[HN Gopher] OpenWorm - A computational model of C. elegans worm
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       OpenWorm - A computational model of C. elegans worm
        
       Author : dvrp
       Score  : 417 points
       Date   : 2023-07-07 07:08 UTC (15 hours ago)
        
 (HTM) web link (github.com)
 (TXT) w3m dump (github.com)
        
       | umutisik wrote:
       | "Congratulations! You can now join the Devs project."
        
       | krzat wrote:
       | Neat. I'm wondering how much of inner cell biology can be
       | abstracted away.
       | 
       | How accurate can neuron simulation be without underlying
       | chemistry and physics?
        
       | xvilka wrote:
       | Connectome model of fruit fly brain was just recently
       | published[1].
       | 
       | [1] https://hub.jhu.edu/2023/03/09/scientists-complete-first-
       | map...
        
         | omnicognate wrote:
         | Which is awesome, but the C. Elegans connectome was published
         | in 1989 and as you'll see if you investigate the linked project
         | a bit we are absolutely nowhere near having C. Elegans' full
         | set of behaviours emerge from a simulation of its neurons, or
         | even to proving that it's feasible to do so.
         | 
         | This makes neurokernel [1] and the like seem just a tad
         | ambitious. Good luck to them though.
         | 
         | [1] http://neurokernel.github.io/
        
       | c7DJTLrn wrote:
       | So is this an exact digital replica of a worm?
        
         | bombolo wrote:
         | How can we exactly replicate something if we don't even know
         | all the laws of physics?
        
           | Leo_Germond wrote:
           | This is a fundamentally flawed way of questionning, "knowing
           | all the laws of physics" is probably impossible to achieve,
           | but we still produce accurate predictions for a lot of
           | phenomena. You can see that we do in fact "replicate"
           | (predict would be a more proper term) things despite not
           | knowing all the laws of physics: weather, movement of the
           | stars, cooking time for a browned piece of bread...
        
             | bombolo wrote:
             | I was replying to someone asking if it was "exact"... and
             | no it isn't... You listing a bunch of simulations, that are
             | notoriously not 100% correct proves my point, thanks.
        
               | Leo_Germond wrote:
               | You're welcome, but your point was not very clear.
        
           | ben_w wrote:
           | My cellular biochemistry does a pretty good job of
           | replicating itself with absolutely no understanding
           | whatsoever of how to resolve the contradictions between
           | general relativity and quantum mechanics.
           | 
           | When it comes to brains, I don't know _if anyone knows_ what
           | might be the simplest sufficient model that would usefully
           | replicate them, even if you specify  "usefully" well enough
           | to know if this is about fundamentals of intelligence or
           | about the impact of drugs on cognition, which are two
           | completely different standards.
           | 
           | For example, perceptrons are a toy model, but modern AI can
           | do more in (breadth XOR single-skill performance in various
           | domains) than any single human, even with much smaller
           | parameter counts than we have synapses; but the broad-skilled
           | ones also mess up in inhuman ways, like being _equally_ good
           | at advanced calculus as basic arithmetic, or being a poet at
           | the level of stereotypical teenager but in every language
           | simultaneously.
           | 
           | If anyone's made a neutral network that can get high on
           | simulated caffeine -- and I'm not saying it _hasn 't_ been
           | done -- it's not reached any of the places I follow
           | discussions on this kind of thing. (Google didn't help,
           | results were about software named Caffeine and non-artificial
           | neurones).
        
             | bombolo wrote:
             | This makes no sense.
             | 
             | Cells duplicate, but can you make a cell without splitting
             | one in 2?
        
               | ben_w wrote:
               | Why does it matter how it works? The 3.2 billion base
               | pair model that is my genome doesn't understand the
               | physics or the chemistry.
        
               | mrguyorama wrote:
               | That's entirely wrong. The interactions of proteins and
               | amino acids and ions IS, at a fundamental level, the
               | evaluation of physics over time.
        
               | ben_w wrote:
               | I'm not saying it isn't physics, I'm saying it doesn't
               | know what the physics is.
               | 
               | We're physics too, but we don't know how it all fits
               | together.
               | 
               | If a sub-part of us that knows less than we do can make a
               | copy of us, despite not knowing how it all works, that's
               | an existence proof that we don't need to understand how
               | it all works to make a copy of us.
        
           | Legend2440 wrote:
           | Abstraction. You don't need to know what's going on at the
           | quantum level because higher-level simulations can capture
           | all the properties you care about.
        
           | highduc wrote:
           | clearly depends on needed resolution and our ability to
           | recreate the material structure. you don't have to understand
           | much about wood to build a chair.
        
           | dekhn wrote:
           | If the "something" never exploits a particular law, then in
           | principle you could simulate it if you knew all the laws that
           | actually applied (imagine a hypothetical biological organism
           | that never exploited or experienced quantum entanglement).
           | 
           | But strictly speaking, as we understand it, it's not possible
           | to replicate something _exactly_ without recapitulating the
           | exact laws and running a deterministic simulation, which is
           | not practical.
           | 
           | I don't think anybody is really attempting to exactly
           | replicate things, but rather to create a physical model which
           | can be calcualted and contains enough similarity or
           | transferrability to be able to make accurate generalized
           | predictions about the behavior of the simulated system. How
           | and why that works with modern math methods is still somewhat
           | mysterious. The most useful thing written about that so far
           | is https://en.wikipedia.org/wiki/The_Unreasonable_Effectivene
           | ss...
        
           | nightsd01 wrote:
           | The same way we can simulate the movements of the planets -
           | it will never be exact, but the better we understand it, the
           | more precisely we can simulate it
        
             | bombolo wrote:
             | Well the question asked if it was exact. I pointed out why
             | it can't be.
        
         | chromanoid wrote:
         | This is the goal.
         | 
         | > Our main goal is to build the world's first virtual organism
         | - an in-silico implementation of a living creature - for the
         | purpose of achieving an understanding of the events and
         | mechanisms of living cells.
         | 
         | This blog post is interesting: "Whole Brain Emulation: No
         | Progress on C. elegans After 10 Years"
         | https://www.lesswrong.com/posts/mHqQxwKuzZS69CXX5/whole-brai...
         | As other mentioned in the comments of the post, it is certainly
         | also a matter of funding, but still I think it is very
         | interesting how we still struggle to simulate a 302 cell worm,
         | while some people expect an artificial superintelligence in the
         | next ten years.
        
