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Comment by fabian2k | Hacker News Reader

I don't think there's any real doubt that memory is stored in neurons, this is really a fringe theory. I haven't looked at it closely, but my first objection would be that RNA would be far too slow for this purpose. It's also not stable over time, cells have mechanisms to intentionally degrade it. It just doesn't make sense.

There are other weird parts in the blog post, for example claiming that a particular protein kinase is involved in mRNA transcription. That is by definition wrong as a kinase is an enzyme that transfers a phosphate, so a protein kinase transfers phosphates to proteins. And the RNA in this hypothetical memory storage would not be mRNA, as that by definition encodes for proteins.

The person cited in the post is also a crackpot, I've quite a lot of experience with his exploits on the Stack Exchange network. And I haven't found a conspiracy theory yet that he didn't like. This is not hyperbole, I learned of a whole bunch of conspiracy theories I didn't know existed through his posts.

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RNA is literally a form of memory. The question should not be whether or not memory is encoded in RNA, it should be "what are all the ways that creatures with RNA can experience the encoding and decoding of information encoded in RNA?"

Memory is literally everywhere. There is already evidence that the brain can encode memory in dynamic molecular processes, and that interference of those process can interfere with an animal's ability to recall memory.

Your point about timescales is a good one, and provides a clue: the timescales over which a given medium of information can be encoded to or decoded from and over which it decays should provide a clue about the timescales we might expect organisms to experience it in. Mammals and other creatures with RNA experience memory over a whole continuous range of timescales. Why wouldn't RNA, which is optimized for encoding information, be just one of many mediators of memory?

Most of the RNA in our cells simply encodes for proteins. The information is entirely redundant as it is simply copied from DNA. I would not call that memory.

Of course there's a lot of other stuff RNA can do like catalytic activity, triggering RNA interference or reacting to other molecules (riboswitches). But information storage isn't really anything RNA is known for.

Protein formation is well known to be involved in at least some long term memory formation and recall: https://en.wikipedia.org/wiki/De_novo_protein_synthesis_theo...

Although I'd again argue that there is no single "true" medium or mechanism of memory.

I'd remind you that DNA is indeed memory. It's memory whose recall is heavily modified and contextualized by its environment, for example methylation, the topology of how it is currently twisted, the kinds of nutrients available for molecular synthesis, etc.

If RNA mediates memory on a sub-generational timescale, it seems that it'd provide a dynamic, contextual bridge between generational memory in DNA and shorter term kinds of memories that play out over timescales less than an individual's life. So that the molecular formation of a given memory would have a semantic basis in the longer term context. A concrete but way oversimplified example of this might work:

You go through a traumatic experience where you almost die. The specific way you almost die is related to a number of factors involving your ability to run fast enough. The long term memories of that experience are then encoded as proteins by a mosaic of genes related to certain muscles, their shape and size, certain metabolic pathways, etc. The way we might unpack or interpret that memory at any given time/context could be as a gutteral impulse that results in such realizations as "I need to get more exercise" or "my grandparents had heart disease, maybe I should go to the doctor" or "wow I'm sure hungry for fish", etc.

Btw I'm not even arguing that it's as clear cut or simple as that, just sharing how I intuitively make sense of all this evidence and these hypotheses.

I'm not sure you can call DNA memory.

Yes, it contains information. But you can't write to it.

Of course you can. See, for example, the Lambda switch. https://en.wikipedia.org/wiki/Lambda_phage#Induction Yeast modifies its own DNA by copying one of two passive templates into an active region to switch its own internal mating state.

Viruses integrate into the human genome, then decay and eventually become fodder for new regulatory regions and genes.

During human life, your genome is mutated, and your body repairs it, sometimes making mistakes, which are permanent (and passed down to your children if it happens to the germ line).

I could go on...

Ok, DNA changes occur, but physiological writing to the DNA does not happen in humans. I'll give you DNA repair, BCR/TCR rearrangement, meiosis, and also the more recently discovered LINE-1 retrotransposons - but they occur at specific times and usually in a random fashion. I don't think this fits any idea of what memory is.

If you're saying it's theoretically possible, I would agree that it might be, and that there is a potential for DNA to be memory. But to claim that DNA is memory without a known write process is premature I think.

