5 ms·

That sort of thing just amazes me. I get that it is "programmed" by DNA, and I understand programming quite well, but the series of chemical reactions that allo

That sort of thing just amazes me. I get that it is "programmed" by DNA, and I understand programming quite well, but the series of chemical reactions that allow the cells to go from gamete to full thing still fills me with wonder.

TaupeRanger 6y ago
Increasingly it's becoming clear that DNA is only a small part of the picture. Cellular electrical dynamics are the forefront of morphogenesis research atm. Look at any recent high profile work out of Michael Levin's lab for an example.
- bigtones 6y ago
  https://en.wikipedia.org/wiki/Bioelectricity https://en.wikipedia.org/wiki/Bioelectricity
- fktnktofk 6y ago
  Aren't those electrical field patterns still somehow encoded in the DNA?
  - ethbr0 6y ago
    Everything is deterministic if you're omniscient. In our more limited experience, certain levels of complexity mean unpredictable outcomes. As for why-not-DNA, I think about it in terms of "If there were some way that was faster able to adapt organisms than DNA changes, wouldn't most organisms accumulate substantial functionality via that pathway over time?"
    - sssilver 6y ago
      > Everything is deterministic if you're omniscient Is this true, given https://en.wikipedia.org/wiki/Uncertainty_principle https://en.wikipedia.org/wiki/Uncertainty_principle ?
      - deleted 6y ago
        [deleted]
      - frutiger 6y ago
        It is indeed not true, even omniscient beings can only produce probability distributions. However it is not clear if quantum effects are relevant at a biomolecular scale. Some experts[1] suggest so but these ideas are considered fringe by the mainstream. 1. Sir Roger Penrose
      - Ixio 6y ago
        I'm of the mind that randomness is only an approximation of complexity, if you're omniscient then randomness doesn't exist and everything is deterministic. However it seems to me the deterministic vs randomness debate is of the same order as the existence of god(s) : we will never be able to prove or disprove it and we aren't able to make useful predictions out of the information one way or the other so we might as well just agree to disagree and move on.
  - TeMPOraL 6y ago
    They don't need to be. I'm not sure what the conclusion of biologists is today, but I have a feeling a lot of important mechanisms aren't encoded in the DNA - or, at least, not anymore. The key insight here is that cell reproduction doesn't happen out of nothing, it's always an existing mechanism working on a new mechanism. The seminal paper of Ken Thompson, "Reflections on Trusting Trust" (1984)[0], demonstrates how you can encode a backdoor in a compiler in such a way that the compiler embeds this backdoor in every program it builds, and embeds the backdoor-embedding machinery in every new compiler binary it builds. You can use it to build a "vanilla" compiler and make it backdoor-embedding, even though the source code doesn't have backdoor-embedding instructions in it. I suspect similar things happen in biology - there is computationally relevant information embedded in the runtime state, that's not explicitly encoded in the DNA - but it carries on, because every new living cell is built by a previous living cell. -- [0] - https://www.cs.cmu.edu/~rdriley/487/papers/Thompson_1984_ReflectionsonTrustingTrust.pdf https://www.cs.cmu.edu/~rdriley/487/papers/Thompson_1984_Ref...
    - fktnktofk 6y ago
      I get your point and I agree, the DNA runs on hardware, which is why you can't take cat DNA and put it in a salamander cell and expect to get a cat. The resulting cell will just die since the hardware is not compatible with the DNA. My point was that there is only so much information capacity in the cell if you exclude DNA, surely much less than needed to store electrical fields patterns for a whole embryo.
      - deleted 6y ago
        [deleted]
      - FartyMcFarter 6y ago
        A cell has a lot of atoms, which may store a lot of information?
        Robotbeat 6y ago
        But not error corrected like DNA.
  - WClayFerguson 6y ago
    DNA is basically digital information. Every rung on the helix ladder is either an AT or GC. Nature found the simplest say to store information in our chemistry set. Couldn't really store any field patterns though.
    - Robotbeat 6y ago
      RNA is simpler but doesn’t error correct as much like DNA. It’s possible the first life forms had only RNA.
  - oconnor663 6y ago
    Speculating for fun based on what scientist people have told me at parties :) I think the idea is that DNA will directly and literally encode things like "the genes for proteins A and B tend to get activated together". But the next thing that happens is that protein B catalyzes some chain of chemical reactions that winds up activating a different gene for protein C. And then maybe protein C causes some sort of mechanical change in the cell, and the resulting mechanical stress triggers the production of protein D in adjacent cells. Mapping the mechanical relationships between cells in an animal with developing bones and muscles gets super complicated. So the question of "does the DNA encode the relationship between A and D" ends up depending on what you mean by "encode".
- jcims 6y ago
  Not sure if this is included in 'cellular electrical dynamics' but it's still amazing: Neuronal Signaling and Sodium-Potassium Pump (from PDB-101) https://www.youtube.com/watch?v=ZKE8qK9UCrU https://www.youtube.com/watch?v=ZKE8qK9UCrU
  - navan 6y ago
    This reminded me of a beautiful animation of "Mitochondria: the cell's powerhouse" which I recently watched. https://www.youtube.com/watch?v=vkYEYjintqU https://www.youtube.com/watch?v=vkYEYjintqU
- ChuckMcM 6y ago
  Excellent reference. Bio papers with electricity in them, that is new for me. This one [1] is currently blowing my mind :-) [1] https://www.the-scientist.com/features/how-groups-of-cells-cooperate-to-build-organs-and-organisms-67881 https://www.the-scientist.com/features/how-groups-of-cells-c...
  - yalok 6y ago
    Totally. And kind of explains why some electrophoresis therapies may be working.
- lurquer 6y ago
