One possible frame from which to examine the question is “Since we have no functioning public system that competently fights infectious diseases, is this a reason to short the stock market and stockpile food and so on?”
This frame is just looking mostly at a biological entity as a biological entitiy. If “sweeping through our population unresisted” is biologically what it would naturally do (since it probably will be unresisted) then… it might do that?
But if not, not. It depends on the biology the epidemiology and also maybe the responses from institutions to try to predict that. I’m pretty blackpilled on institutions at this point, but maybe we’ll get lucky and the disease itself will not have the oomph within itself to actually hurt the herd?
So given its positively known biological capacities, and currently not have strong evidence that this is decisively what’s going to happen.
Thus, I’m not gonna short the stock markets yet (and so on). Not for now anyway? I’m not yet allocating many resources to it myself, so my own answer practical here so far is like: “No, don’t start prepping… (yet)?”
Another possible frame is: “Imagining that one is setting policy for a hypothetical competent public health system that generically prevents all reasonably possible very bad infectious diseases (aiming to eradicate many of them, of course), by always taking preventive actions that would stop every disease (based on each one’s worst possible disease properties that have not been ruled out), so that by following the policy it would be the case that no actual disease ever got through, but also the system didn’t waste a lot of money achieving this outcome… in that case, have observables been in fact observed that should trigger some of these generic policies?”
Applying this filter, over my personal state of knowledge, right now, for this second question, the result I get is:
YES, if a competent public health system existed with my current beliefs (which include huge error bars, and highly limited data right now) then a hypothetically competent public health system would already be acting very fast right now.
Note that I’m not in charge of US Public Medicine (yet?) and if I was then it would be responsible to learn a lot more, very fast, and then use that knowledge to make a detailed and positive case for why action or worry is not justified. I would be pulling all-nighters based on this if I had that responsibility, but I don’t, so I’m not.
Instead I’m just going to drop a few bits of evidence that seem relevant to me.
Question #1: Is the disease horrifically shitty?
Answer #1: Yes. It has some body horror (with pustules and scars and stuff) and a mortality of probably ~1%. Higher mortality in children. This mostly from priors about monkeypox, which we know about from decades of study. (It could be a mortality rate of 0.1% all in by the end, but it also could be 2%. If you get it, and you’re still alive 5 weeks after symptom onset, I think… maybe you lived? This means it could take 5 weeks to get a good idea of the mortality rate for really real.)
Question #2: How does it transmit?
Answer #2: Assume aerosol. Versions of monkeypox can transmit by aerosol, and so everyone working with it (running quarantines, doing medical care, etc) should make that assumption and wear anti-aerosol PPE like they were dealing with measles or covid. This might change with more data.
Question #3: Versions of it? What about THIS version?
Answer #3: I was going to say that maybe no one has sequenced this thing yet… but then my google-fu kicked in, and more searching turned up a preliminary sequencing report for a draft genome that has 92% coverage, and enough data to align against known strains.
This one falls clearly among “the versions with mortality more like 1%” and is not similar to “the example with a 10% mortality” so that’s nice.
That said, it has more SNPs of edit distance away from the normal ones than might be expected? So maybe it has some tricks up its sleeve that are worthy of study? Looking at the phylogentic tree built using the draft sequence (see paper linked above for details and full image, this is a zoom in), OUTBREAK_2022 clearly clusters with other light blues (that is: the west africa strain with lower mortality) BUT is farthest to the right because it has the most mutations.
Quotes that give this suggestion include Portugal:
Portugal has confirmed the presence of the virus in five patients and has another 20 under study
Madrid:
The Community of Madrid, for its part, has put the number of patients whose symptoms suggest that they have contracted the disease at 22 , in addition to the seven already confirmed by PCR.
Then a geographic distribution that suggests that travel is occurring, with bigger (earlier seeded?) places away from the capital having more than smaller (later seeded?) places:
Four hospital sources consulted by EL PAÍS raise the number of patients treated in the last two days in hospitals in the region to “between 40 and 50”. There are 16 patients from the Clinical Hospital pending confirmation of results, a dozen from the Twelve of October and several cases in the Gregorio Marañón, Ramón y Cajal and Fundación Jiménez Díaz hospitals.
