This is very clever - the X chromosome has a mechanism to shut itself down (which makes sense; otherwise cells in women would have twice as many gene products from the X chromosome as cells from men).
The linked research report[1] uses that mechanism, Xist, to shutdown chromosome 21, the extra chromosome whose presence causes Down syndrome. In its present form, it would need to be optimized for each potential patient and is unlikely to be used as a treatment paradigm, but the biological approach is clever.
> the X chromosome has a mechanism to shut itself down (which makes sense; otherwise cells in women would have twice as many gene products from the X chromosome as cells from men).
You can see this visually because not the same X chromosome is deactivated in all cells: it's what gives calico cats their color (almost all of them are female).
Human women have stripey skin too, but you can't see it under normal light because unlike cats, skin tone in humans is not controlled by the X chromosome.
Can you link to a scientific article? I have severe doubts about that claim made on a random youtube video. In fact, I'd go as far as to claim that the content of the words here, are not correct. This is why I think a doi link to a research paper is necessary. I don't doubt that individual cells are, of course, chimeric, but I doubt the "stripey skin" claim. That one makes zero sense.
I just did a google search and this further confirms my suspicion. Thus I would like to ask for a link to a scientific article - until that happens I remain rather unconvinced.
> Human women have stripey skin too, but you can't see it under normal light because unlike cats, skin tone in humans is not controlled by the X chromosome.
Humans have 'stripey' skin because of somatic mutations, and it's not clear that there are X-chromsome-located skin color loci. Don't believe everything you see on Youtube.
For a more practical example, how does this work for the daughter of a colorblind person (the colorblindness gene is on the X chromosome)? Do they have four types of cones?
And how do they ensure that only one X chromosome is inactivated? All three X chromosomes are, for the most part, equal, neglecting differences between father and mother X chromosome and changes during meiosis.
I have very conflicted feelings about this sort of thing. On the one hand, Down's syndrome can make life very hard, for both the person with it, and their carers and the people around them. I can imagine that some people would have preferred it if they were able to "cure" it. I've often felt in the past that I would have preferred to have been born without autism and ADHD, and while I've been coping a little better with it nowadays, it definitely had a large impact on my childhood, and I know my parents struggled with it a lot.
On the other hand, this feels a bit like eugenics, and a slippery slope towards designer babies where you can pick and choose their attributes. I'm of the opinion that we should embrace the full diversity of human life, and if you can just cut out the parts of your children you don't like, that feels quite iffy to me
After skimming through, one obvious question follows:
How can they ensure that (only) one out of three chromosomes only, have XIST integrated? (I assume they can target these three chromosomes due to the CRISPR RNA.)
So down syndrome is trisomy 21, aka three chromosomes 21. Say you have to modify a billion cells, just to give a number. Well, how can you ensure that all those have one XIST gene that is also active (otherwise it would be pointless; XIST produces a RNA which in turn silences the X chromosome by coating it)? Inserting new genes is nothing new, that is already ancient technology at this point in time.
If they're going to all that effort to make allele-specific guides why not just cut out the centromere and eliminate the chromosome entirely? This seems like an overly complicated solution.
hgoel 2 minutes ago | parent | context | on: CRISPR takes important step toward silencing Down ...
I chose to call it quality of life because I don't think that simply being happy is enough to have quality of life, but I don't agree that it's about valuing intelligence over happiness.
It's a condition they, and their family, have to live with their entire life. You can't really be permanently sad about a condition you have literally been born with and can't expect to change.
Meanwhile, there are conditions that significantly decrease quality of life even though one's intelligence is unaffected. I think the factor is better described as choice. There are a large number of things a person with Downs just does not have the choice to do differently.
Great achievement. Sometimes I imagine a world where the LLM-money, will and time was funneled into more aggressive CRISPR research and medical advances in general. If I want to go full sci-fi I even imagine cloning.
I am slightly reminded of Gattaca, the story of which is that certain people are discriminated based on their DNA. Society is built, in general, excluding certain people due to their disabilities. Whether or not a blind person can find meaning or enjoy life has road blocks but is not impossible. Science can provide technologies to potentially improve people's lives -- cochlear implants for those with hearing loss, for example. There are ongoing philosophical discussions of whether or not these technologies and scientific discoveries are actually harming or helping those with these disabilities and the broader discussion of 'normalizing' society at large (I don't want to use the term eugenics).
142 comments
The linked research report[1] uses that mechanism, Xist, to shutdown chromosome 21, the extra chromosome whose presence causes Down syndrome. In its present form, it would need to be optimized for each potential patient and is unlikely to be used as a treatment paradigm, but the biological approach is clever.
[1] https://www.pnas.org/doi/10.1073/pnas.2517953123
> the X chromosome has a mechanism to shut itself down (which makes sense; otherwise cells in women would have twice as many gene products from the X chromosome as cells from men).
You can see this visually because not the same X chromosome is deactivated in all cells: it's what gives calico cats their color (almost all of them are female).
https://www.youtube.com/watch?v=BD6h-wDj7bw&t=225s
I just did a google search and this further confirms my suspicion. Thus I would like to ask for a link to a scientific article - until that happens I remain rather unconvinced.
Here's one link:
https://www.sciencedirect.com/science/article/abs/pii/S07380...
I haven’t read it but I did find this
> Human women have stripey skin too, but you can't see it under normal light because unlike cats, skin tone in humans is not controlled by the X chromosome.
Humans have 'stripey' skin because of somatic mutations, and it's not clear that there are X-chromsome-located skin color loci. Don't believe everything you see on Youtube.
On the other hand, this feels a bit like eugenics, and a slippery slope towards designer babies where you can pick and choose their attributes. I'm of the opinion that we should embrace the full diversity of human life, and if you can just cut out the parts of your children you don't like, that feels quite iffy to me
How can they ensure that (only) one out of three chromosomes only, have XIST integrated? (I assume they can target these three chromosomes due to the CRISPR RNA.)
So down syndrome is trisomy 21, aka three chromosomes 21. Say you have to modify a billion cells, just to give a number. Well, how can you ensure that all those have one XIST gene that is also active (otherwise it would be pointless; XIST produces a RNA which in turn silences the X chromosome by coating it)? Inserting new genes is nothing new, that is already ancient technology at this point in time.
https://en.wikipedia.org/wiki/XIST
I chose to call it quality of life because I don't think that simply being happy is enough to have quality of life, but I don't agree that it's about valuing intelligence over happiness. It's a condition they, and their family, have to live with their entire life. You can't really be permanently sad about a condition you have literally been born with and can't expect to change.
Meanwhile, there are conditions that significantly decrease quality of life even though one's intelligence is unaffected. I think the factor is better described as choice. There are a large number of things a person with Downs just does not have the choice to do differently.