Language is a virus
January 13, 2018 6:28 AM   Subscribe

Brain Cells Share Information With Virus-Like Capsules (slAtlantic) Turns out Burroughs was right. Language - and all long-term learning - really is a virus. Or rather, it depends on a strange, alien gene that now turns out to be co-opted from an ancient virus with striking similarities to HIV. It gets stranger: the same mechanism exists across vertebrates and insects, but was independently acquired. Genuinely mind-altering science that creates far more questions than it answers.
posted by Devonian (41 comments total) 97 users marked this as a favorite
 
MVVV

Mefi Voice Virus Vector
posted by sammyo at 6:49 AM on January 13, 2018


Nam shub! Paging Neal Stephenson, Mister Stephenson to the white courtesy phone.
posted by wenestvedt at 6:57 AM on January 13, 2018 [22 favorites]


Language is a virus from outer space. I mean seriously, what better setup could there be for a sci-fi story than "mysterious virus in all Earth life gifts us with the ability to form memories"?

It's a shame the Atlantic article leaned so heavily on "similar to HIV". HIV is such an emotionally loaded thing and I'm cringing at the anticipation of drive-by comments about sexual transmission. If I understand right the Arc gene is similar to a whole lot of retroviruses, and then there's the specific heritage with the gag viral gene.

Here's the research paper from Cell, but it's not for laymen and is certainly over my head.
posted by Nelson at 7:33 AM on January 13, 2018 [8 favorites]


I think the connection between arc and HIV is that they both evolved from a common ancestor or family of viruses, but I'm far from up to speed on this. Ed Yong tweeted an erratum: "Okay, I fucked up here. The first bit is right. The last bit is wrong. Arc comes from a group of jumping genes that *gave rise to retroviruses* and did not *arise from them*. I've corrected the piece and regret the frankly embarrassing error."

The meat of the story isn't touched, though. It's still a perspective-changing discovery.
posted by Devonian at 7:46 AM on January 13, 2018 [2 favorites]


This is pretty cool. The original paper is here, but unfortunately behind an academic paywall. A full-text version should be available for free on PubMed Central soon.

The evidence has been growing for a while that transfer of genes from viruses to organisms (and back) is an important mechanism in evolution. Darwin's "tangled bank" is more tangled than he ever imagined, and the tree of life is more like a web, with branches occasionally sending little streamers of connections between each other, carried by viruses.

What's even cooler is that it seems that arc mimics that evolutionary-time behavior at the timescale of an individual animal learning from its experiences. arc forms virus-like capsules, and then carries its own mRNA to neighboring cells [1]. I'm not aware of any previously-known mechanism in metazoan biology that is anything like this. Because arc also has the property of promoting synaptic plasticity [2], apparently by helping neurotransmitter receptors make their way to the synapse, what this means is that when a neuron engages arc-mediated mechanisms for synaptic plasticity, it forces neighboring cells to do so as well, at least at nearby synapses.

As an additional historical footnote that I think is interesting, around the time that Darwin was publishing his works of evolutionary theory that followed up on Origin, modern neuroscience as a discipline was being born, midwifed in part by two great researchers, Santiago Ramon y Cajal and Camillo Golgi. The two had rival theories about how the brain was structured. Golgi proposed the "reticular theory," that the brain and the rest of the nervous system are a single uninterrupted network of nerve fibers, while Ramon y Cajal proposed the "neuron doctrine," that the entire nervous system is made of discrete cells which communicate with each other in prescribed ways. Ramon y Cajal, of course, turned out to be correct, but elements of Golgi's reticular theory occasionally reemerge when new mechanisms are discovered that break down the walls between neurons, as it were. We've known for decades about gap junctions, which are physical connections between some neurons which allow for direct electrical coupling and transfer of small molecules. But this new mechanism that arc enables shows that the nervous system is capable also of violating the very central dogma of cell biology. Biology is weird, complicated, and beautiful, and if you're confronted with a question of "does biology do it this way or that way?" the answer is usually "both."

[1] If anyone needs a refresher on basic cell biology, the DNA in cells codes for proteins, which are the main structural building-blocks of cells. DNA is used as a template to make "messenger RNA", mRNA, through a process called transcription, and then mRNA is used as a template to make proteins, through a process called translation. The whole procedure is generally termed the "central dogma" of cell biology. DNA always lives in the nucleus of a cell, but mRNA can be sent out to the rest of the cell for local processing, which is useful in cells like neurons which have very irregular shapes. The proteins translated from mRNA can also be transported ("trafficked") from the place they're made to where they're needed. One of arc's previously-known functions is in this last process, helping other proteins get to where they need to be.

