RNA Memory Hypothesis

https://scottlocklin.wordpress.com/2021/02/03/rna-memory-hypothesis/

by nahuel0x • 5 years ago

156 112 5 years ago

scottlocklin.wordpress.com

nynx3• 5 years ago

Very interesting, but also worrying, in a way. If neurons are actually reasonably large, complex computers in their own right, brain emulation is much further off than some people are thinking. It's possible that ASC brain preservation doesn't preserve the internal details necessary if this hypothesis ends up being true.

asdfasgasdgasdg• 5 years ago

To be fair it's more than just possible that ASC brain preservation doesn't work even under any other hypothesis of cognition.

nynx3• 5 years ago

That's true. I think the fair way to put it that it's possible that ASC preserves the necessary data to simulate a brain.

sailingparrot2• 5 years ago

This is the opposite of worrying.

nynx3• 5 years ago

How so?

subroutine4• 5 years ago

This is nonsense. Evidence collected over the last 40 years have detailed how memory is encoded by synaptic weights, but the premise...

"there’s no obvious way for all that sensory data to be captured in synapses as long term memories"

...just ignores these findings. The model described in the article on the other hand, has never been observed. At the least, if you are going to propose an mRNA hypothesis don't use "T" as one of your RNA bases.

AstralStorm2• 5 years ago

What is the physical realisation of the synaptic weight? (Here's trouble, we do not know. It's not in just connectivity or myelination.)

jrussino2• 5 years ago

See my response to your sibling comment; clearly we still have a lot to learn, but there is already some understanding of the biological mechanisms of synaptic plasticity (which I think is what the parent comment is referring to as "synaptic weights").

https://en.wikipedia.org/wiki/Synaptic_plasticity

subroutine4• 5 years ago

The physical realization is the number of postsynaptic receptors. In terms of fast excitatory transmission it is the quantity of AMPA receptors. You can potentiate or depress synapses by controlling the amount of these receptors. This has been demonstrated in vivo, and in cell culture. We are at the point where we can manipulate the strength of individual synapses.

Here is a nice review article:

https://royalsocietypublishing.org/doi/10.1098/rstb.2013.013...

titzer• 5 years ago

have detailed how memory is encoded by synaptic weights

Synaptic weights is our computational model of neural networks that seems to work pretty well. But this is a model. No one has discovered the biological mechanism by which synapses are "weighted". The actual computation going on in a cell is totally based on chemistry.

There are a lot of different specialized networks in human and animal brains that don't necessarily translate easily to "weighted synaptic networks" all that well. For example, networks that process audio information have been shown to recognize individual frequencies (in fact, they pretty much solely do this!) Such networks seem to be primarily based on the firing rate across a synapse. For such networks is seems more reasonable to think of neurons as signal processors whose internal computation is more based on the time domain, e.g. some kind of Fourier transform-equivalent.

In short, I think you should put less weight (pun intended) in our computational model of neurons (link weights) and look more at biology.

jrussino2• 5 years ago

It has been over a decade since I studied neurobiology, but from what I recall we do have at least some understanding of how synapses become "weighted". For example: long-term-potentiation, the idea that "neurons that fire together wire together" https://en.wikipedia.org/wiki/Long-term_potentiation https://www.khanacademy.org/test-prep/mcat/behavior/learning...

wombatmobile5• 5 years ago

Perhaps mRNA are performing the synaptic weighting.

After gene expression, mRNA's are left floating as debris in the cytoplasm, until they are cleaned up and expelled. If the gene expression continues chronically, the same mRNA sequences will populate the same cells, transiently, for as long as the gene expression recurs. What if the mass of the mRNA sequences influences the electrical conductivity of the cell e.g. functions as a form of antenna. In the aggregate, cells with mRNA populations e.g. neutrons active in particular thought patterns, might have stronger antenna, or differentiated electrical characteristics, and hence influence thought more or less in the network, for the duration of the gene expression.

subroutine4• 5 years ago

We have discovered it, and understand it quite well. It's fairly simple, at the level of the synapse there are ultimately three ways to evoke increased firing in the downstream neuron: (1) the upstream neuron's axon can release more neurotransmitter, (2) the upstream neuron can establish more axon collateral connections with the downstream neuron, or (3) the downstream postsynaptic membrane can express a greater number of neurotransmitter receptors.

tokipin• 5 years ago

One of my theories is that this (or similar virus-like mechanism) is how some memories are transferred to offspring. The reasons are:

* Prodigies which happen to be good in a field related to what their parents are good at. Often the wording used indicates a memory-like reason. For example, finding the rules of chess "familiar."

