This is an interesting post, but it has a very funny framing. Instead of working on enhancing adult intelligence, why don’t you start with:
Showing that many genes can be successfully and accurately edited in a live animal (ideally human). As far as I know, this hasn’t been done before! Only small edits have been demonstrated.
Showing that editing embryos can result in increased intelligence. I don’t believe this has even been done in animals, let alone humans.
Editing the brains of adult humans and expecting intelligence enhancement is like 3-4 impossibilities away from where we are right now. Start with the basic impossibilities and work your way up from there (or, more realistically, give up when you fail at even the basics).
My own guess, by the way, is that editing an adult human’s genes for increased intelligence will not work, because adults cannot be easily changed. If you think they can, I recommend trying the following instead of attacking the brain; they all should be easier because brains are very hard:
Gene editing to make people taller. You’d be an instant billionaire. (I expect this is impossible but you seem to be going by which genes are expressed in adult cells, and a lot of the genes governing stature will be expressed in adult cells.)
Gene editing to enlarge people’s penises. You’ll be swimming in money! Do this first and you can have infinite funding for anything else you want to do.
Gene editing to cure acne. Predisposition to acne is surely genetic.
Gene editing for transitioning (FtM or MtF).
Gene editing to cure male pattern baldness.
[Exercise for the reader: generate 3-5 more examples of this general type, i.e. highly desirable body modifications that involve coveting another human’s reasonably common genetic traits, and for which any proposed gene therapy can be easily verified to work just by looking.]
All of the above are instantly verifiable (on the other hand, “our patients increased 3 IQ points, we swear” is not as easily verifiable). They all also will make you rich, and they should all be easier than editing the brain. Why do rationalists always jump to the brain?
The market has very strong incentives to solve the above, by the way, and they don’t involve taboos about brain modification or IQ. The reason they haven’t been solved via gene editing is that gene editing in adults simply doesn’t work nearly as well as you want it to.
Showing that many genes can be successfully and accurately edited in a live animal (ideally human). As far as I know, this hasn’t been done before! Only small edits have been demonstrated.
This is more or less our current plan.
Showing that editing embryos can result in increased intelligence. I don’t believe this has even been done in animals, let alone humans.
This has some separate technical challenges, and is also probably more taboo? The only reason that successfully editing embryos wouldn’t increase intelligence is that the variants being targeted weren’t actually causal for intelligence.
Gene editing to make people taller.
This seems harder, you’d need to somehow unfuse the growth plates.
on the other hand, “our patients increased 3 IQ points, we swear” is not as easily verifiable
A nice thing about IQ is that it’s actually really easy to measure. Noisier than measuring height, sure, but not terribly noisy.
They all also will make you rich, and they should all be easier than editing the brain. Why do rationalists always jump to the brain?
More intelligence enables progress on important, difficult problems, such as AI alignment.
This seems harder, you’d need to somehow unfuse the growth plates.
It’s hard, yes—I’d even say it’s impossible. But is it harder than the brain? The difference between growth plates and whatever is going on in the brain is that we understand growth plates and we do not understand the brain. You seem to have a prior of “we don’t understand it, therefore it should be possible, since we know of no barrier”. My prior is “we don’t understand it, so nothing will work and it’s totally hopeless”.
A nice thing about IQ is that it’s actually really easy to measure. Noisier than measuring height, sure, but not terribly noisy.
Actually, IQ test scores increase by a few points if you test again (called test-retest gains). Additionally, IQ varies substantially based on which IQ test you use. It is gonna be pretty hard to convince people you’ve increased your patients’ IQ by 3 points due to these factors—you’ll need a nice large sample with a proper control group in a double-blind study, and people will still have doubts.
More intelligence enables progress on important, difficult problems, such as AI alignment.
Lol. I mean, you’re not wrong with that precise statement, it just comes across as “the fountain of eternal youth will enable progress on important, difficult diplomatic and geopolitical situations”. Yes, this is true, but maybe see if you can beat botox at skin care before jumping to the fountain of youth. And there may be less fantastical solutions to your diplomatic issues. Also, finding the fountain of youth is likely to backfire and make your diplomatic situation worse. (To explain the metaphor: if you summon a few von Neumanns into existence tomorrow, I expect to die of AI sooner, on average, rather than later.)
