Cell Intelligence in Physiological and Morphological Spaces | Michael Levin

Write4u. back when we were having our “Microtubule answer to everything” debate, I tried defending that, though they’re important, they are only components of complex systems full of important components, microtubules require other dynamic components. Some of which we aren’t even quite aware of yet.

Here’s a case in point, are you familiar with Michael Levin? If not, strap in and get ready for a heck a ride:

Where is Anatomy Encoded in Living Systems? | Michael Levin

Extract from “Cell Intelligence in Physiological & Morphological Spaces”, kindly contributed by Michael Levin in SEMF’s 2022 Spacious Spatiality.

Michael Levin | Cell Intelligence in Physiological and Morphological Spaces

Michael Levin | Cell Intelligence in Physiological and Morphological Spaces - YouTube (1:11:00)

INTRODUCTION
00:01:27 All intelligence is collective intelligence
00:03:45 Main points of the talk
00:04:32 Single cell spatial competencies
00:06:19 Outline of the talk

PLASTICITY 00:08:18
00:08:18 Planarian memories survive brain regeneration
00:09:29 Tadpoles can see with artificially implanted eyes
00:10:42 Biological systems have competency in different scales and spaces
00:12:56 Planaria regenerates head with new adaptive gene expression
00:15:06 Technological Approach to Mind Everywhere

INTELLIGENT NAVIGATION IN MORPHOSPACE 00:16:34
00:16:34 Where are anatomy and shape encoded in biology?
00:17:55 Biomedical endgame: anatomical compiler
00:19:01 Unpredictability of anatomy of chimeric species: frogolotls
00:19:59 Hardware and software: analogy between nowadays biology and 40s-50s computer science
00:21:15 What is morphospace?
00:23:26 Examples of natural regeneration
00:25:15 Cells change molecular mechanisms to adapt shape to artifical constraints
00:27:05 Induced frog leg regeneration takes different path than default limb development
00:28:08 Facial mispatterning in tadpoles still ends in normal frog faces
00:29:36 Feedback loops in pattern homeostasis and goal-directedness

BIOELECTRICITY 00:31:38
00:31:38 Usual example of bioelectricity explaining goal-directedness: the brain
00:32:49 Generalizing: non-brain tissues also encode goals through bioelectricity
00:34:36 Reading and writing electrical information in non-brain tissues
00:35:29 Reading #1: “electric face” before face development
00:36:45 Reading #2: electric signature before tumor development
00:37:12 Writing electrical information in non-brain tissues using neuroscience tools
00:38:12 Writing #1: inducing voltage patterns that develop organs and limbs
00:40:16 Writing #2: inducing limb regeneration
00:42:08 Writing #3: inducing anatomical memory that produces two-headed planaria when injured
00:47:01 Writing #4: inducing shape changes
00:48:36 Developing quantitative, predictive models
00:49:27 Writing #5: correcting brain defects using model predictions
00:51:14 Electroceutical drugs

TECHNOLOGICAL APPROACH TO MIND EVERYWHERE 00:52:18
00:52:18 Different scales of biological systems have different goals
00:55:00 Potential application to reverse cancer
00:55:48 Diversity of intelligences
00:57:16 Multi-scale control and up-scaling goals across spaces
00:59:01 Behavior of skin cells clusters when isolated: xenobots
01:07:15 Overview of the Technological Approach to Mind Everywhere
01:08:00 The space of intelligent agents and its implications for ethics

Mindscape 132 | Michael Levin on Information, Form, Growth, and the Self

(1:23:35)
Interviewed by Sean Carroll

Oh there’s another aspect to this, listen to how Michael Levin tells his story, presents his evidence and arguments - compare to Hameroff’s way of playing on his audience and conjuring thoughts - rather than a simple, here’s the science the way Levin does. He’s what a scientist sound like, to me.

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I haven’t watched all of Levin’s presentation, but just wanted to address the first 6 minutes of the talk.

Mindscape 132 | Michael Levin on Information, Form, Growth, and the Self

00:00:40 Microtubules organize the location of all the cell parts. The “hardware” and “transport mechanism” Levin is talking about is the microtubule lattice.

