How’d the payload get through the blood brain barrier?
Are there any alleles which if flipped would boost IQ but cause some major harm e.g. Torsion dystonia?
If so, would you offer people the choice of whether they wanted to flip said alleles?
Presumably there are a bunch of alleles correlated with personality. If a large chunk of them also correlated with intelligence, plausibly you’d kill the person’s psyche and replace them with a stranger with similiar memories. Do you think this could be avoided/isn’t a problem in the first place? If so, how do you know that?
Would you do challenge trials?
Would you do your work in a country with laxer rules, both de dicto and dejure, around challenge trials/genetic engineering?
If you succeed, or heck even during development, would you open source your process so that ~anyone can replicate/improve on your results privately?
How would this treatment affect the elderly? Like, would it make them several SD above the mean fluid intelligence amongst their age group or would it have a bigger impact because they’ve got deficits in fluid intelligence or what?
Buddy, if this looks like it might work out, I want to help out. So of course, I’d like to know more about this whole endeavour. Please contact me.
Using a targeting ligand like angiopep attached to the outside of a lipid nanopaticle. There are papers where researchers have already done this.
Yes, probably, though I don’t think it will be particularly common. The way to avoid this is just to incorporate a bunch of predictors for other traits into your allele selection criteria.
Obviously yes, though hopefully we just wouldn’t need to flip those alleles in the first place. I’m still uncertain about the maximum effect size.
Maybe? Our predictors for the genetics of personality still aren’t very good, so it would be hard to evaluate the expected effect size.
I’m not sure what that would mean in this context. I think the first human trials would probably target polygenic brain diseases like Alzheimer’s. If the delivery platform works, you could use it to dramatically adjust someone’s polygenic risk score for many diseases. So you might as well do the first trials on people who are going to die from a degenerative brain disease with no cure or effective treatment, for which in-vivo editing might offer a solution.
I don’t know the answer to this yet. Most of the pioneering work in this field has happened in the US, so my suspicion is it would start here. Pretty much every step except perhaps the human trials could be done in the US.
I would have to think about this one more. If this tech actually works it would become incredibly valuable. Because you could use the delivery platform to basically target any disease of your choosing by adjusting someone’s polygenic risk score. There are still questions around whether you can repeatedly dose someone with the editing agent without provoking an immune response, but there are plausible solutions to all the problems I’ve looked at so far. My biggest concern though relates to AI; I really don’t want this tech to be used to speed up development of world-conquering AI. The main reason I’m interested in the tech is because I think it could potentially result in people capable of solving some of the more difficult problems in AI alignment and coordination around its appropriate use. If I were to open source it I would lose control of that.
And I think in reality there will be a lot of stakeholders in the technology so the decision won’t be mine alone. If I want to bring something like this to market, I’ll need to raise quite a bit of money and work with a lab to run animal trials. So there will be many other stakeholders with input into that decision. I suspect open-sourcing the tech would also diminish the financial gain.
8. Hard to answer, but my default assumption is they would be just like an elderly person with a very high IQ.
9. I’ll let you know when the main post goes up.
Do such people partake in dangerous medical trials today? I couldn’t find anything about it from some quick googling but if such practices don’t already exist, I doubt we would be able to start them for what would be, in most cases, an intervention not designed to cure a disease or treat a disability.
How’d the payload get through the blood brain barrier?
Are there any alleles which if flipped would boost IQ but cause some major harm e.g. Torsion dystonia?
If so, would you offer people the choice of whether they wanted to flip said alleles?
Presumably there are a bunch of alleles correlated with personality. If a large chunk of them also correlated with intelligence, plausibly you’d kill the person’s psyche and replace them with a stranger with similiar memories. Do you think this could be avoided/isn’t a problem in the first place? If so, how do you know that?
Would you do challenge trials?
Would you do your work in a country with laxer rules, both de dicto and dejure, around challenge trials/genetic engineering?
If you succeed, or heck even during development, would you open source your process so that ~anyone can replicate/improve on your results privately?
How would this treatment affect the elderly? Like, would it make them several SD above the mean fluid intelligence amongst their age group or would it have a bigger impact because they’ve got deficits in fluid intelligence or what?
Buddy, if this looks like it might work out, I want to help out. So of course, I’d like to know more about this whole endeavour. Please contact me.
All good questions.
Using a targeting ligand like angiopep attached to the outside of a lipid nanopaticle. There are papers where researchers have already done this.
Yes, probably, though I don’t think it will be particularly common. The way to avoid this is just to incorporate a bunch of predictors for other traits into your allele selection criteria.
Obviously yes, though hopefully we just wouldn’t need to flip those alleles in the first place. I’m still uncertain about the maximum effect size.
Maybe? Our predictors for the genetics of personality still aren’t very good, so it would be hard to evaluate the expected effect size.
I’m not sure what that would mean in this context. I think the first human trials would probably target polygenic brain diseases like Alzheimer’s. If the delivery platform works, you could use it to dramatically adjust someone’s polygenic risk score for many diseases. So you might as well do the first trials on people who are going to die from a degenerative brain disease with no cure or effective treatment, for which in-vivo editing might offer a solution.
I don’t know the answer to this yet. Most of the pioneering work in this field has happened in the US, so my suspicion is it would start here. Pretty much every step except perhaps the human trials could be done in the US.
I would have to think about this one more. If this tech actually works it would become incredibly valuable. Because you could use the delivery platform to basically target any disease of your choosing by adjusting someone’s polygenic risk score. There are still questions around whether you can repeatedly dose someone with the editing agent without provoking an immune response, but there are plausible solutions to all the problems I’ve looked at so far. My biggest concern though relates to AI; I really don’t want this tech to be used to speed up development of world-conquering AI. The main reason I’m interested in the tech is because I think it could potentially result in people capable of solving some of the more difficult problems in AI alignment and coordination around its appropriate use. If I were to open source it I would lose control of that.
And I think in reality there will be a lot of stakeholders in the technology so the decision won’t be mine alone. If I want to bring something like this to market, I’ll need to raise quite a bit of money and work with a lab to run animal trials. So there will be many other stakeholders with input into that decision. I suspect open-sourcing the tech would also diminish the financial gain. 8. Hard to answer, but my default assumption is they would be just like an elderly person with a very high IQ. 9. I’ll let you know when the main post goes up.
What do you mean by challenge trials in this context?
In the vaccine context, a challenge trial is a trial where you expose people who get the vaccine to the virus.
That makes little sense in the context of intelligence improvement.
E.g. pay people who are planning on Euthanasia to undergo the treatment, and if it fails then handle the euthanasia.
Do such people partake in dangerous medical trials today? I couldn’t find anything about it from some quick googling but if such practices don’t already exist, I doubt we would be able to start them for what would be, in most cases, an intervention not designed to cure a disease or treat a disability.
I’m not sure why you would call that a challenge trial.
I would also be surprised if that’s something you can effectively do.