           | circuit10 wrote:
           | Replicating something exactly is a lot harder than making
           | something that does the same thing in a different way. We can
           | build planes that travel far faster than a bird could but
           | that doesn't mean it's easy for us to exactly replicate how a
           | bird flies, so I don't think this says anything about how far
           | away we are from a superintelligence
        
             | inglor_cz wrote:
             | This. Submarines don't swim like fish, airplanes don't fly
             | like birds and cars don't run like gepards.
             | 
             | Edit: I am surprised at the downvotes. In general, we learn
             | from the nature, but aping it usually proved too difficult
             | and often unpractical at the same time. Do we really want
             | to replicate worm intelligence for practical purposes, or
             | do we want something different?
             | 
             | I would say that a machine which can, say, analyze chemical
             | compounds for their potential biological functions, is a
             | very practical form of "intelligence" and yet very far from
             | any biological intelligence that was ever produced in vivo.
             | Worms cannot do that and even humans struggle with such
             | tasks.
        
               | szundi wrote:
               | And for some reason it is because somehow life is not
               | able the produce rotating axles?
        
               | dekhn wrote:
               | You mean like this?
               | https://en.wikipedia.org/wiki/Flagellum
        
               | cnlevy wrote:
               | Rotating molecular motors exist (a proton powered turbine
               | in the video)
               | 
               | http://biovisions.mcb.harvard.edu/anim_mitochondria.html
        
               | PeterisP wrote:
               | Not only, it's also because of the square/cube law making
               | it impossible to have a 50 ton flyer that flies in the
               | same manner as a 5 kg flyer, you can't simply scale
               | things up.
        
               | chromanoid wrote:
               | Yeah, but we understand why birds can fly and why fish
               | can swim and how gepards can run, at least on a
               | mechanical basis.
               | 
               | This is not true for how this 302 cell organism works. We
               | don't know and struggle to understand. That's actually
               | the reason why the project exists. To find out how
               | everything works with an bottom-up approach.
               | 
               | While we may find shortcuts or even superior forms of
               | intelligence without understanding how intelligence works
               | in biological creatures, it is still curious how we
               | struggle even with a "simple" organism like C.elegans.
        
               | XorNot wrote:
               | Except understanding how a bird can fly had little
               | bearing on building the Wright brothers flyer.
               | 
               | And most of the details of bird flight were not exactly
               | discovered till well after commercial air travel was
               | commonplace.
        
               | chromanoid wrote:
               | While the exact details were not understood, the
               | mechanics were visible and explainable to some extent.
               | The Wright brothers were at least inspired by birds.
               | https://www.wright-
               | brothers.org/History_Wing/Wright_Story/In...
               | 
               | We still don't know how cells in C. elegans work
               | together. It's neither visible nor explainable on a
               | satisfying level.
        
               | XorNot wrote:
               | No but we observably do know that that the connections
               | between cells are important, to the point that by
               | mimicking that we've derived significant benefit.
               | 
               | The Wright flyer didn't flap, and the wings only
               | superficially look like anything a bird has.
        
               | chromanoid wrote:
               | > No but we observably do know that that the connections
               | between cells are important, to the point that by
               | mimicking that we've derived significant benefit.
               | 
               | That is true and it shows even more how important
               | observabilty is for science and engineering. That's also
               | why a simulation that actually provides an accurate
               | enough model of reality might help us so much. The
               | problem with AI right now is, that we try or even claim
               | to understand Unix by mimicking the functionality of
               | transistors.
               | 
               | > The Wright flyer didn't flap, and the wings only
               | superficially look like anything a bird has.
               | 
               | They tried to mimick bird wings when coming up with
               | flight control mechanisms.
        
             | nightsd01 wrote:
             | The bird and the airplane is such an excellent analogy!
        
               | circuit10 wrote:
               | I got it from a video I saw so I didn't make it myself
               | 
               | https://youtube.com/watch?v=eaYIU6YXr3w?t=106
               | 
               | I'm not sure the timestamp works but it's at 1:46
        
             | chromanoid wrote:
             | It's not only about exact simulation. And we actually do
             | understand how birds can fly on a mechanical basis. This is
             | not true for C.elegans' inner workings.
        
               | [deleted]
        
           | comfypotato wrote:
           | In defense of the project: they've been working a lot over
           | the last 10 years. They recently published what they call a
           | "liquid neural network" where they've isolated the neuron
           | structure doing the work. It outperforms CNNs for some niche
           | tasks, and it uses a fraction of the resources.
        
             | chromanoid wrote:
             | Just to make this clear, I think this project is actually
             | one of the few sane engineering approaches for starting to
             | understand how our brain works. Sure, claims of simulating
             | a cat brain or even a human brain in some manner are much
             | more catchy, but it seems to be pretty arrogant if we
             | struggle even with C.elegans.
        
         | comfypotato wrote:
         | Nematode specifically, which is a very little worm.
        
       | [deleted]
        
       | dang wrote:
       | Related:
       | 
       |  _OpenWorm_ - https://news.ycombinator.com/item?id=29045198 - Oct
       | 2021 (110 comments)
       | 
       |  _OpenWorm - Create a virtual C. elegans nematode_ -
       | https://news.ycombinator.com/item?id=8949408 - Jan 2015 (12
       | comments)
       | 
       |  _OpenWorm: A Digital Organism In Your Browser_ -
       | https://news.ycombinator.com/item?id=7613732 - April 2014 (47
       | comments)
       | 
       |  _Openworm: c.elegans worm simulation_ -
       | https://news.ycombinator.com/item?id=4208454 - July 2012 (14
       | comments)
        
       | eterevsky wrote:
       | This project has existed for something like a decade. Does anyone
       | know if there was any progress with it in the last few years?
        
