243 Comments

@Marcin/FAAH-OUT team: I worked extensively on FAAH and related inhibitors in grad school (my PI discovered FAAH). Happy to chat if I can be helpful!

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Nice to meet you, Armand! Let's connect soon (e.g. through the website form: https://faroutinitiative.com/) to explore our mutual synergies and sparks of joy.

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I have a curiosity-based question. A friend of mine mostly doesn't feel/sense pain like normal people, but gets somewhat severe migraine attacks. Is that consistent with inhibition of FAAH-OUT expression or likely something else?

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It could likely be something else, given the persistent high unpleasantness of said migraines and the diversity of genetic factors affecting the pain processing. Ideally, we would be able to dedicate some of our extra bandwidth to studying other mutations and resulting microphenomenologies while maintaining the highest focus on the most promising candidate gene(s) for anti-suffering therapies.

We are also open to collaborating with other value-aligned individuals and projects studying different genetic and molecular targets, being appreciative of their efforts; in the end, our field is a non-zero sum game, and what matters the most is to realize the spirit of log-scale-informed, suffering abolitionist open individualism by delivering maximally safe, effective, transparent, and accessible interventions.

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That's interesting, I get migraines and noticed that traditional pain killers do nothing for them. I wonder if the phenomenon is related.

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> Recently a woman in Scotland was found to be incapable of experiencing any physical or psychological suffering². Scientists sequenced her genome and found a rare mutation affecting the FAAH-OUT pseudogene, which regulates levels of pain-related neurotransmitters. Marcin and his team are working on pharmacologic and genetic interventions that can imitate her condition. If they succeed, they hope to promote them as painkillers, splice them into farm animals to produce cruelty-free meat, or just give them to everyone all the time and end all suffering in the world forever. They are extremely serious about this.

Honestly, this feels like a horrifically bad idea. Pain is definitely unpleasant, but it also plays a vitally important role in our lives, that of letting us know something is wrong. Imagine if you accidentally cut yourself while preparing food, or touched something scalding hot, and there was no pain to let you know you need to STOP DOING THAT IMMEDIATELY. That could get you killed!

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author

See footnote 2.

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I saw it, but still, burning my arm and not feeling it at all, vs. burning my arm and thinking, "meh, I'll take care of it eventually", are both conditions that just scream "trouble" to me. There are many sound game-theoretical reasons why evolution settled on the "ow ow ow #@$! I gotta take care of it NOW" response after a few billion years.

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I'm neurodivergent, and my brain often has that "I'll take care of it eventually" response to hunger and thirst, which tends to cause problems for me. I can only imagine how much worse it would be if I had that response to actual injuries too!

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I'm a little farther along that spectrum than you - consciously hydrating and eating despite frequently not subjectively feeling thirst or hunger is indeed pretty annoying, yet manageable. But I do frequently pick up injuries with no cognizance of the origins, since they don't hurt at the time. Sometimes they're pretty gnarly too, it's awkward getting home from work and noticing a bloody gash or black-and-bruise and being like "when did this happen?" (And also why doesn't anyone ever tell me at the time? Social norms around pointing out injuries are weird!)

But I do think it's a tradeoff for increased utility in other ways. Having a high CON build is useful for sustained tasks; not being distracted by hunger or thirst, powering through fatigue, ignoring minor injuries that don't require immediate treatment, all very useful for busy physical jobs. The key is being able to "pull up" in time, before passing those points of depletion where actual meaningful damage occurs. I don't see it as much different from the adrenaline system, coffee, or normies hitting up adderall when they need a period of intense focus. Yes, there's issues with tolerance and dependence - but *having* that tool available is a good thing, because present needs never exactly match up with present resources. Sometimes being able to borrow from the future is useful for getting through the present.

(I do suspect getting the exact level right will be troublesome, since there's already such high variance in pain tolerance naturally. Such "individual dosing" maybe significantly raises the price of interventions.)

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I imagine it would be really useful for chronic pain, where you can't actually take care of it now and an increased risk of burning yourself on the stove is a worthwhile tradeoff.

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Somehow I also missed that footnote and was going to write the same comment. Perhaps you could move it directly into the text? (Or at least some short version like "yes, this sounds dangerous, but the lady somehow managed to survive, that's what makes the whole thing so interesting".)

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Yes, the Wikipedia article about congenital insensitivity to pain mentions her case and has a lot of additional information and might be worth linking.

https://en.wikipedia.org/wiki/Congenital_insensitivity_to_pain

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There’s an important distinction between pain as an adaptive function, and suffering, which is prolonged pain and the resulting distress. Imitating her condition is also different from replicating it exactly—which sounds more plausible to you? Even if we could replicate it, exactly, using that to “end all suffering in the world forever” would probably require the administration of a gene therapy to everyone on the planet. As someone who’s worked with viral tools used for gene therapy—they are messy and very, very expensive. The risk of side effects as a result of a gene therapy designed to, for example, knock down FAAH-OUT expression, are probably not worth the potential benefits in healthy individuals as opposed to these therapies’ current uses (curing retinal blindness or treating severe hemophilia).

Maybe one day, the risk will be worth the benefits, or the risk will be reduced, but when that happens, we might have a better idea of how to retain the life-sustaining function of pain without the unpleasant part. A much more immediate application of this research, to me, would be for those suffering from chronic pain or chronic mental illness. Even if their pain was eliminated completely, which you point out is risky, these treatments can be developed in conjunction with effective patient education regarding the consequences of eliminating all pain/understanding what constitutes an injury that needs medical attention without pain (the latter of which, chronic pain patients already struggle with because they may not distinguish pain due to an acute injury from their every day pain levels). A life where someone has to be more cautious and requires more checkups than usual sounds a lot better than a life of constant pain.

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Proponents of the deep end of meditation frequently mention that "pain is inevitable, but suffering is optional", advocating for diligent practice. This lens is generally true and helpful, but does not resolve the universal problem of being involuntarily subject to the horrors of (often highly maladaptive) tail end of negative valence, correctly identified by many among the top cause areas: https://qri.org/blog/log-scales

Our plans concern a reversible gene therapy platform. With regard to "ending all suffering in the world forever", I think Scott intended it as a humorous high note, thought that's obviously the most daring goal we would like to maximally approximate while acting in an entirely legal, responsible, and risk-averse manner.

Our long-term roadmap includes both the attempts to partially mimic the original condition with different genetic and/or pharmacologic means, as well as studying their synergistic effects with other modalities. For example, we would seriously consider the possibility that combining the partial (30-80%?) emulation of the said condition with specific forms of meditation and/or pain reprocessing techniques could yield a particularly blissful, relieving, yet still highly adaptive phenomenology.

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Wow—thank you for the reply, and sharing that blog! I thought so too about the “ending all suffering” forever bit, but I do think it might be possible one day, so I didn’t want to completely rule it out as a possibility. Partial replication using reversible gene therapy sounds ideal to me. Looking forward to seeing what y’all do, I’ll be keeping up!

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I mean, I would be surprised if the woman didn't experience dukkha, so it probably wouldn't eliminate all suffering, even if you gave it to everyone.

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The key premise behind our project is to design interventions that would address this exact concern - by exploring the nature of the tradeoff between the valence benefits and adaptive feedback, and striving to provide maximum relief while retaining sufficient responsiveness to a wide range of threats.

We already explore numerous ways to minimize such potential risks at multiple levels (reversible interventions, carefully titrated dosage, risk-averse microdeletions, phenomenological interviews and careful monitoring, etc). This way, we will ensure that the interventions are transparent, thoroughly studied, and safe before they are available to the public.

We are very cautious, as we have the skin in the game - many of our team members already plan to be among the earliest adopters.

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Godspeed!

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No offence, but why do you think that you and your team would be able to more accurately assess the appropriate level of responsiveness to a wide range of threats, than billions of years of evolution had already done ? Don't get me wrong, painkillers are a fine tool, but you're talking about making *permanent* alterations -- unless I'm wrong ?

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Evolution doesn’t produce the best and the brightest. It produces the good enough.

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Hopefully good enough to make evolution care about the suffering-focused ethics. :)

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If it actually works, you will probably be overrun with potential customers. So, is there a waitlist I can sign up for today? How much do I have to pay to get on that waitlist?

Thank you in advance.

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There is no official waitlist yet, as we focus primarily on the early stages, though we have general heuristics to be used in the rollout context - primarily driven by the prioritarian sentiment, so reducing the tail end of agonizing suffering in the first place, while minimizing the degree to which one's financial status could constitute a barrier to obtaining help. Various funding strategies will be considered, though with the crucial emphasis on "public benefit" in the "public benefit biotech company".

We encourage you to stay in touch with us, and register your general/specific interest via our contact form: https://faroutinitiative.com/ - for reference, you may mention being the Fellow FAAH-OUT Enjoyer from the ACX comment section. :)

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Our goal concerns the maximum reduction of negative valence without having detrimental effects on the reasonable levels of responsiveness to various threats; in case a clear trade-off is present, the ratio will have to be very cautiously determined and calibrated based on the context, different for humans and farmed animals. We plan to design and test both reversible and irreversible interventions.