  During the initial boredom of Covid, I got very interested in Levin’s lab’s work and morphogenesis in general. I made a program to implement some of my theories. You’re welcome to try it. cycell2d.com My pet theory — morphogenic fields — is described in their on one of the pages. (Caveat: I’m neither a biologist nor a ‘real’ programmer. But, I was able to come up with a system to ‘grow’ certain animals and found it a fun way to spend the lockdown... almost as much fun as posting ‘Covid is a hoax’ comments on HackerNews... ahhh... those were the days.)
  - dgellow 6y ago
    You should submit your website as its own on HN :)
  - plancien 6y ago
    I'm very impressed, this made my day (my month ?). Too bad your site lacks some nice video demos on the front page. To other HN readers, look what I found in it's tutorial : https://www.youtube.com/watch?v=dkvB4nb8PXw https://www.youtube.com/watch?v=dkvB4nb8PXw
- koeng 6y ago
  Small part of the picture is an exaggeration, IMO. Cellular electrical dynamics matter, but we already know that surface physics matter (see: any mammalian lab with those flat little red bottles). Those dynamics (physical, electrical, chemical) are all derived from genes coded in DNA, and so long as you have the basic ribosomes / mitochondrial structures, you can re-instantiate an entire organism from just the DNA.
  - TaupeRanger 6y ago
    DNA is certainly necessary and integral, but not at all sufficient for a full scientific understanding. Just like quantum mechanics is to rocket science. The heavy focus on genetics has hindered our understanding until very recently IMO.
    - koeng 6y ago
      > hindered our understanding until very recently IMO Any specific examples of how it hindered our understanding? Like maybe some grants or something? Because as a synthetic biologist, I've never seen a heavy emphasis on genetics take away from other causes of cellular dynamics - in fact, exactly the opposite, because genetic engineering has allowed tinkering of those cellular dynamics (for example, cardio tissue surface physics). I don't know of any serious biologist that (even historically) disregarded the importance of other physical factors in favor of DNA, but I would love to know compelling counter examples.
    - abandonliberty 6y ago
      Rather than "small part of the picture", you would get less disagreement with something like "beginning of the story." I doubt many people would agree that computer hardware is a small part of the picture of modern computation. They're the foundations that everything else is built on, and with.
  - kaba0 6y ago
    DNA can’t bootstrap itself, so to say. So previous cell-functionality is required for everything, so you can only re-instantiate an entire organism if you have a denucleated pluripotent cell from an evolutionary close enough organism. (But correct me if I’m wrong)
- abledon 6y ago
  have you read "Spark in the Machine"? Its an attempt to connect bioelectric science with ancient notions of 'chi', it goes over neural crest cells, organization centers for cell growth, and the electrosensitive pericardium cage near the heart. They definitely didn't get 100% of it right, buts its quite uncanny how the ancient texts were so accurate at predicting certain things that are only becoming evident in morphogensis research.
- sriku 6y ago
  Link to talk - https://www.youtube.com/watch?v=HwtOZ_WfMw0 https://www.youtube.com/watch?v=HwtOZ_WfMw0 - in which my mind was blown.
p1mrx 6y ago
It is "programmed" by the recursive feedback loop of evolution. If anything fails to work, the program terminates and something more reliable will take its place.
- umvi 6y ago
  Still nothing short of incredible. "the recursive feedback loop of evolution" abstracts a mind boggling amount of complexity. How did such a complex system start? I suppose if we knew, abiogenesis would be a solved problem.
  - lovecg 6y ago
    There are some plausible theories, like RNA randomly crystallizing on a suitable surface. Sooner or later a self-copying one just happened to crystallize by chance, and there was no going back. Fun lecture series: https://youtu.be/PqPGOhXoprU https://youtu.be/PqPGOhXoprU
  - shellfishgene 6y ago
    You may like "The Vital Question" by Nick Lane, a book which presents one possible scenario in a quite readable way. Much of it is quite speculative of course, but you get a good idea what the basic principles are.
  - KineticLensman 6y ago
    > "the recursive feedback loop of evolution" abstracts a mind boggling amount of complexity. How did such a complex system start? From something much simpler, and which has been iterating for approx 4 billion years.
- brbrodude 6y ago
  The trippy detail for me is that the runtime is time and space, thats what its frictioned against, even matter and its states are determined by it. Evolution sure is a word.. Not sure it captures it tho
- WClayFerguson 6y ago
postalrat 6y ago
Trying to figure out how biology works probably isn't much different than it would be to figure out how an alien spacecraft works.
geijoenr 6y ago
Indeed, there are always two parts to it: the software and the machine (the system of chemical structures and interactions inside the cell) , both equally important. We are at the point we can read the software but have a very limited idea on how the machine works.
- holoduke 6y ago
  Mm I would argue that we have a fair understanding on how the hardware works (chemical processes). But we have not clue how things are controlled and how things work together.
lm28469 6y ago
> I understand programming quite well Software programming or biological programming ? These things have the same names but they're not really comparable
- ChuckMcM 6y ago
  Well I think of it as the state machines and cellular automata. And yes, how cellular state machines work is clearly different than how a computer state machines work, they have a surprising (to me) lot in common. If you are interested in these comparisons I can recommend two books, one is Feynman's "Lectures on Computation" which discuss computation (and programming) in a very generalized way, and Nick Lane's "The Vital Question" which looks at the origins of life and discusses the evolution of multicellular organisms in a very approachable way.