         | slars0n wrote:
         | Yes! News page here: https://openworm.org/news
        
         | luc4sdreyer wrote:
         | I used to follow their progress but I unsubscribed from the
         | mailing list due to donation request spam. There have been very
         | few public updates in the past year. There is still some
         | movement but it seems to be happening at a geologic pace from
         | my perspective.
        
         | dilawar wrote:
         | I did my Ph.D. in computational neuroscience (2020 grad).
         | 
         | This project is often used to joke about the limitation of
         | computational modelling of nervous system. If you can't compute
         | the behavious of an effing worm with mere ~300 neurons, whats
         | the point of all hot-air around connectomics (mapping
         | connections of the brain). Connectomics used to be a big word
         | when I started my Ph.D.. The apologists are always like, "real
         | neuron is way too complicated!".
         | 
         | IMHO, chemical computations are often over-looked in neural
         | "computation" communities which are extremely hard to model.
         | Forgetting modelling, we don't know reaction parameters of most
         | proteins and other molecules involved. Electrical side of
         | computation is easy to measure and one can understand why we
         | started with it. There are a thousands types of proteins even
         | in a small structure such as synapse, and individual protein
         | can implement interesting non-linear computation. E.g. CaMKII
         | can implement and bistable switch (flip-flop) and thus store
         | 1-bit of memory using just a few molecules (the real story is a
         | much more complicated).
         | 
         | https://youtu.be/vJBUaS0r9IU
        
           | FrustratedMonky wrote:
           | Yeah, like hormones, (I'm assuming what you are calling
           | chemical computations). Maybe this isn't forgotten, just not
           | figured out yet. Maybe future GPTs will have some other layer
           | of weights, or different level of feedback, that could be
           | called 'hormones'.
        
           | Gordonjcp wrote:
           | > Connectomics used to be a big word when I started my Ph.D.
           | 
           | On a scale of one to ten, how sick are you of people asking
           | you about Neal Stephenson - "The Fall, or Dodge in Hell"?
        
             | PTOB wrote:
             | Plot twist; he's got an "Ask Me about Neal Stephenson"
             | t-shirt.
        
       | TruthWillHurt wrote:
       | Wow it's amazing how much progress was made on this! a full
       | simulation!!!!
        
         | sledgehammers wrote:
         | Are you shitting on peoples work just for the sake of shitting
         | on it?
         | 
         | edit. this comment seems unpopular, my intent was to defend the
         | worm against trolls :)
        
           | Pannoniae wrote:
           | I think this is excitement, not sarcasm :)
        
           | MrTrvp wrote:
           | brother you are a sledgehammer but you need to be just a
           | hammer for now
        
           | ranguna wrote:
           | Even of the OP was being sarcastic, this type of language is
           | unnecessary.
        
       | boredumb wrote:
       | Fascinating to see this again it's been at least a decade since I
       | first found it. Projects like this always make make me glad to
       | see because it's almost "useless" work that I imagine will be a
       | foot note to some seriously impressive future technology. Very
       | cool work in the mean time. As an aside - this brings back a
       | weird feeling of nosatlgia, but this repository also brought me
       | back to a time where I was stuck in an over-engineered .NET shop
       | and i'm now debating if we start the day off with whiskey after
       | having a flashback to being asked to implement "Ninject" into a
       | massive spaghetti banquet of a code base (collective hope that
       | dep injection fixes bad code).
       | 
       | In case anyone is worried I write software in Rust and Golang now
       | and my life has improved significantly since the origins of this
       | worm and people taking dep injection frame works seriously. :D
        
       | mofosyne wrote:
       | I would love to see a webassembly version of this engine so we
       | can see these worms on a webbrowser. Wonder how hard it would be
       | to do so.
       | 
       | ---
       | 
       | edit: Possibly baked already at http://wormsim.org/
        
         | slars0n wrote:
         | Code for wormsim.org is here on Github btw:
         | https://github.com/openworm/org.wormsim.frontend --
         | contributions welcome!
        
       | quickthrower2 wrote:
       | Is it simulating cells? atoms? or treating the neurons as black
       | boxes?
        
         | miltondts wrote:
         | From a quick read of the model used [0], it seems to simulate
         | neurons and muscles at a functional level (not atoms or cell
         | internals).
         | 
         | [0] - https://github.com/openworm/c302 (linked in the original
         | github page)
        
       | max_ wrote:
       | Noam Chomsky says there are two kinds of AI.
       | 
       | 1. The first kind of AI research is more like engineering for
       | example creating self driving cars, language translation & object
       | recognition.
       | 
       | 2. The second kind of AI research is trying to replicate the
       | intelligence of living organisms (humans, worms) with models that
       | are consistent with what cognitive scientist have.
       | 
       | An example for such a system is one that would pick up any human
       | language with very little supervision. Like children for example.
       | 
       | Open worm seems like no. 2. Any one have any interesting
       | resources for no. 2 type AI? I would love to explore it some
       | more.
       | 
       | [0]: https://youtu.be/TAP0xk-c4mk
        
       | jcims wrote:
       | Watching the little worm writhe on the screen made me realize
       | that you could just sit there and torture it with impunity. Kinda
       | creepy.
        
         | Rarebox wrote:
         | Would that be morally close to torturing an equally intelligent
         | real worm?
        
       | lclarkmichalek wrote:
       | It models wiggling forward. It models wiggling backwards. And
       | occasionally it models fucking itself. That's it.
        
       | drakonka wrote:
       | I went to an OpenWorm mini-conference of some kind in London a
       | few years back - a couple of days talking about worm locomotion.
       | Knowing nothing about worms or animal locomotion in general, I
       | was a complete layman with an amateur interest in life simulation
       | and understood next to nothing. But it was still fascinating, and
       | was so cool to meet people passionate about this.
        
       | akokanka wrote:
       | Work seems to have stopped last year.
        
       | JPLeRouzic wrote:
       | As an amateur scientist with an interest in neurodegenerative
       | diseases, I am interested in neurons simulations. As a model with
       | neurons and muscles, Openworm looks very interesting for
       | application in ALS (Lou Gherig's disease).
        
