Michael Levin is coming close to the positions of both Humberto Maturana (autopoiesis) and of Nick Lane (proton pumping).
Autopoiesis is not an easy set of concepts but one of the ideas is that details of structure are much less important that preservation of relationships that allow an entity to replenish its own constituents. Planarian are damn adaptable, but this is hardly news.
Nick Lane emphasizes that DNA is subsidiary to bioenergetics and “proton pumping” across membranes. His recent book “Transformer” focuses on the Kreb’s cycle and mitochondria as the crux of life (and autopoiesis, although he does not use this term).
Lane is extremely readable. Maturana is almost inscrutable.
I enjoined the target article, but am not comfortable boiling down development to “bioelectrics”. A complementary perspective but I do not think this will get us farther than good old developmental molecular biology.
I disagree. An electromagnetic paradigm of cell life is critical to understanding predictive molecular dynamics, particularly where cellular neural recruitment is concerned. Moving passed mass and unto the mathematical perfection of electromagnetic radiation - as idealized as realized in the electrical engineering sciences - demonstrates its exaltedness in theoretical application.
I have created a simulation of how a tree can be grown from a programmable cellular automata. Each cell executes some operations, including replication, based on the surrounding conditions and its age/iteration.
More complex organisms can be grown with this technique.
Hidden in footnote 5 is a significant fact about the two-headed planaria (flatworms) that produce two-headed offspring: they reproduce not by laying eggs, but by fission. In other words, this physiological trait is not passed through the genes (if it were, that would be a rather astounding Lamarckian fact).
Planaria in general reproduce sexually (with eggs and sperm) and asexually (by splitting).
The language in the article is a bit overhyped. There are multiple examples of gradients being involved in pattern formation. It's just that electrical potentials are a bit of a newer area of study.
There's the chemical gradient based on WNT signaling in fruitfly development, the SHH (sonic hedgehog) chemical gradient in limb pattern formation and body planning asymmetry. There's even auxin signaling in plant development.
Heck, one of Alan Turing's (yes, THAT Turing) most famous papers from the 50s described reaction-diffusion mechanisms for pattern formation.
Basically for evolution to invent some kind of reproducible pattern of something, you need to start with a gradient of something and tie that to gene transcription.
In the fruit fly example it's a chemical trigger that reaches the nucleus via wnt signaling. In the flatworm example, it's a membrane polarization gradient that drives the gradient rather than a chemical one.
I'd imagine the patterns you can create from electrical depolarization are simpler than the ones you can get from chemicals interacting as you lose many of the interesting interactions you get from reaction-diffusion
Yes, I believe that the linked article oversimplifies when talking about a "bioelectric" state, perhaps because this sounds more appealing to those familiar with electrical and electronic technologies.
The actual state that is described is determined by the chemical concentrations of various kinds of ions and molecules along and across the body of an animal.
The distribution of electric potential that appears as a consequence of the chemical concentration variations, due to the fact that the atomic ions and also many of the molecules involved are electrically charged, is just a coupling mechanism between those chemical concentrations, so that when one of them is changed that tends to also change the concentrations of other atomic or molecular ions.
The same "bioelectric" state (i.e. electric potential distribution) could appear as a consequence of distinct distributions of the ions and most certainly those seemingly identical "bioelectric" states would behave quite differently.
This is similar with what happens in semiconductors, whose behavior cannot be simulated based on just the distribution of electric charge, but one must account separately the concentrations of all kinds of charge carriers, e.g. electrons, holes, fixed crystal defects etc.
I think I want to clamp down on the hyperbole a bit here, and I think its obvious the author is targeting the software engineer folks who might not be familiar with developmental biology or evolution.
The planaria has evolved a mechanism by which its body plan can be recapitulated from the distribution of electric potential.
When it gets cut in half, the electric potential changes, but this is still enough information for the vivisected halves to redifferentiate. The trade off is, of course, there is only so much information in an electric potential with regard to the patterning of a complex organism, so its hard to imagine a cheetah or a pig pulling off this same kind of trick.
The idea of some subdivision of an animal having its own prerogatives is not some sort of new idea. It goes all the way back to Richard Dawkin's 1970s book "The Selfish Gene" which lays out exactly where the "incentives" are for cells, genes/cistrons, cancer, transposons, etc...
Just because there's some example now of something vaguely reminiscent of semiconductors (which is cool for sure!) does not mean we're gonna start rethinking everything in biology.
> When it gets cut in half, the electric potential changes, but this is still enough information
None of the linked articles contains any evidence about some direct influence of the electric potential, but only about the influence on differentiation of the variable concentration of ions.
They did not manipulate the planaria with electrodes, but with a drug that has manipulated the concentration of ions, by blocking some of the paths through which some ions are transported through membranes.
All the talk about "bioelectricity" appears superfluous. The variable electric potential is just a side effect of the variable ion concentrations, which complicates their behavior by introducing a coupling between the movements of different kinds of ions.
That kind of sounds like saying that talking about "electricity" is superfluous when describing how chemical batteries work, because it's all about ions.
Given a state described by the distributions in space of the various kinds of ions, you can compute the distribution in space of the electric potential. Therefore including the electric potential in the state is superfluous.
Given the distribution in space of the electric potential, you cannot compute the entire state, which includes the distributions in space of many kinds of ions, simply because there are many kinds of ions. Only when there had been a single kind of ions, it would have been possible to describe the state using the electric potential.
All the ions move continuously through very complex circuits comprising a network of pores through the cellular membranes. Through some of the pores the movement is "passive" i.e. for each kind of ion that may pass through a given kind of pore the ionic current is determined by both the local gradient of the concentration of that kind of ion and the local gradient of the electric potential. This is the only place where the electric potential matters. Through other kinds of pores, the ion transport is "active", i.e. the so-called ionic pumps move certain kinds of ions regardless of the gradients of the ionic concentrations and of the electric potential (within certain limits, too large gradients can block an ionic pump).
If you want to simulate the ionic current network of an entire organism, you must compute the electric potential inside the simulation. When you observe a living organism, measuring the electric potential is much easier than measuring directly any kind of ion concentration and in many cases one can estimate the ionic concentrations of interest from the measured electric potential and from additional information.
While accounting for the electric interactions inside an organism is essential, talking about a "bioelectric" state of an organism that would determine its development is just meaningless pseudo-scientific mumbo-jumbo. "Bioelectricity" is an appropriate term when discussing the electric sense organs or the electric weapons of various animals, where the side-effect of the generation of electric potential differences by differences in ion concentrations is exploited in such a way that the effect is cumulative over large ensembles of cells.
This makes a lot more sense. I had a hard time visualizing the existence of a biological voltmeter measuring electric potentials and using that to somehow change development of the organism. Seems like another case of "correlation does not equal causation" based on your comment.
Ditto. The larger question is how does the linear sequence of DNA (primary sequence) ultimately drive the spatio-temporal development program that leads to mature differentiated cells working together at the organoid / organ / organism scale. How do cells know what to do in time and space as the organism grows? How is that logic encoded in the genome?
Eric Davidson did a bunch of pioneering work meticulously "debugging" this spatiotemporal genomic logic in the sea urchin. Pretty amazing. Eukaryotes like us have control elements directly upstream of our genes (trans-acting aka close acting) and also 100,000's of base pairs distant (cis-acting). The region of DNA directly preceding the beginning of an open reading frame at the start of a gene usually has a sequence of DNA motifs that bind proteins that can increase or decrease expression of the gene. Davidson and others showed that the transcription factor proteins that bind to these control motifs actually have additional other proteins that bind to them, in literally a layer on top, and that the sequences of proteins in this second layer recruit a tertiary layer of proteins that conditionally cause more or less gene expression, depending on their identities. You could say the secondary and tertiary layers are a form of "abstraction" in a literal sense, since they encode a hierarchy of logical operations.