Moreover, Levin completely overlooks the fact that microtubules make genetic copies including the DNA of cells during mitosis, where MT function as the “mitotic spindle” and thus repair any cellular defect in the daughter cell via genetic instructions.

This process can go wrong when the DNA itself is damaged or there is an interfering condition. Then we may experience an “uncontrolled cell duplication”, also known as Cancer.

00:03:45 Main points of the talk

Levin seems to be oblivious to the existence of microtubules as the transport and placement mechanism of various proteins within and across cells.

Do microtubules play a role in post-Golgi transport?
A large number of studies have assessed the involvement of microtubules in the transport of cargo from the Golgi complex to the cell surface. We focus here on the role of kinesin motor proteins and protein interactions in post-Golgi transport, as well as the impact of tubulin post-translational modifications.

What Are the Main Function of Microtubules in the Cell? | Sciencing
I think that you will find all the answers to Levin’s questions on this site alone.

Can you recall Levin ever mentioning microtubules in this talk? If not, then he is way behind the current research in both “intra-cellular” and “inter-cellular” communication" as facilitated via microtubules.

I read the article, not sure how you see it answering all (if any) of Levin’s questions, in fact I thought it sort of interesting in how standard that description was, in that nothing was mentioned about the more amazing feats - quantum interactions and source of consciousness, etc, that Hameroff and you make.

Seems to me, looking at some papers Levin’s authored, he does mention “cilia structures” which in turn seems like it’s microtubules he’s referring to. My own gut feeling is that Levin’s work indicates that perhaps this bioelectricity sets up fields that creates pathways for the microtubules to fall in line with. Sort of like metal fillings in a magnetic field. But that’s the picture my mind has produced.

I have written him an email, after an introduction I ask:
Might you be able to suggest an informed educating response to the complaint that you might be ignoring microtubules?
How does your work impact current advances in understanding those very fascinating biological components?
I’ll be sure to let you know if I ever receive a response.

Also where did your post-Golgi quote come from, it’s not in the article you linked to,
nor do I see why it would somehow nullify Levin’s work.

==============================================

Have you really listened to it - I would think these few minutes would have really caught your interest.

start at about 10:40
12:30
13:00 understanding no top down directing?
15:00 global body plan
Swarm intelligence
16:25

To me this is stuff fires my imagination, my mind can work with it and it meshes with what I’ve already learned, in a way that the quantum realm can’t do.

gotta run

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Quickie answer;

Microtubules and the organization of the Golgi complex

Electron microscopic and cytochemical studies indicate that microtubules play an important role in the organization of the Golgi complex in mammalian cells. During interphase microtubules form a radiating pattern in the cytoplasm, originating from the pericentriolar region (microtubule-organizing centre). Microtubules and the organization of the Golgi complex - ScienceDirect

This is all part of the microtubule dominated network that governs the life support system of the organism. This requires at least a quasi-intelligent function to guide the biochemical exchanges that enable homeostasis.

Okay.
Now, can you explain why you think that is in conflict with what Levin is studying and reporting on?

Yes, I agree. But that also means he is nowhere near the functional system itself.

I am not saying that he is wrong. I am saying that he is speaking at a superficial level and unless he studies what microtubules do, he is not close to the basics.

Clarifying the Tubulin bit/qubit - Defending the Penrose-Hameroff Orch OR Model (Quantum Biology) - YouTube

For an extraordinary site on cells;
https://openorganelle.janelia.org/organelles/mt
main page; https://openorganelle.janelia.org/news/2022-12-01-site-update-december-2022

I received this from Dr Levin and thank him for his quick response to my email.

Plus he does a great job of explaining something. Feels to me similar to (or at least harmonious with) my attitude of folds within folds and the interconnectedness and myriad of feedbacks loops and such.


{I added extra paragraph breaks and the highlight}

Levin, Michael
to, me

Hi Peter,

Might you be able to suggest an informed educating response to the complaint that you might be ignoring microtubules?