[2] Synaptic plasticity refers to the phenomenon of a synapse between two neurons getting weaker or stronger, meaning that when the presynaptic "speaking" neuron fires, it evokes a weaker or stronger response from the postsynaptic "listening" neuron. There's lots of mechanisms by which synaptic plasticity happens, but the ones arc participates in seem to be critical for long-term learning and memory.
posted by biogeo at 7:52 AM on January 13, 2018 [44 favorites]


mind-altering science

I see what you did there.
posted by biogeo at 7:54 AM on January 13, 2018 [3 favorites]


Thank you Devonian for posting this fascinating item, and biogeo for the welcome refresher on basic cell biology!

This just blows my mind.
posted by ipsative at 8:01 AM on January 13, 2018 [2 favorites]


This seems big. After spending 10 days with my aging parents, who are experiencing cognitive decline, I’m interested in any breakthroughs.
posted by greermahoney at 8:04 AM on January 13, 2018 [1 favorite]


Bacteria in my gut, viruses in my brain, there’s more of them in me than me.
posted by notyou at 8:56 AM on January 13, 2018 [14 favorites]


Yes we tend to think of ourselves as buttoned up little human forts bristling with defences ready to take down and neutralize foreign invaders but really we are all a soup of bacteria and viruses and people-bits.
posted by fshgrl at 8:59 AM on January 13, 2018 [16 favorites]


This does nothing to salve my ongoing fantasy of going back in time to visit great figures near the end of their lives, and more or less say:

"Hi, I'm from future. I thought you might like to know what your ideas have lead to. It is far stranger, far more interesting, far weirder, than you can possibly imagine. Care to talk over a pint?"

I know it's a terribly common fantasy, but stuff like this is just so damn interesting. It seems terribly unfair there's no way to visit Mr Darwin—and others—and let him know just how fantastically bizarre it all really is.
posted by los pantalones del muerte at 9:01 AM on January 13, 2018 [6 favorites]


btw.this is some good science writing .

exciting but non-hyped, not-too-breathless, just right for a nominally adult audience.
posted by lalochezia at 9:05 AM on January 13, 2018 [6 favorites]


Care to talk over a pint?
I think Burroughs had cut way back on heroin, by the end of his life.
posted by thelonius at 9:22 AM on January 13, 2018 [3 favorites]


Such a fascinating article, and accessible enough for someone like me with little biology background. Thank you. I'm hopeful about the implications for people with Alzheimer's, because I would love to see something stop that pernicious disease from robbing people of their quality of life.

(I confess the first thing the title reminded me of was the horror movie Pontypool: "somehow a virus has found its way into the English language, infecting certain words, and only certain words infect certain people. Once these infected words are said and understood, the virus takes hold of the host, who finds another person to kill themselves with.")
posted by hurdy gurdy girl at 9:40 AM on January 13, 2018 [5 favorites]


It seems terribly unfair there's no way to visit Mr Darwin—and others—

"Good news, Newton! Your work was incredibly influential!"
"It revived interest in alchemy?"
"OK news, Newton!"

"Good news?"
"Yes, Mendel! Your work was incredibly influential!"
"It led people to appreciate the wonder of God's creation? Everyone at the monestary will be so excited!"
posted by justsomebodythatyouusedtoknow at 9:45 AM on January 13, 2018 [23 favorites]


there’s more of them in me than me.

The thems are also you. Even before you start to think about mitochondria. When I first saw a detailed metabolic pathway diagram, I was at first astonished then horrified - how could so many messy systems possibly work together? And what happens if they don't? And every day, more stuff comes out that shows how much more there is we don't even suspect. I don't know how many mutation, co-opting or other events can happen in a billion years or so, but it's clearly rather a lot.

My personal neurobiology (which I really enjoy playing with) features reduced axonal transport in the anterior optic nerve, the nuggety results of which interacted rather spectacularly with yer bog standard inflammation response to trigger neural and retinal apoptosis and the chance to observe how visual processing works with a randomised degradation of stimuli. It's quite fun to have a ringside seat of a worked example of many of the failure modes of intriguing, half-understood systems of perception, but on the whole I suggest you just read up about it instead.
posted by Devonian at 10:13 AM on January 13, 2018 [8 favorites]


Moar exosomes.

Does this imply that cancer might not be so stupid after all? Them malignant cells love to send out “live” m/miRNA payloads to their healthy neighbors. (Ha ha only serious, sort of.)

The radical new findings here are

1) gag has been co-opted, repeatedly and independently across multiple lineages, to do this

2) there are plenty of lipid encapsulated cargo pods that cells send out; this one is a protein encapsulated lipid associated pod that is nonetheless necessary for a basic function of the central nervous system.