Here's an open-access overview of Davidson's work which incidentally illuminates a lot of these concepts in more detail for a lay audience: "ERIC DAVIDSON: STEPS TO A GENE REGULATORY NETWORK FOR DEVELOPMENT" by Ellen Rothenberg, 2016; doi: 10.1016/j.ydbio.2016.01.020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828313/
to see the decoded logic in pseudocode and with a diagram, see "cis-Regulatory control circuits in development", Howard and Davidson, 2004, Developmental Biology, vol 271, https://doi.org/10.1016/j.ydbio.2004.03.031 (open access)
Your response has fascinated me. Listening to podcasts, I have always so dearly wanted to know what Michael or others meant specifically by "Voltage gradient". These have given me great topics to further conduct research into, with my currently fundamental neuroscience knowledge rooted in understanding of memory, learning and Action Potentials.
I have tried to further this understanding with LLMs but am ofcourse not sure if what they are saying is correct (given the understudied and sparse nature of this research).
If you had a moment to help me understand what exactly these voltage gradients are, how they differ from action potentials, and to tie these to the processes at the cellular level to the larger system, I would be so grateful (for example, is SSH used in limb regeneratio nas well as pattern formation? How? Is it dormant in normal limbs? Which cells, in the limb or in the brain? Which research articles found this? I am fascinated!).
In the meantime, here is what Claude told me. I am not sure if it is accurate, I get a sense of "sweeping under the rug":
"Specific ion channels and gradients:
During limb regeneration in amphibians like salamanders, one of the key ion channels involved is the V-gated proton channel (Hv1).
The wound epidermis cells at the amputation site become depolarized due to the influx of protons (H+) through the Hv1 channels, creating a localized region of elevated intracellular pH.
This pH gradient, or proton gradient, is believed to be a crucial signal that initiates and guides the regenerative process.
Other ion gradients, such as calcium (Ca2+) and sodium (Na+), have also been implicated in regulating various stages of limb regeneration, but the proton gradient is particularly well-studied.
Reaching and influencing cells:
The voltage gradients or ion gradients can propagate through tissues and reach distant cells due to a phenomenon called bioelectric signal propagation.
Cells are electrically coupled through gap junctions, which allow for the passive spread of ions and small molecules between cells.
This electrical coupling enables the voltage or ion gradients to be transmitted from the source cells (e.g., wound epidermis) to the target cells (e.g., blastema) over long distances.
The gradients can influence gene expression, cell proliferation, and cell migration in the target cells, guiding the regenerative process.
Pattern effects and limb regeneration processes:
The specific patterns of voltage or ion gradients are crucial for determining the outcomes of regeneration, such as the completeness and proper patterning of the regenerated limb.
For example, manipulating the proton gradient can lead to the formation of supernumerary (extra) limbs or alteration of the limb pattern.
The voltage gradients are involved in various stages of limb regeneration, including wound healing, blastema formation, patterning, and differentiation of cells into specific tissue types (e.g., bone, muscle, nerves).
Gradient vs. specific voltage measurement:
The term "voltage gradient" or "bioelectric field" refers to a spatial pattern of voltage differences, rather than a singular voltage measurement at a specific point.
It's similar to a topographic map, where the voltage (or ion concentration) varies across different regions, creating a gradient or slope.
In contrast, an action potential or membrane potential refers to a specific voltage difference across the cell membrane at a given point in time.
The voltage gradient is a long-range signal that provides positional information and guides cellular behaviors during regeneration, while action potentials are localized electrical signals involved in neuronal communication and muscle contraction.
The voltage gradient, or bioelectric field, is a spatially distributed pattern of voltage differences that serves as a long-range instructive signal for coordinating cellular activities during regeneration. It is distinct from a singular voltage measurement or an action potential, as it represents a gradient or slope of voltage across different regions, providing positional cues and guiding the regenerative process."
Honestly, if you want to dive in more, you'll need to read https://www.amazon.co.uk/Principles-Development-Lewis-Wolper... . Textbooks tend to be gold standards still. You can also look up review articles for the specific thing you want to know more about. Simple googling at google scholar should get you to a good review article in <15 minutes.
I want to caution that in general, DevBio is still an active field. Things are moving and grooving, so you'll need to check back in about every 5 years or so.
In general, DevBio works off of a gradient of some sort (we think). A new daughter cell looks at the gradients that she is in, then uses the genome to figure out what to do next. What to do next and the gradient are both hyper complicated. Think, like, 50+ co-interacting variables for gradient, with functional race conditions then set on the genome. It's rough for us humans to figure it all out, we largely think we haven't a real clue yet.
When we say voltage gradient, think the traditional ions and the like. But also think of the voltage gradient that a protein can have too, with binding pockets and stuff. Think voltage gradients that are held in place by lipid rafts on the membrane too. Think also the osmotic potential that ion concentration will have, not just the raw total voltage of a voltmeter. There are a lot of components, and therefore gradients, that make up the voltage potential.
Also, yes, you're right to think of the action potential. That's a voltage gradient across a membrane. In DevBio though, it's not just the voltage gradient across the membrane, but along the cells and among them too. The pancreas has a lot of this kind of stuff happening, from what I remember of my MolBio classes.
Let me know what other question you have and I'll try to get to them today.
>>When we say voltage gradient, think the traditional ions and the like. But also think of the voltage gradient that a protein can have too, with binding pockets and stuff. Think voltage gradients that are held in place by lipid rafts on the membrane too. Think also the osmotic potential that ion concentration will have, not just the raw total voltage of a voltmeter. There are a lot of components, and therefore gradients, that make up the voltage potential.
It seems that both Claude and you use "voltage gradient" and "ion gradient" interchangeably, which may be not technically correct enough. In electrical engineering voltage = potential = charge difference btw 2 points = the driving force that drives a current to "flow" from a point of bigger potential to a lesser one (typically). Thus it is voltage (or a field) that will drive an ion or any charge gradient.
Yes, ions and charges will flow in Bio too, but that flow is generally restricted and used somehow. Nature is always finding a way to take a toll. Cells will also set up a voltage difference to accomplish things too, all on their own.
Like, cells are quite happy to make massive charge differences (for their size) and then use that to do some little thing. Generally, they use ATP to skit around those pesky little entropy issues to act like Maxwell's Demon.
Like, they are using ion flow/current and deciding how that will benefit them. They gate it, on and off, to induce all kinds of signaling and meiosis and energy transferring.
So, in Bio, a voltage/ion gradient isn't really thought of as the same way in EE. Like, we care about 10 or so K+ ions, that little of a difference can do all sorts of things for a cell. ANd the voltage potentials can be titanic, because the distance are so small. That Van Der Wals force man, you don't think it do, but it do.
One important and subtle thing I learned going from my engineering/physics background and into bio is not assume that cells are little micro machines. They are in fact alive. They study you back, in their own limited ways. They try very hard to stay alive too. So, when bio people talk about cells doing things, we really do mean that they have agency.
I read one neurosurgeon (developing a theory of quantum biology) tell that mitochondria can develop voltage potentials comparable to a lightning bolt. Then searched a bit in PubMed and found something like still up to a couple of hundreds or a hundred milliVolts.
But I was curious, what do you think about the ways by which ligands find their receptors inside or outside cells in a dense bioelectrical and biochemical environment (as described here [0]). When I asked on stackexchange, they gave me a link about gradients and concentrations, but my question was about the very beginning of ligand's effect when it needs to find and activate at least one receptor. And no receptors seem to be able to "sense" a piece of space with a ligand's concentration, as they need direct binding of a ligand, but before this how does a ligand find a way to the receptor?
This may differ whether its a small or large molecule ligand, but my ligands of interest are ions (Ca/Mg, Na, K ,Cl; Li), peptides, anticancer drugs with metallocomplexes, ion channel drugs and similar drugs.
I think you're asking: how does some random bit of protein/ion/drug find it's way to a receptor for it? Is that correct?
Stochasticly. It's all random, as far as we can tell.
The things that make it all work, though, are the large amounts of receptors and binding thingys, the very small spaces, and the temperature. The cell is really kinda jam packed with stuff. But, since we're at ~97F or so, things bounce around a lot. The key here is the mean free path. Depending on the thing you're looking at, the mean free path of that thing is generally sufficient to get the pieces together to party. If not, then you start getting into really complex and hyper specific transport mechanisms. Each of those is going to be it's own little research world and will have little broad applications.
