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Memory transfer between snails challenges view of how brain remembers (statnews.com)
364 points by laurex 9 months ago | hide | past | web | favorite | 124 comments

> Glanzman’s experiments — ... — involved giving mild electrical shocks to the marine snail Aplysia californica. Shocked snails learn to withdraw their delicate siphons and gills for nearly a minute as a defense when they subsequently receive a weak touch; snails that have not been shocked withdraw only briefly.

> Ryan knows Glanzman and trusts his work. He said he believes the data in the new paper. But he doesn’t think the behavior of the snails, or the cells, proves that RNA is transferring memories. He said he doesn’t understand how RNA, which works on a time scale of minutes to hours, could be causing memory recall that is almost instantaneous, or how RNA could connect numerous parts of the brain, like the auditory and visual systems, that are involved in more complex memories.

It sounds less like the standard definition of "memory", and more like RNA stores/caches the response mechanism of a pain receptor. Thoughts on that interpretation (I'm a layman on these subjects)?

> RNA stores/caches the response

tomato / tomato -- right?

what is storage/cache if not memory?

I would argue there is no "standard definition of memory" as it relates to beings / consciousness / qualia.

Even if we limit "memory" to what people have when they reflect on past events.. we don't know /what/ that is; where it is stored, why it is so error prone, etc.

we also don't know much at all about the mechanism behind RNA; we have mapped some genes but afaik, the mechanism for how those sequences actually do anything at all, yet alone things in particular is a huge mystery.

It's interesting how most "skepticism" is exposed for what it truly is, that being unwarranted assumptions and semantics that prop up weak models of reality and block out better fitting ones.

Life force acts at the molecular level. There's a fifth fundamental force of nature, just like gravity/electromagnetic/strong/weak forces, which interacts with specially structured organic matter, like DNA or RNA, that act like antennas to that force.

Anyways that's just my theory and a lot of the skeptics, like the people downvoting this right now, have already made the assumption against it without testing it for some reason.

Science can and will eventually solve everything, including life itself, but we need people to believe in the scientific process.

> There's a fifth fundamental force of nature, just like gravity/electromagnetic/strong/weak forces, which interacts with specially structured organic matter

We can fairly confidently exclude this possibility. Dirac’s equation forbids it [1]. Or, in your specific language (which is good, don’t get me wrong): we have tested this hypothesis, countless times, and conclusively disproved it.

[1] https://blogs.scientificamerican.com/guest-blog/physics-and-...

It's not a complete description; we haven't included the weak nuclear force, or couplings to hypothetical particles like the Higgs boson.

The article literally states that Dirac's equation is incomplete at modeling the full situation.

But that's okay, since those are only important at high energies and/or short distances, very far from the regime of relevance to the human brain.

And the article makes the mistake of assuming that life force is the physical driving energy, instead of electromagnetic energy itself being directed by a life force.

There are lots of randomness in quantum physics. The life force would cause that to be more deterministic. Einstein himself was a proponent of the hidden-variable theory, famously stating that "God does not play dice".

Who are we to argue against Einstein?

The article also states why that omission is irrelevant.

> And the article makes the mistake of assuming that life force is the physical driving energy

No, it’s simply a tautology: if it interacts with physical entities, it’s physical. EM radiation itself is a physical phenomenon, so it doesn’t provide a magical escape hatch. It doesn’t matter what you call this mystical force; by virtue of interacting with a physical system it must be subject to rules of physics, no special pleading can change that.

> There are lots of randomness in quantum physics

Yes, but that is provably a fundamental property of quantum systems, not something we can ignore or manipulate nilly-willy. Your Einstein quote predates relevant experiments that disprove this hypothesis. “Who are we to argue against Einstein?” is therefore a classical argument from authority: we are arguing based on evidence (and new theoretical underpinnings) that Einstein, at the time he uttered the phrase, didn’t possess (in particular, Bell’s theorem). Your objection is exactly like refusing to acknowledge relativity, saying “Who are we to argue against Newton?”

Anyway, if you’re keen on an argument from authority then consider this: who are you to argue against the consensus of the smartest minds working in the field of neurobiology? I hope you can appreciate how this argument sounds less convincing if used against you.

Pretty sure any life force wouldn't be local, and would be faster-than-light..

I don't know how you can be pretty sure about any of that, but I look forward to the faster-than-light signaling devices we can build from this new revelation about nature.

That’s irrelevant. These terms don’t mean anything in isolation. You just picked the two terms on the Wikipedia page on Bell’s theorem that allow you to escape the restrictions of quantum nondeterminism.

But you missed the fact that they don’t allow you to violate causality. In the context of our discussion this means that they cannot be used to circumvent quantum indeterminacy because that would break physical causality.

