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Just want to say that a lot of the conversations here are revolving around using our current model of molecular biology to treat cancer. That model has had a ton of success, and is the best workhorse we have for reliably turning money into life-years probably. I think it's a big reason why a lot of people throw that idea around that cancer is gonna be cured by just developing a super-cornucopia of drugs. 

But I think the heart of this post is in asking "well, are there models that get OUT of that framework? ones that are seismic shifts, like the germ theory of disease?" Yeah, just the one(s) that I've seen are super theoretical. Michael Levin's group, oft heralded on LessWrong bio posts, is in fact starting to study cancer. The argument goes that, like Archimedes mentioned in the comments here, cancer is a disease of individual cells rebelling against multicellularity. Levin's group thinks that the mechanisms for that control might be electrical/physical — as in, the deformity is more in the "software" (transient signals dictating cell behavior) being run by the "hardware" of whatever mutated proteins are in the cell.

It's a cool idea, but the work that I've seen on that front is really preliminary. I think the most experimental work I've read by them is a paper that shows that brain cancer cells are killed by drugs which modulate voltage-gated channels. Ostensibly, this modulates some of the transient signalling on the electrically based "software level" which is driving them away from multicellularity. [I am personally extrapolating these claims.] But I think it's more likely that they're seeing a response b/c voltage-gated protein activity is hard-wired to cell survival mechanisms.

This is what I wanted to get at about your post. There are some people/some environments where I feel totally attached to (what I imagine) are people's models of me. I've worried about my mom's judgement for basically all my life. But she can't know me entirely because as you rightly point out, she isn't me — I've felt a lot of comfort in realizing that her model of me (and my model of her modeling me) is necessarily incomplete, and therefore can't be eternally true. My worthiness isn't dependent on her model. If it's any consolation, having this feeling for the past short while hasn't made me detached from what I generally think is her good judgement.

BUT, at the same time, my mom has been able to like take one look at me and totally figure out motivations that I couldn't articulate beforehand. I don't know myself entirely. There are some motivations which appear transparent to to others, and which I could reasonably say right now "I don't feel", but I actually might. Not saying this is true of most of the A-ful without B-things you're feeling. And obviously people over-extend their heuristics. Still, I think this is the value of putting stock in other people's models of you — different info from the outside. But variable levels of attachment seem to be the problem?

In the past post, I would describe my ADHD as "I am in a hurry, in a hurry for what I don't really know".

This is such a great description of what it feels like whenever I'm having trouble focusing. I start to feel this overwhelming feeling of nervous energy, and this thought process like "why am I reading this when there are so many other things I could be reading/doing" and start to crave attention-suckers like social media, etc. Especially as I've been trying to read or learn more challenging things.

It doesn't seem to me that obviousness is proof enough that an intuition is good, but something appearing "obvious" in your brain might be a marker/enrich for beliefs that have been selected for in social environments.

There are certainly times when it's good to break universal maxims. Yet I don't think it's very easy to be a person who is capable of doing that -- the divergent individual you're talking about. Let's take lying, for example. It is generally good to be honest. There are times when it is really net good and useful to lie. But if you're someone who becomes very good at lying and habituated to lie, you probably start overriding your instincts to be honest. Maybe a divergent individual who says "fuck off" to all internal signals and logically calculates out the results of every decision could get away with that. But I think those people really run the risk of losing out on information baked into the heuristics.

Similarly, I don't think those divergent people are really optimal actors, in the long-run. There are certainly times when it's good to break universal maxims; but even for you, as an individual, it's probably not good to do it all the time. If you get known as a grandma-pusher, you're going to be punished, which is probably net good for society, but you also reduced your ability to add resources to the game. Human interaction is an iterated game, and there are no rings of Gyges.

A few for cell biology:

  • How do we measure what proteins, and other biomolecules, are actually doing in a native context? For tracking where proteins are in the cell: sure, we can pop GFP onto anything we'd like, but now we have a protein that's lugging around a ~20 kilodalton tube on its back. That's got to be skewing that protein's behavior somewhat.
  • Cell signalling as needing a true name. Biologists talk about cell signalling all the time, but the physical mechanisms by which information is propagated in a cell seem incredibly variable. In a lot of mechanistic-style biology, the processes by which signals are transduced are generally handwaved away. I haven't seen a lot of useful explanations on why certain modes of signalling are selected for in different contexts.
  • I think biologists who are working on ways to characterize what the cell is like as a physical environment are going to make a lot of progress on some of the intense variability we see in various phenotypes. Topics like biological noise, phase behaviors within cells, weird poly-/omni-genic phenotypes, all seem really promising to me.