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I was thinking more that the acidic environment of the stomach could break down the aggregates to the protein monomers. This step wouldn't be reliant on proteases, although proteases might then be able to further break down the monomers. But I haven't looked into whether this has been studied.


I'm not convinced that eating prion-contaminated tissue is a major factor in transmitting prion diseases. Prions are still proteins, which are broken down to amino acids very readily by the digestive system. Even if prions are more stable than most proteins because they have formed these crystalline-like oligomers, such large molecules would have little chance of being absorbed intact into the bloodstream. Instead, I would imagine they would pass through the digestive system and be excreted in feces.

The Wikipedia article on kuru proposes an alternate mechanism which seems more plausible to me:

the strong possibility exists that it was passed on to women and children more easily because they took on the task of cleaning relatives after death and might have had open sores and cuts on their hands.

This would allow the prion particles to enter the bloodstream directly where they could be absorbed into tissues and persist for a long time, bypassing the digestive system entirely.

If this is the primary mechanism of transmission, it would support your argument that eating cooked meat would have minimal risk, while handling diseased tissue would actually be the much higher risk activity.

Do you know if any of the 200 people who came down with BSE were involved in handling/butchering the meat, as opposed to just buying contaminated meat at the store and eating it? (I suppose people who bought meat at the grocery store could have still gotten infected during meal prep, but if a substantial number of victims were butchers/slaughterhouse workers/etc., it could be evidence in support of this hypothesis.)


Should we humans broadcast more explicitly to future AGIs that we greatly prefer the future where we engage in mutually beneficial trade with them to the future where we are destroyed?

(I am making an assumption here that most, if not all, people would agree with this preference. It seems fairly overdetermined to me. But if I'm missing something where this could somehow lead to unintended consequences, please feel free to point that out.)


Sorry, I thought that would be more commonly understood. As Carl said, it stands for Contract Research Organization. Hiring one is a way to get additional resources to perform specific tasks without having them be part of your organization, understand your corporate strategy, or even know what project you're working on. For example, a pharma company can hire a CRO to synthesize a specific set of potential drug compounds, without telling them what the biological target is or what disease they are trying to treat. Or think of the scenario where a rogue AGI hires someone to make a DNA sequence which turns out to code for a pathogen that kills all humans. This would likely be done at a CRO.

CRO's are often thought of as being fairly competent at executing the specific task required of them, but less competent at thinking strategically, understanding the big picture, etc. So they are generally only hired for very well-defined trades, as you mentioned above.


Maybe it's better to model the army of ants as a CRO you would hire instead of an employee? And by extension, I would much prefer to be part of an AGI's CRO than be extinct.


I often use the heuristic that if two sources with opposing Narratives both claim that a certain fact is true, it is strong evidence that the fact is indeed true. Are there cases where this heuristic fails? E.g. where both sides claim a fact is true (likely with different motives), but it is actually false?


If you have hierarchy in a company, regardless of whether people are "middle managers" per se, there's a tendency for people to come to care about advancing in the hierarchy. It's a natural thing to want to do.

I would take this a step further and say that once maze levels are high enough, it essentially becomes a requirement to care (or at least pretend to care) about advancing in the hierarchy. Instead of advancement being something that some employees might want and others might not want, it becomes almost an axiom within the organization that everyone must strive for advancement at all times. But although advancement can be a natural thing to want, it's certainly not a universal thing to want. And for people like me who aren't strongly motivated by their place in the hierarchy, this can lead to a lot of conflict, stress, and low morale.

When I was a kid (maybe around 10) I learned about the Peter Principle, how everyone in an organization gets promoted to the level of their incompetence. I thought that was one of the saddest things I'd ever heard. Why would everyone try so hard to get promoted to a role they weren't good at? Just for the extra money? I decided that when I started working, I would rather stay in a role I was good at and enjoyed on a day to day basis than get promoted to a managerial role which already sounded awful, even if it meant staying at a lower salary.

Once in the maze, however, I found it a lot harder to stay in my happy, productive role than I was expecting. I constantly felt pressure to want to get promoted. But I secretly didn't want to, because that would mean spending less time doing the actual hands-on work that I liked and more time spent in the maze world interacting with other managers. This led to a lot of tension with my bosses. They couldn't comprehend why anyone wouldn't be excited about getting promoted. Higher level jobs were just better; why couldn't I see that? But to me, they weren't better and I couldn't get them to see my perspective. Ironically, their desire to promote me incentivized me to be less productive than I would have been otherwise - if we had been able to come to an agreement where I could stay in my desired role, I would have been more motivated to work harder without the fear of accidentally getting promoted too quickly.

This was all very frustrating and confusing to me for a long time. Eventually I came across the Moral Mazes sequence and the Gervais principle, which together seemed to explain a lot of what I was experiencing and ultimately gave me the courage to leave that organization.

Anyway, that's my story of working in a maze - happy to discuss further if this was useful or informative.


Another potential assumption/limitation of the EMH:

  • Socially acceptable to trade: It must be socially acceptable for people who have enough financial resources to noticeably affect market prices to trade based on the new information.

I initially proposed this idea to try to explain the market's slow response to the early warning signs of Covid in this comment. Similar dynamics may come into play with respect to the social acceptability of ESG vs anti-ESG investing based on political affiliation, although in this case I don't think there is enough anti-ESG money to affect the prevailing ESG trends much at this point.


Maybe the market is predicting that R0 will be >1, but isolation and contact tracing will be enough to prevent a wider outbreak?


What about the combo: a tic-tac-toe board position, a tic-tac-toe board position with X winning, and a tic-tac-toe board position with O winning. Would it give realistic positions matching the descriptions?

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