I believe that the CRISPR cost is for treating an already existing adult, and that it would be much cheaper to do it for a newly fertilised egg that is about to implanted as a pregnancy. Looking to the future we could also hope that CRISPR will get cheaper.
The point about creating other problems sounds like it could be a real issue unless people are very careful. Maybe you have good data for identifying medical problems, but not knowing the causal pathway means weird stuff can happen. Lets say their is a gene that effects your sense of taste in such a way as to ruin (or significantly hamper) your enjoyment of food. That gene might anti-correlate with diabetes, but you probably wouldn’t want it.
The point about creating other problems sounds like it could be a real issue unless people are very careful. Maybe you have good data for identifying medical problems, but not knowing the causal pathway means weird stuff can happen. Lets say their is a gene that effects your sense of taste in such a way as to ruin (or significantly hamper) your enjoyment of food. That gene might anti-correlate with diabetes, but you probably wouldn’t want it.
I wouldn’t be suprised to find isolated examples like this, but if it were the case in general we’d expect to see people with low genetic risk scores for diabetes to have noticeably worse outcomes in some other area. And that’s just not what we see.
Frankly, the same can be said for a lot of other traits as well; to the degree that we do see plietropy (i.e. one gene having two effects), it tends to work in our favor: for example there are some genetic variants that both decrease risk of hypertension and decrease risk of heart attack.
I believe that the CRISPR cost is for treating an already existing adult, and that it would be much cheaper to do it for a newly fertilised egg that is about to implanted as a pregnancy. Looking to the future we could also hope that CRISPR will get cheaper.
But then people need to preemptively decide to get IVF, going though all the related pains and troubles, because they sequenced their genomes and realized that one of them carries a gene that might increase that risk of diabetes by 0.3% (and do some other things we are not sure of). It’s still a huge cost, time investment, effort investment, and quality of life sacrifice—IVF isn’t entirely risk-free and there are several invasive procedures involved for the woman. It’s again not obvious why would they do this if the payoff isn’t really worth it.
All true. But, sometimes people are having IVF anyway, for fertility or other reasons, and in that case the argument for doing it is stronger. Also, I am not advocating that you go in and change one gene to reduce the diabetes chance by 0.3%. If you are doing anything at all you are changing many genes, so that the overall change of diabetes is cut by some larger percentage, and the chance of cancer is reduced similarly, and the chance of …
To clarify, I am in no way saying that the current offering is anywhere near being worth the current price for the typical person. I am speculating that in the future the offerings will be more attractive (more diseases reduced by larger percentages) at lower prices, and that there are some atypical scenarios (eg. if you have an awful genetic disease, or are having IVF anyway) where the gap to “worth it” will close relatively fast.
But the reasonable for being careful about this stuff aren’t unfounded. Not only if we don’t get precisely the function of each gene this could cause side effects of arbitrary seriousness, but the child is then stuck with them for life and would potentially pass them to their descendants. Now perhaps we should consider gene therapy more than we are now but it’s far from a “go to the lab and start deploying it now” affair anyway.
I actually think we can pretty much eliminate the risk of arbitrarily large side-effects. There are databases of known genetic variants that cause serious illness or death. As long as you can avoid edits to those varaints you should be fine.
Nearly all the variants you would target are present in at least 1% of some reference population, so the maximum “downside” would be the sum of the differences between that reference populations lives and those without the variant for all variants you edit (plus any effects from off-targets).
Off targets ARE a concern, but there are ways to significantly reduce the risk of such edits. For example if you want to change a sequence AAA to AGA, you’re better off using a prime editor to avoid bystander edits that are common among base editors (at least you’re better off if bystander edits are actually a concern)
so the maximum “downside” would be the sum of the differences between that reference populations lives and those without the variant for all variants you edit (plus any effects from off-targets)
I don’t think that’s true? It has to assume the variants don’t interact with each other. Your reference population would only have 0.01% people with (the rarest) 2 variants at once, 0.0001% with 3 variants, and so on.
If you were to do gene editing on embryos you wouldn’t just target one gene. That would make no sense. You’d target hundreds or maybe even thousands in order of importance. At scale it could actually work assuming you can solve other issues related to off-target editing.
I believe that the CRISPR cost is for treating an already existing adult, and that it would be much cheaper to do it for a newly fertilised egg that is about to implanted as a pregnancy. Looking to the future we could also hope that CRISPR will get cheaper.
The point about creating other problems sounds like it could be a real issue unless people are very careful. Maybe you have good data for identifying medical problems, but not knowing the causal pathway means weird stuff can happen. Lets say their is a gene that effects your sense of taste in such a way as to ruin (or significantly hamper) your enjoyment of food. That gene might anti-correlate with diabetes, but you probably wouldn’t want it.
I wouldn’t be suprised to find isolated examples like this, but if it were the case in general we’d expect to see people with low genetic risk scores for diabetes to have noticeably worse outcomes in some other area. And that’s just not what we see.
Frankly, the same can be said for a lot of other traits as well; to the degree that we do see plietropy (i.e. one gene having two effects), it tends to work in our favor: for example there are some genetic variants that both decrease risk of hypertension and decrease risk of heart attack.
But then people need to preemptively decide to get IVF, going though all the related pains and troubles, because they sequenced their genomes and realized that one of them carries a gene that might increase that risk of diabetes by 0.3% (and do some other things we are not sure of). It’s still a huge cost, time investment, effort investment, and quality of life sacrifice—IVF isn’t entirely risk-free and there are several invasive procedures involved for the woman. It’s again not obvious why would they do this if the payoff isn’t really worth it.
All true. But, sometimes people are having IVF anyway, for fertility or other reasons, and in that case the argument for doing it is stronger. Also, I am not advocating that you go in and change one gene to reduce the diabetes chance by 0.3%. If you are doing anything at all you are changing many genes, so that the overall change of diabetes is cut by some larger percentage, and the chance of cancer is reduced similarly, and the chance of …
To clarify, I am in no way saying that the current offering is anywhere near being worth the current price for the typical person. I am speculating that in the future the offerings will be more attractive (more diseases reduced by larger percentages) at lower prices, and that there are some atypical scenarios (eg. if you have an awful genetic disease, or are having IVF anyway) where the gap to “worth it” will close relatively fast.
But the reasonable for being careful about this stuff aren’t unfounded. Not only if we don’t get precisely the function of each gene this could cause side effects of arbitrary seriousness, but the child is then stuck with them for life and would potentially pass them to their descendants. Now perhaps we should consider gene therapy more than we are now but it’s far from a “go to the lab and start deploying it now” affair anyway.
I actually think we can pretty much eliminate the risk of arbitrarily large side-effects. There are databases of known genetic variants that cause serious illness or death. As long as you can avoid edits to those varaints you should be fine.
Nearly all the variants you would target are present in at least 1% of some reference population, so the maximum “downside” would be the sum of the differences between that reference populations lives and those without the variant for all variants you edit (plus any effects from off-targets).
Off targets ARE a concern, but there are ways to significantly reduce the risk of such edits. For example if you want to change a sequence AAA to AGA, you’re better off using a prime editor to avoid bystander edits that are common among base editors (at least you’re better off if bystander edits are actually a concern)
I don’t think that’s true? It has to assume the variants don’t interact with each other. Your reference population would only have 0.01% people with (the rarest) 2 variants at once, 0.0001% with 3 variants, and so on.
If you were to do gene editing on embryos you wouldn’t just target one gene. That would make no sense. You’d target hundreds or maybe even thousands in order of importance. At scale it could actually work assuming you can solve other issues related to off-target editing.