Oh, and ACX links to https://henryaj.substack.com/p/lifehacks who claims: "in most places you're just allowed to buy and import prescription medication and take it" linking to
UK website looks to still be good. [Edit, but both only ship to the UK, dang. What's the international version, used to be dodgy Indian websites...]
I have been unable to find any source for the powder for suspension you'd need to properly make up the smaller doses for children, if anyone else finds it that'd be helpful.
Are your figures in addition to, or instead of, mortality from a normal flu season? It seems a solid chunk of your found expected h5n1 deaths would be expected to die from normal flu anyway, wouldn't h5n1 replace the normal flu? At the very least, anti pandemic measure would limit normal flu spread similar to anti covid.
Presumably, the anti-pandemic measures would be calibrated to the expected level of danger. An h5n1 pandemic that's closer to the 2009 pig flu outbreak would probably get a pretty tepid response, while something like the 1919 pandemic or worse would get the full Covid treatment.
If an outbreak happens that is seen as bad enough to justify lockdowns, I would expect them to be extremely effective to the extent they're complied with. The Covid response was initially modelled on planned responses for a particularly severe pandemic flu, and they work better on influenza than on covid due to stuff like droplets vs aerosols. "To the extent they're complied with" is the hard part, since everyone is still tired from last time.
Honestly, are governments going to even bother this time, considering the response to the previous lockdowns? People are just going to do whatever the hell they want. And ultimately, a few dozen million deaths isn't a big deal when it's spread out across the globe.
A lot of the effective changes around Covid, at least in the UK, were voluntary and often started among the population before the government changed the advice or issued legal restrictions. The population (and the police…) often went beyond what the government had actually required, because they were worried and trying to protect themselves and others.
Of course, we also know that the UK government and scientific advisors were surprised by the high compliance of the population, making the lockdowns much more effective than expected: they had issued stricter advice than they thought was needed, and emphasised the dire consequences of not following it, because they assumed people would skirt around the rules much more than they did.
The things that needed national government support/central decisions that made a big difference to the spread (rather than the treatment) were the closing of schools (made a huge difference to spread in the UK each time) and the easy, free availability of relatively-reliable testing.
Possibly also the chunks of money paid out for businesses furloughing people, paying them to not work, but I can’t see that happening again.
The closing of schools was disasterous in many ways (rendered more disasterous by the choice to close playgrounds and keep them closed, and the slow introduction of things like ‘bubbles’), but also attendance in schools dropped noticeably before each closure, and every time Covid became more prevalent, and not just because students were actually ill. I also had students I did not see for a long time, because they or family members were immune-compromised. Probably a future pandemic needs something more flexible in place around schooling.
The UK testing system was fantastically expensive (for the taxpayer), but popular and widely-used. It gave people a way to manage risk when things were very uncertain, helped monitor what was going on in terms of spread and mutations, and could justify people taking the necessary time off from work in a legally and socially powerful way while they were contagious. I can see a similar system being used again in future pandemics.
...Maybe I am being too cynical. Still, the political situation in the US is a whole different can of worms. The administration has its own supporters to appeal to, and they absolutely do not want lockdowns again. So that's that.
I agree that the US is in a funny place around this: everything around Covid got fantastically split on political lines, didn’t it? I don’t pretend to know how Americans, or the US government, would react to a serious influenza pandemic.
But I think it is still worth bearing in mind that when people think they are in danger, they tend to move to protect themselves with or without government support. Lockdowns were dreadful and I hope never to see them again, but you probably need some sort of government response if the population starts withdrawing from and getting scared of each other.
I suspect if people started to see non-elderly non-otherwise-sick people dying around them, ESPECIALLY children, they'd comply more readily. I might be biased because I don't know anyone who died of covid but I know two people (both young adults and otherwise healthy) who died of flu related sepsis, but still.
I've never known anyone who died of Covid or the flu. But I did know two formerly healthy people, one a relative, who have died in recent years of antibiotic-resistant bacterial infections. And that could well be the wave of the future.
I'd love to believe this, and I probably even used to. Sandy Hook changed that. Half of (at least the American) population doesn't give two shits about dead children.
I don't mean to undermine the emotions here, but do you literally believe that? Like do you think that if you picked a random American and told them that a child had died, there would be a greater than 50% chance they would go, "I don't care about that at all?"
I think you actually mean something more like "Half of Americans don't support measures that would save children at a cost which (I believe) is negligible." And that might be true! But I doubt your model of the world actually matches what you said.
The "half" may be an exaggeration, but it doesn't change my intent. If you're looking for a more "accurate" sentence, I'd say something like "A significant percentage of the American population is okay with child deaths so long as they aren't inconvenienced in any way that impacts them directly." (Masking, vaccines, sensible gun laws, seat belts, speed limits in school zones, etc etc etc.)
A significant portion of America's population is so selfish, they've proven that they truly don't care ENOUGH about child deaths to be inconvenienced.
Summarized and exaggerated: "Half of (at least the American) population doesn't give two shits about dead children."
Ah, ok - that's clarifying, thank you. I personally think most of that percentage thinks the "inconvenience" is too great for the safety increase. Which, I mean, we all take actions that risk our lives and those of others (e.g. driving a car). Your examples reflect that as well - you say "speed limits in school zones" not "speed limits everywhere" presumably because you recognize that there would be a greater cost to a universal 35 mph speed limit, even though it would also save lives.
All of this is just to say: I think the people you are talking about mostly disagree with you about the efficacy or cost of the measures you have in mind, not whether children's lives are valuable. I find that to be a helpful perspective, because it suggests they could be convinced, or that some other measure might be something everyone could agree on.
Is there actually a droplet vs aerosol distinction for covid vs flu? My understanding is that Lindsey Marr was talking about aerosols for flu as early as 2015, and it took Covid for the mainstream health establishment to realize this can be relevant for this sort of virus. I don’t know how much they’ve changed their opinions on flu.
My info for might be outdated.on that particular point. Although flu spreading at all readily by aerosols seems unlikely to me, based on the differences in R0: the numbers I've seen for flu range from 1.2 (normal seasonal flu) to 3.0 (high estimate for the 1918-1920 pandemic), while I've seen newer covid variants estimated at 5.7. Even discounting for the 1.2 figure for seasonal.flu probably not being a true R0 due to cross-immunity with prior years' strains, that's a pretty big gap that gives me a significant prior for there being substantial differences in mode of transmission.
I have seen some much lower estimates for covid's R0, in the pandemic flu range, but they're either analysing the original outbreaks and thus had extremely wide confidence intervals for want of good data, or they're using data from 2020-2021 and thus measuring covid's R0 under lockdown conditions, not its R0 under normal conditions.
It could well be that the lower R0 is just related to different intrinsic ability to penetrate cells, or easier immune response, even if the aerosol aspect is the same. The issue Linsey Marr focused on is that for decades, aerosol transmission was treated as a weird abnormality a few infections had because of a few early 20th century misprints, rather than because of any evidence that it wasn’t common. This is the 2015 article that suggested to me that there is more to this debate than just covid:
Can someone explain for me how/why strain replacement happens? Why doesn't each new strain that crosses over simply increase the overall rate of flu? Do the strains crowd each other out somehow?
The existing strains typically fade out because of population immunity dynamics, which create a hostile environment for them to continue spreading. Here's why:
After a strain has circulated widely, most of the population develops specific antibodies against it. This means:
1. The old strain has fewer susceptible hosts to infect
2. When it does infect someone, their existing partial immunity often leads to milder illness and reduced transmission
3. People are more likely to have some cross-protection against that strain in future seasons
Meanwhile, the new replacement strain has advantages:
- It can infect people who are immune to the old strain
- It spreads more efficiently through the population
- It may cause more severe symptoms due to lack of pre-existing immunity
This creates a competitive situation where:
- The old strain struggles to find new hosts
- The new strain rapidly spreads through the susceptible population
- Resources (susceptible hosts) become increasingly limited for the old strain
Think of it like market competition - once a new, more successful competitor arrives, the old business (strain) has trouble maintaining its customer base (susceptible hosts) and eventually can't sustain itself.
However, it's worth noting that old strains don't always completely disappear - sometimes they can persist at low levels or in specific geographical regions, potentially re-emerging if conditions become favorable again.
> Think of it like market competition - once a new, more successful competitor arrives, the old business (strain) has trouble maintaining its customer base (susceptible hosts) and eventually can't sustain itself.
This feels a little off. How does the new strain interfere with the old strain? The old strain naturally declines by two methods; the hosts become more resistant to it (real decline) and more resistant to its symptoms (apparent, but false, decline). Neither of those relies on the existence of a newer strain.
(All humans carry a significant number of completely asymptomatic diseases, which is why islanders get sick when they're visited by ships.)
You’re right, it doesn’t come out and say why there are fewer susceptible hosts for the old strain.
I assume for two reasons: Mortality and NPIs (spontaneous and mandated).
And one more: Non-specific antiviral responses such that infections from the new strain induce a temporary shield against the older strain thereby further isolating it.
This herd immunity (and/or mortality) and NPIs have been the accepted explanations for strain replacement. With COVID these explanations don't really fly. Of course, it's hard to compare NPI implementations from country to country, but with a highly contagious pathogen like COVID, even the strictest NPIs couldn't stop its spread once newer, more transmissible variants evolved (see China's attempt at ZeroCOVID).
We've seen...
1. A new variant can push out all the previous variants and become the dominant variant but not create a new wave — i.e., it takes up a bigger piece of a smaller pie. Examples of this are Alpha in the US and Kraken worldwide. In fact, in the US, Kraken may have prematurely ended the BQ.1 wave because (counterintuitively) US COVID cases dropped precipitously as Kraken became the dominant variant.
2. In two countries with a similar variant mix, a new variant can create a wave of new cases in one country but not another. Examples: Lamda and Gamma in South America (although they were roughly contiguous in time, so they may have possibly been burning each other's fuel). XEC seems to be starting a new wave in the US, but it didn't create a wave in Australia.
3. And then we have examples like Omicron that pushed every other variant aside and created new waves everywhere.
Other weirdness that's worth noting...
4. Even though regions may have similar variant mixes, some regions seem to experience two COVID waves each year (US and Australia), and some have three or four waves each year (France, Germany).
5. Possible examples of viral interference: There seems to be some sort of inverse relationship between SARS2 waves and Rhinovirus waves. RhVs peak when COVID is low. COVID peaks when RhVs are low. Influenza cases in the US (and worldwide) dropped precipitously to virtually zero just as COVID cases started ramping up. NPIs have been put forward as the post hoc explanation for the phenomenon, but this dropoff happened before NPIs were mandated. And except for a long, slow burn of Type B cases in China during their ZeroCOVID lockdown, flu stopped circulating until the advent of Omicron. Then it came back with a vengeance.
Makes the carrier confine to home for the duration of illness and avoid seeing strangers? Drives up the fever making the body more hostile to pathogens in general?
"more resistant to its symptoms(apparent, but false, decline)"
some symptoms are among the best ways for diseases to spread, or if (e.g.) a host is less likely to sneeze or cough while having an illness, they're also less likely to spread it, even conditioning upon the same viral load.
"Neither of those relies on the existence of a newer strain."
If two strains of an illness are very similar, there is substantial cross-immunity.
Wild ass guess: most flu strains give cross immunity. The new strain has to have the unusual ability to infect people with immunity to the old strain, or it wouldn't be epidemic. The old strain has no such filtering.
I think this more or less has to be it. It makes sense of the replacement process of Covid strains - the faster spreading strains are providing those who catch them with sufficient immunity against slower spreading strains to eventually reduce the R of the slower spreading strains below 1.
Flu viruses are more immunologically distinct than Covid strains (I'm pretty sure) but it would make sense that the same process could occur with those (although it seems that it also doesn't have to, given the coexistence of multiple endemic strains).
That puzzles me, too. My guess would be that at least part of the answer is behavioral and public health responses: stuff like staying home when sick, avoiding large gatherings, hand washing, etc should "tax" the transmission rate of all flu strains roughly evenly. Seasonal flu has an R value of about 1.2 at the start of the flu season, while pandemic flu usually have R0 of 2-3. If the pandemic response, whether organic or mandated, reduces the rate of spread of all influenza by about a third, then the pandemic flu is still spreading but the established season flu strains are slowly dying out (effective R value of 0.9).
Influenza has a pretty short generation time, about three days according to a preprint paper that came up on Google (Chan et al, 2024, Estimating the generation time for influenza transmission using household data in the United States), so effective R doesn't need to be much below 1 for very long for a given strain to almost disappear. Maybe six months for a 99.9% reduction using my guestimated R of 0.9.
I also find this confusing and I would note that it also happened during COVID, despite different variants giving imperfect protection against each other. In the UK, Alpha, Delta and Omicron each totally replaced the previously predominant strain, which never returned.
likely same as with covid - there's generally some cross-immunity and newer successful strains can outcompete older strains while leaving behind new cross-immunity. It's one of the reasons original covid strains are basically extinct at this point, new strains are very different, and humans are handling infections better even without any treatment.
When a new influenza strain emerges, infection with this strain indeed triggers an immune response not only against its own antigens but also against previously encountered strains, due to original antigenic sin. This cross-reactive immune response effectively suppresses both the new and old strains simultaneously, making it difficult for the old strains to maintain their presence in the population.
This mechanism is particularly important because, as you correctly note, simple competition for susceptible hosts isn't a sufficient explanation given that viral coinfections are possible. The immunological interference created by original antigenic sin provides a more complete explanation for strain succession. When people encounter new strains, their immune systems mount responses that inadvertently provide protection against older strains, even if those older strains weren't directly encountered in that infection.
This creates a powerful selective pressure favoring novel variants that can escape existing immunity while simultaneously suppressing older variants through cross-reactive immune responses.
Can someone explain why we need to cull animals that get the bird flu, instead of just letting them recover? The economic consequences (eggs are over $10 a dozen at my local grocery store) are very severe and at some point is it protecting us from spread anymore or just causing unwarranted supply chain issues?
Whoa, where is that grocery store?? I live in a large city where the cost of living is generally well above the US mean, and eggs here are $3.50/dozen. I just yesterday bought cage-free/no-antibiotics/hand-fed-by-virgins eggs (that last being my wife's description) for $6/dozen.
SF Bay Area. I will admit that I didn’t price shop, I went to go buy eggs at my local non-Whole Foods grocery store and the cheapest I could find was $10 and upwards of $15 and limit of 2. Only a month ago I got it for $5 a dozen and I was told bird flu was the cause of the inflation.
I’m on the Peninsula and see stores with prices of $10-15 (typically these are free-range or cage-free, but they don’t have anything more factory-produced), and stores that simply have no eggs at all. (And no, I’m not talking about hardware stores.)
In the current situation, those "free-range" chicks may well be stuck inside a building, too, to avoid further infections by wild birds. At least, that is how situations are handled in Germany: The "free-range" farmers wait for the admin to call out an "emergency", then (and only then) they put them inside and can still sell those eggs as "free-range". (If the farmers were more pro-active, they would lose that label, so they are contra-active.) - One more reason not to buy free-range ever - good luck to find "caged" anywhere nowadays!
The general strategy thus far for dealing with avian flu is to try to completely stamp it out and prevent spread, which means acting fast to cull all possibly infected birds. It should be noted that in some strains of avian influenza (like the currently circulating H5N1), they're likely to kill the entire flock within 48 hours or so anyway, so it's not just culling of poultry that leads to high egg prices (this is why some strains are labeled "HPAI" or highly pathogenic avian influenza; they're highly pathogenic in poultry).
That's gonna be challenging with the large migratory bird species that are being found dead along the Mississippi flyway. Snow geese and mute swans migrate thousands of miles and the US Midwest is in the middle of their routes.
I think a good argument can be made that the "stamping out" policy has failed as of 2024, yes. What matters now is if that argument is made within the public health bubble and gains enough support for changes to be made.
This is the agricultural bubble that is running things. I don’t think public health people have much power on agriculture, but agriculture people have all sorts of rules about preventing losses to their companies. (Including strict cull requirements to try to prevent virus spread, but implemented by corporate farmers who are just following rules rather than thinking about viral dynamics.)
Re: eggs are over $10 a dozen at my local grocery store
Wow-- where do you live and what grocery store do you shop at? Egg prices are definitely high here in Florida but not that high, not even at Whole Foods. (I assume we're talking about a dozen eggs?)
The response below addresses the incentive to cull birds rather than the need to cull them:
The government reimburses farmers for the loss of birds due to culling to prevent bird flu. According to the Department of Agriculture, farms that report outbreaks of bird flu quickly are eligible for compensation for the birds that are killed through culling. This program aims to encourage rapid reporting of outbreaks to control the spread of the virus. However, the government does NOT compensate for birds that die from the disease itself.
If you are a farmer who wants to stay in business/is risk adverse, what do you do if one birds tests positive?
It appears to me that increases in food prices and the downstream effects do NOT factor into the decision to cull birds.
I wonder if the resilience of farm workers is cos they have a long history of exposure, maybe even to lots of different minor variants, so their immune systems are already primed.
While we're on the subject: I have guy who delivers eggs. The other day I caught him cleaning blood off the eggs with a licked finger. I tried to impress on him that this probably wasn't wise. (We're in southern England, so I think we're mostly OK ATM)
Or then humans in good health, kept warm and well fed die very rarely from any flu, so that older strains were not any deadlier, but humans lived in poorer conditions and were therefore more suspectible.
People have always started dying from various infections when food starts running out.
I would think farm workers are almost all of "working age"; for many diseases, the most vulnerable are the very young and the very old, who are too young or too old to be doing much farm work. Farm children contribute to the farm work, but my impression from my farming cousins is that farm kids today mostly go to school and whatnot just like non-farm kids, and don't do much actual farm labor until they are teenagers who are old enough to no longer be unusually vulnerable to diseases.
My information on modern farming practices comes from my pig-farming cousins in Iowa, so it's possible my knowledge does not generalize across all American farms.
Certainly not the case in the UK: average age of farmers here is 58. Many are working past retirement age (40% of farm holders are over the age of 65). Average age of farm workers is about 40.
Not sure if its any different in the south but in a suburb in the outskirts of Newcastle I get regular letters from DEFRA asking me to declare any bird populations and monitor them for flu due to being a "high risk area"
>If reassortment is sort of like viral sex, pigs are sort of like Tinder.
And ACX is off to a hilarious start in 2025!
Now I'm imagining what H5N1's Tinder profile would be. "Baby I've got a fever... Wanna come back to my place and swap glycoproteins?"
Let's just hope the profile pic looks bad and nobody swipes right.
>Epidemiologists hate raw milk, think there is never any reason to drink it, and will announce that risks > benefits if the risk is greater than zero. I don’t know if the risk level is at a point where people who like raw milk should avoid it.
As a biologist (not an epidemiologist though) I agree. There is never any reason to drink raw milk and it can make you sick in other ways besides H5N1 (like bovine tuberculosis). Cheese made from raw milk is probably OK if it's aged for long enough that all the pathogens die off (several months), but I really don't understand why people like raw milk in the first place.
Huh, I've never noticed a difference. It seems some people are very sensitive to slight differences in milk taste and others are not. Or maybe it's a difference between people who drink large quantities of milk straight and those who mostly mix it with other things (tea, cereal, baked goods).
I've had it many times as a child. It does taste different; most people tend to either love it or find it disgusting.
I personally prefer the raw taste, but not enough to specifically seek it out (it's very hard to find in Canada anyway, as far as I know). But I would have it again if an opportunity presented itself.
I had raw milk on two occasions: 1. in Germany in a small supermarket catering also to some rich people (Heino among them). That milk is ... milked under extremely strict rules which make it more expensive but as safe as it gets. Think: "safe as honey" - still, do not give honey or raw milk to babies! The taste was really nice, and I do like milk (sucker). Would buy and drink again any time (was only double the normal price) 2. In Ukraine on a market in a re-used plastic bottle. Idiot me drunk it. And got so sick, I had to vomit it all out 2 hours later. Looked like pieces of white cheese. Some nearby chickens enjoyed it. Oh, traditional small scale farming, the romance of it!
In the US, cheese made from raw milk is required by law to be aged for at least 60 days, so if you can find it at the store, it'll be at least that aged. This mostly means that you won't see fresh style (e.g. mozzerella) or bloomy (brie) cheeses made from raw milk here; other styles are generally aged at least that long anyway.
Last time raw milk came up, the main argument I found enlightening was to think of it as relative risk vs absolute risk. It's supposedly around 1000x more dangerous than pasteurized milk (risk of hospitalization and death), but pasteurized milk has such insanely low casualty rates anyways that regular consumption of raw milk is practically equivalent (in risk) to increasing your daily car commute by a few meters, or eating one additional charcoal-grilled steak per year.
I grew up on a dairy farm, can attest that raw milk has a different (better for my taste) flavour to an extent. If I still lived on a dairy farm and had confidence in the hygiene practices I would drink it for sure just for the taste. The pro-health arguments are rubbish though, agree it's likely to be a risk not worth it if you are relying on hippie idiots to get their supply chain right, so I never try to find raw milk commercially.
I'm also not sure how many people confuse pastuerisation with homogenisation, I duspect at least a few people who think they don't like pastuerised milk really just don't like homogenised milk and don't know that's two different processes that don't have to go together.
"But the exact mortality pattern was surprising; people between 18 and 28 were especially likely to die, and people older than 88 especially likely to survive. Why? Because an H1N1 flu went pandemic in 1830; anyone who first encountered the flu around then had an immune system synced to H1N1."
