
A (possible) solution to Covid-19 - danieltillett
https://www.tillett.info/2020/04/05/a-solution-to-covid-19/
======
dongping
I'm not qualified to assess the risk, but if the there's indeed ADE (antibody
dependent enhancement),[1][2] people once infected with a milder strain may
suffer from more severe symptom from the deadlier strains, thus killing more
people in the end.

I'm wondering how we may rule out this worst case scenario.

[1] Is COVID-19 receiving ADE from other coronaviruses?
[https://www.sciencedirect.com/science/article/pii/S128645792...](https://www.sciencedirect.com/science/article/pii/S1286457920300344)

[2] New blood tests for antibodies could show true scale of coronavirus
pandemic [https://www.sciencemag.org/news/2020/03/new-blood-tests-
anti...](https://www.sciencemag.org/news/2020/03/new-blood-tests-antibodies-
could-show-true-scale-coronavirus-pandemic)

~~~
danieltillett
ADE is more a problem for the vaccine approaches. It is one reason we may
never have a vaccine for this disease.

Hard to rule out worst case scenarios, we just have to work with what we have
and make hard choices.

~~~
twomoretime
>ADE is more a problem for the vaccine approaches. It is one reason we may
never have a vaccine for this disease.

This is at least partly why there are no SARS/MERS vaccines. There's a paper
I'll try to dig up where 4-8 (can't remember) modified vaccine candidates were
tested in multiple animal species, and in each case except one, immunity was
conferred but exposure to the virus lead to a dangerous autoimmune response
which destroyed lung tissue.

~~~
wbl
That's not ADE as I understand it. ADE is where the virus gets grabbed more
easily by cells thanks to the antibodies on it proving handles.

~~~
twomoretime
Well yes, because of ADE the normal antibodies released by the immune response
immediately increase the replication rate so you have a far more severe
reaction upon infection than you would otherwise.

That's why I'm waiting for confirmation of immunity. So far I've only seen
increasing numbers of reports of reinfection but that may just be faulty
testing.

------
brownbat
I posted and deleted a few comments. I don't know what to make of this and
it's getting controversial. If it could be helpful, I'd love to improve it. I
just don't know where it fits in ongoing discussions by prominent researchers
on analysis of strains and types.

Three things that jump out at me:

a) You'll get more credibility from having a thorough lit review than from
listing credentials. Linking to magazine articles from journalists on genetic
variations, when there's academic research to cite, is a little bewildering.

b) You don't identify something harmless by just testing asymptomatics. This
is counterintuitive, but a great example of the Wason selection task:

[https://en.wikipedia.org/wiki/Wason_selection_task](https://en.wikipedia.org/wiki/Wason_selection_task)

You would probably want to survey the rate of variants in asymptomatics in a
certain community, then compare that with the rate of variants in fatal cases
in the same community to look for significant differences (and be fully
prepared not to find any significant differences beyond chance, a real and
likely possibility).

c) I'm still not sure what the author is specifically recommending we do next.
Researchers are looking for functional variants, we don't have one to
distribute yet, so we should do more sequencing. Ok, great. From what
populations? How many geographic areas? Where do we get the samples? There are
bottlenecks in sample collection, how do we overcome those? Given (b), how can
we get more samples from fatal cases, to compare virulence to those in the
general population? Task overloaded hospitals to send us additional samples
from dying patients? Is there another way we can get this info?

I don't want to dismiss this out of hand, this might be a good area for
additional focused research. I do think there are some key unanswered
questions though, and currently a worrying disconnect with the current state
of research on variants.

EDIT: Daniel, I know you're going through the comments here, and some of them
have gotten pretty harsh, sorry for that. I genuinely hope you're on to
something, and are able to continue to refine the post into a more robust and
specific proposal using all this feedback, despite the tenor of some of the
comments. That's really the best case for all of us, so good luck.

~~~
danieltillett
Just woke up (I am in Australia). I expect some harsh comments as the idea is
controversial. To your specific points.

a) The post was intended for a lay audience, not other scientists directly.
The reason I didn’t write a scientific paper on this is it would sink without
a trace as most scientists and doctors are too conservative. It is quite a
radical idea and while scientifically sound, it will take mavericks outside of
science to see this done. For better or worse it will take the efforts of
someone like on of the tech billionaires to push this forward.

b) If I had to choose one aspect that gets most commonly confused by people
who read the idea it would be the reason for searching only mild/asymptomatic
cases. This is purely an efficiency issue. In an ideal world we would sequence
the strains in all cases, look to see if we can find mutants with deletions,
and then see what was the clinical outcome of those infected with that strain.
If we find that all cases of a particular mutant are mild/asymptomatic then we
would have our candidate.

Because we live in a constrained world where it is not possible to sequence
all cases, where should we first look? Since we are looking for a mutant that
only causes mild/asymptomatic cases we can exclude patients with serious
symptoms as a first pass. Once we find a candidate strain that has the right
sort of mutation we can then sequence all cases in the local area, both
serious and mild to get the full clinical picture. This will make the search
much more efficient.

c) I am recommending that we put b) into action and get on with specifically
looking for an attenuated (only causes mild disease) strain ASAP. If we find
one then we can discuss what to do next, but the first step is to get started.

The good news is this can be done quickly and relatively cheaply provide we
have the will and the support of someone with the clout to make it happen. It
won’t be easy, but it can be done.

~~~
radu_floricica
Tech billionaire for publicity, maybe. But just getting a guide ready might
help more - everybody with a moderate amount of cash and access to the medical
system somewhere can start doing this in his back yard.

------
losvedir
How does the Iceland data suggest the hypotheses that 1) an attenuated strain
exists in the wild and 2) it provides immunity to the worse strain? It's
asserted in the post, but I don't see it. It seems likely to me their
experience isn't any different from any other country's, and they're just
testing more.

The idea in the post is obviously a good one if it can be done, it's just that
it seems like a generic idea that should be considered for any viral pandemic,
which makes me wonder why it's not already an approach people are working on.

~~~
danieltillett
It doesn’t which is why I never claimed it did???

As for why people aren’t working on this idea I don’t know. Maybe someone is
and they will send me an email and I can update my post. I would certainly be
extremely happy with this outcome.

~~~
losvedir
I was responding to this from your blog post:

> This data suggests a simple and testable hypothesis – there are natural
> strains of SARS-CoV-2 in the world that have mutated to be non-pathogenic
> (asymptomatic), but are still infective and will provide immunity to the
> more pathogenic (deadly) strains.

From the structure of the post it sounded like "this data" referred to Iceland
plus the Wuhan study.

If you only meant the Wuhan study then apologies for misunderstanding.

~~~
danieltillett
Yes both. The Icelandic data suggests there is genetic diversity in SARS-CoV-2
and the Wuhan data suggests there are strains that are less pathogenic.

There is also a Singapore study that has identified strains with large gene
deletions, but I haven’t yet updated the post to include it [0].

0\.
[https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1....](https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1.full.pdf)

~~~
LyndsySimon
Here’s a post from late February that enumerates 42 known strains of 2019-nCoV
as a phylogenetic tree: [https://nextstrain.org/narratives/ncov/sit-
rep/2020-01-30?n=...](https://nextstrain.org/narratives/ncov/sit-
rep/2020-01-30?n=5)

I’m a lay person here, but it seems a foregone conclusion that viruses
experience frequent mutation, and that a novel virus infecting a new host
species for the first time is going to see a relative explosion in mutations
due to the extreme increase in the number of opportunities for it to occur.