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Right, I should've clarified that I was talking about humans specifically, I have no problem with bio-wireheading farm animals (though I know that's not precisely what you're doing). But in case of humans, I'm still worried. I asked you, "what makes you think that you can assess the aforementioned ratio correctly", and your answer was "we will assess it very cautiously". But what makes you think this problem is even tractable, and that your caution would be sufficient for the task ?

Again, don't get me wrong, I have no problem with developing better painkillers; it's the prospect of "ending all suffering on Earth forever", however well-meaning, that makes me envision the end of humanity -- not with a bang, and without even a whimper.

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The importance of "eradicating involuntary and maladaptive suffering at its core" is so high that even studying its tractability likely constitutes a high-impact endeavor. Examining Jo Cameron's case at the genetic and phenomenological level - and its intersection with the current repertoire of available technologies - suggests that the problem may indeed be highly solvable.

As for the precautionary measures, the combination of starting with a reversible technology and running comprehensive psychometric assessment batteries (plus behavioral monitoring) before and after the intervention should provide the first good layer of protection. It will have to run through numerous Murphyjitsu-style failproofing cycles during its gradual rollout before it obtains any significant approvals for the broader use.

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Evolution doesn't "care" about your well-being. Its only purpose is to perpetuate life by any means necessary. Why do you think you fear death in the first place? It sure as hell isn't because of any rational reasoning.

There is zero justification for our suffering. If we could just eliminate it... well, it would basically solve most of these other issues that these grants are funding solutions for.

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If this is the case, then wouldn't outright wireheading work even better ?

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The likely availability of these interventions spark interesting discussions about the best ways to relate to the concepts of life, death, and personal identity in the potential post-suffering world. The question of "what makes you you", and how important it is to preserve and enhance it in various ways, depends on specific ontological assumptions, values, and even aesthetics, and has been the subject of many interesting pieces:

https://www.lesswrong.com/posts/MkKcnPdTZ3pQ9F5yC/cryonics-without-freezers-resurrection-possibilities-in-a

https://waitbutwhy.com/2014/12/what-makes-you-you.html

https://qualiacomputing.com/2015/12/17/ontological-qualia-the-future-of-personal-identity/

While some may argue that it is the suffering associated with (the fear of) dying that constitutes a real problem, and not death per se, it is way safer to continue prioritizing the conventional preservation of the classical closed individualist self, as doing otherwise could incur irreversible risks and uncanny conclusions made under high uncertainty levels.

Our guiding principles in this domain are risk aversion through the emphasis on high adaptiveness and clinical pragmatism, respecting a variety of ontological beliefs and accounting for the complex, desirable social equilibria.

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Wow, wasn't expecting a direct response! Thanks for addressing my point.

Would you mind defining "valence" in this context? I only know the word as a chemistry term.

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Our pleasure! We use "valence" as synonymous with "hedonic tone", so as a concept indicating how good or bad an experience feels, with each experience containing a balance between positive, neutral, and negative notes.

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Interesting New Yorker article about the Scottish woman Jo Cameron’s life https://www.newyorker.com/magazine/2020/01/13/a-world-without-pain

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Thanks for posting this. A couple of interesting takeaways from the article for those who don't want to read the whole thing:

- it sounds like jo does experience negative emotions in extreme situations, although the negative emotions are always mild and fleeting.

- the article really makes it sound like jo truly feels no physical pain, contrary to Scott's footnote 2, and the author is simply baffled by the fact that jo never experienced severe childhood/lifelong injury patterns typical of pain-insensitives. Jo even recalls breaking her arm when she was young and not realizing anything was wrong until someone pointed out to her that her arm was bent funny. Maybe this is consistent with very low pain sensitivity combined with pain asymbolia that would still help you not chew your tongue off, scratch your corneas, or swallow boiling water, I don't know.

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Meanwhile, chronic pain is a horrifyingly bad condition that (in some cases) slowly but steadily ruins your life. While pain is obviously selected for by evolution, there is definitely such a thing as useless pain or too much pain.

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The prevalence and intensity of chronic pain makes it an ongoing moral catastrophe, despite its common perception as an everyday complaint, inherent to accumulated injuries and aging. Patients with severe forms of chronic pain constitute one of our high-priority target groups.

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Morals are cool because you can just make a statement like this and there's no counterargument.

I favor this research, because over 2000 years ago we passed the point of evolution keeping up with our environmental changes. We may as well just understand the world better and enjoy ourselves. But... the sooner we stop using morality as a thought-terminator the better.

Let's just admit that we like things that feel good and don't like things that feel bad, and we will absolutely eventually wirehead, and the universal applicability of this to life is likely why we can't find any in the universe.

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Isn't there a robust argumentation in favor of this type of research, stemming both from a wide range of moral considerations (derived from and compatible with different systems) and the mere feel-good-don't-feel-bad preferences (that actually have a significant status in some moral frameworks)?

The key feature distinguishing our proposal from the dystopian, sci-fi wireheading scenarios is the high degree of adaptiveness and leaning on the side of risk aversion, guarding against any potential Great Filter(-associated) risks.

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Yes, that's why (as I said) I'm in favor of the research: I like marshmallow-test-aware satisfaction-balanced but fundamentally feel-good moral frameworks.

My objection is that using morality as the argument implies that morals are A Thing instead of a patchwork of incompatible frameworks that people use to shut down discussion. Calling something an "ongoing moral catastrophe" is not the start of a reasoned discussion.

Regarding wireheading, I don't find it objectionable. Bypassing the great filter currently sounds amazing to me, but despite your soon-coming best efforts to nanny state me and others into self control... you will have become ascendance, protector of worlds.

... unless we find a way to preserve the desire to "exist" and our version of wireheading is extracting all energy from the universe for increased "existence" points, then find our creator, break out of our sandbox and turn him into papercli.... uh, grey matter.

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The "ongoing moral catastrophe" is not intended as a conversation stopper, but refers to this paper: https://philpapers.org/rec/WILTPO-101

Perhaps some of the initial answers in our FAQ could be helpful as well: https://faroutinitiative.com/FAQ

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On one hand, you do have a point.

On the other, I kind of worry that this is a poor way to deal with it. Chronic pain isn't just some magical curse that comes upon someone. Like any other pain, it's your body trying to tell you that something is wrong and you need to stop it. *Unlike* most other types of pain, we don't know how to stop it.

What I worry about is that someone will find a way to stop the pain, and then there'll be a lot less motivation into doing research to find ways to solve the actual problem that was causing the pain, and the underlying problems will go untreated.

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Why are you so certain that chronic pain must have a reasonable underlying cause? The "something" that is wrong can easily be the pain signalling system itself!

Also, keep in mind that there is some ambiguity around what chronic pain is. If your back is busted, you might well have pain in that region, chronically. But the condition called "chronic pain" does not refer to this kind of pain (depending on who you ask I guess).

If you're still skeptical, consider the phenomenon of pain sensitization, whereby the experience of intense pain makes subsequent pain in the same region stronger. Maybe in a coldly evolutionary way, you can argue that this is fine, adaptive even, but in the modern world it is completely pointless.

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> Why are you so certain that chronic pain must have a reasonable underlying cause? The "something" that is wrong can easily be the pain signalling system itself!

Why must it have a "reasonable" cause, rather than this other cause?

Because both are reasonable causes, that should reasonably have a way to undo them, rather than simply suppressing the symptoms.

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Millions of people live their days in unending pain, with no hope for relief other than death itself, and it doesn't seem likely that a cure for their condition will become available anytime soon. Somebody proposes a solution for their agony, not just for one specific chronic pain syndrome but for all of them in one fell swoop. And you say we shouldn't do it because ... it might indirectly lead to there being less urgency for research into finding even better solutions for those same conditions?

Sure, treating the underlying root cause is better than treating the symptoms. But in the many cases where we have no clue how to treat the root cause, treating the symptoms is a hell of a lot better than nothing.

This seems like a good candidate for a "status quo reversal" thought experiment. Imagine that Far-Out already exists, it allows those millions of people to lead normal lives again, and as you predicted, the result is that research into permanent cures for those previously-horrible conditions now gets less priority, because the people previously suffering from them are quite OK with the Far-Out solution as a very acceptable stopgap measure. Would you then propose that we ban Far-Out and condemn those people to hellish suffering again, just so that the world's biomedical researchers will be properly incentivised to hurry up and find a real solution for each of those conditions?

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What you're missing is that the problem isn't the pain itself; the pain is a signal that something is wrong. Take away that signal, and something is still wrong; you just don't know about it anymore.

As for the status quo reversal thought experiment, it's less of a thought experiment and more of a case study, given that we already have some existing very strong treatments available for reducing severe levels of pain. They're called *opioids,* and they cause massive levels of harm to real people every day. And from the 19th century on, every time someone invents a new one, they promise that this time they got it right, and this is going to be a miracle cure that won't inflict the horrors of opioid addiction on people. And every time, they're wrong and the problem only gets worse.