What are the merits of deliberately creating a less lethal, more infectious strain of flu variants that we expect as particularly likely to start a pandemic? Do we have the prediction powers to see what variants are more likely than others to start a pandemic? Is it even possible to create less lethal and more transmissible versions of a virus that would also not cause an increase of overall deaths compared to doing nothing?
I suppose this is just transmissible vaccines, which I've seen discussed before. Is there anything different than what I just mentioned and what people normally discuss when they speak of transmissible vaccines?
Wuhan was I believe going for a more infectious (to humans) bat flu, but indifferent w/re lethality. The objective was not to create a less-lethal variant just to see if they could, and certainly not to create a less-lethal variant and set it loose to build herd immunity, but to answer the question in Scott's part 3: If this flying-critter airborne infection crosses over into humans, how bad would it be? If the crossovers were likely to be highly lethal, they wanted to know that.
Which would have been valuable knowledge, if we had it a few years ahead of the actual pandemic and if it stayed safely contained in a BSL-4 facility.
But the actual crossover might have different mutations and so be different from what they had. Meanwhile the response doesn't really need to know ahead of time.
Maybe, but we can't say if that was a good idea or not. Or rather, if COVID came from bats and not the lab, than the whole pandemic doesn't give us any new evidence on whether what the Wuhan lab was doing was good or bad.
> the Spanish Flu of 1918 was an H1N1 strain that killed about 2% of the world’s population. But the exact mortality pattern was surprising; people between 18 and 28 were especially likely to die, and people older than 88 especially likely to survive. Why? Because an H1N1 flu went pandemic in 1830; anyone who first encountered the flu around then had an immune system synced to H1N1. But an H3N8 flu went pandemic between 1890 and 1900; anyone who first encountered the flu then had an immune system synced to that strain and was unprepared for H1N1. See [here] for the details.
Hmm, I read something that attributed the different profile of the Spanish Flu to the radically different ecology of young men around 1918. To wit, if you were in a trench and got mildly sick, you stayed in your trench, whereas if you were in a trench and became deathly ill, you were shipped to an infirmary behind the lines where you could infect vastly more people drawn from a much wider geographic range. So there was strong selection for high lethality in young men. This contrasts with the normal state of affairs where if you're mildly sick you keep going about your business (just like in the trenches) but if you become severely ill, you withdraw into your personal home (opposite of the trenches).
Why is this theory of the Spanish Flu less convincing than "it was a coincidence"?
> But the biologists I talked to said people tend to overupdate on this, that evolution can do lots of weird things, and that the 1918 flu forgot to read the Evolutionary Virology textbook and actually mutated to get *worse*.
This... looks like strong support for the theory that the virus was selected for high lethality?
Huh, I was reading somewhere... (bad cattitude?) that a lot of Spanish flu deaths among young men was because doctors were treating them with the new wonder drug, Aspirin, and giving them lethal overdoses.
I suspect that towards the end of WW1 most people in Northern Europe weren't eating very healthily, what with the prowling U boats hampering convoys, and naval blockades.
So maybe nutritional deficiencies also made it harder to recover from a dose of Spanish Flu. Cooks back then also boiled vegetables for longer, so maybe lack of Vitamin C was one example of such a deficiency.
I read a book about the Spanish Flu (I believe it was “The Great Influenza”) and he attributed the young deaths to the cytokine storms - ie, young people with stronger immune systems ironically had stronger immune overreactions, and therefore died in greater numbers.
Was the flu selected in the trenches? The disease got its start in the Midwest United States (Kansas). However, it did take a year to get ripping, but I thought that was after the war. I believe people who got it during the war got the earlier, safer variant, and were later protected. Still possible it was selected in the trenches though when it got worse, just not sure about that.
Anyways, it’s less strange than Alexander suggested that a virus gets worse at first and then less dangerous later. Experiments on rabbits show that new viruses can become extremely dangerous as they adapt to a new host - they get better at spreading by bypassing the immune system after all. It takes time for the evolutionary logic to slow down the lethality.
We saw this with Covid: many of the first strains became more dangerous as they became better at spreading (like Delta) and then became less dangerous later (omicron). This was the pattern I was expecting based on some virologists I read, so it was intellectually satisfying to see it play out that way.
> The forecasters I talked to raised one other point of uncertainty: does the flu work more like a dice roll, or like a bus? Dice rolls are uncorrelated with their predecessors; even if it’s been a hundred rolls since you last rolled a 6, your chance this time is still 1/6. But buses come at fixed intervals; if the buses are hourly, and you haven’t seen a bus in the past 59 minutes, then your chance of seeing a bus in the next minute is very high.
This one seems easy; the flu is more like a bus. It's a motivated adversary working against you, not an indifferent phenomenon.
But this doesn't help to predict outbreaks; compare some phenomena that everyone agrees work the same way, earthquakes and volcanic eruptions. We know that the potential for these phenomena accumulates over time until eventually there's a breakout. The implications are... nothing, if you're worried about when exactly the next breakout might happen. They're mostly relevant to how regular a long-term average of the event rate should look.
Hmm, in the relevant sense, I believe that all three of these things are statistically distributed much more like dice than like buses. Even though the naive model of building tension for earthquakes makes you think it should be more bus-like, it turns out that the total amount of stored tension in the plates is so incredibly much greater than the amount of tension accumulated per century or dissipated per earthquake that frequencies don’t change significantly either when the most recent earthquake was recent or was long ago.
I'm not sure that buses have the statistical properties that you'd like to attribute to buses. Here's an example:
1. The bus is scheduled to arrive once per hour.
2. It is currently 45 minutes late.
3. What is the probability that the bus arrives within the next 5 minutes?
It's true that the arrival of buses is regulated. But it's not true that the extended delay we observe makes an imminent arrival likely. It makes it unlikely, because the effect dominating the arrival of the bus is whatever catastrophe has already made it 45 minutes late, not the overall goal of arriving once per hour. The chance of arriving within the next 5 minutes was much higher 48 minutes ago than it is now. If you were 14 minutes early for the bus, you haven't seen it arrive in 59 minutes, but it's not true that the chance of seeing a bus in the next one minute is high.
45 minute delay on a 60 minute bus schedule might be a sign of a “catastrophe” that would stop all bus travel. But 15 minute delay on a 20 minute bus schedule is actually a very common result of ordinary traffic. It’s true that there’s some complexity to it - it’s not just that the longer the delay is, the greater the per minute probability of arrival, because there are also other effects like the one you mention, as well as the fact that if one bus is delayed, the bus after it has a tendency to get *ahead* of schedule, since its less likely to find passengers at the stops and can just keep going.
But I don’t think we need a detailed model of bus arrival probabilities to distinguish the nearly time-independent poisson process of earthquakes and passenger arrivals at bus stops from the highly time-dependent processes of elections and bus arrivals at bus stops.
> Epidemiologists hate raw milk, think there is never any reason to drink it, and will announce that risks [exceed] benefits if the risk is greater than zero. I don’t know if the risk level is at a point where people who like raw milk should avoid it.
This raises an interesting contrast with anal sex. What do epidemiologists think about that?
Epidemiologists recognize value in anal sex (people like having anal sex) and so they spend money advertising public health advisories about using condoms and perhaps a drug regime that makes people having anal sex less likely to become infected with HIV (pre-exposure prophylaxis, advertised as "PrEP").
Epidemiologists don't believe them. They think the difference in flavour isn't real but is an artefact of knowing the milk is raw (ie you could sell pasteurised milk as raw milk and people wouldn't notice). I'm not convinced on this.
I'm not convinced either, having grown up with a house cow and consequently having a prolonged experience with raw milk decades before anyone asked the epidemiologists. (Although we were always very aware of zoonoses and cow health in general; living that closely with an animal makes the reciprocal nature of the relationship effortlessly obvious.)
Raw milk tastes distinctly different from pasturised milk. I mildly prefer pasteurised; raw milk tastes distinctly and quite strongly of 'cow'.
But is there an analogue to all this stuff for raw milk that wouldn't make raw milk less appealing to the people who drink it? If the appeal is a) that it's raw and b) that you don't trust the people who don't want you to drink it because there are unquantifiable health benefits you've ruled out treating the milk and better education/"safe drinking" tips from experts, which are two analogous responses.
It doesn’t seem like prediction markets helped very much? Might as well go with the base rate. It’s not like we are going to make different decisions about preparations based whether it’s 5% or 10%.
A problem with stockpiling medicines is that they expire within a few years or perhaps even less. So you need to have a plan to rotate through them, or you find expired medicines in your stash when you need them. It happens to me fairly ofter for the medicine stash I keep in the car or at a relative’s apartment.
More generally, I’m sure people’s medicine cabinets are full of expired medicines because people rarely clean them. It’s pretty wasteful.
Finding expired medicines when you need them is probably better than nothing since expiration dates are often set conservatively. But it might be more efficient to let pharmacies handle the inventory? Ideally, the stockpiling should be done by some organization with high sales. You want nearly-expired medicines to go to people who will use them before they expire.
Inventory costs money because it takes up space. Retailers and distributors usually try to *reduce* inventory to increase profits. If we want more medicine to be stockpiled, someone needs to pay them to *increase* inventory. We want the opposite of the “just in time” delivery that most modern supply lines are built on.
This might be done with government subsidies or some kind of private insurance scheme. Does anything like that exist?
The concept of expiration dates with medicines is a bit murky. Many of them continue to work just fine decades after their "expiration dates," which may apparently be set somewhat arbitrarily.
> Based on their review of scientific data, FDA has concluded for emergency responses that, provided the Tamiflu product has been stored under labeled storage conditions, it is scientifically supportable for certain lots of Tamiflu® 30mg, 45mg, and 75mg capsules held in the SNS to be used for a maximum of 20 years beyond their date of manufacture.
Last week I commented here on groups of large wild birds being found dead in wetland areas in the Mississippi flyway. Since then several such instances have been confirmed by state agencies as H1 virus deaths, including in my state (Illinois).
Is it worthwhile to try to use new mRNA vaccine tech to shut down the transmission of these various viruses in farmed pigs and fowl? If so is there any funding stream to make this happen? I mean it sounds like the sort of thing that requires government to solve the cooperation problem.
There's a meta study that found the lethality of H5N1 in humans to be about 20%. You're overlooking the effect of antivirals, which all American patients from 2024 received, and which are extremely effective - as long as they last.
Hmmm, I remember the 1977 flu as the swine flu. On SNL, John Belushi lead the Killer Bees to the vaccination center to steal the vaccine supply because they were friends of the swine flu. Nurse Laraine Newman said they had run out of vaccine hours earlier and had just been injecting saline.
Good summary, but you lost at Metaculus. Why would a bunch of uninformed people, misinformed people, plus some informed people be able to predict a pandemic when even super-informed people can't predict a pandemic? But I find it interesting that cultures (even rational-materialist cultures) can't live without their oracles.
This paper may be of interest: "How well did experts and laypeople forecast the size of the COVID-19 pandemic?"
The effect is essentially the wisdom of the crowd. I also don't understand why it works, but the data says that it often does. In forecasting competitions you get consistently better results from crowds than from individuals, and sometimes better results from an uninformed crowd than from better informed experts.
A stopped clock can be correct twice a day. Has the data you're referencing been compared to controls? It seems to me that people are seeing patterns in ambiguously defined events and that predictions can be biased based on the interests and expertise of active forecasters. And, of course, Metaculus has been very poor at predicting black swan events. It seems to be a common human need to want to see order in the future, but I think predictive markets are woo-woo for people who want to have oracles but need a sugar coating of rationality to wash them down. ;-)
I refer you to this paper. Post hoc analysis shows that random-walk predictions provide fewer erroneous forecasts than crowd predictions.
"Forecasting skill of a crowd-prediction platform: A comparison of exchange rate forecasts"
> Open online crowd-prediction platforms are increasingly used to forecast trends and complex events. Despite the large body of research on crowd-prediction and forecasting tournaments, online crowd-prediction platforms have never been directly compared to other forecasting methods. In this analysis, exchange rate crowd-predictions made on Metaculus are compared to predictions made by the random-walk, a statistical model considered extremely hard-to-beat. The random-walk provides less erroneous forecasts, but the crowd-prediction does very well. By using the random-walk as a benchmark, this analysis provides a rare glimpse into the forecasting skill displayed on open online crowd-prediction platforms.
That is certainly an interesting paper, but it only applies to the hyper-special situation of exchange rates. Which is is somewhat outside the range where we need prediction markets, because exchange rates are a prime example for monetary markets that already predict the correct rate. I think the paper essentially shows that prediction markets do not defeat the efficient markets hypothesis, i.e., they do not beat other money markets. Which isn't surprising. I would not trust Metaculus to tell me which stocks to buy, and I don't think many supporters of prediction markets would go so far to recommend that.
Btw, since you mentioned black swans, the paper actually says that the random walk models predict *less* black swan events than Metaculus. This seems to contradict your point.
I’m not being nitpicky - this goes to the core of what Taleb meant by “Black Swan”: it is completely, utterly unpredictable because we have no framework, no data, nothing we can use to predict it it. “Black Swan” isn’t synonymous with “rare”, it means “we literally have no idea how common this is”.
Pandemics are not black swan events. Anything Metaculus can predict is not a black swan event.
Funny, but I'm only now reading Taleb's _The Black Swan_...
However, I beg to differ with you — I think SARS-CoV-2 fits Taleb's definition of a black swan event. Its occurrence wasn't foreseeable through standard methods or models. The event had a massive and transformative impact on individuals, organizations, and societies. And after it happened, humans rationalized it as if it could have been expected or predicted.
Correct me if I'm wrong about this (please!), but AFAIK, none of the predictive markets were taking bets on a pandemic happening before the advent of SARS-CoV-2 and COVID-19. When the outbreak began, it wasn't really on the radar screens of any of the national health authorities or the WHO. Of course, the Chinese were slow to react because the Mayor of Wuhan tried to hide what was going on (Wuhan was about to host a big CCP wingding when people started to get ill). Dr. Gao, the head of the China CDC, only learned about the outbreak in Wuhan on 30 Dec 2019 via social media. Fauci didn't hear about it until a few days later when a reporter called to ask him about what was going on in China. Even once people started dying, the WHO and the CDC were fairly sanguine about the outbreak. I think the WHO said that there "was no evidence of human-to-human transmission," and the CDC echoed that statement. (Didn't Scott post an essay about how confusing a claim of "no evidence" is?)
A Chinese researcher from the Chinese Academy of Medical Sciences in Beijing uploaded a sequence of the virus to Genbank on 28 Dec 2019, but the person who reviewed the sequence rejected it because it was missing some background info (rumor has it that it was rejected because the submission used the names Beijing and Peking in different fields, and the reviewer wanted consistency — but I haven't been able to verify that). It wasn't until 12 Jan 2020 that a sequence was available for scientists to review. By that time people were dying, and SARS2 had spread out of Wuhan. Clearly, no one was prepared for SARS-CoV-2.
Having said that, After SARS1 and MERS-CoV, *some* experts, such as Peter Daszak and Stephen Morse, among others, were worried about the risk of other zoonotic spillovers. Organizations like the Predict Project and EcoHealth Alliance tried to identify and evaluate pathogens in fauna that were candidates for spillovers into humans. Daszak was the most prescient because he focused his efforts on cataloging Coronaviruses endemic to Horseshoe bat populations (because that was where SARS1 came from).
But I think it was Sonia Shah, in her 2016 book _Pandemic_ who emphasized the risks of wet markets as a likely place for spillovers to occur.
To summarize, after SARS1 in 2003, we had a group of experts who were concerned that a pandemic of zoonotic origins would occur. Although Coronaviruses were among the potential candidates, they were not the only candidates. But they had no predictive models for which mutations could trigger a pandemic (that's why Daszak applied to DARPA for a grant to run GoF tests against CoVs — but it wasn't funded). No one had any predictive models for when the next pandemic would occur (and we still don't). And once COVID hit the mainstream media, Metaculus grossly underpredicted the number of deaths it would cause before 2021. What can I say? It sounds black swannish to me.
I have to confess to cheating 🫣 - I knew the answer because I’ve read Taleb’s own opinion on the matter:
“Covid was not a Black Swan, you don’t call something Black Swan that’s already been in the movies. It’s a White Swan; the fact that we didn’t have a pandemic for close to 100 years is the actual Black Swan. You don’ have a Black Swan when movies talk about pandemics. In my book on Black Swan on page 307, I explained that because of extreme connectivity such pandemics are unavoidable.”
Well, I respect Taleb, but in this Youtube video, he's wrong about being able to contain SARS2. New Zealand, as an island, was able to stop all travelers from entering their country, but it got in somehow. Of course, they did a good job playing whack-a-mole with the outbreaks for a while, but once they had vaccines, they basically let it rip. China, with the strictest ZeroCOVID regime of any country couldn't contain it. And it had already spread by flights out of Wuhan before anyone knew what they were dealing with.
And if a scenario is in the popular media before it happens disqualifies it as a black swan, 9/11 wasn't a black swan. Tom Clancy, in his novel "Debt of Honor" (1994) portrayed a jet plane crashing into the capital, killing the President and a joint session of Congress. So 9/11 was in popular culture before it happened. Also, we had intelligence that Al Queda was planning a massive terrorist attack on the US, but Bush decided not to take it seriously. Seems like this is similar to COVID. We had pandemic narratives in the media. We had experts warning it might happen. But no on really believed it would happen.
As a total layperson on this topic I would appreciate an understanding of why Covid isn't a part of this discussion - I'm guessing Covid isn't 'flu' in the strict sense? Is Covid not likely to fade into the background and become indistinguishable from usual seasonal flu? A parenthetical on this would have been handy as it felt like an elephant in the room while reading the article!
Not to my knowledge, coronaviruses and influenza are from different virus families so it would be like a human managing to reproduce with, like, a giraffe or something.
Covid is not flu in ANY imaginable sense, strict or not strict, unless someone decides to use the word "flu" to mean any viral respiratory illness -- which is a colloquial usage I've seen in the UK among older/middle aged people but it's clearly and obviously erroneous, can be confusing and should be avoided.
Thanks. Prior to reading this article I did think Covid was a type of flu or at least closely related. Maybe this is a thinko unique to me, though in my defence I suspect it was discussed as 'flu-like' quite a lot early on. CF the china_flu subreddit (https://www.reddit.com/r/China_Flu/)
I am also from the UK which might be part of my confusion. Occasionally I do hear people mention eg 'stomach-flu' or 'man-flu' where 'flu' is being used quite generically and not confined to a particular category of virus.
A lot of people who are in the anti-vaccine, anti-lockdown, anti-caring-about-covid-stuff cluster go on a lot about how "it's just the flu", so that general thought is out there in the zeitgeist.
I can see how someone who wasn't super into following this stuff could easily pick up the idea that covid == flu.
“Influenza-like illness” is a technical term for a cluster of symptoms that many viruses cause. The CDC has a category where they track this, because they know they aren’t doing viral tests on everyone, and a surprising number of illnesses go through an influenza-like illness phase. (Apparently initial infection with HIV manifests this way, and even monkeypox does before the lesions show up.) But lots of respiratory viruses never manifest as anything other than influenza-like illness.
I think the symptoms of flu and most other infections are mostly just the immune response. You feel terrible not because the influenza virus is doing something nasty to your body, but because your immune system has kicked into high gear, is using a lot of energy that would otherwise be used for other things into fighting off the infection, and is moving the slider bar between "don't harm self" and "be especially harmful to other." That's why something like HIV gives people an influenza-like illness on initial infection.
If you didn't have that immune response and the associated misery, I think those infections would often progress to the point where they were doing something bad to you themselves. (As with HIV, which evades the initial immune response and keeps evolving around it until it finds a gap, at which point it starts wiping out your T cell population.)
Your declaring a strict definition that come after the common use as being authoritative; is a tomato a fruit? Is it literally unimaginable some may call a tomato a vegetable? Shall you get anal abut calling steaks bovine-chops or something?
Heres an imaginable sense: coughs effect lungs, I estimate how strong my lungs are for illnesses that cause coughs for my chances of survival, I group those illnesses together.
Except it turns out to be much more relevant to your survival to know how it interacts with your immune system, not your lungs, and influenza viruses, coronaviruses, rhinoviruses, syncytial viruses all interact differently with your immune system, even though the symptoms you notice are very similar if the case isn’t especially severe.
Doubtful, damage is damage and pain is pain; pill pushers may talk up details as *marketing* that gets into science textbooks; but your immune system is better then anything they make and your extended immune system *also* makes you feel tired or in pain depending on how bad your illness to signal to the lizard brains to actually take a break no matter how important other things seem.
What do you mean? Are you saying that the immune system cells that learn to recognize coronaviruses can *also* automatically recognize influenza viruses and syncitial viruses and so on, because they cause the same symptoms, and that the “pill pushers” who say that biochemical differences are relevant to immunity are just lying?
If you want to survive a cough, and you feel sleepy go to sleep, if you feel cold get warmer, if your throat hurts sip water or make tea. (not that you have much choice in the matter) These are *extended* immune system behaviors(because evolution is holistic) and are more important then a magic pill.
Half of symptoms *are the immune system itself*, viruses dont want fevers. What matters is maintaining the balance of the system beyond our current understanding with dumb, if not faithful responses. So grouping illnesses based off symptoms just makes sense.
Hyper reductionists can go to hell in general; but for biology especially its just delusional, if you ever actually eat "sodium" your mouth will be on fire, you eat salt; you eat fermented foods, you eat based off cravings bacteria wish for, to feed a bio reactor we can not replicate in a lab.