The idea that a life force can violate causality is based on the fact that theories on life/god/spirit center around infinity, and possibly related to the multiverse.

Now, figure out a way to test it.

What you’re saying is just paraphrase for “ignore physics”. If you’re willing to do that, then why bother with quantum mechanics etc at all?

If it can be tested, then it's not "ignore physics".

I keep telling you, it has been tested, and disproved — countless times. That’s what “contradicted by Dirac’s equation” means. If you insist on ignoring that evidence then, yes, you are absolutely ignoring physics.

> without testing it

What is the proposed test methodology to test your hypothesis?

Ask a scientist that.

Any test of life should do. How do scientists tests for life right now?

Also, it could be multiple additional forces..

There is no such thing as a test for life at the molecular level, we only describe it at the system level of a whole organism. Even then there is no hard and fast test because organisms exhibit such diverse ranges of behaviour.

For example the chemicals in cell cytoplasm seem to function identically outside a cell as they do inside one. In the first case they are not part of a living organism but in the latter case they are, but this does not appear to make any difference to their properties or characteristics. What difference would you expect to see?

How are nanobes & prions determined to have life?

Are there microscopic Turing tests?

And cytoplasm isn't DNA/RNA itself.

> How are nanobes & prions determined to have life?

They aren’t.

To quote: “No conclusive evidence exists that [nanobes] are, or are not, living organisms, so their classification is controversial.”

> Are there microscopic Turing tests?

No. That’s what we’re telling you. “Life” is not well-defined. The textbook definition you might have seen in school would misclassify fire as alive.

For a fun take on this, look up the comedy podcast (starring Professor Brian Cox) called “The Infinite Monkey Cage”, specifically all the episodes which ask if a (freshly picked) strawberry is alive and if not when exactly did it die.

They aren’t. To quote: “No conclusive evidence exists that [nanobes] are, or are not, living organisms, so their classification is controversial.”

You say nanobes aren't life, but then you say you don't know? Pick one.

“Life” is not well-defined. The textbook definition you might have seen in school would misclassify fire as alive.

Sorta pretentious to just define life to fit existing narratives when you don't have an explanation. We have to figure out more instead of stopping at what we don't understand.

Will check out the podcast. Love Brian Cox.

> You say nanobes aren't life, but then you say you don't know? Pick one.

No, ben_w said that they “aren’t ‘determined to have life’”. That’s a very different statement.

But I’ll go out and say it: they aren’t life. Nobody is talking about nanobes any more. There is no research on nanobes in the life sciences. This is not a hyperbole, I mean that the number of articles published on nanobes in over two decades is literally zero. No single lab in the whole world is researching them. The last scientific publication on the topic, from 2001, was a review concluding that there’s nothing to it.

They were an embarrassing mistake that briefly made headlines.

To add to the other reply:

> Sorta pretentious to just define life to fit existing narratives when you don't have an explanation.

I’m having trouble understanding where you’re going with this sentence.

I’m not defining life, I’m saying there isn’t a definition of life (that I know of) which seems satisfactory.

Also, I don’t think it would be pretentious to start with a definition that fits existing narratives, because that’s how most words work: a label for a bunch of examples, followed by a rule — a definition — which creates a pattern for those examples. Like fire “metabolising” oxygen and fuel to reproduce and “move”, but not being alive. When you find edge cases, either change the definition to fit the new data or create a new category for the new data [1]. I know that domain experts don’t use that previous definition of life for exactly the reason I gave, but last I checked “are viruses alive?” still got arguments.

Also also, treating life as a fifth fundamental force of the universe when chemistry explains all the components just fine is… well, literally pretentious.

[1] That’s just an IMO about language, of course: if language was that simple then NLP would be a solved problem.

Also also, treating life as a fifth fundamental force of the universe when chemistry explains all the components just fine is… well, literally pretentious.

No. Stating that chemistry explains all the components of life just fine is literally pretentious.

Maybe chemists should stop researching since they already explained everything?

Now you’re just nitpicking. So far every single process we have analysed occurring in living things has worked exactly as we expect from our understanding of chemistry. There just isn’t any reason to expect we will find anything chemistry can’t explain, and you haven’t given us any reason to do so or a way to test for such a thing.

To put it another way, what leads you to your conclusion? What evidence is it based on? What phenomena that we currently observe might such a thing explain, and how?

> Stating that chemistry explains all the components of life just fine is literally pretentious.

Name one biological proces which defies the laws of chemistry.


> Maybe chemists should stop researching since they already explained everything?

Is like saying “Computer scientists should stop researching since they already explained everything in terms of NAND gates”.

Whether or not those things are alive is a matter of debate, many scientists say that they exhibit some of the properties of living things but not all of them.

