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Comment by IdoRA | Hacker News Reader

A naturally attenuated strain would still be regulated. In the US, 21 USC §321(g):

> (1) The term "drug" means… (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals;

CBER would be the responsible center for the FDA. Other countries have analogous regulations.

Could you come to market with a naturally attenuated strain? Yes. Would it take less time? Not really, because you don’t get to do an “end run around the regulations” as you put it in another comment. The logistics of making sure it works and then setting up the supply chain and quality systems are what take the most time. There are no shortcuts in medicine.

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There are plenty of shortcuts in medicine. Think how you would stop this strain from being spread by individuals once it was identified. This strain will spread no matter what the FDA says.

Personally I think the regulatory authorities would rapid approve it based on the epidemiology data collected in the process of finding the strain. The FDA has already shown that it can move faster than its usual glacial pace given sufficient motivation.

The much more important question is when are we going to start seriously looking for such a strain?

Serious question: are we not? People are sequencing these things like crazy (c.f. the nextstrain.org data). Epidemiologists are working like mad to come up with data on severity in regions all over the globe. Virologists everywhere are dropping what they're doing otherwise to work on covid.

It sorta strains reason to argue that none of these people thought of looking for an attenuated strain.

Isn't the simpler truth just that finding one takes a lot of ground work that's already being done, but hasn't born fruit yet?

they re probably not sequencing asymptomatic people's virus, it would require some specific expedition. it doesn't even sound hard or expensive

reply to @ajross:

how would they know someone is asymptomatic? afaik they are mostly testing people who have symptoms , and their contacts (who will have contracted the same , symptomatic strain)

I think in germany they did antibody testing, or PCR of swabs of people who mostly no longer had a live virus infection to sequence. also, it seems the idea has merit; and i havent read about any team looking for this specific method (identify gene deletions and tracing). It certainly doesn't hurt (and doesnt cost much) to try

btw sweden is doing a survey of live infections in stockholm, however i don't think that they sequence the viruses

to @danieltillet:

maybe post about it in reddit on r/covid19, some epidemiologists hang out there for the latest news

Are they not? That seems like a pretty obvious experiment to do.

For reference: I have a family member in virology. He reports that everyone he knows is now working on covid, mostly because if they don't they can't come to work on anything. The biggest problem is finding subjects that will produce a paper of any kind. I really don't think research bandwidth is the issue here.

I guess I have to repeat the question as its converse: is there any evidence that this is not happening? If it isn't, let's figure out the right people to pressure and not just discuss it on HN. And if it is, maybe we should let the experts do their work without pretending to have had their ideas for them?

If you know anyone working on my idea please let me know as I will update my blog post. Nothing would please me more than to learn that someone is already doing this on a serious level.

It is not hard to do the sequencing to find candidate attenuated strains (you are just looking for strains with deletions in key genes). The more difficult part is all the contact tracing in the area around where the strain is first found to check if the strain really is attenuated.

The ideal outcome is you find a strain with a deletion and you then test everyone in the area and you find 10,000 more people infected with the strain that have only a mild case and none of these people are in the hospitals. This strain would be very valuable to have.

> how would they know someone is asymptomatic? afaik they are mostly testing people who have symptoms

There was literally a paper published yesterday (or the day before) on a blanket screen done on a population in germany to get some data on the undercount of asymptomatic cases. It was front page news on all the mainstream news sites...

I gotta be honest. This whole discussion has an "amateur hour" vibe. I have a hard time believing that professional academics in a long-established and very competetive field really failed to remember how the measles vaccine worked.

It's not that I think this is a bad idea, just that (1) it's almost certainly someone else's idea already, (2) is therefore probably harder to do than presented and (3) is thus not the magic bullet people are looking for.

To wit: stay the fuck home. Maybe someone will save us. They probably won't. We beat this with isolation or we wait for a vaccine.

I think what you are missing here is what is the novel part of my idea and what is the conventional. It is not novel to think of an attenuated vaccine, what is novel is to look for an attenuated strain in a pandemic using genome sequencing. I hope someone else has thought of this, but so far I haven’t seen any evidence of this.

Waiting for vaccine is not a good option. This is a situation with only hard choices.

Why else are hundreds of different labs around the world genome sequencing?

To assess the diversity and spread of the virus it appears. To the best of my knowledge nobody is systematically looking for a natural attenuated strain by genome sequencing. If you are then please get in contact with me.