It doesnt matter what the medical textbooks label viruses or think mechinics of systems are, we are not there yet, not even close. You work with and listen to the body, not make demands like you do bunch of gears or computers, thats not what we are nor the nature of the problem.
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Medical lingo is a pale reflection compared to the felt experience what signals an immune system sends out(lingo is a mere map and a shit one, the immune system is the territory and better at its job then us for the time being), so if corona feels like a flu, its a flu; its very arrogant to declare mere lingo is more correct, to assert the medial systems mechanistic control over evolution's playground is pill pushing and wrong.
Covid is likely to fade into the background and become indistinguishable from the usual common cold. Which is a collection of 200+ distinct viruses that we generally don't bother to distinguish because they are very similar and very mild.
The various flus are also very similar and *usually* very mild, but there are enough differences that it's worth distinguishing between the two disease-clusters. And because of those differences, you wouldn't want to mix Covid statistics or common-cold statistics in with your influenza statistics for an analysis like this.
I suspect it’ll be more like RSV, where we didn’t notice it had systematically more significant complications for a few people, and more serious symptoms for many, than other colds, until we started testing for it.
Not a single mention of eggs, which is what's been keeping bird flu on my mind. There's a permanent sign on our usually-empty egg case at work which says, roughly, "yes, this is all the shipments we got, stop asking". But they don't stop asking...I don't attend to the regular news, so have no idea what coverage is like among normies, yet one would expect a greater level of updating. Every single day, several times a day: >asked for more eggs/chicken >reply negatively >incredulous bafflement, explanation demanded >bird flu, supply and demand >ongoing incredulous bafflement at both concepts ... Can't wait until it starts noticeably impacting cow and pig products too. I remember how infuriated customers got at beef <s>hoarding</s> shortages during early covid. "This can't be happening...in America!"
-- not to make light of suffering and loss of life, obviously that's the far greater utilitarian concern. And I do find it comforting that the risk profile so far is mostly still long tail! But I don't put much faith in the "America's pandemic surveillance and response game is competent" part of the assumption (or the unstated voluntary behavioral modifications part), based on the Jellyman Amnesia on display thus far with H5N1. People just seem to really want to roll to disbelieve that it could happen again soon, on a bus-like model. Like, we already had covid, and then monkeypox, shouldn't we at least get another decade before the next pandemic bus comes along? So - hoping for the best, but prepared to be rather disappointed should we fail a Fort save. At least I'll get to be an Essential Worker(tm) again.
(additional context that would have been nice: ballpark comparison to covid impact, exploration of why things keep getting worse despite having a vaccine for chickens and hopefully one for cows soon. FDA Delenda Est? I think I recall reading something about how it's actually due to a trade dispute, where we couldn't do certain poultry exports if it's vaccinated, and there's no political will to do the equivalent of just buying out the mink farms...? I do appreciate the post regardless, more informative than a dozen breathless thinkpieces by thought[less] leaders)
California’s been short, not out but “they’re out of 18s so I got a 12” level. I’ve been avoiding egg-reliant recipes, less because I can’t get them now than because it seems rude in a shortage, and also they keep and I don’t know if I’ll be able to get them next week, or next month (refrigerated eggs really do keep).
I assumed it was a mix of bird flu and everyone making Christmas cookies based purely on “that’s what it was last year.” If so it should even out in a few weeks to a few months; I think it did last year.
We're caught in a bad Our Price Cheap equilibrium, where...without mentioning the company, we're required to always sell <s>vulnerable to predators, weather, and each other</s> cage-free at minimum, and usually with various other pieties like organic or whatever. However, our prices are also kept low, and there's strong resistance to raising them (internally, from customers, and also from various CA/SF-specific laws against "price gouging"). It's also not the kind of place where we can reliably enforce a per-customer limit. Finally, the company's hesitant about short-term temporary contracts with new suppliers; sometimes it'll happen for truly essential basics like rice or pasta, but eggs don't quite reach that standard. Perfect recipe for regular shortages when one can't react meaningfully to shifting supply and/or demand.
I feel about 90% confident there have already been 10,000 cases and they simply weren't symptomatic enough to trigger testing. In my mind, the simplest explanation for the widespread prevalence of bird flu in farm and zoo animals is that low-symptomatic humans are infecting the animals. The only sensible explanation for the fact that many closed sewer systems are currently awash in bird flu sequences is that a lot more than 66 humans have been unknowingly shedding it in their stool.
I know several people who tested positive for influenza A on a rapid home test, but when they asked healthcare providers to be tested to find out whether it was bird flu or seasonal flu they were summarily tuskegeed. You can't argue that we've been looking for bird flu and not seeing it - the sad truth is we simply haven't been looking. Shameful.
That seems very plausible to me. But his 10,000 number is not meant to be a threshold of actual cases - it’s just meant to be a number that will be passed if there is a phase transition in spread, but not otherwise (unless we change detection methods).
I was more thinking about the Metaculus betting - which seems to be couched as "10,000 cases" - as opposed to "10,000 severe cases." I wouldn't bet there have already been 10,000 severe cases. But 10,000 mild cases? Mostly restricted to the gut? I'd offer 14:1 odds:
My guess is that the use of the word “case” rather than “infection” is meant to pick out individuals who have tested positive, rather than individuals who have been infected but were never detected as such.
In the CDC report above, 7% of farm workers tested positive for bird flu antibodies - indicating that they were unknowingly infected with bird flu in the recent past. I'd call them all "cases," even though they never tested positive for shed virus particles.
The sewage data makes me suspect that the currently circulating strains of bird flu are primarily a gut infection. We're hardly testing anybody, and the tiny bit of testing we are doing might be sampling the wrong orifice.
In the UK during Covid, the government spent a vast fortune, in the billions of pounds I think, setting up a Covid test and trace scheme, and (more relevant to your point) sewage monitoring for the presence of viruses or their antibodies (not sure which).
I believe the sewage monitoring has since been discontinued in the UK. This was possibly (I surmise) in part due to political embarrassment at the amount of illicit drugs whose presence was being detected, revealing how much slips past customs etc, and thus their incompetence. But I gather it was relatively cheap, and would no doubt have been able to give a fair idea of the prevalence of new viruses if these were being checked for.
But UK political leadership, both Tory and Labour, in recent years has been atrociously short sighted and bad. (Our EU membership in previous years has apparently caused native political leadership skills to atrophy almost to nothing!)
Brief note about Spanish Flu mortality rate: you might imagine that WWI-era is modern, in a sense. In fact, medical care at the time didn't involve insuring people weren't dehydrated and were staying warm; people slept outside of hospitals in the winter when hospitals were full. And the lack of resources and malnutrition due to wartime shortages in Europe definitely greatly increased the death rate.
(Also, "Spanish Flu" is an unfair misnomer; it was first widely reported in Spain because that was the only place without wartime censors, it certainly didn't emerge there. In fact, the most likely candidate origin is in the United States, in Kansas.)
at least one very popular medical textbook (“The Principles and Practice of Medicine” by Osler) was in use into the 1920s and recommended bloodletting. Modern medicine is indeed very new.
Indeed. Also worth noting that this was before the concept of a "virus" was fully fleshed out. Also before we had antibiotics (for treating secondary infection). Before IV hydration (or really, before IV anything in a modern sense). Before the concept of a "cytokine storm" was developed, and how to treat it. Certainly before antivirals. Medicine has come a very long way.
One question I have is why we've previously seen large outbreaks of H5N1 that have seemingly burned out - e.g. 136 cases in Egypt in 2015, 55 in Indonesia in 2006, 61 in Vietnam in 2005. These are pretty poor countries so I'm assuming far more people were infected in reality.
It's also interesting to think in a post-covid world how much more attention something like the Egypt outbreak would get today. I didn't know about it until I was reading about H5N1 the other day, and I'm pretty sure if it happened now I would be really freaking out.
I think you are really, really underestimating the impact of the other thing going on in 1918. Particularly in terms of what age group it especially impacted (and which did the flu again?), how much damage it is likely to have done to immune systems (how much good sleep do soldiers in a trench get? How much vitamin C? How about nurses? How about when you move a lot of the population that wasn’t in factories into factories, on a sudden emergency basis, and oh coincidentally that is specifically the population segment that usually manages unpaid informal nursing?), and how many resources it diverted - not just governmental, but household. Having slack is very important for disease treatment: time to lie in bed, time to take off work, time to rest without Something Actually Essential Going Undone. You don’t have a lot in the middle of a war.
My personal guess on priors (I am not an epidemiologist, take with requisite salt) is that the Spanish Flu got at least half its lethality from hitting during a world war, with medical systems both official and informal already overwhelmed and most young people desperately overworked, either directly in the war or making up for all the stuff that still needed to be done when the people who should be doing it were in trenches getting shot at or dead. My basis for this is observations about the effects of rest on disease in me (pushing through illness tends to make it much worse, even if it’s just the early stages I push through) and a lot of reading about wars; take that for what you will. A quick Wikipedia scan also suggests it initially spread in America through Army camps, for what that’s worth; boot camp is obviously not the same as getting shot at but it may not be good for the immune system either, and it also seems to have spread through regular troop movements after, focused on the army. (But I am not an expert; this was literally a quick scan, and I stand more by the first half of the argument.)
My certainty in my precise numbers is low; it’s possible the Spanish Flu was just that bad irrespective of anything else. But given the obvious confounder not addressed, and the way it lines up with the lethality demographics, I strongly suspect something important is being missed. We are, thank God, not presently in a world war, and that should not be irrelevant to the odds of another influenza pandemic being as lethal as the one that was.
(Yes, I know that could change. Hope it doesn’t, not necessary to the point.)
That’s why I mentioned the home front - if your husband/father/brothers are off at war and you’re trying to run the household and work a factory job, plus maybe take care of kids solo, when you come down with it who’s there to take care of you? Remember all your friends/relatives are doing the same thing.
That is, you’re correct if the mechanism is purely spread through armies/stress on soldiers. It’s just I’m pretty sure pulling a significant part of the population away (selected for being in good shape, even!) and then raising pressure on the rest (we were supplying a LOT of war materiel, speaking purely of America, on top of all the usual work that needs doing everywhere and everywhen) is going to cause less slack/societal resources to respond to disasters.
According to Wikipedia (not as good a source, I know) the German and French governments were both spending over 50% of GDP, and Britain was close. It doesn’t mention America and I’m sure it was lower, we weren’t under existential threat - but a lot higher than before the war. So thank you for the link, it’s a good point and given the Wiki comments about spread in army camps I’m surprised it isn’t higher in men. But I’m not sure that disproves my main point about societal resources being low, because they were low for women too. Working a factory job on top of running a household is not as bad as getting shot at, but it probably isn’t great for your immune system either, and maybe that cancels out against guys generally being in better health/women being default first-line healthcare workers? Not sure.
(I’m taking your word for the article because I am, ironically, down with the flu at the moment so can’t follow up on it properly, but thank you for the link, it’s nice to get counter-evidence.)
An obvious difference between this and past bird flus is that it's infected dairy cattle. About 1% of Americans consume raw milk weekly, and 4.4% consume it at least once a year. That's not counting the rest of the world:
To my knowledge cowflu is only present in the U.S.? If it were to spread (or co-evolve) to India it would seem like the chance of a pandemic would be much higher.
Ergo it seems like the chance of a pandemic is much higher than it has been in the past? We're not talking just farm workers exposed here, but sizable portions of the population. Moreover, the sort of people who drink raw milk are probably more likely to avoid vaccines and other sensible safety precautions.
Can we make a vaccine? If not a great vaccine (given that the virus has not yet reached the form that would be dangerous to humans) then a better-than-nothing vaccine?
It might be worthwhile reading a summary of ewald's work on the evolution of infectious disease.. Mostly, he describes fluid borne diseases as special cases whose virulence doesn't evolve the way that airborne diseases do, due to increased genetic diversity and competition, exacerbated by rapid passes from one host to another. But as another poster mentioned, the Spanish Flu evolved in very unusual circumstances, with sick young men stuffed into box cars and carted around Europe. This favors virulence. An ambulatory host stops being such an advantage to spread, so there's less of a restraint on overuse of host resources.
>"Much of this discussion hinges on whether we should expect flus to generally become less virulent when adapting to humans and going pandemic. There’s a hand-wavey evolutionary argument that they should: pathogens don’t “want” to kill (or incapacitate) their host before they can spread. But the biologists I talked to said people tend to overupdate on this, that evolution can do lots of weird things, and that the 1918 flu forgot to read the Evolutionary Virology textbook and actually mutated to get worse. There may be a slight tendency for things vaguely like this to happen, but we shouldn’t count on them."
The usual reply I know of, is that there can be positive associations between infectiousness and virulence (e.g. via how much resource it hijacks, or if it attacks the immune system, or if it needs to give you diarrhea to transmit), so a virus can evolve to be more virulent if it comes with a big enough increase in infectiousness. The simplest models have it evolve to maximize R0, though iirc this can depend on details like coinfection. (What maximizes this is also expected to depend on mode of transmission; e.g. if you're laid up in bed you can't go out and cough on people, but a mosquito can still bite you then bite other people.) The association/trade-off theory was developed by Anderson and May (1982) and Ewald (1983) (according to Alizon et al. 2009); Ewald also developed theory about how it's affected by transmission mode etc, which is all now a staple of evolutionary medicine (Williams and Nesse, 1991; Ewald, 1993; Nesse and Williams, 1998). A case study of virulence decreasing at first but then increasing later on is myxoma virus in rabbits in Australia (Zimmer, 2022). Stephen Stearns' Yale course on evolutionary medicine, available on YouTube, has two videos on virulence evolution (Stearns, 2015).
References
Alizon, S. et al. (2008). Virulence evolution and the trade-off hypothesis: history, current state of affairs and the future. J Evol Biol 22: 245-259. https://doi.org/10.1111/j.1420-9101.2008.01658.x
Tl;dr it was released in 1950 to try to control the rabbits; it evolved to be less virulent, but was still pretty virulent; the rabbits evolved immune resistance, but then that provoked an evolutionary response in the virus to become more virulent.
I struggle to understand why there is not a national stockpile of 1 billion doses of Oseltamivir if not Baloxavir. Maybe very effective, maybe a little, maybe not at all, but generally safe and well tolerated. And crucially already in existence—with oseltamivir even off patent. As a practicing physician, I find the pharmacies in Washington DC routinely run out of both drugs in a normal flu season. Why don’t we have better access to these?
I'm pretty sure that there is a 1 billion dose stockpile of medical countermeasures. But a treatment course is 10 doses, so you're down to 100 million treatment courses. That's enough to treat a first wave in the US population, but not enough for everyone, let alone prophylaxis of essential workers for a few months. I think we should assume everyone is going to get a new respiratory virus: non-pharmaceutical interventions are going to spread that out somewhat but eventually it's everyone. If you have a 3 billion dose stockpile you may have to replenish 25% of it per year (generic oseltamavir has a 3 year shelf life in Australia, Tamiflu has a 10 year shelf life to help with the stockpile requirement).
Since this can be devastating to sold bird populations, isn't a major possible vector of transmission people's dogs and cats? Any dog that comes across a dead bird is going to sniff around it and probably roll in it and possibly eat it...same if it finds a sick and dying bird. Cats that go outside spend all day trying to kill birds. The majority of US households have a dog, and about about a third have a cat. This is my primary concern, given that it seems to be quite lethal for cats. My cat doesn't go outside, but my dogs do, and I don't want them snuffling around in some dead/dying bird and bringing something back that they transmit to and kill my cat. If people are finding flocks of dead birds frequently, this seems inevitable if more wild birds get hit.
Thank you for the dice roll vs bus analogy. I've been bothered by "gambler's fallacy" for a while now, mainly that saying that "humans are bad at probability" doesn't seem right. My conclusion is that brain are not trained on pure chances calculations, because they never encounter it.
Almost everything happening influences whether that thing will or will not happen again. In that bus analogy, abscene increase probability. In competent doctor operation analogy, presence increase probability. In any case, even dice roll isn't as pure as dice roll, so gambler's fallacy seems to only apply to artificial environment and theoretical gotchas. This is why I'm more symphatetic to Bayesian, it seems to simulate, either brain or reality, better.
As an aside, whenever I read something touching on evolutionary biology, it seems to reinforce my prior that it's unfalsifiable. By this point it may be a trapped prior, but I think I have been vigilant enough. And I can still bet it'll never reach as high of predictability as particle physics (Maybe an unfair comparison, but I want to assert that degrees of predicting power exist, and evolutionary biology seems to be very low on it).
Evolutionary biology grad student here. I agree that it will never have the same predictive power as e.g. particle physics. There are few general "laws" about what will evolve, partly because it depends on what traits are developmentally feasible and development is complicated (might there be reasons why a pig can't grow wings even if it would be fit to?), and partly because fitness depends on ecological context (compare: whether a key is good depends not just on the key on its own but on whether the key fits the lock).
The comparison, fair or not, does highlight why physics is in a sense "easier" than other less impressive sciences. It's easier to study the interaction of e.g. a hydrogen atom with a photon, than it is to study big messy complicated things made of >septillions of atoms, like organisms and species and societies.
Specific hypotheses within evolutionary biology can be falsifiable (and often are falsified or corroborated), and there are even some areas that do seem to have generalizations that lead to law-like predictions. E.g. sex ratio theory, and more generally sex allocation theory, is pretty successful. It shows how and why 1:1 sex ratios are so common (it's the selective equilibrium given that everyone has one mother and one father, plus some other assumptions), and makes predictions for when deviations from 1:1 can evolve (e.g. when local mate competition means males compete with their brothers for mates). For a lecture on sex allocation theory, from Stephen Stearns' Yale course on evolution, ecology, and behaviour, see https://www.youtube.com/watch?v=buOWEw9AhNE. For more on theory of virulence evolution, see my other comment: https://www.astralcodexten.com/p/h5n1-much-more-than-you-wanted-to/comment/84002911.
Evolution itself isn't unfalsifiable. E.g. DNA-based molecular phylogenies agree with earlier phenotype-based phylogenetic trees, and with our intuition, that chimpanzees are more closely related to humans than elephants or dogs or crocodiles or turnips are. If evolution was false that could have turned out not been the case; it could have been that molecular phylogenies put humans as being most similar to turnips, but it didn't.
Thank you for your kind response! I have to admit that there are several predictions that can be made in the field, regardless of the field as a whole. Regarding evolution, so the main prediction is that the closer the molecular phylogenetic, the more similar they will always be? Is there a jargon or tag where I can read (specifically) about that?
Idk if it's "the main" one, but it's an example. (There are also nuances I didn't get into. E.g. it's better to compare non-functional regions, since a functional region could have similarities due to convergent evolution; e.g. dolphins and bats had similar mutations to evolve echolocation, and if you only looked at that region then you might think they're closer cousins than they are. Or incomplete lineage sorting, followed by loss of some alleles, resulted in some regions in us looking closer to gorillas than to chimpanzees. In general published phylogenies are all estimates. But in broad strokes, yes the data is what we expected, and agrees that humans are closer to chimpanzees or gorillas than to crocodiles or turnips.)
Some stuff you could check out are Richard Dawkins' 1986 "The Blind Watchmaker" (including ch10, "The one true tree of life") or his 2009 "The Greatest Show on Earth" (including ch10, "The tree of cousinship"). The former is the best single-book lay introduction to evolution; the latter is more specifically framed as giving the evidence for evolution.
An accessible intro textbook on molecular phylogenetics is Lindell Bromham's 2008 "Reading the Story in DNA" (or its 2016 revised version, "An Introduction to Molecular Evolution and Phylogenetics"). That might be your best bet if you specifially want to learn about this molecular evolution stuff. A more advanced book is Ziheng Yang's 2006 "Computational Molecular Evolution." A review paper is (Yang and Rannala, 2016, https://doi.org/10.1038/nrg3186). Also fun is Dawkins' 2004 "The Ancestor's Tale" (including the section "The gibbon's tale").
As an evolutionary biology PhD student, I very much agree with the recommendation of "The Greatest Show on Earth".
There's also TalkOrigins' list of predictions of evolution (https://www.talkorigins.org/faqs/comdesc/), which is not entirely up to date and somewhat polemic (being a relic of the great Creationism Wars of bygone times) but is still a pretty good overview.
(Not a biologist but I read a bit about it.) More falsifiable predictions come from evolution of microorganisms and can be verified experimentally. Take some bacteria like E. coli, feed them something they can survive on but aren't particularly adapted to eating. Wait for them to spread, take a sample, put it into the next Petri dish. Repeat. Prediction: after a thousand repetitions, the bacteria will be significantly better adapted to consuming the food they were given.
But is there any precise definition on "survive on but aren't particularly adapted to eating" and "significantly better adapted to consuming the food they were given" that can be declared upon to make a prediction model on how many generations (with normal distribution?) are needed to reach it? I guess it might be something like how many calories could they acquire from that particular food, before and after.
Normally I'd expect the reproduction rate to be a good metric. But since they might get smaller or simpler on account of having simpler environment, biomass/acquired calories probably should be taken into account.
Great write up, especially for the base rate discussion.
I want to add that even accepting these numbers, it is a good idea to have Oseltamivir powder in dry storage at home for if you or any of your kids get any flu. If fear of H5N1 is the juice you need to get on flu precautions (besides the shot) then capitalize now!
And if you are a young lazy guy like me who fears the flu shot but not an oral antiviral, all the more reason!