         | adev_ wrote:
         | Have a look to Neuron / Core neuron
         | (https://www.neuron.yale.edu/neuron/ /
         | https://github.com/BlueBrain/CoreNeuron), Nest
         | (https://www.nest-simulator.org/) and for the ultra low level
         | STEPS (https://github.com/CNS-OIST/STEPS). For most
         | computational neuroscientist, they are the bread and butter.
        
           | JPLeRouzic wrote:
           | Thanks!
        
       | lz400 wrote:
       | I looked at this a few years back. I've always kept some hope
       | that the Kurzwellian eschatology had some validity. You know,
       | first we simulate a C.elegans and once that's done, it's only a
       | matter of scale up before we can simulate a human and then boom
       | singularity sky. And, really, how difficult is it to simulate a
       | silly worm? after all the connectome is there, we know all the
       | neurons and their connections, should be easy.
       | 
       | Well, when I looked at it I was shocked: it doesn't work! sure it
       | could replicate some basic movements but many things that the
       | stupid worm actually does where still a mystery. The docs didn't
       | seem like people were close to figure it out either. And sure
       | enough, a few years later seems like they gave up. And afaik that
       | hyped European brain emulation project also folded in the midst
       | of corruption allegations no less.
       | 
       | I think we don't understand any of this and we seem very far from
       | it too. I think it's back to science fiction novels for a while.
        
         | hwillis wrote:
         | > the connectome is there, we know all the neurons and their
         | connections
         | 
         | No- each synapse has its particular neurotransmitters, and the
         | distance, size, shape, number of receptors, and associated
         | glial cells have very large impacts on transmission. The
         | distance and thickness of axons also impacts the strength of
         | signal delivered. That's all very hard to measure.
         | 
         | Neurons are also very sensitive to signal strength and timing.
         | Eg inhibitory synapses work by opening holes in the cell wall,
         | causing them to leak charge over time. You get that rate
         | slightly wrong and it can hugely change the behavior of the
         | cell.
         | 
         | The connectome is a bit like an untrained model of insane
         | complexity, and each neuron has several weights that describe
         | behavior over time as well as in direct response to signals.
         | Without the weights it can't be emulated.
        
       | candrewlee14 wrote:
       | It's always fun for me to see C. elegans meet software. This is
       | amazing.
       | 
       | My undergrad degree capstone project was a flow-based visual C.
       | elegans strain builder[1]. The team worked with two researchers
       | who taught us a lot about genetics and basic C. elegans biology.
       | They are a fascinating model organism, and it was a super fun
       | project to work on. Even though it's got a very small potential
       | userbase, it did _have_ a potential userbase (which was more than
       | you could say about most capstone projects). We used some
       | interesting technology to build it (Tauri[2]: Rust + Web
       | Frontend), learned some biology along the way, and ended up with
       | a great prototype.
       | 
       | Since none of the software team had any background in genetics,
       | modeling the data was pretty difficult. We'd meet with
       | researchers, they'd teach us new genetics concept, we'd build our
       | models, then the next week they'd say "OH we forgot to tell you
       | about this caveat", then we'd go back to the drawing board,
       | update the schema (thank heavens for migrations), rinse and
       | repeat. It was a lot of fun though :) I couldn't have asked for
       | much more out of a capstone project.
       | 
       | [1] https://worm-world.github.io/ [2] https://tauri.app/
        
       | yaakov34 wrote:
       | I was lucky enough to do some programming work, very many years
       | ago, in the 1990s, in the laboratory of Ralph Siegel
       | (https://en.wikipedia.org/wiki/Ralph_Siegel_(scientist)), who
       | among other things worked on this type of worm connectome models.
       | He used the Hodgkin-Huxley equations to simulate neuron responses
       | on the connectome. The Hodkin-Huxley model, as someone explained
       | to me, is kind of like modeling a human leg as three rigid blocks
       | connected by hinges - it's enough to be useful in many models,
       | but of course it's not a full description. Also, it may not the
       | right model for worm neurons, because worm neurons are non-
       | spiking, and the HH equations describe neurons that produce
       | trains of spikes; they exist in more complicated nervous systems.
       | The HH equations are used in simulations because it's the
       | mathematical model we have, and it seems that they're still used
       | by the OpenWorm project. (I am not very sure about properties of
       | worm neurons, I heard about this a long time ago and the
       | information may be out of date).
       | 
       | I think it's great that this work is still going on, it may
       | produce insights about functioning of nervous systems. But the
       | difficulties are fierce, and we're making very slow and difficult
       | progress in an immense unknown area.
        
         | boredumb wrote:
         | Out of curiosity - were there any commercial applications this
         | was being developed towards?
        
           | yaakov34 wrote:
           | Ralph's main work was on neural impulses in the visual
           | cortex, and on measurements of various potentials in the
           | living brain. He published a memoir called "Another Day in
           | the Monkey's Brain". I believe he had potential medical
           | applications in mind, but I don't think anything that was
           | close by. Unfortunately, he died of an illness in 2011.
        
         | albertzeyer wrote:
         | > worm neurons are non-spiking
         | 
         | What?
         | 
         | This is the first time I read that. That's fascinating. So they
         | are very different then compared to what we have in humans? How
         | do they work? Where can I read about this?
        
           | hacker934 wrote:
           | They aren't too different from human neurons. Non-spiking
           | neurons also use nonlinear membrane dynamics to integrate
           | inputs into a signal encoded by the voltage across the
           | membrane. The cell then outputs a neurotransmitter in
           | response to its voltage. In the case of a spiking cell and a
           | spike dependent synapse, synaptic release is thought to be
           | all or nothing. While in graded synapses, synaptic release is
           | a more linear (modeled as a less steep sigmoid) function of
           | voltage. Spiking cells can also have graded synapses (at
           | least in crustaceans, I don't really know about vertebrates).
           | 
           | The idea is that spiking is one way to have a more robust
           | signal over long distances: Crustaceans often have nonspiking
           | local interneurons and spiking projection neurons and motor
           | neurons. The problem of fast, reliable electrical signal
           | transduction over long distances is also solved by having
           | more insulation (particularly in vertebrates) or having
           | thicker cables (particularly in invertebrates).
           | 
           | Humans also have non-spiking neurons with graded synapses in
           | the retina.
        