------
jka
This seems risky but worth consideration.

Can you provide peer / concept review from virologists?

A few items of feedback:

\- You could use a title that includes a distinct word to identify your
proposed solution: "Using accentuated COVID-19 strains as a (possible)
solution". This helps people to communicate and refer to the idea concisely.

\- The top three paragraphs may be known to your target audience; consider
allowing the reader to get straight to your point.

\- It took me a while (certainly to the Q&A section) to grasp that attenuated
virus strains are different from dangerous ones. Explaining this (perhaps in a
brief sentence, then repeated and elaborated in a more detailed paragraph)
near the top may also help.

\- Further references (especially peer review from respected authors) may help
gain traction. Decision makers can be -- sensibly -- risk averse in global
crises like these.

Good luck!

~~~
danieltillett
I am a virologist - well I have published many papers in this area. I have a
PhD in molecular microbiology and have been a tenured professor (I now work in
the biotech sector). This is not intended to be a scientific paper, but a
layman’s summary of the idea so non-technical people can understand the idea.

It is not risky to go looking for a naturally attenuated virus. This is the
first step that needs to happen.

~~~
baybal2
Wouldn't an attenuated strain vaccine still require years of paperwork and
clinical trials too?

~~~
danieltillett
Yes. This is why I am suggesting an alternative. It is all in the blog post.

~~~
Robotbeat
This is an attenuated live vaccine, though. So the risks are similar or worse
than just doing a real, engineered vaccine.

If it's mere paperwork, we can solve that with a regular vaccine just as fast.
And the regular vaccine would be more likely to be safe, even at an early
stage. (Note: I'm a rando, not a medical or biological professional.)

~~~
ferzul
if bureacracy held up the spread of a live coronavirus, we wouldn't be in this
mess

~~~
Robotbeat
The proposal is to _intentionally_ apply a live virus to people, so
_absolutely_ there are bureaucratic barriers to this (and for good reason).
There is no a priori reason why this should have less red tape than a dead
virus.

If we're just going to ignore any regulations and bureaucracy for a live virus
(like this proposes), we can do the same for a dead virus.

~~~
danieltillett
The reason why this should be able to advance faster than a normal vaccine
approach is that we will have epidemiological data that it is safe in humans.
Sure it would be nice to have double blinded placebo controlled data, but good
epidemiology data is still data on which a regulatory decision could be made.
In the current circumstances I think this will satisfy the regulators.

------
IdoRA
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.

~~~
danieltillett
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?

~~~
ajross
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?

~~~
buboard
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

~~~
ajross
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?

~~~
danieltillett
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.

------
elmolino89
Virus can be asymptomatic for a number of reasons. Host factors, such as age,
(speculation) history of the previous coronavirus but not covid-19 infections,
etc.

Going after covid-19 genomes in a group of asymptomatic and symptomatic 70+
years old with sampling from different regions/countries may give us better
data.

Finding a mutated strain which never gives symptoms in old people from diverse
locations, diet, health status etc. is the holy grail of this approach.

~~~
danieltillett
Yes. What we really want is a strain that has infected a whole lot of people
and all of them have had a mild case.

~~~
londons_explore
You probably won't find that... You might find a strain where 99.9% of people
get a mild case.

Who is going to be the person to recommend deliberately spreading that strain
to the world population, knowing that 0.1% of the world, 7 million people,
will end up in a hospital and die?

Sure, overall, fewer people might die, but the reality is whichever world
leader makes that call has effectively just signed a death warrant for 7
million people. That isn't the way to get re-elected.

~~~
danieltillett
I think we can do better than 0.1% death rate. In principle there is no reason
we can’t find a strain that is no more dangerous than the coronaviruses that
cause the common cold.

One thing is certain and that is unless we go out and look we won’t find
anything.

~~~
Lordarminius
@danieltillett

I could quickly put together a team focused on southern Nigeria and Ghana to
find through word of mouth, medical records, contact tracing lists and social
media, people who have experienced covid-19 symptoms and are likely to have
had the disease. My team would also collect samples from people in the worst
affected areas who are asymptomatic. In this way, we could collect data and
enough samples to isolate a(?the) virus if any.

Do you know any organisations that could provide funding and support for this
?

~~~
danieltillett
It is probably best to contact me offline. My email details are on my website.

------
danieltillett
I have posted this again as dang asked me to put it up again.

Happy to answer questions about the idea, but I am most interested in find
collaborators to make it happen ASAP.

~~~
robomartin
I just sent your article to my contacts at the White House, Department of
Defense, DARPA and a couple of other acronym agencies. I sent this to Director
level people (or just under) at those agencies.

No guarantees (they are all swamped). I hope they respond and put you in touch
with the right people.

~~~
danieltillett
Thanks. This is the problem I have run into which is all the right people are
so busy at the moment that they don’t have time to look at something like this
from someone like me.

~~~
robomartin
Yes.

I can confirm that your information got to one of my contacts at the White
House. He replied saying he would distribute it to the right people. Your
guess is as good as mine as to what happens from there. Even people within the
White House have trouble penetrating through various layers due to just how
busy everyone is (as well as security, etc.).

~~~
danieltillett
Thanks once again.

------
Glavnokoman
I totally missed it from the article but how is he going to tell the deadly
strain from the less deadly one? I mean I understand how they can tell the
difference between the two strains. But how to tell that some particular
strain is less deadly? To the best of my understanding the only way to get
there is to sequence the virus from statistically significant number (~10^5
??) of carriers including the significant proportion of those with
asymptomatic cases. Not realistic IMHO.

~~~
joncrane
Not to mention relying on each person's account of the severity of the
symptoms, and coding that into a dataset that corresponds to the sequencing
results. You need a LOT of asymptomatic people with the strain in order to
draw any strong conclusions.

The upside is, you may draw other very interesting conclusions while
collecting data for this mission, and be able to "pivot" if you will.

------
new299
You make this statement: "The most important thing to note is that such a
virus would not be a vaccine from a regulatory perspective."

Can you provide any evidence to back up this statement? If you were to start
intentionally infecting people with a (naturally) attenuated strain claiming
that it will confer immunity I suspect authorities would request you get
regulatory approval.

If you're approach does require regulatory approval. What advantage does your
approach have over those currently in developement? Some of them are just bits
of the virus (mRNA that codes for the spike protein) packaged with a delivery
mechanism [1].

It's a plausible approach, that has been tested in animal studies. There are a
number of other, similarly plausible vaccines entering human trials.

It is however deemed to be too high risk to just start giving the vaccine to
large numbers of people. So the vaccine will have to go through (an
accelerated) trial process. It will then likely be given to at risk groups
(health care professionals), before becoming widely available. Most experts
expect this to take at least 16 months (which would be a world record).