> Influenza A has two surface antigen proteins, hemagglutinin (18 flavors) and neuraminidase (11 flavors). A particular flu strain is named after which flavors of these two proteins it has - for example, H3N2, or H5N1.
Naively this suggests there should be 18*11=198 different flavors of influenza.
Out of curiosity I looked up some of them (eg H3N7, H3N9, etc), and... most of them don't exist. Going off a quick Wikipedia search, it looks like only 18 of them do. That said, I strongly suggest that people should NOT try to make the other 180 flavors.
I've read that there's something of a balance between the hemagglutinin (HA) and neuraminidase (NA) proteins. The HA facilitates viral entry into the cell, whereas NA allows newly formed virions to detach from the cell upon exit. So their activity needs to be well matched or else the virus will just fail to reproduce effectively. This implies to me that not all types are actually possible. Also there could be new forms of HA or NA that haven't been seen before, so I wouldn't say 198 different types is a hard upper bound.
Duncan Purvis here, thanks for the namecheck Scott! And thanks again for your grant last year. Feel free to contact me if you want another source of help and clarification for future articles, you have my e-mail.
In terms of pre-pandemic preparation, I'd refer anyone to a JAMA viewpoint article from September: https://jamanetwork.com/journals/jama/fullarticle/2823004 . It's a good shopping list of recommendations for the USA in particular.
Influenza has to constantly spread to survive. Cross-immunity is the most likely explanation for the elimination of Influenza A subtypes in the past, e.g. 1968 H3N2 1968 eliminated 1957 H2N2, which had eliminated 1918 H1N1 in turn.
The elimination of Influenza B Yamagata during COVID is likely to have been due to COVID-19 lockdowns in Q2 2020 further reducing its transmission, on the background of Yamagata having an increasingly difficult time vs B Victoria pre-2020, and being in an evolutionary dead-end (fragile). So Yamagate eradication wasn't primarily cross-immunity from COVID
> But the exact mortality pattern was surprising; people between 18 and 28 were especially likely to die, and people older than 88 especially likely to survive. Why? Because an H1N1 flu went pandemic in 1830; anyone who first encountered the flu around then had an immune system synced to H1N1.
Do you put no stock into malnutrition low cleanliness in the trenches and ... questionable medical care (*cough* lethal doses of the hot new drug asprain)?
In terms of the base rate being 5%, and this year of highly elevated risk being 5%, I think there are two partial explanations.
One is what you mention, that there’s some base rate of unpredictable flu pandemics per year.
The other is that out of the predictable ones, likely most years if we try to do a prediction, it’s 0.01% chance of a predictable pandemic. Probably in the immediate vicinity of a predictable pandemic, you might predict a 30% chance per year. But 5% is actually going to only come in relatively few moderately elevated years, even if that’s also the long run average risk. Most years are much lower.
I read a book a while back that attributed the weirdly high death rate among young fit people in the Spanish flue pandemic to cytokine storm. Basically, they have stronger immune systems that can attack the virus more thoroughly and the ensuing battle ends up accidentally killing them.
But there's also an explanation offered here that old people survived largely because they had remaining antibodies from a similar historical pandemic.
Are these ideas in conflict or do they both make sense at once?
I am definitely not any sort of expert on the subject, but on a broader conceptual level "targeted response, following an old precedent" sounds like it would lead to quite a bit less accidental damage than "strong response, but inefficient due to confusion / surprise."
Why is there so much discussion of raw fatality rates instead of “QALYs lost”? If the disease is like Covid and only kills those who were about to die anyway, it’s a lot less big of a deal than the 1918 flu that killed young people at alarming numbers.
It’s like we haven’t learned anything from Covid and keep on pounding the drum of “fatality rates!” when that alone is a meaningless number and you instead want “fatality rates by age bracket” to make any decisions.
A market on “fatality rates for people under 60 with a BMI of 18-25 and no major health conditions” would be *far* more interesting.
"maybe we should just shut them [mink farms] down"
Maybe we should instead be more concerned about keeping the minks healthy? Are the mink farms geared exclusively to raising them, like chickens? My understanding is that an ecosystem interacts with itself, such that, for example, illnesses that minks contract are prevented by other organisms that can coexist with minks. Crop rotation helps prevent diseases in your crops, since if your corn field gets an anti-corn pathogen then the next season it doesn't affect corn, but can only try, futilely, to infect the wheat you plant next.
I'm surprised mink farming is only a $80 million a year.
The biologists Scott talked to should be sent back to school for saying "1918 flu forgot to read the Evolutionary Virology textbook and actually mutated to get worse" (in probably less funny words). The Red Queen of Evolution rulez - and if you do not see how, you need to look harder. The common theory is that WWI itself created a new environment: Many young men stuck close together in the trenches without an option to isolate as in "go home for having a cold". And the worst cases then put together in large field hospitals with lots of other young men with all kind of serious conditions with over-worked medical staff "caring" for all. A virus virulent enough to get you there got favored by the Queen.
So called “Spanish Flu” is probably a suboptimal model for how things will work.
1. Spain was not directly involved in WWI. Other countries had propaganda reasons for not reporting accurately—they being involved in WWI, so only Spain was reporting close to accurate statistics, iirc.
2. Many of the “young and healthy” victims of Spanish Flu were living in trenches in appalling sanitary and unimaginably stressful circumstances, foxholes in a combat zone.
That makes me suspicious of any discussion involving “Spanish Flu” that make no mention of these possible con founders.
I also wonder how often mild infections aren’t identified beyond, “I’ve a cold,” outside of professions with mandatory testing—I don’t bother with medical attention when I can do all my work from my computer any time I have a fever—I’m certain many other professionals who aren’t customer facing. Contrast with my friends in Education who “have COVID” with symptoms that would otherwise barely inconvenience them..
If your infection is severe enough to require powerful drugs, it being “Just a Rhinovirus” isn’t much consolation.
The 5% annual H5N1 pandemic risk estimate is a reasonable conclusion. But I feel less optimistic about the fatality rate. A pandemic influenza virus needs to infect the upper airways to spread efficiently and the neuropathogenic and virulent characteristics would distinguish H5N1 from other influenza viruses. Essentially this virus tends to spread from the nose to the brain.
While H5N1 has evolved significantly, it is important to remember that the 1997 Hong Kong outbreak is the initial reason for concern, and the pandemic potential was obvious.
I want to point out that researchers have of course tried to find more mild cases and despite all uncertainties the historically high CFR is not just a statistical artifact due to a lack of surveillance:
The cow genotype B3.13 has significantly changed the public risk perception, but in my personal opinion this is just one issue of many. The drastic reactions of the prediction markets make me question the expertise of the participants. If reassortment is such a concern, why not H5Nx instead of H5N1 and why specifically clade 2.3.4.4b?
There is totally inadequate surveillance of pigs, cats, and rodents. Millions of birds are spreading the virus worldwide, fur farms remain a risk, poultry workers continue to get infected. There is sustained mammal-to-mammal transmission in pinnipeds with potentially dangerous outcomes, see the 2014 outbreak of H10N7 in seals.
There have been various other estimates and in conclusion I believe that the unprecedented nature of the panzootic significantly reduces the relevance of comparisons with previous events.
In the 2022 British National Risk Register the chance of any pandemic happening in the next 5 years is estimated to be in the 5-25% range:
One statistical approach results in a 3% annual chance of a "mild" pandemic as in 2009, 1% for a pandemic of "medium" severity and only a 0.02% chance of a pandemic as severe as the 1918 pandemic:
One estimate from 2019 of the probability of an H5N1 pandemic resulted in 5% in 10 years, based on occasional bird-to-human transmissions, just before the emergence of H5N1 clade 2.3.4.4b with frequent infections of mammals:
In this case, I think the biggest problem with it is the title. There really isn't much in it that I didn't want to know. It's facts backed up with sources and links.
"the last pandemic as bad as Spanish flu was smallpox hitting the Indians circa 1500"
I assume you mean the indigenous inhabitants of the Western Hemisphere (WHII), not South Asians.
I am not an advocate of politically correct nomenclature. My favorite baseball team is the Cleveland Indians. But, without more the term "Indians" may be ambiguous.
On that subject. WHII, may have suffered from more than one pandemic at a time. They were immunologically naive to a whole raft of Eurasian and African diseases. Further it may be impossible to retroactively diagnose the difference between measles and small pox.
Astral Codex Ten | Scott Alexander. As the avian H5N1 flu spreads from bird flocks to herds of cattle—and isolated human cases—a doctor breaks down the origins of flu and the likelihood of this one to turn into a pandemic (he estimates 5%). (Read)"
To be informed on “how” add function research by Fauci et al, Listen to Tucker Carlson’s interview with a vaccine lawyer. It is not anti-vac but a safeguard against some of the poorly designed research studies that have been utilized to approve some brands of vaccines
Plus it reveals that the process that viruses cross into humans is always “natural”
Covid 19 or “Fauci’s virus” to give credit to its development was from added function research in Wuhnan lab ….
The public is very aware now and absolutely no longer trusts FDA, CDC, NIH or others so called public health agencies due to huge deception and censorship related to vaccines, masking, social distancing or effective treatments
Exercise, lose weight, eat healthy as obesity and diabetes and its subsequent commodities were highest risk factors from dying from covid …all “modifiable”
An epidemiologist -- a professor at Yale's Public Health School and an advisor to among others the CDC -- offers some updates this afternoon about H5N1:
"A Louisiana resident is in the hospital after contracting H5N1 from their backyard flock. This case had the same H5N1 strain as a teenager in Canada who was fighting for their life last month. (A recent NEJM case study described how severely sick this teenager was: intubation for 3 weeks, temporary support to the heart and lungs called ECMO, plasma exchange, 3 antiviral medications, and more.) The H5N1 strain involved in both severe cases—called D1.1—is found among birds and differs from the strain circulating among cows (B3.13)....
....Birds that gather at feeders (like cardinals, sparrows, and bluebirds) do not typically carry H5N1. The USDA does not recommend removing backyard bird feeders for H5N1 prevention unless you also care for poultry. The less contact between wild birds and poultry (by removing sources of food, water, and shelter), the better."
Just want to say that this was an exceptionally clear and well-written post. It was judicious about presenting relevant moving parts and their relationships, at the right level of abstraction, in a straightforward style, with an accurately modeled lay audience in mind. I also appreciate the detail with which you explained each step in reaching your probability estimates. I wish more forecasters were so thorough. I love the "Much More Than You Wanted To Know" series, and this was a top example, probably in the top 3% of SSC/ACX posts of all time.
>the 1918 flu forgot to read the Evolutionary Virology textbook and actually mutated to get worse.
The explanation I've heard for this is that this apparent reversal was caused by the unusual circumstances of WW1. The pandemic initially incubated among servicemen in Europe. Army hospitals were a better place to spread than the front lines. The more virulent cases caused soldiers to be sent to the hospital, so that selected for more virulence.
IANA virologist so I don't know how accurate this is, but it seems plausible to me.
You might have covered this in the article (way too long for my attention span right now), but how are those H and N proteins detected, and how do they know that they come from a virus that is "discovered" by extracting RNA or DNA from an unpurified sample? Are those virus genomes or samples evr tested on living animals to confirm that they are the cause of the symptoms we call "flu"?
You have left out a very important set of facts about H5N1: it's an H5.
The influenza virus is structured as 8 genes: H#, N#, and the other six. The other six are wrapped in a bundle in the center, and H# and N# are on the outside. The other six are heavily conserved, while H# and N# change incessantly.
To infect a mammal, the H1, H2, H3, and H4 genes require an enzyme. The enzyme exists in small amounts all over the body, but is very common in the upper respiratory tract. A mammalian flu infection consists of massive viral load in the upper respiratory tract and small amounts of activity in the rest of the body.
Until H5N1 appeared.
The H# variants H5 through H9 DO NOT NEED this enzyme. You can get a massive infection anywhere, and it will quickly become massive all over the body. This is why the H5N1 variants have caused death rates above 50% in mammals in small infection clusters. I think an early one was 80% of the tigers in a 500-unit tiger farm in Southeast Asia.
This difference in virulence is why the public health folks have been shitting bricks over H5N1 for 20 years: it hitteth like a rock.
This is all memory-dumped from when I was following H5N1 20 years ago. No cites, sorry.
That can be cleaved by furin, in a wider variety of tissues, causing a systemic infection.
I'd also be inclined to think that H5N1 is almost guaranteed to have a higher fatality rate than other flu strains, for that reason. I might also expect wide ranging consequences similar to long covid, from that multi-organ infection.
But a few things still give me pause in saying that with certainty. I suppose we don't know exactly which H5N1 strain would spill over into people, or if it changes in that process. Also, many sources are saying that the fatality rate is only 2% in cows, suggesting maybe it wouldn't be extremely bad in humans. I haven't looked carefully enough to say if that's IFR or CFR or a fraction of the total herd size.
Great summary of threats caused by zoonotic diseases. And here's some small factoids from the Nordic Countries which might be of interest:
"The Finnish Institute for Health and Welfare (THL) in November stated that fur farming in its current form constitutes a constant pandemic risk.
THL reminded that H5N1, a highly pathogenic variant of the avian influenza, caused infections at dozens of fur farms in Finland in 2023. The infections prompted health authorities to order the farms to cull tens of thousands of foxes, minks and other animals that could function as an intermediary host, allowing the virus to mutate into a strain that can transmit to humans."
Also, vaccination against the strain H5N8 is now offered to people in the risk.
"Pale Rider: The Spanish Flu of 1918 and How It Changed the World" if interested how severe the impact of the Spanish flu had in several communities (=a lot).
Nice read. Thank you for the history. I went vegan when I learned about zoonotic diseases when covid hit. I do not want to be apart of the next pandemic. I suggest others do the same!
This isn't a "Much More Than You Wanted To Know" post. This is a Wikipedia-level summary of the different flu types and then some Bayesian hand-waving. Oh how I miss the long, exhaustively researched "Much More Than You Wanted To Know" posts of old.
So where can I buy oseltamivir w/out a prescription?
Following
May well be outdated; but https://www.theindependentpharmacy.co.uk/cold-and-flu/tamiflu in the UK claims to send wo prescription if you do an online-self-diagnosis.
In Mexico, Freddys farmacia is recommended for all stuff wo prescription incl. tamiflu aka Oseltamivir in Puerto Vallarte https://www.tripadvisor.com/ShowTopic-g150793-i46-k10048642-o10-Freddy_s_farmacia-Puerto_Vallarta.html.
Oh, and ACX links to https://henryaj.substack.com/p/lifehacks who claims: "in most places you're just allowed to buy and import prescription medication and take it" linking to
https://www.unitedpharmacies-uk.md/ May be even useful if one wants to save on viagra:
https://www.unitedpharmacies-uk.md/erectile-dysfunction.html?&name-price=Lowest
Have a happy 2025!
Neat!
UK website looks to still be good. [Edit, but both only ship to the UK, dang. What's the international version, used to be dodgy Indian websites...]
I have been unable to find any source for the powder for suspension you'd need to properly make up the smaller doses for children, if anyone else finds it that'd be helpful.
Are your figures in addition to, or instead of, mortality from a normal flu season? It seems a solid chunk of your found expected h5n1 deaths would be expected to die from normal flu anyway, wouldn't h5n1 replace the normal flu? At the very least, anti pandemic measure would limit normal flu spread similar to anti covid.
https://www.cdc.gov/flu-burden/php/about/index.html#:~:text=While%20the%20burden%20of%20flu,the%20United%20States%20each%20year.&text=CDC%20estimates%20that%20flu%20has,annually%20between%202010%20and%202023.
Presumably, the anti-pandemic measures would be calibrated to the expected level of danger. An h5n1 pandemic that's closer to the 2009 pig flu outbreak would probably get a pretty tepid response, while something like the 1919 pandemic or worse would get the full Covid treatment.
If an outbreak happens that is seen as bad enough to justify lockdowns, I would expect them to be extremely effective to the extent they're complied with. The Covid response was initially modelled on planned responses for a particularly severe pandemic flu, and they work better on influenza than on covid due to stuff like droplets vs aerosols. "To the extent they're complied with" is the hard part, since everyone is still tired from last time.
Honestly, are governments going to even bother this time, considering the response to the previous lockdowns? People are just going to do whatever the hell they want. And ultimately, a few dozen million deaths isn't a big deal when it's spread out across the globe.
And of course the pandemic will then be worse, and so people will ask for stronger measures the next time. Weak men create hard times, etc.
A lot of the effective changes around Covid, at least in the UK, were voluntary and often started among the population before the government changed the advice or issued legal restrictions. The population (and the police…) often went beyond what the government had actually required, because they were worried and trying to protect themselves and others.
Of course, we also know that the UK government and scientific advisors were surprised by the high compliance of the population, making the lockdowns much more effective than expected: they had issued stricter advice than they thought was needed, and emphasised the dire consequences of not following it, because they assumed people would skirt around the rules much more than they did.
The things that needed national government support/central decisions that made a big difference to the spread (rather than the treatment) were the closing of schools (made a huge difference to spread in the UK each time) and the easy, free availability of relatively-reliable testing.
Possibly also the chunks of money paid out for businesses furloughing people, paying them to not work, but I can’t see that happening again.
The closing of schools was disasterous in many ways (rendered more disasterous by the choice to close playgrounds and keep them closed, and the slow introduction of things like ‘bubbles’), but also attendance in schools dropped noticeably before each closure, and every time Covid became more prevalent, and not just because students were actually ill. I also had students I did not see for a long time, because they or family members were immune-compromised. Probably a future pandemic needs something more flexible in place around schooling.
The UK testing system was fantastically expensive (for the taxpayer), but popular and widely-used. It gave people a way to manage risk when things were very uncertain, helped monitor what was going on in terms of spread and mutations, and could justify people taking the necessary time off from work in a legally and socially powerful way while they were contagious. I can see a similar system being used again in future pandemics.
...Maybe I am being too cynical. Still, the political situation in the US is a whole different can of worms. The administration has its own supporters to appeal to, and they absolutely do not want lockdowns again. So that's that.
I agree that the US is in a funny place around this: everything around Covid got fantastically split on political lines, didn’t it? I don’t pretend to know how Americans, or the US government, would react to a serious influenza pandemic.
But I think it is still worth bearing in mind that when people think they are in danger, they tend to move to protect themselves with or without government support. Lockdowns were dreadful and I hope never to see them again, but you probably need some sort of government response if the population starts withdrawing from and getting scared of each other.
I suspect if people started to see non-elderly non-otherwise-sick people dying around them, ESPECIALLY children, they'd comply more readily. I might be biased because I don't know anyone who died of covid but I know two people (both young adults and otherwise healthy) who died of flu related sepsis, but still.
I've never known anyone who died of Covid or the flu. But I did know two formerly healthy people, one a relative, who have died in recent years of antibiotic-resistant bacterial infections. And that could well be the wave of the future.
I'd love to believe this, and I probably even used to. Sandy Hook changed that. Half of (at least the American) population doesn't give two shits about dead children.
I don't mean to undermine the emotions here, but do you literally believe that? Like do you think that if you picked a random American and told them that a child had died, there would be a greater than 50% chance they would go, "I don't care about that at all?"
I think you actually mean something more like "Half of Americans don't support measures that would save children at a cost which (I believe) is negligible." And that might be true! But I doubt your model of the world actually matches what you said.
The "half" may be an exaggeration, but it doesn't change my intent. If you're looking for a more "accurate" sentence, I'd say something like "A significant percentage of the American population is okay with child deaths so long as they aren't inconvenienced in any way that impacts them directly." (Masking, vaccines, sensible gun laws, seat belts, speed limits in school zones, etc etc etc.)
A significant portion of America's population is so selfish, they've proven that they truly don't care ENOUGH about child deaths to be inconvenienced.
Summarized and exaggerated: "Half of (at least the American) population doesn't give two shits about dead children."
Ah, ok - that's clarifying, thank you. I personally think most of that percentage thinks the "inconvenience" is too great for the safety increase. Which, I mean, we all take actions that risk our lives and those of others (e.g. driving a car). Your examples reflect that as well - you say "speed limits in school zones" not "speed limits everywhere" presumably because you recognize that there would be a greater cost to a universal 35 mph speed limit, even though it would also save lives.
All of this is just to say: I think the people you are talking about mostly disagree with you about the efficacy or cost of the measures you have in mind, not whether children's lives are valuable. I find that to be a helpful perspective, because it suggests they could be convinced, or that some other measure might be something everyone could agree on.
Is there actually a droplet vs aerosol distinction for covid vs flu? My understanding is that Lindsey Marr was talking about aerosols for flu as early as 2015, and it took Covid for the mainstream health establishment to realize this can be relevant for this sort of virus. I don’t know how much they’ve changed their opinions on flu.
My info for might be outdated.on that particular point. Although flu spreading at all readily by aerosols seems unlikely to me, based on the differences in R0: the numbers I've seen for flu range from 1.2 (normal seasonal flu) to 3.0 (high estimate for the 1918-1920 pandemic), while I've seen newer covid variants estimated at 5.7. Even discounting for the 1.2 figure for seasonal.flu probably not being a true R0 due to cross-immunity with prior years' strains, that's a pretty big gap that gives me a significant prior for there being substantial differences in mode of transmission.
I have seen some much lower estimates for covid's R0, in the pandemic flu range, but they're either analysing the original outbreaks and thus had extremely wide confidence intervals for want of good data, or they're using data from 2020-2021 and thus measuring covid's R0 under lockdown conditions, not its R0 under normal conditions.
