The former thing sounds like overclocking a CPU. The latter instead “erase chunks of someone’s personality and memory and let them rewrite it, turning them into an essentially different person”. I don’t think many people would just volunteer for something like that. We understand still far too little of how brains work to think that tinkering with genes and just getting some kind of Flowers for Algernon-ish intelligence boost is the correct model of this. As it often happens, it’s much easier to break something than to build it up, especially something as delicate and complex as a human brain. Right now this seems honestly to belong in the “mad science” bin to me.
This reply is hilarious in the context of your first one. At first you confidently assert that changing genes in the brain won’t do anything to an adult, followed by your statement that “we understand still far too little of how brains work” to know what’s going to happen following such a therapy along with other predictions like total memory erasure. Which is it?
While the vast majority of neurons are subject to mitotic arrest after adolescence, gene expression, the regulation of gene expression, and morphological/biochemical restructuring of individual neurons (plasticity) doesn’t stop until you’re dead. Additionally, there’s no reason to rule out the possibility of genome changes in adolescence leading to macroscopic changes in brain structure, especially considering that certain histone de-acetylase inhibitors like valproate have been shown to re-activate developmental critical periods in particular areas of the brain, and that cell reprogramming therapies such as those being interrogated by David Sinclair’s lab have been demonstrated to be able to rewind the biological clock on neurons, regaining any lost plasticity, regeneration ability, or otherwise anti-change properties gained with age. Even without such fancy therapies, there is nothing barring the possibility that macroscopic brain morphology is to an extent emergent from gene expression at the level of individual neurons, and that changes at the local scale could reverberate globally to generate different macroscopic morphological characteristics.
But suppose that all of what I said isn’t true, and indeed genetic changes as an adolescent would not lead to the macroscopic morphological characteristics that have been shown to correlate with intelligence, like greater brain volume, shorter white matter path lengths, greater cortical thickness, etc. To kman’s point, alterations at the level of local neurons can still be beneficial for intelligence, which has already been demonstrated unlike my hypotheticals in the last paragraph. This is obviously true to anyone who performs a quick survey of some of the SNPs associated with greater intelligence, such as having a T allele at rs2490272, which is on the FOXO3 gene. The protein encoded by FOXO3 isn’t involved in the macrosopic structural formation of the brain whatsoever, and instead acts on the cellular level to protect neurons from oxidative stress, regulate protein turnover, and regulate DNA repair. It is easy to see why having a better version of this protein would lead to healthier neurons (whatever that means) and thus greater intelligence, which is what all GWASes that investigate this gene show. FOXO3 is just one of many of such genes.
This reply is hilarious in the context of your first one. At first you confidently assert that changing genes in the brain won’t do anything to an adult, followed by your statement that “we understand still far too little of how brains work” to know what’s going to happen following such a therapy along with other predictions like total memory erasure. Which is it?
I mean, you sound like you know far more than me on it so I won’t argue the specifics, but in general, “we know enough about this thing to not be able to safely mess with it, but to be reasonably sure that messing with it will have bad effects” is absolutely possible. It’s in fact the default for really complex black boxes: while understanding their general function may be easy enough, if you don’t know what you’re doing messing with their internals, odds are that you’ll break them rather than improve them.
The prediction of “total memory erasure” was a response to a specific idea, the notion that if intelligence was really mostly determined in childhood/adolescence, then if you could push the brain to regain its original plasticity you could repeat the process with different outcomes, and as I said that sounds like it would change a lot about what a person is (unless you can somehow disentangle experiences and personality from intelligence gained through them). I don’t expect that to be the case if one of the premises doesn’t hold; I was just criticizing that specific strategy. Others would not have this downside.
As for the rest, sure, it’s possible that there might be gene changes that will simply improve neuron health. But if I had to bet I’d imagine it would be easier to gain traits like resistance to dementia and Alzheimer’s or such by tweaking those, than a whole 40 points of IQ or such. I know brains aren’t the same as ANNs, but to make an analogy, if you run GPT-4 on newer hardware it’ll do the same things a bit better and faster, but it won’t be able to make entirely new things out of whole cloth.