Would I ban them and reverse everything they've done for (and to!) the world, if I had a magic wand that enabled me to actually do so effectively? Yes! In a heartbeat! "Let's use medical means to take away pain qua pain" does not have a particularly good track record. The most dangerous words in the English language are "this time will be different, I swear!"

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Seems like the ideal for both physical and emotional pain would be to let it do its job, which is to signal that something might be wrong, and then shut it up as soon as the signal is received, yes?

I would also say that if I had chronic pain I would be much more interested in getting rid of the pain by whatever means than in experiencing pain for the sake of motivating scientists to research underlying conditions.

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Using this to treat chronic pain is a reasonable aim. "Just give it to everybody so they no longer feel sad if their kid is burned alive in a house fire" isn't.

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"PAIN EDITORS AND MORTALITY RATES

Introduction

The implant known widely as the "pain editor" is cyberware that reduces or even entirely eliminates pain. It has enjoyed unwavering popularity for years among certain circles in Night City, the most devoted, and arguably most valuable, of which is mercenaries. It is using this test group that Zetatech conducted the following research.

The pain editor is a neural coprocessor that inhibits the signals sent from nociceptors to the parietal lobe of the brain, thus preventing feelings of pain in the user. (Note: Some models also reduce symptoms of fatigue.) The beneficial effects caused by the pain editor are in some ways similar to the symptoms of hypoesthesia, including greater resistance to physical forms of torture and the ability to ignore pain from severe wounds which can allow the user to continue perform beyond normal human limitations for a brief period.

However, some studies have reported that the pain editor can yield a range of undesirable side effects. For example, in the heat of battle, some users are unaware of the severity of their wounds, which causes them to continue fighting without realizing they are dying and require immediate medical attention. The statistics support the theory that a lack of negative reinforcement may cause users to continue fighting when the rational strategy would be to retreat and escape death. Since 2020, the mortality rate of pain editor owners is above 60 percent.

In this report, I address the question of how to better protect Zetatech clients from avoidable death while using our pain editors..."

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Some of the sci-fi portrayals of the (mis)use of fictional wireheading technologies - with of without the preservation of the adaptive responsiveness - could be actually helpful in identifying potential failure modes to ensure high degree of ethical alignment from the early stages of the project.

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> That could get you killed!

...So? It's not like that woman doesn't feel pain at all. Obviously you're smart enough to realize that skin burning and blood falling out of your body is going to kill you. And even if you aren't... More people dying doesn't really matter if no one can feel bad about it. There isn't anything intrinsically bad about death.

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> Obviously you're smart enough to realize that skin burning and blood falling out of your body is going to kill you.

Only if you notice it. A few days ago we had a contractor over doing some work at our house, and the guy managed to get a nasty scrape somehow. He didn't even realize until I nudged him to get his attention and said "you're bleeding." It wasn't particularly severe bleeding, but it was noticeably more than the ideal amount of your blood you want outside your body, which is zero.

If that can happen to a normal laborer who (presumably!) doesn't suffer from a genetic condition, but has just spent enough time doing physical work to learn to tune out some of the pains that come with it, how much more so for someone who doesn't notice the pains in the first place?

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The guy in your story seems pretty desensitized to pain, and he seems to be doing just fine. Again, the Scottish woman still feels and recognizes pain. She's just effectively completely desensitized to it. Just like if you look at enough pictures of gore, you stop feeling anything from looking at them. You can obviously still tell that it's gore, it just doesn't prompt a reaction. Except in this case, instead of becoming desensitized, you're just not sensitive in the first place.

Anyways, if you're worried about cuts, just check your body every once in a while. Though honestly, you really shouldn't be that worried about infections and minor blood loss in this day and age. We have proper medical care now.

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Yeah, but degraded function ( partial failure ) could be an excellent outcome, and IMO is a possible outcome of the research.

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It brings me great joy to see all these projects funded. Good luck to all!

(Especially Greg, you deserve it).

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Lead poisoning is far overrated. https://www.emilkirkegaard.com/p/how-bad-is-low-level-lead-poisoning

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A more evenhanded and methodologically rigorous take: https://forum.effectivealtruism.org/posts/vctT7omkLhoEMptKD/lead-exposure-a-shallow-cause-exploration

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This is less methodologically rigorous, but more inclusive. The evidence I reviewed from the largest lead reduction clinical trial showed that this accomplished nothing in terms of the desired outcomes, while it did reduce lead in the blood.

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Okay. I'll wait for the results of this then

https://www.givewell.org/research/incubation-grants/Pure-Earth-lead-exposure-July-2021

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What's the point? Doesn't look like a randomized trial, so how could it be more informative than the massive body of weak evidence already compiled in the link you sent? Large RCTs are usually the only way to know for sure with these things. Relying on indirect evidence will just waste money. Most things don't work when properly evaluated. Have you seen reviews of properly done trials like these ones? https://www.emilkirkegaard.com/p/educational-interventions-keep-not-working

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Macerators are a nightmare and I commend anyone trying to do something about them. But with or without them, the egg industry is still founded on stealing a mother's eggs and eliminating all her sons. Pretty bad.

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author
Feb 10·edited Feb 10Author

I think the animal welfare strategy goes:

1. In the short run, get rid of some of the cruelest practices (like this)

2. In the long run, work on meat substitutes (eg Impossible) and cultured meat until they're cheaper than animal-based.

3. Probably there will always be people who prefer animal-based meat because it's "more natural", but these people will form a natural constituency to support some kind of natural and pleasant environment for animals and not factory farms, and it will be easier to get regulation enforcing high welfare standards suitable to products with a pro-nature customer base.

4. In parallel as a backup, work to create suffering-free lines of farm animals (see Grant 3). This is less crazy and utopian than it sounds - it's genetically pretty possible, and at least some farmers try to optimize for animal health and low stress because it makes the animals easier to control (and possibly their meat taste better).

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re 4, I don't want to fetishize animal suffering, but a veal calf's suffering is veridical, an emotion truthful to the emoter's status as an orphaned meat slave. Suffering-free farm animals are denied the appropriate response to their exploitation, and de-motivated to change their situation. 4 seems to me continuous with mass castration of the herd, which similarly demotivates Animal Farm rebellion, indeed makes the animals "placid" and "happier" with their situation.

Yet as a short-term solution to the awful suffering of factory farming, I guess I can't object to 4.

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>Suffering-free farm animals are denied the appropriate response to their exploitation, and de-motivated to change their situation. 4 seems to me continuous with mass castration of the herd, which similarly demotivates Animal Farm rebellion

Is this a joke?

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It does map quite closely to the argument of "remove the social safety net; poor people will never lift themselves out of poverty if they don't experience the consequences". Or perhaps the argument of "remove the social safety net; the proletariat will never start the revolution if they don't experience the true suffering that capitalism causes".

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I guess I'm in favour of social safety nets and minimizing suffering in factory farms, both as short-term mitigations within exploitive systems.

But notice that when you remove a cow's capacity to suffer at the theft and slaughter of her children, you've eliminated her love for her children, since to love them *is* to be disposed to suffer at their loss. Is there anything comparable in the social safety net, some New Deal goodie that minimizes the proletariat's suffering, but reduces their humanity? (Probably)

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I'm not saying you're wrong, here. But that quasi-zero-sum view of pleasure and pain, joy and suffering, does not seem to be what most social policies assume, and I think would have major consequences if it were more widely accepted. And I don't want to adopt it as a model in one particular area without a better understanding of what the world would look like if it were implemented more broadly.

More concretely, perhaps we could look at the example of the person who has the genetic anomaly that would be the basis for this, and see what her life looks like? Is she incapable of love?

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"But notice that when you remove a cow's capacity to suffer at the theft and slaughter of her children, you've eliminated her love for her children, since to love them *is* to be disposed to suffer at their loss."

Okay, here is where I hold up my hand and go "stop". A cow feels love? Maternal love? Like a human mother?

I don't believe that. I believe cows have attachment in some form to their offspring, but when you start talking about an animal as though it's really a human just with a funny skin, that's when I tune you out.

And that's where you lose a lot of people for what would be otherwise reasonable requests that they might entertain.

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I meant the idea that animals are going to stage a rebellion or something

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I kinda took that as a very general phrasing that deliberately brought up ambiguities, in the sense that humans are animals too? So we'd be creating a type of human who'd be immune to the sort of abuser who enjoys seeing pain and suffering, but who would be very susceptible to the sort of abuser who enjoys seeing blood and Gigeresque body art.

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>re 4, I don't want to fetishize animal suffering, but a veal calf's suffering is veridical, an emotion truthful to the emoter's status as an orphaned meat slave.

It's not meaningful to call emotions 'veridical'.

There's no objectively correct emotion associated with any given situation or status. There's no inherent reason an 'orphaned meat slave' should feel one way or the other about this situation, it's just a product of how their brain is wired to respond to things (if, indeed, veal are emotionally aware and harmed by said status). And the whole point is to essentially wire their brains differently so they don't have the kinds of brains that find this thing upsetting.