There are many web sites that discuss the properties of living things, I’ve linked a decent one below. It might be useful to think of it in terms of a ‘running’ engine. If I switch a running engine off, or it runs out of fuel, or someone breaks it with a hammer it stops running. Being alive for an organism is analogous to being in a ‘running’ state for an engine. It’s not an attribute of any individual components, but rather a description of the behaviour of the whole system.


> Science can and will eventually solve everything

Do you really hold this as true? Wouldn't this to some lesser degree seem more probable and therefore less dogmatic?

> we also don't know much at all about the mechanism behind RNA

Wait wait wait. We know a tremendous amount about “the mechanism behind RNA”. Without being more specific it’s hard to say what you mean but we’ve certainly done a lot more than “mapped some genes”. We know pretty precisely how protein-coding genes get transcribed and translated, and how they effect changes in the cell (in general, if not in particular). There are open questions about specific catalytic functions of RNA but it’s certainly not a blank slate.

My thoughts exactly. Another problem with RNA is that it is a few orders of magnitude too slow (minutes versus fractions of a second) to account for memory formation. Which is not to say that gene expression is not involved in memory consolidation; that's been known for a long time.

Genetic storage is a form of "memory" generally speaking. Some state can be stored and transferred, obviously. It's okay to recognize that biological systems have multiple, diverse, and sometimes redundant subsystems operating simultaneously.

It could account for some amount of long term memory formation— or it could ‘color’ our memories in someway— associating them with pain or trauma— or happiness and joy.

Its not just caching. This stuff seems to survive generations too by some as yet unknown magic. Google "inherited PTSD".

There is also a lot of activism masquerading as science in the field of epigenetics, enough so that the journal Cell issued a warning about it: https://www.cell.com/cell/fulltext/S0092-8674(14)00286-4

There have been interesting animal experiments which perhaps avoid that eg

>Perhaps the most intriguing animal paper so far is a study published online in the winter of 2013 that appeared to show that fear memories can be inherited. Researchers from Emory University trained male mice to associate an odor with an electrical shock, so that they would get startled simply by smelling the odor by itself. Surprisingly, the scientists found that the smell also startled the next two generations of mice. https://www.vox.com/2014/8/18/5927269/epigenetics-definition...

Did they rule out learning the behavior from the parent mice?

Yes, by raising pups with surrogate parents. However, the study was criticised for other reasons (lack of statistical power, no explanatory mechanism) and, in the intervening years, nobody has successfully replicated this experiment.

This presupposes that the senior mouse, having been exposed, can describe both a particular smell and the appropriate response to a junior mouse. So I'd guess that's ruled out already.

No study has successfully shown that inherited PTSD actually exists in humans. The studies that purport to show so are plagued by flaws. Here’s a good write-up of the state of the field: https://www.theguardian.com/science/blog/2015/sep/11/why-im-... — this is from 2015 but it’s still current.

At any rate, RNA definitely doesn’t survive generations. It’s a short-lived molecule. Stable epigenetic marks modify the DNA, they don’t involve RNA (except as an intermediary).

Well here's a Google talk from last month https://m.youtube.com/watch?v=SJSJx5slLEM

Elizabeth Rosner isn’t a biologist, and (unintentionally, I’m sure) misrepresents the research. The majority view in the field of epigenetics is that trans-generational epigenetic inheritance of things like trauma currently lacks compelling evidence and, just as importantly, a plausible mechanism. The studies from Emory University and Mount Sinai, for instance, were widely panned (see article) for lack of controls, lack of mechanistic insight, and weak statistical analysis.

What little evidence there exists shows a very narrow range of effect in model animals. I’ve co-authored one such study that specifically shows the heritability of stress in mice. I can confidently say that this only works in very specific, artificially constrained instances, the evidence is tenuous, and mechanisms are elusive.

To clarify, this isn’t to say that trans-generational epigenetic inheritance doesn’t exist. Rather, we know that it does in specific circumstances (in particular in invertebrate models). But the claims by Rosner and in some of the more sensational (and flawed) papers require a big leap of faith that most scientists in the field aren’t willing to take, lacking evidence and a mechanistic explanation.

What’s more, none of the scenarios described by Rosner requires trans-generational epigenetic inheritance. It’s much easier explained by social/cultural transmission. Invoking epigenetics in this context is pseudoscience.

Regarding mechanisms, I was under the impression that DNA methylation was widely accepted as a primary mechanism for epigenetic inheritance. Not so much, or is that one of those artificial scenarios you referenced?

That’s correct but you’re (understandably) confusing “epigenetic inheritance” with “trans-generational epigenetic inheritance”.

The first (i.e. epigenetic inheritance, particularly via DNA methylation) is a ubiquitous biological process by which a state is encoded in the cell and can be passed down to daughter cells upon cell division. Hence the daughter cells inherit the mother cell’s state. At its simplest, it just acts like a “bookmark” in the genome which informs the cell what parts to read, and what parts to skip over.

