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The baffling intelligence of a single cell: The story of E. coli chemotaxis
- scrubs 2y agoGood gracious. A fantastic read. Wow.
- PcChip 2y agoExcellent writeup, i love the interactive animation
- ehmorris 2y agoIf you're interested the code for the simulation all lives here: https://github.com/ehmorris/ecoli-chemotaxis/tree/main/ecoliSimulation https://github.com/ehmorris/ecoli-chemotaxis/tree/main/ecoli...
- dbrgn 2y agoThe random spin followed by a run reminds me a bit of the first-generation Roomba logic...
- 082349872349872 2y agoor VC's between fads and during fads
- swader999 2y agoIncredible to think how something this intricate with so many interdependent parts and integrated systems could have evolved.
- swayvil 2y ago[flagged]
- beders 2y agoI know. But this is very well understood and researched. All it requires is mutations, time and selection pressure. The Blind Watchmaker is still a good read.
- FartyMcFarter 2y agoIt's still incredible despite all that. Not in the sense that one chooses not to believe it, but in the sense that it's hard to fathom that it actually happened.
- singularity2001 2y agoFirst you need the incredible machinery to enable mutations in the first place
- prmph 2y agoSo if a monkeys bangs on keys forever it will eventually produce Shakespeare? I'm quite skeptical
- FartyMcFarter 2y agoThere's no selection pressure when a monkey bangs their hands on a keyboard. It's just randomness without any consequence. The letters are not interacting with each other or their environment in any significant way.
- arkey 2y agoWhat about offering the monkey some peanuts if he bangs correct words, the more correct words the more peanuts he gets? I understand there would be limitations in the lifespan of the monkey and such, but in a hypothetical case, would that work?
- nyc111 2y agoThere is a section at the end "How did we figure all this stuff out?". Really amazing. And the scale invariance of nature is clearly visible here. The cell is "small" compared to human scale but it is as complicated as any machine existing in human scale. There is no absolute small or big in nature.
- beders 2y agoIt is a highly evolved bacterium for sure. It still hasn't figured out how to form multi-cell clusters. And let's hope it stays that way ;) Also scale is subject to physical limitations. Bones can only carry that much weight - chemical processes are limited by - for example - maximum energy dissipation rate.
- roenxi 2y agoI was about to post a very similar comment. That last section elevates the article from "interesting" to "wow, that was great". It isn't just revealed wisdom; the gentleman want to show the limits of the knowledge. And the "in silico" experiments are probably a bit of a sleeper for people outside the field. It is really obvious how improvements in computing power will have/had a transformative impact on this field. To go from poking out random molecules and growing dangerous things in a pitri dish to fast computer simulations from DNA seems like quite a big jump in how quickly the field can learn.
- fartsucker69 2y agothere would be an absolute small, at planck scales (from what we know) there's also an absolute big, known in cosmology, far beyond the scales of galaxies, galaxy clusters, etc... it's your mom
- graemep 2y agoIt is a lot more complex than anything made by humans, but it is nothing like as complicated as a human that consists of a huge number of cells.
- dotnet00 2y agoTechnically humans are also made by humans :)
- janpmz 2y agoI would love to understand how individual cells come together to form functioning organs with clear boundaries.
- dustingetz 2y agoelemental cells also have clear boundaries ie the cell membrane, which evolved as a way to catalyze a chemical reaction by containing all the ingredients in one place. imagine a fatty globule that randomly happens to enclose a set of chemical ingredients that react; that reaction is now far more likely to occur
- janpmz 2y agoThats a nice view. Packages of chemical ingredients that react. And they are in an environment together with gradients of molecules that start reactions at specific concentrations.
- swayvil 2y agoSelf-organizing brownie swarms manage the whole process from the ethereal plane.