* Embeddings in machine learning, which allow encoding of high-dimensional information in a low-dimensional space. This would imply that humans have a somewhat-shared embedding space at some "layers". It's interesting to wonder how similar this space would be across various animals, as it would effectively be an evolved language.

* Other more subtle things, like the "cultural memory" of a society.

One question would be what types of time scales these memories survive across. Maybe some forms of instinct are deep memories that have been directly encoded in DNA.

plutonorm2• 5 years ago

I had to scroll a long way for an intelligent contribution!

https://www.scientificamerican.com/article/prehistoric-virus...

I also wonder if and to what extent this information can transfer between individuals?

I'm reminded of the Jungian collective unconscious.

You're going to think I'm a kook now, but, there's also a panspermia angle on this. Big ifs here, but. If panspermia is true. If evolution on earth is tied to evolution of life in the wider universe via transfer of genetic material. Then it could be possible that the code in which memories (or a learned manifold, encoding useful generalisation) are encoded is compatible with life here today. You could conceivably get not just morphological/physiological changes in terrestrial organisms through viral horizontal gene transfer, but also transfer of cognitive strategy via the same mechanism. X-files kinda stuff. All kind of unlikely, but an interesting possibility.

type02• 5 years ago

But that would imply that evolution was "directed", which I think is proven that it's not. The role of viruses in evolution is almost mainstream now, it is much more likely that virus was just a method for ancient extinct organisms to exchange genes, sort of proto-sex, and not anything else outlandish.

eightails• 5 years ago

Prodigies which happen to be good in a field related to what their parents are good at. Often the wording used indicates a memory-like reason. For example, finding the rules of chess "familiar."

I think this could be equally well explained through 'nurture' rather than 'nature'. If a child's parents are skilled at chess and play it often, the child is going to be exposed to it at a much earlier age and for more often than a child of non-chess-players, making it more 'familiar' and 'intuitive'.

To be honest I'm not super familiar with the research in this area but my sense was that there's some amount of experimental evidence for both genetic and environmental factors playing a part together, rather than just one or the other. It's very interesting though -- might have to go do some reading.

dannyw2• 5 years ago

It would be interesting to see whether this kind of relationship has been seen where parents were separated (eg died).

fabian2k4• 5 years ago

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.

blurbleblurble5• 5 years ago

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?

fabian2k4• 5 years ago

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.

spoonjim• 5 years ago

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.

bencollier49• 5 years ago

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

wombatmobile5• 5 years ago

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.

blackrock3• 5 years ago

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

wombatmobile5• 5 years ago

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."

fabian2k4• 5 years ago

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.

Chris20482• 5 years ago

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

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

Communitivity• 5 years ago

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.

fabian2k4• 5 years ago

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.

cma• 5 years ago

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

aj33• 5 years ago

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

monkeycantype• 5 years ago

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_

kurthr2• 5 years ago

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.

aaron695• 5 years ago

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)

TaupeRanger• 5 years ago

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

yters2• 5 years ago

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.

Bodell4• 5 years ago

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.

knolax• 5 years ago

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

ithkuil2• 5 years ago

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.

Zebrakopf• 5 years ago

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?

shenberg• 5 years ago

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

blackrock3• 5 years ago

What I find fascinating, is that babies are born knowing how to suck.

How? It’s not something you can teach them. They say it’s an innate thing. But what does that even mean.

I think babies are born with this programmed into them. Like a genetic type of memory.