Yes, as someone who has worked both in CS and in neuroscience at the graduate level, I probably do know far more than you about this topic. At the risk of sounding more polemic than I am, it’s posts like yours and others that make excessively reductive inferences about neurons and the brain that invariably end up polluting discussions of this topic and turn it into an unproductive cesspool of ML people offering their two-cents for topics they don’t understand (most of the replies to the original post being the cases in point).
I will grant you that it is indeed possible that we don’t understand enough about the brain to be confident that we won’t just irreversibly ruin test subjects’ brains with such a therapy, but this is much less likely than the possibility that either nothing will happen or that gains will be had, provided such a therapy is successfully developed in a way that makes it feasible. Geneticists and neuroscientists have not been doing nothing for the past century; we understand much more about the brain, neurons, and cell biology than we understand about artificial neural networks, which is why we can be confident that things like this are possible if we can overcome the obstacles in engineering the delivery and editing mechanisms. There is also no reason to get it right on the first try; GeneSmith has sadly had to state the obvious several times in response to others, which is that we have the scientific method and it would take many experiments to get such a therapy right if it is at all possible. Regardless, I don’t think this therapy as OP describes it is possible for reasons that have already been stated by HiddenPrior and other reasons, but not for the inane reasons others have suggested that liken the adult brain to an immutable pre-trained neural net. It will take several breakthroughs in the field before reliable multiplex genome editing in the human central nervous system becomes a reality.
You are right however that without more GWASes, it will likely be impossible to extricate intelligence enhancements and changes to things like one’s psychology and predisposition to psychiatric disorders. It is even possible that these end up being inextricable to an extent, and recipients of this therapy would have to accept sustaining some degree of not only personality change but other introspective “updates” and disease risk changes. This is one aspect of this therapy that the OP has been rather naïve about in the post and replies to others. If a gene’s influence is such that it affects as emergent and complex a trait as intelligence, it is reasonable to suspect that it affects other things. This is demonstrable with GWASes (and has been demonstrated), but the silver lining is that allele flips that enhance intelligence tend to confer positive rather than negative changes to other systems (key word here being “tend”). As far as my personal preference goes, I would gladly accept a different personality if it meant having an IQ of 190+ or something; nonetheless, there’s no reason to believe personality isn’t amenable to the same techniques used to alter intelligence.
I will grant you that it is indeed possible that we don’t understand enough about the brain to be confident that we won’t just irreversibly ruin test subjects’ brains with such a therapy, but this is much less likely than the possibility that either nothing will happen or that gains will be had, provided such a therapy is successfully developed in a way that makes it feasible.
The bit about the personality was specifically in response to the idea that you could revert brains to childhood-like plasticity. That’s like an additional layer of complexity and unlike gene therapy we don’t know how to begin doing that, so if you ask me, I don’t think it would actually be a thing anyway in the near future. My guess is: most of your intelligence, even the genetic component, is probably determined by development during the phase of highest plasticity. So if you change the genes later you’ll either get no effect or marginal ones compared to what would happen if you changed them in embryos—that is, if it doesn’t also cause other weird side effects.
Experiments are possible but I doubt they’d be risk-free, or honestly, even approved by an ethical committee at all, as things are now. It’s a high risk for a goal that would probably be deemed in itself ethically questionable. And the study surviving for example a cohort “gone bad” would be really hard in terms of public support and funding.
I just want to point out that the sentence you replied to starts with an “if”. “If those genes’ role is to alter the way synapses develop in the fastest growth phase, changing them when you’re 30 won’t do anything” (emphasis mine).
You described this as “At first you confidently assert that changing genes in the brain won’t do anything to an adult”. The difference is important.
This is in no way a comment on the object level debate. I simply think Lesswrong is a place where hypotheticals are useful and that debates will be poorer if people cannot rely on the safety that saying “if A then B” will not be interpreted as just saying “B”.