Yeah, I agree- you have to stretch the concept of "brain memories" pretty far to accomodate epigenetics.

For most eukaryotic organisms DNA it might not be "random access memory" but it contains a record of genes that somehow managed to get through the selective pressures they were subjected to over countless generations. I'd say that this information is an imprint of history, and is memory.

My hunch is that you're thinking of memory as being equivalent to RAM in a computer. So I'll remind you that read only memory is still memory.

Some microorganisms, like viruses, do directly modify DNA. That's where CRISPR came from.

I'd encourage you to check out the full range of definitions of the word "memory".

Read only memory was written once.

An imprint of history is not memory, in much the same way that fossils, stars, the environment is not memory. Human DNA has not been written to. It is edited in only very specific circumstances - DNA repair, TCR/BCR recombination, meiosis and interestingly, and possibly relevant - LINE-1 transposons in neural tissue.

Why not? They encode state in a way that is stable over time. Any medium that preserves state over time can and likely does function as memory in some way or another.

At any rate, DNA encodes useful information related to how an organism's ancestors were able to survive their environment. If you prefer not to call it "memory" for semantic reasons, I don't really care too much, although my opinion is that memory is too deep of a concept to be narrowly confined like that. Nevertheless, even if you don't call DNA memory, it doesn't change my point in the comments above, which is that the information encoded in DNA is directly relevant to any survival related memories, and so it would make a lot of sense if such memories were formed in direct, physical reference to that information. Seeing as how it's been shown that protein formation is involved in memory formation and recall, and seeing as RNA is how proteins get their molecular structure, it's not a far reach to see the possibility that RNA is a contextual bridge for memory to be encoded in reference to survival related information provided by DNA.

None of this requires that DNA be writable in the same way that transistor based me let is writeable. DNA is written through a probabilistic, distributed process, but it still encodes information about the molecular tools its carriers successfully managed to survive and reproduce with.

WTF is "generational memory"?

A lot of biologists these days use "generational memory" to refer to epigenetic configurations that are heritable, but in the context of my comment I was using it more to refer generally to information that is typically modified over multigenerational timescales. My point was to frame RNA as a kind of intermediary between longer term and shorter term mediums of memory.

So as an simplified analogy, the DNA would be like a dictionary of common words that could be used to encode a meaningful story about something the organism has experienced. The RNA would be like the handwritten copy of each word as the story is written down on a piece of paper. The paper with the handwritten story is analogous to the proteins that have been shown numerous times to be involved in long term memory storage and recall.

the idea would be that learned behavior which is not genetically encoded is instead passed down in the form of specifically structured information molecules.

I don't think they mean the literal information encoded in the RNA. The fact the RNA exists is, itself, a signal. It shows that there was previously a signal that caused the RNA to be transcribed. And then once you start including concentrations and degradation times for all the various things involved in the system...

Well there's lots of information there which can be used to infer aspects of previous states. I assume it's more of this aspect that is being referenced, rather than what is encoded in the RNA.

98.8% of our DNA is identical with a chimpanzee, and 60% common with a fruit fly.

I am personally interested by the 'RNA Computer' hypothesis which posits an additional layer of differentiation in computations performed by interacting RNA.

I have also read of experiments where memories (learned behaviors) were transplanted by injecting ground-up neural material. Flatworms were the subject I think.

Of course this is all near the edge of mainstream, but I think genuine science demands openness to new ideas.

That's on a GENE level. On a nucleotide base by base we are very different.

From what I understand, most of the RNA just sits there, and people are speculating its role. Did I get that part wrong?

no. RNA is a very active molecule. It rarely sits around, nearly all organisms have RNAses which are eating RNA that is sitting around.

Yes... any human instinct, like the fear of spiders that you can observe in a days old baby, is a form of memory, and DNA/RNA could certainly be a storage mechanism for these.

Evolved behaviours are arguably the opposite of memory: it's the RNA of the people who avoided the spiders that got reproduced.

I mean... By definition isn't that a form of memory?

Whether it's learned or you were born with it doesn't really change that the information had to be stored and transferred which is...memory?

I guess what the OP means is that one definition of memory is that it is generated by your experiences. In this case the memory is the lack of experience (with a spider), because those genes keep you away from spiders. So it is possible that you can develop the RNA without seeing a spider, hence the opposite of memory.