I studied microtubules a lot, in our work on left-right patterning (not cilia, intracellular microtubule organization center), and a bit in planaria patterning. But I would answer a different way.
The bottom line is that everyone has a favorite mechanism. Some people will say you have to study mitochondria, nuclear envelope, ER, golgi, ordered water, ultraweak photons, and on and on it goes.

No one has to study everything - the question is: by studying bioelectricity, we have achieved what we’ve achieved, not needing microtubules. If your colleague is interested in microtubules, he will have achieved whatever advances he’s achieved by focusing on that at the expense of other things. Someone else could tell us that we’re both missing the boat by not focusing on infrared radiation from the DNA or whatever.

The question will be, “what is the evidence that we could do better if we include that?”. So my point is, I would be fine to accept the charge that I’ve ignored microtubules, and ask what the evidence is that I should be changing course. The results of everyone’s research program show clearly the relative merits of different focus areas and one needs evidence that adding favorite element X would actually make a material difference.
Otherwise, we all think others are failing to focus on whatever our favorite thing is :slight_smile:

How does your work impact current advances in understanding those very fascinating biological components?

We’ve actually found that microtubules set up some ion channel distribution in early LR asymmetry, and also reflect the bioelectric axial patterning in planaria. Please find attached a few papers.

Best,
Mike

Excellent response, I agree in general with everything Levin says as I am eager to learn as much about microtubules as possible.

I always keep in mind David Bohm’s warning against fracturing sciences into little niches.

In my research I find many “common denominators”, but sometimes the specialty has strayed from the main so far that people use 3 or 4 different names to identify the same thing, apparently ignorant of that fact. Else I would expect some qualifier explaining the use of a different name for the same thing.

IMO, Dr Levin is missig the main component that gives all cells the ability to communicate at cellular and biometric levels.

I already reported that flagella are driven by a microtubular ion motor.

And inter-cellular communication is facilitated via “gap junctions”:

Gap junctions

Cells have developed specialized regions on their membranes for intercellular communication. Gap junctions mediate and regulate the passage of ions and small molecules through a narrow hydrophilic pore connecting the cytoplasm’s of adjacent cells. These pores are composed of subunits called “connexions”.

REVIEW| 29 JANUARY 2020

The role of microtubules in secretory protein transport

[The role of microtubules in secretory protein transport | Journal of Cell Science | The Company of Biologists]

(The role of microtubules in secretory protein transport | Journal of Cell Science | The Company of Biologists)

I am not denegrading Levin. On the contrary, his work is needed to unravel the patterns. I just like to concentrate on the main actors that comprise the data transport network.
I want to “understand” the concepts.

I thanked Dr. Levin for his response and shared a link to this thread as a courtesy fyi.
“I’m assuming you’re fine with me sharing your response.”

Yesterday I was surprised that he responded and took the time to emphasize what seems to me key point that I’ve been dancing around:

It’s fine.

The bottom line is that it’s easy to say “You need to do focus on X, or else you’re behind/missing it/etc.”

The hard thing is to actually show what specific reason we have to think that this is correct, or better yet, to go ahead, focus on X, and solve some problems that remain open, and thus demonstrate your claim.
Locating proteins within cells doesn’t begin to address the large-scale anatomy problems we’re working on.

Looking at what’s been done by manipulating microtubules, vs. what’s been done by focusing on other components, I see no evidence that anatomical questions (large-scale, not cell-level) will be solved that way.

Having said that, of course microtubules are part of the story, as we’ve said in a number of papers. (which I shared above)

Thank you Dr. Levin,
. . .
It’s nice hearing my perspective reinforced by the words of an actual expert.

I’m sorry, but I believe you are still missing the point. He is talking about the 'information" that is being processed and that has immediate practical application which can be tested in a lab, apparently with good success.

Microtubules are not information, they are processors.
This is like the difference between software and hardware in a computer system.

Mind that I have absolutely no quarrel with his area of inquiry. It is a legitimate part of study in the science of biology.
And that is why you can consider your perspective as being reinforced by Levin’s valuable contribution in the laboratory.

What he’s is doing is testing electrochemical algorithms and that is perfectly appropriate. But when he talks about cellular exchange of ions, he does not identify the biological machinery that makes the exchange possible, i.e. MT.