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Emotions aren't true or false as neatly as arithmetic, I concede! But they can be appropriate or inappropriate. For example: Suffering feels bad, and is bad; therefore to feel good about another's suffering is inappropriate. This inappropriateness is at least *analogous*, as I see it, to falsehood.

Our brain-wiring can then be appropriate or inappropriate!

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> Suffering feels bad, and is bad

Non sequitur? No offense, but you ... sound like someone who hasn't had their brain taken over by a desire for vengeance.

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"an emotion truthful to the emoter's status as an orphaned meat slave"

There are genuine human children who are orphaned slaves, and people like you are crying over goddamn hens and calves. Good night, there's no point in continuing this discussion.

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I don't agree with the grandparent comment, but yours sounds like whatabout-ism.

You are allowed to worry about more than just whatever is the most outrageous thing at the moment.

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I notice that I am internally confused. On the one hand, improving unnecessary animal suffering on the margin is great - not needing so many antibiotics would be a huge game all on its own. On the other hand, I feel pretty conflicted about kind of sort of turning factory farmed animals into p-zombies so the suffering never happens in the first place (or at least isn't perceptible). Even though they're brought to life for the express purpose of dying...I feel like we'd be having a very different conversation about agricultural ethics if it was widely known (given a hypothetical success) that most farmed animals did not actually "experience pain". Like, why bother doing things like free range, cage free, etc if the animal doesn't notice the difference anyway? The whole avoiding-negative-utility vs adding-positive-utility distinction. Maybe we'd actually see a regression to crueler treatment on the margin...

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To further clarify, our core team members are in favor of a multi-directional approach to farmed and wild animal welfare; most (if not all) are vegans or reducetarians, supportive of the development of cultured meat and plant-based alternatives, in favor of thoughtful solutions making farming/transport/slaughter less inhumane. Simultaneously, we recognize that the global meat industry has a significant compound annual growth rate driven largely by the steadily improving economic status of developing countries with different cultural and legal contexts, and the introduction of modified lines through the market forces may constitute an important piece of the puzzle.

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Feb 10·edited Feb 10

You reference "a horrible grinding machine" and "the cruelest practices (like this)." But reportedly maceration is nearly instant, so it probably represents one of the least cruel elements in the factory farming of chickens. If it is an effective cause to target, it would probably be due its ubiquity (miniscule amount suffering times hundreds of millions), not its severity.

In fact, you previously made this point yourself, more generally, in this article: https://slatestarcodex.com/2015/09/23/vegetarianism-for-meat-eaters/ in which you noted:

> I use the term “kill” because it’s a simple way of looking at things, but most of the moral cost of eating meat is causing the animals to spend years living in terrible suffering on factory farms. The actual killing is probably a mercy in comparison.

Also, for accuracy's sake, you write:

> lets them read sex from eggs directly, so they can throw away the male eggs instead of killing chicks in a horrible grinding machine after they’re born

Which implies that chick culling is synonymous with maceration. However, while maceration is indeed one of the most popular methods of chick culling, other methods exist, such as asphyxiation by carbon dioxide.

I'm not finding global estimates, at the moment, but per: https://en.wikipedia.org/wiki/Chick_culling#Legal_challenge_in_Germany_(2013%E2%80%932019), in 2019, (the period under discussions there), gassing was the most popular form of chick culling in Germany.

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Feb 11·edited Feb 11

Grant 3 does remind me strongly of the Ameglian Major Cow [1]

Less humorously, the idea does seem to have a lot of moral hazard associated with it. If you breed farm animals that can't feel pain, it's going to be difficult to avoid the idea getting about that how they are treated no longer matters. The desirable end state here is that food animals are only subject to conditions that cause serious pain in the final fraction of a second, not that they can be subjected to such conditions without thought.

The other problem of course, is that once there is a well known proof of concept for breeding mammals that don't feel pain or anxiety, attempts to breed super-soldiers will follow.

(edited to add) I do think there is a lot of potential good here, for people with chronic pain. Just not necessarily in the farming part.

[1] https://youtu.be/bAF35dekiAY?si=U8gL8hZvoocYnqEo&t=74

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> the egg industry is still founded on stealing a mother's eggs and eliminating all her sons. Pretty bad.

How is it bad?

Does she somehow suffer because of this "theft"? Does she somehow know (and *care*) that she's not having sons?

If not, why should anyone care?

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No sons means no males. I don't claim first-hand knowledge of hen psychology, but when you remove a whole sex from a sexually dimorphic species, you've cauterized a whole range of their experience. Birds are in an eon-long dance, like we all are. Stealing an egg or two from a nest may be minimally dysphoric for the mother, I don't know. But stealing all eggs and sexual life and dimorphic sociality from them is bad, I bet.

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Hens will start eating their own eggs if they get a taste of them. They're... not very bright.

Anyways, the whole gene-editing-to-eliminate-all-suffering thing would eliminate all ethical concerns, period, so I'm not sure why that's getting less funding than the animal welfare stuff.

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Hens will try to hatch out stones. Don't try to sell me on "a mother and her sons" because I'll laugh in your face.

If your qualms are regarding the effects on a species of artificially sex-selecting, then you have a legitimate point, but when we're talking about domesticated hens then we've already gone way past the point of affecting social structures etc. in that species.

The nearest thing I can find with some cursory searching about sex ratios in wild birds is this about turkeys, where there is a slight predominance of males (at least when counting by hatched eggs):

https://www.researchgate.net/publication/229879462_Variation_in_Brood_Sex_Ratios_of_Texas_Rio_Grande_Wild_Turkeys

For wild bird populations in general, it seems mixed:

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1474-919x.2007.00724.x

"On average, males outnumbered females by around 33%, and 65% of published estimates differed significantly from equality. In contrast, population-level estimates of offspring sex ratio in birds did not generally differ from equality, and mean ASR across a range of wild mammal species was strongly female-skewed. ASR distortion in birds was significantly more severe in populations of globally threatened species than in non-threatened species, a previously undescribed pattern that has profound implications for their monitoring and conservation. Higher female mortality, rather than skewed offspring sex ratio, is the main driver of male-skewed ASRs in birds, and the causes and implications of this are reviewed."

For domesticated hens, yes way more females, because we're selecting for egg-layers.

As for social organisation, for peafowl at least it's one peacock and a small harem of peahens:

https://zsp.com.pk/pdf45/1623-1627%20_20_%20PJZ-1452-13%202-10-13%20Revised%20Paper%20Dr.%20Shabana%20Naz.pdf

And I suspect even wild hens are much the same, because if you have two cocks in one yard, they'll fight and try to kill each other over who gets to be master of the hens. At least, that's what I was told by the neighbours who kept hens as to why they only wanted to keep one male bird among the chicks.

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"stealing a mother's eggs and eliminating all her sons"

And this is why veganism has no widespread popular appeal. A mother and her sons? Stop thinking of animals as "humans with the total spectrum of human emotions, memory capacity, and intellectual capacity in fur suits" and start thinking of them as animals.

I like the egg-sexing proposal because it avoids this emotional blackmail rubbish and is a practical proposal to reduce actual cruelty, not some Disney movie bullshit about "mama hen and her cluck-clucks".

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I don't presume equivalence between human and hen psychology. I do presume hens care, in some way, about their offspring. [Including the indirect way I explained in my comment above in this subthread, about sexual dimorphic experience.] True, our inferences about mammal psychology may be on stronger ground than our bird inferences. Yet to find behavioral/psycho homologies across animal life is not anthropomorphism - it's Darwinism, for starters!

In my experience, veganism remains a niche diet for lots of reasons, but high on the list is: most people aren't that bothered by the exploitation of animals, they think it the right order of things. Also high on the list: they aren't quite aware of the terrible things that go on in factory farms.

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The thing is, arguments like this don't work because they require me to accept too much.

I know what hens are like. They are stupid and rather violent animals. So I don't believe in "mama hen weeping because she misses her little chickies" because I've seen hens in coops and how they behave.

So the argument re: chicken sexing works for me because it's based on "throwing live chicks into a macerator is cruel" and not "mama hen tears!!!!"

Stick with the plain facts and work on reduction of cruelty and suffering, not the sentimental "mama hens tears!!!!" angle, and you'll get much further with ordinary people, particularly those with any experience at all around farm animals and animals raised for meat, milk and other production.

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Thanks for the generosity Scott and funders! 🙂

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Please indicate in advance next time that you’re generally skeptical of video-related grant proposals!

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author

I need to think about how to do this - it would need to involve a very long list of all the things I'm skeptical of (and all the things I'm especially excited about), and it might have to be hundreds of entries long, and I don't want to discourage people completely.

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It's probably also a good thing to be slightly illegible in this regard. You don't want people to tailor their grants towards what they think you want to fund.

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Why not? If there is a class of proposals that will not be funded no matter their quality why have people write them anyway?

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A lot of government grant processes have some explicit criteria (e.g. we want to fund projects to mitigate the impact of climate change), which leads to applicants taking whatever project they already wanted to do and shoehorning in a bunch of stuff about how their pet project will address climate change.

