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A lot of the graphics that explain how CRISPR work show this very careful snipping of a strand of DNA. Tiny little scissors making pinpoint accuracy revisions.
by mmcclure 2y ago
A lot of the graphics that explain how CRISPR work show this very careful snipping of a strand of DNA. Tiny little scissors making pinpoint accuracy revisions. I think that's lead to a deep misunderstanding for most people (including myself) on how this technology actually works.
CRISPR is amazing, but it's still a fairly blunt tool. The article talks about one way: guide RNA can often bind to sequences that are very similar to the intended sequence, but not exactly, meaning it's probable that for every intended cut you're making several unintended ones. The "scissor" action itself, Cas9 protein, is less like a scissor cut and more like a jagged tear, which can damage surrounding DNA.
The repair pathways themselves are also imperfect. It's not a copy/paste like infographics show, it's more like emergency duct taping broken ends together.
All of that stuff combined...Again, amazing technology, but I get extremely nervous when I hear people talk about introducing CRISPR-based gene editing into the human gene pool. The generational effects there are still entirely unpredictable at this stage, could be disastrous, and any actual paths to trying to roll things back would be deeply ethically fraught.
- aliasxneo 2y ago> the generational effects there are still entirely unpredictable at this stage Something I've always wondered about CRISPR. It seems the legal case for introducing it is the freedom to perform "body hacking" on yourself. But, at least in this case, isn't it more like "generational hacking?" Maybe I am fundamentally misunderstanding the technology, but it's strange to think about what sort of protections should be put in place to prevent someone being born with severe defects due to messing with the genome.
- dghlsakjg 2y agoI'm not sure about that... Isn't restricting people from reproducing based on their genetic material known as Eugenics?
- mmcclure 2y agoThis is the "ethically fraught" bit I was referencing. Once this genie is out of the bottle and into the gene pool, there's effectively no moral/ethical path to putting it back in.
- aliasxneo 2y agoThis certainly highlights the problem. For context, I wasn't suggesting eugenics, although I suppose that's one way to enforce things (one I would never support, anyways).
- Terr_ 2y agoThought-experiment: Someone modifies their gametes for gene-drive extinction. [0] Failure to disclose it to every potential partner and descendant would be a very serious kind of fraud or potentially child-abuse. [0] https://www.scientificamerican.com/article/gene-drives-could-fight-malaria-and-other-global-killers-but-might-have-unintended-consequences/ https://www.scientificamerican.com/article/gene-drives-could...
- noch 2y ago> Isn't restricting people from reproducing based on their genetic material known as Eugenics? We really need to stop being afraid of words. We don't have to use a neutral word to imply a whole range of ancillary things which we don't name. There's nothing wrong, in principle, with eugenics. (Some bad guys many years ago were really into it for a specific use case, but so what?) While humanity is in the learning phase of gene editing: - High-trust societies can choose to say: "You can get whatever gene mods you want but you will be sterilized." - In freedom societies you could simply ask your partner what modifications she has before you conceive kids with her. Screening and embryo selection would probably be available in such a world and individuals would make their choices.
- pbmonster 2y ago> the freedom to perform "body hacking" on yourself. But, at least in this case, isn't it more like "generational hacking?" The latter would certainly be much easier than the former. But especially people who don't work in bio dream about hand-wavy future biotech that does things like using a virus vector to spread a CRISP/CAS9 payload to all relevant cells in an adult body, and performs in vivo edits.
- ANewFormation 2y agoI'm extremely bearish on genetic tweaking as I think longterm unforseen consequences are essentially guaranteed, but I don't find this exact issue to be much of a problem. It's 100% legal to drink/smoke/etc to your heart's content while pregnant, so I think individual liberty still unambiguously wins here.
- jpalawaga 2y agoPeople like to compare CRISPR as scissors or cut/copy-and-replace, but people should think of it more as 'find and replace all'. in that context, it's much more understandable why the tool has drawbacks.
- mmcclure 2y agoYeah, better analogy, but still a little flawed because that still makes it seem much better/precise than it is. It's "find and replace all" that might: - occasionally match very similar, but not exact text - will often subtly alter the text around the replacement area, either by deleting characters or altering others.
- albertgoeswoof 2y agoIt’s more like pasting your genome into chatgpt and asking it to fix it
- 9dev 2y agoSounds like my junior developer copy-pasting regular expression parts from stack overflow and pressing replace all while not really understanding what the funky character soup actually does. That fits your description pretty nicely
- fastball 2y agoIt's find-replace-all, but instead of being exact string matching, CRISPR uses somewhat imprecise RegEx.
- ttyprintk 2y agoProblems in repair pathways are underappreciated. The mutations causing breast cancer, and Huntington’s disease, for example. Advancements in treating those will be advancements in CRISPR.