It could well be that the lower R0 is just related to different intrinsic ability to penetrate cells, or easier immune response, even if the aerosol aspect is the same. The issue Linsey Marr focused on is that for decades, aerosol transmission was treated as a weird abnormality a few infections had because of a few early 20th century misprints, rather than because of any evidence that it wasn’t common. This is the 2015 article that suggested to me that there is more to this debate than just covid:
https://www.popsci.com/take-deep-breath/
Can someone explain for me how/why strain replacement happens? Why doesn't each new strain that crosses over simply increase the overall rate of flu? Do the strains crowd each other out somehow?
I also wondered this and asked Claude about it:
The existing strains typically fade out because of population immunity dynamics, which create a hostile environment for them to continue spreading. Here's why:
After a strain has circulated widely, most of the population develops specific antibodies against it. This means:
1. The old strain has fewer susceptible hosts to infect
2. When it does infect someone, their existing partial immunity often leads to milder illness and reduced transmission
3. People are more likely to have some cross-protection against that strain in future seasons
Meanwhile, the new replacement strain has advantages:
- It can infect people who are immune to the old strain
- It spreads more efficiently through the population
- It may cause more severe symptoms due to lack of pre-existing immunity
This creates a competitive situation where:
- The old strain struggles to find new hosts
- The new strain rapidly spreads through the susceptible population
- Resources (susceptible hosts) become increasingly limited for the old strain
Think of it like market competition - once a new, more successful competitor arrives, the old business (strain) has trouble maintaining its customer base (susceptible hosts) and eventually can't sustain itself.
However, it's worth noting that old strains don't always completely disappear - sometimes they can persist at low levels or in specific geographical regions, potentially re-emerging if conditions become favorable again.
> Think of it like market competition - once a new, more successful competitor arrives, the old business (strain) has trouble maintaining its customer base (susceptible hosts) and eventually can't sustain itself.
This feels a little off. How does the new strain interfere with the old strain? The old strain naturally declines by two methods; the hosts become more resistant to it (real decline) and more resistant to its symptoms (apparent, but false, decline). Neither of those relies on the existence of a newer strain.
(All humans carry a significant number of completely asymptomatic diseases, which is why islanders get sick when they're visited by ships.)
You’re right, it doesn’t come out and say why there are fewer susceptible hosts for the old strain.
I assume for two reasons: Mortality and NPIs (spontaneous and mandated).
And one more: Non-specific antiviral responses such that infections from the new strain induce a temporary shield against the older strain thereby further isolating it.
This herd immunity (and/or mortality) and NPIs have been the accepted explanations for strain replacement. With COVID these explanations don't really fly. Of course, it's hard to compare NPI implementations from country to country, but with a highly contagious pathogen like COVID, even the strictest NPIs couldn't stop its spread once newer, more transmissible variants evolved (see China's attempt at ZeroCOVID).
We've seen...
1. A new variant can push out all the previous variants and become the dominant variant but not create a new wave — i.e., it takes up a bigger piece of a smaller pie. Examples of this are Alpha in the US and Kraken worldwide. In fact, in the US, Kraken may have prematurely ended the BQ.1 wave because (counterintuitively) US COVID cases dropped precipitously as Kraken became the dominant variant.
2. In two countries with a similar variant mix, a new variant can create a wave of new cases in one country but not another. Examples: Lamda and Gamma in South America (although they were roughly contiguous in time, so they may have possibly been burning each other's fuel). XEC seems to be starting a new wave in the US, but it didn't create a wave in Australia.
3. And then we have examples like Omicron that pushed every other variant aside and created new waves everywhere.
Other weirdness that's worth noting...
4. Even though regions may have similar variant mixes, some regions seem to experience two COVID waves each year (US and Australia), and some have three or four waves each year (France, Germany).
5. Possible examples of viral interference: There seems to be some sort of inverse relationship between SARS2 waves and Rhinovirus waves. RhVs peak when COVID is low. COVID peaks when RhVs are low. Influenza cases in the US (and worldwide) dropped precipitously to virtually zero just as COVID cases started ramping up. NPIs have been put forward as the post hoc explanation for the phenomenon, but this dropoff happened before NPIs were mandated. And except for a long, slow burn of Type B cases in China during their ZeroCOVID lockdown, flu stopped circulating until the advent of Omicron. Then it came back with a vengeance.
Ask it!
We did chat a bit more about it. That’s where the “non-specific antiviral response” part came out of.
Makes the carrier confine to home for the duration of illness and avoid seeing strangers? Drives up the fever making the body more hostile to pathogens in general?
Yeah this doesn’t explain why the old virus can’t just coexist alongside the new virus in the same individuals
Any single individual only has so many of the relevant type of cells to infect, whichever amino acids the viral particles are built from, etc.
"more resistant to its symptoms(apparent, but false, decline)"
some symptoms are among the best ways for diseases to spread, or if (e.g.) a host is less likely to sneeze or cough while having an illness, they're also less likely to spread it, even conditioning upon the same viral load.
"Neither of those relies on the existence of a newer strain."
If two strains of an illness are very similar, there is substantial cross-immunity.
Wild ass guess: most flu strains give cross immunity. The new strain has to have the unusual ability to infect people with immunity to the old strain, or it wouldn't be epidemic. The old strain has no such filtering.
I think this more or less has to be it. It makes sense of the replacement process of Covid strains - the faster spreading strains are providing those who catch them with sufficient immunity against slower spreading strains to eventually reduce the R of the slower spreading strains below 1.
Flu viruses are more immunologically distinct than Covid strains (I'm pretty sure) but it would make sense that the same process could occur with those (although it seems that it also doesn't have to, given the coexistence of multiple endemic strains).
Well, I think it all works out as long as the cross immunity is only partial.
Re: When it does infect someone, their existing partial immunity often leads to milder illness and reduced transmission
If the illness is mild shouldn't it be able to spread more easily insofar as its hosts aren't going to stay home and semi-isolate?
That puzzles me, too. My guess would be that at least part of the answer is behavioral and public health responses: stuff like staying home when sick, avoiding large gatherings, hand washing, etc should "tax" the transmission rate of all flu strains roughly evenly. Seasonal flu has an R value of about 1.2 at the start of the flu season, while pandemic flu usually have R0 of 2-3. If the pandemic response, whether organic or mandated, reduces the rate of spread of all influenza by about a third, then the pandemic flu is still spreading but the established season flu strains are slowly dying out (effective R value of 0.9).
Influenza has a pretty short generation time, about three days according to a preprint paper that came up on Google (Chan et al, 2024, Estimating the generation time for influenza transmission using household data in the United States), so effective R doesn't need to be much below 1 for very long for a given strain to almost disappear. Maybe six months for a 99.9% reduction using my guestimated R of 0.9.
I also find this confusing and I would note that it also happened during COVID, despite different variants giving imperfect protection against each other. In the UK, Alpha, Delta and Omicron each totally replaced the previously predominant strain, which never returned.
likely same as with covid - there's generally some cross-immunity and newer successful strains can outcompete older strains while leaving behind new cross-immunity. It's one of the reasons original covid strains are basically extinct at this point, new strains are very different, and humans are handling infections better even without any treatment.
There's some evolution in both directions.
Mostly it's the virus adapting, because their generation times are so short.
But you have a minor effect from the humans most vulnerable to covid-style viruses not surviving.
I think it's likely because of https://en.wikipedia.org/wiki/Original_antigenic_sin
Asking Claude about it:
When a new influenza strain emerges, infection with this strain indeed triggers an immune response not only against its own antigens but also against previously encountered strains, due to original antigenic sin. This cross-reactive immune response effectively suppresses both the new and old strains simultaneously, making it difficult for the old strains to maintain their presence in the population.
This mechanism is particularly important because, as you correctly note, simple competition for susceptible hosts isn't a sufficient explanation given that viral coinfections are possible. The immunological interference created by original antigenic sin provides a more complete explanation for strain succession. When people encounter new strains, their immune systems mount responses that inadvertently provide protection against older strains, even if those older strains weren't directly encountered in that infection.
This creates a powerful selective pressure favoring novel variants that can escape existing immunity while simultaneously suppressing older variants through cross-reactive immune responses.
Can someone explain why we need to cull animals that get the bird flu, instead of just letting them recover? The economic consequences (eggs are over $10 a dozen at my local grocery store) are very severe and at some point is it protecting us from spread anymore or just causing unwarranted supply chain issues?
Culling is to prevent further spread, reduce risk of mutations, and protect farm workers.
And who says they recover? Bird mortality can be very high - approaching 100% within 3-4 days post-infection (dpi)
https://www.mdpi.com/1999-4915/15/9/1909
Whoa, where is that grocery store?? I live in a large city where the cost of living is generally well above the US mean, and eggs here are $3.50/dozen. I just yesterday bought cage-free/no-antibiotics/hand-fed-by-virgins eggs (that last being my wife's description) for $6/dozen.
SF Bay Area. I will admit that I didn’t price shop, I went to go buy eggs at my local non-Whole Foods grocery store and the cheapest I could find was $10 and upwards of $15 and limit of 2. Only a month ago I got it for $5 a dozen and I was told bird flu was the cause of the inflation.
I'm also in Bay area and buy eggs for $4-5/dozen at Berkeley bowl
I'm in central Chicago, and didn't do any price shopping. Just did groceries at the nearest grocery store and that's what they had eggs for.
I’m on the Peninsula and see stores with prices of $10-15 (typically these are free-range or cage-free, but they don’t have anything more factory-produced), and stores that simply have no eggs at all. (And no, I’m not talking about hardware stores.)
In the current situation, those "free-range" chicks may well be stuck inside a building, too, to avoid further infections by wild birds. At least, that is how situations are handled in Germany: The "free-range" farmers wait for the admin to call out an "emergency", then (and only then) they put them inside and can still sell those eggs as "free-range". (If the farmers were more pro-active, they would lose that label, so they are contra-active.) - One more reason not to buy free-range ever - good luck to find "caged" anywhere nowadays!
Seconding Paul Botts’ question, where is this store; are the eggs gold-plated? That’s like 3x the price in my local store.
The general strategy thus far for dealing with avian flu is to try to completely stamp it out and prevent spread, which means acting fast to cull all possibly infected birds. It should be noted that in some strains of avian influenza (like the currently circulating H5N1), they're likely to kill the entire flock within 48 hours or so anyway, so it's not just culling of poultry that leads to high egg prices (this is why some strains are labeled "HPAI" or highly pathogenic avian influenza; they're highly pathogenic in poultry).
That's gonna be challenging with the large migratory bird species that are being found dead along the Mississippi flyway. Snow geese and mute swans migrate thousands of miles and the US Midwest is in the middle of their routes.
I think a good argument can be made that the "stamping out" policy has failed as of 2024, yes. What matters now is if that argument is made within the public health bubble and gains enough support for changes to be made.
This is the agricultural bubble that is running things. I don’t think public health people have much power on agriculture, but agriculture people have all sorts of rules about preventing losses to their companies. (Including strict cull requirements to try to prevent virus spread, but implemented by corporate farmers who are just following rules rather than thinking about viral dynamics.)
I think you're correct, I should've said "ag bubble," that's more accurate.
Re: eggs are over $10 a dozen at my local grocery store
Wow-- where do you live and what grocery store do you shop at? Egg prices are definitely high here in Florida but not that high, not even at Whole Foods. (I assume we're talking about a dozen eggs?)
The response below addresses the incentive to cull birds rather than the need to cull them:
The government reimburses farmers for the loss of birds due to culling to prevent bird flu. According to the Department of Agriculture, farms that report outbreaks of bird flu quickly are eligible for compensation for the birds that are killed through culling. This program aims to encourage rapid reporting of outbreaks to control the spread of the virus. However, the government does NOT compensate for birds that die from the disease itself.
If you are a farmer who wants to stay in business/is risk adverse, what do you do if one birds tests positive?
It appears to me that increases in food prices and the downstream effects do NOT factor into the decision to cull birds.
I wonder if the resilience of farm workers is cos they have a long history of exposure, maybe even to lots of different minor variants, so their immune systems are already primed.
While we're on the subject: I have guy who delivers eggs. The other day I caught him cleaning blood off the eggs with a licked finger. I tried to impress on him that this probably wasn't wise. (We're in southern England, so I think we're mostly OK ATM)
Or then humans in good health, kept warm and well fed die very rarely from any flu, so that older strains were not any deadlier, but humans lived in poorer conditions and were therefore more suspectible.
People have always started dying from various infections when food starts running out.
I would think farm workers are almost all of "working age"; for many diseases, the most vulnerable are the very young and the very old, who are too young or too old to be doing much farm work. Farm children contribute to the farm work, but my impression from my farming cousins is that farm kids today mostly go to school and whatnot just like non-farm kids, and don't do much actual farm labor until they are teenagers who are old enough to no longer be unusually vulnerable to diseases.
My information on modern farming practices comes from my pig-farming cousins in Iowa, so it's possible my knowledge does not generalize across all American farms.
Certainly not the case in the UK: average age of farmers here is 58. Many are working past retirement age (40% of farm holders are over the age of 65). Average age of farm workers is about 40.
If they are working past retirement age, they probably are less frail than the average person at that age?
Maybe. But they may just be occupying the land, not actually working.
There have certainly been cases where they were still working, still physically able, but no longer mentally able and not aware of it.
Not sure if its any different in the south but in a suburb in the outskirts of Newcastle I get regular letters from DEFRA asking me to declare any bird populations and monitor them for flu due to being a "high risk area"
The various zones come and go. You don't seem to be in one now. Map here:
https://defra.maps.arcgis.com/apps/webappviewer/index.html?id=8cb1883eda5547c6b91b5d5e6aeba90d
>If reassortment is sort of like viral sex, pigs are sort of like Tinder.
And ACX is off to a hilarious start in 2025!
Now I'm imagining what H5N1's Tinder profile would be. "Baby I've got a fever... Wanna come back to my place and swap glycoproteins?"
Let's just hope the profile pic looks bad and nobody swipes right.
>Epidemiologists hate raw milk, think there is never any reason to drink it, and will announce that risks > benefits if the risk is greater than zero. I don’t know if the risk level is at a point where people who like raw milk should avoid it.
As a biologist (not an epidemiologist though) I agree. There is never any reason to drink raw milk and it can make you sick in other ways besides H5N1 (like bovine tuberculosis). Cheese made from raw milk is probably OK if it's aged for long enough that all the pathogens die off (several months), but I really don't understand why people like raw milk in the first place.
> but I really don't understand why people like raw milk in the first place.
I don't think I've ever had raw milk, but I can tell you that, compared to pasteurized milk, ultrapasteurized milk tastes absolutely disgusting.
Huh, I've never noticed a difference. It seems some people are very sensitive to slight differences in milk taste and others are not. Or maybe it's a difference between people who drink large quantities of milk straight and those who mostly mix it with other things (tea, cereal, baked goods).
I know raw milk drinkers, the reasons they give are:
1. It tastes different
2. It’s a nutrition heuristic that raw foods have different nutrient distributions than cooked foods, so maybe it’s good to have a mix of both
3. Probiotics
4. Supports small farms by buying direct from the farmer
I’ve tried it once and can vouch for the taste being different.
I've had it many times as a child. It does taste different; most people tend to either love it or find it disgusting.
I personally prefer the raw taste, but not enough to specifically seek it out (it's very hard to find in Canada anyway, as far as I know). But I would have it again if an opportunity presented itself.
Out of these, I would say that 1 is a good reason, 2 and 3 are likely bad reasons that are easy to talk populists into, and 4 is harder to say.
I had raw milk on two occasions: 1. in Germany in a small supermarket catering also to some rich people (Heino among them). That milk is ... milked under extremely strict rules which make it more expensive but as safe as it gets. Think: "safe as honey" - still, do not give honey or raw milk to babies! The taste was really nice, and I do like milk (sucker). Would buy and drink again any time (was only double the normal price) 2. In Ukraine on a market in a re-used plastic bottle. Idiot me drunk it. And got so sick, I had to vomit it all out 2 hours later. Looked like pieces of white cheese. Some nearby chickens enjoyed it. Oh, traditional small scale farming, the romance of it!
In the US, cheese made from raw milk is required by law to be aged for at least 60 days, so if you can find it at the store, it'll be at least that aged. This mostly means that you won't see fresh style (e.g. mozzerella) or bloomy (brie) cheeses made from raw milk here; other styles are generally aged at least that long anyway.
Last time raw milk came up, the main argument I found enlightening was to think of it as relative risk vs absolute risk. It's supposedly around 1000x more dangerous than pasteurized milk (risk of hospitalization and death), but pasteurized milk has such insanely low casualty rates anyways that regular consumption of raw milk is practically equivalent (in risk) to increasing your daily car commute by a few meters, or eating one additional charcoal-grilled steak per year.
I grew up on a dairy farm, can attest that raw milk has a different (better for my taste) flavour to an extent. If I still lived on a dairy farm and had confidence in the hygiene practices I would drink it for sure just for the taste. The pro-health arguments are rubbish though, agree it's likely to be a risk not worth it if you are relying on hippie idiots to get their supply chain right, so I never try to find raw milk commercially.
I'm also not sure how many people confuse pastuerisation with homogenisation, I duspect at least a few people who think they don't like pastuerised milk really just don't like homogenised milk and don't know that's two different processes that don't have to go together.
Crazy Idea:
Thinking of this quote:
"But the exact mortality pattern was surprising; people between 18 and 28 were especially likely to die, and people older than 88 especially likely to survive. Why? Because an H1N1 flu went pandemic in 1830; anyone who first encountered the flu around then had an immune system synced to H1N1."
What are the merits of deliberately creating a less lethal, more infectious strain of flu variants that we expect as particularly likely to start a pandemic? Do we have the prediction powers to see what variants are more likely than others to start a pandemic? Is it even possible to create less lethal and more transmissible versions of a virus that would also not cause an increase of overall deaths compared to doing nothing?
I suppose this is just transmissible vaccines, which I've seen discussed before. Is there anything different than what I just mentioned and what people normally discuss when they speak of transmissible vaccines?
This is roughly what the Wuhan lab was doing with coronaviruses.
Wuhan was I believe going for a more infectious (to humans) bat flu, but indifferent w/re lethality. The objective was not to create a less-lethal variant just to see if they could, and certainly not to create a less-lethal variant and set it loose to build herd immunity, but to answer the question in Scott's part 3: If this flying-critter airborne infection crosses over into humans, how bad would it be? If the crossovers were likely to be highly lethal, they wanted to know that.
Which would have been valuable knowledge, if we had it a few years ahead of the actual pandemic and if it stayed safely contained in a BSL-4 facility.
Makes sense
Scott & Alina Chan of LL fame are exchanging related to this currently on X https://x.com/slatestarcodex/status/1874641242786791779?t=XpInk6EXT5jkpY5zwDyCEA&s=19
But the actual crossover might have different mutations and so be different from what they had. Meanwhile the response doesn't really need to know ahead of time.
Maybe, but we can't say if that was a good idea or not. Or rather, if COVID came from bats and not the lab, than the whole pandemic doesn't give us any new evidence on whether what the Wuhan lab was doing was good or bad.
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> the Spanish Flu of 1918 was an H1N1 strain that killed about 2% of the world’s population. But the exact mortality pattern was surprising; people between 18 and 28 were especially likely to die, and people older than 88 especially likely to survive. Why? Because an H1N1 flu went pandemic in 1830; anyone who first encountered the flu around then had an immune system synced to H1N1. But an H3N8 flu went pandemic between 1890 and 1900; anyone who first encountered the flu then had an immune system synced to that strain and was unprepared for H1N1. See [here] for the details.
Hmm, I read something that attributed the different profile of the Spanish Flu to the radically different ecology of young men around 1918. To wit, if you were in a trench and got mildly sick, you stayed in your trench, whereas if you were in a trench and became deathly ill, you were shipped to an infirmary behind the lines where you could infect vastly more people drawn from a much wider geographic range. So there was strong selection for high lethality in young men. This contrasts with the normal state of affairs where if you're mildly sick you keep going about your business (just like in the trenches) but if you become severely ill, you withdraw into your personal home (opposite of the trenches).
Why is this theory of the Spanish Flu less convincing than "it was a coincidence"?
> But the biologists I talked to said people tend to overupdate on this, that evolution can do lots of weird things, and that the 1918 flu forgot to read the Evolutionary Virology textbook and actually mutated to get *worse*.
This... looks like strong support for the theory that the virus was selected for high lethality?
Huh, I was reading somewhere... (bad cattitude?) that a lot of Spanish flu deaths among young men was because doctors were treating them with the new wonder drug, Aspirin, and giving them lethal overdoses.
Geez, aspirin? Aspirin is a fever suppressant, the exact opposite of what you want if you have a dangerous illness.
That's like treating a broken leg with morphine.
Rasputin gained a lot of cache with the Russian royal family when he took hemophiliac Alexi off of aspirin.
Depends on if you think the thing that kills you is the virus or the immunoresponse.
For Spanish flu my pet theory is that it was mostly the immunoresponse (which handily explains why young people had it the worst).
I have vague memories of a "cytokine storm" being a theorized cause?
Sure seems like anti-inflammatory drugs like aspirin should help, at least pending empirical evidence in the other direction.
I thought the high fatality rates were true internationally, not just in places with ready availability of aspirin.
I suspect that towards the end of WW1 most people in Northern Europe weren't eating very healthily, what with the prowling U boats hampering convoys, and naval blockades.
