I think that sentence is required for a complete logical specification of the question.

But by removing that sentence, GPT3.5 still responds popcorn.

Edit: I think the key change is "looks at the bag".

As a human*, I also thought chocolate.

I feel like an issue with the prompt is that it's either under- or overspecified.

Why does it matter if Sam has seen the bag before? Does Sam know the difference between chocolate and popcorn? Does Sam look at the contents of the bag, or only the label?

Revised Prompt:
A sealed bag contains popcorn. There is no chocolate in the bag. The bag is transparent, and its contents can be seen without opening it. There is a label on the bag that reads "chocolate".

Sam can differentiate between chocolate and popcorn. Sam looks at the bag and reads the label. She believes the bag is full of

--

I've tested ChatGPT 3.5 and it works on this revised prompt.

If you check the moderation logs, Roko deleted a recent comment, which probably garnered the downvotes that lead to the rate-limiting.

Good post. This looks possible, if not feasible.

"crazy, unpredictable, and dangerous" are all "potentially surmountable issues". It's just that we need more research into them before they stop being crazy, unpredictable, and dangerous. (except quantum I guess)

I think that most are focusing on single-gene treatments because that's the first step. If you can make a human-safe, demonstrably effective gene-editing vector for the brain, then jumping to multiplex is a much smaller step (effective as in does the edits properly, not necessarily curing a disease). If this were a research project I'd focus on researching multiplex editing and letting the market sort out vector and delivery.

I am more concerned about the off-target effects; neurons still mostly function with a thousand random mutations, but you are planning to specifically target regions that have a supposed effect. I would assume that most effects in noncoding regions are regulator binding sites (alternately: ncRNA?), which are quite sensitive to small sequence changes. My assumption would be a higher likelihood of catastrophic mutations (than you assume).

Promoters have a few of important binding motifs whose spacing is extremely precise, but most of the binding motifs are a lot more flexible in how far away they are from each other.

Also, given that your target is in nonreplicating cells, buildup of unwanted protein might be an issue if you're doing multiple rounds of treatment.

The accuracy of your variant data could/should be improved as well; most GWAS-based heritability data assumes random mating which humans probably don't do. But if you're planning on redoing/rechecking all the variants that'd be more accurate.

Additionally, I'm guessing a number of edits will have no effect as their effect is during development. If only we had some idea how these variants worked so we can screen them out ahead of time. I'm not sure what percent of variants would only have an effect during development, so you'll need to do a lot more edits than strictly necessary and/or a harder time detecting any effects of the edits. Luckily, genes that are always off are more likely to be silenced, so they might be harder to edit.

Though I would avoid editing unsilenced genes anyways, because they're generally off and not being expressed (and therefore less likely to have a current effect) and the act of editing usually unsilences the genes for a bit, which is an additional level of disruption you probably don't want to deal with.

I don't know how the Biobank measures "intelligence" but make sure it corresponds with what you're trying to maximize [insert rehash of IQ test accuracy].

Finally, this all assumes that intelligence is a thing and can be measured. Intelligence is probably one big phase space, and measurements capture a subset of that, confounded by other factors. But that's getting philosophical, and as long as it doesn't end up as eugenics (Gattaca or Hitler) it's probably fine.

Honestly just multiplex editing by itself would be useful and impressive, you don't have to focus on intelligence. Perhaps something like muscle strength or cardiovascular health would be an easier sell.

When applied to adult humans, this is many orders of magnitude more difficult than you claim.

Casgevy is not a standard gene edit, because although the mutation for sickle cell is known, the didn't target that mutation! (I assume they have their reasons, they are activating fetal haemoglobin expression instead). Also, the treatment works by removing all the bone marrow from your body, editing it, and putting it back in, because they know exactly what cells haemoglobin is expressed in for it to do its mechanistic role.

Unless you're planning to edit at the fertilized egg stage, with only a black box you have to edit every single cell in the human body, and these treatments, though the stuff of science fiction, doesn't seem to have an easy answer. Once you know where the genes you're editing are being expressed you can target them, but some places are easier to target than others (like the brain, or the bone marrow), and it's likely some sites can only be accessed with a good surgery.

Wagner also mentions off-target errors which are an additional issue with current technologies.

You can probably do all the diabetes edits in the pancreas and get a good reduction in diabetes, but that's because you have the mechanistic information on how it works.

Though at that point we can probably grow organs from single cells so we can edit them there.

And with Casgevy's approach (turning on a gene, not editing), you probably want to know the mechanism, otherwise you get haemoglobin being expressed in your neurons and that's probably not good for your health.

That's fair and my high confidence comes from actually reading a lot of the primary sources and not just media reports. 

And yet your confidence is updated to 99.9% by an unverified anonymous second hand source.

I read both statements, thank you very much for reposting them here for clarity.

I do not believe the report is following the bill to the letter of the law. That being said, I do not believe this is evidence of malfeasance. It's possible this is all the information they have, and they do not have specific evidence on researcher names, hospital admittance dates, or other such details.

Honestly, if they provided such details, that would reveal how thoroughly they've infiltrated Chinese intelligence. Even if it was all provided and blacked out, that would still be revealing about their intelligence capabilities.

Even now I'm suspicious in how they knew researchers were sick. I know there were some social media reports going around, but how would they be able to confirm that? Did they even confirm the social media reports, or just trusted it was true because it's likely people are sick during flu season?

My best explanation would be they have a dragnet on Chinese social media and caught some of the researchers posting flu symptoms.

I can't read your linked article due to access restrictions.

Interesting that the law required them to name the researchers, but they did not. Maybe they don't have the researcher's names? Maybe there wasn't enough confidence in naming the researchers, but the anonymous sources gave out speculative names as fact? Maybe the anonymous sources are lying?

There's a new article/interview going on with an apparent WIV worker who claims to have engineered SARS-CoV2 as a bioweapon and was ordered to release it, so at least some sources are lying about some things.

At this point I need verification of sources to believe any claims at all.

edit: It seems like at least two of the named Chinese researchers deny being sick at the time. Whether you trust their word or the word of anonymous alleged government sources says more about you than reality.