With large molecule drugs, you're likely using some clever transport mechanism with cleavages and digestion steps along the way. These are really some marvels of bioengineering.
With ions, you're just doing simple diffusion modeling, and the body very tightly regulates these ion concentrations
With peptides and these 'medium' sized things, you're looking a combination of diffusion and some hacking of the cell's machinery.
Again, I want to stress something here. We're still on the cusp of really understanding biology as a species. This stuff isn't EE. We're trying to unravel ~4 billion years of random-ass evolution, it's going to take a few thousand years for us to do that. Neither you nor I will see biology as a mature science.
Yea, that's correct. Though I may probably omit proteins and large moelcules, requiring transport vesicles and any specific transport mechanisms.
Stochasticity sounds like there has been performed some theoretical modelling to infer this. But does it imply that there would be some tiny % of any ligand molecules - endogenous or exogenous - which would just by chance get "an empty run" and didn't bind to their receptors (though structurally they're fine ligands with high affinity) and would be removed via waste removal systems? Is there any experimental evidence for this, like some study using radiolabelled high affinity ligand molecules to see what % of them gets into "an empty run"?
The mean free path seems sort of sensible in the extracellular space, though it still seems that the variables affecting mean free path (large amounts of receptors and binding thingys, the very small spaces, and the temperature) may be not enough. But wouldn't mean free path be near zero inside cells, where every nanometer should be occupied by some other biochemical pathway/reaction or bioelectric activity?
>>Neither you nor I will see biology as a mature science.
I personally wouldn't care a lot about proving anything to anybody in some absolute sense, but first of all to prove instrumentally and make stuff work for myself at least. I think that any biology student with the descent understanding should have some mini lab for personalized medicine (as e.g. Sinclair mentioned that his recent research on using 6 chemical compounds for OSK epigenetic reprogramming (rather than bulky viral vectors) can be done by any biology student).
Oh yes, many studies on unused targets/receptors are out there. It's a very common thing in the cell. Sure, yes, there are a lot of transport mechanisms to get the higher Dalton things about. But, again, it's all kinda random down there. Look at a lot of synapse regulation and you'll see that signaling molecules will escape the cleft and have to be digested. There's this really fun 'dance' that astrocytes do to regulate damaged NMDA receptors (and likely all receptors) that kinda makes the synapse just spill out all the signaling compounds for a little while. The cilia in neurons will also act as a kind of passive radar for a cell, just taking in signals and seeing what is going on with all the unused stuff floating about.
The mean free path is pretty much 0 all over, so to speak. I was just trying to tie it back into more EE concepts for you. The idea is that things are just randomly moving about, with a 'free' mean free path, until they aren't, and that stoppage costs energy. At body temperatures, it doesn't take much to knock binding ligands out of a cleft. So the stiffer the bind, the harder to disassociate, and the harder to get it to unbind at the end. Nature kinda figures this all out on her own, and the optimal energies are found out via evolution. It's all a 'good enough' system.
So, the trick with bio is that it's a lot like how Clausewitz thinks of war: War is easy, it's just that all the easy stuff is really hard. In that, it's conceptually easy to do bio. It's just that it's really hard to implement anything. Feynman talked a bit about it in one of his lectures. In that, getting a rat to randomly go into a room and then discover that there is cheese in it will take a tremendous amount of prep and careful cleaning and the like. Rats have really really good noses. It's so easy to fool yourself in bio, because the systems are just so complicated. And, for me, that's been true up and down the size scale, from single cells to whole animals. The systems are just so complex, you really only get to ask simple questions and then hope you controlled the experiment correctly.
All the empirical examples you mentioned pertain to the extracellullar space. So is this stochastic modelling also true in the intracellular space, which is like 100x times denser structurally, biochemically and bioelectrically (given that all biochemistry is effectively a type of electrical process involving very refined transfer/manipulations of charge densities), and allows to explain how do hundreds or thousands of biochemical reaction inside cells happen as required without interfering with each other?
Evolution also "tries" to save energy anywhere possible, so spending energy on the synthesis of endogenous ligands, which eventually will be discarded, seems a bit redundant. There is also a theorem in evolutionary game theory, that probability that natural selection will allow an organism to see reality as it is (=the truth) is exactly zero, as it's enough to make it just "good enough". I was arguing about that with Gemini, and it agreed with me. My point is that "evolution" is just a tool (like ChatGPT) with it's own instrumentally limited pool of empirical data (80% of which was also obtained from macroscopic enough observations rather than reverse engineering or experimentation) to build upon.
I actually want to apply one EE concept, which has some experimental basis. The reason why I am digging this, is that I am searching for some possible explanations of a couple of dozens of experimental studies in bioelectrics/magnetics I found. (though won't discuss in depth on a public forum)
I mean, how is the intracellular space denser than the extracellular? That means they wouldn't float.
The stochastic nature of the cell, as far as I know, exists pretty much the same in and out. With more transport mechanims occurring inside to make sure things get to where they need to be.
It's not that the discarded ligands (for example) are really 'discarded'. There are a few instances I know of that use the 'waste' as a product unto themselves. The ToR network comes to mind here. Still, trying to really figure out what the 'intention' was all those billions of years ago is hard, and networks and feedback loops have been built up over the eons. Like, yeah, nothing is really wasted in a cell, per se. But it can seem that way in the chain that you're looking at.
I'd love to know more about the magnetic side of things here. Is it memristors as synapses? Because that is a criminally misunderstood area of neuroscience.
>>how is the intracellular space denser than the extracellular?
Gemini:
```
Yes, the intracellular space is denser than the extracellular space:
Here's why:
Packing: Cells are packed with molecules like proteins, carbohydrates, and nucleic acids. These molecules take up a significant amount of space within the cell, leaving little room for just water.
Solutes: The intracellular space contains a higher concentration of dissolved molecules (solutes) compared to the extracellular space. This contributes to a higher density.
Extracellular Matrix: The extracellular space, on the other hand, contains a looser network of connective tissues and fluids like interstitial fluid. This allows for more space between molecules, resulting in a lower density.
```
>>Still, trying to really figure out what the 'intention' was all those billions of years ago is hard
With this logic you'll need another billion of years to randomly figure it out. I'd rather focus on how/efficiently does such position contribute to a specific current experimental methodology or results.
Yeah, sure cell densities vary (fat vs muscle) but pretty much any cell sample you're going to gather is going to be near the same density as the surrounding water environment. Again, there is a lot of variation though. The end result is that the density of a cell is near enough the density of water, it's not 100x more dense. I mean, iron is only ~8x more dense than water.
100x was a demo, not an actual number. But please explain how does intracellular content with DNA, RNA, proteins, structural organoids and all of these metabolic constituents [0] is supposed to be the density of water. You want the cells in an endotelium of a blood vessel to float, allow the blood to get into the wall of the vessel and get hematomas and hemmorhages?
Thank you so much for your explanations - I have learned a lot. I have some more questions but also have about 40 tabs of papers and terms to digest first, and I think the thread will probably go stale by then. May I ask what you studied and how you came into this type of knowledge from an engineering background, and whether you'd recommend any recent texts to come up to date on this stuff with?
I did a career change from particle physics to bioengineering and neuroscience ( and now AI/ML for EE applications with bioreactors, but that's another story).
There's not a lot of recent texts really. US based academia in the last few years has been really bad, as the replication crisis turned into a dry cough; I.E. make up data all you want, no one will care.
I'd really recommend reading Darwin though. Going way back to the literal foundation really helps set the stage, mentally, and bring you back to what is really going on with relation to the wider human condition.
Just about any review article more than 10 years old is also going to be pretty good. I'd stay way from review articles less than 5 years old though, as things change and retractions come out.