But things are different when talking about multi-cellular organisms that pass heritable information through the germ line. This is what trans-generational refers to. For the longest time it was assumed that no epigenetic information could be transmitted through the germ line due to a concept known as the “Weismann barrier” (think of it as the librarian: upon return, she removes all the bookmarks from the books). We now know that, under specific circumstances, this barrier can be “violated”, and “leaks”. However, unlike normal (genetic) inheritance, this leak does not allow a structured transmission of information according to our current understanding (that is, a bit of information encoding a phenotype “A” wouldn’t necessarily cause the same phenotype in the offspring; it would simply lead a perturbation). There are more specific exceptions to this rule which, for instance in nematode worms, allow a more structured information transmission (though it’s an open question whether DNA methylation is causally implicated).

Thanks for that clarification. I wish the popular literature on the topic took similar pains to point this out. I can’t help but wonder if this is the root of much of the misguided interest in epigenetics.

> I can’t help but wonder if this is the root of much of the misguided interest in epigenetics.

In a word: yes. Even within the field this causes confusion (researchers of course know the distinction in principle, but the term “inheritance” is suggestive, and has led more than one person down the garden path). To make matters worse, “epigenetics” also can refer to several different things.

Currently in Ubud, Bali, so being exposed to lots of hippie bullshit (crystal reiki healing, anyone?). However, there's an idea floating around alternative medicine that human families can inherit trauma, and perhaps this is a mechanism for it? Seems more likely that the effect (if any) would be passed down through socialization, but food for thought.

Take a look at "Transgenerational epigenetic inheritance" (https://en.wikipedia.org/wiki/Transgenerational_epigenetic_i...) and at research into how epigenetic inheritance is cited as a mechanism for passing down trauma between generations. I read about malnutrition in world war II affecting several generations but I don't remember the source, and the Wikipedia article mentions the Dutch famine

Same caveat as above: the existing studies are deeply flawed. So far, the evidence for this kind of trans-generational inheritance is very week, and there’s no plausible mechanism to explain it, either.

I don't have access to the original paper right now, but Dave does do good stuff, he's no crank, and I'd believe him for the time being.

A possibility to what is occurring is that the RNA is 'interfering' somehow with the DNA synthesis. The synapse is very tightly regulated and getting receptors/transmitters into it may be affected by the production of the proteins in the first place (or the 'state' of the receptors, ie actelyation, methylation, etc). Under this idea, a memory is just the memristive state of the synapse, controlled by the populations of transmitters and receptors (all occurring in a network of neurons and synapses). The RNA may be affecting that downstream network during the DNA>RNA phase. But, I've not read the paper and seen their controls yet. I'd assume Dave really went all out on the controls.

I'm a mammalian/zebrafish guy, and my snail anatomy isn't that robust anymore, and I've not read the paper yet, so I don't really know. Histone methylation is a real thing and a cause of some epigenic phenomena, so I'd think something like this is the culprit.

Still, this is a really surprising result, and (sorry to sound like a broken record) more research in needed.

Yes, this was my initial reaction as well:

Is "memory" a parameter to a variable mechanism? Does a hardcoded/fixed mechanism express "memory" of its design changes, or does it have no "memory" because of its non-parameterized operational characteristics?

As humans, we sort of consider memories to be data parameters to our flexible thinking processes.

>> .. more like RNA stores/caches the response mechanism of a pain receptor.

The point? We all evolved from very tiny/primitive creatures. It's reasonable to speculate that all of our memories are stored in a similar manner. At some root level all of our consciousness may be conditioned responses by individual cells. All our other complex systems evolved from relatively simpler mechanisms.

I can't be bothered to actually read the actual paper, but I assume that snails that have been stabbed and injected with something similarly irritating are absolutely chill with that and won't withdraw any sensitive bodyparts none whatsoever.

I wonder if it's misleading to use the term "brain" here. It's certainly interesting that RNA can modulate the synaptic activity involved in the gill siphon withdrawal reflex, but the system is pretty far from a brain.

Another layman here.

Could this also be described as _muscle memory_?

RNA is too short-lived (in the order of minutes to hours) to serve as a long-term memory. Muscle memory, despite the name, corresponds to changes in the brain structure. In a way muscle memory is the exact opposite: it’s a slowly learned, but long-lasting response. Whereas RNA memory, to the extent that it exists, is an immediate but short-lived memory.

RNA alters the dna of cells and that is a long term change.

Muscle memory mostly takes place in the cerebellum.


The larger hyphothesis, if I understand correctly, is that RNA (and possibly DNA?) is the seat of long-term memory and has some hereditary or otherwise physically transferable component, while synapses would be our short-term memory, as well as the expression or "cache" of the former.

