Links for stuff I may've mentioned this weekend: - Chromosome selection: https://www.gwern.net/Embryo-selection#fn6 … - selection unlimited: https://www.gwern.net/Embryo-selection#limits-to-iterated-selection-the-paradox-of-polygenicity … - Catnip: https://www.gwern.net/Catnip - Advertising A/B test: http://www.gwern.net/Ads - Anti-spaced-repetition: https://www.gwern.net/Statistical-notes#program-for-non-spaced-repetition-review-of-past-written-materials-for-serendipity-rediscovery-archive-revisiter …
-
-
WRT editing, what's your view on toggling SNPs vs fixing rare deleterious variants? The latter in principle does more with fewer edits (how much more, I don't know), provided you can identify relevant variants, which is hard.
-
Rare variants don't help much because anything common enough to show up more than once in a blue moon has a relatively small effect. Like the height/BMI CNVs: -1cm or +1kg. Whoop de doo. Even less so far for IQ, aside from terrible genetic diseases which probably can't be fixed.
-
So, to the extent you can do it for anything, you probably can do it a lot easier by selection, and the variance proportions for intelligence indicate that there's not much there on average. If you can do it, great, but it doesn't break the polygenicity limitation.
End of conversation
New conversation -
-
-
RE: CRISPR, off-targets are massively overrated as problems, on-target low efficiency still a big problem and not sure if we will ever solve it
-
Being overrated is, unfortunately, a major barrier to adoption on its own and so something of a self-fulfilling prophecy.
-
It's just maddening coz you*could*give the final embryo something like 80% lower risk of alzh or heart disease and it would be just*a cheap edit massively worth it in $/QALYs. Obvs things like the George Church list far from current capacity and synthesis would render it obsolete
-
but it's basically the opposite of the common media coverage. "CRISPR causes tons of unintended mutations" tons of headlines for n=3 mice that counted sibling differences as CRISPR mutations, took one year to retract despite key criticisms being made the next day
-
There are more recent results showing other nasty off-target mutations, IIRC.
-
that's just the most egregious example. Studies showing off-target mutations don't beat https://www.nature.com/articles/nature16526 … that showed one in ~3000 editions or https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007503 … that didn't find any. Other recent headline catching studies are stuff like upregulating p53 (if serious..
-
only relevant for ex vivo theraphy with edited stem cells/T cells) or stuff like https://www.nature.com/articles/s41586-018-0380-z … https://www.nature.com/articles/nbt.4192 … that is on target. What I mean is that you get double-digit % efficiency in semi-suspicious Chinese embryo editing studies...
-
or things like https://www.biorxiv.org/content/early/2018/09/01/393231 … giving <1% Efficiency can get higher than 66% or close to 100% or have this very low results, some of the is Cas9 vs. other proteins, sometimes it's sequence to edit, sometimes protein-binding to the DNA, etc. Might improve, might not
End of conversation
New conversation -
Loading seems to be taking a while.
Twitter may be over capacity or experiencing a momentary hiccup. Try again or visit Twitter Status for more information.