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Monicen  3yr ago (doyourownresearch.substack.com)   5218 thread views

Ivermectin: Much Less Than You Needed To Know

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To give an overview of what I believe is a reasonable bounded-rationality basis to dismiss this objection:

  • I am not equipped to evaluate the claims in Alexandros's post in detail without significant effort and time investment (despite being a working academic in a quantitative field).

  • I'm not particularly worried about COVID and the societal excesses of the response seem to have already died down, so I personally don't see much value in learning about a surprising therapy for it. It seems unlikely to me that even if something like the contents of this post became widely accepted as truth, the societal response next time something COVID-shaped happens would be much beter.

  • Superficially, it seems there is no particular reason why something like Ivermectin (an antiparasitic that apparently works by disrupting the metabolism of fairly complex multicellular parasites) would work against COVID (a virus). I have a strong prior on most medicines claimed to have a minor beneficial effect on popular therapeutic targets actually being completely ineffectual (as this has been my experience).

  • On the other hand, the "parasite load" story seems superficially plausible.

  • Due to the culture-war dimension of Ivermectin, whose efficacy the red tribe in the US has entangled its social status with (no point in recounting the way this happened here), there is an obvious motivation for members of that tribe to produce compelling-looking arguments for its efficacy. Since Alexandros posts around this community, he seems a priori likely to harbour Red sympathies.

  • Moreover, there is a "contrarian" tribe that is motivated by taking down the rationality-orthogonal "trust the science" wing of the blue tribe, and therefore would also derive utility from successfully Eulering in favour of Ivermectin. Many people seem to talk about the abrasiveness of Alexandros's tone. This increases the probability that he's Red or Contrarian and would therefore have the motive to come to his conclusion.

In short, a situation that seems fairly symmetrical to "read this long and extremely compelling essay by a Harvard academic who is also a Twitter superstar using Science and Logic to prove that Blank Slatism is true". If you had unlimited time and resources or a particularly high stake in finding out whether desirable qualities of humans are genetic, sure, by all means you ought to read it and analyse the argument. For most everyone else, it would be more rational to ignore the essay, leave your prior largely unshifted and spend the time it would take to read on something with higher expected utility, like planning tomorrow's healthy breakfast or getting on top of your todo list.

Things that could convince me to take the essay more seriously:

  • Establish that the author does not stand to benefit from Ivermectin working, e.g. has impeccable blue tribe credentials.

  • Establish that rehabilitating Ivermectin would benefit me personally a great deal.

  • Propose a plausible mechanism by which Ivermectin (specifically!) might work against COVID. Some general handwaving like "it modulates the way the immune system operates" won't work; lots of drugs do that, so I don't see why specifically the one that the Blues are raging against and the Reds are swearing will prove once and for all they should actually be in charge should be the one that happens to modulate it just right.

  • Relatedly, but harder, shift my prior regarding medicines that purport to do anything more complex than targeting one particular well-understood metabolic pathway not working.

  1. This article has nothing to do with rehabilitating ivermectin. I myself am not sure how well it works today and if I had to guess, it worked a lot better for pre-Omicron variants. Naturally recent data is a mess, so it's hard to know, and I really should do some digging before I say much more because I could be very wrong. On whatever the "red tribe" is - I frequently tweet out about how I could never support a president who allowed Fauci to run the pandemic. As recent immigrant to the US, I have very little interest in whatever partisan bickering y'all are engaged in, other than that I'd prefer if the country my children were born in doesn't implode.

  2. Rehabilitating the rationalist community (the actual intent of the essay) would benefit everyone a great deal. Ivermectin is the perfect case-study of why the rehabilitation is needed.

  3. Once again, the article has nothing to do with defending ivermectin, and everything to do with defeating bad arguments. If you are interested in some material on mechanism of action, my friend Joomi has written a pretty good piece - https://joomi.substack.com/p/misconceptions-about-ivermectin-dosing

  4. There are many drugs we don't understand the mechanisms of, and I can personally confirm that some of these definitely work: https://en.wikipedia.org/wiki/Mechanism_of_action#Drugs_with_unknown_MOA . In fact, as you can read in Joomi's article, ivermectin's anti-parasitic action also is somewhat mysterious, but nobody doubts it works.

I'm not particularly worried about COVID and the societal excesses of the response seem to have already died down, so I personally don't see much value in learning about a surprising therapy for it.

