How About a Remote Variolation Study?

by Liron2 min read3rd Apr 202024 comments

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Covid-19
Frontpage

Robin in Variolation May Cut Covid19 Deaths 3-30x:

Just as replacing accidental smallpox infections with deliberate low dose infections cut smallpox deaths by a factor of 10 to 30, a factor of 3-30 is plausible for Covid19 death rate cuts due to replacing accidental Covid19 infections with deliberate small dose infections.
[...] Systematic variolation experiments involving at most a few thousand volunteers seem sufficient to get evidence not only on death rates, but also on ideal infection doses and methods, and on the value of complementary drugs that slow viral replication (e.g., remdesivir). [...] A small early trial could generate much useful attention and discussion regarding this strategy

Zvi in Taking Initial Viral Load Seriously:

My prior at this point is that the difference between a low and high initial viral load of Covid-19 is large. [...] That difference is a really, really big deal. It’s a much bigger deal than getting enough ventilators. It’s potentially a bigger deal than having a medical system at all.
[...] The more I think about the Covid-19 situation, the more I think the highest leverage thing most people reading this can do is to find ways to get our hands on better data.

Right now we are all very keen to know the values of X and P in this statement:

"If you have an X% risk of infection with a large inoculum in the next month, you should deliberately infect yourself now with a small inoculum via protocol P"


The following are sufficient for many people to undertake variolation for themselves and their loved ones:

A. An easy variolation protocol

B. Proof that variolation works to reduce COVID hospitalization rate 3x+


What we're missing right now:

1. A few plausible ideas for variolation protocols

2. A study where 10k volunteers try the various protocols, then get tested for how large of an inoculum they got (data on the variolation protocols), then report their outcomes (data on variolation itself)


Does anyone have any ideas for #1?


For #2, a remote study on thousands of volunteer heroes self-variolating from within their current self-quarantines (isolated from all non-volunteers) seems like the fastest and cheapest way to get initial data.

This doesn't necessarily have to be a "Scientific" study. It can be a crowdsourced, crowdfunded movement. The data will be lower quality than scientific-study data, but higher quantity. We could plausibly get 100k volunteers' worth of data on variolation protocol design and variolation effectiveness.

How about a remote variolation study?

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  1. Spain has stabilized at 7K new cases/day, Italy at 5K new cases/day. At this rate it will take many months to reach a significant percentage of the population. The same will probably happen in the US. Most people won't get infected, so trying amateur vaccination is more dangerous than doing nothing.

  2. How will you send doses to volunteers? If I were a delivery company, I would refuse to deliver this and would call the cops.

  3. How will you measure the results? People have trouble measuring the death rate from corona, sometimes they can't even agree on the order of magnitude. It's really low and depends on demographic factors, environment, treatment and other things that aren't well understood. If you want to measure a change in that rate by looking at 10k remote volunteers in reasonable time, I'd like to see your methodology and error bounds.

  1. Claiming that infections will halt at a small fraction of the population may be fine for Plan A, but shouldn’t we prepare a Plan B for the case where this claim is false?

  2. Maybe the variolation protocol can include instructions for how someone in your area with COVID can donate e.g. a tube of water mixed with their cough and how to get a small part of that into your rectum or whatever... I know it sounds crazy but proving out a potential 30x CFR reduction is a BIG DEAL

  3. It seems easy enough to at least just have participants report whether or not they ever required hospitalization.

Let's say X% get hospitalized within 2 weeks. What's the highest value of X that would say variolation is a good idea? Keep in mind that:

  • The demographics of your sample aren't the same as the general population, hopefully you didn't include many 60+ folks.

  • You don't know how many botched the protocol. Could botch in any direction (dose too high, too low, or no dose at all).

  • You don't know the hospitalization rate after contacting corona in normal ways, which can also be low dose. Many people don't get tested now and the epidemic is spreading.

  • Etc.

Let's say X% get hospitalized within 2 weeks. What's the highest value of X that would say variolation is a good idea?