"Waiting for a vaccine" is mostly a strawman. We're being asked to wait 2-3 months for the outbreaks to reach a size where they can be contained by testing, tracing and quarantine. But that only works if people take this seriously and honor the lockdowns.

We’re also likely to see convalescent sera available shortly, and neutralizing antibodies available in several months. Those, along with more widely available testing, will help us tread water until we develop a good drug or vaccine.

Even if this would work in rich countries, this is not a realistic option for people in poor countries. They do not have the money to wait in isolation for the next 3 months.

The sequencing is not the important thing here, but the search for strains with gene deletions and contact tracing everyone in the area to find more cases to prove the strain is attenuated. As far as I know nobody is doing this.

You’re fairly hard to get in contact with directly. Would you mind sending me an email? I don’t think I’ll be a your “middle hop”, but I’ll try. My email is lyndsy@<my_HN_username>.com

My username here is my real name, and I should be easy to find. It’s also my username on Twitter, Keybase, and most other popular platforms.

From the update section of the original post:

> If you think you might be that first hop person then please get in contact with me at daniel.tillett@gmail.com

Thank you. I don’t know if that just wasn’t there when I posted, or if I just missed it, but I appreciate it.

It was there, but I put it right at the bottom so at least only people who read the entire post would find it. I am at least a lot easier to get in contact with than anyone with the political clout to make this happen.

I don’t see that any regulatory authority would approve something that is capable of spreading, regardless of the possible benefits: it would violate medical ethics. Reread the Belmont Report.

There are many teams all over the world that are looking for less deadly (and more deadly!) strains to guide development of therapies. They’re too busy right now to post on message boards or speak to reporters. It’s however extremely unlikely that a less deadly strain will become the therapy, although it could be the basis of a therapy (but I think this too is unlikely).

All the attenuated live viral vaccines spread. This is one of the reasons they are so effective since they keep herd immunity up. For example, every kid that gets the live polio vaccine spreads it around to their peers and parents.

That’s a bug, not a feature: the OPV went to bivalent a few years ago to reduce the odds of vaccine-related cases.

Well your bug is a feature.

The polio vaccine actually went to the inactive form to reduce the risk of polio from one of the vaccine strains reverting to wild type and infecting others. It is still less effective at achieving herd immunity than the live version because of the lack of viral spread.

> All the attenuated live viral vaccines spread.

Can you point me to sources supporting that claim? I searched myself, and what I found says that our knowledge is limited to the polio vaccine:

"Little attention has been given to vaccine transmission, possibly because transmission is rarely measured and largely unknown in humans except for the oral polio vaccine. Whether transmission is indeed rare for other live vaccines, or has merely gone unnoticed, is not clear – polio vaccine transmission is accompanied by evolution to high virulence, creating problems that draw attention to transmission."

From "Transmissible Viral Vaccines", James J. Bull et al., Trends in Microbiology, January 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777272/

This is a difficult topic to research these days due to the anti-vax/anti-anti-vax noise. :(

It doesn’t appear that horizontal transfer is absurd, and while I’m not immediately seeing a large body of evidence that it happens all the time, it does seem to be generally accepted that it occurs.

Here’s what I believe to be an informative article on the topic: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667938/

Robin Hanson has been covering variolation: http://www.overcomingbias.com/2020/04/variolation-test-desig... and part of the issue is that the FDA is poorly equipped and set up to respond to a pandemic. One obvious solution is to cut through the bureaucracy and make emergency exceptions, but no one with political power in the US seems to know this, or understand it.

Ultimately a decision to use or not use any attenuated strain found will be a political decision.

There's a lot of differences in risk appetite (and actual risk) from state to state.

Maybe the feds could allow states to get a waiver from FDA regulations if they want to try things like variolation.

This would still require someone at the federal level to stick their neck out a little, but (I think) a lot less than if they were to propose something like this as a federal policy.

We've got a federal system, let's make some use of it.

i doubt that , if this magical strain does exist, any regulation is going to stop people from just getting themselves infected

I doubt the regulators would even try to stop it. They can move fast when they want.

The process of finding any useful strain is going generate good data that it is safe anyway.

Alternatively, if this approach actually works, all the countries in the world that can appropriately adapt their regulations will survive, and the ones that choose not to won't.

Natural selection versus bureaucracy!

It's the "figure out if it actually works" part that is going to take most of the time for any potential prophylactic option for COVID-19. The bureaucratic overhead in this particular case is not going to be the inner loop.

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