Do the rates of full-term and adult survival rates in iPSC mice match that which could be achieved by normal IVF, or do they indicate that there is still some suboptimality in culturing of tetraploid aggregated iPSC embryos? I’m not familiar with the normal rates of survival for mice so I wasn’t able to tell from the graph whether there is still room for improvement.
Using tetraploid complementation, it is possible to achieve up to 70% of full-term development, which is similar rate of mouse natural conception. And this was before we understood how it works. I believe that soon we will be able to outperform nature and achieve close to 100% full term development and survival (I’ve seen 90% efficiency in some experiments). For human, only 30% of naturally conceived embryos are born, and only 10% of IVF, so superseding nature for human will be even easier than for mice.
How epigenetically different are embryos produced with Sox2-17 compared to those produced through the normal IVF process?
In figure 4 we demonstrate that the mice are healthy, and can breed giving rise to healthy progeny, which is the highest bar for the quality of the cells. Again, our current IVF practice has only 10% success rate—the bar is pretty low. Also, the biggest advance of the paper is not creation of Sox2-17, but understanding the mechanism of naive pluripotency in mammals, which gives the unprecedented access to mammalian germline. Before, it was only accessible for mice and rats.
If this process or an improved one in the future were capable of inducing embryo-viable iPSC’s, would you be able to tell this was the case in humans with the current data available? If not, what data are you missing? I’m particularly wondering about whether you feel that there is sufficient data available regarding the epigenetic state of normal embryonic cells at the blastocyst stage.
This is just the first paper on the true nature of naive cells. Mouse is always first. The paper is unusual in the way that it contains 4 more species, including human. The next step would be to achieve tetraploid complementation for non-rodents, such as pigs, cows, sheep, dogs, monkeys, etc. If we could generate various animals and they are heathy and give normal progeny, then only we could think of humans. For humans, the first edits will address horrendous genetic diseases, rather than enhancements.
FYI, your iPSCs would give rise to your clones rather than children, which might only be okay for individuals with high value for society (eg. Einstain-like intelligence). I think it makes more sense to derive ESCs from IVF embryos, edit them in the dish, do QC, then use to create the embryos again—those will obviously be your children. Another option is to use iPSCs for in vitro gametogenesis (IVG), so basically your edited iPSCs are used to derive sperm/eggs. This rout will take longer to perfect, because so far very few mice have been born from IVG.
Do you know a study that has demonstrated enhancement of intelligence by editing adults? It would be a cool study, definitely worth to pursue, but there’s a big change it won’t work at all. I would bet on cell therapy for adults rather than gene therapy.
On the other hand, multiple studies have already shown enhanced intelligence for mice and monkeys by engineering the germline.
AGI will hopefully not kill all the humans. With such pessimism we can just give up and watch tv. If there are any humans in future it makes sense to enhance their intelligence and other talents. I did not suggest enhancing monkeys, I was just trying to say that if we want to achieve a chimp-to-human level transformation for human, we need to target the development.
Do the rates of full-term and adult survival rates in iPSC mice match that which could be achieved by normal IVF, or do they indicate that there is still some suboptimality in culturing of tetraploid aggregated iPSC embryos? I’m not familiar with the normal rates of survival for mice so I wasn’t able to tell from the graph whether there is still room for improvement.
Using tetraploid complementation, it is possible to achieve up to 70% of full-term development, which is similar rate of mouse natural conception. And this was before we understood how it works. I believe that soon we will be able to outperform nature and achieve close to 100% full term development and survival (I’ve seen 90% efficiency in some experiments). For human, only 30% of naturally conceived embryos are born, and only 10% of IVF, so superseding nature for human will be even easier than for mice.
How epigenetically different are embryos produced with Sox2-17 compared to those produced through the normal IVF process?
In figure 4 we demonstrate that the mice are healthy, and can breed giving rise to healthy progeny, which is the highest bar for the quality of the cells. Again, our current IVF practice has only 10% success rate—the bar is pretty low. Also, the biggest advance of the paper is not creation of Sox2-17, but understanding the mechanism of naive pluripotency in mammals, which gives the unprecedented access to mammalian germline. Before, it was only accessible for mice and rats.
If this process or an improved one in the future were capable of inducing embryo-viable iPSC’s, would you be able to tell this was the case in humans with the current data available? If not, what data are you missing? I’m particularly wondering about whether you feel that there is sufficient data available regarding the epigenetic state of normal embryonic cells at the blastocyst stage.
This is just the first paper on the true nature of naive cells. Mouse is always first. The paper is unusual in the way that it contains 4 more species, including human. The next step would be to achieve tetraploid complementation for non-rodents, such as pigs, cows, sheep, dogs, monkeys, etc. If we could generate various animals and they are heathy and give normal progeny, then only we could think of humans. For humans, the first edits will address horrendous genetic diseases, rather than enhancements.
FYI, your iPSCs would give rise to your clones rather than children, which might only be okay for individuals with high value for society (eg. Einstain-like intelligence). I think it makes more sense to derive ESCs from IVF embryos, edit them in the dish, do QC, then use to create the embryos again—those will obviously be your children. Another option is to use iPSCs for in vitro gametogenesis (IVG), so basically your edited iPSCs are used to derive sperm/eggs. This rout will take longer to perfect, because so far very few mice have been born from IVG.
Do you know a study that has demonstrated enhancement of intelligence by editing adults? It would be a cool study, definitely worth to pursue, but there’s a big change it won’t work at all. I would bet on cell therapy for adults rather than gene therapy.
On the other hand, multiple studies have already shown enhanced intelligence for mice and monkeys by engineering the germline.
AGI will hopefully not kill all the humans. With such pessimism we can just give up and watch tv. If there are any humans in future it makes sense to enhance their intelligence and other talents. I did not suggest enhancing monkeys, I was just trying to say that if we want to achieve a chimp-to-human level transformation for human, we need to target the development.