14 ms·

Persuading the Body to Regenerate Its Limbs

138 points by airstrike 6y ago

k2enemy 6y ago
I highly recommend this video from Levin. It was my introduction to his work. What Bodies Think About: Bioelectric Computation Outside the Nervous System - NeurIPS 2018 https://www.youtube.com/watch?v=RjD1aLm4Thg https://www.youtube.com/watch?v=RjD1aLm4Thg
- carapace 6y ago
  Pretty much the most important thing happening right now, IMO. The real information revolution (don't get me wrong, silicon transistors are nice, but life considered as a technology is far far beyond that, eh? It's four billion-year-old self-improving nanotech.) One fascinating thing about this work is that we have a subjective "interface" to the "technology" already. I wouldn't be surprised if it turns out that one can engender e.g. limb regrowth or bone-shaping using some kind of guided meditation. Recall that the "3-Minute Mile" was a psychological, not physical, barrier. I think we're faced with a similar situation here: the only thing preventing us from learning to regrow limbs is the common belief that it's impossible. I find it curious that the very idea of researching limb and organ regeneration is obscure in the first place. Why is that so unthinkably far out but e.g. self-driving cars are taken seriously?
  - ravi-delia 6y ago
    I'd expect the main issues with regrowing limbs are their heterogeneity. Your liver can generate its complex structure via the local communication of cells, but your limbs did that only once. The mechanisms in the body that grew out your more complicated macro qualities are finely tuned to do all of it at once. Maybe we could micromanage it ourselves, but the actual body doesn't know how to do it itself.
    - intergalplan 6y ago
      > The mechanisms in the body that grew out your more complicated macro qualities are finely tuned to do all of it at once. Maybe we could micromanage it ourselves, but the actual body doesn't know how to do it itself. The linked video in the grandparent post argues pretty convincingly that the body might know exactly that, actually.
      - ravi-delia 6y ago
        My reading of the article, admittedly not a professional one, was that there is definitely still some micromanaging to do. That being said, yeah I'm definitely not confident in my position here. Every single damn thing I learn about biology makes it all the more incredible.
        intergalplan 6y ago
        The work seemed to pointedly avoid micromanaging, by instead finding out how to open up the correct pathways between cells in a region and instruct them to become something else. No need to say "OK, these cells need to become a retina, these need to become a cornea" or to figure out how to change the body plan of the creature at the DNA level—just place a "become an eye" marker in the right spot, and boom, the cells self-organize to become an eye, and may even manage to connect themselves to the CNS such that it becomes a functioning eye! The key insight seems to be that you can hack the (as the research put it, by analogy) software of a set of cells and let the hardware (DNA, cell mechanisms) worry about exactly how to do what you told them to do, so rather than, say, figuring out how to read DNA and tell what kind of organism will come out of it such that we can start adding or removing bits here and there (very, very hard), you can instead screw around with inter-cell signaling to hijack functionality that the cells already have, but just aren't using, to get them to do new things. I thought there were several "holy shit" moments in the video. The cancer thing—yikes. Reconnect genetically-broken, actively dangerous cells to the inter-cell communication network and they stop acting crazy, while still having messed-up DNA? That's a surprising result, and a powerful demonstration of what the technique can accomplish (may not be therapeutically useful for a bunch of reasons I can think up, but it still seems like a notable, surprising result) Another was the sticky "memory" of a modified organism, that is, the worm that'd had its tail cut off then been instructed to make a second head there instead, and then had that cut off and... grew a head again, without further prompting, demonstrating that body layout and gene expression is some combination of DNA and a kind of cell-memory or cell-state across the whole organism, not something driven entirely deterministically by DNA alone. The part about tricking worms into growing heads for 100-150 million-year separated evolutionary relatives, complete with the correct-for-the-other-species brain, was nuts. The "instructions" are still there, just dormant, and if you confuse the cell-memory (if you will) of what it's supposed to be it'll sometimes decide to be the wrong species. WTF.
  - throw1234651234 6y ago
    Had the thought before. I think it's self delusion to think this would be true unless we think of humans being designed/modified machines and dreams/meditation are the console.
    - carapace 6y ago
      Well, FWIW, I think one of the straightforward but mind-blowing implications of Levin et. al.'s work is that living organisms are designed, by them themselves. Cells think. There's no a prior reason (I can see) to disallow that humans and other multicellular life forms are the "art" of microbes. (We are Solaris) It seems to me that we are the products of intelligent design, not (necessarily) of the intelligence of God, but of the intelligence of the biosphere itself.
- flobosg 6y ago
  Here’s a newer talk from him: https://www.youtube.com/watch?v=L43-XE1uwWc https://www.youtube.com/watch?v=L43-XE1uwWc
- desperate 6y ago
  Thanks for this, incredibly informative.
igorlev 6y ago