Your approach would have the same issues as are present with any other
vaccine.

If regulatory authorities are willing to skip trials for your approach, then
the same should apply to other vaccines under development.

[1] [https://www.modernatx.com/modernas-work-potential-vaccine-
ag...](https://www.modernatx.com/modernas-work-potential-vaccine-against-
covid-19)

~~~
danieltillett
You are looking at this from the wrong perspective. If people start spreading
this attenuated strain around on their own what are the regulatory agencies
going to do?

Even if you wanted to go down the regulatory pathway for some reason it still
has a number of advantages over other approaches.

1\. We would know it is safe in humans before we began.

2\. We would know what mutations make the virus less pathogenic.

3\. Once used it would drive the pathogenic strains to extinction.

4\. It will be work in poor countries that can’t afford or distribute a
conventional vaccine.

5\. It will infect and protect those that are not deliberately infected
through contact with others.

~~~
new299
> What are regulatory agencies going to to do?

If you were to start doing this without regulatory approval, the most likely
outcomes seems that you’d be arrested [1]. Do you have anything that suggests
otherwise?

> 1\. We would know it is safe in humans before we began.

The regulatory requirements for “knowing it is safe in humans” are currently
quite high. As things stand, I would expect trials to be required. Can you
provide any evidence to suggest trials wouldn’t be required?

You want to know how the vaccine effects individuals with pre-existing
conditions etc. etc. And, as there’s always some risk, you want to be sure
that the vaccine is effective.

> 2\. We would know what mutations make the virus less pathogenic.

Large scale sequencing of the virus, in individuals and populations will be
interesting. Being able to link this patient outcomes is also interesting. And
might help in vaccine development. It would be interesting to have a large
dataset of viral sequences from asymptomatic individuals. Can we see clear
differences between asymptomatic and symptomatic individuals? This would be an
interesting dataset, but I’m not sure that the results would be as clear as
“look this deletion exists in a sub-population of asymptomatic individuals”.
Would be a cool dataset and an interesting project though. There seems to be a
lot of NGS data [2] available. This might be a suitable starting point for
such a project.

> 4\. It will be work in poor countries that can’t afford or distribute a
> conventional vaccine.

If a vaccine is available, then I suspect there will be sufficient
international support to make it widely available. Having an active outbreak
anywhere in the world would likely be deemed an unacceptable risk, given the
potential for further mutation.

[1] [https://www.theverge.com/2020/3/26/21195236/fbi-doj-
arrest-f...](https://www.theverge.com/2020/3/26/21195236/fbi-doj-arrest-fake-
coronavirus-vaccine-cure-covid-19-keith-middlebrook)

[2] [https://www.ncbi.nlm.nih.gov/genbank/sars-
cov-2-seqs/](https://www.ncbi.nlm.nih.gov/genbank/sars-cov-2-seqs/)

~~~
danieltillett
I am not going to be spreading the virus around so why would I be arrested?
Actually once a “safe” strain was identified and could be tested for it would
be impossible to stop it being spread by individuals on their own to those
they know.

As we have seen with the whole HCQ fiasco regulations have a habit of getting
lowered once there is data, even poor data. If we contact trace everyone who
has been infected with the attenuated strain we will get some good data on the
safety of the strain. It might not be 100% safe, and we might have some
questions, but that is a discussion we can have once we find the strain.

We need to make some hard choices here between certainty and action. Waiting
for certainty is a choice that carries a very high cost.

~~~
new299
Perhaps I’ve missed something in your argument then. I’d need to understand
exactly how you are planning to promote the spread of the attenuated form. If
you’re talking about a “sequencing driven” Pox party [1] then I suspect you
will run into issues. Particularly if you were to say that the Pox party will
infect you with an attenuated form of the virus and vaccinate.

Both the diagnostic (sequencing or otherwise) and claim that you are
vaccinating individuals would seem like they’d require regulatory approval.
But I’d be interested in evidence that suggests this is not the case in a
modern context.

Overall, it seems like the idea is as dangerous as deploying an untested mRNA
vaccine. Because of this, I’d suspect that regulatory or other authorities
would get involved.

[1]
[https://en.m.wikipedia.org/wiki/Pox_party](https://en.m.wikipedia.org/wiki/Pox_party)

~~~
danieltillett
I am not planning on doing anything other than trying to look for the
attenuated strain. How it is used is for others - what I am suggesting is once
such a strain is found is it will be impossible to stop people spreading it
around on their own.

~~~
new299
But you do seem to be suggesting that "people spreading it around on their
own" is a "solution to Covid-19"?

Otherwise, what is your plan for this attenuated strain? Don't get me wrong, I
think large scale sequencing or COVID19 is interesting. But think that
attempting to spread a attenuated strain without regulatory approval is
probably a very bad idea.

~~~
danieltillett
Unregulated spread by individuals is a solution, just not the one I think
would be implemented if such a strain were found.

I think it much more likely that the regulatory agency would quickly approve
the use of the strain on the basis of the epidemiological data gathered in the
process of finding it.

~~~
CathedralBorrow
> I think it much more likely that the regulatory agency would quickly approve
> the use of the strain on the basis of the epidemiological data gathered in
> the process of finding it.

Have you had experience with dealing with said regulatory agencies?

~~~
danieltillett
Unfortunately yes and they normally move at a glacial pace and demand 100%
certainty about everything. I do have faith that they are capable of moving
faster when the need is as urgent as the need right now.

------
JohnJamesRambo
I like your idea a lot. It seems that a 12 nucleotide insertion mutation is
responsible for a lot of the Covid-19 virulence. If such a large mutation is
possible, how would we prevent your loss of function asymptomatic strain from
reverting its mutation in the wild? How big of a mutation are you envisioning?
Is it impossible for it to be reverted in the wild or just unlikely?

[https://www.nature.com/articles/s41591-020-0820-9](https://www.nature.com/articles/s41591-020-0820-9)

~~~
danieltillett
I think 12 nucleotides is too small, I would be happier with something north
of 30. There have already been strains identified with a deletion of 382 bases
[0].

0\.
[https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1....](https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1.full.pdf)

------
ziga
> More than 50% of the people infected with SARS-CoV-19 are asymptomatic (i.e.
> they have no illness).

Note: asymptomatic at the time of testing. They may still develop symptoms
over time.

[https://www.icelandreview.com/sci-tech/is-icelands-
coronavir...](https://www.icelandreview.com/sci-tech/is-icelands-coronavirus-
testing-showing-that-50-of-cases-have-no-symptoms/)

[https://twitter.com/cmyeaton/status/1246196001775460358](https://twitter.com/cmyeaton/status/1246196001775460358)

~~~
danieltillett
Yes this is true. For the purpose of my idea it doesn’t matter if the person
is asymptomatic or they just have a mild case. What is important is the strain
identified doesn’t put people in hospital.

~~~
andai
The key here is that the vulnerable population needs to tolerate it, too.

~~~
danieltillett
Technically they don’t provided we can get the herd immunity up to a decent
level in the rest of the population.

While it would be a good idea if the mutated strain was no more dangerous than
a common cold coronavirus, we could drive the dangerous strains to extinction
without having to infect the vulnerable.

