7 ms·

CRISPR, Gene Drive, and IPSC biotech is incredible. Right now I'm killing time until my residency starts and I've been reading recent journal articles relating

by Para2016 10y ago

CRISPR, Gene Drive, and IPSC biotech is incredible. Right now I'm killing time until my residency starts and I've been reading recent journal articles relating to each of these. One of the weirder journal articles I read was about this one group taking fibroblasts from XX and XO (Turner's syndrome) females and XY cells from a male and de-differntiating them into induced pluripotent stem cells. They then re-differentiated the cells into germ cells. Sure, that's not controversial just yet, but then they decided to put the XX female germ cells into a teste. The female germ cells (XX and XO) and the male XY cells all differentiated into cells that could succesfully undergo meiosis. And these cells, could terminally become sperm. That means an XX skin cell could be induced to become a sperm and possibly fertilize an egg from another woman. Of course all offspring would be XX female. This process totally bypasses males. Anyways, very interesting to me, maybe it will be to others. Here's the journal article. http://www.nature.com/articles/srep06432 http://www.nature.com/articles/srep06432 I know this article I'm posting under is about CRISPR, but I feel like new/controversial biology research could be posted here too. Hopefully anyone reading gets the same feeling of discovery/wonder/incredulity that I had when reading about it.

jwilliams 10y ago
Gene drive is particularly interesting and novel approach... And seems like a huge tarpit for ethics of Gene tech.
Edmond 10y ago
the end of men indeed :) as if being automated out of relevance was not enough soon you can take your sperm with you as you retire to the "manly hills"...interesting times ahead.
- m_mueller 10y ago
  Did you know that fetal viability outside of the womb now starts right after 21 weeks (although with a currently still low chance of survival)? At some point science will probably start figuring out the mechanics of gestation and - eventually - synthesise the whole process, at which point you could call it 'the end of woman' as well. What's left then? Maybe "The Matrix" was quite realistic, only, we're building it ourselves.
  - deleted 10y ago
    [deleted]
tmoot 10y ago
I didn't read the paper but it's in scientific reports (minimal and rushed peer review, bottom of the barrel nature subjournal)...I'd be a bit skeptical. It's not exactly anyone's first choice place to publish. Crispr/Cas9 is not as robust as people make it out to be, but it's promising. (I do some work with crispr/cas9)
- Para2016 10y ago
  It's not the only paper I read regarding IPSC and germ cell induction. The Yamanaka paper has been out since 2007, this kind of work is well established. But, this paper is the only one I can find that has researchers attempting to make sperm from a female. There are other papers regarding iPSCs induced to become female germ cells to oocytes and then IVF producing viable offspring, in mouse, pig, and monkey.
- MegaButts 10y ago
  > Crispr/Cas9 is not as robust as people make it out to be, but it's promising. (I do some work with crispr/cas9) Please expand on this. I feel like CRISPR is being overhyped, and would love to hear form someone educated on the subject as to what its possible limitations are, or at least some of the known challenges ahead.
  - jfarlow 10y ago
    Cas9 is a protein with two functions: 1) locate a DNA sequence that matches the little RNA it grabs ahold of, and 2) cut that DNA at that location. The first of those functions, it's ability to locate particular and arbitrary sequences, is its comparative advantage against all other technologies we know of. The second, cutting DNA, well, works I guess, but will likely be engineered to be more useful, or turned off in order to make way for other more useful functions. The protein is special for two different reasons: 1) it is able to locate DNA sequences with very high precision 2) and the sequence it locates can be swapped out as easily as changing the sequence of the RNA it grabs ahold of (trivial to do, can be done in a day, and can cost >$1 per target sequence to swap). Note, it is not special