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

(Especially Greg, you deserve it).

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

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

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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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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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Thanks! And a very happy birthday to Charlie!

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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 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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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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> 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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That Far Out Initiative seems like a likely candidate to have some freaky unintended consequences, if the long-term goal were to be successful. In a world without pain, how much more risk-taking behavior to people engage in? Would there still be a basis for empathy? Would people still be concerned about things like ecological devastation if it doesn't induce any negative psychological feelings? Would art that engaged in feelings like sadness, grief, horror, loneliness, alienation, anxiety, etc. lose its value? Would all art degrade into mere pleasant stimulation? Would people lose the motivation for ambitious pursuits if everything already seems fine as it is? Would the bonds of personal relationships weaken if they do not have shared suffering as a basis? Etc. etc.

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I have already tried the insect-killing drone idea. It doesn't work. What I failed to realize is that, in order to stay aloft, drones have to move an enormous amount of air constantly. They are like extremely powerful (relative to their size) downward-pointed fans. While flying, there is a huge zone of disturbed air around the drone that you can't see, but when you get close to insects, they get pushed down the by the air current before the drone can get anywhere close to them. In my case I was trying to eliminate wasps, but no matter how I approached them with the drone, they just got pushed down and flew away. Even if I came up directly beneath the wasps, they would rapidly get pulled down and would miss the propeller blades. I never killed a single wasp. I doubt that mosquitos would be more vulnerable to this attack strategy. Nevertheless, I wish Alex Touissaint the best of luck. I hope he has some insight that I missed.

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Feb 10·edited Feb 10

Totally biased and ignorant reactions to all these:

(1) The lead battery recycling - excellent! I don't give a rattling damn about global GDP but I do care about children's health. Good work all!

(2) The AI stuff - meh. Your money, you can do what you like with it

(3) Mosquito killer drones - this makes me laugh, so once again good job all! I do find it funny that the technical approaches of insecticides and genetic engineering for sterility don't seem to have panned out (nature is tricky that way) so good old-fashioned 'swat 'em' is the last resort. Will mosquitoes evolve to be able to take out the drones is the next question!

(4) IVF clinic ranking - I'm surprised this isn't already being done, with IVF being such a huge business. So good work here as well, except for this line: "causing a few dozen to a few thousand extra well-loved developed-world children to exist".

Hell and damnation, Scott, I'm not trying to pry into your private life but your children are the result of IVF, do you really mean that you can calculate "I love them 12.39% more than if they had been conceived the traditional way"? I know this has long been an argument for abortion - "every child a wanted child", on the assumption that unwanted/unplanned pregnancy means unwanted child means abused child, but I don't think that "by putting more obstacles in the way of achieving parenthood, we will ensure that the resulting born children are very much wanted and hence very much loved".

People can greatly desire children and still dole out conditional love (see the comments on the poly posts about one family where the parents put their current love interest over their kids) and one way that IVF selection could work is "Well, little Jocelyn or Jonquil, we spent so much money on the IVF procedure and the shopping list of beneficial traits we wanted you to have, you must now perform to our expectations and the amount of love you receive in return will be proportional to how well you meet or exceed those". If we're going this route, we may as well go the whole hog for parenting licenses, which in some moods I'm all for.

I know I have garnered a reputation for being obsessed with this topic, but I honestly do feel that "well-loved" is not doing good work here in that description. It sets up the dichotomy between "well-loved = planned conception with embryonic selection; natural conception = not so loved". You love your kids or you don't, it shouldn't be conditional on "assuming the end product was in accordance with everything I wanted on the shopping list". Dump the well-loved developed-world shit, bringing more children into existence is good on its own and doesn't need any selling on value for money.

(5) Smartphone diagnosis - another good idea. I think giving ordinary people the tools to monitor their own health and conditions is very helpful and can even be more helpful if they're running up against trouble getting doctors to take their complaints seriously ("there's nothing on the last test, don't worry about it" turning into "it's a pity we didn't catch it in time before it got to this stage")

(6) The Scottish pain project - again, this line gave me pause. "(J)ust give them to everyone all the time and end all suffering in the world forever", yes, but what about the "no psychological suffering" part? Part of empathy is being able to identify with another's pain. If I feel no distress whatsoever at seeing the drowning child drown, why would I jump in to save them? No psychological pain sounds great, and I'd love it to happen, but the downside is "can cheerfully watch people being burned alive or publicly executed gruesomely or in trouble and not feel any concern or impulse to help".