This, as well as the worm-eating-worm-acquires-its-memory research, if true (a big if) would vindicate so many theories, findings, and "magic" traditions from around the world.

From Carl Jung's Collective Unconscious: https://en.wikipedia.org/wiki/Collective_unconscious to many old cultural traditions of eating certain animal/human parts in order to acquire their psychological properties such as courage.

I, for one, am looking forward to my injections of foreign languages and musical instrument playing.

> This, as well as the worm-eating-worm-acquires-its-memory research, if true (a big if) would vindicate so many theories, findings, and "magic" traditions from around the world.

We don't have the same digestive metabolism as worms. I don't think the RNA is going to make it from your stomach to your brain.

I don't think so either, but that's not science. I haven't checked, and apparently neither has anyone else. yet

Further study is required. Facts must be established.

I mean if the RNA is going to dissolve in the stomach acid. Then there is no way it is going to make it to the brain? And does the RNA transfer through blood on its own? That's science.

The only possible explanation is that they picked up something else along RNA that does affect memory and they are not aware of it.

I'm by no means educated about ways how RNA could get from food into your own cells, but saying "RNA is dissolved by stomach acid" is a bit too easy. HCl peaks only after a big meal with protein, and some people generally have low stomach acid. Then there's the mucosa of the mouth and esophagus, through which some food is absorbed before it even hits the digestive organs (even bypassing the liver AFAIK). It might still get dissolved as soon as it hits your bloodstream, or destroyed by antibodies, etc..

> some people generally have low stomach acid

Not to the extent that you (and many others) believe. The stomach is always very acidic (pH 1–3), and this acidity is tightly regulated. Contrary to what you’ve said, the pH is raised (and hence acidity lowered) when consuming food (because HCl is used up in the digestive process). That said, much of the digestion of RNAs happens through enzymes, not acid, so the point is moot. It’s known that the human GI tract is highly efficient in digesting oligonucleotides. Very little (and of that, only small fragments) has a chance of being taken up.

A reasonable hypothesis. I like it. I'm not a scientist, so I do not know how to specifically verify or disprove it, but my understanding is that the only way to be sure is to actually perform an experiment to check; removing or controlling for all other variables.

> I haven't checked, and apparently neither has anyone else.

Wait, how did you figure that out? Of course this has been checked. Here’s a review: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446746/

Anyway, the tl;dr is that, at best, very short RNA fragments would survive being digested in vertebrates (but most likely not even that). This doesn’t preclude the transfer of information by RNA via food but it severely limits it.

Also, to reiterate the point I’ve made elsewhere: RNA is unstable and short-lived and therefore unsuitable as a long-term memory carrier. It can act as a short-term carrier under specific circumstances (and that’s arguably its main function in the cell anyway).

Yep. Good and valid point. I should do my homework before posting. :)

Count me out.

If you think we have problems with back doors in systems now, just imagine how that would go in a world of injectable RNA memories.

"So did you learn Chinese?"

"Yeah it was great!"

"Cool, let's go finish that Tor guide for oppressed Chinese citizens!"

"No, you know what, that project makes me feel really uncomfortable now, for reasons I can't quite define. I'm off now, gonna go sell my iPhone on eBay and buy a Huawei. Cya!"

When memories are consolidated at night during NREM sleep there's a lot of information transfer within the brain but not from the brain down to your gonads. Also we can look at the DNA of a gamete and see how it differs from other cells and there are usually a few mutations but you can't encode much in <16 bits.

All this would have been reasonable speculation in the 1960s when Dune was written but science has moved on.

I mean, you’re totally right to be sceptical of heritable learned experience but your description is off: Firstly, what do these 16 bits refer to (a single nucleobase encodes 2 bits of information and there are easily > 8 mutations from a given individual to the next)? Secondly, the posited mechanism for these acquired traits would be epigenetic, not genetic. I.e. it wouldn’t be encoded in genetic mutations but in other chemical modifications of the DNA (and, more generally, the gamete).

This has conceptual and practical problems in itself (notably due to germline reprogramming) and as I explained in other comments, the current majority view in the field is that it plays a minor role in evolution at best. But it’s not fundamentally impossible and, at least under very specific and constrained circumstances in certain species, it does happen.

It also fits the trope of "a writer wrote about the exact thing decades ago!" (Frank Herbert, the Dune series)

I know Kung Fu.

Would this be similar to past studies[1][2] in how stimuli responses (e.g., fear to smell) can be inherited between generations?

The question is if we can ever transfer complex structured memories (knowledge, past experiences) or if these transferable memories are limited to basic emotional responses to specific signals?

I thought more complex memories were spread across many cells in the brain, in a seemingly random structure when compared to another brain, making transfer between brains incompatible.