I'll warn you though, the concepts and mental models that you've built up on the Engineering side are not really going to help you with the bio side. Yes, the study habits will help. But bio is really really complicated. You can't abstract the cow into a meter sphere of water. In bio, you really do care about that cell on the medial side of the fourth mesenchymal layer of the second stomach of the cow. You are going to have to get comfortable memorizing pathways and strange names for a few years before all the pieces will even start fitting together. Again, bio is something that's been surviving, ripping, and gouging, for ~4 billion years. She don't have time to stop and let us know what is up.
In parallel with Darwin also try more recent advancements,like Don Hoffman's "The case against reality", where they prove that the probability that evolution will equip an organism to see the true reality is Zero.
Holy ... he's been features on HN since that long ago ?? I only heard of him from a random partial misclick on a funny youtube thumbnail less than two years ago.
It's incredible that the information necessary to create a human is just about 750 MB uncompressed. For example the very specific shape of the scapula bone or fear of spiders...
It's really not. If nothing else, conditions in the uterus, especially in the first few months, are extremely crucial. Take 10 identical fertilized eggs and put them in 10 different people and you'll get 10 different humans, not 10 clones as people generally assume. And this is not just genetics of the mother, differences in diet and lifestyle will also significantly (not to mention history) impact the development of the fetus, especially in the early months.
> Take 10 identical fertilized eggs and put them in 10 different people and you'll get 10 different humans
Well, some would say if you took 10 identical fertilised eggs and put them in the same human in serial you'd get 10 different humans. Some would say there's no such thing as 10 identical fertilised eggs, or 10 identical anything.
The question is how different? 10 identical eggs in 10 well-nourished, healthy people and the results should be pretty similar, no?
Honestly I don't think it's very clear. The practicalities of cloning processes make it so that we are very far from exploring what's in principle possible. All of the cloned mammals so far have died pretty young even when the original organism lived a long and healthy life, so in that sense they are technically way more different than even siblings. Of course, this is almost certainly just a limitation of our currently imperfect cloning technology, so it's hard to judge what a perfected cloning tech would do.
Of course, certain aspects of appearance are known to be almost exclusively genetically determined, such as eye, hair, and skin color. Some fine details are known from identical twin studies to not be fully determined, such as fingerprints (twins have slightly different fingerprints). For the majority of other fine details, it's actually pretty unclear.
To start, in the 99% of the times this question can be answered with: no.
I bet that the man being promoted here as the best thing since the invention of Banjo, didn't discovered the effect of chemical gradients in Embryology. (I don't know everything, and I could be wrong. I'm open to discuss his published scientific articles in the field).
That the same process that makes your arm will be repeated later to build each one of your fingers is known since many decades ago (count the number of articulations, is always car, car plus a cdr). See the video of U2 "Even better than the real thing" for a graphic representation of the idea. Yes, this is how it works basically.
> Take 10 identical fertilized eggs and put them in 10 different people and you'll get 10 different humans
You can bet it. This big claims always worry me. They either reveal a basic lack of understanding about biology, or are predatory and directed to select people that don't understand even the most basic concepts on Biology.
An spermatozoa can be used just one or zero times. Period.
There is not such thing as "10 identically fertilized eggs put in the same woman will get exactly the same human ten times", because is impossible to find 10 genetically identical spermatozoans and 10 genetically identical ovules to match them. Each time meiosis happens what you have is a similar but genetically different cell
Remember "Reflections on Trusting Trust"[0]? This is biology in a nutshell: the "source code" may be 750MB, but since every organism has been built by another organism, there's $deity knows how much information accumulated in, and copied by, the reproduction mechanism itself, without ever being present in the "source code".
Biological systems don't work this way. You need a fully living organism + DNA to produce a new organism. You can't "bootstrap" just from the DNA. DNA is not a blueprint: it is more like a recipe that assumes an intricate set of tools already exist. If you only had the DNA and not the "tools" (a living, healthy enough mother), you wouldn't get more than a few cells from it.
That's not what I said. The "tools" were also created from DNA, i.e. the mother.
Or are you saying that there's essentially undocumented-code that exists inside a living organisim and is transmitted mother to daughter, by virtue of being gestated, but is not in DNA?
Some of this is actually very well known - at the cellular level, when a cell divides, the nuclear DNA doesn't uniquely determine every aspect of the new cells, certain organelles divide separately and by their own mechanisms. So, it's trivial to observe that you can't recreate a cell fully knowing just its DNA, you also need the mitochondrial DNA but also other bits.
But there is even more than that. Imagine you had a program that explained exactly how to build a PC that can run this same program, starting from raw sand and ending up with a fully powered PC. So, if you boot a PC and give it access to a smart factory, this program will create a new smart factory from scratch that is a near perfect copy of the original smart factory. The question is: if you don't have a smart factory at all, you just found this program on printed paper, would you be able to use it to build a smart factory?
Most likely, no, because the program can easily depend on certain details of the original smart factory that it was used to copy. Let's say, it could have instructions like "measure the length of original.robot_arm_7 and cut this piece of metal to the same length", or, "combine the liquid in original.vat3 with two parts "water" and 1 part liquid from original.vat7, and pour the result in copy.vat3". This is how life works: it uses DNA to build copies of itself, but DNA can't help you build the original base cell, that was arrived at by an entirely different process.
Edit: for another simple example, consider that, if some ultra-advanced alien species found a population of living mammals, but they were all female, they would be fully able to create more females of the same species. But, it would be completely impossible for them to create a male of the original species, because there is no DNA whatsoever in a female mammal that explains how to build a testicle or a sperm cell. They could build artificial males, but they couldn't ever know if those males resemble the originals or not. So again, the DNA of an organism doesn't encode all the information necessary to create the species, that is transmitted through a more complex mechanism.
Thanks for your well-informed contributions to this thread. Food for thought. I must admit that I hadn't known the "factory environment" made such a big difference in outcomes.
In your opinion then, do we need to add a 3rd "variable" to the nature/nurture question? "Nature" is generally understood to be DNA, "Nurture" is generally accepted to be the post-birth development environment. If the "embyronic toolkit" at hand is so important, surely this popular concept needs a 3rd leg.
I'd also be interested in your thoughts on surrogacy. I had naively assumed that, so long as the surrogate mother was well-nourished, the baby would likely be fine. But it seems it's a lot more complicated than that, and I feel like a lot of people are underinformed about this.
Nature is the heritable part nurture is the "seems easiest to change" part.
Of course turns out that gene-environment interactions are common and complicated, so most of the things are mixed.
Brain development takes about 20 years, driven by genes, but the environment is extremely important to help people to learn how to get most out of that setup they got.
This is most evident in learning disabilities, for example stimulants are regularly described as life-changing by ADHD folks.
No, because each baby comes from a uterus, there is a second possible information transmission mechanism at play. Until we see a baby formed outside of a uterus that has a functioning uterus itself, you can’t be certain that the DNA has the requisite data.
People think DNA is the source code. It’s more like an API response. DNA is sufficient to pass traits down to the next generation. It is not sufficient to bootstrap life from nothing. It has to be interpreted by a very specific system.
In compression contests you count the size of both the compressed data (DNA) and the decompressor binary (egg cell).
We don't know how much data is required to fully describe a living cell, but it's not just the DNA since you can't turn that into a cell without using an existing cell
It could be argued that the "decompressor binary" is actually a female human, which sounds a bit like the old "store large parts of the compressed data in the decoder to get a smaller file size" trick. :-) Maybe the sperm / egg are deltas? I wonder if there has been any research done with parental similarity with gestation using surrogacy vs. natural mother.
DNA has been in development hell for billions of years, and yet compile/install times still vary widely between platforms and is not ABI compatible cross-platform.
Don’t get me started on the unauthorized use of proprietary code!
We keep getting asked about “checksums” and “reproducible builds” and if the BDFL is going to implement them, to which they say: “already landed in upstream,” “works on my machine,” “notabug,” and/or “wontfix” sometimes in the same reply.
