Amusingly, this is one of the few cases where - extremely broadly - one general idea of homeopathy works: you're basically just microdosing virus.
This is amusing because a lot of anti-vaxxers (at least in Germany) will also be into homeopathy.
There's possibly a good pro-vax-comms strategy in here: reframe vaccines as homeopathic viral microdoses (instead of complicated pharmaceutical compounds) and you might save a few kids.
That might increase belief in homeopathy, which is bad too.
Homeopathy beliefs are that the stronger the dilution, the more powerful the medication.
Homeopathy would be diluting the virus to the point where there's a strong probability of zero virus particles remaining in the "medicine" because of the belief the water has the memory of the virus.
This is false, because homeopathy has no effect other than placebo and placebo does not stop covid 19 deaths.
Homeopathy assumes that which causes likewise symptoms to be a candidate for cure, while here it is the idea of microdosing the disease, which hopefully would not case symptoms like the full blown disease, and the second tenant of homeopathy, the dilutions increase potency, would also hopefully be absent as that would be like the viral load factor, but in reverse.
Upon what evidence is this generalized statement based? Did you fact check it?
Note: I pose this question not as snark, or as some sort of a "disproof" of the "general truthiness" of your statement (with which I do not disagree, fwiw), but 100% literally.
Although vaccines aren't the same thing as variolation, and were developed because of the inherent risks of microdosing a dangerous pathogen. They are called "vaccines" because of the use of cowpox (a virus related to but much less dangerous than smallpox) in Jenner's vaccine and cow is "vacca" in Latin (similar to modern Spanish vaca).
> I am not anti-vax, but I understand why some parents do not want chemicals in their childrens bodies. I think instead of chemical shots, doctors should give a very small amount of the virus so the body can build up immunity.
Fascinating. Since I never paid attention in history class, I'll admit The Great did remind me of this practice. It's interesting people were experimenting with techniques likes this so long ago, when their understanding of medical science was so rudimentary compared to today.
These aren't to me the clearest Wikipedia pages, but I think I now understand that - in modern usage, ignoring origins - vaccination and inoculation are both types of immunisation; the latter using a sample of the thing to immunise against, while a vaccine is actually strictly speaking immunisation through other means, some other substance to the thing that should be immunised against?
I suppose I thought they were synonyms, but I certainly thought a vaccine was 'a bit of' the thing to immunised against, despite remembering Jenner and his cow.
> certainly thought a vaccine was 'a bit of' the thing to immunised against
A lot of the original vaccines were made from deactivated viruses. I don't know how that process works exactly, but your understanding isn't far off at least for how they were originally produced.
> A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins.
> The virus is killed using a method such as heat or formaldehyde.
> Whole virus vaccines use the entire virus particle, fully destroyed using heat, chemicals, or radiation.
> Split virus vaccines are produced by using a detergent to disrupt the virus.
> Subunit vaccines are produced by purifying out the antigens that best stimulate the immune system to mount a response to the virus, while removing other components necessary for the virus to replicate or survive or that can cause adverse reactions
But my understanding of these Wikipedia pages is that, if the deactivated virus is the same as the one it's designed to immunise against, then the treatment is properly termed an inoculation; not a vaccination (which would strictly speaking imply that it was a deactivated virus B administered in order to protect against a virus A)?
Additional trivia - Benjamin Franklin was a big proponent of inoculation. He tried to spread the awarness and convince people that it's safe and effective. Unfortunately his first son died of smallpox before he could be inoculated. He was 4 and developed some other infection, so BJ decided to wait with inoculation. Before he could perform it, he contracted the disease. It was huge blow to the credibility of BJ claims about inoculation, but he continued his mission nevertheless.
I think it is somewhat incorrect to call this vaccination, because the proper term for what was available in Benjamin Franklin's time was variolation, or inoculation.
An interesting tidbit about the origin of two terms from Wikipedia:
> Until the very early 1800s, inoculation referred only to the practice of variolation, the predecessor to the smallpox vaccine. Edward Jenner introduced the latter in 1798, when it was called cowpox inoculation, or vaccine inoculation (from Latin vacca = cow). Smallpox inoculation continued to be referred to as variolation (from variola = smallpox), whereas cowpox inoculation was referred to as vaccination (from Jenner's use of variolae vaccinae = smallpox of the cow).
I suppose the analogue of Jenner's cowpox innoculations would be infecting people with coronaviruses other than SARS-CoV-2 and hoping that the cross-immunity is helpful.
There is evidence for such cross-immunity, but not strong enough for this to be a strategy you'd bet on.
Benjamin Franklin wrote about the incident in his autobiography nearly a half-century later:
>> In 1736 I lost one of my sons, a fine boy of four years old, by the small-pox, taken in the common way.
>> I long regretted bitterly, and still regret that I had not given it to him by inoculation.
>> This I mention for the sake of parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it; my example showing that the regret may be the same either way, and that, therefore, the safer should be chosen.
Some things to note about variolation wrt Coronavirus:
- About a 2% death rate when used with Smallpox (compared to 20-30% without variolation), so we could expect mortalities from variolation with Coronavirus.
- You actually get infected with the virus, and are contagious, though the effects are lowered and you gain an immunity to the stronger/regular virus. So you'd still need to self-quarantine and people would need to still wear masks/do social distancing and close places with lots of people.
If you read Robin Hanson's blog post on the topic[1], he found data on other diseases:
> The most directly relevant data is on SARS[2] and measles[3], where natural differences in doses were associated with factors of 3 and 14 in death rates, and[4] in[5] smallpox, where in the 1700s low “variolation” doses given on purpose cut death rates by a factor of 10 to 30.
It looks like the initial dose size has a huge impact on mortality for a wide range of diseases.
This man is claiming that staying at home increases deaths... He's also claiming a vaccine could be years away.
I also see zero evidence as to why he should be considered a credible source for effective covid treatments. The man is an economist at a university. Am I looking at the wrong Robin Hanson?
The key argument is that there is lots of uncertainty, but variolation is probably worth trying. And if volunteers can be found, why not? One shouldn't need to be a virologist to credibly make that argument.
Well, for one, orthopoxviruses cause skin lesions, replicate in keratinocytes, dermal fibroblasts and other skin cells and evoke strong immune responses there. Coronaviruses don't.
I'm not a medicine professional, so I'm just curious here.
Since variolation has basically the same principle as vaccination, it's hardly an alternative to vaccination. Is it really worth trying?
To me (with my very crude understanding), proposing variolation as an alternative to vaccination is akin to proposing knife without a handle as an alternative to a regular knife.
Is there any case where vaccination fails to work, while variolation succeed?
>is it suggested to just deploy [variolation] without testing?
Yes: the blog post by economist Robin Hanson suggested deploying it without waiting for the results of testing. (Of course, it would be good to test as fast and as much as possible concurrent with the deployment.)
"deploying it": making available to the public a variolation service or procedure designed by medical experts.
If we're lowering the standard, why only lower it for inoculation? We can just start deploying the dozen+ vaccines we have in development too if we decide testing isn't important.
I'm pretty sure Robin Hanson would want challenge trials with experimental vaccines as well. The issue is that authorities won't allow such trials, not that there is a lack of willing medical experts or volunteers.
Though vaccine trials aren't quite as safe for the public as variolation. If a vaccine doesn't work, the person can spread the disease. If variolation doesn't work, then it has the same mortality as natural infection, but afterwards the person is immune and can't spread the disease.
The reason a vaccine is months or years away is only because we are testing whether it is safe enough to give to billions of people.
The reason we do that is because a virus can cause disease both directly but also in unexpected ways (e.g. by immune over-reaction to some of the viral RNA in some individuals).
Variolation as a public policy would have to go through the same safety testing for the same reasons (as it is a form of vaccination with un-weakened virus).
You would also still have to produce doses of the variolate, both in terms of replicating the virus and bottling it.
There is no real time advantage to variolation. Anybody making the case for variolation without validation would be better off making the case for vaccination with one or several of the 30 vaccine candidates under study for SARS-Cov-2 right now (a case could be made... allow volunteers to be given the candidate vaccine of their choice in larger numbers than normal clinical trials, scaling up as the risk profile of each candidate vaccine is known).
I am not an expert (but neither are you, I am guessing).
>Anybody making the case for variolation without validation would be better off making the case for vaccination with one or several of the 30 vaccine candidates under study for SARS-Cov-2 right now
The advantage variolation has over the 30 vaccine candidates, I am guessing if the question is what to do before the results of testing are available is that most of those 30 candidates will turn out after being tested to fail to confer significant immunity.
I believe that the fate of most vaccine candidates for any disease is that testing reveals that the candidate fails to confer immunity to most or all of the people it is given to. Also I believe that it usually takes at least a year to produce enough of a vaccine to test, then test, then analyze the results of the testing.