In this case no information was "stored" after meeting a spider or getting bitten by it. Rather people who (by accident) had predisposition to avoid spiders happened to survive better.

Selection may be a part of it, but you may be wrong in saying no information was stored.

I remember hearing about this one really interesting experiment where they would expose mice to a specific scent (I think it was citrus), and then give them a shock. Obviously after a while, when the mice smelled that scent they would get nervous and try to hide (or something along those lines, this is from memory so forgive any erroneous details). They then bred those mice and separated the offspring from the parents so that there was no way they could learn about the smell from them.

When they exposed the offspring to the smell, they reacted in the same way their parents did. Without ever having been exposed to it before, or knowing about the shocks. Pretty interesting stuff.

The article points out that while far from being widely accepted, this theory is getting a new look because of some experimental evidence that supports it.

> I don't think there's any real doubt that memory is

> stored in neurons, this is really a fringe theory.

All theories are fringe theories at first, that's where they start (as hypothesis before there's any experimental evidence or mathematical proofs).

I would agree that there is little doubt that memory is stored in neurons. However, that does not exclude some memory being stored elsewhere. It's generally accepted that the brain stores memories first in short term memory, and then after a time some of those memories are stored in long term memory, with the memories chosen according to some criteria.

I could see RNA memory as a third stage of memory storage. Memories that the brain views as high impact to the species according to some criteria might get copied from long term memory into RNA memory to be passed on to future generations, accessible only by subconscious.

That link to the experimental evidence is just an article. And that article mentions experiments by David Glanzman, but I can't find any publications by him on Pubmed in the mentioned timeframe. I don't see any new experimental evidence here.

>that does not exclude some memory being stored elsewhere

If RNA is not simply the conduit between DNA and protein, but the original biological operating system, from which many functions have been refactored out to DNA and protein it's fascinating to think about what other functions may have existed and may still exist entirely in RNA.

I like to assume that RNA is the original biological information store, the original structural material and the original catalyst. DNA is the long term cache version of RNA information, and protein the improved structural and catalytic material. The information in RNA can be translated directly to and from DNA, and there is an interesting idea that the mapping from RNA codon to amino acid may have began directly on the RNA strand, some RNA sequences seem to have an affinity for certain amino acids.

https://www.ncbi.nlm.nih.gov/books/NBK26876/#_A1136_

But RNA rapidly degrades. It would need a mechanism of error correction and regeneration.

That's not how reproduction works though. Losing a limb has zero impact on that person's germline cells.

From my reading it seems as if a rather large subset of neurologist do not believe that memory is stored at all. In fact, I have a book written by a computer scientist and neurologist, intending to be a very long argument for why memory must be stored in the brain, weather by neurons or something else. I happened to read a review published in a neurology journal that was brutally dismissive of the book and near made fun of it. Despite the fact that the reviewer failed at providing any answers for logic problems outlined in the book. The reviewer even mistook a logic gate feed back structure for a dual input (the review quoted a study done that cut the “front processor” of the visual cortex to prove that a back connection also existed, I.e. the poor monkey did not lose sight until they severed both the front and back of his brain.)

The claim as I understand it is that there is no “memory” at all. What we experience as memories are simply input parameters that signal our brain to begin a particular function. In the way a neural net does not “remember” the training data but carries out what it “learned” anyway. I have problems explaining this idea as I think it is full of holes and would require some fundamental changes in how we think about feedback structures (I mean this neurologically as well as mathematical/computational).

Either way if most people don’t doubt memory storage in neurons then they are very quite about it. I’ve rarely ever read an argument for memory storage mechanisms in the brain. A good reason for this is simply the question: Where is it then? Neurons individually can’t really provide this sort of expansive data storage. And what they seem to be able to account for is too little and too widely spaced apart. Interestingly this spacing also provides a counter argument against the complex processing that would be required if there wasn’t a memory mechanism.

Personally I think the dismissal of memory comes with a lot of hubris attached, as well as a total lack of understanding information theory. Information theory itself seems to be popularly bemoaned by neuroscientist as well. But it’s hard to see the alternative and is a bit paradoxical since the only way I can seem to understand the “no memory” claim is by using a computer neural net metaphor.