~~~
jfoster
Very difficult to get herd immunity up to a decent enough level without
putting the vulnerable portion of the population in great danger though. Most
countries are approaching something like 0.1% or 0.2% of the population having
been infected. Herd immunity requires 70% - 80% immunity. About 350x - 800x
more than what's happened already.

Also the whole thing presumes that immunity is lasting. Some of the data is
showing that may not be the case.

~~~
danieltillett
The level of herd immunity needed is related to the R0 which is a function of
behaviour. This is a really complex topic to discuss, but it is only one we
can have once an attenuated strain is found.

Of course the other factor is who is a vulnerable person is a factor of the
pathogenicity of the viral strain.

------
rmu09
The results of a study in austria with 1500 randomly selected citizens have
just been published, just 5 have been found to be currently infected with
SARS-CoV2.

The conclusion is that the prevalence of asymptomatic cases is about 0,32%,
CL95 is 0,12-0,76%.

Link (in german): [https://www.sora.at/nc/news-presse/news/news-
einzelansicht/n...](https://www.sora.at/nc/news-presse/news/news-
einzelansicht/news/covid-19-praevalenz-1006.html)

~~~
FiberBundle
This goes contrary to what other studies have found. In the Stockholm
metropolitan area they found that 2.5% percent of the population was infected
[1]. In in a community in Germany, which was the epicenter of the outbreak for
a time, they found that 15% of the population tested positive for antibodies
[2]. In Iceland they found that 88-93% of the infections are undetected [3].

[1] [https://www.folkhalsomyndigheten.se/nyheter-och-
press/nyhets...](https://www.folkhalsomyndigheten.se/nyheter-och-
press/nyhetsarkiv/2020/april/resultat-fran-undersokning-av-forekomsten-av-
covid-19-i-region-stockholm/)

[2]
[https://www.land.nrw/sites/default/files/asset/document/zwis...](https://www.land.nrw/sites/default/files/asset/document/zwischenergebnis_covid19_case_study_gangelt_0.pdf)

[3] [http://www.igmchicago.org/wp-
content/uploads/2020/04/Covid_I...](http://www.igmchicago.org/wp-
content/uploads/2020/04/Covid_Iceland_v10.pdfhttp://www.igmchicago.org/wp-
content/uploads/2020/04/Covid_Iceland_v10.pdf)

~~~
rmu09
I don't think it is actually contrary to those other studies. The austrian
study randomly selected among the whole population whereas the german study
used a cluster connected to a hot-spot. IMO it is measures like social
distancing in place for more than 3 weeks at the time of sample-taking in
austria that reflect in the data.

~~~
FiberBundle
It does. The german study was conducted in a town that was relatively heavily
tested during its outbreak, and only recorded 2.5% official infections in the
population of that town, so the german study showed the actual number to be 7
times as high. This Austrian study found this number to be only ~2.5 times as
high. Germany and Austria overall seem to test fairly similarly.

~~~
rmu09
The austrian number says currently active cases are probably 2.5 times as much
as official numbers.

German study says in a community linked to an outbreak, there are 14% immune
and 2% to be shedding viral DNA.

Austrian study didn't include antibody test (yet).

------
choeger
Stupid question: if you only search people with mild or even asymptomatic
cases, how does that even tell you something about the virus? Should you not
also search in (many) severe cases for the candidate, to exclude it from the
list of dangerous virii?

~~~
danieltillett
There are no stupid questions, just stupid politicians.

We are looking for an attenuated strain and that will be found in people with
a mild case. We could sequence all cases, but we would exclude any strain that
puts someone in hospital so it is a waste of resources to sequence viruses
from people in hospital. From a practical perspective it is better to
concentrate on people with only mild cases.

~~~
choeger
But honestly, if you only look into people with mild cases, how do you know
the virus causes these mildness?

If I pick 1k people with mild cases at random, I will find pretty much any
strain that currently is in circulation. How do I know which strain is
harmless?

~~~
danieltillett
You don’t, but what you are looking for is a virus with a largish deletion in
an essential gene. You then go and look for anyone in contact with this person
and check them and then expand out to the whole local area. If everyone
infected with this strain has a mild illness they you have hit the jackpot.

I do describe this in my blog post.

~~~
zxcmx
I think GP's point was that if you have a candidate it would also make sense
to use sequences from the hospitalised to try and confirm your strain didn't
put them there.

Aka this being one mechanism by which you confirm it is only producing mild
illness. There's a limited amount you can find out by asking because nobody
knows what strain they had.

~~~
danieltillett
You really want to find every single person who has been infected with the
mutant strain and find out how sick they got. If you find a mutant that
infected 10,000 people and didn’t cause any serious illness then you have a
pretty good idea it safe.

~~~
NyxWulf
I think the point is that you have to sequence people in the hospital as well,
otherwise you won't know if that particular strain is safe or not.

If it is a rare strain, how will you know if it's safe? Seems like it would
have to be a rare strain with thousands of cases and hospitalizations in that
population are extremely rare.

Sampling bias and other confounding factors would be a real problem in this
search, at least from a statistical point of view, imo.

I also think finding everyone who has been infected with a strain isn't
feasible, at best you are sampling from the population.

~~~
danieltillett
You actually want to screen all people in the local area for the strain that
may have it. If all the people have had a mild case and none of them are in
hospital then you have something special.

------
dmichulke
I see two problems with this approach, both political / social:

\- No one will want to be the one "deploying" the attenuated strain in a human
and then be responsible for some unforeseen death (even if it's just 1 in a
billion). Utilitarianism is not widespread nor socially accepted. Even less so
in politicians, who are quite risk averse.

\- There is no lobby supporting it. There's no $$ to be made and the "vaccine"
is basically free.

~~~
FriedPickles
_No one will want to be the one "deploying" the attenuated strain in a human
and then be responsible for some unforeseen death (even if it's just 1 in a
billion). Utilitarianism is not widespread nor socially accepted. Even less so
in politicians, who are quite risk averse._

I would give them more credit, especially in a situation where the status quo
includes so many deaths. I was impressed with how readily most states licensed
self-driving vehicles, knowing that there would certainly be deaths. Their
rationality here likely came from seeing tens of thousands of people dying on
the roads each year.

------
chaseadam17
I am not an expert, so I apologize if these are a dumb questions, but here
goes:

1) Wouldn't natural selection result in a milder strain crowding out a more
deadly strain? After shelter in place lifts, people with a mild strain will be
more likely to go out and spread the virus whereas people with the deadly
strain will be more likely to stay home sick.

2) Is there any consensus on whether we become immune to COVID after getting
it (e.g. if we get a mild strain will we really be immune to a deadly one)?
I've heard different opinions and I'm wondering what the leading hypothesis is
at the moment.

Thanks!

~~~
bob33212
That sounds correct, but "scientifically" we have to spend million of dollars
and months of time to say for sure.