I love the fact that a large portion of medicine is basically debugging and reverse engineering as a profession. It seems to be a good time in the debugging of these complex pathways as there's another, related avenue of signal manipulation research that may lead to scar-less tissue healing (https://science.sciencemag.org/content/372/6540/eaba2374 https://science.sciencemag.org/content/372/6540/eaba2374)
- herval 6y ago
  A large portion of most professions is basically debugging and reverse engineering :) (including non-technical ones, like psychology or law)
  - tooltower 6y ago
    And that tells us that it's a general skill worth teaching in schools. Regardless of the profession a student ends up in, this skill is likely to be useful.
    - nine_k 6y ago
      The whole parable of Chesterton's fence hinges on that: reverse-engineer the weird thing to understand it, before attempting to alter it.
  - xiphias2 6y ago
    It's true for law, but for psychology I found that most practicioners use most of their time to sell the reason of their whole existence, so it seems closer to sales.
- hirenj 6y ago
  I do molecular biology full time, but I truly believe that I learnt the skills I need to do this in my first project where I took over a several thousand line perl web app. The developer had been extremely clever with his use of tricks, which made debugging and reverse engineering a massive challenge. I often needed to internalise the state of the whole app to reason about why things were going wrong. Those skills have served me well in my current work in debugging biological systems, where the organisms responsible for all these “clever” hacks are long gone, and all we’re left with is a system that often doesn’t boot back up after a crash.
tyingq 6y ago
I would think regenerating teeth would be a big market.
- csunbird 6y ago
  I am in such wonder why that teeth care and treatment is still not advanced enough, the main approach of treating cavities are still fillings, which I find it a brutal operation.
  - mikepurvis 6y ago
    How wild would it be if you got a cavity and they just pulled the whole tooth and stimulated your body to grow a new one? That would completely upend orthodontics too, if there was an option to regrow crooked teeth rather than yanking them into position with wires.
    - Keyframe 6y ago
      Not sure how since you are born with both baby and adult teeth.
      - EForEndeavour 6y ago
        The holy grail of dental care would be to trick the body into growing extra adult teeth from scratch.
    - withinboredom 6y ago
      IIRC, you need years of growing to get new teeth. This is certainly viable if you lose all of them at a young age from a car crash but for a single cavity, doubtful.
    - carapace 6y ago
      Not only regrowing whole teeth, it should be possible to reengage the cells that build the teeth in the first place to repair cavities. All the "machinery" is there, it's a matter of figuring out how to reactivate it. As for crooked teeth, it seems to me that Levin et. al. are unlocking the patterns that govern such things, and we can hopefully look forward to even jaws and even correcting deformed bone structures. It's interesting to try to think about what form a machine would take for "re-imprinting" new skeletal structures into existing bones, eh?
BitwiseFool 6y ago
Hopefully they can apply this technology to undo circumcision for those of us who never wanted it in the first place.
- ralusek 6y ago
  The fact that circumcision of unconsenting infants is legal is insane to me.
  - tachyonbeam 6y ago
    The difficulty in banning it is very much political. You would get massive backlash from Jewish groups, you'd probably get accused of being anti-semitic. Also, not to get too cynical, but my perception is that issues affecting men/males are given less importance.
    - gumby 6y ago
      > Also, not to get too cynical, but my perception is that issues affecting men/males are given less importance. Circumcision, and perhaps female breast cancer, aside: the accumulated evidence is pretty strongly in the opposite direction. There have been quite a few studies on the topic over the last 30 years, with little improvement.
    - JMTQp8lwXL 6y ago
      It's a tradeoff between the equal protection clause (FGM is banned, so there is an argument there) and religious freedom. The former should hold more weight as religious freedom doesn't extend to imposing religious beliefs onto others.
  - BitwiseFool 6y ago
    Cultural mores are a powerful thing. Honestly the sheer amount of cultural cognitive dissonance around the practice was seriously eye-opening on the subject of human irrationality. For instance, my mother is aghast at the prospect of clipping a dog's ears or docking it's tail. And yet, when it came to the birth of her sons the same sense of ethics never registered about circumcision.
zabzonk 6y ago
Sod the limbs - I want to have my body regenerate the whole works! Particularly my liver, my knees (OK, I guess that is limbs) and my sex organs.
- ausbah 6y ago
  I'd love to see how much harder brain regeneration is
mensetmanusman 6y ago
Great way to put that, thanks! Part of debugging is turning off something for a short time, moderns have a tendency to assume everything in the past was done out of ignorance and debugging isn’t required, destruction is.
ncmncm 6y ago
For much of the 20th century, studying effects of electric and magnetic fields, and microcurrents in bodies, was effectively forbidden in the US. You couldn't publish, get grants, get tenure. (Robert Becker somehow got a free pass, from the Veterans Administration.) I have no clue how it was enforced, but the best guess I have for the reason is that it was to protect broadcasters and electric power distribution system operators against liability for any such effects they caused that might go wrong.

