What have you learned since then? Have you changed your mind or your ontology?
I’ve learned even more chemistry and biology, and I’ve changed my mind about lots of things, but not the points in this post. Those had solid foundations I understood well and redundant arguments, so the odds of that were low.
What would you change about the post? (Consider actually changing it.)
The post seems OK. I could have handled replies to comments better. For example, the top comment was by Thomas Kwa, and I replied to part of it as follows:
Regarding 5, my understanding is that mechanosynthesis involves precise placement of individual atoms according to blueprints, thus making catalysts that selectively bind to particular molecules unnecessary.
No, that does not follow.
I didn’t know in advance which comments would be popular. In retrospect, maybe I should’ve gone into explaining the basics of entropy and enthalpy in my reply, eg:
Even if you hold a substrate in the right position, that only affects the entropy part of the free energy of the intermediate state. In many cases, catalysts are needed to reduce the enthalpy of the highest-energy intermediate states, which requires specific elements and catalyst molecules that form certain bonds with the substrate intermediate state. Affecting enthalpy by holding molecules in certain configurations requires applying a proportional amount of force, which requires strong binding to the substrate, which requires flexible and substrate-specialized holder molecules, and now you have enzymes again. It’s also necessary to bind strongly to substrates if you want a very low level of free ones that can react at uncontrolled positions. (And then some basic explanation of what entropy/enthalpy/etc are, and what enzyme intermediate states look like.)
When you write a post that gets comments from many people, it’s not practical to respond to them all. If you try to, you have less time than the collective commenters, and less information about their position than they have about yours. So you have to guess about what exactly each person is misunderstanding, and that’s not usually something I enjoy.
What do you most want people to know about this post, for deciding whether to read or review-vote on it?
Of the 7 (!) posts of mine currently nominated for “Best of 2023”, this is probably the most appropriate for that.
Of the 2023 posts of mine not currently nominated, my personal favorites were probably:
How concretely have you (or others you know of) used or built on the post? How has it contributed to a larger conversation
Muireall Prase wrote this, and my post was relevant for some conversations on twitter. I suppose it also convinced some people I had some understanding of chemistry.
Thanks for the update! Let me attempt to convey why I think this post would have been better with fewer distinct points:
In retrospect, maybe I should’ve gone into explaining the basics of entropy and enthalpy in my reply, eg:
If you replied with this, I would have said something like “then what’s wrong with the designs for diamond mechanosynthesis tooltips, which don’t resemble enzymes and have been computationally simulated as you mentioned in point 9?” then we would have gone back and forth a few times until either (a) you make some complicated argument I don’t understand enough to believe nor refute, or (b) we agree on what definition of “enzyme” or “selectively bind to individual molecules” is required for nanotech, which probably includes the carbon dimer placer (image below). Even in case (b) we could continue arguing about how practical that thing plus other steps in the process are, and not achieve much.
The problem as I see it is that a post that makes a large number of points quickly, where each point has subtleties requiring an expert to adjudicate, on a site with few experts, is inherently going to generate a lot of misunderstanding. I have a symmetrical problem to you; from my perspective someone was using somewhat complicated arguments to prove things that defy my physical intuition, and to defend against a Gish gallop I need to respond to every point, but doing this in a reasonable amount of time requires me to think and write with less than maximum clarity and accuracy.
The solution I would humbly recommend is to make fewer points, selected carefully to be bulletproof, understandable to non-experts, and important to the overall thesis. Looking back on this, point 14 could have been its own longform, and potentially led to a lot of interesting discussion like this post did. Likewise point 6 paragraph 2.
make fewer points, selected carefully to be bulletproof, understandable to non-experts, and important to the overall thesis
That conflicts with eg:
If you replied with this, I would have said something like “then what’s wrong with the designs for diamond mechanosynthesis tooltips, which don’t resemble enzymes
Does the recent concern about mirror life change your mind? It’s not nano, but it does imply there’s a design space not explored by bio life, which implies there could be others, even if specifically diamonds don’t work.
