Genetic Engineering and unknown consequences

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J11
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Re: Genetic Engineering and unknown consequences

Post by J11 »

Yes, Brian4, this is quite correct.

Those with a simple minded "this variant good this variant bad" mentality have no understanding of human genetics.
It is more that existing human genetic variation is what gives the opportunity for natural selection and evolution.
Even with our current technology we simply have no idea how to go about finding the variants that will move our species forward.
All gene editing does is take what what nature has provided us.

I am also aware of the intelligence paradox, though I am not sure whether others are.
The current decline in global IQ could be understood as an evolutionary life boat to preserve the continued existence of humanity.

The current decrease in genetic intelligence should eventually bring us back to a more sustainable fertility rate.
However, with our new genetic technology people likely will have substantial ability to thwart the mechanism that
is trying to save our species.

Looked through one of our exome files for the CCR genes. Amazing how many different things can happen with own variant.
One of the variants produced:
more rapid progression to full-blown AIDS and probably increased susceptibility to HIV infection
-Ow, that sounds bad.

But the next annotation was:
reduced risk of acute coronary events

Yeah! That sounds good. I call it a net positive.

But then,
increased risk of age related macular degeneration

Boo, I am still net positive, though somewhat less positive.

And then,
reduced anti-fungal immune response in Crohn's disease patients, at least for minor allele homozygotes

Not sure what to make of this one.

Yes, the medical significance of variants is much more nuanced than a family brawl.
Last edited by J11 on Sat Dec 01, 2018 6:20 pm, edited 1 time in total.
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Rainbow
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Re: Genetic Engineering and unknown consequences

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Brian4 wrote:The empirical evidence – the Fermi Paradox – suggests that at a certain level of development, civilizations may just end. (May – or they ALL become silent, which seems unlikely.) Whether they end after a massive increase in intelligence (the term singularity seems wrong to me) or not, I have no idea. But I'm (barely) young enough to suspect that worrying about dementia is the least of my concerns. By the 2030s or -40s, I think, in all seriousness, the more serious threat will be hyperintelligent machines, most likely created in part by accident (self-learning voice recognition programs or something). So, myself, I think there will be a massive increase in intelligence (almost certainly machine intelligence), but I fear it will only go a bit beyond the level of the smartest humans before it becomes an insane nihilist and destroys itself and everything around it. I really hope I'm wrong, of course!
Thanks, never thought of the Fermi Paradox like this before. And I agree that "singularity" seems like a bad word choice! :?

I'll write down "hyperintelligent machines a more serious threat to society than dementia" on a piece of paper and put it in an envelope labelled "To Be Opened In 2040". (Hopefully that's early enough for our civilization to still exist!)
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mike
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Re: Genetic Engineering and unknown consequences

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Certainly gene editing is a touchy subject. So is giving vaccines...though less so to folks who study it. Is it really so different? I like the way Harvard is doing it - testing at a very basic level. While CRISPR may not work for existing ApoE4s, I would certainly like to give my grandkids a chance not to have to have it...
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J11
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Re: Genetic Engineering and unknown consequences

Post by J11 »

mike, we need to help Harvard out!

For whatever reason a warning message never reached the Chinese researchers that what they were doing was not entirely well considered. The Harvard idea of CRISPRing sperm to prevent APOE e4 might also deserve further contemplation. Why go to the trouble,
expense and likely risk of CRISPRing when you could simply select against embryos without e4? Is their intent to help couples who are both e44?

This is the APOE4 forum, so this is an obvious place to discuss this issue among patient stakeholders with APOE4 dementia. Too often scientists in labs develop technologies without meaningful public input or consent. It would be much better to go through a community consent process beforehand than repeat what happened in Hong Kong. The time for thinking is before and not after babies are born.
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Brian4
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Re: Genetic Engineering and unknown consequences

Post by Brian4 »

Rainbow, I think I'll write a similar letter to myself, to be opened in 2040!

As for the Harvard work, I think it's more of a demonstration for PR purposes than anything else. There's no reasonable scenerio under which babies born in the next few years or later will have to worry about ApoE4-induced pathology.
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Re: Genetic Engineering and unknown consequences

Post by Fiver »

Interesting discussion. I'd humbly suggest that CRISPR editing of the germ-line and vaccines aren't quite comparable. Vaccines train the immune system to do their natural jobs, wear off in a relatively short time, but give us a little head start on devastating diseases. Gene editing has the potential to alter humanity and fracture society along have / have not lines.

I'm even conflicted myself. I think I'd line up to swap a few apoe's. But I really don't think society will be able to control or direct this once it's out there.
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Re: Genetic Engineering and unknown consequences

Post by LanceS »

Confirming my lack of medical background, I thought APOE4 expression would be primarily determined by not the genome itself, but the bone marrow (producing a significant fraction of apoe4 expression). That the african child/teen in france who had partial marrow extraction / gene editing (I don't think CRISPR) / marrow replacement and effectively reduced his symptoms of sickle cell anemia would be a viable model for human APOE4 mitigation. I don't know the economics of this procedure, but the genie and the bottle is a 70s show at this point.

Unintended consequences, etc, etc. I thought Japan and china are allowing phase 1 safety trials for many more drugs these days. What am I missing?
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Re: Genetic Engineering and unknown consequences

Post by Fiver »

****************************************************************
Harvard to working to CRISPR-out apoe4.

https://www.technologyreview.com/s/6124 ... ing-sperm/
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Re: Genetic Engineering and unknown consequences

Post by mike »

Fiver wrote:Harvard to working to CRISPR-out apoe4.
And from that article:

Amid the condemnation, though, it was easy to lose track of what the key experts were saying. Technology to alter heredity is for real. It is improving very quickly, it has features that will make it safe, and much wider exploratory use to create children could be justified soon.

That was the message delivered at a gene-editing summit in Hong Kong on Wednesday, November 28, by Harvard Medical School dean George Daley, just ahead of He’s own dramatic appearance on the stage (see video starting at 1:15:30).

Astounding some listeners, the Harvard doctor and stem-cell researcher didn’t condemn He but instead characterized the Chinese actions as a wrong turn on the right path (see video). “The fact that it is possible that the first instance of human germ-line editing came forward as a misstep should in no way lead us to stick our heads in the sand,” Daley said. “It’s time to ... start outlining what an actual pathway for clinical translation would be.”
J11 wrote:mike, we need to help Harvard out!
Yes, I agree. Just like with drug trials, we need to go slowly and with oversight. The problem with this, unlike drug trials, is if it turns out not to be safe, you can stop the drug, but not the gene change. The disease needs to be severe, and the related genes clearly understood.
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mike
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Re: Genetic Engineering and unknown consequences

Post by mike »

Out of curiosity, if they come up with a way to edit genes in adults, would you get your ApoE4 genes swapped out? If I thought it safe and tested, I would jump at it. Of course, I'm not having more kids, so whatever the result, it stops with me.
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