------
edw519
This reminds me of a story 20 years ago when Pittsburgh Steelers (American
football) announcer Myron Cope ran into head coach Bill Cowher...

Myron said, "I see that Lee Flowers is playing today after a high ankle sprain
2 weeks ago. But I thought that high ankle sprains took 4 weeks to heal. What
gives?"

Coach Cowher replied, "4 weeks is true, Myron, for the _first_ high ankle
sprain. But if you recall, Lee had a high ankle sprain on the same foot last
year. And since subsequent high ankle sprains only take 2 weeks to heal, he's
ready to play."

Myron paused and asked, "Then why don't you just take the whole team out in
February and sprain all their ankles?"

(We laughed 20 years ago. Nobody's laughing today.)

~~~
pjc50
This reminds me of the old joke that, because the possibility of there being
_two_ bombs on a plane is infinitesimally small, you should always bring your
own bomb with you.

------
robocat
Another strain that might be less deadly:
[https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1....](https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1.full.pdf)

Also it is a paper from Singapore which should avoid the China negative bias.

~~~
danieltillett
This is exactly the sort of strain we want to be looking for all though we
want a strain that doesn’t come from hospitalised patients. This deletion is
still too pathogenic for our needs, but it does prove these deletion strains
are out there. If we look we will find.

------
ubercow13
How would you allow the harmless strain to spread without also spreading the
deadly strain? If you relax or reverse social distancing, wouldn't the deadly
strain also have a chance to spread widely again? It seems like you'd need to
manually administer this strain to millions of people, or have very carefully
administered 'contagion parties' where everyone is pre-screened for the deadly
strain, while everyone else keeps social distancing.

~~~
throwaway_pdp09
> you'd need to manually administer this strain to millions of people

Yes. And how would that compare to the various trillions in stimulus to keep a
choking world economy afloat, never mind the deaths that could be avoided?

I don't understand posts like this, they say "if we had a good solution, how
could we possibly use it?"

~~~
ubercow13
I think you’re reading too much into my post, I was just wondering how to
safely carry out this idea.

One reason I was wondering is that manually administering the virus to people
seems more akin to a vaccine in nature.

~~~
danieltillett
Only if you consider hanging out with someone a vaccine.

As I mentioned in my reply to you it will be impossible to stop this strain
from being deliberately spread by people on their own.

~~~
CathedralBorrow
Wouldn't the same social distancing measures that keep the dangerous strain at
bay keep the "good" one from spreading? And vice versa.

~~~
danieltillett
Yes they would, but if people know their friends have the mild version they
might choose to break the social distancing rules and go and visit them for a
tea and nice close chat.

------
user_50123890
I don't think the mutations are the reason for asymptomatic cases.
Coronaviruses mutate very slowly.

More likely, viral load, immune system strength, overall age and the genetics
of the person infected are what determines if the infection is fought off
before any symptoms are shown

~~~
drewblaisdell
For my own understanding: where can I read about how coronaviruses mutate
slowly?

~~~
MichaelJanssen
It is deemed to have an RNA repair mechanism. This is suggested by analogy
with other coronaviruses [1,2] and the length of its RNA of ~30k nucleotides
while the upper limit for RNA without repair mechanism seems to be 10k [3].
The german wikipedia cites [4] which I found nicer to read.

[1]
[https://en.wikipedia.org/wiki/Coronavirus#Replication](https://en.wikipedia.org/wiki/Coronavirus#Replication)
[2]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984655/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984655/)
[3]
[https://de.wikipedia.org/wiki/Coronaviridae#Genom](https://de.wikipedia.org/wiki/Coronaviridae#Genom)
[4]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127101/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127101/)

------
nabla9
There are several pre-clinical studies with live attenuated viral vectors and
replicating viral vectors going on against SARS-CoV-2.
[https://www.who.int/blueprint/priority-diseases/key-
action/l...](https://www.who.int/blueprint/priority-diseases/key-action/list-
of-candidate-vaccines-developed-against-sars.pdf?ua=1)

Developing attenuated-virus vaccines is by screening serially propagated SARS-
CoV-2 for reduced pathogenity has also been suggested already.

1\. The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines
[https://www.nature.com/articles/s41541-020-0170-0](https://www.nature.com/articles/s41541-020-0170-0)

2\. Regla-Nava, J. A. et al. Severe acute respiratory syndrome coronaviruses
with mutations in the E protein are attenuated and promising vaccine
candidates. J. Virol. 89, 3870–3887 (2015).
[https://www.ncbi.nlm.nih.gov/pubmed/25609816/](https://www.ncbi.nlm.nih.gov/pubmed/25609816/)

Authors idea of spreading the attenuated virus is based on the idea that if
the immediate COVID-19 disease can be avoided, increasing viral load in
population is smaller risk. I think that's the weak point. If the vaccine is
developed and the virus establishes itself in the population, the number of
people getting infected will be lower overall and less people will get severe
disease due to natural immunity + vaccine.

ps.

> appears to be killing between 1% to 3.5% of the people it infects

Author is confusing case fatality rate (CFR) with infection fatality rate
(IFR). Infection fatality ratio seems to be something like 0.6% according to
recent estimates. IFR estimates seem to go down over time.

~~~
danieltillett
This is not a proposal for a live attenuated vaccine.

These numbers on the death rate are not mine, but what has been reported in
the scientific literature. Probably the best numbers come from South Korea
where they have done a pretty good job of tracking down everyone infected.
There the fatality rate is around 1.8%.

Even if the true death rate is 0.6% that still means the deaths of nearly 50
million people worldwide.

~~~
nabla9
Even the sources you cite give case fatality rate not infection fatality rate.
You are confusing the two.

~~~
danieltillett
The true infection rate is irrelevant. Nobody knows what it is right now and
by the time we do it will be too late.

~~~
nabla9
We are talking infection fatality rate not infection rate.

Infection fatality rate is number of people who die after they are infected.
That's one of the most important numbers and it can be estimated. It's
different from case fatality rate. Number of people diagnosed with COVID-19
who die.

You started your argument trying to argue based on your understanding of what
the infection fatality rate is.

~~~
danieltillett
Nobody knows the true infection fatality rate. Probably the best estimate we
can make is from South Korea where they have done a pretty good job of testing
everyone infected. There the infection fatality rate is 1.8% and rising as the
cases age out and people in the ICUs die.

~~~
nabla9
> Nobody known the true infection fatality rate.

It can be estimated with increasing accuracy.

> There the infection fatality rate is 1.8% and rising as the cases age out
> and people in the ICUs die.

You continue citing case fatality rate (CFR) numbers and call them infection
fatality rate numbers (IFR). Can you please go back to your sources and read
what they say. I bet they are case fatality rates. In South Korea one IFR
estimates put the number around 0.4 and 0.7%.

Here are some IFR estimates:

1\. Estimating the infection fatality rate of COVID 19 in South Korea by using
time series correlations
[https://figshare.com/articles/Estimating_the_infection_fatal...](https://figshare.com/articles/Estimating_the_infection_fatality_rate_of_COVID_19_in_South_Korea_by_using_time_series_correlations/12083322)

2\. Estimating the infection and case fatality ratio for coronavirus disease
(COVID-19) using age-adjusted data from the outbreak on the Diamond Princess
cruise ship, February 2020
[https://www.eurosurveillance.org/content/10.2807/1560-7917.E...](https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.12.2000256)

3\. Using early data to estimate the actual infection fatality ratio from
COVID-19 in France
[https://www.medrxiv.org/content/10.1101/2020.03.22.20040915v...](https://www.medrxiv.org/content/10.1101/2020.03.22.20040915v2)

4\. Robust Estimation of Infection Fatality Rates during the Early Phase of a
Pandemic
[https://www.medrxiv.org/content/10.1101/2020.04.08.20057729v...](https://www.medrxiv.org/content/10.1101/2020.04.08.20057729v1)

~~~
danieltillett
These lower estimates are all estimates.

