3 ms·

w/r/t the HIV thing - there are HIV immune populations in Scandinavia who have a natural mutation affecting CCR5, so there is at least some reason to believe it

w/r/t the HIV thing - there are HIV immune populations in Scandinavia who have a natural mutation affecting CCR5, so there is at least some reason to believe it’s safe to edit or knock out. https://pubmed.ncbi.nlm.nih.gov/14636691/ https://pubmed.ncbi.nlm.nih.gov/14636691/

pazimzadeh 1y ago
That is interesting. Do Scandinavians have compensatory mutations on other proteins, which allows them to have a mutant CCR5? Presumably CCR5 exists for reason other than attracting HIV.
- philipov 1y ago
  It's dangerous to assume that everything in biology exists because it's useful in some way. Some things are just spandrels* that came along for the ride, vestigial, or otherwise neutral features. Not everything exists because it provides an evolutionary advantage. *: https://en.wikipedia.org/wiki/Spandrel_(biology) https://en.wikipedia.org/wiki/Spandrel_(biology)
  - jl6 1y ago
    If you’re going to assume something, assuming neutrality seems the more dangerous assumption. Chesterton’s gene.
  - pazimzadeh 1y ago
    If a receptor is used as an entry point by a common virus and disabling it prevents infection but evolution has kept it around (cells spend energy actively expressing it, not having it encoded in the genome) then you can assume that there is a function provided by the receptor. Turns out, CD163 already has a known function. A spandrel not only has to have obvious function but removing it has to not be detrimental. I'm questioning the bar that is being used to say that it's not detrimental. Unless humanity was on the brink of starvation and this was the only known way to increase food production then no it's not dangerous to be cautious. On the other hand, I think it's dangerous to assume that a protein only has one function https://en.wikipedia.org/wiki/Protein_moonlighting https://en.wikipedia.org/wiki/Protein_moonlighting
- arrosenberg 1y ago
  I don’t believe so. I looked into it a bit more, and it looks like homozygous variant carriers are more susceptible to other types of infection (West Nile is specifically cited), but I don’t see anything showing the variant causes issues with CCR5s other critical functions. I do think a knockout is probably a bad idea based on further reading, but modification seems like a promising path.
  - pazimzadeh 1y ago
    I meant a compensatory mutation on another receptor or protein besides CD163. I kinda meant it rhetorically. It's not an easy thing to answer.

pazimzadeh 1y ago

That is interesting. Do Scandinavians have compensatory mutations on other proteins, which allows them to have a mutant CCR5? Presumably CCR5 exists for reason other than attracting HIV.

philipov 1y ago
It's dangerous to assume that everything in biology exists because it's useful in some way. Some things are just spandrels* that came along for the ride, vestigial, or otherwise neutral features. Not everything exists because it provides an evolutionary advantage. *: https://en.wikipedia.org/wiki/Spandrel_(biology) https://en.wikipedia.org/wiki/Spandrel_(biology)
- jl6 1y ago
  If you’re going to assume something, assuming neutrality seems the more dangerous assumption. Chesterton’s gene.
- pazimzadeh 1y ago
  If a receptor is used as an entry point by a common virus and disabling it prevents infection but evolution has kept it around (cells spend energy actively expressing it, not having it encoded in the genome) then you can assume that there is a function provided by the receptor. Turns out, CD163 already has a known function. A spandrel not only has to have obvious function but removing it has to not be detrimental. I'm questioning the bar that is being used to say that it's not detrimental. Unless humanity was on the brink of starvation and this was the only known way to increase food production then no it's not dangerous to be cautious. On the other hand, I think it's dangerous to assume that a protein only has one function https://en.wikipedia.org/wiki/Protein_moonlighting https://en.wikipedia.org/wiki/Protein_moonlighting
arrosenberg 1y ago
I don’t believe so. I looked into it a bit more, and it looks like homozygous variant carriers are more susceptible to other types of infection (West Nile is specifically cited), but I don’t see anything showing the variant causes issues with CCR5s other critical functions. I do think a knockout is probably a bad idea based on further reading, but modification seems like a promising path.
- pazimzadeh 1y ago
  I meant a compensatory mutation on another receptor or protein besides CD163. I kinda meant it rhetorically. It's not an easy thing to answer.