These are enough OBSERVATIONS to allow me to infer a mechanistic process (of a really icky disease) that was able to generate viable human-to-human transmission via exponential growth.
Does the R0=1.1 here, or does R0=3?
I have no idea.
In the absence of knowing, it it correct policy (facing a possible exponentially growing monster that is currently small and weak but which might become large and strong in naively surprising ways to people who don’t know what an exponential function is) to assume the number is higher until competently and swiftly determined to be lower and less worrisome.
But even R0=1.1 is worrisome.
The correct policy is to CAUSE the number be LOWER (if active causation is needed to achieve this), like R0=0.8 or even less than that, and then persist in that policy until the number of cases is zero… otherwise you’re just dragging out the big sadness (all the individual, ad hoc, confused coping of many individuals, damaging the economy, while trapped in the fog of a hypothetically avoidable battle against mere biology) over a longer period of time.
The costs of ad hoc individual avoidance is where the huge costs pile up on the members of the public who Public Medicine officials have a duty to serve (in Lawful Good countries, anyway).
The US I think is maybe currently Chaotic Neutral? The US seems to mostly not believe in policies or causation anymore? Or to generally give a fuck, because the bureaucrats are immune from voter backlash and hold the voters in contempt and basically seem to lie to us by default while being incapable of reasoning about object level mechanisms, risks, costs, benefits, etc… For now?
I kind of hope that the 2022 and 2024 election cycles deliver new leaders who win on infectious disease policy and then clean things up… but that doesn’t necessarily help us until 2023 or 2025.
Question #5: Can we effectively test for it?
Answer #5: I don’t know. Everything I’ve heard so far is PCR testing of obviously symptomatic people, which has all kinds of slowness built into it.
I’m not sure what body compartments contain the virus and how far into the incubation period one has to get before various tests work on it.
If there are no tests, and no knowledge of test/incubation interactions then the only way TO BE SURE to prevent it from getting into a country and spreading in the community would be to shut down air travel from infected countries to my country.
Absent more detailed information, and going just from “a horrific infectious disease with R0>1 has started showing up among international travelers” I would be shutting down flights from infected countries, and putting the burden of proof on individual travelers to show positively that they are not infected during the “early confusion” period.
A fully adequate thing is probably to have people test before the flight, get diverted to a 40 quarantine after the flight, and then test out of quarantine (with positive tests diverting to isolated medical care).
I have LOOKED and almost every virus has a shorter maximum incubation period than 40 days, so that would probably be adequate, unless dealing with a bioweapon or something that was someone designed to stretch out the incubation for the sake of making it harder to detect or stop or be sure.
If you don’t want to put up with 40 days in quarantine… maybe you shouldn’t be flying anywhere you can’t drive at the possible beginning of a possibly terrible pandemic?
This won’t necessarily destroy the planet or even hurt that many people. Maybe 1000 total infections ever in the world and then somehow just… done? One can hope.
Don’t personally worry about it IRL yet, probably?
But also another biological disaster is not RULED OUT by the things I know, and therefore I would personally be freaking the fuck out out if I worked at the CDC and it was my responsibility to respond to deal every similar potential problem with systematically adequate levels of caution to generate systematically acceptable outcomesover all similar categories of initially observable risk.
Obviously sane things to do (at a high policy level) include:
It probably costs little to start vaccinating critical people right now with “best bet” vaccines, including people in the transporation and medical industries.
Starting challenge trials with all the known plausible vaccines against this specific disease, plus quite a few control patients (assuming informed consent and high pay) with exposure and no vaccine, with daily testing and so on, to figure out which vaccines might be perfect, and how soon people test positive if they are going to test positive.