I know you were joking, but what I was thinking of was that our DNA creates cells, but I don’t think that we would grow into proper humans without interacting with the rest of the earths environment. And there’s a lot more than 750 MB of information out there
> about the site where the rest of the info is pulled from
That's what Dualism posits: The rest of the info is elsewhere, and joins with the physical body. Dualism is usually discussed in regards to sapience, but it doesn't have to, it can also include the behavior of animals.
DNA is just a "program", and a living cell is basically an advanced programmable nanorobot. When cells divide or reproduce, the whole nanorobot is cloned with some modifications. The DNA tells how to modify the cloned nanorobot, and it is also possible to reprogram any cell back to the original state. Nobody knows how to make a cell i.e the nanorobot from stratch. The information is not in the DNA, like a computer program doesn't contain the instructions to build a computer.
Well until they succeed in creating artificial wombs it's technically a much larger amount of information (e.g. the cellular composition of the womb, how many and what kinds of nutrients that flow through, etc). We are still scratching the surface of epigenetics too.
> Well until they succeed in creating artificial wombs it's technically a much larger amount of information (e.g. the cellular composition of the womb, how many and what kinds of nutrients that flow through, etc).
You might note that this information is also contained in the same notional 750MB bundle.
Imagine a piece of software that works poorly the first time you run it, but modifies its environment so that it will work better in future runs.
There was an experiment in birds related to this. Someone had the question of whether birdsong was genetically or culturally determined.
The cultural side noted that, for whatever species of bird was under investigation, birds raised without parents produced abnormal song.
But upon continuing the experiment, the genetic side noted that the children of those birds, exposed only to the abnormal song of their parents, produced normal song.
Raising one bird in isolation isn't enough to express the information contained in that species' DNA, but the information is there anyway.
> You might note that this information is also contained in the same notional 750MB bundle.
Not necessarily, that's the point. It's uncertain if you can recreate a human being from genome alone even with perfect technology. Some crucial information could be passed from one female to another without being present in the genome at all.
> There was an experiment in birds related to this.
I suspect none of these birds were rebuilt in a laboratory from their genome alone. The experiment proves that information is passed inside the egg but it doesn't specify via which medium.
https://en.wikipedia.org/wiki/Centriole (but it looks like they can grow again "However, [...] cells whose centrioles have been removed via laser ablation [...] centrioles can be synthesized later in a de novo fashion."
In general, the instructions for creating a copy of an object can be very different from instructions for creating an original from scratch, because instructions for copying can use information already in instance A. And DNA is certainly instructions for copying, not for building from scratch.
How far you'd get using DNA to create some organism from scratch is unclear, but it's certainly not very far at all. You certainly can't create a whole eukaryotic cell just from DNA, even with all put current knowledge of organic chemistry plus our ability to study how current cells actually work (no one has come even slightly close to building a self-replicating prokaryotic cell).
Edit: imagine source code for a compiler that is allowed to strcpy() bits of the currently running compiler. It's a legitimate way to create a running compiler, but it's not what we'd normally consider "source code".
> It's incredible that the information necessary to create a human is just about 750 MB uncompressed
Hold up, isn't the point of this article that genes do not have all the information?
The, er, bootup environment of a freshly-fertilized human egg normally provides a lot more than merely protection and raw materials for nine months. Likely a lot of required parameters, and definitely a lot of important tuning optimizations.
> For example the very specific shape of the scapula bone or fear of spiders...
There were some studies a decade back about mice inheriting fears of certain smells from the father, I wonder if anyone discovered the mechanism (or disproved the effect) by now.
To a programmer it's reminiscent of a self-hosting compiler that comes with working source and binary, but not the sequence of bootstraps. "Trusting trust" makes a nice example of the hastiness in taking the source to be all you really need to know. Similarly, metacircular interpreters that leave evaluation order ambiguous.
Should be very interesting to quantify what's needed for a "clean bootstrap" of a minimal model organism that can reproduce.
> Hold up, isn't the point of this article that genes do not have all the information?
Yeah it is. The informational aspect (and the precision level) Levin and his friends are looking for is the main factor here. Cells are not just tissue building blocks, they're agents, limited but still, themselves with a lot more capabilities than we generally assume.
I believe multiple fields are mature enough (biology, computational biology, optics) to care and analyse this and make a new step in our understanding of complex organisms.
I guess that's without considering epigenetics which have some heritable marks. We are very far from knowing how much epigenetics contribute to the making of an organism and as a whole it is controversial. But one of the great lessons of the human genome project is that DNA coding does not account for all of the biologic information and that epigenetics may have a bigger part to play than what was previously thought. If we were somehow able to model every epigenetic marker the uncompressed information would be quite heavier
> His work has been featured everywhere from Scientific American to the Lex Fridman podcast and The New Yorker.
This is a weird way to posit someone's scientific achievements. Had they said eg Lancet, Nature and Science -- ok, clearly someone publishing in those venues is a scientific heavyweight. But being featured in pop-science, a famous podcast and a general audience magazine only tells me how well someone can explain/sell their research, but doesn't actually say anything about the strength of that research.
> They’ve done things like getting frogs to develop extra limbs, and getting them to develop an eye in their gut, or an eye in their tail that they can actually see out of.
I have two contradictory reactions to this. 1. "Isn't science amazing!" 2. "Poor froggy, how horrible."
This “Fractal Intelligence” stuff feels super Wolfram-like. Just as Wolfram argues that simple rules in cellular automata can create complex, intelligent patterns, Levin’s bioelectric networks show how cells and organs have their own built-in smarts and adaptability. Both are about how simple, foundational principles lead to sophisticated behaviour, challenging the old deterministic ways of thinking. It’s basically a fresh take on how complexity and intelligence arise, and could really shake up how we understand biology and systems in general.
That doesn't inspire confidence in Levin's research, if it were true. Wolfram's quixotic quest for a theory of everything is something basically only he believes in, with very little shot at doing anything worthwhile, at least for physics. I hope that Levin's notions are more likely to bear some fruit.
With such apparent speed and quality of research thought we will never have anatomical compiler, let alone electroceutocals and anthrobots, on a routine basis at least in the next couple of hundreds of years.
When in 18xx FDA or its precursor was being formed, its goal was to confine various "bioelectrical woo" present in medicine and biology at that time. And back then there was Rife's microscope, for example, which was able to accurately image living cells.
Yet no-one tried to account for the cumulative damage/adverse effects done by FDA approved treatments in comparison with a potential or actual damage done by such "woo".
>the impact of Levin’s work is a shift away from genes as the only determinant of structure
Nobody was making the claim that genes are the only determinant of structure though. A trivial example is the mother's hormones affecting her child's development in utero. To cause a shift away from genes would require showing that the bioelectric network is not itself caused by genetic factors. Otherwise while it may be useful as a tool to develop treatments for developmental diseases it does not change that genes are the ultimate cause of the bioelectric network itself (except as when directly manipulated by scientists).
Quoting Levin himself:
>Evolution was using bioelectric signaling long before neurons and muscles appeared, to solve the problem of creating and repairing complex bodies.[0]
It sounds like to me from this quote that bioelectric networks are not something outside of genetics but just another important biological system.
It's hard to pin down what the author is really getting at in the first place. For example these two lines:
>genes are great, and they do contain much of the necessary information for building our bodies. But they don’t contain all of it
>[...]
>Levin’s point is that genes are like machine code, and modern-day programmers never think about machine code—they think about higher-level software constructs like objects, modules, and applications.
Yet machine code really is what is being executed by the computer. Nobody would say that the computer is really running c++, for example, or that c++ is a new "determinant of structure" of the program. It is completely subsumed by machine code.
The author is the entire time equating a set of instructions (the genome) to a biological system (the "bioelectric network"). However it does not make sense to equate these things in the way the author has done it (at least not without a lot more elaboration). The genes do not really do anything except get copied and transcribed into mRNA while the bioelectric network clearly is doing something. So it really seems more like the author should be comparing proteins with the bioelectric network. But I think here the problem becomes much more obvious – there is no other way besides proteins for biological organisms to do work. So it is obvious that the bioelectric network is somehow formed by the work of proteins, and the proteins are themselves caused by genes. The human body has within it many systems: the circulatory system, the respiratory system, the endocrine system, the nervous system, the muscular system etc. These all exist at "higher levels of abstraction" than genes and some of them, like the endocrine system, play a role in development. But it wouldn't make sense to say that these system are "in competition" with the genome. Even though we can use the circulatory system to transport a drug to the body that changes the structure of the body.