Tested for safety? We know what it does. It gives a low dose of the virus. If we know most people will get it anyway, then we don't need to know more than that in terms of either safety or efficacy.
A low dose could trigger an incomplete immune response leading to antibody dependent enhancement (ADE) on exposure to the virus in the future. Other Coronavirus are known to have that characteristic, we dont know if this strain does. Safety is making sure that we aren't priming people to get worse versions of the disease like what unfortunately happened with dengue.
Of the 79 infected, 19 died. E block (where the index patient was), had 53 infections and 15 deaths for a mortality rate of 28%. Other units had 26 infections and 4 deaths, for a mortality rate of 15%. The death rate of patients in E7 (closest to the index patient and with the highest viral load) was 70%. That's more than 4x difference in mortality based on viral load!
It would be very surprising if low doses of SARS-CoV-2 caused higher mortality. Therefore should allow researchers and volunteers to experiment with low dose deliberate infection. It could save hundreds of thousands of lives.
There are 30 candidate vaccines (probably a lot more by now). 32 if you include the two that are non-weakened forms of virus that are being proposed for variolation.
Having "candidate vaccines" is very different from having a "vaccine". Variolation is a reasonable alternative to the lack of a known, effective vaccine.
Variolation as a term only applies to smallpox. Giving small doses of the live virus as hanson suggests is literally just a lame vaccine. It's also not known to be safe or effective and would have to go through all the trials anyway.
You have to test variolation too. There are dozens of vaccine candidates, if we are willing to ignore safety and efficacy testing we can start vaccinating people today.
Not entirely accurate. We know variolation will provide immunity. The main risk is to the volunteer, not to others. A vaccine might not provide immunity. That would make the patient a vector for the disease and endanger others.
> Do we really? I don't keep up with the news, did we already dismiss those reports about re-infection? Does it last long enough to be globally useful?
It seems to be extremely rare, and it's hard to know how many of those cases are due to incorrect initial diagnosis or people with odd immune systems. Immunity seems to be much greater than that conveyed by vaccines (which protect 85-95% of recipients).
> The main risk, sure, but the volunteer will become infectious. Vaccines constrain the risk to volunteers a lot better.
In vaccine challenge trials, people are exposed to the virus and kept quarantined until after the incubation period. Those who aren't protected by the vaccine must remain quarantined until their immune system defeats the disease. It would be the same for deliberate infection. Volunteers wouldn't be allowed to leave until the virus is no longer detectable. Hanson makes this clear in his blog post (linked to at the top of this thread).
That said, most vaccine trials are not challenge trials. Researchers give patients the vaccine and wait a while to see how many of them naturally contract the disease. During that time, the patients may or may not have immunity and can potentially infect others.
He's an economist, sure, and is proposing an idea that others can consider and, perhaps, study. I am not looking to this blog post as a source of treatment ideas but instead as a source of ideas.
I've been reading about the importance of the viral load in survival against this disease. His proposed variolation approach is one I've personally considered. Much like families of old had chicken pox parties for their kids, the idea of just getting this over with as safely as possible has some appeal.
Yet it is an approach out of favor for good reason. For most diseases the risk can be significant and historically we've been able to improve survival via quarantine and treatment. This disease is apparently harder to quarantine due to a long latency period and asymptomatic cases. And we have no effective treatment for the worst cases.
It is interesting however to consider that for patients inoculated with preliminary vaccine, it is considered unethical to give a "challenge dose" of virus, while this guy proposes doing so for those with no protection whatsoever. I can't get past that, and am too risk averse to try his idea even in a carefully controlled setting. I'll keep wearing my mask, washing hands and wait it out for now.
There is hope that we will discover a variant of this disease which is less dangerous. In that case I think the approach he recommends is more reasonable.
Ah, RationalWiki. At least it makes Wikipedia look consistently fair and unbiased, I suppose. (Two thirds of that page read to me like "and this is why Hanson should be unpersoned")
Imagine an article on Obama's presidency that devoted a paragraph to his accomplishments, and then several pages to drone strikes on US citizens, use of torture, selling guns to Mexican drug lords, and keeping kids in cages. None of it's wrong, but it's really not a fair assessment.
As you said, Pox parties and all weren't exactly a brilliant solution - now your kid would be carrying the chickenpox virus amd have a risk of shingles later, and using things like saliva from lollipops means that your kids are also now at risk if getting all sorts of fun diseases like hepatitis. There's a reason we use vaccines. We dont know the long term risks of covid (case in point, recently it's become clear that it can trigger blood clots and strokes in otherwise low risk individuals, and the inflammatory syndrome in children is highly concerning). That's why we dont do challenge doses.
There are companies deliberately breeding strains that are less dangerous (attenuated strains) for use as a vaccine, so people are working on that actively. It's not one of the approaches further along in trials though.
He is not a credible source on this, or pretty much anything else. He has some utterly reprehensible views, and is part of a very questionable cult of self-important people.
Meh. I have never heard of him before, but he has a clearly expressed idea which isn't completely unreasonable. I evaluated the idea on its own merits, and that's where I found it lacking. The man matters nothing to me, only his idea.
I submit that this is the only reasonable way of evaluating ideas. We can't all be perfect for all time in history.
Edit. Having now read your link, I am less interested in following his blog, but my analysis of his proposal is unchanged knowing more about him.
Just to clarify further - the man cites nothing but his own blog articles but makes sweeping statements as though they are fact. This is speculation on medical approaches for an understudied virus by a man totally unqualified who feels it unnecessary to inform his audience as such.
When he shows any semblance of Skin in the Game and gets inoculated with the virus, then I will think about listening to him.
There is no amount of money that can be paid to someone where there is non-zero risk of dying or having long-lasting damages to your brain, heart or lungs.
> There is no amount of money that can be paid to someone where there is non-zero risk of dying or having long-lasting damages to your brain, heart or lungs
This is trivially false, as people accept money for health risk every day (see: working in medicine, transportation, mining, leaving your house, etc.)
The risks you mentioned are in no way a direct consequence of the actions people take. No one goes to work in medicine with the purpose of getting infected.
Do not think this rhetorical BS trap is believable for a second. This is the kind of crappy thinking and morality that economists and Robin Hanson proponents defend and pat themselves in the back for sounding oh-so-smart.
Regardless of whether death is a direct consequence or an outside risk from the action you’re still just as dead. It might matter for the court system assigning blame but it doesn’t matter from an economic perspective.
> It might matter for the court system assigning blame but it doesn’t matter from an economic perspective.
Right. To which I say that anyone that only looks at things from the economic perspective is an immoral hack that should never be listened to.
Every larger issue, dear to either conservatives or progressives alike, can find its roots in and be justified by some moron looking for solutions exclusively via an economic perspective. It's a danger to society, plain and simple.
It's a global pandemic. We all have skin in the game whether we want to or not. Unless you're suggesting that before writing a blog post, he should do some amateur virology and variolate himself, I'm not sure what point you're trying to make. If you're trying to say Robin Hanson would see this implemented and then not be among the first volunteers, I think you don't know Robin Hanson.
I mean "Skin in the Game" in the Talebian sense, so yes, I am saying that he may write anything he wants, but I will only give any credit to his ideas if he actually follows through himself, or at the very very least if he accepts responsibility for any damage that he's done and is penalized accordingly.
Losing money in a prediction market does not count as a proportional penalty for the damage that he might be causing to others.
I know very well what you meant, and yet I still struggle to see what you're actually suggesting that he should have done, besides what he did, which was write a blog post about an interesting idea.
Can you actually make a concrete suggestion or are you just blathering because you don't like the guy? The only concrete thing I can see in your comment is that you won't "give any credit to his ideas" unless he, presumably, tries it himself first (how?).
And what exactly is this terrible damage that he might be causing to others by raising awareness of this idea? Are we afraid of infection from blog posts now?
He would be showing a modicum of Skin in the Game if he actually went to infect himself and those close to him with the virus before encouraging others to normalize such a risky experiment.
> Are we afraid of infection from blog posts now?
He is not just "raising awareness" of the idea of variolation. His writing was already trying to argue that government could try a program where volunteers would get paid to be infected.
When asked "if you think this is a good idea, why don't you do it yourself?" he responded with something along the lines of "there is no counterparty to bet with me on it, so what is the point?" Isn't that the answer of someone completely oblivious to the idea of SITG?
He's suggesting a program of trained medical professionals, isolation, observation, and you think he just ought to go off and infect himself in uncontrolled conditions without any medical training or control group? One of the two of you hasn't thought this through, and I'm pretty sure it's you.
