Yeah, if anyone is interested in learning more, this is called the phasing problem. For common enough variants, it’s often possible to figure this out by looking at general patterns of co-inheritance if you have a large reference dataset for the population (see: https://www.nature.com/articles/s41588-023-01415-w). Long read sequencing which you mentioned is another approach. But you’re right that these days it would just be cheapest to get the parental genomes (assuming that’s an option).
Metacelsus
Karma: 1,279
A profile in courage: On DNA computation and escaping a local maximum
Mouse caviar: mass-production of eggs
Thank you!
I really liked the concert at LessOnline (especially “The Ninth Night of November” which is rather personal for me because FTX told me on November 3 2022 that they would fund me, and November 10 that they were in trouble, and November 14 that “the funds to support your work are gone with everything else”.
So, this is just a reminder to please release the album (unless you already did and I just can’t find it).
Specifically the CITES regulation makes it difficult to get nonhuman primate cell lines from researchers outside of the USA, or share our cell lines with them. There’s not any good conservation reason for this.
Thanks for your support! I really think you’re making a great impact here.
I’m sorry to break this to you, but cloning requires live cells, not just DNA. This is one of the reasons why it’s so hard to bring back the woolly mammoth. (The other reason is that it’s really hard to do IVF on elephants.)
So if you want to make a clone, you’ll need to do something like what I did (take cells and preserve them in liquid nitrogen).
Preserving the entire brain is much more difficult than preserving cells, and requires specialized equipment.
I don’t know if targeted crossover is plausibly feasible.
It is definitely feasible. This is how artificial gene drives work.
So that’s why you can’t just make a human baby without knowing what you’re doing: You stand a high risk of making a baby with developmental abnormalities that weren’t severe enough to abort the fetus, but are severe enough that the child is suffering. If for some reason the moral consequences of that aren’t enough to dissuade you, consider that other people would ban you and your children and your children’s children and your artificial children and any similar research for 1000 years.
I cannot overemphasize this!
Phoenix Rising
As a rough estimate, I think 3x to 5x more expensive. Marmosets are smaller (smaller than squirrels) whereas macaques (rhesus/cyno) are about 10x bigger (6 kg). And macaques take longer to develop (3 years vs. 18 months until adulthood). Finally, macaques are in high demand and low supply for pharma research.
But the benefit is that methods developed in macaques are more likely to translate to humans, due to the closer evolutionary relationship. Marmosets are a bit unusual in their embryonic development (two twin embryos share a common, fused placenta!)
Unfortunately monkeys (specifically marmosets) are not cheap. To demonstrate germline transmission (the first step towards demonstrating safety in humans), Sergiy needs $4 million.
And marmosets are actually the cheapest monkey. (Also, as New World monkeys, marmosets are more distantly related to humans than rhesus or cynomolgus monkeys are.)
Ovelle, who is planning to use growth and transcription factors to replicate key parts of the environment in which eggs are produced rather than grow actual feeder cells to excrete those factors. If it works, this approach has the advantage of speed; it takes a long time to grow the feeder cells, so if you can bypass some of that you can make eggs more quickly. Based on some conversations I’ve had with one of the founders I think $50 million could probably accelerate progress by about a year.
A few comments on this:
1. The “feeder cells” you’re discussing here are from the method in this paper from the Saitou lab, who used feeder cells to promote development of human PGC-like cells to oogonia. But “takes a long time to grow the feeder cells” is not the issue. In fact, the feeder cells are quite easy to grow. The issue is that it takes a long time for PGC-like cells to develop to eggs, if you’re strictly following the natural developmental trajectory.2. The $50 million number is for us to set up our own nonhuman primate research facility, which would accelerate our current trajectory by *approximately* a year. On our current trajectory, we are going to need to raise about $5-10 million in the near future to scale up our research. We have already raised $2.15 million and we will start fundraising again this summer. But it’s not like we need $50 million to make progress (although it would certainly help!)
On the topic of SuperSOX and how it relates to making eggs from stem cells:
The requirement for an existing embryo (to transfer the edited stem cells into) means that having an abundant source of eggs is important for this method, both for optimizing the method by screening many conditions, and for eventual use in the clinic.
So, in vitro oogenesis could play a key role here.
For both technologies, I think the main bottleneck right now is nonhuman primate facilities for testing.
Finally: we need to be sure not to cause another He Jiankui event (where an irresponsible study resulted in a crackdown on the field). Epigenetic issues could cause birth defects, and if this happens, it will set back the field by quite a lot. So safety is important! Nobody cares if their baby has the genes for 200 IQ, if the baby also has Prader-Willi syndrome.
I wouldn’t say synthetic biology itself has been a bust. It’s had lots of success in pharma (look at CAR-T, engineered antibodies, gene therapies, etc.) It’s more like, “using synthetic biology to compete with low-margin petrochemicals” has been a bust.
I’m similarly pessimistic about meat produced in cell culture. It’s very hard to compete on price with factory farming. (Stuff like Beyond / Impossible has better prospects though.)
Bottom line up front: with my rough DIY test setup I got 80% filtration with a long beard, 92% with a short one, and 99.7% with stubble.
As a different way of looking at it: a short beard lets 26.7x more particles past than stubble, and a long beard lets 66.7x more particles past.
>Mice lacking the Yap and Taz genes that control liver size have larger livers…but they also have liver cancers, and worse regeneration from liver injury.16 Similarly, mutant mice lacking Hippo signaling have unusually large livers that don’t stop growing when they hit the usual “maximal size”…but they also get lots of liver tumors not seen in wild-type mice.17
Notably, Yap and Taz are downstream mediators of Hippo signaling so these studies are looking at the same thing.
Agreed. Even if this tech gets working, it will be very hard to catch up to photovoltaics.