TaupeRanger 6y ago

Increasingly it's becoming clear that DNA is only a small part of the picture. Cellular electrical dynamics are the forefront of morphogenesis research atm. Look at any recent high profile work out of Michael Levin's lab for an example.

bigtones 6y ago
https://en.wikipedia.org/wiki/Bioelectricity https://en.wikipedia.org/wiki/Bioelectricity
fktnktofk 6y ago
Aren't those electrical field patterns still somehow encoded in the DNA?
- ethbr0 6y ago
  Everything is deterministic if you're omniscient. In our more limited experience, certain levels of complexity mean unpredictable outcomes. As for why-not-DNA, I think about it in terms of "If there were some way that was faster able to adapt organisms than DNA changes, wouldn't most organisms accumulate substantial functionality via that pathway over time?"
  - sssilver 6y ago
    > Everything is deterministic if you're omniscient Is this true, given https://en.wikipedia.org/wiki/Uncertainty_principle https://en.wikipedia.org/wiki/Uncertainty_principle ?
    - deleted 6y ago
      [deleted]
    - frutiger 6y ago
      It is indeed not true, even omniscient beings can only produce probability distributions. However it is not clear if quantum effects are relevant at a biomolecular scale. Some experts[1] suggest so but these ideas are considered fringe by the mainstream. 1. Sir Roger Penrose
    - Ixio 6y ago
      I'm of the mind that randomness is only an approximation of complexity, if you're omniscient then randomness doesn't exist and everything is deterministic. However it seems to me the deterministic vs randomness debate is of the same order as the existence of god(s) : we will never be able to prove or disprove it and we aren't able to make useful predictions out of the information one way or the other so we might as well just agree to disagree and move on.
- TeMPOraL 6y ago
  They don't need to be. I'm not sure what the conclusion of biologists is today, but I have a feeling a lot of important mechanisms aren't encoded in the DNA - or, at least, not anymore. The key insight here is that cell reproduction doesn't happen out of nothing, it's always an existing mechanism working on a new mechanism. The seminal paper of Ken Thompson, "Reflections on Trusting Trust" (1984)[0], demonstrates how you can encode a backdoor in a compiler in such a way that the compiler embeds this backdoor in every program it builds, and embeds the backdoor-embedding machinery in every new compiler binary it builds. You can use it to build a "vanilla" compiler and make it backdoor-embedding, even though the source code doesn't have backdoor-embedding instructions in it. I suspect similar things happen in biology - there is computationally relevant information embedded in the runtime state, that's not explicitly encoded in the DNA - but it carries on, because every new living cell is built by a previous living cell. -- [0] - https://www.cs.cmu.edu/~rdriley/487/papers/Thompson_1984_ReflectionsonTrustingTrust.pdf https://www.cs.cmu.edu/~rdriley/487/papers/Thompson_1984_Ref...
  - fktnktofk 6y ago
    I get your point and I agree, the DNA runs on hardware, which is why you can't take cat DNA and put it in a salamander cell and expect to get a cat. The resulting cell will just die since the hardware is not compatible with the DNA. My point was that there is only so much information capacity in the cell if you exclude DNA, surely much less than needed to store electrical fields patterns for a whole embryo.
    - deleted 6y ago
      [deleted]
    - FartyMcFarter 6y ago
      A cell has a lot of atoms, which may store a lot of information?
      - Robotbeat 6y ago
        But not error corrected like DNA.
- WClayFerguson 6y ago
  DNA is basically digital information. Every rung on the helix ladder is either an AT or GC. Nature found the simplest say to store information in our chemistry set. Couldn't really store any field patterns though.
  - Robotbeat 6y ago
    RNA is simpler but doesn’t error correct as much like DNA. It’s possible the first life forms had only RNA.
- oconnor663 6y ago
  Speculating for fun based on what scientist people have told me at parties :) I think the idea is that DNA will directly and literally encode things like "the genes for proteins A and B tend to get activated together". But the next thing that happens is that protein B catalyzes some chain of chemical reactions that winds up activating a different gene for protein C. And then maybe protein C causes some sort of mechanical change in the cell, and the resulting mechanical stress triggers the production of protein D in adjacent cells. Mapping the mechanical relationships between cells in an animal with developing bones and muscles gets super complicated. So the question of "does the DNA encode the relationship between A and D" ends up depending on what you mean by "encode".