because it can cut DNA - there are lots of proteins that do that, and there are lots of better ways to change or alter DNA once you get to a particular sequence - but Cas9 was originally a self-defense mechanism, so it's evolutionary function in strep throat bacteria was to kill invaders by dicing up their DNA (at particular sequences that strep throat doesn't have). Cas9 is powerful because it could be used to direct any function at a particular DNA sequence, where the sequence can be altered in the lab quickly and cheaply. As it is a protein encoded by a particular sequence, you can fuse it to other proteins with other functions to build a more powerful machine. (see [1] if you want to play with those sequences yourself.) As an experimental tool it will likely become a foundational tool used all throughout molecular biology - and for that alone is is worth it's fame. Thermophilic polymerase used in PCR is another such tool. As are restriction enzymes. As is GFP. That's the scientist's perspective. However, Cas9 also previews the capability of directly and arbitrarily editing of a genome - a holy grail of biomedical sciences. Though unengineered Cas9 it's not great at editing a genome (we're not entirely sure why what it does even works) - but some 2-10% of the time it can actually edit a genome with fidelity. And that's good enough for many experiments (though not good enough for therapies). It has off-target cuts, and when it cuts it slices all the way through the double stranded DNA, and if it isn't properly stitched back together you have a broken chromosome. And getting payload DNA to the site that Cas9 cut is still really tricky. It's also a multi-part system (it needs it's little RNA as well as the protein itself), and so it's hard to deliver directly as a therapeutic. So the wild-type Cas9 is likely limited in its direct therapeutic relevance in terms of pure genome editing. But it will be used extensively for its ability to 1) further research quickly and cheaply, 2) prototype what genomic changes would do if they were successful (when you only need 10% efficacy to conduct a study), and 3) act as an engineering platform upon which other functions can be placed, and its own wild-type limitations can be overcome. It's powerful. It's not perfect, there's lots more engineering to do with/to it. It's not going to get to the holy grail of genome editing all on its own, but it's a very solid platform to start building off of, as well as simply being a solid tool that will become a workhorse of further synthetic biology. [1] https://serotiny.bio/ https://serotiny.bio/
pottersbasilisk 10y ago
why would we even bother? It makes more sense to create perfect humans and clone from them only in artificial wombs to prevent epigenetic defects.
- Para2016 10y ago
  Well the only clinically significant scenario I can think for this kind of thing is for homosexual partners to reproduce with 50% of the genetic material coming from each partner. Right now one partner contributes 50% of the genetic material and the other partner doesn't get to contribute anything. And creating perfect humans and cloning them in artificial wombs sounds beyond the scope of science at this point. The paper I posted could lead to offspring now (viable or perhaps so epigenetically modified they are doomed -although a germ cell undergoes some demodification in the ovary's environment). It wasn't supposed to be an alternative future for humans (such as perfect humans), although I could see a total female society having less anti-social personality disorders and less violent crime.
  - joaomacp 10y ago
    And less research and innovation
    - jacobush 10y ago
      ... into guns
- no1youknowz 10y ago
  If that actually does happen. Do it in conjunction with backing up the brain. Thus achieving true immortality. Have bodies that are engineered to live forever, but accidents abound. Should anything happen to you, they'll re-clone you and restore the last brain backup. Like the cylons did in Battlestar Galactica. Imagine living for 10s of thousands of years and the only way to truly die is for your genetic material to be disposed of and the backups wiped. If tech like that were available. I'd happily sign up. Travel the stars and explore the unknown!