“Mirror life” is beyond the scope of this post, and the concerns about it are very different than the concerns about “grey goo”—it doesn’t have more capabilities or efficiency, it’s just maybe harder for immune systems to deal with. Personally, I’m not very worried about that and see no scientific reason for the timing of the recent fuss about it. If it’s not just another random fad, the only explanation I can see for that timing is: influential scientists trying to hedge against Trump officials determining that “COVID was a lab leak” in a way that doesn’t offend their colleagues. On the other hand, I do think artificial pathogens in general are a major concern, and even if I’m not very concerned about “mirror life”, there are no real benefits to trying to make it, so maybe just don’t.
I’ve learned even more chemistry and biology, and I’ve changed my mind about lots of things, but not the points in this post. Those had solid foundations I understood well and redundant arguments, so the odds of that were low.
The post seems OK. I could have handled replies to comments better. For example, the top comment was by Thomas Kwa, and I replied to part of it as follows:
I didn’t know in advance which comments would be popular. In retrospect, maybe I should’ve gone into explaining the basics of entropy and enthalpy in my reply, eg:
When you write a post that gets comments from many people, it’s not practical to respond to them all. If you try to, you have less time than the collective commenters, and less information about their position than they have about yours. So you have to guess about what exactly each person is misunderstanding, and that’s not usually something I enjoy.
Of the 7 (!) posts of mine currently nominated for “Best of 2023”, this is probably the most appropriate for that.
Of the 2023 posts of mine not currently nominated, my personal favorites were probably:
https://www.lesswrong.com/posts/BTnqAiNoZvqPfquKD/resolving-some-neural-network-mysteries
https://www.lesswrong.com/posts/PdwQYLLp8mmfsAkEC/magnetic-cryo-ftir
https://www.lesswrong.com/posts/rSycgquipFkozDHzF/ai-self-improvement-is-possible
https://www.lesswrong.com/posts/dTpKX5DdygenEcMjp/neuron-spike-computational-capacity
https://www.lesswrong.com/posts/6Cdusp5xzrHEoHz9n/faster-latent-diffusion
Clearly my opinion of my own posts doesn’t correlate with upvotes here that well.
My all-time best post in my view is probably: https://bhauth.com/blog/biology/alzheimers.html
Muireall Prase wrote this, and my post was relevant for some conversations on twitter. I suppose it also convinced some people I had some understanding of chemistry.
Thanks for the update! Let me attempt to convey why I think this post would have been better with fewer distinct points:
If you replied with this, I would have said something like “then what’s wrong with the designs for diamond mechanosynthesis tooltips, which don’t resemble enzymes and have been computationally simulated as you mentioned in point 9?” then we would have gone back and forth a few times until either (a) you make some complicated argument I don’t understand enough to believe nor refute, or (b) we agree on what definition of “enzyme” or “selectively bind to individual molecules” is required for nanotech, which probably includes the carbon dimer placer (image below). Even in case (b) we could continue arguing about how practical that thing plus other steps in the process are, and not achieve much.
The problem as I see it is that a post that makes a large number of points quickly, where each point has subtleties requiring an expert to adjudicate, on a site with few experts, is inherently going to generate a lot of misunderstanding. I have a symmetrical problem to you; from my perspective someone was using somewhat complicated arguments to prove things that defy my physical intuition, and to defend against a Gish gallop I need to respond to every point, but doing this in a reasonable amount of time requires me to think and write with less than maximum clarity and accuracy.
The solution I would humbly recommend is to make fewer points, selected carefully to be bulletproof, understandable to non-experts, and important to the overall thesis. Looking back on this, point 14 could have been its own longform, and potentially led to a lot of interesting discussion like this post did. Likewise point 6 paragraph 2.
That conflicts with eg:
Anyway, I already answered that in 9. diamond.
Does the recent concern about mirror life change your mind? It’s not nano, but it does imply there’s a design space not explored by bio life, which implies there could be others, even if specifically diamonds don’t work.
“Mirror life” is beyond the scope of this post, and the concerns about it are very different than the concerns about “grey goo”—it doesn’t have more capabilities or efficiency, it’s just maybe harder for immune systems to deal with. Personally, I’m not very worried about that and see no scientific reason for the timing of the recent fuss about it. If it’s not just another random fad, the only explanation I can see for that timing is: influential scientists trying to hedge against Trump officials determining that “COVID was a lab leak” in a way that doesn’t offend their colleagues. On the other hand, I do think artificial pathogens in general are a major concern, and even if I’m not very concerned about “mirror life”, there are no real benefits to trying to make it, so maybe just don’t.