Showing that many genes can be successfully and accurately edited in a live animal (ideally human). As far as I know, this hasn’t been done before! Only small edits have been demonstrated.
This is in fact the plan.
2. Showing that editing embryos can result in increased intelligence. I don’t believe this has even been done in animals, let alone humans.
This would be a very big thing in and of itself. Also, it wouldn’t give you much useful information about whether adult editing would work, because most of the uncertainty centers around delivery efficiency, the effect size of edits in adult brains, mosaicism and other things you wouldn’t be able to validate in embryos.
Gene editing to make people taller. You’d be an instant billionaire. (I expect this is impossible but you seem to be going by which genes are expressed in adult cells, and a lot of the genes governing stature will be expressed in adult cells.)
To the best of my knowledge, this is not possible in adults. The growth plates fuse at the end of puberty. This is why bodybuilders taking HGH don’t get taller.
Gene editing for transitioning (FtM or MtF).
I don’t think gene editing will be able to help with this one. You’d need to swap an X chromosome to a Y or vice-versa. None of the delivery vectors are large enough to fit an entire chromosome. They’re not even close.
And even if you could select a subset of the genes most impactful, you’d have to eliminate the existing chromosome, which is not trivial.
And even if you could do that, it wouldn’t be able to undo male or female puberty.
And even if you could do that I have no idea how this tech could be used to grow different sexual organs, which is what you would ideally want.
MAYBE this could be used to enable endogenous sex hormone production or something. But apart from that, nothing comes to mind for ways this tech could help people who want to transition.
Gene editing to cure male pattern baldness.
This one could actually be possible. In fact it would probably be easier than intelligence or brain disorders. But your competition is going to be hair transplants and rogaine, which would be difficult to beat on price.
[Exercise for the reader: generate 3-5 more examples of this general type, i.e. highly desirable body modifications that involve coveting another human’s reasonably common genetic traits, and for which any proposed gene therapy can be easily verified to work just by looking.]
Obviously there are many more examples. That’s one of the exciting things about in-vivo editing. But you have limitations:
The trait must be heritable (true for many things we’d want to change)
We need good genetic predictors for the trait
All of the above are instantly verifiable (on the other hand, “our patients increased 3 IQ points, we swear” is not as easily verifiable). They all also will make you rich, and they should all be easier than editing the brain. Why do rationalists always jump to the brain?
We would not even attempt the therapy unless the difference was easily measurable.
The market has very strong incentives to solve the above, by the way, and they don’t involve taboos about brain modification or IQ. The reason they haven’t been solved via gene editing is that gene editing in adults simply doesn’t work nearly as well as you want it to.
Yeah, this is what I used to think before I actually worked at a bunch of startups and realized that the efficient market hypothesis doesn’t apply to all markets equally. In reality there are hundred dollar bills lying around everywhere, but most people can only see a few, and some can’t see any.
This is particularly true when there are high barriers to entry, hidden information, many steps of inference to reach a conclusion, and cultural taboos that prevent people from looking. Every one of those is getting in the way here.
This is an interesting post, but it has a very funny framing. Instead of working on enhancing adult intelligence, why don’t you start with:
Showing that many genes can be successfully and accurately edited in a live animal (ideally human). As far as I know, this hasn’t been done before! Only small edits have been demonstrated.
Showing that editing embryos can result in increased intelligence. I don’t believe this has even been done in animals, let alone humans.
Editing the brains of adult humans and expecting intelligence enhancement is like 3-4 impossibilities away from where we are right now. Start with the basic impossibilities and work your way up from there (or, more realistically, give up when you fail at even the basics).
My own guess, by the way, is that editing an adult human’s genes for increased intelligence will not work, because adults cannot be easily changed. If you think they can, I recommend trying the following instead of attacking the brain; they all should be easier because brains are very hard:
Gene editing to make people taller. You’d be an instant billionaire. (I expect this is impossible but you seem to be going by which genes are expressed in adult cells, and a lot of the genes governing stature will be expressed in adult cells.)
Gene editing to enlarge people’s penises. You’ll be swimming in money! Do this first and you can have infinite funding for anything else you want to do.
Gene editing to cure acne. Predisposition to acne is surely genetic.