Another major difference is that genetics are continually showing their influence because the body is continually creating proteins from the genome. It sounds from the article that this bioelectric network is really only relevant at the developmental stage (if I am wrong here then I feel the article should have made that more explicit).
Ultimately I feel the article is arguing a bit against a strawman of "genes as the only determinant of structure" and is also making too vague of a claim about genes having a new competitor, so to speak.
Way out of my wheelhouse but after reading this it leads me to believe "heal machines" like in elysium and other scifi movies may not be that much scifi after all.... block an ion channel here, send a signal there... poof, your arm is back!
I think what I’ll do is get a hobby that is not too expensive. Like, you have to buy something overpriced to satisfy a midlife crisis, but at least I will try to get some nice headphones (not harmful at least, and with nice headphones you can play your music quieter, save your hearing) or a good bicycle (healthy!) out of it.
Anything but a sports car, really. Driving around in a sports car is just advanced sitting, which I already do to much of, and they are very expensive.
Sports car does not need to be expensive. I think it's more about having a purpose and being useful rather than anything else. I saw it in me and other people I know that went through that period. The greater the thing you're working on the less you'll feel any change.
Continuing with the dev bio theme, I'd suggest kicking off a mid-life crisis with a decent microscope, petri dishes, and maybe some planeria or something else to study.
By all means go back to university, even do a PhD, if you find a subject you’re passionate about (and have the beans to finance it). That’s what I did and it was great!
I find the probability of someone on the internet being able to give you sound advice, without knowing your situation and personality extremely small.
For me personally it is most of the time about the balance between what you can afford, what would you think you would like to achieve and what you miss would. Reasonably, most of the people can't "have it all" (family, money, peace of mind, results, etc.).
Well it’s not lucrative in the tech company sense but it is interesting science. It keeps the brain engaged. So less competition but a harder space if that makes sense.
The larger breakthroughs will be driven by AI and new instruments. Biological understanding has always been about developing the right tool/instrument to answer a question.
Have you read a book called The Stairway to Life: An Origin-of-Life Reality Check by Tan & Stadler? You can find it on Amazon. It's pretty short and will get you thinking rigorously about the problem.
Also searchable by its other title "God of the Gaps Volume 6,000 - Forget the Other 5999, This Time We're Really Sure, Can You Stop Doing Research Now Please"
And I'm not opposed to doing research, of course (hard to believe I have to clarify this)
In fact I want people to research the question of the origin of life as rigorously and exhaustively as possible because it is just going to make it that much more obvious that life was designed by God.
I have absolutely no fear that this "gap" is going to do anything but widen.
No. But I feel like it is unlikely I'll find much value in it. Part 1 being on the Venter work does NOT inspire confidence at all. Not to dismiss them - they're great I've worked with them on a couple projects - but it frankly doesn't have anything to do with abiogenesis. The other fact that lots of creationists like it doesn't bode well either.
Like, of COURSE the Venter cell looks too complicated to originate from raw chemicals! The lineage it evolved from was far more complex, and Mycoplasma underwent minimization. Minimal life also does not equal simple life, or life that was most probable to arise from chemicals. Just a stupid premise, really.
It’s hard to see how it would be evidence based if the evidence’s premise is fundamentally flawed - just in such a niche way that people not in my field wouldn’t be able to see it. They’re kinda preying on the fact that people like you can’t see it, and that’s sad.
The false premise is that the religious explanation is the default or incumbent explanation, which must then be bettered or countered by "challenger" explanations such as science. It tries to frame the argument with religion as the "defending champion" for challengers to somehow unseat ("atheists need to explain how...").
In reality, of course, religious explanation has no such presumptive default or incumbent status. Religious explanations are just one of many potential explanations for how the world works and compete on equal terms with any other. And when the religious explanation really just boils down to some variant of "god did it", it becomes very obvious how inadequate that is compared to even the worst scientific attempts.
Related: religious apologists constantly try to pretend that criticisms or problems identified with scientific explanations somehow count as points in favor of their religious alternative. This is also a false idea. It is not a debate, where pointing out flaws in your opponent's argument helps yours "win". It is a search for truth, and finding fault with another theory does nothing at all to enhance your own.
Breaking the site guidelines like this will get your account banned on HN, regardless of how wrong someone else is or you feel they are, or how badly someone else is behaving.
The most interesting for me is the offspring, reproducing a different structure with the same genes. I think mathematically this could be the missing link in evolution, where random gene modifications are just not probable enough to drive evolution. 3 billion DNA pairs cannot evolve randomly, there is not enough time and matter in the universe to randomly try successful generations of life forms. However, bioelectric might be a much much more straightforward and fast way of driving evolution instead of randomly mutating DNA.
> I think mathematically this could be the missing link in evolution, where random gene modifications are just not probable enough to drive evolution. 3 billion DNA pairs cannot evolve randomly, there is not enough time and matter in the universe to randomly try successful generations of life forms
This suggests you have not tried writing a simulated evolution based optimiser.
They're quite easy to write, the hard part is what you mean by a "fitness function" (which doesn't matter for nature, it just is whatever it is).
Such algorithms are also more than fast enough — remember that for the first 3 billion years we only had single-celled life, and that can reproduce in 20 minutes, so we had potentially 79 trillion generations (edit because "78.84 trillion" would be overselling the precision) before the first multicellular life. You get good results faster than that.
The number of base pairs is also just a misleading statistic. For example: each of XXX, XXY, XYY, and Downs are found in around 0.1 of human births, each of which gets an extra copy of a chromosome. These specific changes may not be too good for us, but this kind of sudden massive increase is also found in some plants without negative repercussions.
> However, bioelectric might be a much much more straightforward and fast way of driving evolution instead of randomly mutating DNA.
I have no reason to expect bioelectric processes described in this article to be able to direct useful effects on the genome, for the same reasons I think it unlikely your own brain could by sheer willpower turn you into a werewolf.
> For example: each of XXX, XXY, XYY, and Downs are found in around 0.1 of human births, each of which gets an extra copy of a chromosome. These specific changes may not be too good for us, but this kind of sudden massive increase is also found in some plants without negative repercussions.
A couple notes:
Downs is unlike the other defects you mentioned in that it severely impairs the patient while the various extra-sex-chromosome disorders vary from sterility through minor impairment to what basically amounts to behavioral differences.
Downs is unusual, though, in that most extra chromosomes make the fetus nonviable. As far as trisomy disorders go in general, Downs is unusually benign.
Plants are better known for increasing their -ploidy (number of sets of chromosomes) than the count of an individual chromosome. A triploid human, with three copies of every chromosome, would be hopelessly nonviable. Plants are different. Really different.
I learnt that evolution is random mutations of genes + natural selection (selecting the successful random trials).
If you have 10^14 generations on 3 billion years, always use up the mass of the Earth, 10^28g, that is 10^40 cells, so you have 10^54 cells randomly trying the best permutation of DNA, that's suprisingly few to balance the vast amount of possible permutations. 4^100000 being 10^60205
Sure, but my question is what does evolution try? If it is full random, then it will TRY much better and much worse mutations as well, so will go back and forth, and will take a lot of time.
If it is not fully random, e.g. it is not not able to try big changes, then what is the thing that actually determines what is "feasible", BEFORE trying it out.
Environment. You seem to be missing the "natural selection" part of evolution. The optimization process works like this:
- Life reproduces; between imperfections in reproduction and environmental mutagenic factors, there is a certain amount of random mutations;
- The churn happens. Organisms compete for resources; winners reproduce, losers starve. Environment throws curveballs - spills, seasons, volcanos, radiation, oxygen, and a million different things. A lot of organisms are killed, some survive and reproduce. Now, mutations can make organisms better or worse at surviving the challenges. This is the asymmetry you're looking for, the driver of evolution. Helpful mutations propagate, unhelpful mutations die. Where "helpful" means, of course, "helpful locally, at a given moment".
