Persuading the Body to Regenerate Its Limbs(newyorker.com)
newyorker.com
Persuading the Body to Regenerate Its Limbs
https://www.newyorker.com/magazine/2021/05/10/persuading-the-body-to-regenerate-its-limbs
70 comments
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?
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?
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.
> 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.
The linked video in the grandparent post argues pretty convincingly that the body might know exactly that, actually.
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.
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.
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.
On that last note, a similar thing happens with trees. Trees aren't really a distinct class of organism. The last common ancestor of some trees wasn't a tree, and the last common ancestor of some non-trees was a tree. As it turns out, with a few genetic tweaks lots of plants will slow their metabolic processes and construct a sturdy wood stem, and visa-versa.
Even cooler, perhaps, are eyeless cave fish redeveloping eyes quite quickly after a few generations in the light. It seems like a lot of things are like that. When we look at the fossil record it looks like things evolve in leaps and bounds rather than more gradually over time. Maybe that's because organisms are more built with prefabs rather than from scratch.
Even cooler, perhaps, are eyeless cave fish redeveloping eyes quite quickly after a few generations in the light. It seems like a lot of things are like that. When we look at the fossil record it looks like things evolve in leaps and bounds rather than more gradually over time. Maybe that's because organisms are more built with prefabs rather than from scratch.
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.
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.
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.
Here’s a newer talk from him: https://www.youtube.com/watch?v=L43-XE1uwWc
Thanks for this, incredibly informative.
I would think regenerating teeth would be a big market.
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.
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.
That would completely upend orthodontics too, if there was an option to regrow crooked teeth rather than yanking them into position with wires.
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?
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?
Getting a tooth pulled is a much much worse procedure than a simple filling. I'd probably opt for 100 fillings before signing up for getting a tooth pulled.
exactly the opposite experience here.
the grinding/taste/vibration/experience of a filling is much worse for me than the experience of an extraction.
I don't know if that's rare or not -- but I have a very real aversion to the experience of dental grinding equipment, and that stuff tends not to get used much if at all during extractions.
the grinding/taste/vibration/experience of a filling is much worse for me than the experience of an extraction.
I don't know if that's rare or not -- but I have a very real aversion to the experience of dental grinding equipment, and that stuff tends not to get used much if at all during extractions.
I think that orthodontics would be an area where it would be often quite useless, because usually it's not just about moving the teeth, it's about changing shape and alignment of jaws to get enough space for the teeth.
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.
Not sure how since you are born with both baby and adult teeth.
The holy grail of dental care would be to trick the body into growing extra adult teeth from scratch.
The only real thing I remember from a certain SciFi book is a guy who's "First genetic hack was to regrow his teeth every 20 years." that seems entirely plausible.
This is what I wonder as well.
I imagine some kind of gel that would react with the cavity to build some indestructible filling without any mecanical intervention.
I imagine some kind of gel that would react with the cavity to build some indestructible filling without any mecanical intervention.
because teeth are small and delicate and decay, break, and die easily. Livers are big, sturdy, and regenerate.
There was an excellent breakdown about the challenges with growing teeth recently on HN:
https://news.ycombinator.com/item?id=26854080
https://news.ycombinator.com/item?id=26854080
More profitable than the racket they have going on now? Doubt it.
You speak about this as if the entire industry were one entity out to maximize overall profit, as opposed to many individuals, of whom many would gladly harm the overall scheme for the outsized personal profit it surely would generate.
Ironic, given that this is Hacker News and full of talk of “disruption”.
Ironic, given that this is Hacker News and full of talk of “disruption”.
How absurd would be a kind of compromise where they'd be given a license on the procedure and monitoring so that they can keep their career a bit.
it would be huge given how almost every adult has some teeth problems, and also very difficult to do. may not even be possible
it seems like prosthetic teeth are pretty good, definitely a better simulacrum than prosthetic [anything else]
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)
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)
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.
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.
How would a software dev get into doing molecular biology?
Probably a masters program / PhD if you’ve got a compelling argument as to why you would be a good candidate.