I agree, it seems totally bizarre to imagine even a single person reading this post would genuinely want to erase themselves in order to make room for a ‘smarter’ personality.
Even if it was offered for free with no other risks or side effects whatsoever. Let alone in the real world.
The former thing sounds like overclocking a CPU. The latter instead “erase chunks of someone’s personality and memory and let them rewrite it, turning them into an essentially different person”. I don’t think many people would just volunteer for something like that. We understand still far too little of how brains work to think that tinkering with genes and just getting some kind of Flowers for Algernon-ish intelligence boost is the correct model of this. As it often happens, it’s much easier to break something than to build it up, especially something as delicate and complex as a human brain. Right now this seems honestly to belong in the “mad science” bin to me.
This reply is hilarious in the context of your first one. At first you confidently assert that changing genes in the brain won’t do anything to an adult, followed by your statement that “we understand still far too little of how brains work” to know what’s going to happen following such a therapy along with other predictions like total memory erasure. Which is it?
While the vast majority of neurons are subject to mitotic arrest after adolescence, gene expression, the regulation of gene expression, and morphological/biochemical restructuring of individual neurons (plasticity) doesn’t stop until you’re dead. Additionally, there’s no reason to rule out the possibility of genome changes in adolescence leading to macroscopic changes in brain structure, especially considering that certain histone de-acetylase inhibitors like valproate have been shown to re-activate developmental critical periods in particular areas of the brain, and that cell reprogramming therapies such as those being interrogated by David Sinclair’s lab have been demonstrated to be able to rewind the biological clock on neurons, regaining any lost plasticity, regeneration ability, or otherwise anti-change properties gained with age. Even without such fancy therapies, there is nothing barring the possibility that macroscopic brain morphology is to an extent emergent from gene expression at the level of individual neurons, and that changes at the local scale could reverberate globally to generate different macroscopic morphological characteristics.
But suppose that all of what I said isn’t true, and indeed genetic changes as an adolescent would not lead to the macroscopic morphological characteristics that have been shown to correlate with intelligence, like greater brain volume, shorter white matter path lengths, greater cortical thickness, etc. To kman’s point, alterations at the level of local neurons can still be beneficial for intelligence, which has already been demonstrated unlike my hypotheticals in the last paragraph. This is obviously true to anyone who performs a quick survey of some of the SNPs associated with greater intelligence, such as having a T allele at rs2490272, which is on the FOXO3 gene. The protein encoded by FOXO3 isn’t involved in the macrosopic structural formation of the brain whatsoever, and instead acts on the cellular level to protect neurons from oxidative stress, regulate protein turnover, and regulate DNA repair. It is easy to see why having a better version of this protein would lead to healthier neurons (whatever that means) and thus greater intelligence, which is what all GWASes that investigate this gene show. FOXO3 is just one of many of such genes.
I mean, you sound like you know far more than me on it so I won’t argue the specifics, but in general, “we know enough about this thing to not be able to safely mess with it, but to be reasonably sure that messing with it will have bad effects” is absolutely possible. It’s in fact the default for really complex black boxes: while understanding their general function may be easy enough, if you don’t know what you’re doing messing with their internals, odds are that you’ll break them rather than improve them.
The prediction of “total memory erasure” was a response to a specific idea, the notion that if intelligence was really mostly determined in childhood/adolescence, then if you could push the brain to regain its original plasticity you could repeat the process with different outcomes, and as I said that sounds like it would change a lot about what a person is (unless you can somehow disentangle experiences and personality from intelligence gained through them). I don’t expect that to be the case if one of the premises doesn’t hold; I was just criticizing that specific strategy. Others would not have this downside.
As for the rest, sure, it’s possible that there might be gene changes that will simply improve neuron health. But if I had to bet I’d imagine it would be easier to gain traits like resistance to dementia and Alzheimer’s or such by tweaking those, than a whole 40 points of IQ or such. I know brains aren’t the same as ANNs, but to make an analogy, if you run GPT-4 on newer hardware it’ll do the same things a bit better and faster, but it won’t be able to make entirely new things out of whole cloth.