When a neural network "learns" something, it ends up with knowledge encoded in the network parameters. If that's not memory, we're using terminology in a different way.

I don't disagree that this is a possible way of viewing memory. I'm am simply restating the argument that I've heard the best I know how. That usually comes with a "memory is an illusion" caveat. If you want to argue that that is memory instead of a typical "hard drive" sort of situation then sure, okay, but this is not what most people think of when they think "memory". They believe it is something in which individual memories could perhaps be extracted, implanted, etc. I personally believe it's a valid theory, however it lacks experimental evidence and has yet to account for the fact that we can recall individual "training data". To account for this I do think it would require fundamental changes in how we view "computation". If you believe that artificial neural network structures can account for the brains real neuron processing I suggest checking out the book I mentioned, not because it cant be true but that there are still big unknowns left to discover before we know for sure if this is correct.[0]

[0]Memory and the Computational Brain, C. R. Gallistel and Adam Philip King

You can read the main thesis here https://onlinelibrary.wiley.com/doi/pdf/10.1002/978144431049...

I have no idea; this is not my field. Just pointing out it's quite possible people are just talking through each other.

Human language is like that, full of ambiguity, of implicit baggage.

If you feel "memory" means a recording of an event, or a photo book, then faced with the discovery that brains actually don't work like that you may want to state "neurons don't store memories!".

I am sorry in advance if I misunderstood your sentence.

Are you claiming there is a large subset of neurologists how do not believe in long-term potentiation and other plasticity processes driving long-term retention of memoranda? If so, could you please show me to these crowds?

I'm sorry, after the fact, if I've been unclear.

Long-term potentiality is not the point of disagreement. The disagreement is that individual memories are not recalled, as they are not stored, per se. The idea is that neurons acclimate to inputs, so that when we "recall" them we are not retrieving a "memory" from a storage location but instead are being activated in a way that allows us to preform a learned action.

I imagine those marble/cardboard diagrams of logic gates, where the cardboard flap will be left in a particular position after a marble has passed. In this way you can add numbers by dropping marbles into the appropriate input slots. Yet in this way, one could not derive prior calculations, as it does not store this information anywhere.

Can you name the book and the reviews? I'd like to read more but don't know which terms to Google.

Sorry about that. It was late when I posted this.

Book: [0]Memory and the Computational Brain, C. R. Gallistel and Adam Philip King

You can read the main thesis here https://onlinelibrary.wiley.com/doi/pdf/10.1002/978144431049...

Review: https://www.researchgate.net/publication/262093114_Man_as_Ma...

Also please take all my comments with a grain of salt. I am not expert, I'm just trying to restate what I've read and understood.

I was initially skeptical about your statement that Ron Main is avcrackpot, since he comes across as highly intelligent and very well versed in physics and mathematics. However, he also thinks there is a sufficiently strong axiomatic system to resolve all arithmetic questions, and claims Godel did not disprove this. That is indeed quackery. I guess he is one of those geniuses that went off the deep end.

Hard drives couldn't possibly contain operating systems - they're much too slow to run them.

Good comment, but it might be a little too cryptic.

Another attempt:

Straw man:

Phones are too slow and too dangerous to be used as a real time vehicular traffic indicator. If drivers were to text their location back to google every 10 seconds, they would have too many accidents. It isn't even possible to look up the location on google maps and then text a geocoordinate in 10 seconds. Drivers just wouldn't do this anyway because there is no incentive for them to do so. Google would have to pay drivers $2 or so for each location bulletin. That would cost billions and google would go bankrupt.

Are the solid state hard drives of today, faster than the RAM memory from the 1990s?

EDO RAM performs quite comparably to a modern SATA SSD, I think it topped out at around 320MB/s

I don't think it's the bandwidth that was being opposed but the latency. The cell can run multiple transcriptions at a time just like we can increase the number of memory channels, but each one of those molecules is still waiting around for the random chance for their next molecule to physically appear on the reaction stage.

There are a few Cell papers on heritable RNA-mediated behavior change in C. Elegans using siRNA[1] and piRNA[2], both with strong evidence. While the author may be a crackpot and the specific ideas may be wrong, there is strong evidence that RNA-based memory exists in some creatures.