(7) Tax breaks for organ donation - again, your money, you can spend it how you want, but is there really a large pool of people who want to donate and who would donate their organs, except for it's not tax-deductible? I don't know how expensive having elective surgery to donate a kidney would be, but if we take this site and give it an estimated figure of around $150,000 then I think you would need a *very* hefty tax break to pay back that kind of expense, and I don't know if state or federal government would be willing or able to make that kind of sacrifice of revenue:

https://www.talktomira.com/post/how-much-does-surgery-cost-without-insurance

(8) The chicken sexing project - good Lord, a *sensible* intervention in the factory farming and animal cruelty debate? Excellent work once again!

(9) Political programmes stuff - mmmm. I think my main query of effectiveness here is the Australian one - if one crowd had success but are now handing everything over to a new bunch, how effective in the long run is it going to be when it's constant turnover of starting from scratch? I think you need a long-term commitment by a set of people to work on this for maximum effectiveness, otherwise you get piece-meal successes on small issues here and there, but nothing in the greater field of political organisation changes very much.

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"Joel Tan, $100,000, for the Center For Exploratory Altruism Research."

The one thing I'd say here is change the name to produce a better acronym. Right now, this gives us CFEAR which, in current media usage, will be reduced to "Cfear". "Fear" is not a good word for the subconscious associations it evokes.

Changing this to "Center for Altruism Research Exploration" (yes, the small 'f' is important here) gives us "CARE" or "Care". Much better associations, and so evokes positive response in audience! Audience feels positive about this, audience more likely to donate!

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"There are a few organizations working on lobbying for land reform on a political level. Mark wants to try something different and just buy land directly. "

I don't know if he's aware of it, but I'd recommend he read up on things like the Encumbered Estates Act. That acted indirectly for land reform by re-distribution, and it had both good results and not so good results. Who do you want to get the land? Do you want to distribute it directly to the tenants, or do you want to set up a class of small-scale proprietors who will continue to extract rents from a tenantry? Historical precedent often helps in clarifying what you intend to do and what the likely effects may be:

http://www.tara.tcd.ie/bitstream/handle/2262/68931/v3n31972_4.pdf?sequence=1&isAllowed=y

"The Devon Commissioners had exposed the plight of the cottier class in Ireland, and to all intents and purposes presented that plight as an apparently insuperable obstacle to social and economic progress. The consideration that must have arisen in Peel's mind at that juncture was the favour shown by contemporary political economists to the introduction of capitalistic agriculture as a panacea for remedying the problems presented by the cottier class. The economists believed that a re-orientation of the cottiers to a wage-paid labouring class would provide lebensraum for progressive farmers in a high-farming system and thus end the unemployment that had bedevilled both the cottiers and the authorities. Peel believed that a repeal of the corn laws would favour the wagepaid labourers of a high-farming system by bringing the cost of bread within reach of their wages and so keep them from drifting away from agricultural work.

…They urged in particular that any measure should arrange for the sale of properties in lots o f a moderate or small size. They were thus, in a sense, taking cognisance of contemporary agricultural thought which discountenanced the spreading of agricultural capital on too thin a base over extensive estates. They adduced further reasons: "We believe that there is a large number of persons in Ireland possessing a small amount of capital which they would gladly employ in the purchase and cultivation of land and a still larger number, now resident in different parts of the country and holding land for uncertain or limited terms at a rent, who would most cheerfully embrace the opportunity of becoming proprietors." They were undoubtedly reflecting the contemporary view (and Peel's also, as we have seen) that middle-class wealth in the towns should be tapped for agricultural capital by enabling the possessors of it to buy landed property. The Commissioners' reference to tenant purchase here can be construed as more a recognition of the number of progressive yeomen in England than an obeisance to the advocates of a tenant proprietary. In England such yeomen owned properties of "a moderate extent,” and Peel appears, later at any rate, to have favoured their introduction as a class into Ireland. In reference to middle-class and tenant investors, the Commissioners thought that "the gradual introduction of such a class of men would be a great improvement in the social condition of Ireland. A much larger proportion than at present would become personally interested in the preservation of peace and good order and the prospect of gaining admission into this class of small landowners would often stimulate the renting farmer to increased exertion and persevering industry"."