138 points by airstrike 6y ago

I highly recommend this video from Levin. It was my introduction to his work. What Bodies Think About: Bioelectric Computation Outside the Nervous System - NeurIPS 2018 https://www.youtube.com/watch?v=RjD1aLm4Thg https://www.youtube.com/watch?v=RjD1aLm4Thg

carapace 6y ago
Pretty much the most important thing happening right now, IMO. The real information revolution (don't get me wrong, silicon transistors are nice, but life considered as a technology is far far beyond that, eh? It's four billion-year-old self-improving nanotech.) One fascinating thing about this work is that we have a subjective "interface" to the "technology" already. I wouldn't be surprised if it turns out that one can engender e.g. limb regrowth or bone-shaping using some kind of guided meditation. Recall that the "3-Minute Mile" was a psychological, not physical, barrier. I think we're faced with a similar situation here: the only thing preventing us from learning to regrow limbs is the common belief that it's impossible. I find it curious that the very idea of researching limb and organ regeneration is obscure in the first place. Why is that so unthinkably far out but e.g. self-driving cars are taken seriously?
- ravi-delia 6y ago
  I'd expect the main issues with regrowing limbs are their heterogeneity. Your liver can generate its complex structure via the local communication of cells, but your limbs did that only once. The mechanisms in the body that grew out your more complicated macro qualities are finely tuned to do all of it at once. Maybe we could micromanage it ourselves, but the actual body doesn't know how to do it itself.
  - intergalplan 6y ago
    > The mechanisms in the body that grew out your more complicated macro qualities are finely tuned to do all of it at once. Maybe we could micromanage it ourselves, but the actual body doesn't know how to do it itself. The linked video in the grandparent post argues pretty convincingly that the body might know exactly that, actually.
    - ravi-delia 6y ago
      My reading of the article, admittedly not a professional one, was that there is definitely still some micromanaging to do. That being said, yeah I'm definitely not confident in my position here. Every single damn thing I learn about biology makes it all the more incredible.
      - intergalplan 6y ago
        The work seemed to pointedly avoid micromanaging, by instead finding out how to open up the correct pathways between cells in a region and instruct them to become something else. No need to say "OK, these cells need to become a retina, these need to become a cornea" or to figure out how to change the body plan of the creature at the DNA level—just place a "become an eye" marker in the right spot, and boom, the cells self-organize to become an eye, and may even manage to connect themselves to the CNS such that it becomes a functioning eye! The key insight seems to be that you can hack the (as the research put it, by analogy) software of a set of cells and let the hardware (DNA, cell mechanisms) worry about exactly how to do what you told them to do, so rather than, say, figuring out how to read DNA and tell what kind of organism will come out of it such that we can start adding or removing bits here and there (very, very hard), you can instead screw around with inter-cell signaling to hijack functionality that the cells already have, but just aren't using, to get them to do new things. I thought there were several "holy shit" moments in the video. The cancer thing—yikes. Reconnect genetically-broken, actively dangerous cells to the inter-cell communication network and they stop acting crazy, while still having