3) we have some work in process showing what mechanisms govern maternal/paternal and epi/genetic control of endogenous retroviruses as well as supposedly-pseudo genes (spoiler: most aren’t). But this mechanistic paper casts all such efforts in a completely different light: it may be that our “junk DNA” being co-opted for neural and immune functions is what, to a first approximation, makes us human.

Congratulations to Jason and all of the authors on an epochal piece of work.
posted by apathy at 10:24 AM on January 13, 2018 [5 favorites]


btw.this is some good science writing .

exciting but non-hyped, not-too-breathless, just right for a nominally adult audience.


Ed Yong generally does this very well. He's a great example of why the science journalism beat needs dedicated science journalists.
posted by biogeo at 10:36 AM on January 13, 2018 [2 favorites]


Wouldn't it be awesome? Get sick and pick up Armenian? Better yet, get laid, and instead of picking up a Russian, you pick up Russian.
posted by Oyéah at 10:40 AM on January 13, 2018 [3 favorites]


biogeo: arc forms virus-like capsules, and then carries its own mRNA to neighboring cells. I'm not aware of any previously-known mechanism in metazoan biology that is anything like this.

I recall reading about cancer cells which do something like that, which I think is what apathy is also referring to.
posted by clawsoon at 10:41 AM on January 13, 2018 [1 favorite]


apathy: ...is what, to a first approximation, makes us human.

Given how many other animals are also doing this, maybe "makes us human" isn't the most accurate phrase. :-)
posted by clawsoon at 10:46 AM on January 13, 2018


(Ah, but the cancer cell exosomes appear to be carrying microRNA, not mRNA. Nevermind.)
posted by clawsoon at 10:49 AM on January 13, 2018


Better yet, get laid, and instead of picking up a Russian, you pick up Russian.

This has huge implications for the Yakov Smirnoffs of the future.
posted by PlusDistance at 10:50 AM on January 13, 2018 [2 favorites]


Darwin's "tangled bank" is more tangled than he ever imagined, and the tree of life is more like a web, with branches occasionally sending little streamers of connections between each other, carried by viruses.

This. So much this. And it was invisible for so long (until the development of full-genome sequencing and the computer power to compare those enormous files of AGT&Cs with those from other organisms to find all the identical bits. You can even put a (general) date on the transfer by looking at the number of errors (random mutations...mostly from environmental radiation, which happen at a (mostly) constant rate over time) in the transferred segments. The search term (if you want to know more) is 'Sideways Genetic Transfer' (since it's 'sideways' to the branches of the tree of life) and it's now considered to be the most important aspect of evolution, up there with natural selection (with mutation being their much slower cousin).
Sort of related, the organism with the longest/largest DNA: the lily. Lots of organisms will protect themselves from viruses by absorbing it into their DNA, then isolating it structurally by throwing in a bunch of 'junk' DNA around it to keep it from activating/co-opting cellular processes (in the case of the lily, this has left it with the majority of its genome being junk-broken virus-junk-virus-junk). That the lily contains so much of this is probably due to its swampy environment filled with viruses and virus-carrying parasites.
posted by sexyrobot at 11:35 AM on January 13, 2018 [5 favorites]


Re: clawsoon: it was sort of a joke — this mechanism has seemingly been co-opted independently, over and over again, such that the particular retrovirus being co-opted might have something to do with the particulars of the result. (It also might not matter)

Not so much “makes us human” in the exceptionalism sense, but more “makes us not-mice/not-flies”.

So, ha ha only serious :-)
posted by apathy at 11:45 AM on January 13, 2018


This immediately made me wonder about drugs that have antiretroviral effects, such as minocycline, and whether they have an effect on brain function. That journal article I just linked suggests that minocycline, for instance, is being investigated as an existing drug that may have beneficial effects on neurodegenerative diseases and neurological injuries, including hemorrhagic and ischemic stroke, multiple sclerosis, spinal-cord injury, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. That's fascinating!
posted by limeonaire at 11:54 AM on January 13, 2018 [1 favorite]


Blue Brain and similar projects have got some unexpected extra work to do.
posted by Segundus at 12:06 PM on January 13, 2018 [1 favorite]


I had only just recently learned about the role of proteins in cementing long term memory, via a discussion of a 2005 case from Germany, where a guy went in for a root canal and came out with anterograde amnesia. But not the famous kind of people like Clive Wearing or Henry Molaison, where the hippocampus is damaged and they have a memory span from seconds to a few minutes. In this case, the hippocampus is fine and the functional memory span is around 90 minutes.

The doctor studying the case found 5 other similar cases, each seemingly triggered by a stressful event. Their theory is that it was genetic, that for certain people the genes that make these kind of proteins get flipped off. So memories go to long-term storage, but instead of getting locked down, they just fray away.