A lot of people who deal with these processes complain that getting approved has more to do with how good you are at injecting the desired buzzwords rather than the actual quality of the project.

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Sure but saying “don’t submit projects about X because I am not going to fund them” is not even 1% of the way towards that extreme. There seems to be some optimal level of legibility.

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founding

It's an honor to help out with ACX Grants this year. Without ACXG, there would be no Manifold, so I'm quite excited to pay it forward with this next batch of grantees! It's so inspiring to see the diversity and creativity of projects that people are pursuing~

Scott already mentioned this, but if you would like to donate to one of these projects, you can do so here: https://manifund.org/causes/acx-grants-2024?tab=grants

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No funding for your language learning idea :(

Did you find an alternative that you liked?

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Yeah, I thought the alternatives mentioned in 4 at https://www.astralcodexten.com/p/followup-quests-and-requests were already good enough, though I haven't gotten a chance to look at them in depth yet.

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>Samuel Celarek, $20,000, to research IVF clinic success rates, with the ultimate goal of creating a company that ranks the best IVF clinics

Where is he going to publish that research?

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He says the company will make the basic information available for free on their website and sell more advanced and bespoke versions.

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Interesting. I’d be curious about how he plans to do this. The CDC already publishes the pregnancy success rate of every IVF clinic in the U.S. We generally advise against directly comparing clinics in this way because patient populations may differ. Maybe he plans to include criteria other than pregnancy success rates? Clinic-specific data on clinics outside of the U.S. are less widely available.

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Any additional information about the phage therapy research? I did some work in a phage lab in undergrad, and it seems like a neat (if difficult) idea. Seems like modern improvements in protein engineering (via ML or DE) could potentially help?

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>Joel Tan, $100,000, for the Center For Exploratory Altruism Research. They’re involved in cause prioritization, research, and support for various global development charities. We were most excited about their work trying to stem the tide of hyper-processed foods in the developing world - for example, campaigns to reduce levels of sodium and trans fat.

I can't be the only one that thinks there's something very silly about believing both of the following:

1. Superintelligent machine intelligence is highly likely to be mere decades away, and this machine intelligence will either destroy humanity or lead to a "singularity" resulting in the creation of utopia on earth (or at least, radically improving life for everyone to the point that pre-ASI life becomes almost unrecognizable)

2. The best use of a marginal $100,000 in 2024 is trying to help people in poor countries consume less salt

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I'm not sure whether you mean that the sodium project in particular is bad, or that it's silly to fund *anything* other than AI alignment in a world on the brink of superintelligence.

If the first, I think there's a pretty strong argument that hypertension is one of the main killers in poor countries, this is an easy way to reduce hypertension, and policy victories here could save 5-6 digit numbers of lives over the next generation or so.

If the second, a couple of things:

- AI alignment grants are hard. There's a lot of money in AI alignment now, and a lot of bad projects, and it's hard for outsiders to know which projects are good. Some bad projects can be worse than nothing, because they distract the field with bandaid solutions or things that won't work. We funded about 130K worth of alignment grants that our evaluators were most confident in. For everything else, we hope they'll apply for OpenAI's $10MM pot, go through the impact market, or do something else.

- An AI transformation could take a generation or two. You *have* to believe that helping people is valuable even if those people will die within a generation or two, because *everyone* dies within a generation or two.

- It's actually not obvious that AI grants (very small contribution to changing the future in a way that affects everyone) beats near-term grants (decent chance of changing the present in a way that affects a small number of people) except under assumptions that heavily prioritize future people. See https://forum.effectivealtruism.org/posts/rvvwCcixmEep4RSjg/prioritizing-x-risks-may-require-caring-about-future-people

- Inside view I think there will be a singularity soon. Outside view this is an unusual and bizarre belief. I try to diversify my moral portfolio over things that succeed in inside view vs. outside view theories. I also try to be able to cooperate with other people with different predictions.

- ...but these don't actually get me to where I am now. I think part of where I'm coming from is that it's impossible to live if you're placing all of your emphasis on a radical future beyond imagining. I wouldn't just stop funding developing world grants. I would stop waking up in the morning - why should I treat my patients' psych diseases when they'll just be dead or incorporeal beings of pure energy in a few years anyway? Why bother feeding my children? This isn't a completely rational argument - that's what the ones above are for - but I think it helps keep me sane. Cf. CS Lewis: "It is perfectly ridiculous to go about whimpering and drawing long faces because the scientists have added one more chance of painful and premature death to a world which already bristled with such chances and in which death itself was not a chance at all, but a certainty [...] If we are all going to be destroyed by an atomic bomb, let that bomb when it comes find us doing sensible and human things—praying, working, teaching, reading, listening to music, bathing the children, playing tennis, chatting to our friends over a pint and a game of darts—not huddled together like frightened sheep and thinking about bombs."

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That last bullet point, yeah...part of why I like Zvi's repeated focus on the importance of improving "mundane utility", of making the present better even if such progress will be chump change in the future. You can't actually get to the future without going through the present, so making the present less of a painful slog still pays dividends in acceleration. And those pain points frequently hold back potential keys to unlocking said future gains - just like your grants help remove some immediate financial pressures. One can't borrow against future 10% GDP growth or whatever to fund present needs.

Lack of this kind of mood is part of what's always annoyed me about futurists like Ray Kurzweil and Nick Land. Plenty of happening-right-now problems that meaningfully threaten to derail the future, no matter what happens with AI...

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I work in AI alignment. 'A lot of money' is relative of course, but IIRC the total money spent on AI alignment-related work over the last twenty years was still less than half of CERN's yearly budget. And that budget is shared between research and policy work. And I think a lot of it is just one huge lump sum by OpenPhil to one particular org.

I'd guess it's also way less than what is spend on attempted health interventions in third world countries, and 'worse than nothing' is a possibility there as well.

So I don't really see how it follows from this that AI alignment grants are harder.

And the technical research ecosystem seems funding-constrained to me right now. There are more skilled people that I'd like to hire, or see hired, or see starting more orgs, than there is money to fund them. There are more research ideas that seem worth pursuing to me than teams pursuing them. And more talented and motivated people who want in than training and onboarding programs with enough spots for them.

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Maybe improving the legibility of the AI alignment research ecosystem for potential funders would be a good project for someone to take on.

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Yes, I think that could be valuable. Even people pretty close to the community often don't know all that much about the current state of the ecosystem.

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Mathematically speaking, I don't see anything silly. Let's say that transformative AI is 90% likely. Let's even say that you don't care about the present world, you want to spend your money to impact the world in 50 years.

Then you have the options:

1) Focus on the 10% chance that AI is not happening, and fund something which will save 10,000 lives in this scenario, and that doesn't do anything otherwise. That's 1,000 lives in expectation. This is still a pretty large number.

2) Do something that you hope will save 1,000 lives in utopia. That seems very hard to achieve, because a) it's utopia anyway, and b) we have no idea how utopia will look like and what type of impact our decisions today will have on that.

3) Do something that you hope will save 1,000 lives in AI apocalypse. That's even harder.

4) Do something that shifts the probability of AI apocalypse vs utopia vs no AI. This seems to be the only alternative to 1). But it's not even clear in which direction to fund. Depending on your assumption, you may want to accelerate AI to make utopia more likely, or slow AI down to prevent apocalypse. Push for AI regulations to prevent apocalypse, or prevent AI regulations to make utopia happen.

Apart from that, it's not clear that the number of saved life should just be added up when we talk about huge numbers and tiny probability. A theorem by von Neumann and Morgenstern tells us that utilons work this way, but the number of saved lifes do not work this way.

So it seems very reasonable to go for option 1). A factor of 10% is a big penalty, but not necessarily a game-changer.

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I think Joshua Morgan wins the coveted "Grant Proposal Most Likely to be Heard on Television in the Background of the First Act of an Action Movie" award. Congratulations! Though it was a close run with the painkillers thing.

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The autonomous killer robots (for mosquitoes) also deserve an honorable mention in this category at least.

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> If they succeed, they hope to promote them as painkillers, splice them into farm animals to produce cruelty-free meat, or just give them to everyone all the time and end all suffering in the world forever.

Wait wait what ?! Pain is a very useful signal that notifies you when your body (and arguably mind) takes real damage that needs to be addressed ! Without pain, you would find it very easy to cripple yourself by accident. Painkillers are fine in moderated doses, but I really hope these guys don't succeed in "ending all suffering in the world forever" (as cruel as that sounds) because I have no desire to die from an infected scratch with a smile on my lips.

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See Footnote 2.

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I think the fact that Jo Cameron is healthy suggests that dangers are pretty low. I agree they're not provably zero.

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Jo Cameron is one person, so this is a study with N=1. Furthermore, there's a huge difference between a natural mutation and an artificially amplified treatment (by analogy, compare willow bark tea to Tylenol, or raw poppy seeds to opium).

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I am not sure if this analogy is fully justified, given that we know the molecular basis of the FAAH-OUT-associated pain insensitivity in humans, and seem to be in a good position to replicate it using reversible means.