So maybe nutritional deficiencies also made it harder to recover from a dose of Spanish Flu. Cooks back then also boiled vegetables for longer, so maybe lack of Vitamin C was one example of such a deficiency.
I agree with the implicit claim that if the Spanish Flu were to happen today, fatality rates will likely be lower even without vaccines.
Yeah this is the first time I see someone linking it to a 1830 pandemic. Is this a new theory?
I read a book about the Spanish Flu (I believe it was “The Great Influenza”) and he attributed the young deaths to the cytokine storms - ie, young people with stronger immune systems ironically had stronger immune overreactions, and therefore died in greater numbers.
Was the flu selected in the trenches? The disease got its start in the Midwest United States (Kansas). However, it did take a year to get ripping, but I thought that was after the war. I believe people who got it during the war got the earlier, safer variant, and were later protected. Still possible it was selected in the trenches though when it got worse, just not sure about that.
Anyways, it’s less strange than Alexander suggested that a virus gets worse at first and then less dangerous later. Experiments on rabbits show that new viruses can become extremely dangerous as they adapt to a new host - they get better at spreading by bypassing the immune system after all. It takes time for the evolutionary logic to slow down the lethality.
We saw this with Covid: many of the first strains became more dangerous as they became better at spreading (like Delta) and then became less dangerous later (omicron). This was the pattern I was expecting based on some virologists I read, so it was intellectually satisfying to see it play out that way.
Check out the wikipedia page. The wave that originated in Kansas was mild, but the second strain originated in France and was much deadlier.
> The forecasters I talked to raised one other point of uncertainty: does the flu work more like a dice roll, or like a bus? Dice rolls are uncorrelated with their predecessors; even if it’s been a hundred rolls since you last rolled a 6, your chance this time is still 1/6. But buses come at fixed intervals; if the buses are hourly, and you haven’t seen a bus in the past 59 minutes, then your chance of seeing a bus in the next minute is very high.
This one seems easy; the flu is more like a bus. It's a motivated adversary working against you, not an indifferent phenomenon.
But this doesn't help to predict outbreaks; compare some phenomena that everyone agrees work the same way, earthquakes and volcanic eruptions. We know that the potential for these phenomena accumulates over time until eventually there's a breakout. The implications are... nothing, if you're worried about when exactly the next breakout might happen. They're mostly relevant to how regular a long-term average of the event rate should look.
Hmm, in the relevant sense, I believe that all three of these things are statistically distributed much more like dice than like buses. Even though the naive model of building tension for earthquakes makes you think it should be more bus-like, it turns out that the total amount of stored tension in the plates is so incredibly much greater than the amount of tension accumulated per century or dissipated per earthquake that frequencies don’t change significantly either when the most recent earthquake was recent or was long ago.
I'm not sure that buses have the statistical properties that you'd like to attribute to buses. Here's an example:
1. The bus is scheduled to arrive once per hour.
2. It is currently 45 minutes late.
3. What is the probability that the bus arrives within the next 5 minutes?
It's true that the arrival of buses is regulated. But it's not true that the extended delay we observe makes an imminent arrival likely. It makes it unlikely, because the effect dominating the arrival of the bus is whatever catastrophe has already made it 45 minutes late, not the overall goal of arriving once per hour. The chance of arriving within the next 5 minutes was much higher 48 minutes ago than it is now. If you were 14 minutes early for the bus, you haven't seen it arrive in 59 minutes, but it's not true that the chance of seeing a bus in the next one minute is high.
45 minute delay on a 60 minute bus schedule might be a sign of a “catastrophe” that would stop all bus travel. But 15 minute delay on a 20 minute bus schedule is actually a very common result of ordinary traffic. It’s true that there’s some complexity to it - it’s not just that the longer the delay is, the greater the per minute probability of arrival, because there are also other effects like the one you mention, as well as the fact that if one bus is delayed, the bus after it has a tendency to get *ahead* of schedule, since its less likely to find passengers at the stops and can just keep going.
But I don’t think we need a detailed model of bus arrival probabilities to distinguish the nearly time-independent poisson process of earthquakes and passenger arrivals at bus stops from the highly time-dependent processes of elections and bus arrivals at bus stops.
>45 minute delay on a 60 minute bus schedule might be a sign of a “catastrophe” that would stop all bus travel.
Might be, but ime it's much more likely a sign of a "catastrophe" that stopped or significantly delayed the travel of that particular bus.
> Epidemiologists hate raw milk, think there is never any reason to drink it, and will announce that risks [exceed] benefits if the risk is greater than zero. I don’t know if the risk level is at a point where people who like raw milk should avoid it.
This raises an interesting contrast with anal sex. What do epidemiologists think about that?
Epidemiologists recognize value in anal sex (people like having anal sex) and so they spend money advertising public health advisories about using condoms and perhaps a drug regime that makes people having anal sex less likely to become infected with HIV (pre-exposure prophylaxis, advertised as "PrEP").
Surely the people who drink raw milk do like to eat raw milk though, no?
Epidemiologists don't believe them. They think the difference in flavour isn't real but is an artefact of knowing the milk is raw (ie you could sell pasteurised milk as raw milk and people wouldn't notice). I'm not convinced on this.
I'm not convinced either, having grown up with a house cow and consequently having a prolonged experience with raw milk decades before anyone asked the epidemiologists. (Although we were always very aware of zoonoses and cow health in general; living that closely with an animal makes the reciprocal nature of the relationship effortlessly obvious.)
Raw milk tastes distinctly different from pasturised milk. I mildly prefer pasteurised; raw milk tastes distinctly and quite strongly of 'cow'.
Raw milk cheese also tastes different.
This, at least, is definitely not true. Raw milk has a distinct sulfur note and smells like... cow.
People who drink raw milk have the option to switch to pasteurised milk; gay men don’t have comparable alternatives to anal sex. Though it seems that the risks to women of anal sex aren’t sufficiently advised about. https://amp.theguardian.com/society/2022/aug/11/rise-in-popularity-of-anal-sex-has-led-to-health-problems-for-women.
New EconTalk episode dishing raw milk: https://podcasts.apple.com/au/podcast/econtalk/id135066958?i=1000682124667
Gay men have alternatives. There are plenty of other ways to get each other off.
None of them are all that less likely to get you infected than either anal or vaginal sex (unless you’re talking specifically about HIV).
But is there an analogue to all this stuff for raw milk that wouldn't make raw milk less appealing to the people who drink it? If the appeal is a) that it's raw and b) that you don't trust the people who don't want you to drink it because there are unquantifiable health benefits you've ruled out treating the milk and better education/"safe drinking" tips from experts, which are two analogous responses.
I assume they're generally against doing it unprotected. Pasteurization is condoms/prophylactics. Raw milk is the unprotected anal sex of milks.
>Raw milk is the unprotected anal sex of milks.
Please put that on a t-shirt.
It doesn’t seem like prediction markets helped very much? Might as well go with the base rate. It’s not like we are going to make different decisions about preparations based whether it’s 5% or 10%.
A problem with stockpiling medicines is that they expire within a few years or perhaps even less. So you need to have a plan to rotate through them, or you find expired medicines in your stash when you need them. It happens to me fairly ofter for the medicine stash I keep in the car or at a relative’s apartment.
More generally, I’m sure people’s medicine cabinets are full of expired medicines because people rarely clean them. It’s pretty wasteful.
Finding expired medicines when you need them is probably better than nothing since expiration dates are often set conservatively. But it might be more efficient to let pharmacies handle the inventory? Ideally, the stockpiling should be done by some organization with high sales. You want nearly-expired medicines to go to people who will use them before they expire.
Inventory costs money because it takes up space. Retailers and distributors usually try to *reduce* inventory to increase profits. If we want more medicine to be stockpiled, someone needs to pay them to *increase* inventory. We want the opposite of the “just in time” delivery that most modern supply lines are built on.
This might be done with government subsidies or some kind of private insurance scheme. Does anything like that exist?
The concept of expiration dates with medicines is a bit murky. Many of them continue to work just fine decades after their "expiration dates," which may apparently be set somewhat arbitrarily.
Here's a letter from the HHS that states that at least certain, properly stored lots of Tamiflu (oseltamivir, an influenza antiviral medication) is still effective up to 20 years past its labeled expiration date: https://aspr.hhs.gov/SNS/Documents/Antiviral-Dear-HCP-letter-21Dec2022.pdf
> Based on their review of scientific data, FDA has concluded for emergency responses that, provided the Tamiflu product has been stored under labeled storage conditions, it is scientifically supportable for certain lots of Tamiflu® 30mg, 45mg, and 75mg capsules held in the SNS to be used for a maximum of 20 years beyond their date of manufacture.
Yes, it would be great to have more research into how long various medicines can safely be stored and to use that to set longer expiration dates.
The amount of waste from *not knowing* whether medicines are safe can be pretty high. And not just waste, but bad outcomes when there are shortages.
it’s unreasonable to expect consumers to figure out for themselves whether it’s safe to ignore expiration dates.
Well, telling you that the base rates are good in this case is a valid outcome.
It's a bit like complaining about a study that had a negative result, ie null hypothesis was not rejected.
Last week I commented here on groups of large wild birds being found dead in wetland areas in the Mississippi flyway. Since then several such instances have been confirmed by state agencies as H1 virus deaths, including in my state (Illinois).
Is it worthwhile to try to use new mRNA vaccine tech to shut down the transmission of these various viruses in farmed pigs and fowl? If so is there any funding stream to make this happen? I mean it sounds like the sort of thing that requires government to solve the cooperation problem.
There's a meta study that found the lethality of H5N1 in humans to be about 20%. You're overlooking the effect of antivirals, which all American patients from 2024 received, and which are extremely effective - as long as they last.
Not all American patients received antivirals, see this paper: https://www.nejm.org/doi/full/10.1056/NEJMoa2414610
Hmmm, I remember the 1977 flu as the swine flu. On SNL, John Belushi lead the Killer Bees to the vaccination center to steal the vaccine supply because they were friends of the swine flu. Nurse Laraine Newman said they had run out of vaccine hours earlier and had just been injecting saline.
Edit: Okay swine flu was 1976. My mistake.
But wait. I guess it was Gilda not Laraine!
https://tr.pinterest.com/pin/snl-retro-eric-idlejoe-cocker-stuff-10276--102105116524623130/
Good summary, but you lost at Metaculus. Why would a bunch of uninformed people, misinformed people, plus some informed people be able to predict a pandemic when even super-informed people can't predict a pandemic? But I find it interesting that cultures (even rational-materialist cultures) can't live without their oracles.
This paper may be of interest: "How well did experts and laypeople forecast the size of the COVID-19 pandemic?"
https://pmc.ncbi.nlm.nih.gov/articles/PMC8099086/
The effect is essentially the wisdom of the crowd. I also don't understand why it works, but the data says that it often does. In forecasting competitions you get consistently better results from crowds than from individuals, and sometimes better results from an uninformed crowd than from better informed experts.
A stopped clock can be correct twice a day. Has the data you're referencing been compared to controls? It seems to me that people are seeing patterns in ambiguously defined events and that predictions can be biased based on the interests and expertise of active forecasters. And, of course, Metaculus has been very poor at predicting black swan events. It seems to be a common human need to want to see order in the future, but I think predictive markets are woo-woo for people who want to have oracles but need a sugar coating of rationality to wash them down. ;-)
I refer you to this paper. Post hoc analysis shows that random-walk predictions provide fewer erroneous forecasts than crowd predictions.
"Forecasting skill of a crowd-prediction platform: A comparison of exchange rate forecasts"
> Open online crowd-prediction platforms are increasingly used to forecast trends and complex events. Despite the large body of research on crowd-prediction and forecasting tournaments, online crowd-prediction platforms have never been directly compared to other forecasting methods. In this analysis, exchange rate crowd-predictions made on Metaculus are compared to predictions made by the random-walk, a statistical model considered extremely hard-to-beat. The random-walk provides less erroneous forecasts, but the crowd-prediction does very well. By using the random-walk as a benchmark, this analysis provides a rare glimpse into the forecasting skill displayed on open online crowd-prediction platforms.
That is certainly an interesting paper, but it only applies to the hyper-special situation of exchange rates. Which is is somewhat outside the range where we need prediction markets, because exchange rates are a prime example for monetary markets that already predict the correct rate. I think the paper essentially shows that prediction markets do not defeat the efficient markets hypothesis, i.e., they do not beat other money markets. Which isn't surprising. I would not trust Metaculus to tell me which stocks to buy, and I don't think many supporters of prediction markets would go so far to recommend that.
Btw, since you mentioned black swans, the paper actually says that the random walk models predict *less* black swan events than Metaculus. This seems to contradict your point.
I’m not being nitpicky - this goes to the core of what Taleb meant by “Black Swan”: it is completely, utterly unpredictable because we have no framework, no data, nothing we can use to predict it it. “Black Swan” isn’t synonymous with “rare”, it means “we literally have no idea how common this is”.
Pandemics are not black swan events. Anything Metaculus can predict is not a black swan event.
Funny, but I'm only now reading Taleb's _The Black Swan_...
However, I beg to differ with you — I think SARS-CoV-2 fits Taleb's definition of a black swan event. Its occurrence wasn't foreseeable through standard methods or models. The event had a massive and transformative impact on individuals, organizations, and societies. And after it happened, humans rationalized it as if it could have been expected or predicted.
Correct me if I'm wrong about this (please!), but AFAIK, none of the predictive markets were taking bets on a pandemic happening before the advent of SARS-CoV-2 and COVID-19. When the outbreak began, it wasn't really on the radar screens of any of the national health authorities or the WHO. Of course, the Chinese were slow to react because the Mayor of Wuhan tried to hide what was going on (Wuhan was about to host a big CCP wingding when people started to get ill). Dr. Gao, the head of the China CDC, only learned about the outbreak in Wuhan on 30 Dec 2019 via social media. Fauci didn't hear about it until a few days later when a reporter called to ask him about what was going on in China. Even once people started dying, the WHO and the CDC were fairly sanguine about the outbreak. I think the WHO said that there "was no evidence of human-to-human transmission," and the CDC echoed that statement. (Didn't Scott post an essay about how confusing a claim of "no evidence" is?)
A Chinese researcher from the Chinese Academy of Medical Sciences in Beijing uploaded a sequence of the virus to Genbank on 28 Dec 2019, but the person who reviewed the sequence rejected it because it was missing some background info (rumor has it that it was rejected because the submission used the names Beijing and Peking in different fields, and the reviewer wanted consistency — but I haven't been able to verify that). It wasn't until 12 Jan 2020 that a sequence was available for scientists to review. By that time people were dying, and SARS2 had spread out of Wuhan. Clearly, no one was prepared for SARS-CoV-2.
Having said that, After SARS1 and MERS-CoV, *some* experts, such as Peter Daszak and Stephen Morse, among others, were worried about the risk of other zoonotic spillovers. Organizations like the Predict Project and EcoHealth Alliance tried to identify and evaluate pathogens in fauna that were candidates for spillovers into humans. Daszak was the most prescient because he focused his efforts on cataloging Coronaviruses endemic to Horseshoe bat populations (because that was where SARS1 came from).
https://www.ecohealthalliance.org/2013/10/new-sars-like-coronavirus-discovered-in-chinese-horseshoe-bats
I may be misremembering, but I think most researchers were more concerned about the risk of another influenza pandemic, though.
https://www.smithsonianmag.com/science-nature/china-ground-zero-future-pandemic-180965213/
But I think it was Sonia Shah, in her 2016 book _Pandemic_ who emphasized the risks of wet markets as a likely place for spillovers to occur.
To summarize, after SARS1 in 2003, we had a group of experts who were concerned that a pandemic of zoonotic origins would occur. Although Coronaviruses were among the potential candidates, they were not the only candidates. But they had no predictive models for which mutations could trigger a pandemic (that's why Daszak applied to DARPA for a grant to run GoF tests against CoVs — but it wasn't funded). No one had any predictive models for when the next pandemic would occur (and we still don't). And once COVID hit the mainstream media, Metaculus grossly underpredicted the number of deaths it would cause before 2021. What can I say? It sounds black swannish to me.
I have to confess to cheating 🫣 - I knew the answer because I’ve read Taleb’s own opinion on the matter:
“Covid was not a Black Swan, you don’t call something Black Swan that’s already been in the movies. It’s a White Swan; the fact that we didn’t have a pandemic for close to 100 years is the actual Black Swan. You don’ have a Black Swan when movies talk about pandemics. In my book on Black Swan on page 307, I explained that because of extreme connectivity such pandemics are unavoidable.”
Well, I respect Taleb, but in this Youtube video, he's wrong about being able to contain SARS2. New Zealand, as an island, was able to stop all travelers from entering their country, but it got in somehow. Of course, they did a good job playing whack-a-mole with the outbreaks for a while, but once they had vaccines, they basically let it rip. China, with the strictest ZeroCOVID regime of any country couldn't contain it. And it had already spread by flights out of Wuhan before anyone knew what they were dealing with.
And if a scenario is in the popular media before it happens disqualifies it as a black swan, 9/11 wasn't a black swan. Tom Clancy, in his novel "Debt of Honor" (1994) portrayed a jet plane crashing into the capital, killing the President and a joint session of Congress. So 9/11 was in popular culture before it happened. Also, we had intelligence that Al Queda was planning a massive terrorist attack on the US, but Bush decided not to take it seriously. Seems like this is similar to COVID. We had pandemic narratives in the media. We had experts warning it might happen. But no on really believed it would happen.
https://www.youtube.com/watch?v=BVHBszRrkbg
As a total layperson on this topic I would appreciate an understanding of why Covid isn't a part of this discussion - I'm guessing Covid isn't 'flu' in the strict sense? Is Covid not likely to fade into the background and become indistinguishable from usual seasonal flu? A parenthetical on this would have been handy as it felt like an elephant in the room while reading the article!
Also, could the new bird flu "reassort" with covid infected people?
No, they're completely unrelated viruses.
Not to my knowledge, coronaviruses and influenza are from different virus families so it would be like a human managing to reproduce with, like, a giraffe or something.
...or a giraffe reproducing with a squirrel. But I don't really know; I'm just sticking my neck out and going out on a limb here.
Covid is not flu in ANY imaginable sense, strict or not strict, unless someone decides to use the word "flu" to mean any viral respiratory illness -- which is a colloquial usage I've seen in the UK among older/middle aged people but it's clearly and obviously erroneous, can be confusing and should be avoided.
Thanks. Prior to reading this article I did think Covid was a type of flu or at least closely related. Maybe this is a thinko unique to me, though in my defence I suspect it was discussed as 'flu-like' quite a lot early on. CF the china_flu subreddit (https://www.reddit.com/r/China_Flu/)
I am also from the UK which might be part of my confusion. Occasionally I do hear people mention eg 'stomach-flu' or 'man-flu' where 'flu' is being used quite generically and not confined to a particular category of virus.
A lot of people who are in the anti-vaccine, anti-lockdown, anti-caring-about-covid-stuff cluster go on a lot about how "it's just the flu", so that general thought is out there in the zeitgeist.
I can see how someone who wasn't super into following this stuff could easily pick up the idea that covid == flu.
Early on a lot of people assumed it was a flu, and a lot of the existing pabdemic preparation was modelled on that. Which caused some confusion.
On the linguistics side I think that's why "influenza" is often used to avoid the ambiguity
“Influenza-like illness” is a technical term for a cluster of symptoms that many viruses cause. The CDC has a category where they track this, because they know they aren’t doing viral tests on everyone, and a surprising number of illnesses go through an influenza-like illness phase. (Apparently initial infection with HIV manifests this way, and even monkeypox does before the lesions show up.) But lots of respiratory viruses never manifest as anything other than influenza-like illness.
I think the symptoms of flu and most other infections are mostly just the immune response. You feel terrible not because the influenza virus is doing something nasty to your body, but because your immune system has kicked into high gear, is using a lot of energy that would otherwise be used for other things into fighting off the infection, and is moving the slider bar between "don't harm self" and "be especially harmful to other." That's why something like HIV gives people an influenza-like illness on initial infection.
If you didn't have that immune response and the associated misery, I think those infections would often progress to the point where they were doing something bad to you themselves. (As with HIV, which evades the initial immune response and keeps evolving around it until it finds a gap, at which point it starts wiping out your T cell population.)
Your declaring a strict definition that come after the common use as being authoritative; is a tomato a fruit? Is it literally unimaginable some may call a tomato a vegetable? Shall you get anal abut calling steaks bovine-chops or something?
Heres an imaginable sense: coughs effect lungs, I estimate how strong my lungs are for illnesses that cause coughs for my chances of survival, I group those illnesses together.
Except it turns out to be much more relevant to your survival to know how it interacts with your immune system, not your lungs, and influenza viruses, coronaviruses, rhinoviruses, syncytial viruses all interact differently with your immune system, even though the symptoms you notice are very similar if the case isn’t especially severe.
Doubtful, damage is damage and pain is pain; pill pushers may talk up details as *marketing* that gets into science textbooks; but your immune system is better then anything they make and your extended immune system *also* makes you feel tired or in pain depending on how bad your illness to signal to the lizard brains to actually take a break no matter how important other things seem.
What do you mean? Are you saying that the immune system cells that learn to recognize coronaviruses can *also* automatically recognize influenza viruses and syncitial viruses and so on, because they cause the same symptoms, and that the “pill pushers” who say that biochemical differences are relevant to immunity are just lying?