Yes, as someone who has worked both in CS and in neuroscience at the graduate level, I probably do know far more than you about this topic. At the risk of sounding more polemic than I am, it’s posts like yours and others that make excessively reductive inferences about neurons and the brain that invariably end up polluting discussions of this topic and turn it into an unproductive cesspool of ML people offering their two-cents for topics they don’t understand (most of the replies to the original post being the cases in point).
I will grant you that it is indeed possible that we don’t understand enough about the brain to be confident that we won’t just irreversibly ruin test subjects’ brains with such a therapy, but this is much less likely than the possibility that either nothing will happen or that gains will be had, provided such a therapy is successfully developed in a way that makes it feasible. Geneticists and neuroscientists have not been doing nothing for the past century; we understand much more about the brain, neurons, and cell biology than we understand about artificial neural networks, which is why we can be confident that things like this are possible if we can overcome the obstacles in engineering the delivery and editing mechanisms. There is also no reason to get it right on the first try; GeneSmith has sadly had to state the obvious several times in response to others, which is that we have the scientific method and it would take many experiments to get such a therapy right if it is at all possible. Regardless, I don’t think this therapy as OP describes it is possible for reasons that have already been stated by HiddenPrior and other reasons, but not for the inane reasons others have suggested that liken the adult brain to an immutable pre-trained neural net. It will take several breakthroughs in the field before reliable multiplex genome editing in the human central nervous system becomes a reality.
You are right however that without more GWASes, it will likely be impossible to extricate intelligence enhancements and changes to things like one’s psychology and predisposition to psychiatric disorders. It is even possible that these end up being inextricable to an extent, and recipients of this therapy would have to accept sustaining some degree of not only personality change but other introspective “updates” and disease risk changes. This is one aspect of this therapy that the OP has been rather naïve about in the post and replies to others. If a gene’s influence is such that it affects as emergent and complex a trait as intelligence, it is reasonable to suspect that it affects other things. This is demonstrable with GWASes (and has been demonstrated), but the silver lining is that allele flips that enhance intelligence tend to confer positive rather than negative changes to other systems (key word here being “tend”). As far as my personal preference goes, I would gladly accept a different personality if it meant having an IQ of 190+ or something; nonetheless, there’s no reason to believe personality isn’t amenable to the same techniques used to alter intelligence.
The bit about the personality was specifically in response to the idea that you could revert brains to childhood-like plasticity. That’s like an additional layer of complexity and unlike gene therapy we don’t know how to begin doing that, so if you ask me, I don’t think it would actually be a thing anyway in the near future. My guess is: most of your intelligence, even the genetic component, is probably determined by development during the phase of highest plasticity. So if you change the genes later you’ll either get no effect or marginal ones compared to what would happen if you changed them in embryos—that is, if it doesn’t also cause other weird side effects.
Experiments are possible but I doubt they’d be risk-free, or honestly, even approved by an ethical committee at all, as things are now. It’s a high risk for a goal that would probably be deemed in itself ethically questionable. And the study surviving for example a cohort “gone bad” would be really hard in terms of public support and funding.
Can you elaborate on this? We’d really appreciate the feedback.
I posted my reply to this as a direct reply to the OP because I think it’s too huge and elaborate to keep hidden here.
I just want to point out that the sentence you replied to starts with an “if”. “If those genes’ role is to alter the way synapses develop in the fastest growth phase, changing them when you’re 30 won’t do anything” (emphasis mine). You described this as “At first you confidently assert that changing genes in the brain won’t do anything to an adult”. The difference is important. This is in no way a comment on the object level debate. I simply think Lesswrong is a place where hypotheticals are useful and that debates will be poorer if people cannot rely on the safety that saying “if A then B” will not be interpreted as just saying “B”.
I agree, it seems totally bizarre to imagine even a single person reading this post would genuinely want to erase themselves in order to make room for a ‘smarter’ personality.
Even if it was offered for free with no other risks or side effects whatsoever. Let alone in the real world.