I'd add that you need to do the homework first: If you can adequately formulate and articulate the problem that the lab is solving, and that one cool trick you have that can solve it, that's already a great signal that you would work well (Chances are your trick won't work, but that's only because biology is merciless).
Live debugging
A large portion of most professions is basically debugging and reverse engineering :) (including non-technical ones, like psychology or law)
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.
The whole parable of Chesterton's fence hinges on that: reverse-engineer the weird thing to understand it, before attempting to alter it.
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.
Hopefully they can apply this technology to undo circumcision for those of us who never wanted it in the first place.
The fact that circumcision of unconsenting infants is legal is insane to me.
When my son was born (in the USA) there was an employee of the hospital who mounted an aggressive effort to have this done (doing these amputations was her job). Finally I made her go away by saying "It's his body and he can choose for himself when he is a legal adult".
Her disturbing response: "But if you let him choose he will say no."
Her disturbing response: "But if you let him choose he will say no."
I'll be the first to admit that I don't know enough about circumcision to hold any kind of firm opinion on the matter. That said, my understanding has been that circumcision isn't just a religious practice, there are practical reasons too, namely hygiene.
There's plenty of examples where we do what's "best" for kids without their consent. Vaccines for example. So I don't really buy this "their body" argument, although I respect the merits.
There's plenty of examples where we do what's "best" for kids without their consent. Vaccines for example. So I don't really buy this "their body" argument, although I respect the merits.
> there are practical reasons too, namely hygiene.
That's not a valid reason to have it done.
It's easy to keep yourself clean and I've never once heard of anyone getting sores because they failed to wash for an extended period of time.
That's not a valid reason to have it done.
It's easy to keep yourself clean and I've never once heard of anyone getting sores because they failed to wash for an extended period of time.
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The health/hygiene argument has been thoroughly dismantled. That argument is akin to saying that we should remove people's teeth so that they don't have to deal with cavities. The only time there is a difference in hygiene between a circumcised and uncircumcised penis is if they both go unwashed for an extended period of time. I also don't buy these utilitarian arguments. If someone wants to trade the benefits of an uncircumcised penis for those of a circumcised penis, they can make that permanent decision for themselves.
While I generally agree with you and wouldn't circumcise any child, data seems to support that circumcision reduces transmission of some STIs
> Three randomized clinical trials showed that adult male circumcision significantly reduced the risk for HIV acquisition among heterosexual males by 51%–60% (95% confidence interval 16%–76%) over time. These trials also found that medically performed adult circumcision significantly reduced the risk of men acquiring two common sexually transmitted infections (STIs), including genital ulcer disease (GUD) prevalence by 47% and incidence by 48% and high-risk (i.e. oncogenic) types of human papilloma virus (HR-HPV) prevalence by 23%–47%.
It also seems to reduce the risk of UTIs
> Male circumcision has been shown to reduce the risk of urinary tract infections inmales aged 0–1 years by 90%, in males aged 1–16 years by 85%, and in males >16 years by 71%.
This data is from a report from the CDC https://stacks.cdc.gov/view/cdc/58456
> Three randomized clinical trials showed that adult male circumcision significantly reduced the risk for HIV acquisition among heterosexual males by 51%–60% (95% confidence interval 16%–76%) over time. These trials also found that medically performed adult circumcision significantly reduced the risk of men acquiring two common sexually transmitted infections (STIs), including genital ulcer disease (GUD) prevalence by 47% and incidence by 48% and high-risk (i.e. oncogenic) types of human papilloma virus (HR-HPV) prevalence by 23%–47%.
It also seems to reduce the risk of UTIs
> Male circumcision has been shown to reduce the risk of urinary tract infections inmales aged 0–1 years by 90%, in males aged 1–16 years by 85%, and in males >16 years by 71%.
This data is from a report from the CDC https://stacks.cdc.gov/view/cdc/58456
Sure, it reduces STI transmission rates, because the mucous membrane (the inside of the foreskin) gets cut off, and the exposed glans also becomes keratinized due to years of abrasion against the underwear. No mucous membranes = lower chance for pathogens to enter the body.