Roughly X <= 1%. Something like 1/10 to 1/30 of the average 2-week hospitalization rate for a similar data set of non-study people is the success case. Assuming that the total study size has a sample of 10k+ participants, it's not that hard to get a strong signal of success out of the data.

What's special about this situation, besides the desperate emergency, is that the effect size we're hoping to detect here is nothing short of huge.

You don't know how many botched the protocol.

If video documentation of the full protocol is required to count someone in the study, the protocol accuracy could probably get within a 2x factor of having a professional administering it in meatspace.

You don't know the hospitalization rate after contacting corona in normal ways, which can also be low dose. Many people don't get tested now and the epidemic is spreading.

Aren't we confident that the hospitalization rate from getting it normal ways is 2-20%, and isn't that enough to go on?

Yes, if the potential effect size is large, you can get away with imprecise answers to some questions. But if there are many questions, at some point your "imprecision budget" will be spent. For example, will you be able to detect if your dosing leads to later hospitalization instead of no hospitalization? Or it weakens immunity instead of strengthening it?

I'm pretty optimistic that we have enough imprecision budget to work with if we put our heads together. Unfortunately, this comment section hasn't been very lively so far.

Does anyone have an estimate of how effective convalescent serum is in giving the recipient immunity?

"deliberate low dose infections" is a method of VACCINATION. ( or could be referred to as inoculation)

The usage of the term "variolation" is not correct. Variolation is specific to smallpox.

Language use is not either correct or incorrect. Good language use helps the reader to understand what's meant and how the entity that's named relates to other entities.

While this usage of the word "variolation" doesn't seem to be standard usage, I don't see how it's a naming choice with bad consequences. No reader is going to assume that we want to give people smallpox when we talk about it with those terms.

The terms "vaccination" and "inoculation" seem to me very broad for this case.

Do you have a more concrete argument why another term would be benefitial to use here?

Language use is not either correct or incorrect.

When it comes to medical issues language can be correct or incorrect. It matters.

If I went into hospital to have a debridement and someone decided amputation was an alternative I'd be pretty pissed waking up to find something had been chopped off rather than cleaned up.

It's not a matter of using variolation having a "standard usage" - it has a specific meaning. I don't think anyone will assume you want to give someone smallpox, but it does reduce the credibility of what is being said when variolation is the term chosen. (edited to add: variolation from variola = smallpox).

This website is called lesswrong, here's an opportunity to be a lot less wrong about something.

I'm not here to make friends, or get praise, or karma points and I will continue to point out errors made by people who are dabbling in subjects that they have little/no prior knowledge of.

Either people will consider what I've said and do some research for themselves. Or not.

Couldn't you have also made the exact same argument for the word "vaccination" some number of generations ago, for almost exactly the same reason? It too derives from root words about a practice intended for protecting specifically against smallpox. (Namely, infecting someone with cowpox).

https://www.etymonline.com/word/vaccination

When words are so overly specific so as to almost completely fall out of usefulness for their original meaning (as in the case of both vaccination and variolation, since smallpox is not in circulation any more), it seems pretty natural to see people to repurpose them for other closely-related or more general meanings - that's certainly one common way language evolves.

If the original meaning is no longer even remotely relevant (so misunderstanding is vanishingly unlikely) and the new meaning is a natural-to-infer and useful extension for the topic being discussed, then this seems like good communication, which is what words are for.

No it doesn't seem "pretty natural to see people re-purpose" variolation for something that would be labelled in standard and accepted medical terms as vaccination with a live virus.

Find some people in the medical profession that think it's a good idea then I may reconsider my stance, otherwise I've made my point and don't intend to post any more comments on the subject.

This website is called lesswrong, here's an opportunity to be a lot less wrong about something.

Wrong in the sense of the sequences doesn't mean Inconsistent with how authorities define a term or Not in line with the platonic form towards which a word points. It's rather about having a map of the world that makes wrong empiric predictions.