[1] https://www.cell.com/cell/fulltext/S0092-8674(19)30448-9 [2] https://www.cell.com/cell/fulltext/S0092-8674(19)30552-5

Memory isn't stored "in neurons". It is stored in electrochemical oscillations created by interactions between a plethora of different biochemicals.

Yes, I do not consider myself an expert, but reading this post just makes me think it is not EVEN wrong. It looks like self contradictory gibberish. I worry that a well trained ML tool could generate a million such posts of equally illucid commentary without substance. Whether the purpose of such discussion is to slow down understanding and scientific inquiry, I don't know, but the confusion sowed appears to have that effect.

This is not a GPT.

But it is a thing to write in GPT style.

GPTs want to be human like, for funding.

Chess AI's still can't play like a human (but people are working on it), chess AIs were designed to solve problems.

The easiest way to pretend to write 'human like' for a computer is to say as little as possible with tiny contractions and poetic words.

Some humans similarly do this, if you get paid by the word it makes sense.

OP style fails on this topic because it's so technical.

GPT-3 wasn't even designing to mess with our heads, but it does, wait till someone designs it to. It's very possible, because it's not about intelligence, making it worse is easier than making it better. If you use engagement as a measure of 'success' you can see you can evolve GPT-3 quickly to a worst nightmare. (It is already a nightmare)

Exactly, I didn't think that it was auto generated, but as you say it is exactly the sort of non-sense that could be generated... of course you can have more than a million GPT monkeys so in this case one of them might actually come up with something clever!

> The person cited in the post is also a crackpot

My first reaction was to downvote your comment for the ad hominem, which doesn't contribute to the discussion. But I can see you are giving consideration to the article, and want to discuss it further - it's just that you haven't got enough out of it to make much of a start, and so this is your conversation starter.

I'm assuming you've labelled this a "fringe theory" by a "crackpot" not to be nasty, buy in order to start a conversation.

Let's start with your statement:

> I don't think there's any real doubt that memory is stored in neurons

The question is "how?". The article is postulating that each neuron is a computer, and RNA is a storage medium.

You say "my first objection would be that RNA would be far too slow for this purpose." That's because your thinking about RNA is limited to what you understand about RNA. You've learned about mRNA, which is one application that uses this molecular format, but it's not the only possible application.

The article suggests that the data transmission protocol which leads to thought and/or behaviour could be electrical, through simultaneous aggregated neuronal RNA based data processing.

Read the section he quotes from Ron Maimon, subtitled RNA ticker tape. What do you make of this statement?

"The RNA in a cell is the only entity which is active and carries significant bit density."

There are a lot of claims without any evidence in that blog post. "The RNA in a cell is the only entity which is active and carries significant bit density." is one of them.

DNA certainly encodes for a significant amount of information as well. And why not proteins, there are a lot of proteins in a cell and you can also modify them in various ways. A cell has an enormous amount of state, any of it could theoretically store information like memory. There are a lot of different molecules active in a cell, in various modification states, at various locations, and all of that could encode information.

What this blog posts doesn't provide is any experimental evidence, this is a pure thought experiment. If RNA were to actually store memory, that would be great. Because determining the RNA sequences inside a cell is something we can do.

I was going to say, that the DNA in all the brain cells is identical and unchanging, so it cannot possibly record memories. But I decided to google first, and found this: https://onlinelibrary.wiley.com/doi/full/10.1002/dneu.22626

It appears that the brain cells in particular actually do develop significant changes to their DNA.

He wrote "active and [has encoded information]".

mRNA and tRNA move, so "active". Ribosome is also (re)active, and "the ribosome is itself composed of both RNA and protein, likely reflecting its own descent from an RNA world." [1]

[1]: The Ribosome Moves: RNA Mechanics and Translocation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581036/

> DNA certainly encodes for a significant amount of information as well. And why not proteins

True!

> What this blog posts doesn't provide is any experimental evidence, this is a pure thought experiment.

Yeah, so?

> My first reaction was to downvote your comment for the ad hominem

Why? Ad-homs aren't necessarily bad, it's contextual.

It’s lazy and uninformative to call someone a crackpot.

More informative to state the views you disagree with and say why.

It's entitled to demand someone provide that, or be "lazy". Inform yourself - checkout said users post on stack exchange.

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