Then over time, the neurons establish more connections, and learn more advanced things. But the spark for that was set off at birth.

woeirua• 5 years ago

I agree that there must be some genetic component to it, but if that were the case then by the law of large numbers we should have seen some counter examples by now too, i.e. babies that lack the instinct to suck or cry, etc. It'd be interesting to know if they show any obvious genetic changes that could explain that behavior. Casual googling hasn't turned up anything, but I'm sure someone has looked into it somewhere...

aeternum• 5 years ago

Behaviors like sucking and grasping are considered reflexes. Those reflexes are present in all mammals and are relatively primative, the more modern parts of our brain eventually learn to suppress them and they typically disappear in most humans after around 1 year old.

Interestingly, patients with brain lesions in certain places or with diseases like parkinsons sometimes lose the ability to suppress these reflexes.

More info: https://www.ncbi.nlm.nih.gov/books/NBK395/

blobster• 5 years ago

You might want to look into ethology, which studies innate behavior like the one you referenced.

https://en.wikipedia.org/wiki/Ethology

blackrock3• 5 years ago

accounts of people “inheriting” memories after organ transplants

This is interesting.

So if you transplant a liver, you get memories of the donor’s eating habits? LOL.

type02• 5 years ago

LOL indeed. And if you eat an apple, you would become an Apple fanboy.

pippy• 5 years ago

There's clear evidence of epigenetics playing a role in brain activity, though these are more linked to hormonal responses such as stress. It's also been proven that RNA transcripts are used to trigger maternal instincts when a zygote is present in a mother: https://en.wikipedia.org/wiki/Epigenetics

Scientists have already modeled memory retrieval using current neural network models. There's literally videos on youtube demonstrating this. I'd be surprised if RNA was used to encode memories to the extent OP is suggesting: there would have to be a mechanism for storing this RNA inside cells or there would be evidence of random strands of RNA floating around in the body. We would have been found it a long time ago, and scientists would also be able to decode it if these strands of RNA were standardized and could be transferred person to person.

Though the way evolution works and how complicated the body is, it could be occurring in a small sub process in a neurons somewhere in the body. though this would likely be tied to hormonal responses or something equally boring.

phyalow• 5 years ago

Human memory is truly fascinating. I recently was trying to remember the name of a software vendor sales contact who I dealt with early last year.

For the better part of the past week, try as I might I couldn't remember either his first name or last, but I had a vague feeling about the "fit" or "taste" for lack of a better word of his name. After a few days of conscious effort, yesterday I remembered his first name spontaneously and then suddenly his last name too. Almost like a AWS Glacier request.

avaldeso• 5 years ago

After a few days of conscious effort, yesterday I remembered his first name spontaneously and then suddenly his last name too.

A background process completing and notifying the result to the frontend.

mjfl• 5 years ago

RNA has a half life of 8 hours, so uh... no.

Edit: 10 hours... https://bionumbers.hms.harvard.edu/bionumber.aspx?id=104747

ajb• 5 years ago

A similar idea was discussed in 2018: https://news.ycombinator.com/item?id=16139798 "Brain Cells Share Information With Virus-Like Capsules". It would be interesting to know how the science of that article panned out.

greyface-• 5 years ago

A relevant paper (authored in part by the subject of the Atlantic piece being discussed): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884693/

nabla92• 5 years ago

I think RNA memory hypothesis is not popular because there exist better, less controversial memory systems in the cell. For example gene regulatory network or bioelectric circuits in the cell (or, more likely a combination of them).