Rinse and repeat. The randomness isn't the driver - it's just jitter preventing evolution from getting stuck in a local minimum. The life cycle of birth and death is what drives evolution, specifically because it depends on both how the organism is built, and on the environment.
Full random. Something like 50% of human babies have random mutations which make them unable to develop past the stage of being invisible to the naked eye. Such miscarriages seem like normal menstruation.
There's a knack to optimizing the mutation rate. If you mutate too much, 99.9999% of offspring can't develop and in the end there's too little reproduction. If you don't mutate enough, you don't evolve. Evolution has already optimized this hyperparameter.
That said, my experiments in silico say that what matters most is the pressure from the utility function, more so than the rate of mutation.
So if some organism is in an environment where only a few mutations help, then evolution progresses slowly; and when most possible changes are improvements, then evolution progresses faster.
Both environments can happen even without any dynamic change to the rate of mutations themselves.
It will try much better and much worse, those that are much better will produce a lot of offspring while those that are a lot worse will produce few to none, and so in the next generation there will be a lot more starting from "much better" than "much worse."
> where random gene modifications are just not probable enough to drive evolution. 3 billion DNA pairs cannot evolve randomly, there is not enough time and matter in the universe to randomly try successful generations of life forms.
As a biologist, I don't think this really follows. From my perspective of studying life, 3 billion DNA pairs can definitely evolve randomly - it's not even really that hard. Eukaryotic life just happened to get that because the fitness deficit from the retrotransposons weren't too bad. On the contrary, I can't actually see how bioelectric could drive evolution - only the creation of more complex structures
Indeed, they do not evolve randomly. There’s this thing called natural selection that is relatively crucial.
Your interpretation of bioelectric effects as summarized in this article seems to have missed something. The bioelectric network is itself an expression of the genes involved in development. It’s not a separate magical force.
>>The bioelectric network is itself an expression of the genes involved in development.
Yes, you may need genes to express the proteins of ion channels and gap junctions, but there is no anatomy coded by genes, no genes code for how many limbs will a biosystem have (as reiterated by Levin). And it is this level of resolution that actually mattered for years before the launch of molecular biology and medicine.
>>It’s not a separate magical force.
Indeed, it sort of (suppose - by up to 70%) is. If the fine structure constant, which defines the strength of the interaction between a charge and an electric field, were 4% less or more than its current value, the current world and biosphere wouldn't exist. So far physics can't explain why the fine structure constant has this exact value (~1/137, which is also unique that it is a dimenionless constant). (I'm not inferring anything, just presenting raw data).
At least in a specific experimental context and with specific animal models. When they mixed the embryos of a frog and an axolotl, there were no genes in their genome which could predict whether a "frogolotl" will have legs.
That's been reiterated by Levin at almost every presentation. Maybe he's overgeneralizing or there's actually a lack of specific experimental context or reference to a specific study. Maybe "anatomy" is a bit too broad of a term, and the thing inferred is some overall macroscopic patterning, so can't say definitely "untrue", as I haven't yet dedicated time to delve into specific articles and been just consuming lectures/presentations.
But I remember he was mentioning some study in left/right asymmetry in DevBio, where they've shown that it's cell potentials/bioelectric signalling and not genes that determine the left/right asymmetry in embryos.
> where they've shown that it's cell potentials/bioelectric signalling and not genes that determine the left/right asymmetry in embryos.
No, they've shown that electric signaling is how the genes determine the left/right asymmetry in embryos.
How do you think it is that the same thing happens so consistently every time a new organism develops? Where do you think the electric gradients come from?
It's not any different from the nervous system, really, it's just that we're now recognizing that those fields are involved in things other than sensation, perception, etc..
> reproducing a different structure with the same genes
This a-ha moment for me with respect to this is that some biological processes are of the type [random process -> selection -> stable result]. This means that the genetics actually _don't_ store the information for what is ultimately produced, only the information necessary to trigger a random exploratory process and to stabilize that process when it reaches a suitable target. This is one reason why animals can flexibly adapt their development to different conditions as described in the above article.
As I understand, the worm cells act differently because the worm is placed in a solution which interferes with their electrical messaging, so it makes sense that the offspring growing up in the same solution would grow with the same defects as the parents. I think that's all there is to it.
> Two-headed worms made this way reveal a permanent revision of the target morphology: subsequent rounds of regeneration in plain water, long after the reagent is gone from the tissue, continue to make two-headed worms.
No, I want the computational feasibility explanation with some nice O(function) on biological processes. To the best of my knowledge, we still have no idea.
Something like "the computational complexity of a beached fish to invent and grow a leg is O(n^2 log n) hours where n is the number of neural spikes in frontal cortex" or similar.
Those are great models for local adaptations. They won't grow a leg with extricate mechanical properties we have trouble modeling in state-of-art robotics/mechanics.
I didn't say it had to simulate real physics. Have you ever tried *a* genetic algorithm? They grow legs all the time in their toy universes, if that helps them increase their objective function.
All genetic algorithms are created by conscious intelligent beings. So I'm more interested in how a genetic algorithm develops by chance, with what probability. I guess typing monkeys wouldn't create genetic algorithms in the existing universe's timeframe even if the monkeys themselves have some (also random) fitness function that by chance has the ability to replace dumb monkeys with smarter ones.
Genetic algorithms are everywhere. Every time (1) something copies itself with mistakes, and (2) ....... actually there's just (1), no (2). Every time things copy themselves imperfectly, you have a genetic algorithm, and the fitness function is how much they copy themselves in the long run.
The current best hypothesis is that RNA randomly developed and evolved. Some if it happened to be self-copying. If there are self-copying things, there will be lots of self-copying things - that's common sense. And a genetic algorithm fitness function. In an ocean with RNA, sometimes it will happen to bump into other bits of RNA and swap over. Sometimes they randomly get better at copying. Zillions of molecules and hundreds of millions of years is a long time for small chances to happen. We want genetic algorithms to run in seconds on a PC. Ones that run for millions of years in the Earth's whole ocean don't have to be nearly as good.
The Miller-Urey experiment demonstrated that chemicals we know as building blocks of life can come into existence by themselves in early Earth conditions. What we don't know yet is exactly how they got from there to cells, since we don't have a time machine to go and look. Scientists keep finding plausible stepping stones, though.
my favourite far out there version of chemical evolution is the one where the entire Hubble volume was in the goldilocks zone for a few million years! sadly we may never be able to confirm it with samples, as there will always be the worry of contamination from earth.
Fish aren't the only things that live in water. There are other marine organisms, some of which have leg-like things. What if one of those organisms, already equipped with legs, evolved to survive on the surface?
While metabolic advantage is a thing, I'm not sure if organisms are expected to carry minimum amount of genetic code that they actually use; in what little I know about developmental biology, I recall there's a high-level structure to the genetic code - some genes are doing more of flow control than encoding actual proteins. It's conceivable that the fish which walked on Earth was the one that managed to accumulate inactive adaptations for walking and switched them on.
Also, there's horizontal gene transfer to account for. It further complicates the picture.
Genes get duplicated by accident, then accumulate mutations which are usually neutral or worse. Occasionally they help you achieve something slightly more useful than before. Lobed fins that helped you heave yourself back into water when you get beached would have helped. bigger lobed fins would help you get back when stranded further up the beach, or get from pool to pool. It's unlikely that an entire set of limbs, other necessary body upgrades to support them and neural circuits would just hang around waiting for all the right mutations to collect like hole punches on a restaurant loyalty card before some critter slapped their thighs and stood up and walked. Evolution does not plan ahead.