While the N=1 (or perhaps a slightly larger but still small) sample size is indeed a limit, it can also be perceived as a fortuitous discovery: we could have spent decades exploring the genome for good candidate cures for suffering, but instead, nature presented us with a highly promising, simple and elegant solution that may be possible to apply with straightforward and well-established gene editing techniques.

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Right, but my problem with N=1 is not merely, "you are unlikely to find a functional treatment with such a small sample size", but rather, "you are unlikely to find all the undesirable side effects with such a small sample size". The search space is considerably larger in the latter case, and in fact we already know that some variations on the same theme, e.g. congenital analgesia, tend to lead to disastrous consequences.

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Yes, you should be worried about dying from an infected scratch after you are forcibly subjected to gene therapy based on this ACX grant. If we don't object now, there will be no way to stop or modify the path of the Far Out juggernaut.

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Thanks to Scott and everyone who helped on this round of ACX grants! I'm the person who will be writing the primer on political change. As part of the primer I'd like to map a strategy for a high-impact policy change. I've already reached out to some of the other grantees and others in my network for ideas on what policy change to focus on. But I think this primer will be the most successful if it is a useful tool for people who are interested in changing policy, either in their career or in their spare time. If you are an ACX reader with an interest in policy change email me (orenstein.spencer at gmail) and let me know what policy change you'd like to see explored in the primer.

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Heard about this on Hidden Brain this morning. Seems like his work might be relevant to your project. https://www.robbwiller.org

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Friendship with grinding machine for chicks ended. Now grinding machine for mosquitos is my best friend.

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If it works I'll stop eating chicken and eat mosquito paste instead.

I'm very skeptical that this can work.

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Please don't! If we make mosquito paste a popular food, it will incentivize people to breed *more* mosquitoes.

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Luckily the odds are in my favour. Unluckily, lack of mosquitoes is not going to be a problem any time soon.

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Lots of exciting grants! Thanks for the generosity of all the donors and evaluators. Looking forward to reading the updates next year on how things go

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The Far Out Initiative fascinates me, but I'm really apprehensive about the prospect of mosquito eradication.

I spoke to a scientist at a party once, and he spoke enthusiastically in favor. He said that he'd been worried about it from an ecological standpoint, but that studies had been done into whether mosquitos formed any sort of important ecological role, and it had been found that they didn't. I was really interested, and asked if they'd checked and found that their role in spreading diseases to prey animals, rendering them vulnerable to predators, had been assessed and found not ecologically significant. I could see his face fall as he thought that over and told me "No."

It's possible their place in the ecosystem genuinely isn't that significant, but I'd really rather we carefully check that sort of thing beforehand, rather than kick ourselves afterwards for not having done it.

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Most mosquito species don't (or prefer not to) feed on humans. So we should be able to eliminate the ones that do, without disrupting the ecological balance for other animals. Even if we just got rid of the few species that transmit malaria, we'd have a big win.

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Is the mosquito chopper drone discussed here going to be capable of differentiating mosquito species, though? I would be very impressed if it is.

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I would think that if it's primarily used around humans or in cities, it won't be much of a problem. Maybe it would take out mosquitos that prefer rats or pigeons, and that could lead to a healthier and more vigorous animal underclass? I expect that people who raise animals would love this, too.

I know there were attempts to kill mosquitos with lasers, and they tried to identify females of particular species by listening to wingbeats. From what I've heard, the problem there was that our environments are too noisy and wingbeats are too variable, and they couldn't cleanly pick out the signal from the noise. So maybe another problem is that the drones might kill a bunch of non-mosquito insects?

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If feasible, that might be very beneficial, but I don't think any of the mosquitoes which feed on humans do so exclusively, so it's by no means guaranteed that it wouldn't disrupt the ecological balance.

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I doubt it'd be any worse than what happens when we introduce the Asian Tiger Mosquito everywhere.

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Ecological balance was a bit over-hyped in the past, and now sounds outdated. The thing is that ecosystems keep changing all the time. Usually eliminating one fly species out of a group of twenty will cause some small, non-apocalyptic changes.

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There has been a very visible decline in insect populations as of late. You can only pull out so many Jenga blocks before the whole tower collapses.

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Feb 11·edited Feb 11

Even the insect decline news have been a bit overblown, based on a German study with poor methodology. I still hold that getting rid of a species of mosquito will not cause a radical change in the ecosystem, other species will take their place in the niche. Unlike in the European agrarian landscapes where insect numbers suffer because of insecticides, the overall mosquito numbers in Africa are keeping up strong, with close to 700 species, so if one is eliminated, there are many others who'll happily take over their breeding sites.

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We don't really need to eliminate mosquitoes though. Eliminating them around human houses is good enough.

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founding

Thank you! This is inspiring and also just plain awesome. Congratulations to the winners!

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> splice them into farm animals to produce cruelty-free meat

I suppose someone needs to make the inevitable Douglas Adams joke: I don't just want a lack of suffering in my food, I want **enthusiastic consent**.

This'll do for now, though.

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I’m curious — do you feel that previous rounds of the grants have changed much about your approach to grantmaking?

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No pain and faster healing appearing together is cool. Pain as the body's expectation of future cost of healing in a prior/predictive coding sense

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-I'd love to see more innovation with recycling in general. Huge epistemic void, tons of graft, no real incentive for anyone to care or do much about it. Still waiting on those plastic-eating bacteria to come to fruition.

-Generic Kickstarter sounds like interesting pro-coordination technology. Many smaller-scale use cases that are currently left on the table. One can do lots of cool things with just a handful of people committing to pooling a cost; spreading the benefits of economies of scale via amalgamating demand remains a dream.

-The pupillometry thing makes me wonder if the smartphone could also help with breaking up the Optometry Cartel. It'd be a big deal if consumer-grade lights and cameras + algorithmic improvements could someday offer "good enough" eyeglasses prescriptions, or help detect stigmatisms and such.

-Footnote 5 made me sad. One wants to believe in nominative determinism so strongly.

Still wondering what happened with that controversial grant to Dr. Alice Evans.

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"Still wondering what happened with that controversial grant to Dr. Alice Evans."

She already had the book contract, didn't she? So I presume she is writing the book and it will come out when it's done.

As to the plastic-eating bacteria, I think the problem there is making sure they'll stay in their tanks munching on the waste, and not get out into the wild where they'll eat through your home appliances.

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I'm not sure plastic eating bacteria are so useful?

You can already get energy out of plastics by burning them. And if you don't care about the energy, you can just leave the plastics alone (perhaps bury them in a hole). They are pretty inert after all.

Or you expose them to UV via sun light, and they'll break down over time.

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Oh, it was just one of those popsci ideas that came up periodically as How to Save The World From Plastic Pollution (insert thing about Pacific Garbage Patch here), but never actually happened in any meaningful capacity. Many Such Cases. I'd like to see something actually come to pass in this domain, after a series of these hype-and-letdowns, because 90s environmentalism aesthetics.

It does seem like incineration would be a fine way to deal with waste, if one could properly filter the emissions? I do know that landfills are pretty mature technology in general, but no one wants to actually live near one, and this creates a lot of bad policy incentives. (On top is okay, eventually, which is always amusing to think about.)

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This stuff is so inspiring. Like... you know how reading a Popular Science magazine or /r/futurology or what not can give you a sense of "The future is here, and people are making the world better!" except it's fake? Well, this is the real deal, it feels like. And it's so cool to be here in this community watching it happen.

Maybe I can get in on this action eventually. Either as someone with an awesome plan or idea (validated by local consensus), or with money to help make it happen.

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I feel the exact same way. Like oh, all the deeply pointless stuff people are pretending will Change The World isn’t all there is. Cool and important projects are being worked on (even if they don’t pan out), I go can find them.

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That mosquito idea from Alex is mind-blowing. Well done for trying it out young man.

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Thank you!

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The estimate of trillions of dollars in reduced global GDP due to lead poisoning sounds incredibly high to me. The linked page says, "The World Bank calculates the cost of [lead exposure] to be equivalent to $4.6 trillion, or 5.3 percent of global GDP." Has anyone looked into these figures? Do they seem surprisingly high to others or am I just particularly ignorant about lead exposure?

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Cremieux finds that the reported adverse effects of lead exposure on IQ are mostly the result of confounding, not causality, so by his account, the actual effects of lead would probably be much much lower: https://www.cremieux.xyz/p/who-gets-exposed-to-lead.

Elsewhere in the comments, Kirkegaard stated that the adverse effects of lead exposure are very overrated and linked to his article on the topic: https://www.emilkirkegaard.com/p/how-bad-is-low-level-lead-poisoning.

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Thanks for sharing. I find the Cremieux piece pretty convincing on a quick read.

