sarahconstantin
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20
Funding individuals doesn't seem at all ruled out by our mission and I agree it's a good thing.
IANAL and I don't know much about how that interacts with tax deductibility.
links 12/4/2024: https://roamresearch.com/#/app/srcpublic/page/12-04-2024
- https://substack.com/home/post/p-149058187 Gena Gorlin hosts a discussion on "psychological safety"
- https://psychiatryonline.org/doi/full/10.1176/appi.ajp.21080800 new antidepressant just dropped: bupropion + dexmethorphan, appears to be more effective than bupropion alone
- registering my concern that someday we will find that NMDA inhibitors do something bad to cognition. but all these recent studies are 6-week only and don't report any side effects that look like cognitive impairment, but maybe wouldn't have been able to pick it up even if it existed.
- https://slatestarcodex.com/2015/07/13/things-that-sometimes-work-if-you-have-anxiety/ Scott Alexander on anxiety treatments.
- "Azapirones (example: BuSpar) is, unusually, a rare drug which is specifically targeted at anxiety, rather than a being a repurposed antidepressant or something. BuSpar is very safe, not at all addictive, and rarely works. Every so often somebody comes out with a very cheerful study saying something like “Buspar just as effective as benzodiazepines if given correctly!” and everybody laughs hysterically and goes back to never thinking about it."
- gabapentin for anxiety -- meh, some positive results but they're not extraordinary.
"three cultures of self-criticism" https://roamresearch.com/#/app/srcpublic/page/zzRZnCLd_
- non-self-critical culture (Barbarians):
- baseline assumptions:
- people generally think they are okay and good, and they are generally right.
- self-criticism is rare.
- if someone is being self-critical, guilty, ashamed, etc, that indicates an unusual problem.
- implications:
- intense self-criticism will be taken as evidence of something actually wrong with the person -- either they really did screw up quite badly, or they have poor judgment.
- criticism is direct and overt.
- if someone objects to what you've done, they'll tell you straight out, and expect that this will clear the air and lead to a resolution of the problem.
- "negative" judgments are not necessarily intended, or expected, to be painful; the listener may very well disagree with the judgment or find it helpful feedback.
- as a corollary, nobody assumes that an ambiguous comment or facial expression is a hint at criticism or disapproval. The default assumption is that people are fine with you, that you're fine, and if there's a problem it'll become obvious.
- baseline assumptions:
- pro-self-criticism culture (Puritans):
- baseline assumptions:
- people are generally deeply flawed; we are constantly screwing up, sinning, etc. this is the universal or near-universal human condition, not something limited to unusually bad people. but it really is genuinely Bad and Not Okay.
- people tend to be complacent -- by default we engage in far too little self-criticism. We are screwing up without knowing it. We let ourselves off the hook, make excuses for ourselves, ignore warning signs. It takes active, continual effort to be vigilant against our own flaws.
- implications:
- intense self-criticism and guilt is normative. virtuous people will not think well of themselves. in fact, if someone does think well of themselves, that means they're lazy and have low standards.
- corollary: an intensely self-critical or guilty person is not assumed to be an unusually bad person or to have a mental health problem; they are just doing what we're all supposed to do!
- criticism can be harsh and intentionally painful, because the assumption is that it needs to be "strong enough" to overcome natural human complacency
- it's also common to read criticism into subtle or ambiguous signs. the assumption is that there are always more problems than the obvious ones; it's never safe to presume things are fine.
- intense self-criticism and guilt is normative. virtuous people will not think well of themselves. in fact, if someone does think well of themselves, that means they're lazy and have low standards.
- baseline assumptions:
- counter-self-criticism culture (Therapy Patients):
- baseline assumptions:
- people generally are too self-critical. most people are basically fine but torture themselves over minutiae.
- complacency -- failing to self-criticize enough about genuine faults -- is literally monstrous. complacent people are rare, and pathological; we might call them sociopaths. you absolutely would not want to be one, and you're almost certainly not.
- "healing" or "growth" means learning to quiet the overactive inner critic. this is very difficult; people need help with it.
- everybody always needs validation and reassurance that they're ok, and the kindest thing you can do for anyone is give them permission not to worry or self-criticize. the cruelest thing you can do is trigger their insecurities and intensify their (already painful) self-criticism.
- implications:
- self-criticism is not normative; it's an affliction we all suffer from and long to be freed from.
- like sin in pro-self-criticism cultures, misery in counter-self-criticism culture is seen as Genuinely Terrible, Deeply Not Okay, but also a part of the human condition, not a sign that something has gone unusually wrong with you. you're mentally ill, like everyone else.
- criticism is mild and gentle, or suppressed altogether, because it's assumed everybody is already torturing themselves and doesn't need other people piling on.