But if you want to have practical application of the data, you need the hardware that processes the data. Microtubules are the hardware that do the processing.

AFAIK, microtubules can only be studied “in vitro” because their variable functions rest on the in vitro environment that determines their variability and the results they produce. They do the “sorting” and delivery of the informational cargo.

MT are the highways that transport the EM data and are chemically directed to drop off their cargo at specific in vitro locations. And that is the problem.

At that scale any measurement of causal changes are extremely difficult to capture and quantify. We are talking about an interactive “network”, not individually deterministic results that can be simulated in a laboratory.

The irony is astounding. In my heart it feels like that is exactly what you’re guilty of.

After all, Levin is the one working with a complete organism.

Well he is not (currently) working with microtubules, the main part of communication and data processing in a complete organism.

He admits he is specializing and there is no shame in that at all. I support specialization. My main complaint is lack of communication between the specializations, ironic as that may sound.

And this is where Penrose and Hameroff make a wonderful team.
A theoretical physicists and a practicing anesthesiologist (MD) who actually does clinical work with all the specialized parts of data transmission in the brain that create consciousness.

Please Write4u, you’re starting to lose credibility, “My main complaint is lack of communication between the specializations,” seriously? First aim, then shoot. Levin seems plenty willing to collaborate and think outside the box.
No one is dismissing the fundamental level importance of microtubules! But there simply doesn’t seem to be the evidence to enable the communicators tell the more compelling story, you are trying to convince me is a done deal. The quantum foam is just that, sure it forms the glue that enables everything else. But that’s not where the story ends.

Allen Discovery Center - Our Mission

The mission of the Allen Institute is to unlock the complexities of bioscience and advance our knowledge to improve human health. Using an open science, multi-scale, team-oriented approach, the Allen Institute focuses on accelerating foundational research, developing standards and models, and cultivating new ideas to make a broad, transformational impact on science.

https://alleninstitute.org/search/?q=Levin

Exploring Frontiers: Nature’s Blueprint

…Levin, Ph.D. Leader of Allen Discovery Center at Tufts University Prior to college, Michael Levin worked as a software engineer and independent contractor in the field of scientific computing. He attended Tufts University, interested in artificial intelligence and unconventional computation. To expl…

Allen Discovery Center at Tufts University

…Levin, Ph.D. Prior to college, Michael Levin worked as a software engineer and independent contractor in the field of scientific computing. He attended Tufts University, interested in artificial intelligence and unconventional computation. To explore the algorithms by which the biological world impl…

Discovery Centers

…Levin, Ph.D. Learn more Allen Discovery Center at Stanford University The Allen Discovery Center for Multiscale, Systems Modeling of Macrophage Infection at Stanford University was announced in 2016 to drive progress in cutting-edge cell systems modeling to understand the complex multicellular basis…

Allen Frontiers Symposium 2017

…Levin, Allen Discovery Center at Tufts University Markus Covert, Allen Discovery Center at Stanford University Jay Shendure and Michael Elowitz, Allen Discovery Center at UW Medicine Christopher Walsh, Allen Discovery Center at Boston Children’s Hospital and Harvard Medical School learn more about a…

Allen Frontiers Symposium

…Levin, Tufts University Allen Discovery Center - Reading and Writing the Morphogenetic Code New Approaches to Big Questions in Antibiotic Resistance, Behavior and Development Ethan Bier, University of California, San Diego James J. Collins, Massachusetts Institute of Technology Bassem Hassan, Instit…

Tracking cell fate decisions in single cells

Dr. Michael Elowitz and Dr. Long Cai will develop a platform through which cells can self-record their lineage and molecular event histories directly into their own DNA as they create new tissues, particularly in the brain. This research will help to address one of the most fascinating questions in …

Allen Frontiers Symposium 2019

…Levin, Allen Discovery Center at Tufts University, Reading and Writing the Morphogenetic Code Markus Covert*, Allen Discovery Center at Stanford University, Systems Modeling of Infection Jay Shendure and Michael Elowitz, Allen Discovery Center at UW Medicine, Cell Lineage Tracing Christopher Walsh, …