How to infect himself? A short walk in a busy hospital would take care of that quickly... but that really doesn't matter for the argument.
> He's suggesting a program of trained medical professionals, isolation, observation (...) he just ought to go off and infect himself
Yes, that is the point! He is suggesting something that medical experts already consider dangerous and unethical, otherwise it would already be done. He wants medical experts give some veneer of science to something completely immoral just by seeking higher financial compensation to those that might be affected.
So what he is "proposing" involving everyone else taking a lot more risk, without any real consequence for him. This is no display of SITG, quite the opposite. He just sees it as a game of "Heads some might lose their life, but tails we might win a little, so let's find the price point where this is even".
By asking if he is willing to infect himself to do it, it is not a matter of doing it for the science or the economics of betting. It is just a pure ethical filter: "So far your words only risk the lives of others, but if you really think this is the best course of action then you need to demonstrate you are willing to put your ass on the line. Can you?"
You demonstrate utter failure to understand the idea. A controlled, known, small viral load is the idea. Controlled: not from a random walk through a hospital, but administered under controlled conditions. Known: a measured quantity, not an unknown quantity from a random walk through a hospital, of a known viral strain. Small: maybe 1/50th the kind of load you would get if you were exposed in a busy hospital and someone sneezed on you.
You so spectacularly missed all these points that it's clearly not worth continuing this conversation further.
You are focusing on the practicality of the whole argument while I am trying to show that the practicality of it is irrelevant if the whole idea is immoral and starts from wrong principles.
Let me try again: there is a reason that no one is doing "small, controlled, small virus load experiments": it is because they are illegal, unethical and potentially bring more harm than benefit. If they are supposed to be done properly, they should be done with the same standards that are adopted for those that want to develop vaccines and other medicines.
What Hanson is proposing requires doctors and scientists to drop already established ethical principles and adopt practices that have unknown risks and can be potentially catastrophic.
He puts it as the whole "we already test vaccines on humans, and vaccines are made from the virus itself, so why not just test the actual virus" was just an issue of testing on dosage/response. He wants to argue that the risk people take is just proportional to the amount of contact they have to the virus.
It is not. Just as an example: suppose that inoculation by a weak version of the virus does not help our immune system to create antibodies and just instead make us more susceptible to a future, more lethal mutation of another Coronavirus? This is a very-tiny-but-plausible possibility, and that alone should stop us from abandoning current safe practices for research.
He wants you and I and other doctors to just squint our eyes and pretend it is okay to do what he is proposing if the participants take a little bit more risk (compared to drug trials conducted ethically) and that just by compensating them properly, it would be fair and ethical.
It is not. Trials for drugs and vaccines go through a bunch of other steps before to try to determine its safety on humans. He sidesteps the whole thing and wants medical practices to go back centuries in time for no good reason other than "economic theory"
---
So, we have this guy who is trying to convince others to take risks of unknown magnitude and to break traditional practices with unknown benefit. We have this guy who is willing to play fast and loose with the rules without ever facing any consequence of the potential downside of these measures.
What do you do with it? What I am saying is that anything he is defending should not have any weight until he shows willingness to face the consequences of his risky proposal. And given that we do not know the behavior of the virus and we do not know what are the "safe" parameters for it, the only way that he can show SITG is by facing the highest possible risk.
This is why I say I don't particularly care about the practicality of it all. There is no way to quantify the risk anyone is being exposed to it, so whoever is asking others to take the risks should give the example by taking the maximum risk possible. And it is not that he is making himself "more right" or "less wrong" (pun intended) if he does show SITG. It is just that I am just allowing myself to take any risky proposal into consideration when those doing the proposal are also facing the risks. It is a simple filter.
I hope at least now I could make myself clearer. Thanks for the discussion anyway.
> the practicality of it is irrelevant if the whole idea is immoral
Agreed.
I didn't read his post as saying that the payment had anything to do with the ethics of it, and we routinely pay participants in clinical trials for their time. I don't see the idea as something that's impossible to do ethically, and you do, but apart from that we are in agreement. Thanks to you too.
I'm guessing he isn't doing it himself because he's 61 years old. His odds of dying are maybe 10-100x higher than the perfectly healthy twentysomethings that he's proposing for an initial trial.
Well, he is the one that is arguing that there is some linearity between cost-benefit of such a research. So following his own reasoning, as long as he gets 10x-100x bigger payment compared to a twentysomething, all is good and clean.
There are moral considerations to be done before proposing something ridiculous like what he is doing, and yet he is trying to reduce all ethical considerations into a "simple" matter of economics. Life can not be reduced to spherical cows and trolley problems.
> There is no amount of money that can be paid to someone where there is non-zero risk of dying or having long-lasting damages to your brain, heart or lungs.
Hard disagree based on experience. The clinical testing of many drug classes are entirely dependent on many people being too uneducated or desperate to consider those types of risks.
The fact that something is possible or economically advantageous does not make it moral.
In the crazy scenario that I had to participate in drug trials, I would instate a pretty simple rule: I would only accept those substances if everyone involved in the drug creation and test taking had themselves participated in the trial.
> "In the crazy scenario that I had to participate in drug trials, I would instate a pretty simple rule: I would only accept those substances if everyone involved in the drug creation and test taking had themselves participated in the trial."
That's a simple rule, but it's ridiculous. The costs and benefits of taking a new drug are heterogeneous. Do you think people who develop anti-psychotics should be required to take anti-psychotic medications they have no need for?
No. I do not think that. It does not make my statement invalid. Does it?
(Come to think of it, it is interesting to see how the US is so addicted to pills and the opiate epidemic. The doctors are free to prescribe willingly, receive incentives from pharma companies and there is almost zero downside paid by them for those that get addicted. Don't you think this would be a much smaller problem if there was a way to get Skin in the Game from the doctors and companies and make them pay for cases of opiate abuse?)
Anyway, I was thinking of drugs that may affect anyone, like treatments for common diseases. For those, the idea is that I would like to have some sense of symmetry in the risk taking for all parties.
As perhaps a better way illustrate what I mean: whenever I had to take my kids to the pediatrician, I would listen to the doctor's recommendations and would ask "If it was your kid, would you still do the same you are telling me?"
Here in Germany the practices are way more conservative and less pill-happy in the US, so I can't recall any time where the doctor would propose something that was not willing to apply to one of her own. In Brazil, however, I do remember in 2017 during an outbreak of Yellow Fever when I everyone was rushing to the hospitals to get a vaccine. I talked to a nurse who basically said "If it was my kid, I wouldn't give it. The side-effects are too strong and it is only sensible if you live really close to the Forest." The doctor later confirmed, and we walked out.
One thing to point out is that, as the wikipedia article makes clear, variolation refers explicitly to inoculation with smallpox. What he is proposing is literally just a really mediocre vaccine. Instead of killing or weakening the virus, or expressing subunits to build immunity against, hes suggesting just vaccinating with the normal live virus. And by exposing to a very low dose, it might not even be enough to trigger a strong enough immune response to generate long term memory against the virus, since we're already seeing people with little or no antibody response after getting sick. So of course wed need a rigorous, well run trial to evaluate this, at which point what's the advantage compared to a well made vaccine again? You don't get to have lower standards for your vaccination approach because you call it something else incorrectly.
It's actually even harder, as the starting point is much, much worse. That's the reason the modern vaccines were developed: they are much safer from the very start. We simply know much more today than at these times, so we can know (almost) exactly what is going on in the building blocks, and actually use the building blocks and track the effects of the building block without ever having the risk of having to handle and manage the more dangerous thing -- the complete, fully functioning and easy to spread virus -- applying it to every human that we want to "protect".
In analogy world for the modern vaccines, imagine a science fiction scenario: the evil aliens look like humans, can and want to easily kill them, but look exactly like humans and we don't know how to recognize them. Variolation is like catching them but them setting them free to go around and kill more in order to train us, expecting that it is possible to set free small enough number of them over and over so that in the fight we will "manage somehow" to win and also learn something while fighting, wheres, producing modern vaccines is like just finding out that the evil aliens look differently in infrared light and just teaching us to use infrared cameras to locate them, completely avoiding the real additional fights among the population "just for training."
Variolation, as defined in the article, was the best method that we knew a few centuries ago, but now we simply know much more now. And solving the problem is still complicated enough even with the "better start." We want to minimize false alarms, friendly fire etc. practically, we know what we want and how to measure it and we do all we can to minimize the number of bad outcomes.
Variolation is a form of vaccination like any other (a treatment given to healthy individuals) so is subject to all the safety requirements of any other vaccine. So its an idea for a vaccine but it's not a magical shortcut compared to all the other vaccines under development (some of which are based on attenuated virus).