- corollary: it's common to read a lot of criticism or disapproval into subtle or ambiguous signals because it's assumed that people are holding back their true negative opinions. The absence of reassurance or validation is considered a sign of severe, harsh disapproval.
- self-criticism is not normative; it's an affliction we all suffer from and long to be freed from.
- baseline assumptions:
- relationships:
- Barbarians see Puritans as totally excessive, and see Therapy Patients as trying to counteract a problem that one can just...not have.
- Puritans see both Barbarians and Therapy Patients as dangerously complacent.
- Therapy Patients see Puritans as a familiar enemy -- something they understand but reject and want to get away from, like an unhappy childhood home -- and see Barbarians as incomprehensible, alien, insane, not-even-human.
links 12/03/2024: https://roamresearch.com/#/app/srcpublic/page/12-03-2024
- https://sashachapin.substack.com/p/my-mind-transformed-completely-and Sasha Chapin on how meditation changed him
- it doesn't seem clear to me whether this is better or not!
- reduced anxiety seems great, but reduced sense of narrative drama is a big cost. part of what makes life seem meaningful to me is the sense of being part of a story, and if anything i feel like my current arc involves gaining abilities to envision myself as inside a narrative.
- https://www.wired.com/story/murderbot-she-wrote-martha-wells/ Martha Wells seems like a lovely person
- https://www.orcasciences.com/articles recommended by Ben Reinhardt, great example of rigorous analyses of potential future technologies.
- https://www.orcasciences.com/articles/checking-my-prejudices-on-materials-decarbonization eg: where does it make economic sense to use electrochemical or biological manufacturing? (compared to "thermochemical", fossil-fuel-powered). For biomanufacturing, only for complex molecules like proteins; for electrochemical processing, mostly metals and things with big voltage potentials in the chemical reaction (zinc, cobalt, copper, lithium, etc) but not simple organic molecules (methane, ethanol, etc)
- https://www.biotech.senate.gov/press-releases/interim-report/ "US National Security Commission on Emerging Biotechnology", a congressional advisory committee led by Jason Kelly of Gingko Bioworks
- their purpose seems to be getting biotech-friendly policies through congress, with the rationale that this is good for national security/defense.
- a lot of naive boosterism about biomanufacturing without engaging with the question of "is this better than alternative manufacturing techniques?"
- https://www.aria.org.uk/request-for-opps/ new opportunities for program managers at ARIA: lead a scientific research program!
links 11/26/2024: https://roamresearch.com/#/app/srcpublic/page/11-26-2024
- https://chrislakin.blog/archive sensible, but not actionable for me, advice on becoming less insecure.
- https://abundance.institute pro-progress think tank, where Eli Dourado works
- The Myth of Er is the final scene of Plato's Republic.
- it is a very strange story. in the afterlife, the good are rewarded in heaven and the bad are punished in hell; and then everyone lines up to choose their new reincarnated life. they get to see how each possible life will play out. people who have led unhappy lives often prefer to reincarnate as animals. people who were only virtuous out of habit and went to heaven often choose to be all-powerful tyrants, not realizing how this will backfire and hurt them. people who have learned philosophy are more likely to choose lives of virtue; they also "forget less" about their past lives by drinking from Lethe.
- so in one sense it's straightforwardly a pitch for philosophy...but it has more moving parts than would seem to be necessary just to make that point.
- most myths/stories about "good is rewarded, evil is punished" don't have this homeostatic mechanism where the good are most likely to turn bad (since Heaven makes them complacent) and the bad are more likely to turn good (since Hell makes them wish for a better next life.) why put that in?
- how does this whole reincarnation thing relate to the rest of the Republic, which is ambiguous between being a plan for an ideal city and a metaphor for the ideal internal organization of the soul?
- so in one sense it's straightforwardly a pitch for philosophy...but it has more moving parts than would seem to be necessary just to make that point.
- https://beccatarnas.com/2013/10/17/the-myth-of-er/
- it is a very strange story. in the afterlife, the good are rewarded in heaven and the bad are punished in hell; and then everyone lines up to choose their new reincarnated life. they get to see how each possible life will play out. people who have led unhappy lives often prefer to reincarnate as animals. people who were only virtuous out of habit and went to heaven often choose to be all-powerful tyrants, not realizing how this will backfire and hurt them. people who have learned philosophy are more likely to choose lives of virtue; they also "forget less" about their past lives by drinking from Lethe.