This argument is however an argument from faith and not from computability perspective. Random garbage genes flipped on won't grow a leg with intricate mechanical abilities. Those abilities have to be computed somewhere and need to be useful right from the start to appear in offsprings otherwise they get eliminated as a waste. Yet everyone puts their faith in some random process instead of pinning down the concrete mechanisms how does this happen. So you basically end up forcing some idiotic faith on everyone instead of digging deep and figuring it finally out. I would be more inclined to believe if you told me that pre-adolescent brain spends 25% of its computing capacity on figuring out how to improve its body and encoding it into genes instead of trusting some random mutation (likely error-corrected) to do the heavy lifting.
It's not a faith thing. Yes, metabolic advantage is a thing and useless adaptations can get eliminated over time (it seems to matter more in single-cellular organisms, though). However, often enough, unused adaptations can persist for a long time - for example, pythons still have the whole blueprint for "a leg with intricate mechanical abilities" and nerves and stuff, it's literally just switched off. We know because some researchers figured out how to flip it back on, and behold, snakes grew their legs back. That's what I've been alluding to in the prior comment - genes aren't encoding a flat blueprint, but a complex program with many genes working as flow control or signalling superstructure, able to toggle or modify whole complex body parts.
> I would be more inclined to believe if you told me that pre-adolescent brain spends 25% of its computing capacity on figuring out how to improve its body and encoding it into genes instead of trusting some random mutation (likely error-corrected) to do the heavy lifting.
this is an argument from personal incredulity. just because you are too dumb to understand how something works doesn't mean that your fantasy/sci-fi version is accurate. brains changing genes belongs in a discussion of Neal Asher's polity, not in a biology discussion.
So you are saying that e.g. a large mammal lifespan of 70 years is sufficient to generate as many good random mutations as needed to grow a new leg over 10,000 generations if necessary? Where is the evidence of a fast algorithm requiring so few selections to come up with a complex new organ? How is that not blind faith? Not sure who is the dumb one here...
I offer paid tuition. For £50/h, I will learn stuff for you and then teach you. Prep time is typically ~3h for each hour I teach you. Minimum 1h lessons.
I will pay you £50,000/h if you could give me a convincing answer like "the computational complexity of a beached fish to invent and grow a leg is O(n^2 log n) hours where n is the number of neural spikes in frontal cortex".
> where n is the number of neural spikes in frontal cortex
If neural spikes had anything to do with it, if any of this worked like that, bacteria wouldn't develop resistance to antibiotics (they can), and I would be able to shapeshift (I can't).
So that question is like asking for a route finding algorithm that's O(n) where n is the number of letters in the destination.
And my point is the the question suggests a worldview so incorrect that the question is meaningless.
If you seek understanding, you must decide upon a specific better question of your choice; if you leave it up to us to devise the question, we can do that, but it's overwhelming unlikely that our free choice will connect with whatever it is that led you to ask the question in the first place.
For example, I could ask you to consider a model of a fish where each bone length is controlled by some gene, and then evolution converting fins to legs is some function of the magnitude of reproduction selection pressure on those changes over multiple individuals and generations… and nothing at all to do with one individual's brain.
Or were you thinking of a specific fish species which develops legs when it reaches adulthood?
You were giving examples of local adaptations (bacteria building resistance) instead of paradigm shifts (beached fish growing legs). The science behind the former is established (mutations favored by environment); the science behind the latter is not. You are mixing the two together and complaining the second one is non-sense, but is it? Somehow fish had to learn to walk ("evolution from one organism to another") in a limited time including complex mechanics that our computers can't solve exactly; I am waiting for any computational biologist to give us some mechanism behind it that is realistic, i.e. computable. So far nothing and people keep mentioning local adaptations only.
> The science behind the former is established (mutations favored by environment); the science behind the latter is not.
That's not even an example of a paradigm shift. Continuous transformation trivially gets us between superficial differences like mere body shape, there are many examples of us applying selection pressure to other species to make that category of thing happen, including our crops, livestock, and pets — no more than 10k years separated Chihuahuas and Corgis from Newfoundlands and Afghan Hounds. Likewise even more extreme changes between crops and their wild relatives, the wild versions are almost unrecognisable except to experts.
> You are mixing the two together and complaining the second one is non-sense, but is it?
What I'm calling nonsensical is your description. You're calling for the time complexity for a brain to invent changes that aren't caused directly by brains.
> Somehow fish had to learn to walk ("evolution from one organism to another") in a limited time including complex mechanics that our computers can't solve exactly
1) Exact solutions aren't necessary; 2) computers have solved walking; 3) the boundary between walking and floundering is an arbitrary one. And #4 after the next quote…
> I am waiting for any computational biologist to give us some mechanism behind it that is realistic,
4) One of the ways computers solve problems like this is simulated evolution.
If you don't consider the working demonstrations to be realistic, that's a "you" problem, not something the rest of us care to waste time on.
> So far nothing and people keep mentioning local adaptations only.
Do you also insist nobody has ever climbed Mount Everest on the grounds that nobody has legs long enough to do it in one step?
Or that motion pictures are impossible because each frame is stationary?
Can you prove it? Show me some sort of an environment where a water-based complex organism is able to survive and thrive in dry environment prompting it to grow a new movement organ useless in the water but needed on surface and give me some less-than-exponential algorithmic complexity bound for it. If you can't do it, you don't offer valuable lessons.
The Lungfish survives prolonged droughts where its freshwater habitat dries up. It has evolved the ability to breath fresh air, secrete a mucous membrane to form a protective cocoon that helps it retain moitsture, and its fins are heavily modified to aid with land based locomotion. Lungfish are the closest relatives to tetrapods who likely evolved under similar conditions.
i told you something that you claim to be true isn't what is claimed to happen by the theory of evolution by natural selection, and you want me to provide proof that it does in fact happen? have you taken leave entirely of your senses?
edit: sorry dang, I fell for it again, didn't I?
edit 2: actually treprinum, I have a sensible answer here, although you're not going to like it. if you were smart enough to understand what you are asking, you really wouldn't have picked body plan as your "gotcha". you would have picked something truly wonderful like the genetic code, or the ribosome, or mechanisms of gene regulation, or embryology, or eukaryotic cells.
the evolution of new body plans is very well understood. i won't explain it to you though, until and unless I get paid. I believe we agreed £50,000/h for an hour minimum lesson which is three hours of prep - so £200,000 total for the first paid lesson? this one here is free.
The first observation is that DNA, on its own, is useless. It has no causal power. It doesn't generate or explain life or cells. You need an existing cell, an existing organism, to make use of the DNA, as it were. Of course, without DNA, the cell cannot proceed. So this mutual dependence tells you that they're a package deal, and neither can be reduced to the other.
The second is that you really cannot get away from telos. The ostensible banishment of telos is not a scientific conclusion, but a metaphysical choice, and one that is incoherent. Telos isn't will or desire or planning or intent per se, though these are examples. Telos is what explains why an effect follows from a cause, and does so with regularity. That striking a match (efficient cause) results in fire (effect) is a question of telos, of the match being ordered toward the effect of fire, effected and actualized by striking. The match obviously is not planning to produce fire, it doesn't will it or want it. But it is causally ordered toward that end or effect. Otherwise, you could not explain why striking it actualizes this potential for fire. You could not make sense of any phenomena, why striking a match results in fire instead of, say, nothing or the appearance of an elephant or whatever.
Biology is no different, but here we can speak of higher order telos. And as biology progresses, the more difficult it is to maintain the crude mechanistic view of life reaching back to the 17th century, that is, one modeled on the machine metaphor. Living things, strictly speaking, are not machines. They're integral wholes, not accidental arrangements.
Autopoiesis is not an easy set of concepts but one of the ideas is that details of structure are much less important that preservation of relationships that allow an entity to replenish its own constituents. Planarian are damn adaptable, but this is hardly news.
Nick Lane emphasizes that DNA is subsidiary to bioenergetics and “proton pumping” across membranes. His recent book “Transformer” focuses on the Kreb’s cycle and mitochondria as the crux of life (and autopoiesis, although he does not use this term).
Lane is extremely readable. Maturana is almost inscrutable.
I enjoined the target article, but am not comfortable boiling down development to “bioelectrics”. A complementary perspective but I do not think this will get us farther than good old developmental molecular biology.