Ivermectin is used as a weapon against the right in the culture war. Whether the right is actually correct, and whether the left made baseless attacks against the right for political reasons, will be important as long as we have a left and right around.

But I think it is clear what the collective knowledge about Ivermectin was at the time. Whether we later learned (or will learn) that it actually works against Covid (or not) will not change anything about how justifies these attacks were.

We had a time when the best meta-analysis as evaluated on LessWrong was pro-Ivermectin and the institutions were anti-Ivermectin.

The question of whether to follow the highest quality published metastudies or the institutions in cases where those differ is an important one. If the highest quality published metastudy was right about ivermectin and the institutions wrong that's a lesson for the future.

If the institutions are wrong and generally suppress the use of generics for important illnesses that suggests we should invest more money into studying whether generics are useful for problems that arise.

Lastly, if Ivermectin works for COVID there's a decent chance that it also works for other viruses. If we have another pandemic it's important to know whether we should run trials to test whether Ivermectin helps or don't run those trials.

I for my part am already fairly convinced that the left makes baseless attacks against the right for political reasons. (Of course, the converse is also true.) Is it that important whether there is one more or one fewer example?

"Baseless attacks for political reasons" was only a rough description. Maybe "baseless attacks for political reasons, that are highly signal-boosted by the media and social media", would be closer.

But again: this was definitely done for political reasons [0] at a time when the evidence was still inconclusive.

Whatever we found out between then and now doesn’t change anything about that.

[0] There are of course more benign motivations one could assume, e.g. protecting people from what was perceived as “false cures” that would end up harming people.

Just because the evidence was inconclusive doesn't mean that the attack was unimportant. For one thing, it's a signal that anyone who does try to do actual research and produce actual evidence in the future would be mercilessly attacked. Even if there's little evidence at the moment, this is a huge deal.

Politically, what matters is who controls the institution that determines who is right. I could list a hundred things about which the left is wrong and yet which have been ascertained as true by consensus reality. It has always been so, those who are familiar with Roman history know how much who determines what is true has always been the decisive force in politics.

Bounded rationality is a real field of study, describing optimal behaviour for agents who can't actually reason and obtain information infinitely for free.

Even Yudkowsky concedes that rationality is about winning. It seems pretty straightforward to see that someone who is still busy calculating probabilities to see if some skub paper checks out while the police remove him from the premises as the debt collector wants to foreclose his home is not winning. As a corollary, if the gut feeling strategy consistently gets better outcomes than the "reason and logic" one, it's more rational.

As I said in a parallel comment, I am meaning to explain why people can rationally choose to leave these essays unread and not have their beliefs shifted by them much, to push back against the "rationalists are ignoring this high-quality argument, which proves they are not so rational after all" rhetoric that the essay itself and its proponents are employing. Also, both the addressee of the essay and the backdrop community of this forum use a much more specific definition of "rationality" and "rationalism" than the dictionary one as a core part of their identity. I doubt that Alexandros does not know this, so to suddenly insist on the dictionary definition seems rather disingenuous.

project your distrust on to others as if they must rely their trust upon you more than their own cognitive skills

I think something is still off about your use of words (the "project", "rely their trust") which might result in us talking past each other to some extent, but I'm emphatically not trying to say that anyone should take my word for it. I've already declared that I know little about the field! However, with bounded resources, two rational actors can in fact arrive at different beliefs. I'm asserting that I'm acting rationally in continuing to treat Ivermectin as ineffectual and not reading the essay, and other people who do the same may be doing so as well. Some other people who did not read the essay and continue believing that and acting as if Ivermectin works against COVID may also be acting rational. People who actually read the essay and updated their beliefs to treat Ivermectin as effective may also be acting rational. Therefore, the circumstance that the essay is being dismissed is not prima facie evidence that the community is widely lacking in rationality. (Of course, someone who would stand to benefit a great deal from being convinced that Ivermectin works and can afford understanding the essay would be irrational to ignore it, and conversely someone who should have better things to do with their time may be irrational in reading and updating on the essay.)

The Wikipedia page you linked to makes it clear that "bounded rationality" is a theoretical concept used in posthoc decision-making modeling (such as in economics) and is not something one uses, as your comment does, to buttress a rationalizing of their subjective-intuitive belief giving an impression of it being more factual that it actually is.