Speakers

…Levin, Ph.D. Will Ratcliff, Ph.D. James Briscoe, Ph.D. Wallace Marshall, Ph.D. Friday, May 3 Veronica Grieneisen, Ph.D. Wendell Lim, Ph.D. Arthur Prindle, Ph.D. Jessica Whited, Ph.D. Dagmar Iber, Ph.D. | ETH Zurich “From Networks to Function - Computational Models of Organogenesis” Abstract : One of…

Team

…Levin, Ph.D. Prior to college, Michael Levin worked as a software engineer and independent contractor in the field of scientific computing. He attended Tufts University, interested in artificial intelligence and unconventional computation. To explore the algorithms by which the biological world impl…

Check out our history and accomplishments at-a-glance.

This isn’t that sort of contest. Besides, look at what you’re doing, five year old talk, what’s new?
Besides, to my perspective much of it is asking the wrong questions anyways. quantum foam and biology and philosophizing. :wink:

Beyond that, I recall you skirting my complaints of another Hameroff talk of about the same vintage. Oh another complain, from my sampling his talks seem to keep covering the same ground. Someone like Solms do a sampling of his talks and you’ll see a dynamic development and scope. Levin, I haven’t sampled enough to form an opinion.

That was a generalized statement. Why you see that as an attack on Levin escapes me.

I am not a scientist and numbers mean very little to me. I want a generalized overview that identifies the parts of the pattern that yields the emergence of consciousness. Such a book is not yet available.

I have other people tell me that my approach is scattered and littered with irrelevant bits and pieces, but to me they all have one thing in common and that is microtubules. That means they process data. A description of what the data does is more important to me than specific values and atomic make-up of that data.

[quote=“citizenschallengev4, post:14, topic:10077”]
No one is dismissing the fundamental level importance of microtubules! But there simply doesn’t seem to be the evidence to enable the communicators tell the more compelling story, you are trying to convince me is a done deal. The quantum foam is just that, sure it forms the glue that enables everything else. But that’s not where the story ends.

Does it look like I am satisfied with the story? Where have I said its a done deal?

All I have said is let’s begin with microtubules, because they do provide the data transport in ALL eukaryotic organisms. I am not all that interested in the data itself, unless it relates to the emergence of a model that presents an internalization of observed reality.

Compare it to the evolution of the new text based GPT series AI, that are beginning to show signs of autonomous intelligence.

I haven’t a clue as to the actual programming, but I understand the fundamental cyclical processes that allow the AI to make decisions between “superposed potentials” which is a form of making “best guesses”, what Anil Seth describes.

I am less interested in the technical minutia, than in the general blueprint that describes the concepts.

To the scientists minutia are important. It represents the data, so that it can be used in labs for testing and experimentation. I don’t have a lab. I have a cheap old computer running WIN 7

Not so hasty. I do try to follow up on related perspectives.

I find this very interestinfg and informative.

And I think that microtubules are the heart of the biological computing network.
Note that microtubules form the mitotic spindles that control the actual cell division of every cell in you body.

I still believe that Levin underestimates the role microtubules play in say Xeno bots .

He seems unaware that cilia are controlled by microtubules and that microtubules are ubiquitous in the cell’s cytoskeleton and cytoplasm and conduct intracellular and intercellular communication in addition to being the long range information transport system in neural axons for communication with the brain.

And hearts don’t need to be told what to do?

Apparently he’s in good company.
I’ve spent a few minutes (it’s adding up to a lot of minutes) doing some Google searching - even used “role microtubules play in Xenobots” out of a half dozen articles regard xenobots I could not find any thing discussing “microtubules.”

I did find: Non-Equilibrium Assembly of Microtubules: From Molecules to Autonomous Chemical Robots but it seems informed speculation, rather than specific observations or acquired understanding.
H. Hess and J. L. Ross - September 2017.

Abstract

"Biological systems have evolved to harness non-equilibrium processes from the molecular to the macro scale. It is currently a grand challenge of chemistry, materials science, and engineering to understand and mimic biological systems that have the ability to autonomously sense stimuli, process these inputs, and respond by performing mechanical work. New chemical systems are responding to the challenge and form the basis for future responsive, adaptive, and active materials.