Biswas, S., Manicka, S., Hoel, E., and Levin, M., (2021), Gene Regulatory Networks Exhibit Several Kinds of Memory: Quantification of Memory in Biological and Random Transcriptional Networks, https://www.cell.com/iscience/fulltext/S2589-0042(21)00099-7

AstralStorm2• 5 years ago

The bigger problem with most of these memory systems is eliciting correct behavior of amnesia in case of both electric and chemical shock, as well as permanence or lack of permanence of those amnesic inputs.

nabla92• 5 years ago

Short term memory and problems with recall are different issues from long term memory.

mrfusion2• 5 years ago

I would think dna methylation would be a better candidate.

mrfusion2• 5 years ago

It’s definitely fun to think about. Are vesicles in synapses really the whole story? It’s amazing how much we don’t know.

daemonk• 5 years ago

We've sequenced a lot of RNA in the past decade. A lot of that were extracted from neurons. I don't think we've seen evidence of this memory storing function through sequencing.

robbiep• 5 years ago

Not to mention the persistence of these memories over long periods of time, or the protein infrastructure that would be needed to decode them in real time

eternalban2• 5 years ago

Assuming this speculation is correct (just for fun), then we can wonder about the memory model of the body.

This would be a distributed memory system, as obviously not all RNA molecules in the body could transit from memory state M0 to M1 spontanuously. So there has to be a consensus and propagation mechanism. Wouldn't it be cool if it turned out to be something like CRDTs?

yters2• 5 years ago

Very weird

Maybe the ancients are right and the soul resides somewhere in the liver. Don’t laugh; people have led normal lives with giant pieces of their brain removed, but nobody has survived the death of their livers. The former fact; normal people getting by without much brain tissue, at least, ought to be the end of the argument: purely Hebbian models of the brain are obviously false.

breatheoften• 5 years ago

There was a really interesting episode of the mindscape podcast[0] recently which discusses a system in Planaria where the expression of the way the worm grows (with one head or two) is found to be encoded in an electronic structure within the tissue of the worm -- rather than within the worm's DNA.

In a very real and observable sense, the 'blueprint' for the target worm is stored in the tissue system rather than as a 'plan' stored in the DNA itself. I think it feels surprising to see something that seems a lot like 'memory' influencing the action that results in the expression of the complete organism via the cellular level processes in this way.

I find it easy to postulate from the example of planaria that analogous 'memory encoding' systems probably exist in all sorts of cellular systems ... though I think the information theoretic reasoning referenced by the participants in that podcast for how life creates and operates these systems makes it likely that 'the existence of information storage and retrieval' in a cellular system is not at all required to imply that 'this kind of system is therefore the storage model for long term cognition'.

[0] https://www.preposterousuniverse.com/podcast/2021/02/01/132-...

pharke• 5 years ago

Michael Levin's work seems incredibly important and one of the most likely truly breakthrough discoveries I've heard of in a long while. I'm not so sure about RNA memory storage but the point about unicellular life possessing some form of information processing ability is certainly something more people should be thinking about. The fact that such complex behaviour is possible on that minuscule of a scale means there is really something special about the computational properties of organic chemistry. I can't help but feel a lot of the hardware that makes up macro scale life is really just used for dealing with the inefficiencies of getting so many individual cells to cooperate and interface with their environment in a coordinated manner. Single celled organisms have a shorter round trip time for their decision - action - sensation loop but are generally unable to make major modifications to their surroundings by acting or moving. Nonetheless, I think they're a lot smarter than we give them credit for.

jodrellblank2• 5 years ago

"The fact that such complex behaviour is possible on that minuscule of a scale"

It's a small scale, but it's not empty; ask yourself how many atoms are in a human cell, then check this link for an answer and see how close you are: https://www.thoughtco.com/how-many-atoms-in-human-cell-60388...

jodrellblank2• 5 years ago

I had surgery which left me with scar tissue; years later another surgery removed it, and I carefully padded and taped over it, hoping it would settle at skin level. It pushed on, I got nurses to apply chemical cauterization, it still filled out until it was back the same as before, then stopped. Maybe 1 cubic cm of flesh. That's not in my DNA, I wasn't born with that, why did it grow and why did it regrow both times differently to how I grew from conception?

