a culture that reveres vengeance.  The majority of the U.S. worships a deity who was praised for his violence.

Sometime around 600 BCE, a kingdom that worshiped a local deity called Yahweh was conquered by Nebuchadnezzer, whose people worshiped the storm god Marduk.  After the surrender, many of the conquered people were deported to Babylon, where they would help make that city the most splendid in the world.

But some of the conquered Hebrews were allowed to remain in Jerusalem, where they still worshiped Yahweh in traditional ways – mostly by ritually killing animals – until they attempted to regain their independence.  Then the Babylonian king Nebuchadnezzer sent an army to circle the city.  The people began to starve.  The uprising was crushed.

102.Zedekiah's_Sons_Are_Slaughtered_before_His_EyesThe Hebrew leader was captured.  He was held, struggling, a soldier on either side restraining his arms.  One by one the Babylonian conquerors brought Zedekiah’s children.  The leader surely screamed, begging to die.  The soldiers gripped his arms more tightly.  And (2 Kings 25) they slew the sons of Zedekiah before his eyes, and put out the eyes of Zedekiah.  Those murders were his last sights, lingering in his blinded mind.  His sons bodies spilling blood from their slit necks into the dust.

Many more of the remaining Hebrews were then deported to Babylon, to slave for the greatness of that city.  They carted stones to build monuments to Marduk.  This god’s temples soared into the sky, one some seven stories high.

And the Hebrews saw the ceremonies held to celebrate Marduk.  On the fourth day of the New Year’s festival, priests read from a sacred text, the Enuma Elish, describing the origin of the world.  The old gods had sex; they were murdered by their children; the flesh of their bodies was used to construct heaven and earth.  Other sacred texts included the Atrahasis – which describes the flood that nearly destroyed humanity when we became too noisy and disturbed the gods’ rest – and Gilgamesh which celebrates fraternal love.

The-Rise-and-Fall-of-Adam-and-Eve_Stephen-Greenblatt_coverIn The Rise and Fall of Adam and Eve, Stephen Greenblat writes that “These works feature gods – a whole pantheon of them – but Yahweh is nowhere among them, let alone their lord and master.

The Hebrew people were crushed, their god so insignificant that he appeared in none of the victors’ stories.  And so the Hebrews fought back … with words.  They wrote a sacred text of their own, one in which Yahweh reigned supreme and the Babylonian tales were mockingly tweaked.  The glorious temples gave rise to “The Tower of Babel,” symbol of mankind’s unwarranted arrogance.  In the Hebrew flood story, humans were killed because the city people – and none were more urbane than the Babylonians – were corrupt.  Sex did not mark the origin of the world, but rather began after the fall.

And they sang psalms to a deity patiently waiting to enact murderous revenge:

By the rivers of Babylon, there we sat down, yea, we wept, when we remembered Zion

We hanged our harps upon the willows in the midst thereof.

For there they that carried us away captive required of us a song; and they that wasted us required of us mirth, saying, Sing us one of the songs of Zion.

How shall we sing the Lord’s song in a strange land?

… and, in answer of their own question, the conquered people begin to sing …

If I forget thee, O Jerusalem, let my right hand forget her cunning.

If I do not remember thee, let my tongue cleave to the roof of my mouth; if I prefer not Jerusalem above my chief joy.

Remember, O Lord, the children of Edom in the day of Jerusalem; who said, Raze it, raze it, even to the foundation thereof.

O daughter of Babylon, who art to be destroyed; happy shall he be, that rewardeth thee as thou hath served us.

Happy shall he be, that taketh and dasheth thy little ones against the stones.

After the siege, Hebrew sons were murdered, daughters were raped, those of able body were made slaves.  They asked of their god revenge.  They prayed to a lord who would kill, and abet their killing, to restore their kingdom.

bible-1623181_640And … several millennia later … our philosophical traditions are rooted in their prayers.  Our nation is embroiled in retributive wars.  Our punitive prisons are overflowing, with those unfortunate enough to land inside often made worse by their time there.

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Yahweh was praised for his patient pursuit of vengeance.  And we celebrate those qualities – in school, especially, we praise those able to dispassionately sit for hours, ingesting knowledge.  Those with difficulty sitting still, we drug.

Which is sad – there are many ways of being smart, even if our culture celebrates only one of them.

Indeed, many cultures have told myths with ADHD heros.  In the Apache myth of the origin of fire, Fox joined a flock of geese in flight … but then forgot the rules for staying in the air.  But that was okay – it was only after he tumbled to earth that he had a chance to steal fire from a tribe of fireflies and bring it to mankind.

In many Polynesian myths of the origin of fire, it was brought by Maui … whose impulsiveness would almost surely lead to an ADHD diagnosis in the contemporary United States.  Each time he received a gift of fire from his ancestor in the underworld – she was pulling off burning finger- or toe-nails and giving them to him – he intentionally quenched them in a nearby stream, just to see what she’d do next.  His curiosity was nearly the death of him.  Irked, she lit the world on fire.

In the Norse pantheon, Loki sometimes plans … but more often pursues whatever rebellious notion pops into his head.  The mutant children he sired will destroy the world.  His penchant for vicious barroom taunting (and impromptu murder) angered all other gods and led to his repeated exile from their kingdom.

But his exploits were still celebrated.

lightning.jpgOr there’s Annabeth in Rick Riordan’s The Lightning Thief, a daughter of Athena who helps the protagonist recover after a battle with a minotaur:

“And the ADHD – you’re impulsive, can’t sit still in the classroom.  That’s your battlefield reflexes.  In a real fight, they’d keep you alive.  As for the attention problems, that’s because you see too much, Percy, not too little.  Your senses are better than a regular mortal’s.  Of course the teachers want you medicated.  Most of them are monsters.  They don’t want you seeing them for what they are.”