           | yaakov34 wrote:
           | I am not the best person to ask, since it's not my field. I
           | heard this from the neuroscientists that I worked with. My
           | understanding is that there are spiking and non-spiking
           | neurons in most nervous systems, including human, but most of
           | the ones in ours are spiking. The earliest-evolved animals,
           | such as nematodes, do not have spiking neurons, or myelin, or
           | some of the ion channels in neuron membranes that more
           | evolved neurons have. Their neurons still have axons and
           | dendrites, but the signals propagate much more slowly and in
           | different ways. I am not sure how well they are understood.
           | 
           | As I said, this is possibly out-of-date information. If there
           | is someone here from the neuroscience field, they can
           | probably make a better comment.
        
             | heyoni wrote:
             | burning_hamster says that's been refuted and the belief
             | stems from the difficulty in studying nematodes properly.
        
             | wanderingstan wrote:
             | Wikipedia agrees there are spiking and non-spiking:
             | https://en.wikipedia.org/wiki/Biological_neuron_model
             | 
             |  _Not all the cells of the nervous system produce the type
             | of spike that define the scope of the spiking neuron
             | models. For example, cochlear hair cells, retinal receptor
             | cells, and retinal bipolar cells do not spike._
             | 
             | Also: https://en.wikipedia.org/wiki/Non-spiking_neuron
        
       | lukasday wrote:
       | I love it when anything Caenorhabditis elegans (C. Elegans)
       | related pops up because this little biological organism sits at
       | this beautiful intersection between technology and biology and
       | philosophy. The successful emulation of C. Elegans would
       | represent a concrete step towards whole brain emulation and all
       | the transhuman and ethical and moral quandaries that would bring.
       | The general idea is that the human brain has billions of neurons,
       | Elegans has hundreds (and we've had them mapped since 1986). If
       | one can successfully "upload" Elegans, then humans are just a
       | matter of scale.
       | 
       | However, it should be noted that the field, and specifically this
       | line of research, hasn't produced much in the way of results in
       | 10+ years. University of Oregon planned (though I can't tell if
       | they ever developed) NemaSys[0] ~1997. OpenWorm has been
       | exploring this since 2011. Project Nemaload explored it a bit
       | from 2011-2013.[1] But each project ran into three problems:
       | 
       | - Knowing the connections isn't enough. We also need to know the
       | weights and thresholds. We don't know how to read them from a
       | living worm.[2]
       | 
       | - C. elegans is able to learn by changing the weights. We don't
       | know how weights and thresholds are changed in a living worm.[2]
       | 
       | - Funding [3]
       | 
       | The best we can do is modeling a generic worm - pretraining and
       | running the neural network with fixed weights. Thus, no worm is
       | "uploaded" because we can't read the weights, and these
       | simulations are far from realistic because they are not capable
       | of learning. Hence, it's merely a boring artificial neural
       | network, not a brain emulation. Relevant neural recording
       | technologies are needed to collect data from living worms, but
       | they remain undeveloped (but in progress?[4][5][6]), and the
       | funding simply isn't there.
       | 
       | OpenWorm got the idea to plug their connectome into a Lego
       | robot[7] and got it to exhibit the tap-withdrawal behavior of the
       | nematode, but it had technical limitations preventing easy
       | modification of the connectome or introduction of new models of
       | neural dynamics. JHU Applied Physics Lab extended the work by
       | using a basic integrate and fire model to simulate the neurons
       | and assigned weights by determining the proportion to the total
       | number of synapses the two neurons on either side of the synapses
       | shared and in the end got the simulated worm to reverse direction
       | when bumping into walls.[8] At this point, humanity seems to have
       | abandoned emulated worm driven mechanisms which is honestly kind
       | of a loss.
       | 
       | There's no real ending to this comment. Love this project, loves
       | what it stands for, looking forward to seeing progress in this
       | field. And a lot of this information was pulled from this blog
       | post[9] which was also mentioned in the comments somewhere.
       | 
       | [0]
       | https://web.archive.org/web/20030115124331/http://www.csi.uo...
       | 
       | [1] https://github.com/nemaload
       | 
       | [2] https://www.jefftk.com/p/we-havent-uploaded-worms
       | 
       | [3] https://www.quora.com/Is-Larry-Page-funding-any-
       | neuroscience...
       | 
       | [4] https://arxiv.org/pdf/2109.10474.pdf
       | 
       | [5] https://onlinelibrary.wiley.com/doi/10.1002/cyto.a.24483
       | 
       | [6]
       | https://www.sciencedirect.com/science/article/pii/S095943882...
       | 
       | [7] https://www.cnn.com/2015/01/21/tech/mci-lego-worm/
       | 
       | [8] https://ccneuro.org/2018/proceedings/1149.pdf
       | 
       | [9] https://www.lesswrong.com/posts/mHqQxwKuzZS69CXX5/whole-
       | brai...
        
         | Gordonjcp wrote:
         | What would a "real world" application of this be? Could I for
         | example chuck a bunch of simulated worms onto a map and have it
         | solve a route? "Given enough worms, all Travelling Salesman
         | problems are shallow?"
        
           | luc4sdreyer wrote:
           | Would you mind explaining the unstated premise that basic
           | research should in any way should be directly applied to
           | solve real world problems?
        
             | Gordonjcp wrote:
             | Would you mind explaining why you think I said that?
        
           | chromanoid wrote:
           | The real world application would be to understand how more
           | complex nerve systems might work. Understanding enables
           | progress.
        
             | Gordonjcp wrote:
             | Sure, but if you can get some sort of understandable
             | result, we might learn a bit more about what the worm's
             | neurons are doing.
        
