(Here I try to put my recent arguments together into an integrated essay, suitable for recommending to others.) When facing a new pandemic, the biggest win is to end it fast, so that few ever suffer. This prize makes it well worth trying hard to trace, test, and isolate those near the first few cases. Alas, for Covid-19 and the world, this has mostly failed, though not yet everywhere.
For a massive, quick fix volunteers only wouldn't suffice. But smallpox is good example of how much good voluntary vaccination can do. Plenty of children were save because mothers took the risk of getting them vaccinated when it was still controversial.
I've tackled some of the same issues from a very different standpoint and with different reasoning. I do think variolation should be pursued aggressively as a prudent Plan B in case a vaccine doesn't turn up quickly. See "Exit Route? The Case for Variolation Against COVID-19" https://papers.ssrn.com/sol...
You gotta love how this sentence: "This isn’t just a theory. The medical literature consistently finds strong relations, in both animals and humans, between initial virus dose and symptom severity, including death."
Includes three links to three articles, NONE OF WHICH ARE MEDICAL LITERATURE, and which basically refer to a single COVID-19 study in Wuhan that substantiates the claim.
Which makes it meaningless. You would have to infect almost everyone under 70 who was not seriously ill. So we can also forget the bit about "volunteers".
One thing that is particularly silly here is this.
What happens if you use larger viral doses, but add a little formaldehyde? (Test on a mouse or a cat that it is no longer infectious).
You get an ordinary inactivated virus vaccine. You also remove a lot of delivery issues (live viruses are tricky!) and a lot of the dosing issues (overly high dose is a lot less harmful).
The rest of his proposal would work out exactly the same except with lower costs, less personal risk, less load on the medical system, and less collateral damage.
> dose-response for immunity better/different than that leading to severe complications/death ('therapeutic window')
Yep, that too. No particular reason why it would be.
This isn't measles in infants. In fact it seems to rarely if ever put children in an ICU. A healthy naive immune response is sufficient for surviving it.
People who are dying from this have some issues with their immune response to SARS-CoV-2 , and it is entirely unclear whether a "small dose" followed a month or two later with an ordinary infection (that may be a large dose), would result in a lower mortality rate. That is not in any way guaranteed by the dose severity dependence itself.
Variolation - not as described by Hanson but as described by everyone else: drying smallpox scabs for about a week or so.
First dead virus vaccine: drying infectious tissue (from a rabbit) for a week or so.
Come on. Why in the world do you and Hanson jump from actual variolation to this idea of simply giving people the actual fully potent live virus?
It looks more like an inactivated virus vaccine (with half a dozen other alternative explanations). Maybe not fully inactivated, but there's going to be a LOT of dead virions in a dried scab, why in the world do you think it didn't matter? When you can literally stop someone who got bit by a zombie from turning into a zombie with nothing but the drying-killed virions (see rabies vaccine).
As for the live virions in a dried scab. Arrhenius equation rings a bell? No? They didn't have thermostats back then. Warm week they'd get a small dose, cold week they'd get a million times that dose. Humidity too. It is literally physically impossible that it worked the way you two believe it could have worked, because drying is not a way to obtain a reliably small dose.
And can you explain to me what exactly do you win by not trying to inactivate the virus? I really don't get it.
That in your head you don't label it a "vaccine" if you don't inactivate?
You still need the safety study, you don't know what dose to use, everything about the process is infectious (and infecting bystanders / medical workers / etc). The manufacturing is no less difficult, either. For all intents and purposes it's a live virus vaccine (except with extra hazard and stricter dosing requirements).
The reason this sounds like you just want to get people killed, is perhaps not that you are solving a trolley problem, but that you're inventing yourself a new track from scratch and asking people to please stand on it for the greater good. And all the pre-laid tracks are considerably less populated.
edit: also your government action proposals remind me of the story of USSR and Lysenko.
As horrible as it sounds, I think if I were the prime minister of India, I would start large-scale variolation experiments right now. It appears that they are already in a nightmare situation, with no chance for "social distancing" to be effective. For them "Plan A" and "Plan B" have already failed.
Sorry. I thought I read all your recent blog posts but must have missed where you argued for variolation combined with vaccine trials. Seems like an obvious combination that makes your arguments stronger.
He proposes naysaying new ideas and ridiculing those who come up with them.
For a massive, quick fix volunteers only wouldn't suffice. But smallpox is good example of how much good voluntary vaccination can do. Plenty of children were save because mothers took the risk of getting them vaccinated when it was still controversial.
I've tackled some of the same issues from a very different standpoint and with different reasoning. I do think variolation should be pursued aggressively as a prudent Plan B in case a vaccine doesn't turn up quickly. See "Exit Route? The Case for Variolation Against COVID-19" https://papers.ssrn.com/sol...