Epidemiologists and virologists have literally dedicated their lives to effectively containing and dealing with infectious agents. Other medical doctors have focused at least a decade of intense study on the human body and the processes by which human life perpetuates and ends.
But by all means, let's all presume that an economist like Robin Hanson—whose primary interest it would seem to be opening up commerce during a pandemic—has somehow come up with an idea that has escaped the notice of that entire segment of the population dedicated to human health.
Let's ask Mike Pence about his thoughts on the use of bloom filters as relational database indexes while we're at it. I'm sure he'll point out that mauve seems to have the most RAM.
I'm a physicist and I cringed hard when the HEP people in my department started pushing out arXiv papers about covid-19. I see this a lot in CS too. It's easy for people in these more abstract fields to look at another problem space and see patterns that remind them of their own work. They seem to discount experience and familiarity.
Sometimes you need an outsider. I don't think that the issue with this is scientific -- basically we know that it might work, but we'd have to test it to know. The problem is that medical ethics deviates from everyday ethics, and also ethics in other government regulated fields.
This is mostly the legacy of Josef Mengele and to some extent the Tuskegee experiment, but collectively we essentially said "we never want to do that again, so let's make rules that keep us well away from that line."
The reason the idea isn't getting much attention is that anyone in the field that is serious knows that the study would never get past an Institutional Review Board, so it's pointless to even try.
It seems to me that we need to revisit our tenets of medical ethics in borderline cases like this one, where the stakes are so high. To me, you should be able to do riskier experiments in these cases if the subjects are truly informed volunteers, and you keep the risk to them to an absolute minimum consistent with doing the experiment. There's a very similar issue with vaccine challenge trials.
The thing is, we already are doing way riskier experiments to deal with COVID. We sent the Moderna vaccine into human trials with barely any mouse data at all. What Hanson is proposing is giving his pet approach, inoculation with live virus, special treatment. The reason we're not pouring time and money into validating inoculation is because we have literally dozens of vaccine platforms, some with decades of evidence backing them up, that promise far higher theoretical safety and efficacy than inoculation's theoretical safety and efficacy. We'd rather pour our focus into approaches like moderna's vaccine, which could be highly scalable, and J&Js vaccine and AstraZeneca's vaccine because those platforms are known to work in other diseases. We've got companies like Codagenix using the tools of molecular biology to create attenuated forms of the virus without tradition time consuming development techniques. When we already have these candidates developed and have them barreling forward, why would anyone want to spend time and effort developing and testing a worse approach? The risk/reward doesn't make sense.
Yes, but it's uncertain when those vaccines will be available or whether they will work. Even as a backup plan, it makes sense to me to evaluate variolation. With millions of lives worldwide and the entire global economy on the line, you do not want to put all your eggs into even ten baskets.
As for the time and effort, I'm assuming that the existing vaccine developments are adequately staffed. There are many other medical researchers that are working on other things that could work on this.
As someone that makes a living at the intersection of a couple of different fields maybe that is true. But the last person to take advice from is an academic economist. We literally have thousands of different trained professionals working on this right now and NONE of them think what Robin Hanson wants to do is a good idea.
You are misconstruing Hanson. He's not saying that we should mass-variolate tomorrow. He just wants it to be legal for such experiments to be tried (including experiments with unproven vaccines). There are doctors and domain experts who are willing to try this approach, and there are volunteers who are willing to be infected. The problem is that our institutions have made such trials illegal.
It looks like at least half the population will contract this disease over the next couple of years. Around 0.5% of those will die. If we wait until an extremely safe vaccine is mass produced, far more lives will be lost than if we use methods that the authorities consider unsafe. The main issue seems to be that people attribute COVID-19 deaths to nature, while they blame any experimental immunity deaths on the researchers. It's the same logic that anti-vaxxers use. Yes, some vaccines do have side-effects and every once in a while, someone does die from them. But that's a far better outcome than the disease itself, so we accept the tradeoff.
As I said, in this emergency, around 0.5% of people infected will die. That means that a treatment with a 0.1% mortality rate would reduce overall deaths by 4x! That's a far more effective intervention than say... ventilators (which only reduce mortality by around 20%). Yet no government will allow volunteers to get a treatment with such a high mortality rate, so we're all stuck with "natural" infection and its 0.5% mortality. This is peacetime thinking in the middle of a war.
It should be clear by now that our institutions have failed us. The CDC & FDA forbade researchers from testing for a month. It's only because some researchers decided to break the law that we discovered community spread when we did.[1] The Surgeon General repeatedly told the public that masks don't work.[2][3] The WHO said the same thing.[4][5]
If we judged these institutions by the same standard that people in this thread are using for Robin Hanson, we'd want to drastically curtail their power and allow for more experiments. That's exactly what Hanson is proposing.
Folks are still justifiably gun shy about Tuskegee and the various eugenicist procedures from the 20th century. The reason we have restrictions on this kind of thing is precisely because it has been grossly abused whenever it has been permitted in the US.
And yet it's still being discussed, not dismissed outright by the experts. I for one am happy with allowing epidemiologists and virologists to lead the discussion, but not economists and political appointees. No way.
Trump has so far advocated for not wearing masks, inciting armed (white) citizens to storm state capital buildings, the use of hydroxychloroquine despite being found now to be worse than ineffective, sidelined Fauci (going so far as to retweet a call for his removal), and other nonsense, all to boost economic numbers for November and/or fulfill a (toxic) political ideology. And you want the likes of him to determine the best course of action for fighting disease?
F— that noise. If the health research community looks at the problem and decides it's a good idea, I'm on board. Everyone else can take a huge fat seat in their La-Z-Boy and STFU about how soon human trials should begin.
See earlier note about political appointees, especially by this administration. This isn't about health for them; it's about PR. Countries where its citizens wear masks have done much better against the disease. Countries where citizens claim "freedom" from wearing masks have just tallied 100,000 deaths so far.
Japan has an extremely high population density. One of the highest proportions of elderly citizens in the world. Had cases arrive earlier there than in the US, so less warning. 869 deaths so far total.
Why?
For the most part, masks. Everywhere. Everyone. That and not waiting until it was too late to shut down public gatherings and schools. In other words, they had adults in charge and its citizens don't treat basic precautions like masks as some sort of tyrannical plot against democracy. (Last I checked, Japan was still a democracy.)
The best way to prevent the spread of viruses like Corona is to put everyone in a straightjacket and chain them to the floor in their home. Epidemiologists will keep saying people need to stay inside because that’s safer.
You need the other people to have a voice as well because you can’t live and eliminate all risks at the same time.
> The best way to prevent the spread of viruses like Corona is to put everyone in a straightjacket and chain them to the floor in their home. Epidemiologists will keep saying people need to stay inside because that’s safer.
This is a hyperbolic take on shelter in place orders and wearing masks. You have replaced the actual recommendations and public orders with a call for complete removal of bodily autonomy even though this was never the case. At no time were people unable to drive to the grocery store for example. They were however restricted from congregating at the beauty salon because of obvious issue with viral transmission.
You have substituted "we need to take precautions as a society" with "let's remove everyone's ability to use their arms and move more than a few feet". Then you went on to suggest that this is akin to what epidemiologists would have us do if given their preference.
If you honestly believe what is happening now is just a precursor to your replacement premise, profound elimination of bodily autonomy, this would fall under another common logical fallacy known as the slippery slope.
> You need the other people to have a voice as well because you can’t live and eliminate all risks at the same time.
Has anyone said, "We want to eliminate all risks"? Has anyone said, "Hanson must not be allowed to speak"?
No. The actual proposed arguments have been, "We want to mitigate risk while looking more closely at what the risks levels actually are," and "Hanson is an economist, not a medical professional who has dedicated their life to the study of infectious disease; therefore his opinion should not carry as much weight as theirs."
So you see? The actual arguments have been substituted for your more hyperbolic and untenable remarks. The hyperbolic remarks are then refuted, not the original arguments.
> You have replaced the actual recommendations and public orders with a call for complete removal of bodily autonomy even though this was never the case.
Scientists do not put out orders, that is the job of politicians. Science can only tell you, if you this you run the risk of that. A proper scientist would tell you the only way to avoid being infected or infecting others is to be chained into place.
> Has anyone said, "We want to eliminate all risks"?
People won’t say ‘we want to eliminate all risks’ but if the consequences are presented as being scary enough, they will take any action to avoid them, which factually is the same thing. Concretely many people want to ‘shelter in place’ until there is no more risk they can be infected and a lot of these people want everyone else to do that as well.
It is the job of politicians to evaluate these risks properly and for that they need to listen to both medical scientists, like epidemiologists, so they know what risks they can avoid using their orders, but also economists so they know what costs they incur by these orders.