messed-up DNA? That's a surprising result, and a powerful demonstration of what the technique can accomplish (may not be therapeutically useful for a bunch of reasons I can think up, but it still seems like a notable, surprising result) Another was the sticky "memory" of a modified organism, that is, the worm that'd had its tail cut off then been instructed to make a second head there instead, and then had that cut off and... grew a head again, without further prompting, demonstrating that body layout and gene expression is some combination of DNA and a kind of cell-memory or cell-state across the whole organism, not something driven entirely deterministically by DNA alone. The part about tricking worms into growing heads for 100-150 million-year separated evolutionary relatives, complete with the correct-for-the-other-species brain, was nuts. The "instructions" are still there, just dormant, and if you confuse the cell-memory (if you will) of what it's supposed to be it'll sometimes decide to be the wrong species. WTF.
- throw1234651234 6y ago
  Had the thought before. I think it's self delusion to think this would be true unless we think of humans being designed/modified machines and dreams/meditation are the console.
  - carapace 6y ago
    Well, FWIW, I think one of the straightforward but mind-blowing implications of Levin et. al.'s work is that living organisms are designed, by them themselves. Cells think. There's no a prior reason (I can see) to disallow that humans and other multicellular life forms are the "art" of microbes. (We are Solaris) It seems to me that we are the products of intelligent design, not (necessarily) of the intelligence of God, but of the intelligence of the biosphere itself.
flobosg 6y ago
Here’s a newer talk from him: https://www.youtube.com/watch?v=L43-XE1uwWc https://www.youtube.com/watch?v=L43-XE1uwWc
desperate 6y ago
Thanks for this, incredibly informative.

igorlev 6y ago

I love the fact that a large portion of medicine is basically debugging and reverse engineering as a profession. It seems to be a good time in the debugging of these complex pathways as there's another, related avenue of signal manipulation research that may lead to scar-less tissue healing (https://science.sciencemag.org/content/372/6540/eaba2374 https://science.sciencemag.org/content/372/6540/eaba2374)

herval 6y ago
A large portion of most professions is basically debugging and reverse engineering :) (including non-technical ones, like psychology or law)
- tooltower 6y ago
  And that tells us that it's a general skill worth teaching in schools. Regardless of the profession a student ends up in, this skill is likely to be useful.
  - nine_k 6y ago
    The whole parable of Chesterton's fence hinges on that: reverse-engineer the weird thing to understand it, before attempting to alter it.
- xiphias2 6y ago
  It's true for law, but for psychology I found that most practicioners use most of their time to sell the reason of their whole existence, so it seems closer to sales.
hirenj 6y ago
I do molecular biology full time, but I truly believe that I learnt the skills I need to do this in my first project where I took over a several thousand line perl web app. The developer had been extremely clever with his use of tricks, which made debugging and reverse engineering a massive challenge. I often needed to internalise the state of the whole app to reason about why things were going wrong. Those skills have served me well in my current work in debugging biological systems, where the organisms responsible for all these “clever” hacks are long gone, and all we’re left with is a system that often doesn’t boot back up after a crash.