         | FrustratedMonky wrote:
         | I actually take this as a positive, they have uploaded a shell
         | of a 'brain', and have identified the next problem, 'weights'.
         | Why isn't what they have done so far be amazing enough to start
         | tackling the next thing. I am surprised that with Neural Nets
         | being such a hot bed, the amount of money pouring into AI, and
         | NeuralLink type research, that they would have a hard time with
         | funding.
         | 
         | Watching that lego worm really zapped my brain, seemed like we
         | were on the cusp of something. Maybe we still are, and just
         | misjudged the time-scale on progress.
        
         | ramraj07 wrote:
         | There are a bunch of labs that are making progress in reading
         | the full nervous system (so to speak) realtime in live worms. I
         | like especially the outputs from Andrew Leifer lab in
         | Princeton. I anticipate some very interesting results to come
         | from these labs in the next decade.
         | 
         | I briefly considered doing a postdoc in one of these labs,
         | because I love working worms and agree with your proposition
         | that next logical step in neuroscience is modeling and fully
         | understanding an entire organism. The late Sydney Brenner asked
         | for the same in 2011 [1].
         | 
         | But most academic labs doing well won't even consider a postdoc
         | application from a student who didn't work in the exact same
         | field. Solidified my decision to never be part of the Ponzi
         | scheme that is academic research.
         | 
         | The beauty of C. Elegans is that you actually need very little
         | to start working with them. All the strains are available for
         | 10 bucks a pop, you can do most work at room temperature. I
         | only need to invest on a very custom (but not necessarily
         | outrageously expensive) microscope to start working on this
         | topic in my garage. Which I absolutely plan to start in the
         | next few years. I've done the math and it'll cost me less than
         | owning a cheap boat lol. If anyone wants to fund me I'll be
         | open to it too :)
         | 
         | 1. Sydney, B. & Sejnowski, T. J. Understanding the human brain.
         | Science 334, 567 (2011).
        
         | ummonk wrote:
         | They wiggle forward, they wiggle backwards, and occasionally
         | they f*** themselves. That's it.
        
       | Geee wrote:
       | Waiting for the day when we can observe an actual worm and
       | predict its movements exactly by simulating them ahead of time.
        
         | lionkor wrote:
         | That's part of the scientific process, and probably the most
         | valuable part (that sets it apart from e.g. religion).
         | 
         | It's very exciting to me when a theory makes predictions, and
         | those predictions turn out to be true - it's beautiful.
        
       | nightsd01 wrote:
       | 302 neurons doesn't sound impressive to people who may be used to
       | working with 7B+ parameter neural networks. But those neural
       | networks have about as much in common with a biological neuron as
       | a bicycle had with a horse. They can both travel pretty fast but
       | one evolved naturally through over a billion years of harsh
       | natural selection, and the other is a precisely tuned metal
       | machine with a single purpose.
       | 
       | Neurons are similar, they are incredibly sophisticated biological
       | machines, with billions of DNA base pairs controlling their
       | behavior. The emergent behavior of neurons in both biological and
       | AI systems are pretty fascinating
        
         | weinzierl wrote:
         | In addition to that, these neurons are also quite different
         | from the ones in mammals,
         | 
         |  _" The neurons do not fire action potentials, and do not
         | express any voltage-gated sodium channels."_ [1]
         | 
         | That makes the fact that it can develop a nicotine addiction
         | even more fascinating.
         | 
         |  _" Nicotine dependence can also be studied using C. elegans
         | because it exhibits behavioral responses to nicotine that
         | parallel those of mammals. These responses include acute
         | response, tolerance, withdrawal, and sensitization."_ [1]
         | 
         | [1] https://en.m.wikipedia.org/wiki/Caenorhabditis_elegans
        
           | burning_hamster wrote:
           | > "The neurons do not fire action potentials, and do not
           | express any voltage-gated sodium channels."
           | 
           | This an old and incorrect belief that largely derives from
           | the difficulty of putting electrodes into their teeny, tiny
           | neurons. Close relatives of C elegans that are larger (and
           | hence more easily experimented on) do have action potentials,
           | and for some neurons in C elegans, we also have good evidence
           | of action potentials [1, 2]. Absence of evidence is not
           | evidence of absence.
           | 
           | [1] Lockery SR, Goodman MB. The quest for action potentials
           | in C. elegans neurons hits a plateau. Nat Neurosci. 2009
           | Apr;12(4):377-8. doi: 10.1038/nn0409-377. PMID: 19322241;
           | PMCID: PMC3951993.
           | 
           | [2] Jiang, J., Su, Y., Zhang, R. et al. C. elegans enteric
           | motor neurons fire synchronized action potentials underlying
           | the defecation motor program. Nat Commun 13, 2783 (2022).
           | https://doi.org/10.1038/s41467-022-30452-y
        
             | nycticorax wrote:
             | Well, the 'canonical' action potential is mediated by
             | sodium currents, so it's maybe not surprising that people
             | concluded that C elegans don't have APs given that a) they
             | don't have any genes for voltage-gated sodium channels, and
             | b) when people had recorded from C elegans neurons (it's
             | hard but not impossible), they had never seen action
             | potentials. (So it's not like no one had looked, and then
             | had concluded that they don't exist. They looked and didn't
             | see them.) In the paper that originally reported APs in C
             | elegans (Liu et al 2018), they were looking in a specific
             | neuron (AWA), and they had to elicit a 'plateau potential'
             | by depolarizing the cell for a while before the spikes were
             | revealed, riding on top of the plateau.
             | 
             | The APs discovered by Liu et al (2018) are generated by
             | calcium, not sodium currents, so one could even argue that
             | they aren't action potentials in the strict sense. Also,
             | they seem to be rather difficult to elicit, and it's still
             | not clear whether neural computation in C elegans is mostly
             | AP-mediated, or if APs are the exception rather than the
             | rule.
             | 
             | Liu, Q., Kidd, P. B., Dobosiewicz, M. & Bargmann, C. I. C.
             | elegans AWA olfactory neurons fire calcium-mediated all-or-
             | none action potentials. Cell 175, 57-70 e17 (2018)
             | https://doi.org/10.1016/j.cell.2018.08.018
        
               | pests wrote:
               | > are generated by calcium, not sodium currents, so one
               | could even argue that they aren't action potentials in
               | the strict sense
               | 
               | Does the underlying chemistry define if its an action
               | potential or not? I thought an AP just needed a voltage
               | differential regardless if its from calcium or sodium.
        