If you want to survive a cough, and you feel sleepy go to sleep, if you feel cold get warmer, if your throat hurts sip water or make tea. (not that you have much choice in the matter) These are *extended* immune system behaviors(because evolution is holistic) and are more important then a magic pill.
Half of symptoms *are the immune system itself*, viruses dont want fevers. What matters is maintaining the balance of the system beyond our current understanding with dumb, if not faithful responses. So grouping illnesses based off symptoms just makes sense.
Hyper reductionists can go to hell in general; but for biology especially its just delusional, if you ever actually eat "sodium" your mouth will be on fire, you eat salt; you eat fermented foods, you eat based off cravings bacteria wish for, to feed a bio reactor we can not replicate in a lab.
It doesnt matter what the medical textbooks label viruses or think mechinics of systems are, we are not there yet, not even close. You work with and listen to the body, not make demands like you do bunch of gears or computers, thats not what we are nor the nature of the problem.
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Medical lingo is a pale reflection compared to the felt experience what signals an immune system sends out(lingo is a mere map and a shit one, the immune system is the territory and better at its job then us for the time being), so if corona feels like a flu, its a flu; its very arrogant to declare mere lingo is more correct, to assert the medial systems mechanistic control over evolution's playground is pill pushing and wrong.
Covid is likely to fade into the background and become indistinguishable from the usual common cold. Which is a collection of 200+ distinct viruses that we generally don't bother to distinguish because they are very similar and very mild.
The various flus are also very similar and *usually* very mild, but there are enough differences that it's worth distinguishing between the two disease-clusters. And because of those differences, you wouldn't want to mix Covid statistics or common-cold statistics in with your influenza statistics for an analysis like this.
I suspect it’ll be more like RSV, where we didn’t notice it had systematically more significant complications for a few people, and more serious symptoms for many, than other colds, until we started testing for it.
Thanks Scott! I didn't really know what to think about bird flu, and now I know much better. This is exactly why I support this blog.
Not a single mention of eggs, which is what's been keeping bird flu on my mind. There's a permanent sign on our usually-empty egg case at work which says, roughly, "yes, this is all the shipments we got, stop asking". But they don't stop asking...I don't attend to the regular news, so have no idea what coverage is like among normies, yet one would expect a greater level of updating. Every single day, several times a day: >asked for more eggs/chicken >reply negatively >incredulous bafflement, explanation demanded >bird flu, supply and demand >ongoing incredulous bafflement at both concepts ... Can't wait until it starts noticeably impacting cow and pig products too. I remember how infuriated customers got at beef <s>hoarding</s> shortages during early covid. "This can't be happening...in America!"
-- not to make light of suffering and loss of life, obviously that's the far greater utilitarian concern. And I do find it comforting that the risk profile so far is mostly still long tail! But I don't put much faith in the "America's pandemic surveillance and response game is competent" part of the assumption (or the unstated voluntary behavioral modifications part), based on the Jellyman Amnesia on display thus far with H5N1. People just seem to really want to roll to disbelieve that it could happen again soon, on a bus-like model. Like, we already had covid, and then monkeypox, shouldn't we at least get another decade before the next pandemic bus comes along? So - hoping for the best, but prepared to be rather disappointed should we fail a Fort save. At least I'll get to be an Essential Worker(tm) again.
(additional context that would have been nice: ballpark comparison to covid impact, exploration of why things keep getting worse despite having a vaccine for chickens and hopefully one for cows soon. FDA Delenda Est? I think I recall reading something about how it's actually due to a trade dispute, where we couldn't do certain poultry exports if it's vaccinated, and there's no political will to do the equivalent of just buying out the mink farms...? I do appreciate the post regardless, more informative than a dozen breathless thinkpieces by thought[less] leaders)
Huh, there are plenty of eggs in Western NY where I live.
California’s been short, not out but “they’re out of 18s so I got a 12” level. I’ve been avoiding egg-reliant recipes, less because I can’t get them now than because it seems rude in a shortage, and also they keep and I don’t know if I’ll be able to get them next week, or next month (refrigerated eggs really do keep).
I assumed it was a mix of bird flu and everyone making Christmas cookies based purely on “that’s what it was last year.” If so it should even out in a few weeks to a few months; I think it did last year.
We're caught in a bad Our Price Cheap equilibrium, where...without mentioning the company, we're required to always sell <s>vulnerable to predators, weather, and each other</s> cage-free at minimum, and usually with various other pieties like organic or whatever. However, our prices are also kept low, and there's strong resistance to raising them (internally, from customers, and also from various CA/SF-specific laws against "price gouging"). It's also not the kind of place where we can reliably enforce a per-customer limit. Finally, the company's hesitant about short-term temporary contracts with new suppliers; sometimes it'll happen for truly essential basics like rice or pasta, but eggs don't quite reach that standard. Perfect recipe for regular shortages when one can't react meaningfully to shifting supply and/or demand.
I guess the demand response comes via people going to more expensive stores, when you run out.
I feel about 90% confident there have already been 10,000 cases and they simply weren't symptomatic enough to trigger testing. In my mind, the simplest explanation for the widespread prevalence of bird flu in farm and zoo animals is that low-symptomatic humans are infecting the animals. The only sensible explanation for the fact that many closed sewer systems are currently awash in bird flu sequences is that a lot more than 66 humans have been unknowingly shedding it in their stool.
https://cbuck.substack.com/p/h5n1-is-messing-with-texans
I know several people who tested positive for influenza A on a rapid home test, but when they asked healthcare providers to be tested to find out whether it was bird flu or seasonal flu they were summarily tuskegeed. You can't argue that we've been looking for bird flu and not seeing it - the sad truth is we simply haven't been looking. Shameful.
That seems very plausible to me. But his 10,000 number is not meant to be a threshold of actual cases - it’s just meant to be a number that will be passed if there is a phase transition in spread, but not otherwise (unless we change detection methods).
I was more thinking about the Metaculus betting - which seems to be couched as "10,000 cases" - as opposed to "10,000 severe cases." I wouldn't bet there have already been 10,000 severe cases. But 10,000 mild cases? Mostly restricted to the gut? I'd offer 14:1 odds:
https://www.cdc.gov/mmwr/volumes/73/wr/mm7344a3.htm
I'd also offer tall odds on the grim side-bet that mild now doesn't necessarily mean mild later this year:
https://www.the-sentinel-intelligence.com/p/mild-at-first-a-brief-history-of
My guess is that the use of the word “case” rather than “infection” is meant to pick out individuals who have tested positive, rather than individuals who have been infected but were never detected as such.
In the CDC report above, 7% of farm workers tested positive for bird flu antibodies - indicating that they were unknowingly infected with bird flu in the recent past. I'd call them all "cases," even though they never tested positive for shed virus particles.
The sewage data makes me suspect that the currently circulating strains of bird flu are primarily a gut infection. We're hardly testing anybody, and the tiny bit of testing we are doing might be sampling the wrong orifice.
In the UK during Covid, the government spent a vast fortune, in the billions of pounds I think, setting up a Covid test and trace scheme, and (more relevant to your point) sewage monitoring for the presence of viruses or their antibodies (not sure which).
I believe the sewage monitoring has since been discontinued in the UK. This was possibly (I surmise) in part due to political embarrassment at the amount of illicit drugs whose presence was being detected, revealing how much slips past customs etc, and thus their incompetence. But I gather it was relatively cheap, and would no doubt have been able to give a fair idea of the prevalence of new viruses if these were being checked for.
But UK political leadership, both Tory and Labour, in recent years has been atrociously short sighted and bad. (Our EU membership in previous years has apparently caused native political leadership skills to atrophy almost to nothing!)
Brief note about Spanish Flu mortality rate: you might imagine that WWI-era is modern, in a sense. In fact, medical care at the time didn't involve insuring people weren't dehydrated and were staying warm; people slept outside of hospitals in the winter when hospitals were full. And the lack of resources and malnutrition due to wartime shortages in Europe definitely greatly increased the death rate.
(Also, "Spanish Flu" is an unfair misnomer; it was first widely reported in Spain because that was the only place without wartime censors, it certainly didn't emerge there. In fact, the most likely candidate origin is in the United States, in Kansas.)
at least one very popular medical textbook (“The Principles and Practice of Medicine” by Osler) was in use into the 1920s and recommended bloodletting. Modern medicine is indeed very new.
Indeed. Also worth noting that this was before the concept of a "virus" was fully fleshed out. Also before we had antibiotics (for treating secondary infection). Before IV hydration (or really, before IV anything in a modern sense). Before the concept of a "cytokine storm" was developed, and how to treat it. Certainly before antivirals. Medicine has come a very long way.
One question I have is why we've previously seen large outbreaks of H5N1 that have seemingly burned out - e.g. 136 cases in Egypt in 2015, 55 in Indonesia in 2006, 61 in Vietnam in 2005. These are pretty poor countries so I'm assuming far more people were infected in reality.
It's also interesting to think in a post-covid world how much more attention something like the Egypt outbreak would get today. I didn't know about it until I was reading about H5N1 the other day, and I'm pretty sure if it happened now I would be really freaking out.
I think you are really, really underestimating the impact of the other thing going on in 1918. Particularly in terms of what age group it especially impacted (and which did the flu again?), how much damage it is likely to have done to immune systems (how much good sleep do soldiers in a trench get? How much vitamin C? How about nurses? How about when you move a lot of the population that wasn’t in factories into factories, on a sudden emergency basis, and oh coincidentally that is specifically the population segment that usually manages unpaid informal nursing?), and how many resources it diverted - not just governmental, but household. Having slack is very important for disease treatment: time to lie in bed, time to take off work, time to rest without Something Actually Essential Going Undone. You don’t have a lot in the middle of a war.
My personal guess on priors (I am not an epidemiologist, take with requisite salt) is that the Spanish Flu got at least half its lethality from hitting during a world war, with medical systems both official and informal already overwhelmed and most young people desperately overworked, either directly in the war or making up for all the stuff that still needed to be done when the people who should be doing it were in trenches getting shot at or dead. My basis for this is observations about the effects of rest on disease in me (pushing through illness tends to make it much worse, even if it’s just the early stages I push through) and a lot of reading about wars; take that for what you will. A quick Wikipedia scan also suggests it initially spread in America through Army camps, for what that’s worth; boot camp is obviously not the same as getting shot at but it may not be good for the immune system either, and it also seems to have spread through regular troop movements after, focused on the army. (But I am not an expert; this was literally a quick scan, and I stand more by the first half of the argument.)
My certainty in my precise numbers is low; it’s possible the Spanish Flu was just that bad irrespective of anything else. But given the obvious confounder not addressed, and the way it lines up with the lethality demographics, I strongly suspect something important is being missed. We are, thank God, not presently in a world war, and that should not be irrelevant to the odds of another influenza pandemic being as lethal as the one that was.
(Yes, I know that could change. Hope it doesn’t, not necessary to the point.)
I think if the war were a big factor then you'd see men hit worse than women, but Figure 5 in this paper suggests more or less the same, of if anything slightly worse among women of fighting age: https://eprints.lse.ac.uk/108853/1/Basco_unequal_mortality_during_the_spanish_flu_published.pdf
That’s why I mentioned the home front - if your husband/father/brothers are off at war and you’re trying to run the household and work a factory job, plus maybe take care of kids solo, when you come down with it who’s there to take care of you? Remember all your friends/relatives are doing the same thing.
That is, you’re correct if the mechanism is purely spread through armies/stress on soldiers. It’s just I’m pretty sure pulling a significant part of the population away (selected for being in good shape, even!) and then raising pressure on the rest (we were supplying a LOT of war materiel, speaking purely of America, on top of all the usual work that needs doing everywhere and everywhen) is going to cause less slack/societal resources to respond to disasters.
According to Wikipedia (not as good a source, I know) the German and French governments were both spending over 50% of GDP, and Britain was close. It doesn’t mention America and I’m sure it was lower, we weren’t under existential threat - but a lot higher than before the war. So thank you for the link, it’s a good point and given the Wiki comments about spread in army camps I’m surprised it isn’t higher in men. But I’m not sure that disproves my main point about societal resources being low, because they were low for women too. Working a factory job on top of running a household is not as bad as getting shot at, but it probably isn’t great for your immune system either, and maybe that cancels out against guys generally being in better health/women being default first-line healthcare workers? Not sure.
(I’m taking your word for the article because I am, ironically, down with the flu at the moment so can’t follow up on it properly, but thank you for the link, it’s nice to get counter-evidence.)
Fun to read while I'm battling an upper respiratory infection. Happy New Year, ACX.
An obvious difference between this and past bird flus is that it's infected dairy cattle. About 1% of Americans consume raw milk weekly, and 4.4% consume it at least once a year. That's not counting the rest of the world:
https://www.statista.com/statistics/272003/global-annual-consumption-of-milk-by-region/
To my knowledge cowflu is only present in the U.S.? If it were to spread (or co-evolve) to India it would seem like the chance of a pandemic would be much higher.
Ergo it seems like the chance of a pandemic is much higher than it has been in the past? We're not talking just farm workers exposed here, but sizable portions of the population. Moreover, the sort of people who drink raw milk are probably more likely to avoid vaccines and other sensible safety precautions.
> But it was 40 years between the Spanish and Hong Kong flus
Wasn't it 50 years?
Can we make a vaccine? If not a great vaccine (given that the virus has not yet reached the form that would be dangerous to humans) then a better-than-nothing vaccine?
What part of the discussion of this in the article is not clear? We already have vaccines, just not enough for everyone to get them
The way we make influenza vaccines involves culturing the virus in eggs, and apparently takes many months, so it can’t be ramped up quickly.
Point 3 in the summary hits hard. I also can't really think of anything else.
It might be worthwhile reading a summary of ewald's work on the evolution of infectious disease.. Mostly, he describes fluid borne diseases as special cases whose virulence doesn't evolve the way that airborne diseases do, due to increased genetic diversity and competition, exacerbated by rapid passes from one host to another. But as another poster mentioned, the Spanish Flu evolved in very unusual circumstances, with sick young men stuffed into box cars and carted around Europe. This favors virulence. An ambulatory host stops being such an advantage to spread, so there's less of a restraint on overuse of host resources.
> give suggest
Typo
>"Much of this discussion hinges on whether we should expect flus to generally become less virulent when adapting to humans and going pandemic. There’s a hand-wavey evolutionary argument that they should: pathogens don’t “want” to kill (or incapacitate) their host before they can spread. But the biologists I talked to said people tend to overupdate on this, that evolution can do lots of weird things, and that the 1918 flu forgot to read the Evolutionary Virology textbook and actually mutated to get worse. There may be a slight tendency for things vaguely like this to happen, but we shouldn’t count on them."
The usual reply I know of, is that there can be positive associations between infectiousness and virulence (e.g. via how much resource it hijacks, or if it attacks the immune system, or if it needs to give you diarrhea to transmit), so a virus can evolve to be more virulent if it comes with a big enough increase in infectiousness. The simplest models have it evolve to maximize R0, though iirc this can depend on details like coinfection. (What maximizes this is also expected to depend on mode of transmission; e.g. if you're laid up in bed you can't go out and cough on people, but a mosquito can still bite you then bite other people.) The association/trade-off theory was developed by Anderson and May (1982) and Ewald (1983) (according to Alizon et al. 2009); Ewald also developed theory about how it's affected by transmission mode etc, which is all now a staple of evolutionary medicine (Williams and Nesse, 1991; Ewald, 1993; Nesse and Williams, 1998). A case study of virulence decreasing at first but then increasing later on is myxoma virus in rabbits in Australia (Zimmer, 2022). Stephen Stearns' Yale course on evolutionary medicine, available on YouTube, has two videos on virulence evolution (Stearns, 2015).
References
Alizon, S. et al. (2008). Virulence evolution and the trade-off hypothesis: history, current state of affairs and the future. J Evol Biol 22: 245-259. https://doi.org/10.1111/j.1420-9101.2008.01658.x
Anderson, RM. and May, RM. (1982). Coevolution of hosts and parasites. Parasitology 85: 411-426. https://doi.org/10.1017/s0031182000055360
Ewald, PW. (1983). Host-parasite relations, vectors, and the evolution of disease severity. Ann Rev Ecol Syst 14: 465-485. https://doi.org/10.1146/annurev.es.14.110183.002341
Ewald, PW. (1993). The evolution of virulence. Sci Am 268: 86-93. https://www.jstor.org/stable/24941444
Nesse, RM. and Williams, GC. (1998). Evolution and the origins of disease. Sci Am 279:86-93. https://doi.org/10.1038/scientificamerican1198-86
Stearns, S. (2015). Evolution and Medicine. https://www.youtube.com/playlist?list=PLh9mgdi4rNezvm7QkQ_PioadoAWqfa2L0
Williams, GC. and Nesse, RM. (1991). The dawn of Darwinian medicine. Q Rev Biol 66: 1-22. https://doi.org/10.1086/417048
Zimmer, C. (20 June 2022). Think all viruses get milder with time? Not this rabbit-killer. New York Times. https://www.nytimes.com/2022/06/20/science/myxoma-virus-rabbits-covid.html; archived with no paywall at https://archive.ph/Ry3dy.
Andrew Read's summary of the myxoma virus in Australian feral rabbits ("Andrew Read: An evolutionary arms race," https://www.youtube.com/watch?v=_I8UlL-OeXk).
Tl;dr it was released in 1950 to try to control the rabbits; it evolved to be less virulent, but was still pretty virulent; the rabbits evolved immune resistance, but then that provoked an evolutionary response in the virus to become more virulent.
Also the paper (Peter Kerr et al., 2017, https://doi.org/10.1073/pnas.1710336114) and another lay article from when it came out (Ed Yong, 2017, https://www.theatlantic.com/science/archive/2017/08/rabbit-virus-arms-race/536796/)
I struggle to understand why there is not a national stockpile of 1 billion doses of Oseltamivir if not Baloxavir. Maybe very effective, maybe a little, maybe not at all, but generally safe and well tolerated. And crucially already in existence—with oseltamivir even off patent. As a practicing physician, I find the pharmacies in Washington DC routinely run out of both drugs in a normal flu season. Why don’t we have better access to these?
I'm pretty sure that there is a 1 billion dose stockpile of medical countermeasures. But a treatment course is 10 doses, so you're down to 100 million treatment courses. That's enough to treat a first wave in the US population, but not enough for everyone, let alone prophylaxis of essential workers for a few months. I think we should assume everyone is going to get a new respiratory virus: non-pharmaceutical interventions are going to spread that out somewhat but eventually it's everyone. If you have a 3 billion dose stockpile you may have to replenish 25% of it per year (generic oseltamavir has a 3 year shelf life in Australia, Tamiflu has a 10 year shelf life to help with the stockpile requirement).
Since this can be devastating to sold bird populations, isn't a major possible vector of transmission people's dogs and cats? Any dog that comes across a dead bird is going to sniff around it and probably roll in it and possibly eat it...same if it finds a sick and dying bird. Cats that go outside spend all day trying to kill birds. The majority of US households have a dog, and about about a third have a cat. This is my primary concern, given that it seems to be quite lethal for cats. My cat doesn't go outside, but my dogs do, and I don't want them snuffling around in some dead/dying bird and bringing something back that they transmit to and kill my cat. If people are finding flocks of dead birds frequently, this seems inevitable if more wild birds get hit.
*wild bird populations, not sold bird
Thank you for the dice roll vs bus analogy. I've been bothered by "gambler's fallacy" for a while now, mainly that saying that "humans are bad at probability" doesn't seem right. My conclusion is that brain are not trained on pure chances calculations, because they never encounter it.
Almost everything happening influences whether that thing will or will not happen again. In that bus analogy, abscene increase probability. In competent doctor operation analogy, presence increase probability. In any case, even dice roll isn't as pure as dice roll, so gambler's fallacy seems to only apply to artificial environment and theoretical gotchas. This is why I'm more symphatetic to Bayesian, it seems to simulate, either brain or reality, better.
As an aside, whenever I read something touching on evolutionary biology, it seems to reinforce my prior that it's unfalsifiable. By this point it may be a trapped prior, but I think I have been vigilant enough. And I can still bet it'll never reach as high of predictability as particle physics (Maybe an unfair comparison, but I want to assert that degrees of predicting power exist, and evolutionary biology seems to be very low on it).
Evolutionary biology grad student here. I agree that it will never have the same predictive power as e.g. particle physics. There are few general "laws" about what will evolve, partly because it depends on what traits are developmentally feasible and development is complicated (might there be reasons why a pig can't grow wings even if it would be fit to?), and partly because fitness depends on ecological context (compare: whether a key is good depends not just on the key on its own but on whether the key fits the lock).
The comparison, fair or not, does highlight why physics is in a sense "easier" than other less impressive sciences. It's easier to study the interaction of e.g. a hydrogen atom with a photon, than it is to study big messy complicated things made of >septillions of atoms, like organisms and species and societies.
Specific hypotheses within evolutionary biology can be falsifiable (and often are falsified or corroborated), and there are even some areas that do seem to have generalizations that lead to law-like predictions. E.g. sex ratio theory, and more generally sex allocation theory, is pretty successful. It shows how and why 1:1 sex ratios are so common (it's the selective equilibrium given that everyone has one mother and one father, plus some other assumptions), and makes predictions for when deviations from 1:1 can evolve (e.g. when local mate competition means males compete with their brothers for mates). For a lecture on sex allocation theory, from Stephen Stearns' Yale course on evolution, ecology, and behaviour, see https://www.youtube.com/watch?v=buOWEw9AhNE. For more on theory of virulence evolution, see my other comment: https://www.astralcodexten.com/p/h5n1-much-more-than-you-wanted-to/comment/84002911.