This is PROBABLY an OVERREACTION. However the whole point of having the capacity for abstract mechanistic reasoning in service of “getting good outcomes in the world using science and policies and stuff” is that you do cheap efficient “correct” overreactions every time, and it only costs millions to overreact on the little stuff, but it saves trillions of dollars to avoid the really bad pandemics, and therefore DOING IT RIGHT EVERY TIME probably comes out “worth it on average”.
I don’t think challenge trials are warranted. There’s real harm arising from doing challenge trials. They made sense for Covid because hundreds of millions of people caught it, thousands were dying every day, and getting an effective vaccine or treatment just one day sooner could save thousands of lives. So accepting a level of harm during testing is warranted. For a disease where R seems to be not much above 1, but CFR might be as high as 10%, I would say, even if we had a competent and well-funded pandemic prevention authority, they might pass on the challenge trials this time around.
Thank you for the response! I’m gonna jump in to places where we might disagree, and that disagreement might be productive for readers.
I’m pretty sure that mortality “in the wild” will be less than 3% even in populations without insurance, without a doctor, and without high enough intelligence to manage their own care competently using internet lookups and OTC meds and so on.
The biology here just seems plain to me:
I’m pretty sure that the cousin strains of OUTBREAK_2022 have a mortality of roughly 1% just from like… wikipedia and so on.
This looks like a variant of the “West Africa” strain (not the scary strain, that had 10% mortality).
In general: most infectious diseases tend towards higher R_t (because duh).
In general: they also tend (under normal circumstances with no superspreader events in ICUs) towards lower mortality/morbidity over time because it makes them “less scary” and so people don’t do big mitigations (and that buys any virus a bit more R_t which is what the viral evolution process (modeled using the intentional stance) “actually wants”).
ALSO, I’m pretty sure that mortality in a competent/expensive clinic will be pretty low. They’ll simply be able to just look at the patient, and notice problems starting to arise, and have antibody therapies ready to titrate the disease effects down, and so on.
For all the above reasons: I’m just quite confident that a challenge trial with monkey pox would not be a big scary thing. Maybe a person or two might have weird genes, and react in a weird way, and have a doctor that isn’t actually clinically competent, and then tragically die in a 500 person trial? But very very likely: NOT.
Then, if the information is valuable to society (which IT IS VALUABLE and if someone disagrees on that score I’m happy to unpack how and why there is high VoI here) then you could pay the people retrospectively once group assignments are unblinded.
So, for example, maybe everyone who got “a placebo vax, then challenged with monkeypox, and likely case of the pox, and some scars maybe from the blisters” as part of the control group gets $30k in payment (or whatever their cheerful price probably is).
Basically: the humans in a challenge trial are grownups, and this wouldn’t be that dangerous, and the residual danger/sadness is their own business which a competent ethical infectious disease fighting institution (which I grant does not currently exist in the US) would get informed consent about, and then just PAY FOR WITH MONEY. More risk? More pay. Then “competent informed consent by grownups” is ethical pixie dust to make it OK <3
So under my models and under my ethical system, challenge trials are all of (1) safe-ish and (2) deontically permitted and (3) insanely valuable.
The reason they probably won’t happen is because our institutions cannot actually reason coherently about value or probability or ethics or any of it. They’re just idiots basically, and that’s why we can’t have nice things.
...
Maybe you have evidence that I lack that OUTBEAK_2022 has a CFR around 10%? If that is true I would ask for that evidence!
What are the observations? What are the statistical summaries? Do you have links please?
(Also, just to mention this: if CFR>9% for OUTBREAK_2022 then I would update pretty strongly towards “OUTBREAK_2022 was caused by either (1) GoF research or (2) some sort of nosocomial disaster where a clinic was spreading the worst variants to diseases to new patients in some sort of morbidity amplification process, and either way it would be good to start looking for the guilty parties, to correct them, if they can be found”.
An increase in mortality is not how diseases normally evolve, and would thus require some surprising/unusual cause to be true of an actual disease.)
...
SEPARATELY WHERE I HAVE LOW CONFIDENCE:
For a disease where R seems to be not much above 1 … I would say, even if we had a competent and well-funded pandemic prevention authority, they might pass on the challenge trials this time around.
