> They injected a synthetic healthy DNA sequence into the fertilized egg, expecting that the male genome would copy that sequence into the cut portion ... Instead, the male gene copied the healthy sequence from the female gene. The authors don’t know why it happened.
This seems like the most remarkable part of this entire article. It sounds like a huge discovery. There's a lot of ethical concerns that can be laid aside if the embryo is simply replacing genes from the other parent. That's still just a healthy baby, not a "designer" baby.
I went through a human neural development class in grad school and the most interesting thing I learned is that we have no/little idea what is going on. We know that rostralization/posteriorization is set up at initial fertilization in most vertebrates, but we have no what causes it (utube-spindles? actin responses to puncture?). Same with dorsal/ventralization. The way we know this small bit? Toads' (xenopus) have a dark/light side to their eggs and we can track that, but other 'clear' egged species are assumed to be like that, as we can't 'tattoo' a cell membrane reliably yet.
In general, I was really stunned at the insane complexity and fervor of development. I mean, you go from one tiny little cell and one tiny little sperm, and then you end up with a trillion little cells all different and all really specialized in under a year. And it mostly all works! Some of those cell migrate a very long way (from a baby elephant's head to it's toes with some nerves) almost perfectly. Some of the time, tons of cells are born, shepherd other cells about, and then die off in about a day (like apoptosis in breast-feeding). Why? No clue. Maybe evolutionary 'holdovers', dunno, more funding please. Really, the shear complexity and energy of the system, with things crashing into each other, traffic jams of cells in a neural cleft, all going about all at once, it is stunning. I can understand a lot of researchers that are in that field and how deeply religious they are, seeing and 'understanding' it all can be moving.
It almost sounds like there's an anti-tampering (i.e. counter-mutagenic) system in place we don't understand. Makes sense. Not only is meiosis more error-prone than mitosis, there's also a wide difference in error rates between the sexes (40 to 60% for women and 3% for men) [1].
That is pretty interesting... I've hit a wall on figuring out what they did here but maybe have missed the info.[1]
1a) One male who was heterozygous for a certain mutation donated his sperm:
-"only three adult heterozygous patients were identified by OHSU Knight Cardiovascular Institute physicians and referred to the research team, one of whom agreed to participate in the study."
1b) X females donated Y amount of eggs:
- I didn't see these numbers discussed anywhere
2) One sperm each was matched to each of Y eggs for Intracytoplasmic sperm injection (ICSI). It isn't clear whether any selection for sperm went on here:
-"Oocytes were fertilized by ICSI using frozen and thawed sperm. Fertilization was determined approximately 18 h after ICSI by noting the presence of two pronuclei and second polar body extrusion."
3) Z zygotes were found at the end of the above 18 hours:
-"zygotes were collected 18 h after ICSI and placed in a micromanipulation drop...Injected zygotes were
cultured...for up to 3 days to the 4–8-cell stage"
4) 131 embryos formed from those Z zygotes that got injected with CRISPR-Cas9, consisting of 830 cells total:
-"A total of 830 blastomeres were isolated from 131 embryos, including 19 from control, 54 from zygote-injected and 58 from M-phase-injected groups."
5) A sequence was attained for 730 of those 830 cells:
-"Of 830 blastomeres, 730 (88%) resulted in successful libraries and produced PCR products for MYBPC3 while the remaining 100 blastomeres (12%) failed to generate PCR products and were excluded from the study."[2]
I mostly wanted to know Z, how many and what percent of zygotes survived the CRISPR/Cas-9 treatment. It seems to be missing. I would also like to know X and Y (initial number of women and eggs donated) though.
On the other hand, being completely unfamiliar with genetic imprinting as we are, we have no idea what the effects that this kind of single-gender inheritance may be.
This seems like the most remarkable part of this entire article. It sounds like a huge discovery. There's a lot of ethical concerns that can be laid aside if the embryo is simply replacing genes from the other parent. That's still just a healthy baby, not a "designer" baby.