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.
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).
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.
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.
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.
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.
Let's not conflate eugenics with gene editing or "designer babies." On the contrary, there is little overlap between eugenics and any of the three other topics, but for the vaguest vernacular sense.
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
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.
Of course gene editing has the potential to go very wrong, and will almost certainly go very wrong. But trisomy 31 is a well defined genetic defect with heavy consequences on the person having it and his or her entourage and there is no ethics preventing to correct the issue even if the technology used can be also used for nefarious means. It would be like not using dynamite for freeing miners in a collapsing mine because in the future there will be bombs made from dynamite targeting children.
What would be the difference between curing a fetus versus a newborn? Isn't editing out the bad gene better than just aborting gestation? For the person gestating too, since going through an abortion is psychologically damaging
I'm sorry but if elimination of crippling disease sounds like eugenics to you, then you should deeply think about your moral compass. Comparing autism (I guess some mild form since you put it next to ADHD) and ADHD to Down's syndrome shows that you are completely clueless. I'm sorry for the harsh tone but your comment is absolutely awful and has zero empathy towards people (and their caretakers) suffering from condition much worse than what you are going through.
Natural Selection might as well be called Natural Eugenics.
I have people in my family with Downs. It made the early pregnancies for every one of my children a terrifying ordeal. Luckily my children were all born perfectly healthy.
I love my family members with it, but their lives have been so much more difficult than they needed to be. It’s not just massively difficult for the disabled, it financially ruined their parents and their care is also a massive tax burden on the community.
If we can eliminate a crippling disease by “just” turning off a gene we should absolutely do it. The alternative is aborting them as soon as it is detected, and even then it isn’t always caught in-utero.
I have worked with people will all sorts of disabilities my entire life. I can confidently say that if I asked any of my blind or deaf colleagues that if they could take a simple gene therapy so they could see/hear again that they would do it without hesitation. Why would Down Syndrome be any different?
I can’t think of a single valid argument against it other than “eugenics bad”. We aren’t talking about Nazi-era human experimentation here.
Ignore commenters trashing you. It is very ok to have conflicted feelings about something like this. I think this is a good thing but understand where you're coming from. Let me tell you my family's story.
I have a brother with developmental disabilities. Not Down Syndrome, but something similar. He (and I) were lucky enough to be born into an upper-middle class family where my brother went to a school where people were kind to him and where services were available. Despite everything going about as well as it could, it still is a major tax on my family. Constant fund-raising for the home he's living in. Major medical problems through out his life. Things like that. When I agreed to kids with my wife it was on the condition that we do genetic testing and abort the fetus if there was an issue.
My mother has invested her life into this child and loves him more than anything. One day we were talking about death and I casually said something along the lines of "as long as I don't see you at <brother's name> funeral" I'll be ok. Implying she should die first so she doesn't have to deal with the sadness of seeing him die. She then said that she wanted my brother to die first. I was stunned. I asked why. She said she wanted to know he was taken care of. It completely floored me. People with Down's (and similar disabilities) can bring so much joy into this world. They can live very happy lives. I understand how it can be hard for people who don't have my experience to feel like you're feeling. However, I wouldn't wish it on anyone. And I think it's a good thing for society to stop babies being born that are so disabled they'll never be able to take care of themselves.
> 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.
We can discuss pros and cons of freedom of choice of genetics for your children (an opposite spin on the same idea as calling it "designer babies"), but eugenics is a thought-terminating cliche at this point. There's whole space of useful genetics-based treatments and interventions that do not imply involuntary sterilization of people one group deems lesser.
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.
22 comments
[ 6.0 ms ] story [ 51.9 ms ] threadThe 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
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
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
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.
I have people in my family with Downs. It made the early pregnancies for every one of my children a terrifying ordeal. Luckily my children were all born perfectly healthy.
I love my family members with it, but their lives have been so much more difficult than they needed to be. It’s not just massively difficult for the disabled, it financially ruined their parents and their care is also a massive tax burden on the community.
If we can eliminate a crippling disease by “just” turning off a gene we should absolutely do it. The alternative is aborting them as soon as it is detected, and even then it isn’t always caught in-utero.
I have worked with people will all sorts of disabilities my entire life. I can confidently say that if I asked any of my blind or deaf colleagues that if they could take a simple gene therapy so they could see/hear again that they would do it without hesitation. Why would Down Syndrome be any different?
I can’t think of a single valid argument against it other than “eugenics bad”. We aren’t talking about Nazi-era human experimentation here.
I have a brother with developmental disabilities. Not Down Syndrome, but something similar. He (and I) were lucky enough to be born into an upper-middle class family where my brother went to a school where people were kind to him and where services were available. Despite everything going about as well as it could, it still is a major tax on my family. Constant fund-raising for the home he's living in. Major medical problems through out his life. Things like that. When I agreed to kids with my wife it was on the condition that we do genetic testing and abort the fetus if there was an issue.
My mother has invested her life into this child and loves him more than anything. One day we were talking about death and I casually said something along the lines of "as long as I don't see you at <brother's name> funeral" I'll be ok. Implying she should die first so she doesn't have to deal with the sadness of seeing him die. She then said that she wanted my brother to die first. I was stunned. I asked why. She said she wanted to know he was taken care of. It completely floored me. People with Down's (and similar disabilities) can bring so much joy into this world. They can live very happy lives. I understand how it can be hard for people who don't have my experience to feel like you're feeling. However, I wouldn't wish it on anyone. And I think it's a good thing for society to stop babies being born that are so disabled they'll never be able to take care of themselves.
Just my two cents.
We can discuss pros and cons of freedom of choice of genetics for your children (an opposite spin on the same idea as calling it "designer babies"), but eugenics is a thought-terminating cliche at this point. There's whole space of useful genetics-based treatments and interventions that do not imply involuntary sterilization of people one group deems lesser.
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.