It should be clear that if they do not do this properly the result can be taking measures that are unsustainable or incur new, worse risks.
> Has anyone said, "Hanson must not be allowed to speak"?
> But by all means, let's all presume that an economist like Robin Hanson [...] has somehow come up with an idea that has escaped the notice of that entire segment of the population dedicated to human health.
If Robin Hanson speaks he must be ridiculed because what could he possibly have to bring to the table that no one has thought of before (and then I even cut out the vague insinuations about his motives).
But anyway I have no idea who he is and did not refer to him in my comment. My only point is that if you immediately dismiss the input of economists and others outside medical science, you’re only looking at one side of the story and are bound to take poor decisions.
False dichotomy. Not only are there more than two options, looking to economists among others without medical training on epidemiological matters as though they should have equal standing is asinine. Dunning-Kruger applies here. As said before, might as well ask Mike Pence whether bloom filters are an effective relational database indexing strategy.
"There is a cult of ignorance in the United States, and there always has been. The strain of anti-intellectualism has been a constant thread winding its way through our political and cultural life, nurtured by the false notion that democracy means that “my ignorance is just as good as your knowledge.”"
– Isaac Asimov
> Doctors sought to monopolize the simple treatment by convincing the public that the procedure could only be done by a trained professional. The procedure was now preceded by a severe bloodletting, in which the patient was bled, often to faintness, in order to 'purify' the blood and prevent fever. Doctors also began to favour deep incisions [versus superficial scratches], which also discouraged amateurs.
Variolation refers specifically to smallpox. The terminology for a similar approach against COVID is "inoculation" not "variolation." I understand the proponent of it for COVID is an economist and not a medical professional, but keeping the terminology clear is important to avoid confusion. Inoculation is not guaranteed to be effective against covid. Just because there was a version of it called variolation that worked against smallpox before being eliminated because it was not as good as other approaches does not mean inoculation is automatically safe and effective against a completely unrelated virus. Other coronavirus are known to display antibody dependent enhancement, where a weak immune response makes following infections worse, and we already don't see consistent, strong responses from people who were sick.
What the economist Hanson is essentially suggesting is that we take a worse method of immunization (just the normal live virus) and waive the regulatory burden to show safety and efficacy because a similar approach worked with smallpox. If we are getting into the business of ignoring the requirement for an immunization approach to be clinically validated, then there are a few dozen vaccines with far better theoretical safety and efficacy profiles that we should be using instead. The reason a vaccine isn't coming immediately is because we have to show they wont kill people and that they'll work, and then we have to scale up production. You dont get to rebrand your worse vaccine approach as "variolation" and then say it should be held to a different standard so you can get the economy humming again.
Thanks for making the point about the name. I got in touch with Hanson after his blog post[1] and co-authored a proposal with Hanson and three doctors on low-dose inoculation of respiratory system, gut or skin[2]. We ended up not using the name Variolation since it has too many connotations and it's necessary to distinguish modes of inoculation for vaccination.
I think Hanson's blog post[1] about the general idea of variolation was useful to get discussion going but agree that as stated it was not a good approach.
In contrast, the proposal we developed subsequently focused on making use of human challenge trials[3] (where the control arm of the clinical trial is actively exposed to the pathogen) to search for safer forms of inoculation, hopefully benign.
I disagree with your point that live virus is necessarily a worse form of immunization; I think it actually depends on the route of inoculation and on finding a reasonable dose. I am working on the skin route separately[4] and from this I've learned live-viruses are used in some (many?) of the most successful vaccines (adeno, polio, measles, smallpox)[See appendix in 4.1]. In polio and measles the virus was attenuated, but in the case of adenovirus, it's used in its original wild-type form and inoculated into the gut via oral dose to avoid the primary respiratory infection. Adenovirus is also notable for comparison as it causes an ARDS-like condition and the gut infection (benign diarrhea and fever) was considered secondary and acceptable enough that the US Military doses all recruits this way since the 80s. And although smallpox variolation had relatively high mortality rates, it's unclear how specific the methods in use were. It's possible that the primary (respiratory!) infection wasn't avoided e.g. by the methods of scab snuff (ew!). Lastly, non-live virus vaccines may not provoke a sufficient immune response, e.g. in the killed polio vaccine that was eventually retired. I think this is generally a concern for potential synthetic CoV vaccines as well.
So it seems like the idea from smallpox and adenovirus is to inoculate where the body has a good chance of dealing with the infection (skin and gut, respectively) when the primary infection (respiratory in both cases) is dangerous and there aren't better alternatives. I'm working on the skin route since it seems plausible (it appears skin can be infected by CoV2) and the least risky (almost all reports of associated infections are benign; though there are some reports of skin tissue necrosis). The gut route is also interesting but in my opinion we're too early in the clinical understanding to prioritize it since it is often associated with the primary infection.
I'm just starting to treat this as an open-source project[5]. Please feel free to join!
The use of human challenges get trials is a very different situation, and the decision of whether or not to engage in one is definitely a question where economists and ethicists have a lot to contribute, I'm glad you're engaged in the conversation. Its a tough utility/risk-reward/ethics question, where we'd be able to speed up development of immunization approaches by a LOT, but with a virus we still don't fully understand and that keeps surprising us. Definitely a decision that needs cross discipline input and discussion.
It's not a totally different situation. In fact, since with a human challenge trial, you're probably going to be inoculating both arms of the trial with a variable dose, you can use the data from the control arm of the challenge trial as essentially a phase 1 of the variolation trial.
121 comments
[ 3.7 ms ] story [ 180 ms ] threadHomeopathy beliefs are that the stronger the dilution, the more powerful the medication. Homeopathy would be diluting the virus to the point where there's a strong probability of zero virus particles remaining in the "medicine" because of the belief the water has the memory of the virus.
This is false, because homeopathy has no effect other than placebo and placebo does not stop covid 19 deaths.
Homeopathy assumes that which causes likewise symptoms to be a candidate for cure, while here it is the idea of microdosing the disease, which hopefully would not case symptoms like the full blown disease, and the second tenant of homeopathy, the dilutions increase potency, would also hopefully be absent as that would be like the viral load factor, but in reverse.
Note: I pose this question not as snark, or as some sort of a "disproof" of the "general truthiness" of your statement (with which I do not disagree, fwiw), but 100% literally.
https://twitter.com/Golfergirl2018/status/121690584817960960...
> I am not anti-vax, but I understand why some parents do not want chemicals in their childrens bodies. I think instead of chemical shots, doctors should give a very small amount of the virus so the body can build up immunity.
I suppose I thought they were synonyms, but I certainly thought a vaccine was 'a bit of' the thing to immunised against, despite remembering Jenner and his cow.
A lot of the original vaccines were made from deactivated viruses. I don't know how that process works exactly, but your understanding isn't far off at least for how they were originally produced.
https://www.who.int/blueprint/priority-diseases/key-action/n...
Check out the history of the Rabies vaccine, where the virus was weakened through aging:
> derived from the spinal cord of an inoculated rabbit which had died of rabies 15 days earlier.
https://en.wikipedia.org/wiki/Rabies_vaccine#History
> A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins.
https://en.wikipedia.org/wiki/Inactivated_vaccine
> The virus is killed using a method such as heat or formaldehyde.
> Whole virus vaccines use the entire virus particle, fully destroyed using heat, chemicals, or radiation.
> Split virus vaccines are produced by using a detergent to disrupt the virus.
> Subunit vaccines are produced by purifying out the antigens that best stimulate the immune system to mount a response to the virus, while removing other components necessary for the virus to replicate or survive or that can cause adverse reactions
> Until the very early 1800s, inoculation referred only to the practice of variolation, the predecessor to the smallpox vaccine. Edward Jenner introduced the latter in 1798, when it was called cowpox inoculation, or vaccine inoculation (from Latin vacca = cow). Smallpox inoculation continued to be referred to as variolation (from variola = smallpox), whereas cowpox inoculation was referred to as vaccination (from Jenner's use of variolae vaccinae = smallpox of the cow).
The article goes on to explain how the meanings of the terms have since expanded: https://en.m.wikipedia.org/wiki/Inoculation
There is evidence for such cross-immunity, but not strong enough for this to be a strategy you'd bet on.
>> In 1736 I lost one of my sons, a fine boy of four years old, by the small-pox, taken in the common way.
>> I long regretted bitterly, and still regret that I had not given it to him by inoculation.
>> This I mention for the sake of parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it; my example showing that the regret may be the same either way, and that, therefore, the safer should be chosen.
- About a 2% death rate when used with Smallpox (compared to 20-30% without variolation), so we could expect mortalities from variolation with Coronavirus.
