Yes, generating lots of embryos will help, but the marginal returns decline extremely quickly because you’re taking the maximum of a Gaussian distribution.
Gain is proportional to sqrt(ln(number of embryos))
Going from 30 embryos (roughly the upper bound of what you can get with normal IVF) to 1000 will only increase gain 43%.
43% is still pretty big, but it’s not going to radically change the world. For that you’re going to need massive parallel gene editing, iterated embryo selection or whole genome synthesis.
I did a calculation a while back and estimated it would cost about $200 million to synthesize an entire human genome at today’s prices. But there’s a bunch of other technical challenges you’d have to overcome.
Gene editing seems to be improving but there are still some weird issues with CRISPR where it seems to randomly chop off chromosomes sometimes.
There are a couple groups working towards in-vitro oogenesis, which is probably the most important step to making iterated embryo selection work. I think the main blocking step there is making the environment in which the eggs mature. You need a bunch of follicle cells and the only source for those currently is abortion tissue. There’s a couple groups trying to make them from stem cells instead: https://www.technologyreview.com/2021/10/28/1038172/conception-eggs-reproduction-vitro-gametogenesis/
So lots of stuff in the pipeline, but nothing seems to be imminent.
(In particular, trying to understand what you’re saying made me understand something basic about IES vs just embryo selection: with IES you’re actually doing many iterations of sexual reproduction with a population, so you can get a genotype composed of any alleles that are present in any of the starting embryos.)
If you read the Technology Review article I posted, there is a Japanese team that managed to do it in mice, but it took them 4 years. I don’t really know that much about the technical details, but just judging from the empirical results it does not appear to be an easy problem.
I guess the social/logistic one is not wanting to create a solution that relies on a supply of abortion tissue, which leads to the scientific/technological one of how to create the follicle cells.
Thanks!
And, hypothetically, generating lots of embryos to choose from? Or is that not in the cards?
Yes, generating lots of embryos will help, but the marginal returns decline extremely quickly because you’re taking the maximum of a Gaussian distribution.
Gain is proportional to sqrt(ln(number of embryos))
Going from 30 embryos (roughly the upper bound of what you can get with normal IVF) to 1000 will only increase gain 43%.
43% is still pretty big, but it’s not going to radically change the world. For that you’re going to need massive parallel gene editing, iterated embryo selection or whole genome synthesis.
I did a calculation a while back and estimated it would cost about $200 million to synthesize an entire human genome at today’s prices. But there’s a bunch of other technical challenges you’d have to overcome.
Gene editing seems to be improving but there are still some weird issues with CRISPR where it seems to randomly chop off chromosomes sometimes.
There are a couple groups working towards in-vitro oogenesis, which is probably the most important step to making iterated embryo selection work. I think the main blocking step there is making the environment in which the eggs mature. You need a bunch of follicle cells and the only source for those currently is abortion tissue. There’s a couple groups trying to make them from stem cells instead: https://www.technologyreview.com/2021/10/28/1038172/conception-eggs-reproduction-vitro-gametogenesis/
So lots of stuff in the pipeline, but nothing seems to be imminent.
Thanks, this is an enlightening summary!
(In particular, trying to understand what you’re saying made me understand something basic about IES vs just embryo selection: with IES you’re actually doing many iterations of sexual reproduction with a population, so you can get a genotype composed of any alleles that are present in any of the starting embryos.)
Hmm, that seems like it shouldnt be that hard of a problem to solve, but idk. I hope someone takes this on if that’s really a bottleneck.
If you read the Technology Review article I posted, there is a Japanese team that managed to do it in mice, but it took them 4 years. I don’t really know that much about the technical details, but just judging from the empirical results it does not appear to be an easy problem.
Oh, I assumed the problem was a social / logistic one, but now I’m assuming there’s also a scientific / technological one
I guess the social/logistic one is not wanting to create a solution that relies on a supply of abortion tissue, which leads to the scientific/technological one of how to create the follicle cells.