[1] Worms: https://www.cell.com/cell/fulltext/S0092-8674(16)30207-0

[2] Mice: https://www.nature.com/articles/nn.3594.epdf?referrer_access...

I wonder if environmentally ambient RNA could impact gene expression in humans. RNA directly impacts gene expression: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612776/

Say we swap some bacteria by using the same public restroom paper towel dispenser. Your bacteria happens to carry some tragic memory of stress encoded into some miRNA that formed when traveling to somewhere with very cold temperatures. Certainly gene expression wouldn't be affected by a small bacteria colony, but maybe if there was repeated exposure, every day in the same place or with the same people, would I think twice about visiting Alaska?

I have observed how places like cities tend to affect people's 'look' in semi-coordinated ways. How spending sustained time with a group of friends really does change a person in subtle ways. Is there any way that ambient miRNA could be a part of that process? Is there a way we can be sure that it isn't a factor?

It's going to be hard for enough RNA to do anything to get in to your nervous system from the towel dispenser. I'd put peoples looks changing that way down to peer pressure and the like.

It says that the snails retracted only briefly as a baseline, but learned to retract for longer periods of time to avoid the jarring electrical stimuli. I’m totally unfamiliar with this stuff, but it seems to me that injecting a snail with RNA would also be a jarring stimulus. Therefore, wouldn’t it be learning from the injection itself to remain in its shell for longer at a sign of human touch?

They injected the other snails with control RNA from snails which were not subject to the shocks. In other words, they did control for this.

Came back here to say this. The relevant part: “Control snails that received injections of RNA from snails that had not received shocks did not withdraw their siphons for as long.”

I missed that - thank you for clearing this up!

may be the control injection doesn't hurt as much as the rna injection?

Control was also RNA, but from unschocked snail.

I suppose we could call this effect "snail mail" :-)

More seriously though, while I understand the basic method they used for their experiment, where is the theory about how the brain can catalyze the RNA into understanding in millisecond times rather than days.

Or is it perhaps an epigenetic marker that signals "danger" ala the learned muscle memory 'flex' from negative stimulus?

>where is the theory about how the brain can catalyze the RNA into understanding in millisecond times rather than days.

Maybe the brain often serializes memories from neurons into RNA and vice versa often in order to replicate the memories throughout the brain. The RNA injection caused some memories to be deserialized into the snail's neurons, and the memory now in the neurons is what is affecting the snail's reaction.

Let's not forget that it's also perfectly possible to have multiple mechanisms for remembering things; there seems to be a false dichotomy being presented here, either RNA or synaptic strength or synaptic topology. There are different modes of memory too: the way you remember something as muscle memory, vs short term memory, vs associative memory, etc.

The possibility that different types of memories are stored in varying places or ways based on unknown criteria is highly intriguing. If there is more than one way to store/trigger a memory, that means a larger 'attack surface', and therefore the process should be easier to hack.

Maybe someone can take a second look at the paper. I couldn't find the published version, just a manuscript[1] (kudos to the authors for making it available under CC license). But... The only reference I could find about the sample size says:

> "To prepare a single RNA injection, the pleural-pedal and abdominal ganglia were removed from 4-5 sensitization-trained animals—or from 4-5 untrained controls—immediately after the 48-h posttest"

4-5??? I really hope that I'm missing something here, otherwise I find truly depressing how low the bar is for scientific journals.

[1] http://www.eneuro.org/content/eneuro/early/2018/05/14/ENEURO...

Figure legend 1D says: “Control RNA (5.4 ± 3.9 s, n = 7) and Trained RNA (38.0 ± 4.6 s, n = 7)”

That’s a relatively low n but it might be sufficient. However, they don’t explain how the number was reduced from ~30 donor animals to 7 test animals. This might be entirely reasonable though (I know nothing about working with Aplysia).

I'm sorry, Sturgeon's Law is in full effect and the current system encourages spamming out low-tier research for grants/etc.. So the bar is on a completely different metric altogether from what a normal person would expect

Transfer of fluid in fluid based capacitors at different level of charche would basically also exchange circuit response times (in specific cases) so I'm not too keen on making ut memory transfer. What if they transfered a snail equivalent of cortisol ("stress hormone").

This was my first though too. Something happened, but it was not memory transfer.

However RNA and biological indicators like hormones could (and probably do) have a big effect on learning, in terms of how fast we learn, how aware to be, feedback mechanisms, triggering long-term memory formation etc.

The idea of storing memories in genetic materia has been really popular for a long time, but imo this is mostly due to either hope/belief for immortality and romantic trans-generational memory transfer, or new age trends.

Of course it's not impossible, but it's very unlikely.