On CRISPR and the future of humanity.

On CRISPR and the future of humanity.

I think most laypeople understand that academic scientists, in order to keep their jobs, have to publish new findings.  I assume most people also intuitively understand that not all venues for publication are equal.  Not to malign my hometown newspaper, but it’s less impressive to write an editorial for Bloomington’s Herald Times than the New York Times.

In the research world, journals are ranked by “impact factor.”  At the top of the heap are journals like Cell, Nature, and Science; these have “impact factors” in the 30s.  The Journal of Cell Biology, where I published my thesis work, has an impact factor around 10.

And the Journal of Assisted Reproduction & Genetics?  Its impact factor is slightly below 2.  My local university’s medical library doesn’t even subscribe.

So I was puzzled: why did the research paper with one of the flashiest single-sentence summaries land in J Assist Reprod Genet?

 

journals
Research journals: tiny nudges to the frontier of human knowledge, & a whole lotta people who got to keep their jobs.

Here’s the summary, in case you missed it: a new genome editing technique was used to insert an HIV-resistance gene into human IVF embryos.

To my mind, that’s a pretty big deal.  It’s not that genetically-modified organisms are anything new.  The big difference is that the technique this group used, CRISPR, makes the whole process incredibly fast, precise, and cheap.  The difference is that sculpting the genome of a human embryo will be easy soon.

CRISPR-Cas9_mode_of_action
A charming schematic of CRISPR from Wikipedia. To use CRISPR for a new gene modification, only the short blue / orange targeting strand in the schematic above needs to be synthesized. Eazy-peezy, right?

At the moment, nobody understands the human genome well enough to propose the sort of editing that shows up routinely in science fiction movies — probably the best way to convince you quickly, without getting into too much detail, is to slap up the title of a recent paper: “Most reported genetic associations with general intelligence are probably false.”  We know that many aspects of human physiology and personality are partially controlled by genetics, but we haven’t yet decoded which genes in which combination give any particular effect.

superman_autism_by_sircle-d5zm8k8
Not all differences are detriments.  Clever image by sircle on Deviantart.

I don’t think we even understand fully the trade-offs inherent in human personality.  We’ve recently begun to understand that many traits designated “mental illnesses” exist on a spectrum and that the challenges are inextricably linked to good qualities — creativity and schizophrenia, puzzle solving and autism, awareness and ADHD.  It’s unlikely that any recipe for a “perfect” human brain exists.

Still, there are traits that parents prefer.  Male height.  Facial symmetry.  Disease resistance.  We’ll soon know which genes modulate these.

Which was why, I assume, Xiangjin Kang et al. wrote their paper, “Introducing precise genetic modifications into human embryos by CRISPR/Cas-mediated genome editing.”  They may have felt a moral imperative to draw attention to these issues.

As far as I can tell, this is also the explanation for why their super-flashy experiment landed in a low impact factor journal.  It’s not a typical research paper.  They wrote an opinion piece about scientific ethics with a somewhat-unsuccessful experiment grafted on in order to get the thing published.

I don’t mean that as criticism.  I think they’ve done the right thing.  If anything, the problem is with scientific publishing; I assume their paper was rejected by a higher impact factor journal.  This paper, with its focus on ethics, is not what fancy journals typically publish.

For instance, the reason why their experiment was somewhat unsuccessful?  Kang et al. were using CRISPR to introduce HIV resistance into a human embryo.  But, because they think that using CRISPR on human embryos is unethical, they specifically chose polyploid embryos — these are non-viable cells produced when two sperm fuse with a single egg.  They have too much DNA and can’t possibly become people.

Because CRISPR uses a DNA-reading guide strand to direct a DNA-modifying enzyme to a particular location, and because the experiment would be “successful” only if all copies of a gene were modified, using a polyploid embryo with more copies of each gene increases the chance of “failure.”  In basketball, making three free throws in a row is obviously more difficult than making two in a row.  That’s what they were trying to do.

Which is why, even though the typical way to read a research paper is to look at the pictures, then read the captions, then maybe read the results section — to wit, ignoring the bulk of the text — the most important part of Kang et al.’s paper is the discussion section.  From their paper:

Because human in vitro fertilization methods are well established and site-specific nuclease technologies are readily available, it is foreseeable that a genetically modified human could be generated.  We believe that any attempt to generate genetically modified humans through the modification of early embryos needs to be strictly prohibited until we can resolve both ethical and scientific issues.

That’s a sentiment a lot of people probably agree with.  But I think it carries more weight in a paper that demonstrates just how easy this process is.

And, sure, they did not sequence the full genomes of their modified embryos.  One risk with CRISPR genome editing is that you’ll have “off target effects” — you might change more of the genome than you were intending.  But there are plenty of very smart people working to make the technology more precise.  Within five years, I’d guess, you’ll be able to change single target genes reliably.

Gattaca chillingly illustrates the dystopia of unregulated genetic manipulation, but even that film understates what we’ll soon be capable of.  The premise of Gattaca is that, by sequencing IVF embryos, parents can choose what sort of child they want.  From hundreds of options, parents pick one.

Scary, sure.  But not this scary.  CRISPR could let parents sculpt the child they want.

GFP_Mice_01
Not that you’d want this, but it wouldn’t be that hard to make your kid glow in the dark.  Maybe you’d want your progeny to be eight-feet tall and brilliant, too.  You could do it.  But, should you?