You seem to have assumed a low R, but my current state of knowledge here is: wide error bars and therefore maybe R is high?
A competent publicly funded infectious disease fighting system would have a pro-active responsibility to clearly falsify the bad parts of the plausible range very fast.
Then once the falsification of “bad possibilities” has occurred, they could properly BACK OFF on the “correct pre-emptive measures that one should take in the absence of coherent knowledge that we are very very very likely to be in the safe regime”.
I don’t personally currently have evidence that “the bad possibilities are clearly false based on definite observations”. If you know for sure that R is low, that would be a pleasant relief <3
Could you drop a link to thorough reasoning over adequate observations that makes it very clear that R_t < 1.15? :-)
Thanks for your thorough response. It is well-argued and as a result, I take back what I said. I’m not entirely convinced by your response but I will say I now have no idea! Being low-information on this, though, perhaps my reaction to the “challenge trial” idea mirrors other low-information responses, which is going to be most of them, so I’ll persist in explaining my thinking mainly in the hope it’ll help you and other pro-challenge people argue your case to others.
I’ll start with maybe my biggest worry about a challenge trial: the idea you could have a disease with an in-the-wild CFR of ~1%, that you could put 500 people through a challenge trial, and “very likely” none of them would die. With a CFR of 1%, expected fatalities among 500 people is 5. If medical observation and all the other precautions applied during a challenge trial reduces the CFR by a factor of 10, to 0.1%, your expected deaths is only 0.5, but that still seems unacceptably high for one trial, to me? To get the joint probability of zero deaths across all 500 people above 95%, you need closer to 0.01% CFR, (1−0.01%)500=0.951. Is it realistic to think all the precautions in a challenge trial can reduce CFR by a factor of 100 from 1% to 0.01%? I have no idea, perhaps you do, but I’d want to know before being feeling personally comfortable with a challenge trial.
Regaring R values and monkeypox generally, my understanding on this topic doesn’t go much beyond this post and the group of responses to it, so I’m pretty low-confidence on anything here. Thus, if you say the R is potentially quite high, I believe you.
Monkeypox virus is transmitted from one person to another by close contact with lesions, body fluids, respiratory droplets and contaminated materials such as bedding.
I’d have to guess it’s going to be less infectious than covid, which had an R around 5? On the other hand, since OP asked the question, there’s more speculation about chains of transmission that seem to indicate a higher R. I acknowledge “lower than 5” is a high error!
Having said that, to my mind, I now feel very conflicted. Having read AllAmericanBreakfast’s comment and their headline, I felt reassured that monkeypox wasn’t much for the public to be worried about, and the CDC and WHO would figure it out. But on my own understanding, if R is high (as you say) and CFR is anywhere much above 0.1%, and there’s a widespread outbreak, that is pretty scary and we should all be much more on the alert than we already are?
And that would affirm your conclusion that challenge trials would be a good idea, as long as we have confidence the risk to participants is low.
Why is it assumed that diseases evolve towards lower mortality? Every new disease is an evolved form of an old disease, so if that trend were true we’d expect no disease to ever have noticeable mortality.
Lower mortality is just generally more efficient, even from the disease perspective. Typhoid Mary was a great success for the typhoid, precisely because it didn’t take her out or slow her down.
Over the long run, most diseases find a balance. The balance is almost never “kill the host really fast”. Your gut microbiome is basically made out of a bunch of “infectious diseases” that play nicely with their host. That’s the normal thing. Symbiosis is efficient and normal. Depending on how you count, there are 10s or 100s or 1000s of essentially friendly bacteria species in a modern human GI tract.
When a bat virus, like SARS or Ebola, jumps to humans, the species it came from often wasn’t even really bothered by it any more… but the disease does not start out in evolutionary equilibrium with humans.
Its is usually only only when you have high enough mixing (or a new kind of mixing over barriers of separation that previously kept things separate (or some idiot not inside a BSL5 does GoF research and mixes biological reality with their scary imaginations)) that ancient equilibriums of default symbiosis seriously break down.