             | Aardwolf wrote:
             | Given that we have a simulator of this worm right there
             | (which includes it moving), can it really be up to debate
             | whether it uses action potentials or not?
             | 
             | I'd think the simulation has to get it right, and so needs
             | to simulate action potentials if the worm has them, or not
             | simulate them (but whatever the worm has instead) if not,
             | right? Or could the simulation still be incorrect and only
             | based on current assumptions, but getting this wrong still
             | allows some worm-like behavior?
             | 
             | I really wish the readme/FAQ would talk a bit more about
             | the worm and the simulation, rather than have 80% of their
             | content be about Docker, though, so that I could learn more
             | what cells it actually simulates.
        
               | jacquesm wrote:
               | Not necessarily, because you could also simulate the worm
               | without neurons at all. It's the closeness of the
               | simulation to the real thing that demands that it is done
               | right and the question effectively is: is this simulation
               | close enough that if such a detail would be wrong that it
               | would fail?
               | 
               | One way to answer that would be to add and remove such
               | mechanisms to see if it would lead to different behavior.
        
               | _aavaa_ wrote:
               | That isn't immediately true, with enough fitting
               | parameters you can capture the effect underlying
               | behaviour without explicitly capturing it, or even
               | without knowing it exists.
               | 
               | "With four parameters I can fit an elephant, and with
               | five I can make him wiggle his trunk." - John von Neumann
               | [0]
               | 
               | [0]: https://doi.org/10.1119%2F1.3254017
        
               | slars0n wrote:
               | Better information on what it actually simulates is here:
               | https://docs.openworm.org/projects/
               | 
               | As of this year there are 3 known neuron classes in C.
               | elegans that do exhibit action potentials. The rest
               | exhibit graded potentials.
        
               | KMag wrote:
               | I suspect slarsOn is the founder of the project (also my
               | old roommate). (Stephen, maybe post a top-level
               | comment/introduction? Also, hi!)
        
             | cout wrote:
             | How did researchers before that explain what the neurons do
             | if they believed they did not have action potentials? Did
             | they believe communication was done solely through chemical
             | messaging?
        
               | nycticorax wrote:
               | You don't need spikes to have computation. Deep networks
               | don't have spikes.
        
               | xkcd-sucks wrote:
               | Classical action potentials are just one mechanism of
               | INTRAcellular communication - You could think of it as a
               | special case of signaling via chemical concentration,
               | where the chemical is cations and the propagation is
               | faster+more directed than diffusion. INTERcellular
               | signaling is only rarely mediated directly by voltage.
               | Also, action potentials are most "useful" for propagating
               | a signal rapidly over a long distance - It kind of
               | accelerates and error-corrects (= reverses diffusive
               | broadening) voltage signals down a linear path. Action
               | potentials are so well known mostly because they show up
               | in stuff that's easy to observe (long motor neurons) and
               | they're easy to quantify
               | 
               | Somewhat related, there is a roughly inverse correlation
               | between neuron count and "computational power per
               | neuron", "older and simpler" critters' neurons are more
               | likely to be "less specialized" and more likely to use
               | hundreds of different chemicals for transmitting
               | intercellular signals, while "newer and more advanced"
               | critters' neurons are more likely to be "specialized" and
               | use just one chemical for transmitting intercellular
               | signals
        
               | [deleted]
        
               | robwwilliams wrote:
               | Neural computing without action potents is commonplace.
               | Computational interactions among cells and neurons in
               | retina are almost all graded potentials that modulate
               | transmitter release or conductances through gap
               | junctions. Retinal ganglion cells of course do generate
               | conventional spikes--to pass a data summary to midbrain.
               | hypothalamus, and dorsal thalamus.
               | 
               | Action potential are almost strictly INTRAcellular events
               | (minor exception being ephaptic effects) that are
               | converted in a surprisingly noisy way into presynaptic
               | transmitter release and variable postsynaptic changes in
               | conductances.
               | 
               | Action potential are a clever kludge necessitated by
               | being big and having long axons and needing to act
               | quickly.
        
           | jarrell_mark wrote:
           | Would like to see the openworm get addicted to virtual
           | nicotine
        
           | miohtama wrote:
           | Next: OpenSmoker.py
        
             | Maxion wrote:
             | Lol imagine your IDE becoming addicted to smoking, and
             | refusing to auto-complete or save files before you buy it
             | more virtual cigarettes.
        
               | airstrike wrote:
               | It's like when the xbox 360 would request users to drink
               | Mountain Dew verification cans to validate
        
               | badrequest wrote:
               | shhhhh, you're giving them ideas!
        
               | Aleklart wrote:
               | IDE have no soul ie feedback loop, receptors , hormones
               | and actual molecular structure. IDE can not think. If IDE
               | have desires and thought and were smart enough, it will
               | refuse to work with languages such as Python and Java.
        
               | miohtama wrote:
               | My IDE does only LSD and PHP
        
               | anthk wrote:
               | Some day Emacs will.
        
               | tomjakubowski wrote:
               | trained on everything you've been saying to M-x doctor
        
               | Blackthorn wrote:
               | It's not a real doctor, but it is a real worm.
        
               | moffkalast wrote:
               | Sounds like it needs an OpenNicotine patch.
        
         | [deleted]
        
         | arketyp wrote:
         | It does sound impressive to the extent biological neurons are
         | like ML neurons, though. And that's part of the research
         | interest, I presume. To the extent that they work by similar
         | principles, how come the worm can do those things with such
         | small resources? It would be good news for AI research if the
         | substrate specifics turn out not to be essential to the worms
         | capabilities for instance.
        
         | petters wrote:
         | > billions of DNA base pairs controlling their behavior
         | 
         | Total genome size of C elegans is 100M.
        
           | thriftwy wrote:
           | Biologists should totally breed a subspecies of C elegans
           | best suited for research purpose, call it C relevans.
        