In this article, we describe a particular biochemical-biomechanical network based on the microtubule cytoskeletal filament – itself a non-equilibrium chemical system. We trace the non-equilibrium aspects of the system from molecules to networks and describe how the cell uses this system to perform active work in essential processes. Finally, we discuss how microtubule-based engineered systems can serve as testbeds for autonomous chemical robots composed of biological and synthetic components."

Introduction

… Our discussion of recent contributions to the field is loosely organized around the “distance from equilibrium,” starting with microtubule assembly and ending with molecular robotics.

Microtubules are polymers of alpha-beta tubulin dimers that assemble non-covalently using hydrophobic and electrostatic interactions (Fig. 1a). They are important biological structures that form the structural support girders of the cell (Fig. 1b). They mechanically support long extensions in axons, dendrites, cilia, and flagella. Microtubules act as load-bearing compression rods in muscle that enable contracting muscle fibers to spring back fully3. They set up the cell division machinery, the mitotic spindle, and their disassembly acts to pull apart chromosomes in the dividing cell (Fig. 1b).

And you still haven’t provided any articles to support that supposition, please no more Hameroff, come up with someone less biased (intellectually & financial).

This you say about a scientist who has actually studies and published peer reviewed papers regarding microtubules? That’s weirder than me trying saying Tegmark doesn’t know anything beyond how to weave a beguiling story for his audience. I won’t and I don’t, even if there’s a sliver of truth in it. :wink:

And finally, I’m familiar with that video and listen to it again for your sake, now I’m wonder what was your point? Was there something, or was something missing, that you wanted to point out?

[quote=“citizenschallengev4, post:17, topic:10077”]
And hearts don’t need to be told what to do?

Yes they do and it is microtubules that tell it what to do. All neural activity is MT driven.

[quote=“citizenschallengev4, post:17, topic:10077”]
This you say about a scientist who has actually studies and published peer reviewed papers regarding microtubules?

Question is when he studied this area. Apart from a single mention of cilia as little hairs that make movement possible, he completely ignores microtubules that do all the actual work.

[quote=“citizenschallengev4, post:17, topic:10077”]
And finally, I’m familiar with that video and listen to it again for your sake, now I’m wonder what was your point? Was there something, or was something missing, that you wanted to point out?

It is valuable in one area of research, but it is limited in scope and does not dig down to where all the action occurs.

Apparently I need to clarify,
from the top

You said “microtubules are the heart of the biological computing network.”

Okay, let’s extend your heart metaphor, we both agree with the scientific consensus that hearts require signaling to properly function. Even though individual heart cells will beat on their own, the organ needs those cells to orchestrate the beating hearts cells.

That’s why I was wondering,
How do microtubules receive signals?

On the one hand, I don’t agree with your dismissive assessment, and neither of us are expert enough to fully understand let alone judge those papers.

On the other hand, I’ve looked at many microtubule papers and articles, pretty much all of them seem to “ignore that microtubules that do all the actual work

When I ask you to provide papers supporting your position you always seem to come to the same group, Hameroff, Penrose, et al. and all they offer is speculation built more on deep faith in their assumptions, than building blocks of explanatory papers. Or you divert attention.

[quote=“citizenschallengev4, post:19, topic:10077”]
Even though individual heart cells will beat on their own, the organ needs those cells to orchestrate the beating hearts cells.

Heart cells beat on their own because microtubules and related filaments produce the action potentials that make the muscles contract.

That’s why I was wondering,
How do microtubules receive signals?

The produce them as directed by the brain. Will your fists to clench and your fists will clench.

In the case of the heart, it shows the autonomy of MT networks that can produce regulatory functions on their own.

Cilia are purely controlled by MT and still allow the single-celled brainless Paramecium to navigate in ponds, as well as sweep your lungs clean from debris.

Always realize that any and all cellular functions are regulated by microtubules and their related filaments.

I just realized that human microtubules communicate with bacterial microtubules! Interspecies communication!