- seatac76 2y agoFantastic read! If y’all are into this kind of stuff I highly recommend reading “The Song of the cell” by Siddhartha Mukherjee[1], it is one of the best books I’ve read that made the topic of biology approachable. [1] https://www.amazon.com/Song-Cell-Exploration-Medicine-Human/dp/1797147080/?tag=hyprod-20&linkCode=df0&hvadid=598250015901&hvpos=&hvnetw=g&hvrand=12773952844159733002&hvpone=&hvptwo=&hvqmt=&hvdev=m&hvdvcmdl=&hvlocint=&hvlocphy=1015307&hvtargid=pla-1646681468812&psc=1&mcid=d9718bc6bc223e48a7ceccc5cb749828 https://www.amazon.com/Song-Cell-Exploration-Medicine-Human/...
- sublimefire 2y agoHe is a great storyteller, 2 other very successful and interesting books of his: - The emperor of all maladies - about cancer research, for which he got a Pulitzer - The gene - about the evolution of the field and the discoveries and what is the latest thinking
- ramraj07 2y agoWhat does this book talk about that his previous book the Gene doesn’t?
- lmiller1990 2y agoI found Song of the Cell a bit underwhelming. The Gene really was fantastic - I think he ran out of steam a bit with Song of the Cell. The majority of the cell related history is also contained in The Gene.
- verisimi 2y ago> How did we figure all this stuff out? > We don’t yet have the technology to just observe all of the activity inside a living cell. That Goodsell painting above that shows the crowded cytoplasm packed with proteins is an artistic composite—backed by rigorous research to be sure—because there’s no way to capture all the different players in situ at once. > A group at University of Illinois at Urbana-Champagne uses atomic-scale molecular dynamics simulations, in software, to understand structural details > It’s a world that’s hard to see; sometimes you just have to imagine what’s going on down there, and back up those imaginings with the right experiments. > One reason I’m particularly attracted to studies of E. coli chemotaxis is that it’s an early star of what’s been called “in silico” biology. It’s been the subject of many computer models. Honest, at least.
- burnished 2y agoYeah I always appreciate that, I hate it when people shy away from honesty because they think some heckler won't understand the subtlety of the observations at play.
- verisimi 2y agoYou realise of course that models can be wrong. The map is not the terrain. Models are not reality. The observations here are on models. If I knock up something in excel, and other people use that thinking it is how things are, but do not refer to the reality the model represents because there is no way to do that, how useful is the model? Have you ever looked at old medieval beastiaries? Information is being relayed, but how useful is it? https://alexanderadamsart.wordpress.com/2019/07/30/the-bestiary-in-the-medieval-world/ https://alexanderadamsart.wordpress.com/2019/07/30/the-besti... Without a means to view the underlying thing the model is meant to represent, to check and correct one's misunderstandings, how useful can the model be?
- burnished 2y agoYou ask good questions but act like you already know the answers which is really unfortunate. you are mixing up models and simulations. A simulation can be a great way of exploring something unknown if you understand the rules in enough granularity. Models can be judged by their ability to make accurate predictions. Electrical engineering depends on both a great deal, I expect you agree that it is useful as a field given the method of communication we're using.
- wslh 2y agoIf you like this, there is a book about the complexity of a single neuron of the brain "Information Processing in Single Neurons" [1]. [1] https://www.amazon.com/Biophysics-Computation-Information-Computational-Neuroscience/dp/0195181999 https://www.amazon.com/Biophysics-Computation-Information-Co...
- stephc_int13 2y agoImagine a microscopic, fully autonomous and self-replicating Roomba that is also able to adapts at the individual and population levels. We're still quite far from replicating this kind of tech.
- agumonkey 2y agoyes evolution/nature .. life .. did a lot with very few long ago, any insect is a technological marvel if you look at it right
- CyberEldrich 2y ago> Imagine a microscopic, fully autonomous and self-replicating Roomba that is also able to adapts at the individual and population levels. Well, if the Roomba could exchange genetic information with the surrounding population and adapting to a changing environment would give the appearance of intelligence and design.
- retskrad 2y agoFrom a laymans perspective, can human beings create our own version of DNA, let's say with the use of transistors instead of biological cells, long into the future? Or is DNA just magic and we can't recreate it inside solid state objects like a robot made out of transistors?
