I like the premise. I’m glad this is getting researched. But:
Lots of things in the space are understudied and the startup-vibe approach of “we’ll figure this all out on the way because previous papers don’t exist” seems way less likely to work with bio than tech because of the length of iteration cycles. But props if it does?
Black swan effects of polygenic edits
cellular stress if on a large scale?
might be an exception where pleiotropy does actually matter, which would suck. the table in another comment showing correlations between illnesses is pretty convincing however it’s possible there are effects that aren’t quantified there (doesn’t present as diagnosable disease)
???? not sufficiently enmeshed in the bio space but this entire post gives off the vibe of “most of the components are bleeding edge and there aren’t many papers, esp not large scale/long term ones” and I imagine that’ll cause more issues than you expect and streeeetch timescales
given black box bio and difficulty of studying the brain, it’s really hard to tell what’s being left out in studies that measure only change in intelligence/what other things are being affected
We have gotten nowhere near as much as we could out of behavioral interventions (on long timescales) and nootropics, and both of those seem like better areas to put research time into. I don’t actually think a research project of this scale will be faster (for AI safety research etc) than either of those.
counterpoint: this will just make it easier/lower ‘energy’ to apply interventions and is hence worthwhile?? but it’s still so risky that I maintain the above approaches are more worthwhile in the short term
We already expect that too many editor proteins in the cells could be a problem. But that will show up in cell culture experiments and animal studies and we can modify doses, use more efficient editors, and do multiple rounds of editing to address it.
We also know about liver toxicity from too many lipid nanoparticles, but that’s an addressable concern (use fewer nanoparticles, ensure they get into the target organ quickly)
I’m sure there will be others that I don’t expect, but that’s true with literally every new medical treatment. That’s the whole point of running experiments in cell cultures and mice.
might be an exception where pleiotropy does actually matter, which would suck. the table in another comment showing correlations between illnesses is pretty convincing however it’s possible there are effects that aren’t quantified there (doesn’t present as diagnosable disease)
We actually have some pretty good studies on plietropy between intelligence and other traits. The only consistently replicated effect I’ve seen which could be deemed negative is a correlation with mild aspbergers-like symptoms.
But you can just look at current people already alive to test the plieotropy hypothesis. Do unusually smart people have any serious problems that normal people don’t?
The answer is pretty clearly “no”. I expect that to continue being the case even if we push intelligence to the extremes of the current human range.
???? not sufficiently enmeshed in the bio space but this entire post gives off the vibe of “most of the components are bleeding edge and there aren’t many papers, esp not large scale/long term ones” and I imagine that’ll cause more issues than you expect and streeeetch timescales
This is true almost by definition for any new technology.
We have gotten nowhere near as much as we could out of behavioral interventions (on long timescales) and nootropics, and both of those seem like better areas to put research time into. I don’t actually think a research project of this scale will be faster (for AI safety research etc) than either of those.
I would be very surprised if a pharmaceutical, or even a bunch of pharmaceuticals could replicate the effects of gene editing. Imagine trying to create a set of compounds that coul replicate the effects of gene editing: you would need thousands of different compounds to individually target the pathways affected by all the variants. And you would need pharmaceuticals that would modulate their activity based on the current state of the cell. After all, that’s how a lot of promoters and repressors and enhancers work; their activity depends on the state of the cell!
I still think people should work on nootropics. And you may of course be right that this won’t be ready before AGI. I’d put the odds at maybe 20%.
But it COULD actually work! And if it did the impact would be absolutely massive! So like… why not? I might as well try.
Do unusually smart people have any serious problems that normal people don’t?
Torsion dystonia seems to add 10 IQ points. I think there are a few other genetic diseases more common among Ashkenazi Jews that are also associated with higher intelligence.
I like the premise. I’m glad this is getting researched. But:
Lots of things in the space are understudied and the startup-vibe approach of “we’ll figure this all out on the way because previous papers don’t exist” seems way less likely to work with bio than tech because of the length of iteration cycles. But props if it does?
Black swan effects of polygenic edits
cellular stress if on a large scale?
might be an exception where pleiotropy does actually matter, which would suck. the table in another comment showing correlations between illnesses is pretty convincing however it’s possible there are effects that aren’t quantified there (doesn’t present as diagnosable disease)
???? not sufficiently enmeshed in the bio space but this entire post gives off the vibe of “most of the components are bleeding edge and there aren’t many papers, esp not large scale/long term ones” and I imagine that’ll cause more issues than you expect and streeeetch timescales
given black box bio and difficulty of studying the brain, it’s really hard to tell what’s being left out in studies that measure only change in intelligence/what other things are being affected
We have gotten nowhere near as much as we could out of behavioral interventions (on long timescales) and nootropics, and both of those seem like better areas to put research time into. I don’t actually think a research project of this scale will be faster (for AI safety research etc) than either of those.
counterpoint: this will just make it easier/lower ‘energy’ to apply interventions and is hence worthwhile?? but it’s still so risky that I maintain the above approaches are more worthwhile in the short term
We already expect that too many editor proteins in the cells could be a problem. But that will show up in cell culture experiments and animal studies and we can modify doses, use more efficient editors, and do multiple rounds of editing to address it.
We also know about liver toxicity from too many lipid nanoparticles, but that’s an addressable concern (use fewer nanoparticles, ensure they get into the target organ quickly)
I’m sure there will be others that I don’t expect, but that’s true with literally every new medical treatment. That’s the whole point of running experiments in cell cultures and mice.
We actually have some pretty good studies on plietropy between intelligence and other traits. The only consistently replicated effect I’ve seen which could be deemed negative is a correlation with mild aspbergers-like symptoms.
But you can just look at current people already alive to test the plieotropy hypothesis. Do unusually smart people have any serious problems that normal people don’t?
The answer is pretty clearly “no”. I expect that to continue being the case even if we push intelligence to the extremes of the current human range.
This is true almost by definition for any new technology.
I would be very surprised if a pharmaceutical, or even a bunch of pharmaceuticals could replicate the effects of gene editing. Imagine trying to create a set of compounds that coul replicate the effects of gene editing: you would need thousands of different compounds to individually target the pathways affected by all the variants. And you would need pharmaceuticals that would modulate their activity based on the current state of the cell. After all, that’s how a lot of promoters and repressors and enhancers work; their activity depends on the state of the cell!
I still think people should work on nootropics. And you may of course be right that this won’t be ready before AGI. I’d put the odds at maybe 20%.
But it COULD actually work! And if it did the impact would be absolutely massive! So like… why not? I might as well try.
Torsion dystonia seems to add 10 IQ points. I think there are a few other genetic diseases more common among Ashkenazi Jews that are also associated with higher intelligence.
See here
side comment that I’ve been reminded of: epigenetics *exist(s?)*. I wonder if that could somehow be a more naturally integrate-able approach
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251063/