Ah, so mortality almost always trends downwards except when it jumps species, at which point there can be a discontinuous jump upwards. That makes sense, thank you.
One possible frame from which to examine the question is “Since we have no functioning public system that competently fights infectious diseases, is this a reason to short the stock market and stockpile food and so on?”
This frame is just looking mostly at a biological entity as a biological entitiy. If “sweeping through our population unresisted” is biologically what it would naturally do (since it probably will be unresisted) then… it might do that?
But if not, not. It depends on the biology the epidemiology and also maybe the responses from institutions to try to predict that. I’m pretty blackpilled on institutions at this point, but maybe we’ll get lucky and the disease itself will not have the oomph within itself to actually hurt the herd?
So given its positively known biological capacities, and currently not have strong evidence that this is decisively what’s going to happen.
Thus, I’m not gonna short the stock markets yet (and so on). Not for now anyway? I’m not yet allocating many resources to it myself, so my own answer practical here so far is like: “No, don’t start prepping… (yet)?”
Another possible frame is: “Imagining that one is setting policy for a hypothetical competent public health system that generically prevents all reasonably possible very bad infectious diseases (aiming to eradicate many of them, of course), by always taking preventive actions that would stop every disease (based on each one’s worst possible disease properties that have not been ruled out), so that by following the policy it would be the case that no actual disease ever got through, but also the system didn’t waste a lot of money achieving this outcome… in that case, have observables been in fact observed that should trigger some of these generic policies?”
Applying this filter, over my personal state of knowledge, right now, for this second question, the result I get is:
YES, if a competent public health system existed with my current beliefs (which include huge error bars, and highly limited data right now) then a hypothetically competent public health system would already be acting very fast right now.
Note that I’m not in charge of US Public Medicine (yet?) and if I was then it would be responsible to learn a lot more, very fast, and then use that knowledge to make a detailed and positive case for why action or worry is not justified. I would be pulling all-nighters based on this if I had that responsibility, but I don’t, so I’m not.
Instead I’m just going to drop a few bits of evidence that seem relevant to me.
Question #1: Is the disease horrifically shitty?
Answer #1: Yes. It has some body horror (with pustules and scars and stuff) and a mortality of probably ~1%. Higher mortality in children. This mostly from priors about monkeypox, which we know about from decades of study. (It could be a mortality rate of 0.1% all in by the end, but it also could be 2%. If you get it, and you’re still alive 5 weeks after symptom onset, I think… maybe you lived? This means it could take 5 weeks to get a good idea of the mortality rate for really real.)
Question #2: How does it transmit?
Answer #2: Assume aerosol. Versions of monkeypox can transmit by aerosol, and so everyone working with it (running quarantines, doing medical care, etc) should make that assumption and wear anti-aerosol PPE like they were dealing with measles or covid. This might change with more data.
Question #3: Versions of it? What about THIS version?
Answer #3: I was going to say that maybe no one has sequenced this thing yet… but then my google-fu kicked in, and more searching turned up a preliminary sequencing report for a draft genome that has 92% coverage, and enough data to align against known strains.
This one falls clearly among “the versions with mortality more like 1%” and is not similar to “the example with a 10% mortality” so that’s nice.
That said, it has more SNPs of edit distance away from the normal ones than might be expected? So maybe it has some tricks up its sleeve that are worthy of study? Looking at the phylogentic tree built using the draft sequence (see paper linked above for details and full image, this is a zoom in), OUTBREAK_2022 clearly clusters with other light blues (that is: the west africa strain with lower mortality) BUT is farthest to the right because it has the most mutations.
Question #4: Is the R0 greater than 1?
Answer #4: Probably yes. Looking at the situation in Spain suggests GROWTH inside of localized communities. This article seems to be gleaning numbers from relatively direct reports that include: a sense of time, with few early patients, and then, later in time, more patients.