Really it is not important from the perspective of doing something about this
pandemic as a huge number of people will die at all estimated levels.

~~~
nabla9
Maybe you can now correct the "killing between 1% to 3.5% of the people it
infects" part. It's horribly misleading.

IFR < CFR and IFR estimates go always down over time and never up due to the
skewed nature of the data. Antibody tests are coming in already and based on
them you get very accurate numbers.

~~~
danieltillett
I am going to update the post this morning - lots of good feedback from people
here on which sections are confusing. I will update this section :)

------
ImaCake
I want to argue that the flaw in this is with the ability to find any strain
that consistently causes only minor symptoms. If you infect a whole group of
people with Covid-19 then we would see a distribution of severity from no
symptoms to lethal. This broad spectrum is really just it's statistical
variance (whatever the underlying distribution really looks like).

It is worth comparing this to things like SARS. The distribution of SARS
symptoms would be pretty narrow - everyone gets really sick. So the variance
for SARS is small compared to Covid-19. The same could be observed for
influenza or rhinoviruses.

The problem with a "milder" Covid-19 is that it might still have the same
massive variance in symtpom severity. It might kill less people, but it would
still be morally bankrupt to let it spread. In fact, it might be preferable to
not reduce the mean severity, but just decrease the variance so it never gets
nasty enough to kill without being immuno-compromised.

~~~
buboard
This paper argues on the basis of symptoms that there might be a milder strain
that has dominated some countries vs others

[https://www.medrxiv.org/content/10.1101/2020.03.28.20036715v...](https://www.medrxiv.org/content/10.1101/2020.03.28.20036715v2)

~~~
dboreham
There may be other explanations such as past use of vaccines for other
diseases, that varies country to country.

~~~
ImaCake
Yes. Or just variations in our immune systems. Immune systems are incredibly
complex systems. It is difficult to overstate just how complex and varied they
are. And they differ between individuals to an amazing extent.

If immunity is important to symptom severity, it may manifest as some weird
correlation you might find in a cross-sectional study. Maybe gluten
intolerance or a history of acid reflux will be a marker that lets you know
what your risk of severe disease are.

------
xvilka
In one of the article comments there is an interesting suggestion on reviving
the research on DRACO[1]:

> In cell culture, DRACO was reported to have broad-spectrum efficacy against
> many infectious viruses, including dengue flavivirus, Amapari, and Tacaribe
> arenavirus, Guama bunyavirus, H1N1 influenza, and rhinovirus, and was
> additionally found effective against influenza in vivo in weanling mice. It
> was reported to induce rapid apoptosis selectively in virus-infected
> mammalian cells while leaving uninfected cells unharmed.

They even had a crowdfunding campaign on Indiegogo[2] but as usual, nobody
cares about infectious diseases until the pandemic...

Now the crowdfunding seems moved to another page[3]

[1] [https://en.wikipedia.org/wiki/DRACO](https://en.wikipedia.org/wiki/DRACO)

[2]
[https://www.indiegogo.com/projects/1641241](https://www.indiegogo.com/projects/1641241)

[3]
[https://riderinstitute.org/discovery/](https://riderinstitute.org/discovery/)

~~~
enchiridion
Why did they choose indiegogo over traditional medical research funding?

~~~
X6S1x6Okd1st
The source that wikipedia cites says the following:

"However, research on DRACOs has entered the well-known “Valley of Death” in
which a lack of funding prevents DRACOs, and many other promising new drugs,
from being developed and advancing toward human medical trials. To progress
DRACOs research it needs to be demonstrated against clinically relevant
viruses (i.e; HSV). To that end an IndieGoGo campaign
([http://igg.me/at/EndTheVirus](http://igg.me/at/EndTheVirus)) was started on
October 13, 2015."

They don't seem to elaborate on what the hell they mean by the valley of
death.

[http://www.prweb.com/releases/2015/10/prweb13018147.htm](http://www.prweb.com/releases/2015/10/prweb13018147.htm)

~~~
mtnGoat
Basically there is funding for early research, and for drugs that are really
close to release, but the years in between (the drudgery) aren't very
interesting to investors so capital is hard to come by to keep projects alive.

An acquaintance is $600m into a new type of Malaria testing and his funding is
slowing, but is frustrated because he feels he is closer then ever. Frankly im
amazed he got this far, thats a lot of burn.

Basically funding for drug research is all screwy!

------
tomohawk
Apparently China has at least one hospital full of asymptomatics.

[https://www.straitstimes.com/asia/east-asia/mystery-of-
long-...](https://www.straitstimes.com/asia/east-asia/mystery-of-long-term-
patients-confounds-wuhan-doctors)

------
p1mrx
> it would be much better to just post a sample of the virus to everyone for
> example

If COVID-19 is human malware, then this is a human software update.

~~~
oezi
At what probability of bricking during update would you stay on the old
vulnerable version?

------
annoyingnoob
How do we know that a less deadly strain actually provides some immunity to a
more deadly strain? That seems like an assumption here.

~~~
Amygaz
His assumption is based on live-attenuated vaccines. The measles vaccine being
one of those. All the early vaccines where like that. The process only
requires heat inactivation. So you end up with a dead or almost dead virus,
which can't replicate anymore. Your immune system recognizes it as a foreign
agent, makes antibodies to tag it for removal.

Today we prefer to immunize with a part of the virus structure, which end up
doing the same thing.

~~~
annoyingnoob
Still seems like an assumption until its tested/proven. I'd prefer a more
evidence based approach, evidence from this virus.

~~~
danieltillett
You can only get evidence if you go out and collect the evidence. I am
proposing a way we can actually collect this evidence. Saying something won’t
work because there is no evidence when you haven’t look for any evidence is
not very logical.

~~~
annoyingnoob
Just questioning assumptions, in a healthy skepticism kind of way. I have no
expertise here. There is a lot of speculation and general fud surrounding
covid-19, seems right to question potential 'solutions' when we are light on
facts. To be clear, I never said it wouldn't work, I'm saying that it looks
like you assume it will work.

~~~
danieltillett
I most certainly have not assumed it will work, in fact I say there is a
pretty good chance it won’t. What I do think it could work and that the cost
in minor compared to the payoff if it does work.

~~~
annoyingnoob
In which case, we need to think about Medical Ethics. Do we start
experimenting with you and your loved ones?