This post had more links: http://www.overcomingbias.c...
You gotta love how this sentence: "This isn’t just a theory. The medical literature consistently finds strong relations, in both animals and humans, between initial virus dose and symptom severity, including death."
Includes three links to three articles, NONE OF WHICH ARE MEDICAL LITERATURE, and which basically refer to a single COVID-19 study in Wuhan that substantiates the claim.
What a bunch of nonsense.
If combined with infusions of plasma from recovered victims, a large dose of gamma globulin, and a BCG vaccination, this could work well.
I'm betting that regardless of its merits this won't happen on a significant scale.
Which makes it meaningless. You would have to infect almost everyone under 70 who was not seriously ill. So we can also forget the bit about "volunteers".
"sufficiently" allows for a wide range of cutoffs.
"Hero Hotels welcome sufficiently young and healthy volunteers. "
It is not enough to variolate the "sufficiently young and healthy". You have to do it to three-quarters of the population.
So it is not something to be done to young healthy volunteers. It is something you enforce on almost everyone.
You can argue for that, but stop talking about "young healthy volunteers".
> must be faster than fast-tracked RCTs
Yeah.
One thing that is particularly silly here is this.
What happens if you use larger viral doses, but add a little formaldehyde? (Test on a mouse or a cat that it is no longer infectious).
You get an ordinary inactivated virus vaccine. You also remove a lot of delivery issues (live viruses are tricky!) and a lot of the dosing issues (overly high dose is a lot less harmful).
The rest of his proposal would work out exactly the same except with lower costs, less personal risk, less load on the medical system, and less collateral damage.
> dose-response for immunity better/different than that leading to severe complications/death ('therapeutic window')
Yep, that too. No particular reason why it would be.
This isn't measles in infants. In fact it seems to rarely if ever put children in an ICU. A healthy naive immune response is sufficient for surviving it.
People who are dying from this have some issues with their immune response to SARS-CoV-2 , and it is entirely unclear whether a "small dose" followed a month or two later with an ordinary infection (that may be a large dose), would result in a lower mortality rate. That is not in any way guaranteed by the dose severity dependence itself.
Indeed. Let's start adding up the rather lengthy list of assumptions that this 'variolation' argument is based upon:
- must be faster than fast-tracked RCTs
- immunity is achievable with Sars-Cov-2 [https://www.npr.org/section...]
- dose-response for immunity better/different than that leading to severe complications/death ('therapeutic window')
- testing for immunity is achievable/specific/reliable given the low prevalence of immunity/testing
- https://blogs.sciencemag.or... - https://twitter.com/zbinney...
Did you ever read up on the rabies vaccine?
Variolation - not as described by Hanson but as described by everyone else: drying smallpox scabs for about a week or so.
First dead virus vaccine: drying infectious tissue (from a rabbit) for a week or so.
Come on. Why in the world do you and Hanson jump from actual variolation to this idea of simply giving people the actual fully potent live virus?
It looks more like an inactivated virus vaccine (with half a dozen other alternative explanations). Maybe not fully inactivated, but there's going to be a LOT of dead virions in a dried scab, why in the world do you think it didn't matter? When you can literally stop someone who got bit by a zombie from turning into a zombie with nothing but the drying-killed virions (see rabies vaccine).
As for the live virions in a dried scab. Arrhenius equation rings a bell? No? They didn't have thermostats back then. Warm week they'd get a small dose, cold week they'd get a million times that dose. Humidity too. It is literally physically impossible that it worked the way you two believe it could have worked, because drying is not a way to obtain a reliably small dose.
And can you explain to me what exactly do you win by not trying to inactivate the virus? I really don't get it.
That in your head you don't label it a "vaccine" if you don't inactivate?
You still need the safety study, you don't know what dose to use, everything about the process is infectious (and infecting bystanders / medical workers / etc). The manufacturing is no less difficult, either. For all intents and purposes it's a live virus vaccine (except with extra hazard and stricter dosing requirements).
The reason this sounds like you just want to get people killed, is perhaps not that you are solving a trolley problem, but that you're inventing yourself a new track from scratch and asking people to please stand on it for the greater good. And all the pre-laid tracks are considerably less populated.
edit: also your government action proposals remind me of the story of USSR and Lysenko.
As horrible as it sounds, I think if I were the prime minister of India, I would start large-scale variolation experiments right now. It appears that they are already in a nightmare situation, with no chance for "social distancing" to be effective. For them "Plan A" and "Plan B" have already failed.
I know you are just being emotional and snarky because variolation makes you feel icky to consider, but toddlers can't give consent
Sorry. I thought I read all your recent blog posts but must have missed where you argued for variolation combined with vaccine trials. Seems like an obvious combination that makes your arguments stronger.