- http://strangehorizons.com/fiction/the-spindle-of-necessity/
- war in the Middle East
- https://www.fairobserver.com/politics/fo-exclusive-the-israel-iran-conflict-is-getting-more-dangerous/
- https://indianexpress.com/article/world/iran-vows-response-israeli-airstrikes-escalating-tensions-9688373/
- https://www.aljazeera.com/news/2024/11/2/khamenei-warns-israel-us-of-crushing-response-for-actions-against-iran
- https://www.aljazeera.com/news/2024/10/26/israel-strikes-iran-what-we-know-so-far-and-whats-next
- what went wrong with Gingko Bioworks?
- first of all, their stock price crashed after short seller Scorpion Capital reported that most of their "revenue" was from self-funded "related parties" that often had the same staff and office space...aka they weren't "really" selling to other companies much at all.
- but what was the underlying technical problem? why couldn't they sell biomanufactured compounds profitably?
- one possibility: they were focusing on compounds that could be synthesized chemically, much more cheaply, that you would only grow from microbes if you wanted some sort of "all-natural" label
- another possibility: their service was limited to (parallelized, automated) yeast strain optimization in very small samples -- 384-well plates. they didn't do scale-up (growing the yeast in large reactors) and they didn't do downstream processing (extracting the product from the yeast). this may have lowered their rate of generating successful products, because many failures happen in the parts of the process they didn't specialize in.
- this is the manufacturing equivalent of what, in drug discovery, would be a CRO that only does a certain range of in-vitro screens. obviously many things that pass the screens will fail in animals or clinical trials. and obviously the value of an early screening service is quite low compared to the value of a successful end product.
- https://www.reddit.com/r/biotech/comments/1cwlpj3/whats_wrong_with_ginkgo_bioworks/
- https://www.technologyreview.com/2021/08/24/1032308/is-ginkgos-synthetic-biology-story-worth-15-billion/
- https://www.pagetwentyone.com/post/ginkgo-bioworks-rise-and-fall-of-15-billion-biotech-unicorn
- https://www.reddit.com/r/ginkgobioworks/comments/qgx2t1/updated_ginkgo_partner_tracker/
- https://healthandwealth.substack.com/p/ginkgo-bioworks-part-2
- https://www.living.tech/articles/ginkgo-bioworks-original-sin
- https://www.nanalyze.com/2023/03/ginkgo-bioworks-bait-switch/
- https://seekingalpha.com/article/4691850-ginkgo-bioworks-broken-narrative
- https://medium.com/@kahunacapbio/ginkgo-bioworks-cell-program-success-and-failure-7eb988c6d549
- https://scorpioncapital.s3.us-east-2.amazonaws.com/reports/DNA1.pdf
- https://foundrytheory.substack.com/ I'm gonna be real with you -- for all the bad results, I love Gingko's marketing. It makes me sad when people slam "hype" because this is so beautiful. Aesthetically tasteful, intellectually stimulating, emotionally inspiring. Everything they've done on the marketing front is just the best. and tbh it's worked for them -- the one thing even the damning reports show is how great they are at starting early-stage conversations with Fortune 500 companies. (they just rarely get all the way to actual products, revenue, and happy customers.) I'll be sad if the end of the ZIRP era means the end of pretty design and delightful copy.
- https://www.isomorphiclabs.com/ AI-for-bio company
- https://www.maximumnewyork.com/p/political-capital-savings-plan
- I'm sure Daniel Golliher is doing a healthy thing but I struggle to get on board myself.
- I think he's probably right that in order to actually make a political impact you have to pick a very small issue (like basketball courts in your city) to spend a lot of time on and you have to, um, have friends.
- I looked into public art one time -- how do people get their murals etc into public spaces? -- and the answer was, simply, that they are full time on that project. they live eat sleep and breathe public art. now, do I like pretty things? yes. do I care so much about public art in particular that i would want to be full time on it? no.
- Given that I don't want to spend my life on the issues "small enough" that i could actually shift them, it is absolutely rational for me not to participate in politics and to find it an uncongenial place! i can make a way bigger impact, much faster, with the reputational capital (and literal money) I've built up in more SV-adjacent circles than I can by grinding on NYC neighborhood issues.
- I'm sure Daniel Golliher is doing a healthy thing but I struggle to get on board myself.
- https://www.nature.com/articles/s41593-024-01784-3
- Is connectomics actually useful for anything? here’s strong evidence for “yes.”
- Mapping how neurons connect and using graph clustering gives you (anatomically sensible) functional distinctions into systems like “oculomotor” (which governs eye movements) and “axial” (which governs movements along the body axis.)
- Looking at the spectrum of the graph also predicts a chunky “wiring diagram”. Simulating the dynamics of this wiring diagram recapitulates real electrophysiology. In other words, just doing mathy graph stuff allowed the researchers to infer a modular organization at an intermediate scale between neurons and gross anatomy, a useful scale for predicting neural behavior. This is literally “cutting reality at the joints”.