- You actually get infected with the virus, and are contagious, though the effects are lowered and you gain an immunity to the stronger/regular virus. So you'd still need to self-quarantine and people would need to still wear masks/do social distancing and close places with lots of people.
> The most directly relevant data is on SARS[2] and measles[3], where natural differences in doses were associated with factors of 3 and 14 in death rates, and[4] in[5] smallpox, where in the 1700s low “variolation” doses given on purpose cut death rates by a factor of 10 to 30.
It looks like the initial dose size has a huge impact on mortality for a wide range of diseases.
1. http://www.overcomingbias.com/2020/03/variolation-may-cut-co...
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367618/
3. https://pubmed.ncbi.nlm.nih.gov/3723239/
4. https://www.nlm.nih.gov/exhibition/smallpox/sp_variolation.h...
5. https://www.npr.org/sections/goatsandsoda/2018/02/01/5823701...
http://www.overcomingbias.com/2020/03/variolation-may-cut-co...
I also see zero evidence as to why he should be considered a credible source for effective covid treatments. The man is an economist at a university. Am I looking at the wrong Robin Hanson?
The key argument is that there is lots of uncertainty, but variolation is probably worth trying. And if volunteers can be found, why not? One shouldn't need to be a virologist to credibly make that argument.
https://docs.google.com/document/d/1x91Ef7G6xbm77DcRDvjAXbFm...
Since variolation has basically the same principle as vaccination, it's hardly an alternative to vaccination. Is it really worth trying?
To me (with my very crude understanding), proposing variolation as an alternative to vaccination is akin to proposing knife without a handle as an alternative to a regular knife.
Is there any case where vaccination fails to work, while variolation succeed?
Yes: the blog post by economist Robin Hanson suggested deploying it without waiting for the results of testing. (Of course, it would be good to test as fast and as much as possible concurrent with the deployment.)
"deploying it": making available to the public a variolation service or procedure designed by medical experts.
Though vaccine trials aren't quite as safe for the public as variolation. If a vaccine doesn't work, the person can spread the disease. If variolation doesn't work, then it has the same mortality as natural infection, but afterwards the person is immune and can't spread the disease.
There is no real time advantage to variolation. Anybody making the case for variolation without validation would be better off making the case for vaccination with one or several of the 30 vaccine candidates under study for SARS-Cov-2 right now (a case could be made... allow volunteers to be given the candidate vaccine of their choice in larger numbers than normal clinical trials, scaling up as the risk profile of each candidate vaccine is known).
>Anybody making the case for variolation without validation would be better off making the case for vaccination with one or several of the 30 vaccine candidates under study for SARS-Cov-2 right now
The advantage variolation has over the 30 vaccine candidates, I am guessing if the question is what to do before the results of testing are available is that most of those 30 candidates will turn out after being tested to fail to confer significant immunity.
I believe that the fate of most vaccine candidates for any disease is that testing reveals that the candidate fails to confer immunity to most or all of the people it is given to. Also I believe that it usually takes at least a year to produce enough of a vaccine to test, then test, then analyze the results of the testing.
https://www.pnas.org/content/117/15/8218
https://en.m.wikipedia.org/wiki/Dengvaxia_controversy
Of the 79 infected, 19 died. E block (where the index patient was), had 53 infections and 15 deaths for a mortality rate of 28%. Other units had 26 infections and 4 deaths, for a mortality rate of 15%. The death rate of patients in E7 (closest to the index patient and with the highest viral load) was 70%. That's more than 4x difference in mortality based on viral load!
It would be very surprising if low doses of SARS-CoV-2 caused higher mortality. Therefore should allow researchers and volunteers to experiment with low dose deliberate infection. It could save hundreds of thousands of lives.
If there was, no one would consider variolation.
I'm working on just such a public proposal [1] and have been in correspondence with Hanson but haven't heard of any registered.
[1] "SARS-CoV2 Live Virus Skin Vaccine" - https://tinyurl.com/y8ujrcze
Do we really? I don't keep up with the news, did we already dismiss those reports about re-infection? Does it last long enough to be globally useful?
> The main risk is to the volunteer, not to others.
The main risk, sure, but the volunteer will become infectious. Vaccines constrain the risk to volunteers a lot better.
It seems to be extremely rare, and it's hard to know how many of those cases are due to incorrect initial diagnosis or people with odd immune systems. Immunity seems to be much greater than that conveyed by vaccines (which protect 85-95% of recipients).
> The main risk, sure, but the volunteer will become infectious. Vaccines constrain the risk to volunteers a lot better.
In vaccine challenge trials, people are exposed to the virus and kept quarantined until after the incubation period. Those who aren't protected by the vaccine must remain quarantined until their immune system defeats the disease. It would be the same for deliberate infection. Volunteers wouldn't be allowed to leave until the virus is no longer detectable. Hanson makes this clear in his blog post (linked to at the top of this thread).
That said, most vaccine trials are not challenge trials. Researchers give patients the vaccine and wait a while to see how many of them naturally contract the disease. During that time, the patients may or may not have immunity and can potentially infect others.
I've been reading about the importance of the viral load in survival against this disease. His proposed variolation approach is one I've personally considered. Much like families of old had chicken pox parties for their kids, the idea of just getting this over with as safely as possible has some appeal.
Yet it is an approach out of favor for good reason. For most diseases the risk can be significant and historically we've been able to improve survival via quarantine and treatment. This disease is apparently harder to quarantine due to a long latency period and asymptomatic cases. And we have no effective treatment for the worst cases.
It is interesting however to consider that for patients inoculated with preliminary vaccine, it is considered unethical to give a "challenge dose" of virus, while this guy proposes doing so for those with no protection whatsoever. I can't get past that, and am too risk averse to try his idea even in a carefully controlled setting. I'll keep wearing my mask, washing hands and wait it out for now.
There is hope that we will discover a variant of this disease which is less dangerous. In that case I think the approach he recommends is more reasonable.
There are companies deliberately breeding strains that are less dangerous (attenuated strains) for use as a vaccine, so people are working on that actively. It's not one of the approaches further along in trials though.
https://rationalwiki.org/wiki/Robin_Hanson
I submit that this is the only reasonable way of evaluating ideas. We can't all be perfect for all time in history.
Edit. Having now read your link, I am less interested in following his blog, but my analysis of his proposal is unchanged knowing more about him.
How else can one describe fraud?
https://rationalwiki.org/wiki/Robin_Hanson
There is no amount of money that can be paid to someone where there is non-zero risk of dying or having long-lasting damages to your brain, heart or lungs.
This is trivially false, as people accept money for health risk every day (see: working in medicine, transportation, mining, leaving your house, etc.)
Do not think this rhetorical BS trap is believable for a second. This is the kind of crappy thinking and morality that economists and Robin Hanson proponents defend and pat themselves in the back for sounding oh-so-smart.
Right. To which I say that anyone that only looks at things from the economic perspective is an immoral hack that should never be listened to.
Every larger issue, dear to either conservatives or progressives alike, can find its roots in and be justified by some moron looking for solutions exclusively via an economic perspective. It's a danger to society, plain and simple.
Losing money in a prediction market does not count as a proportional penalty for the damage that he might be causing to others.
Can you actually make a concrete suggestion or are you just blathering because you don't like the guy? The only concrete thing I can see in your comment is that you won't "give any credit to his ideas" unless he, presumably, tries it himself first (how?).
And what exactly is this terrible damage that he might be causing to others by raising awareness of this idea? Are we afraid of infection from blog posts now?
He would be showing a modicum of Skin in the Game if he actually went to infect himself and those close to him with the virus before encouraging others to normalize such a risky experiment.
> Are we afraid of infection from blog posts now?
He is not just "raising awareness" of the idea of variolation. His writing was already trying to argue that government could try a program where volunteers would get paid to be infected.
When asked "if you think this is a good idea, why don't you do it yourself?" he responded with something along the lines of "there is no counterparty to bet with me on it, so what is the point?" Isn't that the answer of someone completely oblivious to the idea of SITG?
Again: How?
He's suggesting a program of trained medical professionals, isolation, observation, and you think he just ought to go off and infect himself in uncontrolled conditions without any medical training or control group? One of the two of you hasn't thought this through, and I'm pretty sure it's you.
> He's suggesting a program of trained medical professionals, isolation, observation (...) he just ought to go off and infect himself
Yes, that is the point! He is suggesting something that medical experts already consider dangerous and unethical, otherwise it would already be done. He wants medical experts give some veneer of science to something completely immoral just by seeking higher financial compensation to those that might be affected.
So what he is "proposing" involving everyone else taking a lot more risk, without any real consequence for him. This is no display of SITG, quite the opposite. He just sees it as a game of "Heads some might lose their life, but tails we might win a little, so let's find the price point where this is even".