https://en.wikipedia.org/wiki/Encumbered_Estates%27_Court

"The Encumbered Estates' Court was established by an Act of the British Parliament in 1849, the Incumbered Estates (Ireland) Act 1849, to facilitate the sale of Irish estates whose owners, because of the Great Famine, were unable to meet their obligations. It was given authority to sell estates on application from either the owner or an encumbrancer (somebody who had a claim on it) and, after the sale, distribute the proceeds among the creditors, granting clear title to the new owners."

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Excellent stuff! I'm glad these projects are getting funded.

I've also read lots of critiques of grant-making processes recently. The whole thing consumes a lot of grant proposal writer time and reviewer time, and Scott's comments on the process really bring that to life. So is ACX Grants building on a creaky foundation? Should there be some less onerous way to get money to people working on useful projects? I have no strong ideas on this front, but it's interesting to think about alternative processes that would scale better.

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Feb 10·edited Feb 10

Looking at S's proposal makes me worried. My main concern with forecasting markets boils down to Goodhart's Law: every measure which becomes a target becomes a bad measure. If forecasting becomes a part of governmental decision making, won't bad/influential actors try to game the markets as a way of influencing policy? This kind of manipulation is already a problem in more traditional markets, and those have a robust regulatory framework dedicated to stopping it.

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Speaking of grants . . . Today's WSJ announces that an AI team working on deciphering a two-millennia-old papyrus scroll won close to a million USD. They figured out a way to read at least portions of it by scanning the rolled-up scroll with a particle accelerator. It's to scholars almost what Lidar is to archeologists (Ben Cohen, 'The World's Smartest Minds And a 2,000-Year-Old Mystery," page B5). Tech comes through.

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So exciting and uplifting to see all over these great projects getting funded!

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Well, all of these sound nice, but the relative amounts given sure don't seem to represent a sensible cause prioritization to me. Humanity has a serious chance of ceasing to exist, and taking the rest of the biosphere with it, within the next 10 years. If humanity gets its act together and successfully safely manages the transition to AGI, then the world will be radically transformed for the better. Seems like from Scott's AI-related posts he kinda gets this. But you wouldn't notice his understanding by looking at this set of grants. Either we win, and a bunch of these things just get solved quickly thereafter, or we lose, and these things become impossible. Therefore, not worth funding unless you don't believe that AGI is in fact around the corner. #missingmood

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1.4 million US-$ well spent.

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Oof. As an embryologist working with IVF clinics, I have to respectfully raise an issue with the IVF clinic success rates. SART data show a pretty stark statistic on IVF success - with only 40-50% chance of live term births even in fertile women. Knowing which clinics to go to in a given neighborhood is nice, i guess, but a quick google search can get you there. How do you assess a clinics success rates? By live births? In the end even the most “successful” clinics, when it comes down any given woman, will show a 50-50 on whether you succeed in uterine transfer for any given IVF cycle. Also, the success rates for any given IVF clinic are for a highly self-selected group for frequently infertile women, older women, etc. the sheer costs of many of these clinics excludes socioeconomically challenged and minority groups. Getting lots of people to use IVF has to come from lowering costs and increasing success rates of embryo selection, uterine transfer, #cycles to embryo implantation, and these clinical processes – not just an app to tell you where to go. the real way to have an impact is to invest in reproductive science, because only then can success rates increase for IVF, driving down the timeline to live birth, reducing the number of IVF cycles, etc. Also the consensus in the field is that we have absolutely ZERO information on what a "good" or "successful" embryo looks like. Most PGT screening methods are highly speculative, are not predictive of a successfully implanted embryo, and recent papers suggest that genetic tests for aneuploidies increase the prevalence of genetic abnormalities! I’d like to also get a reasoning into why polygenic screening is useful and not a pseudonym for eugenics

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