See also this talk by Prof. Michael Levin, same guy as your podcast - https://news.ycombinator.com/item?id=18736698 - titled "What Bodies Think About: Bioelectric Computation Outside the Nervous System", including from the top comment by keithwhor:

" - Organism morphology seem to be highly dependent upon large-scale electrical potential differentials between cells

- These electrical networks are primarily regulated by cell-to-cell gated ion channels; simple chemical pumps (the same types of membrane proteins that control faster-acting electric potentials that enable muscle contraction, neural activity)

- These networks and patterns of bioelectric signalling have stable memory (once a pattern between cells is induced, it remains stable) and are responsible for driving "subroutines" of large groups of cells -- morphological gene, protein expression downstream of this "

ckemere• 5 years ago

As someone who's lab studies how memories are stored and recalled in the mamalian brain, I was excited to see a headline in the top list of Hacker News. Unfortunately, I was disappointed to see what was actually there.

As is often the case, this article conflates some ideas that are truly remarkable and interesting (how are memories stored?) and mixes them with very strong statements that are clearly wrong. In this case, it is clear that synapses (connections between neurons) HAVE to be involved in memory, as the only way that a memory can ever be expressed is if a neuron triggers another neuron, etc, down the chain to a muscle. (OK, thoughts don't necessarily involve muscles, but to show your thoughts to the world.) And if synapse *dynamics* are not involved in memory, then either they never change, or they change randomly, both of which will lead to problems. (That's an exercise left to the reader.) So dynamic synapses are involved in memory, definitely, no question.

The article mentions a couple of things that are interesting misdirection, like invertebrate models where "memories" are transmitted via serum. These are super cool experiments, but these are memories in the same way your immune system "remembers" a virus. Despite Tonegawa's best efforts, I think most researchers are quite confident that recalling your memory of last Christmas uses a very different mechanism than your immune system does to generate imagined tastes and smells and warm feelings.

The article also talks about RNA ticker tapes. There is some super cool neuroengineering research around the idea of making a designer protein that would record a neurons activity in nucleotide chains as a readout. Definitely worth a dive if you're interested.

And how neural activity drives synapse dynamics is a very big open question. It's known to involve protein synthesis (pkm-zeta, anyone?), so RNA is definitely involved.

Finally, for those curious about how memories work, look up the "cognitive map" or the "index theory of memory".

garblegarble• 5 years ago

That's very interesting, thank you! Do you know of any good video series / lectures that would be a good primer for a layperson on the topics you touched on?

mjg59• 5 years ago

People love bringing up E. coli whenever this sort of thing comes up, but it's not a compelling argument. It generally refers to the observation that if you have a bacterium swimming towards something that's bad (ie, an increasing concentration of a toxic molecule), it'll tend to start swimming away. The obvious implication is that the bacterium has to remember that it's trying to swim away from something in order to keep doing so.

In reality, we've had an alternative explanation for about 20 years. The chemical receptors that respond to the molecules E. coli wants to get away from activate and generate a cascade that causes the flagella (the stranded "tail" molecules that allow them to swim) to start rotating in the opposite direction. This causes them to become tangled, and this results in the bacterium moving around randomly rather than making any progress in one direction. If it heads away from the noxious source, the receptors stop activating, the flagella start rotating in the correct direction, and it heads off in a straight line again.

But what about the memory? If the bacterium didn't remember what happened, isn't there a high chance that it would just end up doing the same thing again? Yes, but we don't need to bring RNA into this. One of the molecules involved in the cascade is activated by phosphorylation - once phosphorylated, its sensitivity changes. Over time, another molecule dephosphorylates it, but this altered sensitivity means the bacterium is more sensitive to the noxious molecule than it was previously and biases the bacterium to move away.

So "memory" in this case is actually just a modification of the gain in the response to a stimulus. Does it demonstrate that responses can be influenced by something that happened in the past without requiring a nervous system? Yup, absolutely. Is it something that gives us a better understanding of how rich long term memories are stored in the brain? Not really.

(Source: my first attempt at a PhD was working with https://en.wikipedia.org/wiki/Dennis_Bray who did a bunch of the computational modelling that demonstrated we didn't need anything overly complicated to understand what was going on here. Absolutely wonderful scientist, but I fell out with departmental IT staff over network security stuff. Ironic with hindsight. Also, this is my recollection from almost 20 years ago, so details may be inaccurate)

RNA Memory Hypothesis

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