- dweekly 2y agoNot sure if it's what you meant, but DNA Computing is a whole field! https://en.m.wikipedia.org/wiki/DNA_computing https://en.m.wikipedia.org/wiki/DNA_computing
- retskrad 2y agoThank you, that sounds interesting
- two_handfuls 2y agoIt’s not magic, we can synthesize DNA. But we don’t yet have the kind of nanotechnology that cells do.
- burnished 2y agoDNA sequences are instructions that get printed on the spot and self assemble. This requires a great deal of flexibility so any reproduction would probably look much like what we find in nature. Or did you understand that and were wondering if we'd ever coopt the bodies mechanisms to create familiar logic gate based compute? Personally I doubt that we'd use already familiar transistors because the process requires ultra pure materials that are modified in very thin layers using gasses to scrape or place individual layers, but maybe we'd find a mechanical analogue expressible via protein, or at that point use purpose built neurons instead.
- bell-cot 2y agoOn the one hand, this is extremely cool science. OTOH, English really needs another word, meaning "like intelligence, but it could be simulated by an analog computer with a good handful of of discrete components".
- whelp_24 2y agoI think intelligence is the correct word. Why not?
- bell-cot 2y agoUseful languages can succinctly distinguish things which are qualitatively quite different. Describing everything in the world as "intelligent" sounds kinda cool and Zen, and may reflect some peoples' worldviews - but it also make "intelligent" pretty useless as an adjective.
- whelp_24 2y agoWhy is intelligence a bad descriptor?
- bell-cot 2y agoIf "hot" described any temperature from "the dark side of Pluto" to "the core of a brand-new neutron star" - then how useful a word would "hot" be, for communication between humans?
- HarHarVeryFunny 2y agoBecause: 1) It's a poorly defined word that means different things to different people 2) The word "mechanism" perfectly describes what it is At the end of the day it's just using the detection of food, to switch from "tumble" (try a random direction to find food) to "run" (assume we're near, or in, a patch of food, and move forward to consume more).
- burnished 2y ago
- singularity2001 2y agoThese ribbons look a bit like wires, transforming the information of an attached molecules through the membrane through physical tension
- gilleain 2y agothe red helices? those are transmembrane helices, and i guess yes they can transmit information in some cases. there are receptors in the membrane of our cells that respond to mechanical force
- londons_explore 2y ago> We don’t yet have the technology to just observe all of the activity inside a living cell. How close are we to being able to make a map of all atoms within a cell? There are 1E23 atoms in 1 ml of water, and an ecoli is about 500nmx500nmx1um. That means there are only about 2E10 atoms in the whole cell! Would it be possible to somehow freeze a whole cell, then use an electron beam to knock off and identify (via mass) every atom there?
- koeng 2y agoWe’re pretty close. There’s TEM microscopy tech which basically tilts a sample to get a bunch of lines, which is then reconstructed as a 3d model. It’s stupid expensive though, and you can only really identify whole proteins. But you can do that in context, which is massive
- namaria 2y agoKey word here is activity. Even if you froze a cell and mapped it down to an atom, you'd need to do it again for a cell you somehow managed to freeze in the state immediately after the first one, and so on. What granularity would be significant? What branching of what process would you like to follow?
- talkingtab 2y agoThe way I think about this comes from reading John Holland's "Hidden Order". If you read that book not as a book but as a way to build a Complex Adaptive System, then it comes down to a few essentials. An environment, a bunch of entities, a read/write messaging bus so the entities can interact. The entities need a set of rules and sensors. Put it together and what have you got? Thinking. Or intelligence. Try building one. Is the RIP routing protocol a complex adaptive system? Part of our problem is the way we think. I am a person. I am not a complex adaptive system. And yet I am. I am made of entities. There is a messaging bus, the entities sense, act and interact. But I don't think of myself as a CAS or talk about We. Wecellfs? Perhaps this a Sapir-Whorf thing. Our language limits what we can think. What is the difference between a pile of ants and an ant colony? A colony is collection of entities, but what do we call the entity that is the colony? Are the ants smart or is the colony smart.