Now, whether these would worth the tradeoff with reduced sensitivity, surgical risks (e.g. reduced sexual function due to tight scar formation), the psychological trauma for the infant, etc. is another question.
Now, whether these would worth the tradeoff with reduced sensitivity, surgical risks (e.g. reduced sexual function due to tight scar formation), the psychological trauma for the infant, etc. is another question.
Look, I agree with you. I don't think we should mess with anyone's genitals without their consent. I'm just pointing out that there's data to support the health concerns.
Let's take it a step further. We can reduce STI transmission to zero if we remove all of everyone's genitals.
Look, I agree with you. I don't think we should mess with anyone's genitals without their consent. I'm just pointing out that there's data to support the health concerns.
Obviously there's some trade off here, and I don't think it's worth it to circumcise anyone without their consent or medical necessity.
Obviously there's some trade off here, and I don't think it's worth it to circumcise anyone without their consent or medical necessity.
Exactly. Also, we can 100% eliminate nail fungus and ingrown nails (it can cause serious infections!) if we surgically remove the nail root of infants. It's a super simple surgery, and modern men has no use for nails anyway!
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.
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.
I agree that it's one of the best litmus tests we have regarding moral critical thinking.
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.
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.
> 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.
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.
Yes, given that the evidence in support of it being cleaner is not only slim, but has been shown to suffer from extreme methodological errors, the resulting situation is that of cultural or religious genital mutilation.
And I should add that even if it were shown to be 'cleaner' (as far as the reduction of the chance to contract STD's), I would not find that compelling enough to cut off the most nerve dense part of the penis before the person is able to consent.
And I should add that even if it were shown to be 'cleaner' (as far as the reduction of the chance to contract STD's), I would not find that compelling enough to cut off the most nerve dense part of the penis before the person is able to consent.
I wouldn't need to wash my hands if you chopped them off.
You can restore a foreskin to some extent, an early form of this was practiced in the 8th century BC.
https://en.wikipedia.org/wiki/Foreskin_restoration
https://en.wikipedia.org/wiki/Foreskin_restoration
As bad as male circumcision can be, female circumcision is next level terrible. A Google points Wikipedia to an entry for “Female Genital Mutilation” which seems appropriate.
https://en.m.wikipedia.org/wiki/Female_genital_mutilation
https://en.m.wikipedia.org/wiki/Female_genital_mutilation
Appreciate this, but the discussion is about male circumcision.
"It is estimated that more than 200 million girls and women alive today have undergone female genital mutilation in the countries where the practice is concentrated. Furthermore, there are an estimated 3 million girls at risk of undergoing female genital mutilation every year." - https://www.who.int/teams/sexual-and-reproductive-health-and...
"In 2010, the World Health Organization (WHO) estimated 30% of adult males worldwide (aged 15+) are circumcised, with about two-thirds of those being Muslims" - https://en.wikipedia.org/wiki/Prevalence_of_circumcision
While female genital mutilation is far more horrific, male genital mutilation is far more common. Both should be ended and the movements should be combined.
I actually make this my single largest political issue and the fact that most people laugh at this idea is evidence for the shockingly bad ethical systems that most individuals have.
"In 2010, the World Health Organization (WHO) estimated 30% of adult males worldwide (aged 15+) are circumcised, with about two-thirds of those being Muslims" - https://en.wikipedia.org/wiki/Prevalence_of_circumcision
While female genital mutilation is far more horrific, male genital mutilation is far more common. Both should be ended and the movements should be combined.
I actually make this my single largest political issue and the fact that most people laugh at this idea is evidence for the shockingly bad ethical systems that most individuals have.
If only there were more people like you 30+ years ago...
I will point out that people typically avoid anything that has even a remote chance of harming their genitalia, especially when it's as voodoo-seeming as the bioelectric systems here.
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.
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.
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.
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.
What Bodies Think About: Bioelectric Computation Outside the Nervous System - NeurIPS 2018 https://www.youtube.com/watch?v=RjD1aLm4Thg