6 ms·

This is absolutely awesome. I look forward to finding out if this has an effect on the germ line as well. Imagine, ending genetic illnesses like these for the r

by foxyv 3y ago

This is absolutely awesome. I look forward to finding out if this has an effect on the germ line as well. Imagine, ending genetic illnesses like these for the rest of human history. I look forward to forgetting these diseases even exist, except in the archives of medical history.

7thaccount 3y ago
I watched a special on this and all interviewed scientists were drastically against any germ line edits (as in something that would then be passed to offspring) as we simply don't understand things well enough yet. Some groups will eventually do this in a less regulated nation, but for now we have to be very careful.
- couchand 3y ago
  "Eventually" already passsed five years ago. https://en.m.wikipedia.org/wiki/He_Jiankui_affair https://en.m.wikipedia.org/wiki/He_Jiankui_affair
  - 7thaccount 3y ago
    I remembered that, but since it was an isolated incident chose to ignore it. I meant at some point China or some other country is going to just give a blanket approval or just not enforce any restrictions and then the game is on.
- foxyv 3y ago
  I imagine this wouldn't be a huge issue with women since they don't produce eggs after birth, but men continue to produce gametes for life. Is there a way to prevent the introduction of the CRISPR edits to spermatocytes? Or do you just have to bank sperm and sterilize as a condition for the treatment?
  - ch4s3 3y ago
    They’re targeting specialized cells that make blood cells outside of the body. Once they’re reimplemented they don’t move around.
    - foxyv 3y ago
      Okay, so they modify outside of the body and then transplant. So that's why it's sickle cell first, because they can do self-transplantation with bone marrow.
  - dekhn 3y ago
    Speaking generally, I think you could perform something like this on sperm stem cells. Sperm turn over (the full population dies and is replaced) fairly quickly, but the stem cells last a long time. It seems more likely they would just, uh, collect a sample of a single sperm cell and treat that, then use it with a treated egg using IVF.
- ch4s3 3y ago
  It seems like we should collectively decide on a reasonable pathway to germ line edits for single gene disorders. If we don’t and keep waiting, someone will do it somewhere. And once the taboo is broken things might get weird in a hurry of the global scientific and medical communities aren’t prepared.
  - JumpCrisscross 3y ago
    > seems like we should collectively decide on a reasonable pathway to germ line edits for single gene disorders Genuine question: why? Isn't the argument against germ-line editing one for diversity? If so, it seems fine to have some populations who ban it while others experiment with it.
    - Nasrudith 3y ago
      The argument I have heard for CRISPR are if I recall correctly more about avoiding mutations from "accidental matches" and what that would do to patients and possible descendants.
- dborzov 3y ago
  These scientists could not publicly and unambiguously condone this for the fear of being singled out and picked out as "playing god" extremists.So they have to say the platitudes about "being careful" and ethical concerns. However, when you suffer all your life from a genetic disease such as, say, the sickle cell or diabetes type 1, it is very obvious that it is any delay or hinderance in this direction that is deeply unethical, not the practice. Your germ line gets hundreds of random mutations at every conception, and your gamets get tons more mutations and errors as you age. It's not a dynasty hairloom.
AlexErrant 3y ago
We could eliminate heart disease, which is still the number 1 killer of men, women, in the US, and globally. https://www.wired.com/story/a-single-infusion-of-a-gene-editing-treatment-lowered-high-cholesterol/ https://www.wired.com/story/a-single-infusion-of-a-gene-edit...
- deleted 3y ago
  [deleted]
- sxg 3y ago
  That trial was specifically for familial types of hypercholesterolemia, which are strongly genetic. Not clear that it would also work for run-of-the-mill high cholesterol, although it is possible.
  - AlexErrant 3y ago
    Fair point. I subscribe to the idea that LDL causes heart disease: > Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel https://pubmed.ncbi.nlm.nih.gov/28444290/ https://pubmed.ncbi.nlm.nih.gov/28444290/ The trial inhibited PCSK9, and this study says "other PCSK9 mutations result in unusually low concentrations of plasma LDL cholesterol and a reduced risk of atherosclerotic disease". https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079795/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079795/ I'm optimistic about this.
    - DoreenMichele 3y ago
      There are other things that also cause heart disease.
      - AlexErrant 3y ago
        As far as I know, ApoB is the only "necessary but not sufficient" molecule, and that's mostly in LDL. There's also IDL and VLDL, but AFAIK those are in insufficient quantities to have clinical significance - please LMK if you know otherwise. There's also Lp(a), but PCSK9 inhibitors also work there: > For PCSK9 inhibitors a small reduction of Lp(a) levels could be shown, which was associated with a reduction in cardiovascular events, independently of the effect on LDL cholesterol. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469722/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469722/ I hate to sound like I'm only focused on PCSK9i - there's also ezetimibe/bempedoic acid/statins, but AFAIK only PCSK9 has been shown to be a viable target of CRISPR. Perhaps that's your point, but I wonder what would happen if we flattened ApoB starting at age, say, 25. Perhaps the residual Lp(a) wouldn't be enough to cause any MACE.
jryb 3y ago
This particular treatment can't. They perform the gene editing on cells outside of the body before transplanting them back into the patient.
tetramer 3y ago
No, this treatment would not - it does not act by "fixing" hemoglobin S (which causes sickle cell disease), but rather increasing production of hemoglobin F (fetal hemoglobin).
imtringued 3y ago
Editing the germline is a terrible idea. Governments should instead fund IVF with genome sequencing of the embryos so that you can pick an embryo that doesn't have the disease. Of course only for people with genetic diseases.