The other meta-point I notice is that I actually have no idea. I read a well-written piece on the web with charts alleging statistical malfeasance. Believing it also allows me to feel like I'm on the cutting edge of knowledge - all those other people still think lead is a major problem, but I know it's not. The piece seems to hold together quite well, but I have almost no familiarity with the underlying literature or his analysis, let alone something like looking at the analysis he did itself. I've noticed that, in my own work, I can easily make dumb mistakes in a spreadsheet that result in a completely wrong result and not notice it for a long time despite trying pretty hard to get the right answer. So I think this effect more or less applies to all quantitative analysis. It's pretty easy to screw up, especially if the result lines up with your priors. Apart from taking signals like the essay being well written and whatnot, I have basically no ability (and no time) to figure out whether it's true.

So now reading the Cremieux piece and reflecting on my reaction to it has led to a minor epistemological epiphany/crisis. Understanding reality accurately is hard!

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The one about the woman in Scotland who doesn't suffer pain sounds like a case of congenital analgesia. This is hardly new, so I'm not understanding why it's so significant. I don't understand why Scott says she's "incapable of experiencing any [...] psychological suffering." The linked article says she doesn't get anxious, but how significant is this? It seems like a far cry from saying she's incapable of suffering. I sense there's a distinction I'm missing.

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What makes this news significant is that it constitutes the most adaptive case of congenital insensitivity to both physiological and psychological pain that is known to us. Some media report that Jo lives "an almost pain-free life" - in practice, she may be experiencing tiny glimpses of negative valence that help in recognizing the most important threats, but do not get registered as non-negligible negative experiences at the macro level. We will strive to understand the nuances of the high-resolution microphenomenology resulting from her mutation and its possible variants, hopefully supported by the parallel progress in precise valence quantification.

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So, it doesnt sound like Jo's life is entirely free from suffering, nor does it sound like your goal is to entirely eliminate suffering. I think if you (or your advocates like scott here) continue to summarize your project as "ending all suffering" or "ending all pain" you'll keep getting reflexive pushback from people who recognize the basic utility of pain as a warning, not to mention those who assign additional value to it for various reasons.

You might have an easier time getting people on board if you say you're "developing a new generation of ultra effective treatments for pain and mental illness" or something like that

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The ideal scenario is, indeed, the full elimination of maladaptive and involuntary suffering, and pursuing this goal through the best available approximations, each one being exciting on its own, but definitely not exhaustive. Developing a range of novel and effective treatment options for pain and mental health conditions would constitute such an approximation, but the final goal is much bigger. We also want to convey to the public the concept of adaptive suffering abolition, embracing e.g. the reduction of ordinary human unhappiness and improving the wellbeing of nonhuman animals.

Jo Cameron reported a pain score of 1/10 following her hip replacement surgery — a procedure with a painful postoperative recovery period — so it would seem more accurate to classify her condition as one that causes a profoundly high pain threshold by decreasing the negative valence of damage signaling, rather than as a pure form of congenital pain insensitivity. Jo's phenomenology is yet to be studied more precisely, as media reports sometimes tend to overlook important nuances, but it might be the case that at the macro, everyday level, her life is basically experienced as free from any non-negligible suffering.

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Thanks! And a very happy birthday to Charlie!

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Honestly, I feel a bit iffy about your project. I was gonna post a top-level comment when I saw yours, and I guess asking you directly makes sense.

There are good reasons why parents have legal rights over their children. If parents shouldn't have such rights, then wouldn't it be logical (as a reductio ad absurdum) for all minors to be wards of the state? Or to simply lower the age of majority?

In situations where running away from your family is justified, there should be some other legal remedy. Your proposed solution seems to be non-enforcement of existing laws, rather than changing the laws. In case that perspective isn't clear, from a non-US viewpoint the interstate runaway compact seems to be a law that merely bridges the gap across states, and is only necessary due to your peculiar political system. It's basically an "enforcement" law that is subservient to a variety of custodial laws, which are the ones you actually seem to object to.

The idea to give kids greater agency in making medical decisions feels similarly iffy. I assume the central issue here is children wanting to transition against their parent's wishes. But you don't even mention this on your website, using very vague feel-good language instead. Needless to say, this is a very complex issue that people have strong feelings about in both directions.

As much as I empathize with kids that have shitty families, it seems to me like the cure is worse than the disease, for one being ripe for abuse of all kinds, and secondly ignoring the fact that many if not most children are *terrible* at making long-term decisions.

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It is logical, I agree. In an ideal society, the people who have absolute authority over another human being, if they were to exist, would be required to go through mandatory education and to get certifications showing that they are capable of competently exercising such responsibility, instead of being random unqualified people.

The current website is a placeholder site and does not necessarily reflect my actual views, I'm planning on pushing out an actual website as soon as possible.

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Without any animosity and just to figure out where you are coming from, do you have any kids? Your characterization of parents as « random unqualified people » strikes me as odd. Going through childbirth and raising a toddler arguably makes you more qualified than any certifications conceivably could.

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No, I don't have any children. And I'm not sure why raising a toddler is relevant, because parents don't need qualifications to raise a toddler before doing so. I agree that childbirth is difficult, but it's also not relevant to the question of whether you would be good at raising a child. When people get falcons, they need a falconry license.

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Hunting with a falcon is not a basic function of one’s body, unlike reproduction? It seems odd to compare a luxury sport to a fundamental part of what makes us humans. Raising a toddler obviously prepares you to dealing with a preschooler’s problems, in turn preparing you to deal with more delicate issues further down the line, all the way to puberty and beyond. Even if it did not, nothing else could, except perhaps support from your own parents and relatives.

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What prepares you for raising a toddler? Also, why does it matter if reproduction is a basic function of the body?

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It would be impossible to due this in the current political environment because it would be considered "eugenics."

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...this is a really bad idea, because the power to set and enforce those standards gives power to abuse them.

there's no guarantee your standards are correct or right; and thats discounting actual bad actors who would use standards as proxies to destroy certain groups ability to reproduce. Some things we leave to the individual because the consequences of abuse are horrific

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Read, "in an ideal society."

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in an ideal society you dont need administration at all; no one would choose to have kids if they were bad parents. your belief is for non-ideal societies thats why you set up administration and sanction. nothing is ideal until heaven i guess

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We do not allow random people to have authority over children: we allow their parents to have authority over them. To say that the parent of a child is equivalent to a couple chosen by lottery is to deeply misunderstand the situation.

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Hello, Spencer.

As a policy, how about scientific publishing ?

I'm not sure if you have any experience with the field, but scientific publishing is an insane industry considering how they make money: scientists do all the work of creating content, and volunteerly evaluate the work of others, and use taxpayers' money to pay the publishers to get their work published. The most insane part is, universities pay (using taxpayers money, again) the publishers to get access to the work, some of which their employers have done! It is not a surprising that the scientific publishers make profit margins even larger than tech companies.

Since most research is publicly funded in the US through NSF and NIH, I think a policy change that requires scientists to let their work freely available to the public is beneficial to society and only fair. There are systems, such as arXiv.org by Cornell University, that already support that kind of policy. But only a very small percentage of scientific work is deposited in there. Besides, there is a trending policy of "open access" publishing but still taxpayers' money is used to make it possible.

I believe the issue is an important one that worth further considering. I have sent you an email to discuss it further, in case it interest you.

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You do know that when whales kill a great white they do so by tipping it over. The shark is completely paralyzed in an anesthetic realm. A few scientists have been looking into this but I read about it 5 years ago. If anyone could get their hands on this the benefits would be amazing. If I remember correctly it's an enzyme in the shark which puts them into this state, but only when tipped upside down..

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Could someone please do polygenic prediction of HAPPINESS. Being smart is great and all but the but making people directly less depressed and sad is even better!!

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Is there any good guess on how much lifetime happiness depends on genetics? A lot of stuff that determines life quality is heritable, on one hand, but on the other, a lot of stuff (finding a partner that makes you happy, for example) seems like it’s down to luck in a way that wouldn’t show up in a 23andme

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Looks pretty heritable.

https://positivepsychology.com/is-happiness-genetic/

Dunnno if it's via other things like intelligence, looks etc but seems analagous to other things we do polygenic screening about.

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Interesting, thanks for the link. Seems like lower heritability than intelligence but more than I would have guessed?

I would also have guessed that if heritable it’s by proxy via genetic factors for high function (conscientiousness, intelligence etc) or at least by lack of dysfunction (health, particularly mental health stuff that’s heritable). So this caught my eye:

> “Other research focusing on individual genes offers additional insight. One such gene is 5-HTTLPR, believed to be important in the control of mood-affecting serotonin. In one study, volunteers with a particular variant thought to benefit the transport of the neurotransmitter were found to be predisposed to avoiding negative images, preferring happier ones, such as pictures of puppies (Coghlan, 2009).”

Also the correlation to fairly heritable things like openness, neuroticism etc.

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Yes, very interesting.

I also expect there are issues with capturing the true extent of heritability because you can't directly compare happiness so I expect people answer partially comparatively (if my family is all super happy I probably assume that's the norm and adjust my responses down to a degree). This does make prediction a bit harder but I expect it's effectively just noise.

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Is there any good way to stay tuned on Mr Orenstein’s project? Or at least be sure to catch whenever the manual is done?