Gene editing for transitioning (FtM or MtF).
Gene editing to cure male pattern baldness.
[Exercise for the reader: generate 3-5 more examples of this general type, i.e. highly desirable body modifications that involve coveting another human’s reasonably common genetic traits, and for which any proposed gene therapy can be easily verified to work just by looking.]
All of the above are instantly verifiable (on the other hand, “our patients increased 3 IQ points, we swear” is not as easily verifiable). They all also will make you rich, and they should all be easier than editing the brain. Why do rationalists always jump to the brain?
The market has very strong incentives to solve the above, by the way, and they don’t involve taboos about brain modification or IQ. The reason they haven’t been solved via gene editing is that gene editing in adults simply doesn’t work nearly as well as you want it to.
This is more or less our current plan.
This has some separate technical challenges, and is also probably more taboo? The only reason that successfully editing embryos wouldn’t increase intelligence is that the variants being targeted weren’t actually causal for intelligence.
This seems harder, you’d need to somehow unfuse the growth plates.
A nice thing about IQ is that it’s actually really easy to measure. Noisier than measuring height, sure, but not terribly noisy.
More intelligence enables progress on important, difficult problems, such as AI alignment.
It’s hard, yes—I’d even say it’s impossible. But is it harder than the brain? The difference between growth plates and whatever is going on in the brain is that we understand growth plates and we do not understand the brain. You seem to have a prior of “we don’t understand it, therefore it should be possible, since we know of no barrier”. My prior is “we don’t understand it, so nothing will work and it’s totally hopeless”.
Actually, IQ test scores increase by a few points if you test again (called test-retest gains). Additionally, IQ varies substantially based on which IQ test you use. It is gonna be pretty hard to convince people you’ve increased your patients’ IQ by 3 points due to these factors—you’ll need a nice large sample with a proper control group in a double-blind study, and people will still have doubts.
Lol. I mean, you’re not wrong with that precise statement, it just comes across as “the fountain of eternal youth will enable progress on important, difficult diplomatic and geopolitical situations”. Yes, this is true, but maybe see if you can beat botox at skin care before jumping to the fountain of youth. And there may be less fantastical solutions to your diplomatic issues. Also, finding the fountain of youth is likely to backfire and make your diplomatic situation worse. (To explain the metaphor: if you summon a few von Neumanns into existence tomorrow, I expect to die of AI sooner, on average, rather than later.)
This is in fact the plan.
This would be a very big thing in and of itself. Also, it wouldn’t give you much useful information about whether adult editing would work, because most of the uncertainty centers around delivery efficiency, the effect size of edits in adult brains, mosaicism and other things you wouldn’t be able to validate in embryos.
To the best of my knowledge, this is not possible in adults. The growth plates fuse at the end of puberty. This is why bodybuilders taking HGH don’t get taller.
I don’t think gene editing will be able to help with this one. You’d need to swap an X chromosome to a Y or vice-versa. None of the delivery vectors are large enough to fit an entire chromosome. They’re not even close.
And even if you could select a subset of the genes most impactful, you’d have to eliminate the existing chromosome, which is not trivial.
And even if you could do that, it wouldn’t be able to undo male or female puberty.
And even if you could do that I have no idea how this tech could be used to grow different sexual organs, which is what you would ideally want.
MAYBE this could be used to enable endogenous sex hormone production or something. But apart from that, nothing comes to mind for ways this tech could help people who want to transition.
This one could actually be possible. In fact it would probably be easier than intelligence or brain disorders. But your competition is going to be hair transplants and rogaine, which would be difficult to beat on price.
Obviously there are many more examples. That’s one of the exciting things about in-vivo editing. But you have limitations:
The trait must be heritable (true for many things we’d want to change)
We need good genetic predictors for the trait
We would not even attempt the therapy unless the difference was easily measurable.
Yeah, this is what I used to think before I actually worked at a bunch of startups and realized that the efficient market hypothesis doesn’t apply to all markets equally. In reality there are hundred dollar bills lying around everywhere, but most people can only see a few, and some can’t see any.
This is particularly true when there are high barriers to entry, hidden information, many steps of inference to reach a conclusion, and cultural taboos that prevent people from looking. Every one of those is getting in the way here.