Does it? Provide a citation saying that it's only used in post-hoc modelling. I'm not a fan of waving around real-life credentials in general, but here it's probably worth saying that I've actually published in the field and I can assure you there is a plethora of papers written explicitly from the perspective of planning future actions - and, either way, the separation between post-hoc and non-post-hoc you seem to be postulating does not exist, since anything that can be used to evaluate an outcome can also be used to estimate optimal actions, if you know anything about the relationship between actions and expected outcomes at all.

That's the kind of sophistry only rationalists can come up with!

By "rationalists", do you now mean people who swear by "reason and logic", or are you back to using the more specific definition?

I don't think your impression is correct, and moreover this kind of attempt to psychoanalyse your interlocutor is really not conducive to having a conversation where even one of the participants walks away with a benefit. Could you please actually engage with the content of my claim, instead of trying to dismiss it by way of something that seems to amount to "dictionary definitions say this is now how you do rationality"? The claim is not that complex: for many people in the community, it is utility-maximising to ignore this essay and continue disbelieving in Ivermectin's efficacy, because the essay takes a lot of time and effort to evaluate, the extra utility gained if it is in fact correct is small, and there are common priors that it would be surprising (that is: unlikely) if Ivermectin works against COVID. Therefore, because the definition of "rational" used by "rationalists" is very close to "utility-maximising", as far as rationalists are concerned the essay and discourse around it are not in fact strong evidence that rationalists are failing to be rational. If you disagree with any part of this, state which one! I would find it interesting to see your counterarguments about that. I would not find it interesting to see further arguments that I am only thinking those thoughts because I hate the author.

We can see the results of arguments that someone who aims to be X (their definition) is betraying their principles because they are failing to be X (your definition) around us every day, for X="not racist", "just" etc.; personally, at least, I don't like these results.

I'm not disputing your rationalization per see.

So you think the argument is correct? In that case, what are we even disagreeing about? The argument concluded that the rationalist community is not being particularly "irrational" or even doing anything clearly wrong in not reading and reacting to the text. Do you want this to change? If not, I don't see why you even bother posting about it. If yes, I think I offered some reasonably actionable ways in which you could make it change. Of course, if you think those ways are not actually actionable, this does reflect badly on the case itself: for instance, if even people interested in and informed on the topic can't propose a mechanism of action by which Ivermectin is supposed to help against COVID, this makes it more likely that such a mechanism doesn't exist.

And Instead of "continue disbelieving in Ivermectin's efficacy" it would be more accurate to say people "don't care to change one's mind based on new information because one cannot even be bothered to understand it".

The world is full of texts that claim to improve your life drastically which I assume you haven't all read, ranging from self-help books to religious scriptures. If I tell you that Dianetics (the Scientology book) is very definitively correct and will improve your life for the better, will you go read it? If not, why not? Do you also "not care to change your mind based on new information because you cannot even be bothered to understand it"? Is every explanation you have for not reading those texts also a "rationalisation" as you define the term, or do you figure that your reasoning there is more legitimate somehow?

[...] your orignal comment [...] saying "[...] I suggest everyone do so."

Can you quote where you think I said that?

More comments

By your reasoning, shooting your enemy in the head rather than arguing against him is the most rational thing you can do.

"Rationality is about winning" is affected by the question of "rationality towards doing what?" Rationality towards beating your enemies is won by having enemies who are beaten, but rationality about making correct arguments is only won by having correct arguments.

Sometimes it is. Sometimes you have other enemies though, and signalling to them that you will shoot them might inspire them to gang up against you and shoot you first.

Most people reading this post will have some value functions that are not actually that different from each other, which are meant to optimise for general day-to-day flourishing of themselves and some limited set of other people they care about, and then perhaps to a lesser extent some aesthetic and moral preferences about the larger society they find themselves in. What I was aiming to demonstrate is that those people can quite rationally - towards their own value function - decide to dismiss this essay and not shift their opinion on Ivermectin, contra the "rationalists proven not so rational after all!" rhetoric that has been surrounding its propagation.

What I was aiming to demonstrate is that those people can quite rationally - towards their own value function - decide to dismiss this essay and not shift their opinion on Ivermectin

Only if their value function is not about making correct arguments and believing accurate things.

Of course, this then becomes a motte and bailey, where the motte is "it's rational because it wins according to a value function that doesn't value truth" and the bailey is "it's rational in the way that 'rational' is ordinarily used in this context".

