The baffling intelligence of a single cell: The story of E. coli chemotaxis

The way I think about this comes from reading John Holland&#x27;s &quot;Hidden Order&quot;. 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&#x2F;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?<p>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&#x27;t think of myself as a CAS or talk about We. Wecellfs?<p>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.

Fantastic 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.<p>[1] <a href="https:&#x2F;&#x2F;www.amazon.com&#x2F;Song-Cell-Exploration-Medicine-Human&#x2F;dp&#x2F;1797147080&#x2F;?tag=hyprod-20&amp;linkCode=df0&amp;hvadid=598250015901&amp;hvpos=&amp;hvnetw=g&amp;hvrand=12773952844159733002&amp;hvpone=&amp;hvptwo=&amp;hvqmt=&amp;hvdev=m&amp;hvdvcmdl=&amp;hvlocint=&amp;hvlocphy=1015307&amp;hvtargid=pla-1646681468812&amp;psc=1&amp;mcid=d9718bc6bc223e48a7ceccc5cb749828" rel="nofollow">https:&#x2F;&#x2F;www.amazon.com&#x2F;Song-Cell-Exploration-Medicine-Human&#x2F;...</a>

&gt; 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.<p>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?

This kind of unicellular complexity &amp; 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&#x27;ll have a machine with the computational power of the brain!<p>But of course, every neuron in the brain is bafflingly complex and we still don&#x27;t know or understand how that complexity manifests itself in thought and intelligence. Given physics and the interactions of &quot;things&quot;, every cell in the brain is more complex than the LLMs we&#x27;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.

I was introduced to the idea of even single cells can exhibit &quot;learning&quot; and &quot;culture&quot; via John Bonner excellent book The Evolution of Culture in Animals.<p>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,<p><a href="https:&#x2F;&#x2F;press.princeton.edu&#x2F;books&#x2F;paperback&#x2F;9780691023731&#x2F;the-evolution-of-culture-in-animals" rel="nofollow">https:&#x2F;&#x2F;press.princeton.edu&#x2F;books&#x2F;paperback&#x2F;9780691023731&#x2F;th...</a><p>This post of course goes deep in the rabbit hole so to speak.

If you like this, there is a book about the complexity of a single neuron of the brain &quot;Information Processing in Single Neurons&quot; [1].<p>[1] <a href="https:&#x2F;&#x2F;www.amazon.com&#x2F;Biophysics-Computation-Information-Computational-Neuroscience&#x2F;dp&#x2F;0195181999" rel="nofollow">https:&#x2F;&#x2F;www.amazon.com&#x2F;Biophysics-Computation-Information-Co...</a>

Great writeup. Here&#x27;s a full-text review that contains all the math needed to build a model of this process (2013):<p>&quot;Quantitative modeling of bacterial chemotaxis: Signal amplification and accurate adaptation, Yuhai Tu&quot;<p><a href="https:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pmc&#x2F;articles&#x2F;PMC3737589&#x2F;" rel="nofollow">https:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pmc&#x2F;articles&#x2F;PMC3737589&#x2F;</a><p>The main points are:<p>* Both receptor cooperativity and accurate adaptation can be described quantitatively by simple mathematical models.<p>* 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.<p>* Exponential ramps induce activity shifts, which depend on the ramp rate through the methylation rate function F(a).<p>* Responses to oscillatory signals reveal that E. coli computes time-derivative in the low-frequency regime.<p>* E. coli memorizes the logarithm of the ligand concentration and the Weber-Fetcher law holds in E. coli chemotaxis.<p>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.

&gt; We don’t yet have the technology to just observe all of the activity inside a living cell.<p>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!<p>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?

The random spin followed by a run reminds me a bit of the first-generation Roomba logic...

There is a section at the end &quot;How did we figure all this stuff out?&quot;. Really amazing.<p>And the scale invariance of nature is clearly visible here. The cell is &quot;small&quot; 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.

So I have three thoughts about this.<p>The first is cell specialization, particularly neurons. It seems like nature really came up with a universal neuron. There aren&#x27;t neurons for eyesight vs thinking, etc. They&#x27;ve experimented with this on frogs where they&#x27;ve reweired the optic nerve to a different part ofd the brain and the frog seems to see just fine. They&#x27;ve even added an eye and the frog seems to cope and use it just fine.<p>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&#x27;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&#x27;s clearly wholly inadequate for any realistic modelling. The protein interactions in a cell are mind-bogglingly complex.<p>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&#x27;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&#x27;t be computationally viable to simulate even a single realistic cell given all th einteractions that go on. We&#x27;re simply left to make estimations.<p>[1]: <a href="https:&#x2F;&#x2F;openworm.org&#x2F;" rel="nofollow">https:&#x2F;&#x2F;openworm.org&#x2F;</a>

&gt; How did we figure all this stuff out?<p>&gt; <i>We don’t yet have the technology to just observe all of the activity inside a living cell</i>. 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.<p>&gt; A group at University of Illinois at Urbana-Champagne uses atomic-scale molecular dynamics <i>simulations, in software</i>, to understand structural details<p>&gt; It’s a world that’s hard to see; sometimes <i>you just have to imagine what’s going on down there</i>, and back up those imaginings with the right experiments.<p>&gt; One reason I’m particularly attracted to studies of E. coli chemotaxis is that it’s an early star of what’s been called <i>“in silico” biology</i>. It’s been the subject of many <i>computer models</i>.<p>Honest, at least.

This is wonderful! If you want to go deeper, I highly recommend the textbook &quot;Molecular Biology of the Cell&quot;. 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&#x27;re now reading together and I&#x27;m still mesmerized. Nothing compares to the astonishing complexity of a cell.

Excellent writeup, i love the interactive animation

<i>CheA 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><p>I guess &#x27;naming things&#x27; isn&#x27;t just hard in CompSci.

If 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.<p>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.<p>More musings in this direction <a href="https:&#x2F;&#x2F;sites.google.com&#x2F;site&#x2F;pablomayrgundter&#x2F;mind" rel="nofollow">https:&#x2F;&#x2F;sites.google.com&#x2F;site&#x2F;pablomayrgundter&#x2F;mind</a>

The 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.<p>Kinda felt similar to the cell comms. I wonder what interesting distributed coordination ideas we could learn in distributed systems computing from cellular biology.

&gt; 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.<p>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.

I would love to understand how individual cells come together to form functioning organs with clear boundaries.

The video embedded in the article is a great and more brief explanation of what&#x27;s written: <a href="https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=LgPDOSou1tw" rel="nofollow">https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=LgPDOSou1tw</a>

These ribbons look a bit like wires, transforming the information of an attached molecules through the membrane through physical tension

From a laymans perspective, can human beings create our own version of DNA, let&#x27;s say with the use of transistors instead of biological cells, long into the future? Or is DNA just magic and we can&#x27;t recreate it inside solid state objects like a robot made out of transistors?

Am I allowed to think this is too complicated to be an accident?

On the one hand, this is extremely cool science.<p>OTOH, English really needs another word, meaning &quot;like intelligence, but it could be simulated by an analog computer with a good handful of of discrete components&quot;.

Incredible to think how something this intricate with so many interdependent parts and integrated systems could have evolved.

Imagine a microscopic, fully autonomous and self-replicating Roomba that is also able to adapts at the individual and population levels.<p>We&#x27;re still quite far from replicating this kind of tech.

Good gracious. A fantastic read. Wow.

Haha. 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.

God 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.