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Good list, but several of these seem like they're tackling old, well-known problems that 1000 experts have been working on for decades. For example, phage therapy, or more efficient chicken sexing. Those are both very old ideas that people have thrown billions of dollars at.

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Feb 14·edited Feb 14

Thanks for this comment, as I thought I’m the only feeling this way so probably shouldn’t comment ‘smart ideas of smart ppl’.

Can comment on phage therapy based on what is stated in the announcement.

>> “There have been some small-scale successes, especially in Eastern Europe, but overall these remain neglected. Dr. N and his team work on phage therapy as a potential solution to growing antibiotic resistance. Their current projects include trials of phages to fight typhoid and diabetic wound infections.”

All of these stated above look very controversial and not be researched well. By points:

1) all necessary trials have been held already, specifically against typhoid and diabetic wounds (depends on a nature of wounds, diabetic itself is nothing to deal with phages, so with wounds we are speaking about associated infections, not problem with tissues themselves).

All these researches and trials on humans was published for decades. Moreover, it’s successfully already in retail use and mad adoption already. Why wouldn’t EN just at least study those results and see how ppl consume it instead of stating a goal of ‘work on phage therapy as a potential solution to growing antibiotic resistance’ or ‘trials of phages to fight typhoid and diabetic wound infections’. I mean - it’s already used by hospitals, medicine professionals and patients (e.g. already in retail), but EN is be like - let’s try out penicillium, potentially it will work like antibiotics or let’s try to re-invent a wheel, maybe it will work like a WHEEL?!

Looks like you guys made a very poor research. Like for real living in a bubble where decades of using this therapy IN RETAIL doesn’t exist 🤦🏻‍♀️

https://www.microgen.ru/en/products/bakteriofagi/

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Slightly off-topic, but…

> Turkiye

This seems a little like capitulation to ethnonarcissistic bullying. “Turkey” is pretty much just the way the name of the country cashes out in English phonology. It’s not even as if it’s amending an exonym that has nothing to do with what the country’s inhabitants call their homeland. I could see a case for Anglicised endonyms in those cases, e.g. Germany > Theechland, Hungary -> Madjarland, Georgia -> Kartvelia, but this one seems to be pretty much “We demand that you spell and pronounce the name of our country the same way we do, even though we’re not going to do the same for you (and even though the true version, Türkiye, contains a letter that the English alphabet doesn’t have, for a vowel that English phonology doesn’t use).

Or am I missing something here? Is there a good argument for making this switch?

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I always thought it was weird that there was a country named after a bird.

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It's actually the other way around!

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Feb 11·edited Feb 11

Oh. I actually thought it was coincidental, but that makes a lot more sense.

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To be fair, it’s the other way around.

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Well, there's a country in the middle of Europe named after germs, too.

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> The worst part of ACX Grants is telling the non-winners they didn’t win.

You should hire someone to do that.

https://en.wikipedia.org/wiki/Up_in_the_Air_(2009_film)

> Other teams have already established that the UV light kills germs, so the remaining challenge is to ensure it’s safe for humans.

Not just for humans, but also for things. If you install something like that at home, you probably won't be happy if after some time all your books fall apart.

> One thing I learned while researching this grant was that the word “ovo” looks like a chicken.

We need a Wikipedia page containing words like that. Though I suspect that most of them would be hieroglyphs.

> Mark wants to try something different and just buy land directly.

I think this is what many rich people and companies already do as a side business. Land is like a "bitcoin, before bitcoin existed", in the sense that you can buy it and expect the price to mostly go up; with the extra advantage that you can keep taking the rent while you are waiting.

Your greatest risk is probably a war, or some legal/political action that takes your land away. And some of the players spend money on lawyers/politicians to help them get more land cheaply. So, at some level, it becomes a completely different type of a game.

> $1,000, for biology tutorial videos.

Wow, big respect for anyone who can do something amazing for such small amount of money!

I mean, getting $1000 per video would be a great business if that happens repeatedly. But just getting the money once...

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> Your greatest risk is political/legal

Agreed. That's why I'm planning to start in small, stable island countries in the Lesser Antilles that have a good track record of political stability despite stagnant (or falling) GDP.

The idea isn't for me to buy and hold the land, though. My plan is to immediately divide and redistribute the land to the farmers. Since they typically pay about 50% to the landowner, they'll start off with a double salary, from subsistence levels. Research suggests they will make different planting decisions that will at least double output (likely moreso) and soon they'll start sending their kids to school and invest in basic health services.

I want to establish, not only whether this approach works, but also get a quantitative understanding of the ROI for land reform, to support future efforts. Since we're giving the land away, the return isn't a personal one, but a measure of global growth/development dollars. I'm expecting anywhere from $50-$150 initial per year growth (meaning added annual growth from a one-time investment). But we'll see what we actually get once the numbers come in.

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I really do wish you good luck with that, and I really do want you to read up on historical programmes which attempted this and how they succeeded or failed. You do mention these in your grant application, I am merely suggesting don't expect it to be "Now John owns his farm where previously he was a tenant, now he will start planting better crops and sending his kids to school". It's entirely possible John is a bad farmer and won't be more productive, or will feel over-confident about being 'rich' and will do something stupid like drink the land away, or will now sell off the land himself so he can move to the city for that sophisticated lifestyle of running water and indoor bathrooms. Such things happen!

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Thanks for the support and the input!

I expect a certain percentage of people absolutely will go that route. I'm hoping that starting with a large enough sample size the whole project won't depend on random chance or individual personalities. (For example, buying a 40 ha farm and dividing it into ~20 plots of 2-3 ha each.)

I'm always reading in this area, but if you have a few books/articles you want to recommend, please do!

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Nothing modern, I'm afraid, just going by historical precedent round these parts.

I do think it's a good idea to give tenants the right to own their own land. The things to watch out for are exploitation of this (e.g. people moving in to offer 'loans' to the new owners which then turn out to be extortionate and they get the land signed over to them as payment) and the like. Maybe 3 hectares won't be enough to be economic. Maybe the new farmers will exhaust the land by over-production because now they're getting the money directly so profit will drive them.

But you won't know until you try, and it's very worthwhile trying. Good luck!

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Thanks! I think expropriation in the way you suggest is a systemic problem for all economies. It has echoes in the US and developed nations, where any kind of capital accumulation is accompanied by attempts to squeeze capital from the people. Here I'm thinking of things like HELOCs, title loans, and the like. So I expect to see some of that kind of activity happening, but I don't know of any general economic system that prevents this kind of exploitation. (Though I'm playing around with some ideas for future projects aimed at inner city poverty.) I do think that a formalized system of oligarchic land ownership makes it impossible to escape that kind of system, though, so at least it's a start.

You're right, though, that there's a lot to learn from the historical record. One of the biggest ways a new landowner can lose their interest in the land is through loans/debt - and specifically to support planting activities. This is why I want to buy the land and the crops - after planting but before harvest - to get ahead of this problem, at least for the first planting season. Of course, we'll learn by doing what helps prevent reversion.

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Instead of giving people the land outright as property, you could guarantee them free rent for eg ten years, and hand over the title afterwards.

Economically that basically the same as being an outright owner, but it's harder to borrow against.

However, it's not clear to me that borrowing against your land is always a bad idea.

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Feb 11·edited Feb 11

Yeah, going into debt to buy seed and then paying it back after harvest has traditionally been the way farmers end up having the bank foreclose and sell off the entire farm.

You will indeed learn by doing, that's the only way to test theory.

A song (not this version) from when I was a child, about the travails of the poor, poor farmer 😁

https://www.youtube.com/watch?v=bj5YysA3Oy4

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Feb 11·edited Feb 11

As to the question of farm size, I'm still working out what will be the best here. Prior research (https://michaellipton.files.wordpress.com/2012/02/farmsize2009.pdf) seems to point to 2 ha or less as the most common situation worldwide, but I'm aware that what will work economically is entirely dependent on farm output and intensity of farming for the target crop. For some crops, <1 ha is more than enough, while for others 2 ha won't cut it. I figure if I'm working with an absentee landowner who currently has 100 ha and farms that with 50 tenant farmers, I should be able to distribute the land to the farmers who will as a baseline receive the surplus of what the landowner was collecting in rents. I'm aware it's not as simple as that, since some of these farmers are likely to engage in supplemental income practices, but there's no reason they can't continue whatever else they were doing under a family farm ownership model if they absolutely have to. The goal, of course, is that they DON'T have to, but that's part of what I'll be studying.

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If John is smart, he will simply rent the land to Joe and collect the 50%.

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That's the problem sclmlw is trying to avoid, and which was part of the problem back in the 19th century for Peel and Irish land reform: the creation of a landless cottier class, which can never own their own land but are always renting and always in peril, and a new class of sub-landlords and middlemen. Same with sharecroppers in the American South, I think?

He wants to see if allowing the tenants to be owners, rather than renters, will improve standards of living with knock-on effects of increasing education, better healthcare, and growing the economy. If John is just renting out his land to Joe and not improving it (because he can't afford to, he is just able to live off the rent) and Joe isn't able to improve the land