Brains are weird and wonderful objects.
posted by tavella at 12:17 PM on January 13, 2018 [3 favorites]


Blue Brain and similar projects have got some unexpected extra work to do.

Some of us have expected this extra work, which is why some of us thought Blue Brain was oversold. Biology isn't engineering, and while the "wiring diagram" of the brain clearly matters, it's not even close to being enough to understand what the brain is doing. Neurobiologists who study invertebrates with relatively simpler wiring diagrams have known this for 20 years. This study is yet another in a long line of examples which should put the "connectomics first" argument to bed. But it won't, because an unfortunately large fraction of neuroscientists really, really want biological complexity not to matter.
posted by biogeo at 12:45 PM on January 13, 2018 [7 favorites]


Blue Brain and similar projects have got some unexpected extra work to do.

Oh, I dunno. They're using Intel processors, right?
posted by Devonian at 1:09 PM on January 13, 2018 [2 favorites]


All over my head, but who cares, this is super cool scientific news!
posted by xammerboy at 2:45 PM on January 13, 2018


"They can make new copies of themselves, and paste those duplicates elsewhere in their host genomes." This immediately took me to the concept of, "The persistence of memory." And then, of course, the painting, by Dali. However the description almost describes will as well as persistence. A part of our will, or a part of planning on or beneath the cellular level. This is interesting. This makes me think about how we learn and store information. A lot of memory is stored in body tissues, outside the verbal realm, and more into the emotional and accessible with feeling. Like smell being a gateway to vivid memory. You wonder how it all happens and this is part of the mechanism. The fine tuning, perhaps.
posted by Oyéah at 4:20 PM on January 13, 2018 [2 favorites]


I wonder if other cells besides neurons do this (probably nobody has checked). I also wonder about the true function of some heat shock proteins now.
posted by 445supermag at 4:46 PM on January 13, 2018 [2 favorites]


I know it's a terribly common fantasy...

My version is the other way -- a brilliant and influential figure from the past arrives in our society and I get to explain things, especially those that they were in some way responsible for.
posted by Foosnark at 5:12 PM on January 13, 2018 [1 favorite]


LAFORGE: And then if you want to recall any one of those moments, you just access the proper memory circuit.
DATA: My understanding of the human brain suggests that the process is the same for you. Each memory is encoded in chains of molecules. If you want to retrieve it, you simply access the proper RNA sequence.
LAFORGE: Yeah, that's true.
DATA: Then in what way is it different?
LAFORGE: Sometimes there are memories we just can't access at the spur of the moment. For instance, I have no recollection of how I spent my last birthday. Birthdays are important occasions, and you would think that I'd remember how I spent the day, but right now I can't even remember where I was.
Star Trek: The Next Generation, /Violations/
posted by oonh at 8:01 PM on January 13, 2018 [3 favorites]


And the word (RNA) was made flesh (protein) and dwelt among us (our cells).
posted by runcifex at 9:51 PM on January 13, 2018 [3 favorites]


When I was a kid, DNA was like punched paper tape: a series of instructions for building an organism. When I was older it was like a library: a collection of resources that the organism's mechanisms would refer to. Then more recently it was like a computer, and it would intelligently expose, conceal, or sometimes modify instructions as needed. Now it's like what, an office maybe? And Jim keeps sneaking out for a smoke, but he's kept around because he's so good with the accounts; and Donna has a back channel with her girlfriend in the office next door which is the only thing that keeps the place going. Oh, and they subcontracted shipping to some Romanian guys who can't really speak English but they get the stuff delivered anyway, so it's better not to ask questions.
posted by Joe in Australia at 10:04 PM on January 13, 2018 [14 favorites]


But this new mechanism that arc enables shows that the nervous system is capable also of violating the very central dogma of cell biology.

Nope:
The figures in the note are particularly illuminating since it is clear that Crick in 1956 realized that the transfer of information from RNA to DNA is not a logical impossibility. The dashed line merely indicates that as of 1956, the transfer of information from RNA to DNA had not been discovered yet.
posted by kersplunk at 10:09 PM on January 13, 2018


OK, since no one has done this yet, I call dibs on "The Gypsy Retrotransposons" as a band name.
posted by oheso at 11:52 PM on January 13, 2018 [2 favorites]


I'd put off reading the Cell paper until right now, although I've been following the Twitter thread from the corresponding author with interest. I've gotten super interested in RNA localization in neurons over the past couple of years, so on top of this being such a cool finding it is really really exciting to think about for my own future career options of Weird Biological Mysteries To Help Unravel.
posted by deludingmyself at 9:11 AM on January 14, 2018 [3 favorites]


John Baez on Subcellular Life Forms: "Just how much of us is made of retroviruses? It's hard to be sure!" :P
posted by kliuless at 6:29 AM on January 31, 2018 [1 favorite]


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