~~~
danieltillett
Nobody is being experimented on or proposed to be experimented on. The
proposal is to go and look for an attenuated strain and then decide what to do
with it if we find one.

~~~
annoyingnoob
[https://www.npr.org/sections/coronavirus-live-
updates/2020/0...](https://www.npr.org/sections/coronavirus-live-
updates/2020/04/25/844939777/no-evidence-that-recovered-covid-19-patients-are-
immune-who-says)

------
hilbertseries
You say

> The reason why is immunity to respiratory viruses (like corona) doesn’t last
> long – 6 months to 2 years.

I haven’t read anything like this before. It seems like you’re extrapolating
from the flu vaccine, which doesn’t last because the flu mutates too quickly.
Coronavirus mutate much slower and the thought is that we’ll likely only need
one vaccine. Have we actually found any less deadly strains? My understanding
is that there have been mutations, but all are small and as far as we can tell
superficial. You would likely need to create such a mutation and then you’re
back in vaccine trial territories, except dozens of labs that are experts on
this have a head start.

~~~
DanBC
[https://www.nature.com/articles/d41586-020-00798-8](https://www.nature.com/articles/d41586-020-00798-8)

> If humans do develop immunity, how long does it last?

> That’s another big unknown. Immunity is short-lived for the coronaviruses
> that cause common colds; even people who have high levels of antibodies
> against these viruses can still become infected, says Stanley Perlman, a
> coronavirologist at the University of Iowa in Iowa City.

> The evidence is more equivocal for the two other coronaviruses that have
> triggered epidemics: those that cause severe acute respiratory syndrome
> (SARS) and Middle East respiratory syndrome (MERS). Perlman says his team
> has found that after people recover from MERS, their antibodies against the
> virus drop precipitously. He also says that his team has gathered data — not
> yet published — showing that SARS antibodies are still present in the body
> 15 years after infection. But it’s not clear whether this immune response is
> enough to prevent reinfection. “We don’t have good evidence of long-lasting
> immunity, but we also don’t have really good data from both SARS and MERS,”
> Perlman adds.

~~~
danieltillett
This is a huge problem for the whole vaccine approach and is one of the
reasons that it may not be possible to create a conventional vaccine.

------
ed_balls
I've been thinking about this a few days ago when I went into the wikipedia
rabbit hole about vaccinations and inoculation.

A few questions:

\- How about the dengue fever scenario? (Immunity to less pathogenic strain
can cause more severe reaction with a different strain). Can we asses the risk
somehow?

> Apart from the time it will take to develop, trial, and mass produce a
> vaccine (12-18 months), it is unlikely that any vaccine will be practicable.
> The reason why is immunity to respiratory viruses (like corona) doesn’t last
> long – 6 months to 2 years

Is there any proof that this is the case with this virus?

Is is possible to do the infection outside the human body?

~~~
cjbprime
We just don't know. Either case (short immunity like the common cold, or
permanent immunity) is possible.

~~~
ed_balls
It seem the permanent immunity is unlikely
[https://youtu.be/4EUZEtJHQhE?t=639](https://youtu.be/4EUZEtJHQhE?t=639)

------
tim333
Sounds like a good idea.

Another interesting possible solution which can be used now but is a bit
unproven is to use hydroxychloroquine + zpak + zinc or some variation on that
on people with symptoms or who test positive as it seems to reduce viral
spreading.

Bit controversial but the results in Marseille look quite good - the infection
rate in those tested has roughly halved recently while France as a whole is
going up. [https://madeinmarseille.net/64805-covid-19-didier-raoult-
res...](https://madeinmarseille.net/64805-covid-19-didier-raoult-resultat-
chloroquine/) [https://www.mediterranee-
infection.com/covid-19/](https://www.mediterranee-infection.com/covid-19/)

And the anecdotal reports from the Zeleko guy are good even if people think
he's a nut.

Also in the Rome area "every single person with Covid-19 that has early signs,
like a cough or a fever for example, is now being treated with the anti-
malaria drug." Which may provide data going forward
[https://www.trustnodes.com/2020/03/29/italy-finally-
starts-m...](https://www.trustnodes.com/2020/03/29/italy-finally-starts-mass-
treatment-with-hydroxychloroquine)

Anyway unproven but may be a way forward if the results prove good.

------
lpa22
Agreed that the risk:reward ratio here would be worth it. This sounds super
promising. That being said, how is it known that having had the mutated strain
provides immunity to the dangerous strain?

~~~
danieltillett
The reason why it would provide immunity is all the structural proteins would
be the same. To our immune system it would look like the same virus as the
pathogenic strains.

This is not really anything unusual and is exactly how viral live vaccines
work. The vaccine for live polio and measles work exactly this way.

------
efavdb
Pooling could be used to more rapidly test the asymptomatic population:

[https://github.com/EFavDB/pooling](https://github.com/EFavDB/pooling)

~~~
danieltillett
Even better than pooling is griding [0].

0.[https://twitter.com/rwade300/status/1247340350076628992](https://twitter.com/rwade300/status/1247340350076628992)

~~~
sampo
If B2 and D4 are positive, then in the marginals B,D,2,4 will show positive,
but you don't know which of B2, B4, D2, D4 are positive.

~~~
danieltillett
Yes that is true, but when the case rate is low this is not a common problem.
The ideal size of the grid is adjusted to expected case rate.

If you get ambiguity then you just move those samples across to a new grid (in
locations that won’t be ambiguous) and test again.

------
rediguanayum
(caveat: amateur)

I think this is a great idea to get community involvement upon. I'm sure you
know there's a network of researchers on Twitter (I'm aware of the one
centered around the Krogan lab in UCSF i.e. @KroganLab), and on Reddit
(reddit.com/r/covid19) that have been posting ideas back and forth. Consider
posting there.

I like your idea because it circumvents a number of ethical issues, but may be
time/resource consuming. Another approach but one that quickly hits those
ethical issues during testing would be to knockout immunosuppressant genes as
popularly described by:
[https://www.nytimes.com/interactive/2020/04/03/science/coron...](https://www.nytimes.com/interactive/2020/04/03/science/coronavirus-
genome-bad-news-wrapped-in-protein.html) (preprint
[https://www.biorxiv.org/content/10.1101/2020.03.22.002386v3....](https://www.biorxiv.org/content/10.1101/2020.03.22.002386v3.full.pdf+html)).
Perhaps mice model? An in between approach that might be better, would be to
target your search by looking for changes that likely inactivates the
immunosuppressant genes.

I and I'm sure many others dearly hope your approach works. Godspeed sir.

------
beoh
This might be a naive question, but could this strain be created by some kind
of gene editing?