- swayvil 2y agoSo as we add layers of language, intelligence goes down. (Of course, to the residents of that layer, only the residents of that layer are intelligent. The depths are inscrutable chaos. And further layers are ... Tools? Toys?) Individuals are smart, committees are dumb. Fundamental particles must be geniuses.
- Jensson 2y ago> Individuals are smart, committees are dumb. But a human isn't a bunch of individual cells, it is a cell that cloned itself many times. Those cells all have the same base code and can thus become an intelligent committee.
- swayvil 2y agoSo the more identical the committee members are, the smarter the committee?
- Jensson 2y agoAt least a committee of 10 identical members wont be dumber than a single member most of the time. A committee of clones is just scaling up compute in order to solve larger problems. Imagine if you could clone yourself with your knowledge and mental state, much more useful than trying to cooperate with another human.
- ta8645 2y ago> I never liked the way biology was taught in high school. It was too much about the names of things. A subject so vast is spoiled by a textbook, which can only point at the endless parade of stuff-there-is-to-know. Amen. You could easily teach quite intricate biology in grade school, if you focused on a fascinating example or two. How many more people would be inspired, rather than bored?
- m3kw9 2y agoIt turns out the curriculum was made by a bunch of teachers that has been old school taught. Seniority and entrenchment, nobody in that group risking their heads to suggest any deviation from old beliefs
- lostemptations5 2y agoOr maybe it wasn't done maliciously -- rather that's the way they thought it should be taught...
- atticora 2y agoThere's a nice discussion of this in Surely You're Joking, Mr. Feynman! > I discovered a very strange phenomenon: I could ask a question, which the students would answer immediately. But the next time I would ask the question – the same subject, and the same question, as far as I could tell – they couldn’t answer it at all! > Then I say, “The main purpose of my talk is to demonstrate to you that no science is being taught in Brazil!” https://v.cx/2010/04/feynman-brazil-education https://v.cx/2010/04/feynman-brazil-education
- magicalhippo 2y agoWe had a student in class which was so brilliant at memorizing stuff. But each test had one or two questions where you had to put together the knowledge, not just regurgitate, and that student consistently failed those question on each and every test. Yet the student got top scores on each and every test, because the accumulated number of points was enough to get them into the top bracket. I was so annoyed with that, asking the teacher how they could get top scores while clearly demonstrating they didn't understand the subject matter. Of course, all in vain. edit: Great read BTW
- jmyeet 2y agoSo I have three thoughts about this. The first is cell specialization, particularly neurons. It seems like nature really came up with a universal neuron. There aren't neurons for eyesight vs thinking, etc. They've experimented with this on frogs where they've reweired the optic nerve to a different part ofd the brain and the frog seems to see just fine. They've even added an eye and the frog seems to cope and use it just fine. The second is the OpenWorm project [1]. This is an attempt to simulate a relatively simple organism with IIRC ~280 neurons. Despite lots of effort, the simulated version just doesn't match up to the real thing. In artificial neural networks we have a stupidly simplified model of neurons that tends to get reduced to a binary signal and an activation function. Thius can do a lot but it's clearly wholly inadequate for any realistic modelling. The protein interactions in a cell are mind-bogglingly complex. The third is the three-body problem. To summarize, we have a general solution for the grvity interactions of two bodies. Add one more and we don't. We have classes of solutions but no general solution. This is why JPL needs to use supercomputers to calculate flight plans with a relatively low number of bodies. We see a relatively simple set of interactions lead to massive complexity with protein folding. I imagine that it just won't be computationally viable to simulate even a single realistic cell given all th einteractions that go on. We're simply left to make estimations. [1]: https://openworm.org/ https://openworm.org/
- m3kw9 2y agoMy one thought is that at the atomic level it is also “doing calculations” where by the interactions were evolved over eons to work they way it does. It’s like 3 body problem X a million, but it actually have a purpose and not chaos. If you know what I’m getting at
- dekhn 2y agoAre you sure JPL needs supercomputers to calculate flight plans? Please, if you know of more details, I'd like to see them. I was reading the NASA supercomputer complaint and it looks like trajectories can be calculated on extremely conventional small high performance computers now.