jwilliams 10y ago

Gene drive is particularly interesting and novel approach... And seems like a huge tarpit for ethics of Gene tech.

Edmond 10y ago

the end of men indeed :) as if being automated out of relevance was not enough soon you can take your sperm with you as you retire to the "manly hills"...interesting times ahead.

m_mueller 10y ago
Did you know that fetal viability outside of the womb now starts right after 21 weeks (although with a currently still low chance of survival)? At some point science will probably start figuring out the mechanics of gestation and - eventually - synthesise the whole process, at which point you could call it 'the end of woman' as well. What's left then? Maybe "The Matrix" was quite realistic, only, we're building it ourselves.
- deleted 10y ago
  [deleted]

tmoot 10y ago

I didn't read the paper but it's in scientific reports (minimal and rushed peer review, bottom of the barrel nature subjournal)...I'd be a bit skeptical. It's not exactly anyone's first choice place to publish. Crispr/Cas9 is not as robust as people make it out to be, but it's promising. (I do some work with crispr/cas9)

Para2016 10y ago
It's not the only paper I read regarding IPSC and germ cell induction. The Yamanaka paper has been out since 2007, this kind of work is well established. But, this paper is the only one I can find that has researchers attempting to make sperm from a female. There are other papers regarding iPSCs induced to become female germ cells to oocytes and then IVF producing viable offspring, in mouse, pig, and monkey.
MegaButts 10y ago
> Crispr/Cas9 is not as robust as people make it out to be, but it's promising. (I do some work with crispr/cas9) Please expand on this. I feel like CRISPR is being overhyped, and would love to hear form someone educated on the subject as to what its possible limitations are, or at least some of the known challenges ahead.
- jfarlow 10y ago
  Cas9 is a protein with two functions: 1) locate a DNA sequence that matches the little RNA it grabs ahold of, and 2) cut that DNA at that location. The first of those functions, it's ability to locate particular and arbitrary sequences, is its comparative advantage against all other technologies we know of. The second, cutting DNA, well, works I guess, but will likely be engineered to be more useful, or turned off in order to make way for other more useful functions. The protein is special for two different reasons: 1) it is able to locate DNA sequences with very high precision 2) and the sequence it locates can be swapped out as easily as changing the sequence of the RNA it grabs ahold of (trivial to do, can be done in a day, and can cost >$1 per target sequence to swap). Note, it is not special because it can cut DNA - there are lots of proteins that do that, and there are lots of better ways to change or alter DNA once you get to a particular sequence - but Cas9 was originally a self-defense mechanism, so it's evolutionary function in strep throat bacteria was to kill invaders by dicing up their DNA (at particular sequences that strep throat doesn't have). Cas9 is powerful because it could be used to direct any function at a particular DNA sequence, where the sequence can be altered in the lab quickly and cheaply. As it is a protein encoded by a particular sequence, you can fuse it to other proteins with other functions to build a more powerful machine. (see [1] if you want to play with those sequences yourself.) As an experimental tool it will likely become a foundational tool used all throughout molecular biology - and for that alone is is worth it's fame. Thermophilic polymerase used in PCR is another such tool. As are restriction enzymes. As is GFP. That's the scientist's perspective. However, Cas9 also previews the capability of directly and arbitrarily editing of a genome - a holy grail of biomedical sciences. Though unengineered Cas9 it's not great at editing a genome (we're not entirely sure why what it does even works) - but some 2-10% of the time it can actually edit a genome with fidelity. And that's good enough for many experiments (though not good enough for therapies). It has off-target cuts, and when it cuts it slices all the way through the double stranded DNA, and if it isn't properly stitched back together you have a broken chromosome. And getting payload DNA to the site that Cas9 cut is still really tricky. It's also a multi-part system (it needs it's little RNA as well as the protein itself), and so it's hard to deliver directly as a therapeutic. So the wild-type Cas9 is likely limited in its direct therapeutic relevance in terms of pure genome editing. But it will be used extensively for its ability to 1) further research quickly and cheaply, 2) prototype what genomic changes would do if they were successful (when you only need 10% efficacy to conduct a study), and 3) act as an engineering platform upon which other functions can be placed, and its own wild-type limitations can be overcome. It's powerful. It's not perfect, there's lots more engineering to do with/to it. It's not going to get to the holy grail of genome editing all on its own, but it's a very solid platform to start building off of, as well as simply being a solid tool that will become a workhorse of further synthetic biology. [1] https://serotiny.bio/ https://serotiny.bio/

pottersbasilisk 10y ago

why would we even bother? It makes more sense to create perfect humans and clone from them only in artificial wombs to prevent epigenetic defects.

Para2016 10y ago
Well the only clinically significant scenario I can think for this kind of thing is for homosexual partners to reproduce with 50% of the genetic material coming from each partner. Right now one partner contributes 50% of the genetic material and the other partner doesn't get to contribute anything. And creating perfect humans and cloning them in artificial wombs sounds beyond the scope of science at this point. The paper I posted could lead to offspring now (viable or perhaps so epigenetically modified they are doomed -although a germ cell undergoes some demodification in the ovary's environment). It wasn't supposed to be an alternative future for humans (such as perfect humans), although I could see a total female society having less anti-social personality disorders and less violent crime.
- joaomacp 10y ago
  And less research and innovation
  - jacobush 10y ago
    ... into guns
no1youknowz 10y ago
If that actually does happen. Do it in conjunction with backing up the brain. Thus achieving true immortality. Have bodies that are engineered to live forever, but accidents abound. Should anything happen to you, they'll re-clone you and restore the last brain backup. Like the cylons did in Battlestar Galactica. Imagine living for 10s of thousands of years and the only way to truly die is for your genetic material to be disposed of and the backups wiped. If tech like that were available. I'd happily sign up. Travel the stars and explore the unknown!