I was surprised to find so many studies regarding the relationship between long-term memory, an enzyme (PARP-1, usually associated with DNA repair and inflammation), and RNA. Seems relevant to Glanzman's research, but not cited.

In 2004 the enzyme PARP-1 was linked to long-term memory in Aplysia[1]. In 2009 another study claimed that PARP-1 was also required long-term memory in Mammals[2]:

"Previous results linked the activation of PARP‐1 with long‐term memory formation during learning in the marine mollusk Aplysia (Science 2004, 304:1820–1822).. Mice were tested in two learning paradigms, object recognition and fear conditioning.. These findings implicate PARP‐1 activation in molecular processes underlying long‐term memory formation during learning."

Another study of mice "demonstrated that augmentation of the stability of pro-inflammatory mediator mRNAs presenting a regulatory mechanism of PARP1 in gene expression at the post-transcriptional level".[3]

[1] http://science.sciencemag.org/content/304/5678/1820 [2] https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1471-4159.... [3] https://www.nature.com/articles/ncomms14632

I think this was proposed back in the 60s with flatworms. There are some recent experiments, again with flatworms, where they studied this.

Flatworms can regenerate heads. So they trained a flatworm to avoid a certain type of light and cut the head off and allowed the tail to regenerate back a new head. I think they claimed that the newly regenerated animal exhibit the same behavior.

>>I think they claimed that the newly regenerated animal exhibit the same behavior.

As directly referenced in the article, flatworm experimenters (James McConnell in the 50's and 60's, and Michael Levin in 2015[1]) definitely claimed regenerated flatworms exhibited the same behaviour.

[1] https://www.theverge.com/2015/3/18/8225321/memory-research-f...

It would be interesting to see a "diff" on the injection samples. With brute forcing we could figure out how to program these sequences. Biological robot snails!

That’s probably the next step (the authors raise the question of the identity of the implicated RNA). Transcriptome profiling (which this is) has become extremely routine recently. In fact, it’s highly unorthodox that this analysis isn’t already part of the original paper (to clarify: it’s completely fine, but quite unusual, to leave it as a follow-up study).

> It is generally accepted that long-term memory (LTM) is encoded as alterations in synaptic strength.

> RNA from a trained animal might be capable of producing learning-like behavioral change in an untrained animal.

Why did the author jump to the conclusion that RNA == LTM, when that RNA is most likely just the driver for modulating synaptic strength? Whatever RNA they extracted could easily just encode for various synaptic proteins.

But wouldn't that still inevitability lead to the conclusion that rna is where memories are stored and synaptic strength is just how memory gets expressed in a way our brains can interact with.

Maybe there's a transitive relationship between the environment before and during transcription and the resulting RNA that in turn can affect its environment. It would be difficult to identify in vivo because the environment is already synchronized with the changes that may have been introduced from the RNA, but in vitro maybe the effects of the altered RNA would become apparent in an unmodified environment. Vice versa, if you could measure enough samples of RNA from the same organism and source DNA I wonder if there'd be a quantifiable difference when the environment was subject to the same sort of changes that occur when memories are formed and an unmodified environment.

Really cool research!

So synapses are like a fast cache for memory stored in neurons nucleus?

Maybe. Maybe there was a problem or it will fail to replicate.

Finally a childhood dream of the many can be established through this alleged innovation: Learning math, physics, etc. through simple injection, information pills, etc.

Not sure how good this would be, deviations in learning creates further developments in the fields. A child prodigy's idea of some odd physics occurrence might one day grow into some completely new field of science.

I suppose I'm a memory conservative, I think I'll prefer the good old way, no matter how cool that scene from the Matrix is

Interestingly, L. Ron Hubbard put forth the notion of cellular memory a long time ago -- it is part of the premise of Dianetics. I think Gene Roddenberry may have believed this too. I recall an early Star Trek NG episode where Data told Geordi that's how human memory works, contrasting it to how his positronic brain worked.

A lot of creatures reduce contact with something that just caused them a lot of pain. I'd have asked if they ruled out whether the snails also withdraw a bit after someone stabbed them with a needle. The subsequent test on Petri dishes lends more credence to the theory, though, that the reaction is stored and moving.

> “It’s as if we transferred a memory,” Glanzman said.

No, sorry. They did not transfer "memory", they transferred some specific RNA which modulates some specific neuron activity. "Memory transfer" is a gross misinterpretation of what they actually did there. Ugh.

I know this will be an unpopular comment, but I've had a long-held theory that past lives / reincarnation is a real phenomenon with a biological mechanism that is as-yet unknown.

The theory being that trauma at time of death is somehow encrypted for the next generation and passed on shortly after death, particularly if a corpse enters the water or food supply.