"Due to the culture-war dimension of Ivermectin, whose efficacy the red tribe in the US has entangled its social status with (no point in recounting the way this happened here), there is an obvious motivation for members of that tribe to produce compelling-looking arguments for its efficacy."

The corollary to this is that the FDA itself went out of its way to smear Ivermectin as horse dewormer. The FDA tweeted the following over a year ago. Is it normal for the FDA to mock drugs like this?

"You are not a horse. You are not a cow. Seriously, y'all. Stop it."

This seems to me way worse than Bret Weinstein getting overly excited about Ivermectin and jumping the gun on a study that turned out to be no good.

So I have the opposite point in favor of Ivermectin, and in fact, Scott makes a similar point in saying that big pharma suppresses cheap old generic drugs all the time to get people to take their new expensive drugs. It's their marketing model. So we know at least millions of dollars of marketing are being spent to take down Ivermectin. Who is spending the big money in favor of Ivermectin?Nobody.

I don't understand the usage of "corollary" (a straightforward consequence of a previous nontrivial statement) here. Is that the word you were meaning to use?

The FDA tweeted the following over a year ago. Is it normal for the FDA to mock drugs like this?

No, but on culture war it is. This was already after Red cultural authorities had thrown their clout behind Ivermectin, no? The FDA, too, is a Blue technocratic institution; of course it would be tempted to put out communication that lowers the status of the Reds, and in this particular case there was the additional motivation for it that the Ivermectin push was a direct attack on the FDA's authority. One would therefore expect the FDA to attack it independently of whether it works, and so the FDA attacking it is not a signal for or against it working.

I thought it was unnecessary to rehash the backstory, but maybe not. My understanding was that it was associated with culture warring almost from the start: the Blue team occupied the "COVID is scary and untreatable, therefore we need lockdowns, mask-wearing and more powers for our technocrats" position. The Red team found the suggested conclusion unbearable, and tried to respond by attacking every point of the premise. One such push was against the "untreatable" part, and took the shape of asserting that a series of widely available remedies that ranged from completely implausible (bleach) to the merely seemingly random (hydroxychloroquine, ivermectin) worked against it (with the implication that if it did, the power grab by Blue authorities would be proven unjustifiable). Therefore, on the balance, up to this point the situation is still as I described: Reds would push Ivermectin regardless of whether it works, and the FDA would pan it regardless of whether it works, so neither observation tells us anything about it. The prior still is that a random drug with no evident mechanism of action on COVID would not work on it.

The "cheap old generic drugs suppressed for profit" argument is a better one, though (there, you would actually suspect more effort to suppress effective ones, as if someone takes a cheap old ineffective drug, they don't get cured and are still on the market for the more expensive one afterwards).

corollary- a proposition that follows from (and is often appended to) one already proved.

If we grant that Ivermectin's effectiveness is a red tribe talking point, then it follows that Ivermectin's ineffectiveness is culturally important to blue tribe.

However- in a sane world, we would still expect a few Joe Rogan's and Bret Weinstein's to weigh in on their far out beliefs on a podcast. What we wouldn't expect in a sane world is for the FDA to snarkily take a side using a national institution of science, well before the fog of war had cleared.

However, the FDA receives much of their funding from Pfizer/Moderna/JnJ and there is a revolving door among board members.

I doubt Rogan is getting paid by Ivermectin advocates. There's no money in it. You could argue that he gains more followers by choosing the fault line, a kind of reverse audience capture.

I find it easier to place the cultural war aspect of Ivermectin into the category of, probably more effective than it appears since even the FDA will go out of its way to smear the cheap and safe drug as "horse dewormer."

Again, maybe I'm wrong but that was my internal assesment. It was odd to see someone making a symmetrical but opposite argument.

I find it easier to place the cultural war aspect of Ivermectin into the category of, probably more effective than it appears since even the FDA will go out of its way to smear the free and safe drug as "horse dewormer."

Yeah, I don't see how this follows. I would expect both P(FDA smears Ivermectin | Ivermectin doesn't work) and P(FDA smears Ivermectin | Ivermectin works) to be close to 1 under our conditions of Ivermectin's culture war role and the FDA, so P(Ivermectin works | FDA smears Ivermectin) is basically the same as the prior P(Ivermectin works).

( P(W|F) = P(F|W)P(W)/P(F) = ~= (1/1) * P(W) = P(W) )

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