By asking if he is willing to infect himself to do it, it is not a matter of doing it for the science or the economics of betting. It is just a pure ethical filter: "So far your words only risk the lives of others, but if you really think this is the best course of action then you need to demonstrate you are willing to put your ass on the line. Can you?"
You demonstrate utter failure to understand the idea. A controlled, known, small viral load is the idea. Controlled: not from a random walk through a hospital, but administered under controlled conditions. Known: a measured quantity, not an unknown quantity from a random walk through a hospital, of a known viral strain. Small: maybe 1/50th the kind of load you would get if you were exposed in a busy hospital and someone sneezed on you.
You so spectacularly missed all these points that it's clearly not worth continuing this conversation further.
Let me try again: there is a reason that no one is doing "small, controlled, small virus load experiments": it is because they are illegal, unethical and potentially bring more harm than benefit. If they are supposed to be done properly, they should be done with the same standards that are adopted for those that want to develop vaccines and other medicines.
What Hanson is proposing requires doctors and scientists to drop already established ethical principles and adopt practices that have unknown risks and can be potentially catastrophic.
He puts it as the whole "we already test vaccines on humans, and vaccines are made from the virus itself, so why not just test the actual virus" was just an issue of testing on dosage/response. He wants to argue that the risk people take is just proportional to the amount of contact they have to the virus.
It is not. Just as an example: suppose that inoculation by a weak version of the virus does not help our immune system to create antibodies and just instead make us more susceptible to a future, more lethal mutation of another Coronavirus? This is a very-tiny-but-plausible possibility, and that alone should stop us from abandoning current safe practices for research.
He wants you and I and other doctors to just squint our eyes and pretend it is okay to do what he is proposing if the participants take a little bit more risk (compared to drug trials conducted ethically) and that just by compensating them properly, it would be fair and ethical.
It is not. Trials for drugs and vaccines go through a bunch of other steps before to try to determine its safety on humans. He sidesteps the whole thing and wants medical practices to go back centuries in time for no good reason other than "economic theory"
---
So, we have this guy who is trying to convince others to take risks of unknown magnitude and to break traditional practices with unknown benefit. We have this guy who is willing to play fast and loose with the rules without ever facing any consequence of the potential downside of these measures.
What do you do with it? What I am saying is that anything he is defending should not have any weight until he shows willingness to face the consequences of his risky proposal. And given that we do not know the behavior of the virus and we do not know what are the "safe" parameters for it, the only way that he can show SITG is by facing the highest possible risk.
This is why I say I don't particularly care about the practicality of it all. There is no way to quantify the risk anyone is being exposed to it, so whoever is asking others to take the risks should give the example by taking the maximum risk possible. And it is not that he is making himself "more right" or "less wrong" (pun intended) if he does show SITG. It is just that I am just allowing myself to take any risky proposal into consideration when those doing the proposal are also facing the risks. It is a simple filter.
I hope at least now I could make myself clearer. Thanks for the discussion anyway.
Agreed.
I didn't read his post as saying that the payment had anything to do with the ethics of it, and we routinely pay participants in clinical trials for their time. I don't see the idea as something that's impossible to do ethically, and you do, but apart from that we are in agreement. Thanks to you too.
There are moral considerations to be done before proposing something ridiculous like what he is doing, and yet he is trying to reduce all ethical considerations into a "simple" matter of economics. Life can not be reduced to spherical cows and trolley problems.
Hard disagree based on experience. The clinical testing of many drug classes are entirely dependent on many people being too uneducated or desperate to consider those types of risks.
In the crazy scenario that I had to participate in drug trials, I would instate a pretty simple rule: I would only accept those substances if everyone involved in the drug creation and test taking had themselves participated in the trial.
That's a simple rule, but it's ridiculous. The costs and benefits of taking a new drug are heterogeneous. Do you think people who develop anti-psychotics should be required to take anti-psychotic medications they have no need for?
(Come to think of it, it is interesting to see how the US is so addicted to pills and the opiate epidemic. The doctors are free to prescribe willingly, receive incentives from pharma companies and there is almost zero downside paid by them for those that get addicted. Don't you think this would be a much smaller problem if there was a way to get Skin in the Game from the doctors and companies and make them pay for cases of opiate abuse?)
Anyway, I was thinking of drugs that may affect anyone, like treatments for common diseases. For those, the idea is that I would like to have some sense of symmetry in the risk taking for all parties.
As perhaps a better way illustrate what I mean: whenever I had to take my kids to the pediatrician, I would listen to the doctor's recommendations and would ask "If it was your kid, would you still do the same you are telling me?"
Here in Germany the practices are way more conservative and less pill-happy in the US, so I can't recall any time where the doctor would propose something that was not willing to apply to one of her own. In Brazil, however, I do remember in 2017 during an outbreak of Yellow Fever when I everyone was rushing to the hospitals to get a vaccine. I talked to a nurse who basically said "If it was my kid, I wouldn't give it. The side-effects are too strong and it is only sensible if you live really close to the Forest." The doctor later confirmed, and we walked out.
In analogy world for the modern vaccines, imagine a science fiction scenario: the evil aliens look like humans, can and want to easily kill them, but look exactly like humans and we don't know how to recognize them. Variolation is like catching them but them setting them free to go around and kill more in order to train us, expecting that it is possible to set free small enough number of them over and over so that in the fight we will "manage somehow" to win and also learn something while fighting, wheres, producing modern vaccines is like just finding out that the evil aliens look differently in infrared light and just teaching us to use infrared cameras to locate them, completely avoiding the real additional fights among the population "just for training."
Variolation, as defined in the article, was the best method that we knew a few centuries ago, but now we simply know much more now. And solving the problem is still complicated enough even with the "better start." We want to minimize false alarms, friendly fire etc. practically, we know what we want and how to measure it and we do all we can to minimize the number of bad outcomes.
But by all means, let's all presume that an economist like Robin Hanson—whose primary interest it would seem to be opening up commerce during a pandemic—has somehow come up with an idea that has escaped the notice of that entire segment of the population dedicated to human health.
Let's ask Mike Pence about his thoughts on the use of bloom filters as relational database indexes while we're at it. I'm sure he'll point out that mauve seems to have the most RAM.
Sure, experts can have blind spots, but c'mon!
This is mostly the legacy of Josef Mengele and to some extent the Tuskegee experiment, but collectively we essentially said "we never want to do that again, so let's make rules that keep us well away from that line."
The reason the idea isn't getting much attention is that anyone in the field that is serious knows that the study would never get past an Institutional Review Board, so it's pointless to even try.
It seems to me that we need to revisit our tenets of medical ethics in borderline cases like this one, where the stakes are so high. To me, you should be able to do riskier experiments in these cases if the subjects are truly informed volunteers, and you keep the risk to them to an absolute minimum consistent with doing the experiment. There's a very similar issue with vaccine challenge trials.
As for the time and effort, I'm assuming that the existing vaccine developments are adequately staffed. There are many other medical researchers that are working on other things that could work on this.
As someone that makes a living at the intersection of a couple of different fields maybe that is true. But the last person to take advice from is an academic economist. We literally have thousands of different trained professionals working on this right now and NONE of them think what Robin Hanson wants to do is a good idea.
It looks like at least half the population will contract this disease over the next couple of years. Around 0.5% of those will die. If we wait until an extremely safe vaccine is mass produced, far more lives will be lost than if we use methods that the authorities consider unsafe. The main issue seems to be that people attribute COVID-19 deaths to nature, while they blame any experimental immunity deaths on the researchers. It's the same logic that anti-vaxxers use. Yes, some vaccines do have side-effects and every once in a while, someone does die from them. But that's a far better outcome than the disease itself, so we accept the tradeoff.
As I said, in this emergency, around 0.5% of people infected will die. That means that a treatment with a 0.1% mortality rate would reduce overall deaths by 4x! That's a far more effective intervention than say... ventilators (which only reduce mortality by around 20%). Yet no government will allow volunteers to get a treatment with such a high mortality rate, so we're all stuck with "natural" infection and its 0.5% mortality. This is peacetime thinking in the middle of a war.
It should be clear by now that our institutions have failed us. The CDC & FDA forbade researchers from testing for a month. It's only because some researchers decided to break the law that we discovered community spread when we did.[1] The Surgeon General repeatedly told the public that masks don't work.[2][3] The WHO said the same thing.[4][5]
If we judged these institutions by the same standard that people in this thread are using for Robin Hanson, we'd want to drastically curtail their power and allow for more experiments. That's exactly what Hanson is proposing.
1. https://www.nytimes.com/2020/03/10/us/coronavirus-testing-de...
2. https://twitter.com/Surgeon_General/status/12337257852839321...