Quotes that give this suggestion include Portugal:
Madrid:
Then a geographic distribution that suggests that travel is occurring, with bigger (earlier seeded?) places away from the capital having more than smaller (later seeded?) places:
These are enough OBSERVATIONS to allow me to infer a mechanistic process (of a really icky disease) that was able to generate viable human-to-human transmission via exponential growth.
Does the R0=1.1 here, or does R0=3?
I have no idea.
In the absence of knowing, it it correct policy (facing a possible exponentially growing monster that is currently small and weak but which might become large and strong in naively surprising ways to people who don’t know what an exponential function is) to assume the number is higher until competently and swiftly determined to be lower and less worrisome.
But even R0=1.1 is worrisome.
The correct policy is to CAUSE the number be LOWER (if active causation is needed to achieve this), like R0=0.8 or even less than that, and then persist in that policy until the number of cases is zero… otherwise you’re just dragging out the big sadness (all the individual, ad hoc, confused coping of many individuals, damaging the economy, while trapped in the fog of a hypothetically avoidable battle against mere biology) over a longer period of time.
The costs of ad hoc individual avoidance is where the huge costs pile up on the members of the public who Public Medicine officials have a duty to serve (in Lawful Good countries, anyway).
The US I think is maybe currently Chaotic Neutral? The US seems to mostly not believe in policies or causation anymore? Or to generally give a fuck, because the bureaucrats are immune from voter backlash and hold the voters in contempt and basically seem to lie to us by default while being incapable of reasoning about object level mechanisms, risks, costs, benefits, etc… For now?
I kind of hope that the 2022 and 2024 election cycles deliver new leaders who win on infectious disease policy and then clean things up… but that doesn’t necessarily help us until 2023 or 2025.
Question #5: Can we effectively test for it?
Answer #5: I don’t know. Everything I’ve heard so far is PCR testing of obviously symptomatic people, which has all kinds of slowness built into it.
I’m not sure what body compartments contain the virus and how far into the incubation period one has to get before various tests work on it.
If there are no tests, and no knowledge of test/incubation interactions then the only way TO BE SURE to prevent it from getting into a country and spreading in the community would be to shut down air travel from infected countries to my country.
Absent more detailed information, and going just from “a horrific infectious disease with R0>1 has started showing up among international travelers” I would be shutting down flights from infected countries, and putting the burden of proof on individual travelers to show positively that they are not infected during the “early confusion” period.
A fully adequate thing is probably to have people test before the flight, get diverted to a 40 quarantine after the flight, and then test out of quarantine (with positive tests diverting to isolated medical care).
I have LOOKED and almost every virus has a shorter maximum incubation period than 40 days, so that would probably be adequate, unless dealing with a bioweapon or something that was someone designed to stretch out the incubation for the sake of making it harder to detect or stop or be sure.
If you don’t want to put up with 40 days in quarantine… maybe you shouldn’t be flying anywhere you can’t drive at the possible beginning of a possibly terrible pandemic?
Covid was handled poorly in MANY ways. One of the ways it was handled poorly is that quarantines were 14 days long despite early evidence of 27 day incubation in some cases.
Summarizing:
This won’t necessarily destroy the planet or even hurt that many people. Maybe 1000 total infections ever in the world and then somehow just… done? One can hope.
Don’t personally worry about it IRL yet, probably?
But also another biological disaster is not RULED OUT by the things I know, and therefore I would personally be freaking the fuck out out if I worked at the CDC and it was my responsibility to respond to deal every similar potential problem with systematically adequate levels of caution to generate systematically acceptable outcomes over all similar categories of initially observable risk.
Obviously sane things to do (at a high policy level) include:
It probably costs little to start vaccinating critical people right now with “best bet” vaccines, including people in the transporation and medical industries.
Starting challenge trials with all the known plausible vaccines against this specific disease, plus quite a few control patients (assuming informed consent and high pay) with exposure and no vaccine, with daily testing and so on, to figure out which vaccines might be perfect, and how soon people test positive if they are going to test positive.