Evolution itself isn't unfalsifiable. E.g. DNA-based molecular phylogenies agree with earlier phenotype-based phylogenetic trees, and with our intuition, that chimpanzees are more closely related to humans than elephants or dogs or crocodiles or turnips are. If evolution was false that could have turned out not been the case; it could have been that molecular phylogenies put humans as being most similar to turnips, but it didn't.
Thank you for your kind response! I have to admit that there are several predictions that can be made in the field, regardless of the field as a whole. Regarding evolution, so the main prediction is that the closer the molecular phylogenetic, the more similar they will always be? Is there a jargon or tag where I can read (specifically) about that?
Idk if it's "the main" one, but it's an example. (There are also nuances I didn't get into. E.g. it's better to compare non-functional regions, since a functional region could have similarities due to convergent evolution; e.g. dolphins and bats had similar mutations to evolve echolocation, and if you only looked at that region then you might think they're closer cousins than they are. Or incomplete lineage sorting, followed by loss of some alleles, resulted in some regions in us looking closer to gorillas than to chimpanzees. In general published phylogenies are all estimates. But in broad strokes, yes the data is what we expected, and agrees that humans are closer to chimpanzees or gorillas than to crocodiles or turnips.)
Some stuff you could check out are Richard Dawkins' 1986 "The Blind Watchmaker" (including ch10, "The one true tree of life") or his 2009 "The Greatest Show on Earth" (including ch10, "The tree of cousinship"). The former is the best single-book lay introduction to evolution; the latter is more specifically framed as giving the evidence for evolution.
An accessible intro textbook on molecular phylogenetics is Lindell Bromham's 2008 "Reading the Story in DNA" (or its 2016 revised version, "An Introduction to Molecular Evolution and Phylogenetics"). That might be your best bet if you specifially want to learn about this molecular evolution stuff. A more advanced book is Ziheng Yang's 2006 "Computational Molecular Evolution." A review paper is (Yang and Rannala, 2016, https://doi.org/10.1038/nrg3186). Also fun is Dawkins' 2004 "The Ancestor's Tale" (including the section "The gibbon's tale").
As an evolutionary biology PhD student, I very much agree with the recommendation of "The Greatest Show on Earth".
There's also TalkOrigins' list of predictions of evolution (https://www.talkorigins.org/faqs/comdesc/), which is not entirely up to date and somewhat polemic (being a relic of the great Creationism Wars of bygone times) but is still a pretty good overview.
(Not a biologist but I read a bit about it.) More falsifiable predictions come from evolution of microorganisms and can be verified experimentally. Take some bacteria like E. coli, feed them something they can survive on but aren't particularly adapted to eating. Wait for them to spread, take a sample, put it into the next Petri dish. Repeat. Prediction: after a thousand repetitions, the bacteria will be significantly better adapted to consuming the food they were given.
But is there any precise definition on "survive on but aren't particularly adapted to eating" and "significantly better adapted to consuming the food they were given" that can be declared upon to make a prediction model on how many generations (with normal distribution?) are needed to reach it? I guess it might be something like how many calories could they acquire from that particular food, before and after.
Normally I'd expect the reproduction rate to be a good metric. But since they might get smaller or simpler on account of having simpler environment, biomass/acquired calories probably should be taken into account.
Great write up, especially for the base rate discussion.
I want to add that even accepting these numbers, it is a good idea to have Oseltamivir powder in dry storage at home for if you or any of your kids get any flu. If fear of H5N1 is the juice you need to get on flu precautions (besides the shot) then capitalize now!
And if you are a young lazy guy like me who fears the flu shot but not an oral antiviral, all the more reason!
really well done. thanks.
> Influenza A has two surface antigen proteins, hemagglutinin (18 flavors) and neuraminidase (11 flavors). A particular flu strain is named after which flavors of these two proteins it has - for example, H3N2, or H5N1.
Naively this suggests there should be 18*11=198 different flavors of influenza.
Out of curiosity I looked up some of them (eg H3N7, H3N9, etc), and... most of them don't exist. Going off a quick Wikipedia search, it looks like only 18 of them do. That said, I strongly suggest that people should NOT try to make the other 180 flavors.
I've read that there's something of a balance between the hemagglutinin (HA) and neuraminidase (NA) proteins. The HA facilitates viral entry into the cell, whereas NA allows newly formed virions to detach from the cell upon exit. So their activity needs to be well matched or else the virus will just fail to reproduce effectively. This implies to me that not all types are actually possible. Also there could be new forms of HA or NA that haven't been seen before, so I wouldn't say 198 different types is a hard upper bound.
Duncan Purvis here, thanks for the namecheck Scott! And thanks again for your grant last year. Feel free to contact me if you want another source of help and clarification for future articles, you have my e-mail.
In terms of pre-pandemic preparation, I'd refer anyone to a JAMA viewpoint article from September: https://jamanetwork.com/journals/jama/fullarticle/2823004 . It's a good shopping list of recommendations for the USA in particular.
Influenza has to constantly spread to survive. Cross-immunity is the most likely explanation for the elimination of Influenza A subtypes in the past, e.g. 1968 H3N2 1968 eliminated 1957 H2N2, which had eliminated 1918 H1N1 in turn.
The elimination of Influenza B Yamagata during COVID is likely to have been due to COVID-19 lockdowns in Q2 2020 further reducing its transmission, on the background of Yamagata having an increasingly difficult time vs B Victoria pre-2020, and being in an evolutionary dead-end (fragile). So Yamagate eradication wasn't primarily cross-immunity from COVID
So you're saying there's a chance? 😏
> But the exact mortality pattern was surprising; people between 18 and 28 were especially likely to die, and people older than 88 especially likely to survive. Why? Because an H1N1 flu went pandemic in 1830; anyone who first encountered the flu around then had an immune system synced to H1N1.
Do you put no stock into malnutrition low cleanliness in the trenches and ... questionable medical care (*cough* lethal doses of the hot new drug asprain)?
In terms of the base rate being 5%, and this year of highly elevated risk being 5%, I think there are two partial explanations.
One is what you mention, that there’s some base rate of unpredictable flu pandemics per year.
The other is that out of the predictable ones, likely most years if we try to do a prediction, it’s 0.01% chance of a predictable pandemic. Probably in the immediate vicinity of a predictable pandemic, you might predict a 30% chance per year. But 5% is actually going to only come in relatively few moderately elevated years, even if that’s also the long run average risk. Most years are much lower.
I read a book a while back that attributed the weirdly high death rate among young fit people in the Spanish flue pandemic to cytokine storm. Basically, they have stronger immune systems that can attack the virus more thoroughly and the ensuing battle ends up accidentally killing them.
But there's also an explanation offered here that old people survived largely because they had remaining antibodies from a similar historical pandemic.
Are these ideas in conflict or do they both make sense at once?
I am definitely not any sort of expert on the subject, but on a broader conceptual level "targeted response, following an old precedent" sounds like it would lead to quite a bit less accidental damage than "strong response, but inefficient due to confusion / surprise."
Why is there so much discussion of raw fatality rates instead of “QALYs lost”? If the disease is like Covid and only kills those who were about to die anyway, it’s a lot less big of a deal than the 1918 flu that killed young people at alarming numbers.
It’s like we haven’t learned anything from Covid and keep on pounding the drum of “fatality rates!” when that alone is a meaningless number and you instead want “fatality rates by age bracket” to make any decisions.
A market on “fatality rates for people under 60 with a BMI of 18-25 and no major health conditions” would be *far* more interesting.
"maybe we should just shut them [mink farms] down"
Maybe we should instead be more concerned about keeping the minks healthy? Are the mink farms geared exclusively to raising them, like chickens? My understanding is that an ecosystem interacts with itself, such that, for example, illnesses that minks contract are prevented by other organisms that can coexist with minks. Crop rotation helps prevent diseases in your crops, since if your corn field gets an anti-corn pathogen then the next season it doesn't affect corn, but can only try, futilely, to infect the wheat you plant next.
I'm surprised mink farming is only a $80 million a year.
the estimate of annual profits on mink are only an estimate of producer surplus. the total benefit of mink farms also includes consumer surplus
The biologists Scott talked to should be sent back to school for saying "1918 flu forgot to read the Evolutionary Virology textbook and actually mutated to get worse" (in probably less funny words). The Red Queen of Evolution rulez - and if you do not see how, you need to look harder. The common theory is that WWI itself created a new environment: Many young men stuck close together in the trenches without an option to isolate as in "go home for having a cold". And the worst cases then put together in large field hospitals with lots of other young men with all kind of serious conditions with over-worked medical staff "caring" for all. A virus virulent enough to get you there got favored by the Queen.
So called “Spanish Flu” is probably a suboptimal model for how things will work.
1. Spain was not directly involved in WWI. Other countries had propaganda reasons for not reporting accurately—they being involved in WWI, so only Spain was reporting close to accurate statistics, iirc.
2. Many of the “young and healthy” victims of Spanish Flu were living in trenches in appalling sanitary and unimaginably stressful circumstances, foxholes in a combat zone.
That makes me suspicious of any discussion involving “Spanish Flu” that make no mention of these possible con founders.
I also wonder how often mild infections aren’t identified beyond, “I’ve a cold,” outside of professions with mandatory testing—I don’t bother with medical attention when I can do all my work from my computer any time I have a fever—I’m certain many other professionals who aren’t customer facing. Contrast with my friends in Education who “have COVID” with symptoms that would otherwise barely inconvenience them..
If your infection is severe enough to require powerful drugs, it being “Just a Rhinovirus” isn’t much consolation.
> five in the past century = one per twenty years = 5% chance per year
I find this superfluous middle step funny :)
4 per four score years.
Cool iteration of this post taking place between Scott and Alina Chan on X focusing on gain-of-function leak risk angle.
https://x.com/slatestarcodex/status/1874641242786791779?t=XpInk6EXT5jkpY5zwDyCEA&s=19
The 5% annual H5N1 pandemic risk estimate is a reasonable conclusion. But I feel less optimistic about the fatality rate. A pandemic influenza virus needs to infect the upper airways to spread efficiently and the neuropathogenic and virulent characteristics would distinguish H5N1 from other influenza viruses. Essentially this virus tends to spread from the nose to the brain.
https://www.reddit.com/r/H5N1_AvianFlu/comments/1dajeru/comment/l7tckbx/
While H5N1 has evolved significantly, it is important to remember that the 1997 Hong Kong outbreak is the initial reason for concern, and the pandemic potential was obvious.
https://pubmed.ncbi.nlm.nih.gov/10608786/
https://academic.oup.com/jid/article/180/6/1763/866721?login=false
I want to point out that researchers have of course tried to find more mild cases and despite all uncertainties the historically high CFR is not just a statistical artifact due to a lack of surveillance:
https://wwwnc.cdc.gov/eid/article/25/11/18-1844_article
https://pubmed.ncbi.nlm.nih.gov/18477756/
https://www.ijidonline.com/article/S1201-9712(23)00706-3/fulltext
While we can learn from past influenza pandemics, there are limitations, and it is crucial to study H5N1 to gain insights:
https://www.science.org/content/article/why-hasn-t-bird-flu-pandemic-started
The 1918 pandemic is not an outlier, the 1830 pandemic has been similar:
"The pandemic of 1830-3 ranks in terms of severity with the pandemic of 1918-20 (Beveridge 1977; Pyle 1986; Patterson 1987)"
https://sci-hub.se/https://doi.org/10.1046/j.1365-2672.2001.01492.x
"We have had only three pandemics in the 20th century. That is not a good base on which to build models."
https://www.ncbi.nlm.nih.gov/books/NBK22148/
The cow genotype B3.13 has significantly changed the public risk perception, but in my personal opinion this is just one issue of many. The drastic reactions of the prediction markets make me question the expertise of the participants. If reassortment is such a concern, why not H5Nx instead of H5N1 and why specifically clade 2.3.4.4b?
There is totally inadequate surveillance of pigs, cats, and rodents. Millions of birds are spreading the virus worldwide, fur farms remain a risk, poultry workers continue to get infected. There is sustained mammal-to-mammal transmission in pinnipeds with potentially dangerous outcomes, see the 2014 outbreak of H10N7 in seals.
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2024.29.44.2400326
https://www.nature.com/articles/s41586-024-08054-z
https://www.biorxiv.org/content/10.1101/2024.05.27.596080v1.full.pdf
https://www.biorxiv.org/content/10.1101/2023.05.02.539182v1
https://www.vetres.org/articles/vetres/full_html/2010/05/v100006/v100006.html
https://www.nature.com/articles/s41467-024-53766-5
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2023.28.31.2300400
There have been various other estimates and in conclusion I believe that the unprecedented nature of the panzootic significantly reduces the relevance of comparisons with previous events.
In the 2022 British National Risk Register the chance of any pandemic happening in the next 5 years is estimated to be in the 5-25% range:
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1175834/2023_NATIONAL_RISK_REGISTER_NRR.pdf
One statistical approach results in a 3% annual chance of a "mild" pandemic as in 2009, 1% for a pandemic of "medium" severity and only a 0.02% chance of a pandemic as severe as the 1918 pandemic:
https://www.ncbi.nlm.nih.gov/books/NBK525302/
One estimate from 2019 of the probability of an H5N1 pandemic resulted in 5% in 10 years, based on occasional bird-to-human transmissions, just before the emergence of H5N1 clade 2.3.4.4b with frequent infections of mammals:
https://www.tandfonline.com/doi/full/10.1080/17513758.2021.1942570
Another statistical approach results in a 2.5-3.3% annual chance of a pandemic as lethal as Covid-19 or worse:
https://www.cgdev.org/blog/the-next-pandemic-could-come-soon-and-be-deadlier
These Much More Than You Wanted to Know posts are great work, especially when they're sort of ahead of the timeline like this one.
In this case, I think the biggest problem with it is the title. There really isn't much in it that I didn't want to know. It's facts backed up with sources and links.
"the last pandemic as bad as Spanish flu was smallpox hitting the Indians circa 1500"
I assume you mean the indigenous inhabitants of the Western Hemisphere (WHII), not South Asians.
I am not an advocate of politically correct nomenclature. My favorite baseball team is the Cleveland Indians. But, without more the term "Indians" may be ambiguous.
On that subject. WHII, may have suffered from more than one pandemic at a time. They were immunologically naive to a whole raft of Eurasian and African diseases. Further it may be impossible to retroactively diagnose the difference between measles and small pox.
This article is linked in 1440, a free daily news compendium.
https://join1440.com/newsletter/new-orleans-update-dino-highway-and-generation-beta
It's in the In Depth section.
"Bird Flu, Explained
Astral Codex Ten | Scott Alexander. As the avian H5N1 flu spreads from bird flocks to herds of cattle—and isolated human cases—a doctor breaks down the origins of flu and the likelihood of this one to turn into a pandemic (he estimates 5%). (Read)"
To be informed on “how” add function research by Fauci et al, Listen to Tucker Carlson’s interview with a vaccine lawyer. It is not anti-vac but a safeguard against some of the poorly designed research studies that have been utilized to approve some brands of vaccines
Plus it reveals that the process that viruses cross into humans is always “natural”
Covid 19 or “Fauci’s virus” to give credit to its development was from added function research in Wuhnan lab ….
The public is very aware now and absolutely no longer trusts FDA, CDC, NIH or others so called public health agencies due to huge deception and censorship related to vaccines, masking, social distancing or effective treatments
Exercise, lose weight, eat healthy as obesity and diabetes and its subsequent commodities were highest risk factors from dying from covid …all “modifiable”
An epidemiologist -- a professor at Yale's Public Health School and an advisor to among others the CDC -- offers some updates this afternoon about H5N1:
"A Louisiana resident is in the hospital after contracting H5N1 from their backyard flock. This case had the same H5N1 strain as a teenager in Canada who was fighting for their life last month. (A recent NEJM case study described how severely sick this teenager was: intubation for 3 weeks, temporary support to the heart and lungs called ECMO, plasma exchange, 3 antiviral medications, and more.) The H5N1 strain involved in both severe cases—called D1.1—is found among birds and differs from the strain circulating among cows (B3.13)....
....Birds that gather at feeders (like cardinals, sparrows, and bluebirds) do not typically carry H5N1. The USDA does not recommend removing backyard bird feeders for H5N1 prevention unless you also care for poultry. The less contact between wild birds and poultry (by removing sources of food, water, and shelter), the better."
https://yourlocalepidemiologist.substack.com/p/the-dose-january-3
Just want to say that this was an exceptionally clear and well-written post. It was judicious about presenting relevant moving parts and their relationships, at the right level of abstraction, in a straightforward style, with an accurately modeled lay audience in mind. I also appreciate the detail with which you explained each step in reaching your probability estimates. I wish more forecasters were so thorough. I love the "Much More Than You Wanted To Know" series, and this was a top example, probably in the top 3% of SSC/ACX posts of all time.
Another Metaculus market has the risk of human-to-human transmissibility at 25%. Why the >5x discrepancy? Is it really five times likelier to gain the ability to spread from human to human than it is to infect 10,000 people? https://www.metaculus.com/questions/26328/human-transmission-of-h5n1-before-2026/
>the 1918 flu forgot to read the Evolutionary Virology textbook and actually mutated to get worse.
The explanation I've heard for this is that this apparent reversal was caused by the unusual circumstances of WW1. The pandemic initially incubated among servicemen in Europe. Army hospitals were a better place to spread than the front lines. The more virulent cases caused soldiers to be sent to the hospital, so that selected for more virulence.
IANA virologist so I don't know how accurate this is, but it seems plausible to me.
Any reason vaccine development doesn't fall into these predictions?
You might have covered this in the article (way too long for my attention span right now), but how are those H and N proteins detected, and how do they know that they come from a virus that is "discovered" by extracting RNA or DNA from an unpurified sample? Are those virus genomes or samples evr tested on living animals to confirm that they are the cause of the symptoms we call "flu"?
No mention or calculus re: post Covid infection damage to immune system and how would affect severity/mortality.
Agree. Huge elephant in the room.
You have left out a very important set of facts about H5N1: it's an H5.
The influenza virus is structured as 8 genes: H#, N#, and the other six. The other six are wrapped in a bundle in the center, and H# and N# are on the outside. The other six are heavily conserved, while H# and N# change incessantly.
To infect a mammal, the H1, H2, H3, and H4 genes require an enzyme. The enzyme exists in small amounts all over the body, but is very common in the upper respiratory tract. A mammalian flu infection consists of massive viral load in the upper respiratory tract and small amounts of activity in the rest of the body.
Until H5N1 appeared.
The H# variants H5 through H9 DO NOT NEED this enzyme. You can get a massive infection anywhere, and it will quickly become massive all over the body. This is why the H5N1 variants have caused death rates above 50% in mammals in small infection clusters. I think an early one was 80% of the tigers in a 500-unit tiger farm in Southeast Asia.
This difference in virulence is why the public health folks have been shitting bricks over H5N1 for 20 years: it hitteth like a rock.
This is all memory-dumped from when I was following H5N1 20 years ago. No cites, sorry.
Good summary.
Flu strains like H1N1 have a single base (R) at the HA cleavage site. One example might be:
PQIETR↓GL
I think the enzymes cleaving that would generally be HAT or TMPRSS2.
The highly pathogenic strains of H5N1 have a multibasic cleavage site like RRKR or similar variations:
https://pmc.ncbi.nlm.nih.gov/articles/PMC5057330/
That can be cleaved by furin, in a wider variety of tissues, causing a systemic infection.
I'd also be inclined to think that H5N1 is almost guaranteed to have a higher fatality rate than other flu strains, for that reason. I might also expect wide ranging consequences similar to long covid, from that multi-organ infection.
But a few things still give me pause in saying that with certainty. I suppose we don't know exactly which H5N1 strain would spill over into people, or if it changes in that process. Also, many sources are saying that the fatality rate is only 2% in cows, suggesting maybe it wouldn't be extremely bad in humans. I haven't looked carefully enough to say if that's IFR or CFR or a fraction of the total herd size.
Great summary of threats caused by zoonotic diseases. And here's some small factoids from the Nordic Countries which might be of interest:
"The Finnish Institute for Health and Welfare (THL) in November stated that fur farming in its current form constitutes a constant pandemic risk.
THL reminded that H5N1, a highly pathogenic variant of the avian influenza, caused infections at dozens of fur farms in Finland in 2023. The infections prompted health authorities to order the farms to cull tens of thousands of foxes, minks and other animals that could function as an intermediary host, allowing the virus to mutate into a strain that can transmit to humans."
Also, vaccination against the strain H5N8 is now offered to people in the risk.
https://thl.fi/en/-/avian-influenza-vaccinations-begin-vaccine-to-be-offered-to-persons-at-increased-risk-of-infection
And also, I recommend reading a book
"Pale Rider: The Spanish Flu of 1918 and How It Changed the World" if interested how severe the impact of the Spanish flu had in several communities (=a lot).
https://pmc.ncbi.nlm.nih.gov/articles/PMC5914470/
Nice read. Thank you for the history. I went vegan when I learned about zoonotic diseases when covid hit. I do not want to be apart of the next pandemic. I suggest others do the same!
This isn't a "Much More Than You Wanted To Know" post. This is a Wikipedia-level summary of the different flu types and then some Bayesian hand-waving. Oh how I miss the long, exhaustively researched "Much More Than You Wanted To Know" posts of old.