3. https://twitter.com/Surgeon_General/status/12456974534138511...
4. https://twitter.com/WHO/status/1234095938555260929
5. https://twitter.com/WHOWPRO/status/1243171683067777024
And yet it's still being discussed, not dismissed outright by the experts. I for one am happy with allowing epidemiologists and virologists to lead the discussion, but not economists and political appointees. No way.
https://www.nbcnews.com/health/health-news/why-have-14-000-p...
Trump has so far advocated for not wearing masks, inciting armed (white) citizens to storm state capital buildings, the use of hydroxychloroquine despite being found now to be worse than ineffective, sidelined Fauci (going so far as to retweet a call for his removal), and other nonsense, all to boost economic numbers for November and/or fulfill a (toxic) political ideology. And you want the likes of him to determine the best course of action for fighting disease?
F— that noise. If the health research community looks at the problem and decides it's a good idea, I'm on board. Everyone else can take a huge fat seat in their La-Z-Boy and STFU about how soon human trials should begin.
https://www.newsmax.com/us/surgeon-general-face-masks-jerome...
See earlier note about political appointees, especially by this administration. This isn't about health for them; it's about PR. Countries where its citizens wear masks have done much better against the disease. Countries where citizens claim "freedom" from wearing masks have just tallied 100,000 deaths so far.
Japan has an extremely high population density. One of the highest proportions of elderly citizens in the world. Had cases arrive earlier there than in the US, so less warning. 869 deaths so far total.
Why?
For the most part, masks. Everywhere. Everyone. That and not waiting until it was too late to shut down public gatherings and schools. In other words, they had adults in charge and its citizens don't treat basic precautions like masks as some sort of tyrannical plot against democracy. (Last I checked, Japan was still a democracy.)
Grow up. Wear the damn masks already.
You need the other people to have a voice as well because you can’t live and eliminate all risks at the same time.
> The best way to prevent the spread of viruses like Corona is to put everyone in a straightjacket and chain them to the floor in their home. Epidemiologists will keep saying people need to stay inside because that’s safer.
This is a hyperbolic take on shelter in place orders and wearing masks. You have replaced the actual recommendations and public orders with a call for complete removal of bodily autonomy even though this was never the case. At no time were people unable to drive to the grocery store for example. They were however restricted from congregating at the beauty salon because of obvious issue with viral transmission.
You have substituted "we need to take precautions as a society" with "let's remove everyone's ability to use their arms and move more than a few feet". Then you went on to suggest that this is akin to what epidemiologists would have us do if given their preference.
If you honestly believe what is happening now is just a precursor to your replacement premise, profound elimination of bodily autonomy, this would fall under another common logical fallacy known as the slippery slope.
> You need the other people to have a voice as well because you can’t live and eliminate all risks at the same time.
Has anyone said, "We want to eliminate all risks"? Has anyone said, "Hanson must not be allowed to speak"?
No. The actual proposed arguments have been, "We want to mitigate risk while looking more closely at what the risks levels actually are," and "Hanson is an economist, not a medical professional who has dedicated their life to the study of infectious disease; therefore his opinion should not carry as much weight as theirs."
So you see? The actual arguments have been substituted for your more hyperbolic and untenable remarks. The hyperbolic remarks are then refuted, not the original arguments.
Ergo: straw man fallacy
Good day, sir.
Scientists do not put out orders, that is the job of politicians. Science can only tell you, if you this you run the risk of that. A proper scientist would tell you the only way to avoid being infected or infecting others is to be chained into place.
> Has anyone said, "We want to eliminate all risks"?
People won’t say ‘we want to eliminate all risks’ but if the consequences are presented as being scary enough, they will take any action to avoid them, which factually is the same thing. Concretely many people want to ‘shelter in place’ until there is no more risk they can be infected and a lot of these people want everyone else to do that as well.
It is the job of politicians to evaluate these risks properly and for that they need to listen to both medical scientists, like epidemiologists, so they know what risks they can avoid using their orders, but also economists so they know what costs they incur by these orders.
It should be clear that if they do not do this properly the result can be taking measures that are unsustainable or incur new, worse risks.
> Has anyone said, "Hanson must not be allowed to speak"?
> But by all means, let's all presume that an economist like Robin Hanson [...] has somehow come up with an idea that has escaped the notice of that entire segment of the population dedicated to human health.
If Robin Hanson speaks he must be ridiculed because what could he possibly have to bring to the table that no one has thought of before (and then I even cut out the vague insinuations about his motives).
But anyway I have no idea who he is and did not refer to him in my comment. My only point is that if you immediately dismiss the input of economists and others outside medical science, you’re only looking at one side of the story and are bound to take poor decisions.
False dichotomy. Not only are there more than two options, looking to economists among others without medical training on epidemiological matters as though they should have equal standing is asinine. Dunning-Kruger applies here. As said before, might as well ask Mike Pence whether bloom filters are an effective relational database indexing strategy.
"There is a cult of ignorance in the United States, and there always has been. The strain of anti-intellectualism has been a constant thread winding its way through our political and cultural life, nurtured by the false notion that democracy means that “my ignorance is just as good as your knowledge.”" – Isaac Asimov
https://aphelis.net/wp-content/uploads/2012/04/ASIMOV_1980_C...
> Doctors sought to monopolize the simple treatment by convincing the public that the procedure could only be done by a trained professional. The procedure was now preceded by a severe bloodletting, in which the patient was bled, often to faintness, in order to 'purify' the blood and prevent fever. Doctors also began to favour deep incisions [versus superficial scratches], which also discouraged amateurs.
What the economist Hanson is essentially suggesting is that we take a worse method of immunization (just the normal live virus) and waive the regulatory burden to show safety and efficacy because a similar approach worked with smallpox. If we are getting into the business of ignoring the requirement for an immunization approach to be clinically validated, then there are a few dozen vaccines with far better theoretical safety and efficacy profiles that we should be using instead. The reason a vaccine isn't coming immediately is because we have to show they wont kill people and that they'll work, and then we have to scale up production. You dont get to rebrand your worse vaccine approach as "variolation" and then say it should be held to a different standard so you can get the economy humming again.
I think Hanson's blog post[1] about the general idea of variolation was useful to get discussion going but agree that as stated it was not a good approach.
In contrast, the proposal we developed subsequently focused on making use of human challenge trials[3] (where the control arm of the clinical trial is actively exposed to the pathogen) to search for safer forms of inoculation, hopefully benign.
I disagree with your point that live virus is necessarily a worse form of immunization; I think it actually depends on the route of inoculation and on finding a reasonable dose. I am working on the skin route separately[4] and from this I've learned live-viruses are used in some (many?) of the most successful vaccines (adeno, polio, measles, smallpox)[See appendix in 4.1]. In polio and measles the virus was attenuated, but in the case of adenovirus, it's used in its original wild-type form and inoculated into the gut via oral dose to avoid the primary respiratory infection. Adenovirus is also notable for comparison as it causes an ARDS-like condition and the gut infection (benign diarrhea and fever) was considered secondary and acceptable enough that the US Military doses all recruits this way since the 80s. And although smallpox variolation had relatively high mortality rates, it's unclear how specific the methods in use were. It's possible that the primary (respiratory!) infection wasn't avoided e.g. by the methods of scab snuff (ew!). Lastly, non-live virus vaccines may not provoke a sufficient immune response, e.g. in the killed polio vaccine that was eventually retired. I think this is generally a concern for potential synthetic CoV vaccines as well.
So it seems like the idea from smallpox and adenovirus is to inoculate where the body has a good chance of dealing with the infection (skin and gut, respectively) when the primary infection (respiratory in both cases) is dangerous and there aren't better alternatives. I'm working on the skin route since it seems plausible (it appears skin can be infected by CoV2) and the least risky (almost all reports of associated infections are benign; though there are some reports of skin tissue necrosis). The gut route is also interesting but in my opinion we're too early in the clinical understanding to prioritize it since it is often associated with the primary infection.
I'm just starting to treat this as an open-source project[5]. Please feel free to join!
[1] "Variolation (+ Isolation) May Cut Covid19 Deaths 3-30X" http://www.overcomingbias.com/2020/03/variolation-may-cut-co...
[2] "Targeted Immunization of Low-Risk Individuals Using a Low-Dose Inoculation (LDI)" - https://docs.google.com/document/d/1gSj-mrjFwswU35RzBnkjTt9E...
[3] https://academic.oup.com/jid/article/221/11/1752/5814216
[4] "SARS-CoV2 Live Virus Skin Vaccine" - https://tinyurl.com/y8ujrcze
[4.1] "Appendix: Live Virus Vaccines" - https://tinyurl.com/y8u...