This is PROBABLY an OVERREACTION. However the whole point of having the capacity for abstract mechanistic reasoning in service of “getting good outcomes in the world using science and policies and stuff” is that you do cheap efficient “correct” overreactions every time, and it only costs millions to overreact on the little stuff, but it saves trillions of dollars to avoid the really bad pandemics, and therefore DOING IT RIGHT EVERY TIME probably comes out “worth it on average”.
I agree that this is probably an overreaction.
I don’t think challenge trials are warranted. There’s real harm arising from doing challenge trials. They made sense for Covid because hundreds of millions of people caught it, thousands were dying every day, and getting an effective vaccine or treatment just one day sooner could save thousands of lives. So accepting a level of harm during testing is warranted. For a disease where R seems to be not much above 1, but CFR might be as high as 10%, I would say, even if we had a competent and well-funded pandemic prevention authority, they might pass on the challenge trials this time around.
Thank you for the response! I’m gonna jump in to places where we might disagree, and that disagreement might be productive for readers.
I’m pretty sure that mortality “in the wild” will be less than 3% even in populations without insurance, without a doctor, and without high enough intelligence to manage their own care competently using internet lookups and OTC meds and so on.
The biology here just seems plain to me:
I’m pretty sure that the cousin strains of OUTBREAK_2022 have a mortality of roughly 1% just from like… wikipedia and so on.
This looks like a variant of the “West Africa” strain (not the scary strain, that had 10% mortality).
In general: most infectious diseases tend towards higher R_t (because duh).
In general: they also tend (under normal circumstances with no superspreader events in ICUs) towards lower mortality/morbidity over time because it makes them “less scary” and so people don’t do big mitigations (and that buys any virus a bit more R_t which is what the viral evolution process (modeled using the intentional stance) “actually wants”).
ALSO, I’m pretty sure that mortality in a competent/expensive clinic will be pretty low. They’ll simply be able to just look at the patient, and notice problems starting to arise, and have antibody therapies ready to titrate the disease effects down, and so on.
For all the above reasons: I’m just quite confident that a challenge trial with monkey pox would not be a big scary thing. Maybe a person or two might have weird genes, and react in a weird way, and have a doctor that isn’t actually clinically competent, and then tragically die in a 500 person trial? But very very likely: NOT.
Then, if the information is valuable to society (which IT IS VALUABLE and if someone disagrees on that score I’m happy to unpack how and why there is high VoI here) then you could pay the people retrospectively once group assignments are unblinded.
So, for example, maybe everyone who got “a placebo vax, then challenged with monkeypox, and likely case of the pox, and some scars maybe from the blisters” as part of the control group gets $30k in payment (or whatever their cheerful price probably is).
Basically: the humans in a challenge trial are grownups, and this wouldn’t be that dangerous, and the residual danger/sadness is their own business which a competent ethical infectious disease fighting institution (which I grant does not currently exist in the US) would get informed consent about, and then just PAY FOR WITH MONEY. More risk? More pay. Then “competent informed consent by grownups” is ethical pixie dust to make it OK <3
So under my models and under my ethical system, challenge trials are all of (1) safe-ish and (2) deontically permitted and (3) insanely valuable.
The reason they probably won’t happen is because our institutions cannot actually reason coherently about value or probability or ethics or any of it. They’re just idiots basically, and that’s why we can’t have nice things.
...
Maybe you have evidence that I lack that OUTBEAK_2022 has a CFR around 10%? If that is true I would ask for that evidence!
What are the observations? What are the statistical summaries? Do you have links please?
(Also, just to mention this: if CFR>9% for OUTBREAK_2022 then I would update pretty strongly towards “OUTBREAK_2022 was caused by either (1) GoF research or (2) some sort of nosocomial disaster where a clinic was spreading the worst variants to diseases to new patients in some sort of morbidity amplification process, and either way it would be good to start looking for the guilty parties, to correct them, if they can be found”.
An increase in mortality is not how diseases normally evolve, and would thus require some surprising/unusual cause to be true of an actual disease.)
...
SEPARATELY WHERE I HAVE LOW CONFIDENCE:
You seem to have assumed a low R, but my current state of knowledge here is: wide error bars and therefore maybe R is high?