The basis for this is a little embarrassing.. I had memories of being a bridge engineer, frequent dreams of falling off a very specific truss bridge in my head in childhood. To this day I'm terrified of certain types of truss bridges, which are coincidentally quite common upriver of where my parents lived when I was born, and where our water came from.

This theory would also explain why river burial is commonly associated with reincarnation. Committing the tissue of a deceased person into a community water supply would increase transfer of memory.

It doesn't seem physically impossible, but this would mean "past lives" can only be from your direct ancestors.

But regardless, there's no evidence to support it and even this snail experiment is a far cry from proving memories can even be transferred to humans, let alone inherited.

I think, on the positive side, it'll make people reconsider that genetics and race affect intelligence (and maybe gender?). We are too stubborn and politically correct to discuss it. I kinda think it is true because my dog (a german shepherd) is definitively a lot smarter and dexterous than the other "normal" dogs. Hopefully, we'll be able to inject the intelligence DNA and everyone can get a fair share of intelligence.

> He said he doesn’t understand how RNA, which works on a time scale of minutes to hours, could be causing memory recall that is almost instantaneous, or how RNA could connect numerous parts of the brain, like the auditory and visual systems, that are involved in more complex memories.

I was puzzled by that too. Also, it is not like they go pick a fork and select the RNA. I wonder if they "picked up" something else along the way?

> I think, on the positive side, it'll make people reconsider that genetics and race affect intelligence

I’m wondering why people dig at this so much, what is the answer you are looking for? To me the reason it’s not “politically correct” is because it comes off like the answer you want is for whatever race you believe yourself to be, to be superior to other races in a fundamental way, which would justify subjugating them.

There’s seems to be quite a bit of research done around genetics and intelligence. But every definition of race I’ve seen is either an ill-defined regional genetic stereotype or a description of physical appearance.

Now if some genes are associated with high intelligence or happiness or conscientiousness or empathy, and you want to engineer your children to have those genes, that’s understandable, if an ethical minefield. It also has nothing to with race.

Isn't it likely that training has a significant effect on the apparent "intelligence" of different dogs?

No. The german shepherd picks up very fast comparing to other dogs. It also has dexterity. My dog figured out how to open various door by just watching us come and go. The opening mechanism required some dexterity and manipulation. No other dogs did that before.

> it'll make people reconsider that genetics


> and race affect intelligence


To clarify: it’s extremely well established that genetics strongly affects intelligence [1]. Nobody in the field is denying (or ignoring) this. It’s just hard to exploit at the moment. But “race” is a different matter, and other people have written eloquently (e.g. [2]) about it so I won’t rehash the argument.

As a tl;dr: the social construct we call “race” has no relationship with genetic variability in humans. If somebody tells you otherwise, they don’t understand genetics. To put it simply, the labels “Black”, “Caucasian” or “Asian” don’t corresponds to our evolutionary heritage. Actual races (if we were to define them) would look something like “Bantu”, “Yoruba”, 10 more African races, and “pretty much all the rest” (see e.g. [3]).

Contrary to the frequent suggestion that science ignores race due to “political correctness”, this simply isn’t true (have you met scientists? they’re not generally known for being politically correct). Science is aware of race, but it’s an unhelpful concept for modern research.

[1] https://en.wikipedia.org/wiki/Heritability_of_IQ [2] https://www.salon.com/2017/10/18/how-genetics-undermines-sci... [3] http://www.pnas.org/content/107/2/786

The RNA can turn off and on production of proteins no? If so, then surely the ratio of proteins can affect the touch response sensitivity?

After all, it's not like he transferred memory of a complex maze.

“It’s pretty shocking,” said Dr. Todd Sacktor, and giggled internally

My guess is that their RNA solution also contained neurotransmitters

Even if: neurotransmitters are extremely short-lived, and almost completely unspecific: they’re either generally excitatory or inhibitory, they don’t encode complex messages. They experimental setup sufficiently controls for that due to the duration of the wait between the RNA injection and the stimulus exposure.

"neurotransmitters are extremely short-lived, and almost completely unspecific"

That's the assumption that I think needs to be further validated.

offtopic but, I find this "magazines" that use to appear on HN interesting

Which ones do you guys recommend and what's the best way to be subscribed to them?

I wonder how this relates to Slime Molds. There was a Science Friday segment on them and, if I remember correctly, they showed memory and memory transfer too.

layperson's question:

Since rna is gets information from the dna and is involved in the expression and regulating of genes, does this mean that memory somehow becomes encoded in our genes?

I for one welcome our new hive mind snail overlords.

lol...thanks for this

Apparently fun is not allowed in HN, judging by the gray text.

So sad to know that this will be downvoted to oblivion. I would like to subscribe...

But /. still flourishes on hot-grits and such, so don't be sad, just go there. Not all communities need [devolve] to be the same.

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