jcims 6y ago
Not sure if this is included in 'cellular electrical dynamics' but it's still amazing: Neuronal Signaling and Sodium-Potassium Pump (from PDB-101) https://www.youtube.com/watch?v=ZKE8qK9UCrU https://www.youtube.com/watch?v=ZKE8qK9UCrU
- navan 6y ago
  This reminded me of a beautiful animation of "Mitochondria: the cell's powerhouse" which I recently watched. https://www.youtube.com/watch?v=vkYEYjintqU https://www.youtube.com/watch?v=vkYEYjintqU
ChuckMcM 6y ago
Excellent reference. Bio papers with electricity in them, that is new for me. This one [1] is currently blowing my mind :-) [1] https://www.the-scientist.com/features/how-groups-of-cells-cooperate-to-build-organs-and-organisms-67881 https://www.the-scientist.com/features/how-groups-of-cells-c...
- yalok 6y ago
  Totally. And kind of explains why some electrophoresis therapies may be working.
lurquer 6y ago
During the initial boredom of Covid, I got very interested in Levin’s lab’s work and morphogenesis in general. I made a program to implement some of my theories. You’re welcome to try it. cycell2d.com My pet theory — morphogenic fields — is described in their on one of the pages. (Caveat: I’m neither a biologist nor a ‘real’ programmer. But, I was able to come up with a system to ‘grow’ certain animals and found it a fun way to spend the lockdown... almost as much fun as posting ‘Covid is a hoax’ comments on HackerNews... ahhh... those were the days.)
- dgellow 6y ago
  You should submit your website as its own on HN :)
- plancien 6y ago
  I'm very impressed, this made my day (my month ?). Too bad your site lacks some nice video demos on the front page. To other HN readers, look what I found in it's tutorial : https://www.youtube.com/watch?v=dkvB4nb8PXw https://www.youtube.com/watch?v=dkvB4nb8PXw
koeng 6y ago
Small part of the picture is an exaggeration, IMO. Cellular electrical dynamics matter, but we already know that surface physics matter (see: any mammalian lab with those flat little red bottles). Those dynamics (physical, electrical, chemical) are all derived from genes coded in DNA, and so long as you have the basic ribosomes / mitochondrial structures, you can re-instantiate an entire organism from just the DNA.
- TaupeRanger 6y ago
  DNA is certainly necessary and integral, but not at all sufficient for a full scientific understanding. Just like quantum mechanics is to rocket science. The heavy focus on genetics has hindered our understanding until very recently IMO.
  - koeng 6y ago
    > hindered our understanding until very recently IMO Any specific examples of how it hindered our understanding? Like maybe some grants or something? Because as a synthetic biologist, I've never seen a heavy emphasis on genetics take away from other causes of cellular dynamics - in fact, exactly the opposite, because genetic engineering has allowed tinkering of those cellular dynamics (for example, cardio tissue surface physics). I don't know of any serious biologist that (even historically) disregarded the importance of other physical factors in favor of DNA, but I would love to know compelling counter examples.
  - abandonliberty 6y ago
    Rather than "small part of the picture", you would get less disagreement with something like "beginning of the story." I doubt many people would agree that computer hardware is a small part of the picture of modern computation. They're the foundations that everything else is built on, and with.
- kaba0 6y ago
  DNA can’t bootstrap itself, so to say. So previous cell-functionality is required for everything, so you can only re-instantiate an entire organism if you have a denucleated pluripotent cell from an evolutionary close enough organism. (But correct me if I’m wrong)
abledon 6y ago
have you read "Spark in the Machine"? Its an attempt to connect bioelectric science with ancient notions of 'chi', it goes over neural crest cells, organization centers for cell growth, and the electrosensitive pericardium cage near the heart. They definitely didn't get 100% of it right, buts its quite uncanny how the ancient texts were so accurate at predicting certain things that are only becoming evident in morphogensis research.
sriku 6y ago
Link to talk - https://www.youtube.com/watch?v=HwtOZ_WfMw0 https://www.youtube.com/watch?v=HwtOZ_WfMw0 - in which my mind was blown.