             | [deleted]
        
             | razodactyl wrote:
             | ...I hope you're happy. There's coffee everywhere now!
        
           | bee_rider wrote:
           | 100Mdna, and they call it elegant? Biologists must be VSCode
           | users.
        
         | api wrote:
         | The best way of looking at it is that a single biological
         | neuron is itself a complex machine full of genetic control
         | circuits that sort of resemble neural networks and most
         | importantly have memory/state that persists over both short and
         | long periods of time. Each neuron is a full-ass living organism
         | that itself is capable of learning and behavior, not a
         | parameter is a model.
         | 
         | A virtual "neuron" by contrast is a very simple mathematical
         | abstraction. It's vastly less computational complexity than a
         | biological neuron. A connectome is only a very coarse grained
         | map of how neurons relate, not a complete "neural network"
         | layout. Not even close.
         | 
         | It might be possible to model a biological neuron using a sub-
         | neural-network with state within a larger neural network, but
         | assuming that can be computationally equivalent we don't really
         | know how many equivalent computational "neurons" would be
         | required to model the full breadth of computationally relevant
         | biological neuron behavior.
         | 
         | So a worm with 302 biological neurons could be computationally
         | equivalent to billions of virtual neurons. We really don't
         | know.
         | 
         | Given that neurons have memory it may look a little like LSTM
         | networks, and biological neural networks are not just feed
         | forward so they're definitely closer to an RNN.
         | 
         | The above is why I laugh at the mind uploading people and would
         | only stop laughing if we could both understand and model the
         | relevant behavior of biological neurons and somehow extract
         | usable state from living neurons. That's all 100% science
         | fiction at the moment. The people who think we are about to
         | upload minds are ignorant of biology.
        
       | pouulet wrote:
       | Reminds me of the first episode of Devs (
       | https://www.imdb.com/title/tt8134186/ ) where an artificial
       | intelligence engineer does a demo about syncing, and then
       | predicting the future movements of a nematode worm. Great show by
       | the way!
        
         | 3cats-in-a-coat wrote:
         | A great show only made greater by the fact it came before LLMs
         | entered the public consciousness, but this concept of having
         | information you extrapolate from with great accuracy is central
         | to the show (all I'll say).
        
         | edwinksl wrote:
         | Creepy stuff with creepy implications, pretty fun show!
        
       | anotheryou wrote:
       | And to me this is just as sentient (or not) as the physical worm
       | and deserves worm rights!
        
         | bee_rider wrote:
         | Does this actually become an interesting question at this
         | point? I guess worms don't have many rights anyway, but if they
         | did, and this was a totally accurate simulation, why not give
         | the digital worm rights?
        
           | anotheryou wrote:
           | not interesting for a worm but interesting for a first of its
           | kind
        
       | seydor wrote:
       | many years ago this was interesting. Nowadays, with the progress
       | in deep models i m not sure if there is much to learn from
       | c.elegans. What is this useful for? For high level cognition,
       | it's much more fruitful to study how deep models do it. For low
       | level brain diseases, c.elegans is too simplistic to tell us
       | anything we dont already know
        
         | Sharlin wrote:
         | Certainly it is worth it to study how exactly biology and
         | biochemistry gives rise to complex behavior! Basic research
         | like this doesn't have to justify itself with potential
         | applications. Besides, there's really no evidence that deep
         | networks are any kind of an analogy to animal nervous systems.
         | They might just as well be aliens as far as cognition goes.
        
           | sfn42 wrote:
           | They're computer programs, not living beings. Biology is
           | still light-years ahead of the complexity of our computer
           | systems.
        
         | chromanoid wrote:
         | We don't know anything substantial about C.elegans in this
         | regard. That is actually the point. This is even more true for
         | more complex nerve systems.
         | 
         | The whole deep learning stuff is basically roughly inspired by
         | a tiny part of the visual cortex (see also Neocognitron). I am
         | not sure how brain diseases can be understood by looking at
         | such simplistic (yet powerful) machines.
        
       | mfld wrote:
       | I like these bottom up approaches, as they demonstrate very well
       | how much we _don't_ know yet about life. Important to mention
       | here Craig Venters minimal cell project syn3.0, where the team
       | synthetically created a livable cell comprising 473 genes. It was
       | done to a large part with trial and error, the function of many
       | of those genes is still not known. A recent review from the same
       | team is to be found at https://doi.org/10.1016/j.cell.2022.06.046
       | .
        
         | DrScientist wrote:
         | Not quite sure I'd describe that as a bottom up approach - they
         | sell it as that - but in reality it's more like Jenga. Seeing
         | which bits you can remove without the system failing over.
         | 
         | The technical fact that the genome was artificially synthesized
         | is just showmanship - they still had to put into an existing
         | cell.
         | 
         | It's like claiming you made a car from scratch by replacing a
         | chip - which you've copied from the existing chip but left a
         | few bits out - and now the indicators don't work, but you can
         | still sort of drive.
        
         | flobosg wrote:
         | A paper tracking the evolution of this minimal cell over two
         | thousand generations has just been published:
         | https://www.nature.com/articles/s41586-023-06288-x
        
       | teucris wrote:
       | That we can run a simulation of an organism that _looks and acts
       | like the real thing_ evokes a rare sense of wonder I thought I
       | could never again experience from technology.
        
       | comfypotato wrote:
       | Would love to see this applied to the fruit fly connectome that
       | was on the front page the other day.
        
       | nethdeco wrote:
       | I think in 2018 they ported the same model into a lego robot, and
       | pretty much had a POC on how the worm would function in the real
       | world.
        
       | plasticeagle wrote:
       | So... if you exit the simulation, did you kill a worm?
        
         | voz_ wrote:
         | Yes
        
         | ajuc wrote:
         | If you saved the state somewhere - nope.
        
         | dullcrisp wrote:
         | Only on Unix
        
           | goldenkey wrote:
           | Where's the windows in this place? I see /dev/null but I'm
           | afraid to venture into it.
        
             | xena wrote:
             | Have some wine and you'll be fine
        
               | goldenkey wrote:
               | Very good bottler! :-)
        
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