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(At least in the UK, numbers starting 077009 are never assigned. So I've memorized a fake phone number that looks real, that I sometimes give out with no risk of accidentally giving a real phone number.)
Okay. Make it £5k from me (currently ~$6350), that seems like it'll make it more likely to happen.
3If you can get it set up before March, I'll donate at least £2000.
(Though, um. I should say that at least one time I've been told "the way to donate with gift said is to set up an account with X, tell them to send the money to Y, and Y will pass it on to us", and the first step in the chain there had very high transaction fees and I think might have involved sending an email... historical precedent suggests that if that's the process for me to donate to lightcone, it might not happen.)
Do you know what rough volume you'd need to make it worthwhile?
1I don't know anything about the card. I haven't re-read the post, but I think the point I was making was "you haven't successfully argued that this is good cost-benefit", not "I claim that this is bad cost-benefit". Another possibility is that I was just pointing out that the specific quoted paragraph had an implied bad argument, but I didn't think it said much about the post overall.
My guess: [signalling] is why some people read the Iliad, but it's not the main thing that makes it a classic.
Incidentally, there was one reddit comment that pushed me slightly in the direction of "yep, it's just signalling".
This was obviously not the intended point of that comment. But (ignoring how they misunderstood my own writing), the user
- Quotes multiple high status people talking about the Iliad;
- Tantalizingly hints that they are widely-read enough to be able to talk in detail about the Iliad and the old testament, and compare translations;
- Says approximately nothing about the Iliad;
- And says nothing at all about why they think the Iliad is good, and nor do roughly 3/4 of the people they quote. (Frye explains why it's important, but that's different. The last 6 lines of Keats talk about how Keats reacted to it, but that doesn't say what's good about it. Borges says a particular line is more beautiful than some other line (I think both lines are fine). Only Santayana tells me what he thinks is good about the Iliad.)
So like, you're trying to convince me the Iliad isn't just signalling by quoting Keats, saying essentially "I'd heard the Iliad was so good, but it took me forever to track down a copy[1]. When I did? Blew my mind, man. Blew my mind." Nonspecific praise feels like signalling, appeal to authority feels like signalling, and the authority giving nospecific praise? This just really solidly rings my signalling bells, you know?
- ^
I misunderstood Keats when I first replied to the comment. I'd assumed that when he said he "heard Chapman speak out loud and bold", he had, you know, heard someone named Chapman speak, perhaps loudly and boldly. Apparently it was what is called a "metaphor", and he had actually just read Chapman's translation.
Complex Systems (31 Oct 2024): From molecule to medicine, with Ross Rheingans-Yoo
When you first do human studies with a new drug, there's something like a 2/3 chance it'll make it to the second round of studies. Then something like half of those make it to the next round; and there's a point where you talk to the FDA and say "we're planning to do this study" and they say "cool, if you do that and get these results you'll probably be approved" and then in that case there's like an 85% chance you'll be approved; and I guess at least one other filter I'm forgetting. Overall something like 10-15% of drugs that start on this pipeline get approved, typically taking at least 7 years.
A drug that gets approved needs to make about $2 billion, to make up for the costs of all those trials plus the trials for the drugs that didn't get approved. And it has about 10 years to do that before patent protections expire, because you filed the patent before doing the first human studies and you only get 20 years from that point.
Typically what happens is someone forms a company for a specific drug, and while it's in fairly early trials the company gets bought by a big pharma company. The trials themselves are done by companies that specialize in running clinical trials.
Ross says Thalidomide was sort of the middle of a story. The story started with Upton Sinclair's The Jungle, which he wrote as a "look at the horrible conditions meat packers have to endure" but what the public took from it is "excuse me, there are human fingers in my sausages?" So after that was the pure food and drug act which said that anything had to be just the thing it said it was.
But then a drug came which was exactly what it said it was, and that thing was bad for people. So after that you needed to do studies to show safety, but they were less rigorous than they are now?
And then thalidomide happened, which was fine for most people but caused birth defects when taken by a pregnant person. When it came up for approval, the beurocrat looking at it happened to have previously looked at rabbits and seen that drug uptake and metabolization could be different in pregnant rabbits, making something otherwise non-toxic become toxic. And so she said the company needed data about safety in pregnant people, even though this was a non-standard requirement at the time. The company tried to avoid that, she insisted, and it never got approved in the US. But standards still got stricter.
(It did get approved in Europe. It's relevant that Germany didn't like tracking birth defects due to previous history, so the problems weren't noticed as early as they might have been.)
One of the times when regulations got stricter, part of the story is that at the same time as public outrage, there also happened to be a bill in progress for reasons of punishing pharma for something something, so that's the bill that got through.
At some point you started to get patient advocacy groups, saying "we are dying while you hold this drug up", and the FDA would pay attention to that. And then the pharma companies would get involved in those groups, and now it's at the point where you kinda need one of those or the FDA will be like "why would we prioritize you?"
There are drugs that the FDA wants to encourage but which aren't profitable, e.g. helping with diseases common in the third world and rare in the US. One motivation is if you make one they'll give you a priority review voucher, good to help another drug of yours get approved faster. These vouchers are transferrable, and the market price is... I think $100k or $200k?
With covid vaccines, the government said "if you produce a thing that satisfies these criteria, we will buy X amount of it for sure". That took some uncertainty out of the process and helped things get made.
Sometimes a drug will succeed in trials but not get pushed forward for various reasons, sometimes just falling through cracks. One drug this happened with was a covid treatment, which seemed to reduce hospitalizations by 70% in vaccinated people. When it was in development the FDA said it was unlikely to get emergency use authorization, and the company dropped it.
(Related: VaccinateCA got a lot of funding for a while, and then after the funders themselves got vaccinated, it got less funding.)
Later the company was going bankrupt, and they sold off their assets, which included "drugs that seemed promising but we never went anywhere with", including this one. Ross was involved in some other company buying up that drug.
You can do trials for covid much cheaper than for cancer drugs. For cancer you'll often have a list of a smallish number of people and try to find the specific individuals who give you the best chance of a statistically significant result based on comorbidities and such, and have someone specifically approach the people you want. For covid the cheap thing to do is: everyone who comes to your clinic with a cough gets the drug and gets a covid test. Later you find out if they had covid and (thanks to a phone call) what happened to their symptoms. And you can do this sort of thing somewhere like Brazil, instead of doing it in the most prestigious hospital (where there are a bunch of other studies going on distracting people). But it's kind of a weird thing to do, and if trials fail your investors might be like "why didn't you do the normal thing?"
Though this particular story for weight exfiltration also seems pretty easy to prevent with standard computer security: there’s no reason for the inference servers to have the permission to create outgoing network connections.
But it might be convenient to have that setting configured through some file stored in Github, which the execution server has access to.
Yeah, if that was the only consideration I think I would have created the market myself.
Launching nukes is one thing, but downvoting posts that don't deserve it? I'm not sure I want to retaliate that strongly.
Self review: I really like this post. Combined with the previous one (from 2022), it feels to me like "lots of people are confused about Kelly betting and linear/log utility of money, and this deconfuses the issue using arguments I hadn't seen before (and still haven't seen elsewhere)". It feels like small-but-real intellectual progress. It still feels right to me, and I still point people at this when I want to explain how I think about Kelly.
That's my inside view. I don't know how to square that with the relative lack of attention the post got, and it feels weird to be writing it given that fact, but oh well. There are various stories I could tell: maybe people were less confused than I thought; maybe my explanation is unclear; maybe I'm still wrong on the object level; maybe people just don't care very much; maybe it just happened not to get seen.
If I were writing this today, my guess is: