CRISPR takes important step toward silencing Down syndrome’s extra chromosome

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aamichail about 22 hours ago 125 commentsRead Article on medicalxpress.com

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bonsai_spool•about 20 hours ago

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.

[1] https://www.pnas.org/doi/10.1073/pnas.2517953123

sheept•about 12 hours ago

> 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).

dreamcompiler•about 11 hours ago

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.

https://www.youtube.com/watch?v=BD6h-wDj7bw&t=225s

rendaw•about 10 hours ago

That video seems to imply you can't see it under any light and the image there is pure visualization.

bonzini•about 9 hours ago

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?

shevy-java•about 10 hours ago

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.

shevy-java•about 10 hours ago

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.

samus•about 5 hours ago

Presumably by targeting them toward these differences.

voidUpdate•about 6 hours ago

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

Tade0•about 5 hours ago

Not to downplay your situation, but this is Down's syndrome we're talking about, so a whole menagerie of both physical and mental conditions, including, but not limited to: higher risk of epilepsy and heart failure, aside from almost universal infertility in men.

It's a serious disability even today decreasing life expectancy by 10-15 years.

One may have different opinions regarding the quality of life of these people while they're alive, but I think we can agree that 60 years is a short lifespan for a human.

EDIT: also main point of eugenics, which seems to be not widely understood, was that the state would decide both what kind of children are born and who gets to have them. It was not unheard of to take sufficiently "aryan"-looking newborns from their "inferior race" parents and give them to "master race" adoptive parents.

This lack of agency on part of biological parents is a core tenet of eugenics.

dpiers•about 6 hours ago

We already live in a world where parents decide whether or not a child with Down Syndrome will be born.

60-90% of prenatal diagnoses in the US result in an elective termination. The number is nearly 100% in Iceland and some other Nordic countries. Unlike autism or ADHD, we have a very clear understanding of exactly what causes Down Syndrome and now potentially how to correct it. A treatment like this is no different from correcting a congenital heart defect - it gives a baby a chance at normal, healthy development.

fainpul•about 5 hours ago

I understand the concerns, but some things just make life much harder. I would definitely want to spare my child from living with autism, ADHD and certainly Down syndrome, given the choice. It's not like we're talking about choosing eye color, height or gender here.

c048•about 6 hours ago

The full diversity of life sounds wonderful, as long as you're not the one suffering painful, disfiguring or crippling conditions.

voidUpdate•about 5 hours ago

I am the one suffering from multiple of those conditions

anhner•about 5 hours ago

I'm sorry to hear that. So would you like others to suffer from them as well if given the choice?

mkesper•about 6 hours ago

You got to weigh this against abortions for unborn children diagnosed (maybe even wrongly, the tests are really not that exact) with Down's syndrome. The slippery slope already began a long time ago probably.

robertjpayne•about 5 hours ago

By week 20 there is practically no chance you're not going to know if you're carrying a baby with downs or not unless you refuse all the modern screening/tests available.

NIPT tests can be done at week 8 and give a very high indicator that can be followed up with close monitoring/invasive tests at week 14-15 that give a 99% accuracy. That's hardly "are really not that exact".

exe34•about 6 hours ago

I've always thought we should maintain a list of people like you. Every time we cure something, like blindness in one person, one of you gets picked and your eyes get poked out. That way the total amount of suffering will be conserved, but those who think that's necessary get to be the ones who pay the price for their beliefs.

voidUpdate•about 6 hours ago

In the first half of my comment, I explained that I don't think people should suffer. I'm just also aware that if everyone can pick their child's attributes, it could lead to a nation of blond-hair, blue-eyes kids

mmustapic•about 5 hours ago

Would you pick blond hair, blue eyes for your kids? Would black people pick it? Asian?

lofaszvanitt•about 5 hours ago

What are you talking about? WHAT are you talking about?

equinox6380•about 3 hours ago

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.

Metacelsus•about 14 hours ago

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.

russdill•about 14 hours ago

My understanding is that crispr is less like a scalpel and more like a chainsaw. Great care just be taken to avoid introducing cancer causing mutations.

colechristensen•about 12 hours ago

I wouldn't characterize it like that. It makes mistakes. It's a scalpel in shaky hands. When it works correctly it is very precise but just not 100% reliably.

in vitro there are various techniques where you use crispr on a cell line and then purify it by killing off the cells with errors and only then implant them

in vivo... well there are errors and among other effects are potential cancer

shevy-java•about 10 hours ago

But this has the same problem as before - how can you ensure that only one X-chromosome is killed off? Or at the least one?

irjustin•about 14 hours ago

I wondered the same thing and according to Gemini a chromosome is massive vs a few genes. Cutting it out with crispr is possible, but it's too big of a change and would lead to cell death rendering whatever change either useless or kills the host given the possible stage this treatment could be delivered at.

samus•about 5 hours ago

Since the presence of that chromosome causes problems in an organism that functions normally with just two of these chromosomes, the change is actually not that big. And the therapy might also not be intended for adults or even children - most of the developmental impediments have already happened at that stage, and neither cutting out the extra chromosome or silencing it will fix this up.

kriro•about 7 hours ago

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.

Cthulhu_•about 5 hours ago

Cloning isn't even sci-fi or imaginary, just morally questionable and... variably legal (https://en.wikipedia.org/wiki/Human_cloning#Legal_status_of_...). Same goes for gene editing / designer babies / eugenics, which overlaps strongly with the subjects in this discussion.

shevy-java•about 10 hours ago

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.

https://en.wikipedia.org/wiki/XIST

memonkey•about 20 hours ago

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).

hgoel•about 11 hours ago

Recognizing that certain mutations very blatantly reduce a person's quality of life and making it possible to revert those mutations does not require treating the people who have not had those mutations reverted as lesser.

Thinking of them as lesser leads to a society that prefers to drag each other down instead of lifting each other up.

TurdF3rguson•about 10 hours ago

I don't know about this argument because they seem a lot happier than I am.

That's not to say that it's unreasonable to value intelligence over happiness, but framing it as quality of life seems off.

amunozo•about 7 hours ago

I had a uncle with Down syndrome. He was the sweetest and funniest person, we remember him every day more than 10 years after he passed away. Down syndrome carries a lot of physical health problems like heart or lung diseases which make their life very painful. He suffered from lung problems since he was 18 until he passed away at 49, living in a lot of pain and being a big burden to my mum and my grandma, who took care of him. Still, it's true, he never lost his smile and love her sister and mother back as much as it's possible, giving all of us who lived with him a lot of joy.

I am very conflicted with these kind of issues, but I think I am of the opinion that it's better to prevent this suffering, but once they're already here we should make their life as easier as possible.

wqaatwt•about 8 hours ago

That’s still eugenics, though. Except this time it’s not pseudoscience.

RobotToaster•about 7 hours ago

Until a certain Austrian painter decided to practice eugenics in a uniquely negative way, the term was value neutral.

The motor bus was hailed as a eugenic invention because it helped prevent inbreeding in small villages, for instance.

colechristensen•about 12 hours ago

There are arguments about various "conditions" being diseases or not, Down Syndrome really isn't one of them.

AussieWog93•about 9 hours ago

The grilled cheese sandwich industry are going to be fighting this tooth and nail.