A competent publicly funded infectious disease fighting system would have a pro-active responsibility to clearly falsify the bad parts of the plausible range very fast.
Then once the falsification of “bad possibilities” has occurred, they could properly BACK OFF on the “correct pre-emptive measures that one should take in the absence of coherent knowledge that we are very very very likely to be in the safe regime”.
I don’t personally currently have evidence that “the bad possibilities are clearly false based on definite observations”. If you know for sure that R is low, that would be a pleasant relief <3
Could you drop a link to thorough reasoning over adequate observations that makes it very clear that R_t < 1.15? :-)
Thanks for your thorough response. It is well-argued and as a result, I take back what I said. I’m not entirely convinced by your response but I will say I now have no idea! Being low-information on this, though, perhaps my reaction to the “challenge trial” idea mirrors other low-information responses, which is going to be most of them, so I’ll persist in explaining my thinking mainly in the hope it’ll help you and other pro-challenge people argue your case to others.
I’ll start with maybe my biggest worry about a challenge trial: the idea you could have a disease with an in-the-wild CFR of ~1%, that you could put 500 people through a challenge trial, and “very likely” none of them would die. With a CFR of 1%, expected fatalities among 500 people is 5. If medical observation and all the other precautions applied during a challenge trial reduces the CFR by a factor of 10, to 0.1%, your expected deaths is only 0.5, but that still seems unacceptably high for one trial, to me? To get the joint probability of zero deaths across all 500 people above 95%, you need closer to 0.01% CFR, (1−0.01%)500=0.951. Is it realistic to think all the precautions in a challenge trial can reduce CFR by a factor of 100 from 1% to 0.01%? I have no idea, perhaps you do, but I’d want to know before being feeling personally comfortable with a challenge trial.
Regaring R values and monkeypox generally, my understanding on this topic doesn’t go much beyond this post and the group of responses to it, so I’m pretty low-confidence on anything here. Thus, if you say the R is potentially quite high, I believe you.
I do have additional uncertainty about R. From public reports about the means of transmission that [say](https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON385) things like
I’d have to guess it’s going to be less infectious than covid, which had an R around 5? On the other hand, since OP asked the question, there’s more speculation about chains of transmission that seem to indicate a higher R. I acknowledge “lower than 5” is a high error!
Having said that, to my mind, I now feel very conflicted. Having read AllAmericanBreakfast’s comment and their headline, I felt reassured that monkeypox wasn’t much for the public to be worried about, and the CDC and WHO would figure it out. But on my own understanding, if R is high (as you say) and CFR is anywhere much above 0.1%, and there’s a widespread outbreak, that is pretty scary and we should all be much more on the alert than we already are?
And that would affirm your conclusion that challenge trials would be a good idea, as long as we have confidence the risk to participants is low.
Why is it assumed that diseases evolve towards lower mortality? Every new disease is an evolved form of an old disease, so if that trend were true we’d expect no disease to ever have noticeable mortality.
Lower mortality is just generally more efficient, even from the disease perspective. Typhoid Mary was a great success for the typhoid, precisely because it didn’t take her out or slow her down.
Over the long run, most diseases find a balance. The balance is almost never “kill the host really fast”. Your gut microbiome is basically made out of a bunch of “infectious diseases” that play nicely with their host. That’s the normal thing. Symbiosis is efficient and normal. Depending on how you count, there are 10s or 100s or 1000s of essentially friendly bacteria species in a modern human GI tract.
When a bat virus, like SARS or Ebola, jumps to humans, the species it came from often wasn’t even really bothered by it any more… but the disease does not start out in evolutionary equilibrium with humans.
Its is usually only only when you have high enough mixing (or a new kind of mixing over barriers of separation that previously kept things separate (or some idiot not inside a BSL5 does GoF research and mixes biological reality with their scary imaginations)) that ancient equilibriums of default symbiosis seriously break down.
Ah, so mortality almost always trends downwards except when it jumps species, at which point there can be a discontinuous jump upwards. That makes sense, thank you.