- javajosh 2y agoCheA phosphorylates CheY to become CheY-p, and CheZ dephosphorylates it back to CheY; CheW couples CheA to the receptors, and CheR methylates those receptors’ struts; CheB, meanwhile, “clips off” the methyl groups added to the struts by CheR. I guess 'naming things' isn't just hard in CompSci.
- the-mitr 2y agoI was introduced to the idea of even single cells can exhibit "learning" and "culture" via John Bonner excellent book The Evolution of Culture in Animals. Instead of thinking in terms of a discontinuity between animals or putting humans categorically different, Bonner builds this idea of a continuum instead for both culture and learning. Of course there are differences, https://press.princeton.edu/books/paperback/9780691023731/the-evolution-of-culture-in-animals https://press.princeton.edu/books/paperback/9780691023731/th... This post of course goes deep in the rabbit hole so to speak.
- yehosef 2y agoAm I allowed to think this is too complicated to be an accident?
- wiz21c 2y agoGiven the size of the universe and its age, I'd say we have waited long enough for probabilities to line up and produce such a complicated design.
- voidmain0001 2y agoI read a quote once that said “Simple bacteria can divide about every 20 minutes and have many hundreds of different proteins, each containing 20 types of amino acids arranged in chains that might be several hundred long. For bacteria to evolve by beneficial mutations one at a time would take much, much longer than three or four billion years, the time that many scientists believe life has existed on earth.” I haven't performed the math to back up the quote. As well would it change the time required if the bacteria mutate in parallel rather than in series?
- pishpash 2y agoIt's called the plasmid exchange. The search is parallelized to however many individuals there are, which is arbitrarily large, then the result is shared.
- jjk166 2y agoIt's the "one at a time" that is the issue here. Evolution is a massively parallel process. If a beneficial mutation happens once every million gnerations, and a generation is 20 minutes, that's a beneficial mutation every 38 years. If you have a million cells, that's a beneficial mutation every 20 minutes. If you have a billion cells, that's 1000 beneficial mutations every 20 minutes. In your body there are around 40 trillion cells. There are something like 10^31 cells on earth.
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- pmayrgundter 2y agoIf you do an accounting of all the organ functions, and then ask if the cell has this function independently, nothing is left out... but only if you allow that intelligence arises from the cells. So I believe intelligence arises from the cells and is an essential function of life, not only an emergent phenomena. The organs serve as division of labor amongst the cells in community for what they are already originally capable of themselves. More musings in this direction https://sites.google.com/site/pablomayrgundter/mind https://sites.google.com/site/pablomayrgundter/mind
- tonyhhey 2y ago[dead]
- photochemsyn 2y agoGreat writeup. Here's a full-text review that contains all the math needed to build a model of this process (2013): "Quantitative modeling of bacterial chemotaxis: Signal amplification and accurate adaptation, Yuhai Tu" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737589/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737589/ The main points are: * Both receptor cooperativity and accurate adaptation can be described quantitatively by simple mathematical models. * An integrated model (the “standard model”), which contains both signal amplification and adaptation, is developed to predict responses of it E. coli cells to any time-dependent stimuli quantitatively. * Exponential ramps induce activity shifts, which depend on the ramp rate through the methylation rate function F(a). * Responses to oscillatory signals reveal that E. coli computes time-derivative in the low-frequency regime. * E. coli memorizes the logarithm of the ligand concentration and the Weber-Fetcher law holds in E. coli chemotaxis. It also goes into cooperative phase transitions in the receptor complexes as a means of signal amplification, using the same model as in Ising ferromagnetic spin-spin interactions in physics.