p1mrx 6y ago

It is "programmed" by the recursive feedback loop of evolution. If anything fails to work, the program terminates and something more reliable will take its place.

umvi 6y ago
Still nothing short of incredible. "the recursive feedback loop of evolution" abstracts a mind boggling amount of complexity. How did such a complex system start? I suppose if we knew, abiogenesis would be a solved problem.
- lovecg 6y ago
  There are some plausible theories, like RNA randomly crystallizing on a suitable surface. Sooner or later a self-copying one just happened to crystallize by chance, and there was no going back. Fun lecture series: https://youtu.be/PqPGOhXoprU https://youtu.be/PqPGOhXoprU
- shellfishgene 6y ago
  You may like "The Vital Question" by Nick Lane, a book which presents one possible scenario in a quite readable way. Much of it is quite speculative of course, but you get a good idea what the basic principles are.
- KineticLensman 6y ago
  > "the recursive feedback loop of evolution" abstracts a mind boggling amount of complexity. How did such a complex system start? From something much simpler, and which has been iterating for approx 4 billion years.
brbrodude 6y ago
The trippy detail for me is that the runtime is time and space, thats what its frictioned against, even matter and its states are determined by it. Evolution sure is a word.. Not sure it captures it tho
WClayFerguson 6y ago

postalrat 6y ago

Trying to figure out how biology works probably isn't much different than it would be to figure out how an alien spacecraft works.

geijoenr 6y ago

Indeed, there are always two parts to it: the software and the machine (the system of chemical structures and interactions inside the cell) , both equally important. We are at the point we can read the software but have a very limited idea on how the machine works.

holoduke 6y ago
Mm I would argue that we have a fair understanding on how the hardware works (chemical processes). But we have not clue how things are controlled and how things work together.

lm28469 6y ago

> I understand programming quite well Software programming or biological programming ? These things have the same names but they're not really comparable

ChuckMcM 6y ago
Well I think of it as the state machines and cellular automata. And yes, how cellular state machines work is clearly different than how a computer state machines work, they have a surprising (to me) lot in common. If you are interested in these comparisons I can recommend two books, one is Feynman's "Lectures on Computation" which discuss computation (and programming) in a very generalized way, and Nick Lane's "The Vital Question" which looks at the origins of life and discusses the evolution of multicellular organisms in a very approachable way.