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Cersad t1_iw31yul wrote

Reply to comment by Chiperoni in How do medical researchers obtain lab animals with diseases like specific forms of cancer which arise spontaneously? Do they raise thousands of apes and hope some eventually develop the disease? by userbrn1

There have been papers out recently showing CRISPR in primates, so I expect gene edited marmosets or macaques could be feasibly studied these days.

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Chiperoni t1_iw32elo wrote

Oh definitely feasible. We already do it on human cells and even have done it on human embryos. As long as we have the genome sequenced. I just meant more and more people are stepping away from primate research due to ethics and practicality.

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triffid_boy t1_iw3qvhw wrote

It's not the technical difficulty, but the ethical difficulty.

Crispr is already in use in patient cells for things such as Car-t therapy. And we are primates.

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Cersad t1_iw3sn6i wrote

Right, but primates are also the only animal model that is appropriate for more complex etiologies. A genetically-defined model marmoset or macaque of neurological disorders would arguably be a better model than any rodent could aspire to.

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FiascoBarbie t1_iw43vel wrote

For some things. Rodents with Parkinson’s like syndromes have most of the same stuff as humans. Linguistic aphasia’s not so much.

What particular neurological disorders do you think are not well modeled in rodents and what would the better alternative be ?

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Welpe t1_iw4td6q wrote

Linguistic aphasia not so much?! So the rodents could speak perfectly? And here I was thinking all rodents had problems communicating linguistically!

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FiascoBarbie t1_iw5j82l wrote

No, obviously rodents don’t have language so they are not a good model for language problems.

That wasn’t clear when I said they weren’t a good model for linguistic aphasia?

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Delta9ine t1_iw6xhcw wrote

Nah. It was very clear to anyone following the thread who has even the most basic reading comprehension skills.

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triffid_boy t1_iw40zwc wrote

I mean sure, but you said could feasibly be studied since those recent papers - they were feasible models for a long time now.

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Cersad t1_iw422d5 wrote

I thought the CRISPR in primates only dated back to 2018-ish, but my memory could be a bit hazy. In the world of NHP research, six years is less than the useful life of the rhesus macaques I've seen in labs.

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gwaydms t1_iw3s5hv wrote

A young man who had spent much of his life in and out of hospitals with sickle-cell anemia is now being observed for a happier reason: he no longer has the disease. Genetic editing enables him to produce normal red cells. And his germ cells were edited as well, so he doesn't need to worry about having children with SCA.

To him and his family, the risk was worth it. He's just another healthy young man, with the prospect of a normal life.

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triffid_boy t1_iw40t17 wrote

Risk is minimal, I didn't say there was a risk concern?

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Chemputer t1_iwol41l wrote

Yes, we are primates. That's why we call non-human primates "non-human primates" when referring to them in a technical capacity, not necessarily when casually discussing something on Reddit, to avoid confusion.

It is, though, due to ethical reasons, much more practically and technically difficult to work with primates than, say, rodents. Getting any procedure approved on primates is going to be infinitely harder, and involve far more precautions, extra steps, difficulty, etc. than a similar procedure with mice, and be far more limited in number of subjects.

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triffid_boy t1_iwp60md wrote

I think you missed the point of my comment. The implication from the comment I replied to was the technical challenge of Crispr in primates was limiting factor, I used the example of current, clinical, use in humans of Crispr as an argument that it's not a technical limitation that prevents more widespread research in primates.

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Chemputer t1_iwwh6gt wrote

No, I understood what you were saying. I agree with you to a large extent.

I'm simply saying that ethical difficulty and technical difficulty are intrinsically linked. When you have to jump through more hoops for ethical reasons, it makes it more technically difficult.

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wolfgang784 t1_iw3cwvj wrote

There's that Chinese doctor who illegally edited two human babies (twin girls iirc?) with CRISPR in an attempt to make them immune to something, HIV or something along those lines.

Nobody else knew and he lied to the parents about what he was doing, so the study wasn't cut off at an early developmental stage like usual. The news didn't break till after the children were already born, so now they get to enjoy lots of testing and study for the rest of their lives.

So far they seem healthy and like the immunity part indeed worked, but the thing the doctor edited also does/effects more than he knew/expected and it is theorized that the girls may develop/suffer from a different issue (I can't remember what exactly) as a result.

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CrateDane t1_iw3i3q7 wrote

It was a knockout of the gene for CCR5, a coreceptor for (some types of) HIV. That gives resistance to infection. The coreceptor does not seem to be that important, as some people are in fact born without a functional copy of the gene and appear to be normal (aside from resistance to HIV infection).

We just don't really know enough yet to say whether you're better off with or without CCR5, even putting all the ethical issues aside.

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triffid_boy t1_iw3ram7 wrote

CCR5 is useful in cold/flu response and that's a hell of a lot more common than HIV. even in people with close contact with someone with HIV. Hell these days colds and flus are more of a faff than HIV is for those people infected but taking PReP!!

It was such a ludicrously ethically dumb experiment.

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BorneFree t1_iw33ajn wrote

Take a look at Guoping Feng’s Shank3 macaque KO paper

The off target effects make Crispr primates incredibly expensive to make, and an overall inefficient experiment

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Ph0ton t1_iw46mel wrote

Echoing this. CRISPR is a sea change but not a silver bullet. More developments in the vein of CRISPR-Prime will be great for developing models but besides cytotoxicity, currently there is an issue of cell-cycle arrest with most kinds of edits.

This will cause a survivorship bias among edited cells for those that can avoid that checkpoint and/or avoid cell death for critical, off-target effects.

Lots of work is being done though to minimize off-target edits, prevent cell-cycle arrest, and generally make CRISPR safer for therapy. With the millions of tools in nature, it's only a matter of time for us to find and perfect the right one that can make this viable.

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BorneFree t1_iw47e0v wrote

This is interesting I’m actually not well versed in cell cycle arrest in CRISPR editing.

However, regardless of advancements in CRISPR, I don’t think genetically engineered primates will ever become a mainstay of research - the time and expense of generating these animals is exuberant. I have a friend at NIH who occasionally works with primates and the amount of money invested in their primate center is absolutely absurd.

From the time the first embryo is edited, to the F1 generation alone is what, 4-5 years!? It’s just not feasible imo

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Ph0ton t1_iw4949s wrote

That's a good point. Technical limitations are nothing compared to the logistics.

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zebediah49 t1_iw6ci53 wrote

> With the millions of tools in nature, it's only a matter of time for us to find and perfect the right one that can make this viable.

With the millions of tools in nature, our immune systems have acquired methods of defeating a frustratingly large fraction of them.

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