- begueradj 2y ago> An individual E. coli has no brain, obviously, and is even many orders of magnitude simpler than a human cell, and yet already it possesses something like a sense of smell, drive, even a memory. A person is billions of billions of more effective cells than an E.coli cell: still our sense of smell, drive and memory do not seem to be billions of billions times more efficient.
- Biganon 2y agoBecause they don't need to be.
- chahex 2y agoHaha. I know you try to persuade me that consciousness as life force intelligence does not exist. But as far as I am concerned, I am and I am sentient and that is the only thing in my life I do not need any proof.
- oersted 2y agoThe video embedded in the article is a great and more brief explanation of what's written: https://www.youtube.com/watch?v=LgPDOSou1tw https://www.youtube.com/watch?v=LgPDOSou1tw
- crudcodersare 2y agoGod designing us in an emergent manner or through a static blueprint are the same thing. Someone had to create the laws, the genetic algorithm idea itself and all of these components and the environment for it to operate within never mind things like colors, matter etc. Evolutionists cant see the forest for the trees.
- deleted 2y ago[deleted]
- ihumanable 2y agoSo your answer to "where did this complexity come from?" is to invent an even more complex celestial being that just did it. Creationists can't see the forest for the trees.
- pinkmuffinere 2y ago> “ God designing us in an emergent manner or through a static blueprint are the same thing.” Perhaps I’m misunderstanding you, but to me it seems like you have no argument with evolutionists. Your beliefs seem to permit evolution. I think your disagreement is actually with people that see evolution as evidence for atheism.
- sethammons 2y agoThe one way signaling of the cell to alter tue production of chemicals kinda reminds me of thermostat adaptive weighted load balancing. Signals from nodes say that it can take more or should take less load, hot nodes shed automatically to cold nodes. And since it is weighted, if all nodes report hot, no load is shedded until full saturation of the cluster. Kinda felt similar to the cell comms. I wonder what interesting distributed coordination ideas we could learn in distributed systems computing from cellular biology.
- jonnycat 2y agoThis kind of unicellular complexity & intelligence has long been my soapbox material in the AGI debate. Even long before the current LLM craze, people were counting neurons in the brain and making bold claims about machine intelligence - in just X years, we'll have a machine with the computational power of the brain! But of course, every neuron in the brain is bafflingly complex and we still don't know or understand how that complexity manifests itself in thought and intelligence. Given physics and the interactions of "things", every cell in the brain is more complex than the LLMs we're using today. Not to say that every cell is capable of producing the same output as an LLM of course, just that the behavior that it contributes to the overall system is that complex.
- krzat 2y agoBrain is basically running a matrix-like simulation with a central person in it, for AGI we just need to simulate the thinking parts which is a simpler problem. But who knows how much simpler...
- thelastgallon 2y ago> But of course, every neuron in the brain is bafflingly complex and we still don't know or understand how that complexity manifests itself in thought and intelligence. Indeed. Biophysics of Computation: Information Processing in Single Neurons challenges this notion, using richly detailed experimental and theoretical findings from cellular biophysics to explain the repertoire of computational functions available to single neurons. The author shows how individual nerve cells can multiply, integrate, or delay synaptic inputs and how information can be encoded in the voltage across the membrane, in the intracellular calcium concentration, or in the timing of individual spikes: https://www.amazon.com/Biophysics-Computation-Information-Computational-Neuroscience/dp/0195181999/ https://www.amazon.com/Biophysics-Computation-Information-Co...
- oefnak 2y agoOn the other hand, AI doesn't have to be intelligent to be dangerous. Think of viruses for example.
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- kaiwen1 2y agoThis is wonderful! If you want to go deeper, I highly recommend the textbook "Molecular Biology of the Cell". I discovered it in a bookstore 20 years ago and it consumed me for months. Every paragraph was a revelation. After hearing me speak in awe of this book for years, my wife recently bought the latest (7th) edition, which we're now reading together and I'm still mesmerized. Nothing compares to the astonishing complexity of a cell.