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?


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.

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.

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.

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?

On mental architecture and octopus literature.

CaptureI might spend too much time thinking about how brains work.  Less than some people, sure — everybody working on digital replication of human thought must devote more energy than I do to the topic, and they’re doing it in a more rigorous way — but for a dude with no professional connection to cognitive science or neurobiology or what-have-you, I spend an unreasonable amount of time obsessing over ’em.

What can I say?  Brains are cool.  That they function at all is pretty amazing, and that they do it in a way that gives us either free will or at least the illusion of having it is even better.

Most of my “obsessing over brains” time is devoted to thinking about how humans work, but studies on animal cognition always floor me as well.  A major focus of these studies, though, is often how similar human minds are to those of other animals… for instance, my recent hamsters & poverty essay was about the common response of most mammalian species to unfair, unrectifiable circumstance, and I’m planning a piece on the (mild) similarities between prairie dog language and our own.

The only post I’ve slapped up lately on differences between human and animal cognition was about potential rattlesnake misconceptions, but even that piece hinged upon a difference in the way they see, not the way they think.

Today’s post, though, will be about octopi.

A baby octopus (graneledone verrucosa)  moves across the seafloor as ROV Deep Discoverer (D2) explores Veatch Canyon.

A study on octopus evolution was recently published in Nature (Albertin et al., “The octopus genome and the evolution of cephalopod neural and morphological novelties”), and the main thing I learned from that paper & some background reading is that octopus brains are wicked cool.

Honestly, if we asked Superman to spin our planet backward some twenty billion times in order to re-run evolution, I think cephalopods could give apes a run for their money on potential planetary dominance.  Cephalopods are quite intelligent, adept problem solvers, have tentacles sufficiently agile for tool use, and can communicate by changing colors (although with much less finesse than the octospiders in Arthur C. Clarke’s Rama series. The octospiders used a language based on shifting striations of color displayed on their skin).


The biggest obstacle holding octopi back from world domination is the difficulty for a water-dwelling species to harness fire or electricity.  But octopi can make brief sojourns onto dry land… and even land-dwelling apes took something like 20 million years to discover fire and some 22 million for electricity.

Sure, that’s faster than octopi — they’ve had a hundred million years already and still no fire — but once Superman spins the planet (first he fought crime!  Now he’ll muck up our timeline to investigate evolution!), there’ll be a chance for him to stop that asteroid and save the dinosaurs.  I imagine that living in constant terror of T-Rex & friends would slow the apes down a little.

I’ve never had to work under that kind of pressure, but it’s probably much more difficult to discover fire if you’re worried that a dinosaur will stomp by, demolish your laboratory, and eat you.

Octopi ingenuity might be similarly stymied by pervasive fear of giant monsters: sharks, dolphins, sea lions, seals, eels, and, yes, those ostensibly land-bound hairless apes.  Voracious, vicious predators all… especially those apes.


And yet.  Despite the fear, octopi are extremely clever.  They have a massive genome, too.  In itself, genome size is not a measure of complexity, in part because faulty cell division machinery sometimes results in the duplication of entire genomes — no matter how many copies of Fuzzy Bee & Friends you staple together, even if you create a 1,000+ page monstrosity, you won’t create a narrative with the complexity of The Odyssey.

That’s what researchers thought had happened with the octopus genome.  Sure, they have more genes than us, but they’re probably all duplicates!  Albertin et al. were the first to actually test that hypothesis, though… and it turns out to be wrong.  The octopus genome underwent massive expansion specifically for neural proteins & regulatory regions.  Which suggests that their huge genome is not dreck, that it is actually the product of intense selection for cognitive performance.  It isn’t proof, but it’s definitely consistent with selection for greater mental capacities.

There isn’t any octopus literature yet, but evolution isn’t done.  As long as octopus survival & mating success is bolstered by intelligence, there’s a chance the species will continue to slowly “improve.”

(I am biased in favor of smart creatures, but more brainpower is not necessarily better in an evolutionary sense.  For an example, here’s my essay on starfish zombies.)


But even if a species derived from contemporary octopi eventually gains cognitive capacities equivalent to our own, we may never grasp the way they perceive the world.  Their brains are organized very differently from our own.  Our minds are highly centralized — our actions result from decisions passed down from on high.

For most human actions, it seems that the mind subconsciously initiates movement, firing off instructions to the appropriate muscles, and then the conscious mind notices what’s going on and concocts a story to rationalize that action.  For instance, if you touch something hot, nociceptors (pain receptors) in your hand send an “Ouch!” signal to your brain, your brain relays back “Pull yer damn hand away!”, then the conscious mind types up a report, “I decided to pull my hand away because that was too hot.”

(Some people have argued that this sequence of timing indicates that we lack free will, by the way.  Which seems silly.  Our freedom doesn’t need to be at the level of conscious decision-making to be worthwhile.  Indeed, your subconscious is as much you as your consciousness.  Your subconscious reflexes reflect who you are, and with concerted effort you can modify most if not all of them.)

Octopi minds are different.  They seem to be much more decentralized.  Each tentacle has a significant neural network and can act independently.  Octopus tentacles can still move and make minor decisions even if cleaved away… like the zombie movie trope where a severed arm continues to strangle someone.

Since we have no good way to communicate with octopi, we don’t know whether their minds are wired for storytelling the way ours are.  Whether they also construct elaborate internal rationalizations for every action (does this help explain why I’m so fascinated by free will?  Even if our freedom is illusory, the ability to maintain that illusion underpins our ability to tell stories).

But if octopi do explain their world with stories, the types of stories they tell would presumably seem highly chaotic to us humans.  Our brains are building explanations for decisions made internally, whereas an octopus would be constructing a narrative from the actions of eight independently-acting entities.

Who knows?  Someday, many many years from now, if octopi undergo further selection for brain power & communication, we might find octopus literature to be exceptionally rambunctious.  Brimming with arbitrary twists & turns.  If their minds also tend toward narrative storytelling (and it’s worth mentioning that octopi also process time in a cascade of short-term and long-term memory the way mammals do), their stories would likely veer inexorably toward the inexplicable.

Toward, that is, actions & consequences that a human reader would perceive to be inexplicable.

Octopi might likewise condemn our own classics as overly regimented.  Lifeless, stilted, formulaic.  And it’d be devilishly hard to explain to an octopus why I think In Search of Lost Time is so good.



p.s. I should offer a brief mea culpa for having listed different lengths of time that apes & octopi have had with which to discover fire.  All known life uses the same genetic code, so it’s extremely likely that we all share a common ancestor.  Everything alive today — bacteria, birds, octopi, humans — have had the same length of time to evolve.

This is part of why it sounds so silly when people refer to contemporary bacteria as being “lower” life forms or somehow less evolved.  Current bacteria have had just as long to perfect themselves for their environments as we have, and they simply pursued a different strategy for survival than humans did.  (For more on this topic, feel free to read this previous post.)

I listed different numbers, though… mostly because it seemed funny to imagine a lineage of octopi racing the apes in that “decent of man” cartoon.  Who will conquer the planet first?!

I chose my times based on the divergence of great apes from their nearest common ancestor (gibbons, whom we’ve rudely declared to be “lesser apes”) and the divergence of octopi from theirs (squids, ca. 135 million years ago).  The numbers themselves are pretty accurate, but the choice of those particular numbers was arbitrary.  You could easily rationalize instead starting the clock for apes in their quest for fire as soon as the first primates appeared, ca. 65 million years ago… then octopi don’t look so bad.  Perhaps only two-fold slower than us.  Or you could start the apes’ clock at the appearance of the very first mammals… in which case octopi might beat us yet.