- One thing that has frustrated me as an amateur learning neuroscience is that we have a microscale (cells) and a macroscale (brain anatomy) but function — the brain’s ability to carry out specific tasks — has to happen at some kind of meso-scale regarding the interaction of groups of neurons. Clearly there’s redundancy — it’s possible for two different neuron-by-neuron patterns of activity to reflect “the same” functional behavior — so we need a “unit of function” that’s “all the activity patterns that do the same thing” — probably that coincides somewhat with spatial co-location, similar cell type, etc, but not at all necessarily! Only once you have “units of function” can you talk about the brain like a machine, know what its “state” is and how that “state” would change under specific interventions, simulate it efficiently, etc.
- To understand brain function, we’d need to be able to discern human-interpretable “parts” of brain activity, like “remembering your grandmother just is the fizz blorking the buzz”…but we don’t seem to know what the “fizz”, the “buzz” or “blorking” are. We’d need to have “chunky things” in the brain-activity space, the way molecules, cells, or anatomical structures are “chunky things” at the micro and macro scales. And I felt like “what am I missing? does anybody in neuroscience even care about chunky-things? am I wrong to care? or do I just have the wrong keyword?”
- This paper definitely seems like an example of “chunky things neuroscience”, which is encouraging!
links 11/25/2024
- https://www.theguardian.com/commentisfree/2024/nov/17/how-to-survive-the-broligarchy-20-lessons-for-the-post-truth-world-donald-trump
- I was looking forward to a genuine practical how-to, but this isn't really it; while I can't argue with the value of "stick to your principles even in the face of authoritarianism" and "people who think they'll be targeted by authoritarians need to be especially mindful of communications & payments privacy" I think this author is envisioning scenarios worse than I think are likely.
- https://nadia.xyz/jhanas unusually straightforward explanation of one person's experience learning the jhanas
- https://en.m.wikipedia.org/wiki/The_Shop_Around_the_Corner
- https://www.complexsystemspodcast.com/episodes/drug-development-ross-rheingans-yoo/ Ross Rheingans-Yoo on drug development
- https://www.aljazeera.com/news/2024/11/13/what-do-we-know-about-the-north-korean-troops-joining-russias-war North Korean troops are now supporting Russia in the Ukraine war.
- https://www.complexsystemspodcast.com/episodes/money-movement-erik-torenberg/ Erik Torenberg on finance
- https://drdevonprice.substack.com/p/i-dont-feel-safe-around-cis-women a rant about a particular kind of cis women who feel entitled to be extremely rude and intrusive because they assume "women = inherently benign".
- reading about the Inca:
- https://www.wrecka.ge/against-the-dark-forest/ not very solution-oriented piece about problems with the internet
- ok, you blame Big Tech, and you see "Dark Forest" discourse as insufficiently hard on Big Tech.
- you also think that retreat to "private" nooks is not adequate (I agree) and that different cultures around the world should get to choose their own forms of online networking instead of being lumped into a US-centric paradigm (sure) and that we need ways to connect around the world (yes)...but what do you propose and who will pay for it etc are the questions coming to my mind
- https://endpts.com/trump-picks-hopkins-researcher-marty-makary-to-lead-the-fda/
moderately reformist, critical of COVID-19 response but not of vaccines per se
50
From the POV of this piece, whether you want process or outcome neutrality...depends. You're being "neutral" so you can enlist the trust and cooperation of a varied range of people, in order to pursue some purpose that all of you value. Do the relevant people care more about process or outcome?
Another way to look at it is that it's ultimately always a question of process. "Ensuring equality/neutrality of outcome" means "I propose a process that makes adjustments so that outcomes end up in a desirable "neutral" configuration." Then the questions are: a.) does that process result in that "neutral" configuration? b.) is that configuration of outcomes what we want? c.) is the process of adjustment itself objectionable? (e.g. "whether or not material equality is desirable, I don't believe in forced redistribution to equalize wealth").
When you are building an institution that aims at neutrality, ultimately you're proposing a set of processes, things the institution will do, and hoping that these processes engender trust. "I can't accept the likely outcome of this process" and "I can't accept the way this process works" are both ways trust can break down.
links 11/22/2024: https://roamresearch.com/#/app/srcpublic/page/11-22-2024
- https://www.slowboring.com/p/can-we-have-a-family-friendly-high Matt Yglesias designs a family-friendly high rise. i want this!
https://www.experimental-history.com/p/underrated-ways-to-change-the-world
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I don't know where I got that last sentence; that's clearly bogus. If you knew that a certain drug, target, or research strategy was going to work, of course you could profit off it. That is literally what the biotech industry does.
1
https://www.darpa.mil/work-with-us/heilmeier-catechism good advice for how to write proposals