by foxyv 3y ago

7thaccount 3y ago

I watched a special on this and all interviewed scientists were drastically against any germ line edits (as in something that would then be passed to offspring) as we simply don't understand things well enough yet. Some groups will eventually do this in a less regulated nation, but for now we have to be very careful.

couchand 3y ago
"Eventually" already passsed five years ago. https://en.m.wikipedia.org/wiki/He_Jiankui_affair https://en.m.wikipedia.org/wiki/He_Jiankui_affair
- 7thaccount 3y ago
  I remembered that, but since it was an isolated incident chose to ignore it. I meant at some point China or some other country is going to just give a blanket approval or just not enforce any restrictions and then the game is on.
foxyv 3y ago
I imagine this wouldn't be a huge issue with women since they don't produce eggs after birth, but men continue to produce gametes for life. Is there a way to prevent the introduction of the CRISPR edits to spermatocytes? Or do you just have to bank sperm and sterilize as a condition for the treatment?
- ch4s3 3y ago
  They’re targeting specialized cells that make blood cells outside of the body. Once they’re reimplemented they don’t move around.
  - foxyv 3y ago
    Okay, so they modify outside of the body and then transplant. So that's why it's sickle cell first, because they can do self-transplantation with bone marrow.
- dekhn 3y ago
  Speaking generally, I think you could perform something like this on sperm stem cells. Sperm turn over (the full population dies and is replaced) fairly quickly, but the stem cells last a long time. It seems more likely they would just, uh, collect a sample of a single sperm cell and treat that, then use it with a treated egg using IVF.
ch4s3 3y ago
It seems like we should collectively decide on a reasonable pathway to germ line edits for single gene disorders. If we don’t and keep waiting, someone will do it somewhere. And once the taboo is broken things might get weird in a hurry of the global scientific and medical communities aren’t prepared.
- JumpCrisscross 3y ago
  > seems like we should collectively decide on a reasonable pathway to germ line edits for single gene disorders Genuine question: why? Isn't the argument against germ-line editing one for diversity? If so, it seems fine to have some populations who ban it while others experiment with it.
  - Nasrudith 3y ago
    The argument I have heard for CRISPR are if I recall correctly more about avoiding mutations from "accidental matches" and what that would do to patients and possible descendants.
dborzov 3y ago
These scientists could not publicly and unambiguously condone this for the fear of being singled out and picked out as "playing god" extremists.So they have to say the platitudes about "being careful" and ethical concerns. However, when you suffer all your life from a genetic disease such as, say, the sickle cell or diabetes type 1, it is very obvious that it is any delay or hinderance in this direction that is deeply unethical, not the practice. Your germ line gets hundreds of random mutations at every conception, and your gamets get tons more mutations and errors as you age. It's not a dynasty hairloom.

AlexErrant 3y ago

We could eliminate heart disease, which is still the number 1 killer of men, women, in the US, and globally. https://www.wired.com/story/a-single-infusion-of-a-gene-editing-treatment-lowered-high-cholesterol/ https://www.wired.com/story/a-single-infusion-of-a-gene-edit...

deleted 3y ago
[deleted]
sxg 3y ago
That trial was specifically for familial types of hypercholesterolemia, which are strongly genetic. Not clear that it would also work for run-of-the-mill high cholesterol, although it is possible.
- AlexErrant 3y ago
  Fair point. I subscribe to the idea that LDL causes heart disease: > Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel https://pubmed.ncbi.nlm.nih.gov/28444290/ https://pubmed.ncbi.nlm.nih.gov/28444290/ The trial inhibited PCSK9, and this study says "other PCSK9 mutations result in unusually low concentrations of plasma LDL cholesterol and a reduced risk of atherosclerotic disease". https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079795/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079795/ I'm optimistic about this.
  - DoreenMichele 3y ago
    There are other things that also cause heart disease.
    - AlexErrant 3y ago
      As far as I know, ApoB is the only "necessary but not sufficient" molecule, and that's mostly in LDL. There's also IDL and VLDL, but AFAIK those are in insufficient quantities to have clinical significance - please LMK if you know otherwise. There's also Lp(a), but PCSK9 inhibitors also work there: > For PCSK9 inhibitors a small reduction of Lp(a) levels could be shown, which was associated with a reduction in cardiovascular events, independently of the effect on LDL cholesterol. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469722/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469722/ I hate to sound like I'm only focused on PCSK9i - there's also ezetimibe/bempedoic acid/statins, but AFAIK only PCSK9 has been shown to be a viable target of CRISPR. Perhaps that's your point, but I wonder what would happen if we flattened ApoB starting at age, say, 25. Perhaps the residual Lp(a) wouldn't be enough to cause any MACE.

jryb 3y ago

This particular treatment can't. They perform the gene editing on cells outside of the body before transplanting them back into the patient.

tetramer 3y ago

No, this treatment would not - it does not act by "fixing" hemoglobin S (which causes sickle cell disease), but rather increasing production of hemoglobin F (fetal hemoglobin).

imtringued 3y ago

Editing the germline is a terrible idea. Governments should instead fund IVF with genome sequencing of the embryos so that you can pick an embryo that doesn't have the disease. Of course only for people with genetic diseases.