In the course of my life, there have been a handful of times I discovered an idea that changed the way I thought about the world. The first occurred when I picked up Nick Bostrom's book “superintelligence” and realized that AI would utterly transform the world. The second was when I learned about embryo selection and how it could change future generations. And the third happened a few months ago when I read a message from a friend of mine on Discord about editing the genome of a living person.

We’ve had gene therapy to treat cancer and single gene disorders for decades. But the process involved in making such changes to the cells of a living person is excruciating and extremely expensive. CAR T-cell therapy, a treatment for certain types of cancer, requires the removal of white blood cells via IV, genetic modification of those cells outside the [...]

---

Outline:

(03:02) If this works, it's going to be a very big deal

(05:28) How does intelligence even work at a genetic level?

(07:29) Total maximum gain

(11:56) Why has it been so hard to get larger sample sizes?

(12:59) How can you even make these edits anyways? Isn’t CRISPR prone to errors?

(15:26) The first base editor

(17:27) Prime editors; the holy grail of gene editing technology?

(19:47) How do you even get editors into brain cells in the first place?

(20:14) Dual use technology

(23:11) So you inject lipid nanoparticles into the brain?

(26:13) What if administration via lipid nanoparticles doesn’t work?

(27:36) But there are other viral delivery vectors

(29:05) Would edits to the adult brain even do anything?

(32:18) What if your editor targets the wrong thing?

(33:23) What about off-target edits in non-coding regions?

(34:41) How about mosaicism?

(36:18) Can we make enough edits in a single cell to have a significant effect?

(38:23) Why hasn’t someone already done this?

(39:30) Black box biology

(40:21) Vague association with eugenics make some academics shy away

(42:58) Maybe there's some kind of technical roadblock I’m missing

(43:57) People are busy picking lower hanging fruit

(44:29) The market is erring

(46:20) Can we accelerate development of this technology?

(46:31) Problems I expect the market to work on

(46:56) Problems the market might solve

(48:15) Problems I don’t expect the market to work on

(49:15) How do we make this real?

(51:45) My current plan

(52:52) Short-term logistics concerns

(52:56) A rough outline of my research agenda

(54:09) Rough estimate of costs

(54:15) Conclusion

(56:11) Appendix (Warning: boredom ahead)

(56:16) Additional headaches not discussed

(56:20) Regarding editing

(59:19) Regarding fine-mapping of causal variants

(01:00:32) Regarding differential gene expression throughout the lifespan

(01:01:13) Regarding immune response

(01:02:07) Regarding brain size

(01:03:01) Editing induced amnesia?

(01:03:57) Model assumptions

(01:06:38) Editor properties

---

First published:
December 12th, 2023

Source:
https://www.lesswrong.com/posts/JEhW3HDMKzekDShva/significantly-enhancing-adult-intelligence-with-gene-editing

---

Narrated by TYPE III AUDIO.

“Significantly Enhancing Adult Intelligence With Gene Editing May Be Possible” by GeneSmith

LessWrong (30+ Karma)