one needs to only make a low-hundreds number of edits to one cell to make someone smarter than any human that has ever lived.
This is probably not true unless you start out with an embryo that already has a very high polygenic score for intelligence. To a first approximation, 15 IQ points = 75 edits of causal variants. And since we aren’t precisely sure which variant is causal, the needed number of edits will be higher (perhaps 100-300).
Am I just wrong here? Is somatic gene therapy really robust and error-free enough to safely edit billions of cells?
It depends heavily on your editing vector and your target site. Base editors and prime editors have significantly higher ratios for on-target / off target edit rates. They also don’t introduce double strand breaks like CRISPR does, which means you won’t randomly get entire cells being eliminated if the DNA repair machinery doesn’t work.
I am writing a more detailed post about this that will answer most of these questions. In short, the answer to your question is maybe. It is much more plausible we could make edits in billions of somatic cells than I would have though even two months ago.
If three years has passed, and substantial capabilities progress has occurred and we still don’t seem close to a solution to alignment, and good progress was made on this project in animal studies.… I’d definitely volunteer. The EV calculation (for the safety of society and for my loved ones, not just for myself) seems pretty clear.
This is probably not true unless you start out with an embryo that already has a very high polygenic score for intelligence. To a first approximation, 15 IQ points = 75 edits of causal variants. And since we aren’t precisely sure which variant is causal, the needed number of edits will be higher (perhaps 100-300).
It depends heavily on your editing vector and your target site. Base editors and prime editors have significantly higher ratios for on-target / off target edit rates. They also don’t introduce double strand breaks like CRISPR does, which means you won’t randomly get entire cells being eliminated if the DNA repair machinery doesn’t work.
I am writing a more detailed post about this that will answer most of these questions. In short, the answer to your question is maybe. It is much more plausible we could make edits in billions of somatic cells than I would have though even two months ago.
I think I may be almost crazy enough to volunteer for such a procedure, ha, should you convince me.
If three years has passed, and substantial capabilities progress has occurred and we still don’t seem close to a solution to alignment, and good progress was made on this project in animal studies.… I’d definitely volunteer. The EV calculation (for the safety of society and for my loved ones, not just for myself) seems pretty clear.
This comment was assuming causal variants are known, which I admit is a big gimme. More of a first-principles type eye-balling.