tyingq 6y ago

I would think regenerating teeth would be a big market.

csunbird 6y ago
I am in such wonder why that teeth care and treatment is still not advanced enough, the main approach of treating cavities are still fillings, which I find it a brutal operation.
- mikepurvis 6y ago
  How wild would it be if you got a cavity and they just pulled the whole tooth and stimulated your body to grow a new one? That would completely upend orthodontics too, if there was an option to regrow crooked teeth rather than yanking them into position with wires.
  - Keyframe 6y ago
    Not sure how since you are born with both baby and adult teeth.
    - EForEndeavour 6y ago
      The holy grail of dental care would be to trick the body into growing extra adult teeth from scratch.
  - withinboredom 6y ago
    IIRC, you need years of growing to get new teeth. This is certainly viable if you lose all of them at a young age from a car crash but for a single cavity, doubtful.
  - carapace 6y ago
    Not only regrowing whole teeth, it should be possible to reengage the cells that build the teeth in the first place to repair cavities. All the "machinery" is there, it's a matter of figuring out how to reactivate it. As for crooked teeth, it seems to me that Levin et. al. are unlocking the patterns that govern such things, and we can hopefully look forward to even jaws and even correcting deformed bone structures. It's interesting to try to think about what form a machine would take for "re-imprinting" new skeletal structures into existing bones, eh?

BitwiseFool 6y ago

Hopefully they can apply this technology to undo circumcision for those of us who never wanted it in the first place.

ralusek 6y ago
The fact that circumcision of unconsenting infants is legal is insane to me.
- tachyonbeam 6y ago
  The difficulty in banning it is very much political. You would get massive backlash from Jewish groups, you'd probably get accused of being anti-semitic. Also, not to get too cynical, but my perception is that issues affecting men/males are given less importance.
  - gumby 6y ago
    > Also, not to get too cynical, but my perception is that issues affecting men/males are given less importance. Circumcision, and perhaps female breast cancer, aside: the accumulated evidence is pretty strongly in the opposite direction. There have been quite a few studies on the topic over the last 30 years, with little improvement.
  - JMTQp8lwXL 6y ago
    It's a tradeoff between the equal protection clause (FGM is banned, so there is an argument there) and religious freedom. The former should hold more weight as religious freedom doesn't extend to imposing religious beliefs onto others.
- BitwiseFool 6y ago
  Cultural mores are a powerful thing. Honestly the sheer amount of cultural cognitive dissonance around the practice was seriously eye-opening on the subject of human irrationality. For instance, my mother is aghast at the prospect of clipping a dog's ears or docking it's tail. And yet, when it came to the birth of her sons the same sense of ethics never registered about circumcision.

zabzonk 6y ago

Sod the limbs - I want to have my body regenerate the whole works! Particularly my liver, my knees (OK, I guess that is limbs) and my sex organs.

ausbah 6y ago
I'd love to see how much harder brain regeneration is

mensetmanusman 6y ago

Great way to put that, thanks! Part of debugging is turning off something for a short time, moderns have a tendency to assume everything in the past was done out of ignorance and debugging isn’t required, destruction is.

ncmncm 6y ago

For much of the 20th century, studying effects of electric and magnetic fields, and microcurrents in bodies, was effectively forbidden in the US. You couldn't publish, get grants, get tenure. (Robert Becker somehow got a free pass, from the Veterans Administration.) I have no clue how it was enforced, but the best guess I have for the reason is that it was to protect broadcasters and electric power distribution system operators against liability for any such effects they caused that might go wrong.