~~~
danieltillett
Yes it could, but we wouldn’t know what edits to make. What this idea is using
is nature to tell us what mutations make the virus less dangerous.

~~~
beoh
I see, thanks!

------
buboard
Considering that we are now in a shutdown, and assuming that most symptomatic
people do get tested and isolate themselves, doesnt that mean there is
pressure for asymptomatic strains to evolve and keep spreading faster in the
population anyway? they would be more likely to exist in the early epidemics,
specifically south korea which aggressively quarantines people, but does not
impose lockdowns, letting the asymptomatic spread

~~~
danieltillett
There is really no selection pressure on the current dangerous strain right
now. If it was killing 50-60% of people infected then yes the selection
pressure would be there, but at a death rate of 1.5%-2% there basically is
very little selection pressure on the timescales we are interested in.

It doesn’t really matter to us today if this virus eventually becomes less
dangerous in the next 500 years. We need to speed things up a little.

~~~
buboard
> If it was killing 50-60% of people infected then yes the selection pressure
> would be there

it isnt killing, but it's isolating them, preventing its spread

~~~
notahacker
That's already baked in to human responses to suspected COVID-19 though, and a
chance mutation to a less lethal strain would be unlikely to change human
responses to an outbreak in a way which benefited the virus' ability to
spread.

~~~
buboard
i assume we re looking for asymptomatic people, they won't have quarantined
themselves

------
bserfaty
Can't the attenuated strain mutate back to a strong dangerous one after we
spread it? (Hope this isn't a stupid question)

~~~
ztjio
In theory any coronavirus could, including the 4 we consider absolutely
harmless.

In fact, with existing attenuated virus approaches that eventually becomes the
problem, the "last mile" of this approach usually sees you needing a real
vaccine to cap off the disease. Otherwise the virus kinda circulates around in
a tight enough cycle that you see most if not all eventual mutations including
dangerous ones that kill. Communities using attenuated virus vaccination
approaches for Polio faced this in recent times, for example. And it becomes a
problem in places where you can't get people to afford or accept the real
vaccine.

Anyway it's a tried/tested approach to solving a pathogen problem, so it's
hardly some crazy idea this person has. They do point out the there will be
specific types of mutations that are less likely to mutate back if you read
the whole article.

~~~
danieltillett
The problem with polio back mutating is limited to one of the three strain in
the live vaccine and is due to the mutations not being deletion mutations. The
live polio vaccine was developed before people knew this and for regulatory
reasons the problem has never been fixed.

This problem is easy to avoid these days.

~~~
ztjio
I have no reason to believe you're wrong, I just wanted to point out that we
(as a whole community of scientists etc.) can observe an entire range and
lifecycle of this approach and that we're aware of the risks based not only on
theory but on practice.

Personally I see your proposal as a relatively worthy endeavor to consider.

------
ck2
This is why scientists and mathematicians never make it as politicians in the
USA

You may have the best idea in the world, but your presentation is terrible,
the rambling is terrible, the assumption you are the only person to think of
this is terrible and the urge to get the attention of someone important to pay
for it is terrible.

The sad truth is you need to fit your idea into the size of a tweet, write the
long version elsewhere linked. If you can't do that, someone else can and will
and their idea will win over yours because you can't get attention rambling
like that

And governments are never going to purposely infect their populations, if you
think anti-vaxers are bad, imagine when people in the USA have the choice not
to get the injection, 99% of the fox news viewers will refuse and the
president will say "well you can if you want but I won't" (I mean he won't
even stop shaking hands or wear a mask)

~~~
danieltillett
You are welcome to rewrite my post and even claim the idea as your own if you
want. Make it as short as a tweet (which I have done by the way) and send it
out into the world.

------
robocat
Another relevant link:
[https://www.medrxiv.org/content/10.1101/2020.04.14.20060160v...](https://www.medrxiv.org/content/10.1101/2020.04.14.20060160v1)

~~~
robocat
And another about mutation rate being a lot higher than thought:
[https://www.scmp.com/news/china/science/article/3080771/coro...](https://www.scmp.com/news/china/science/article/3080771/coronavirus-
mutations-affect-deadliness-strains-chinese-study)

------
conductr
Any back of envelope math on how much this "search" will cost? Does it require
someone with Bill Gates sized bank account or are you mentioning him because
you know he is specifically active in this area of philanthropy/very
influential?

~~~
danieltillett
Yes. Less than a million dollars - I actually can afford to pay the whole
thing myself. The only reason to get someone like Bill Gates involved it to
get access to the samples and the required political capital to make it
happen.

~~~
tim333
Cool. I hope you get it done.

------
anonymouz
It seems the reason the vaccine will take so long (12-18months) to develop is
because it needs to be tested for long-term safety which takes a trial with
long-term monitoring. As this is essentially a sort of (active) vaccine, how
do you propose ensuring it's long-term safety? It seems you'd run into
essentially the same problem as with developing the vaccine.

~~~
riedel
It seems to me that the whole article describes to me an alternative way to
find a vaccine . Maybe someone can enlighten me: aren't there vaccines that
are simply rather harmless mutations/relatives of the virus but trigger the
same immune reaction?

~~~
grey-area
Yes, there are

[https://en.m.wikipedia.org/wiki/Attenuated_vaccine](https://en.m.wikipedia.org/wiki/Attenuated_vaccine)

------
patall
A huge problem I see with this is that already circulating coronaviruses cause
immunities as short as 3 months. While the SARS virus seems to cause much
longer immunity (same for MERS), this may be linked to the strong symptomes
that people have, thus may be due to a stronger immune reaction. Asymptomatic
cases and people with mild symptoms may therefore be immune only for a short
time. If this is the case, any herd immunity strategy will achieve not much
but endanger many many people.

~~~
danieltillett
This is the exact problem my idea solves.

Please take some time to read through the whole proposal again. I know this
sound snarky, but yours is a really common response that has been addressed.

~~~
NyxWulf
I did read through your entire proposal, this is a legitimate question, and is
not address in your proposal. It is definitely not the problem your proposal
is aimed at solving.

The question posed is would an attenuated virus create a much short immunity
reducing efficacy of the overall approach. It seems like the only answer can
be we don't know, we'd have to look at that.

~~~
patall
Exactly. His whole proposal is based on the assumption that an attenuated
strain imuunizes enough people long enough. This has been possible in other
diseases. But for example not the common cold, and not only because many
different virus belong to that category.

So yes, I read your proposal. No, this is not addressed.

------
nickthemagicman
"We have a choice of taking some small risk now, or face the certainty of a
much worse problem later. Time to accept some risk and do something."

Agreed 100%.

What about simply letting the people who young and healthy or immune go about
their lives?

Letting the young and healthy get sick and then become immune is essentially
using an attenuated human instead of an attenuated virus. Same outcome though.

This would both build herd immunity and keep the economy going.

~~~
danieltillett
This seems to the Swedish plan. What I have noticed with this plan is that a
lot of vulnerable Swedes have died from this plan. I think we can do better.

~~~
nickthemagicman
Please post numbers instead of sensational posturing next time.

Sweden has no quarantine and has been averaging around 400 to 500 new cases
daily while UK quarantined everyone and has 4000 to 5000 new cases daily.

The interesting thing is that the UK has 60 million people while Sweden has 10
million people.

So according to those numbers...how effective is quarantine?

~~~
danieltillett
Sweden is not doing too much testing either. I am not sure if the UK is a good
comparison as they are not really in lockdown at the moment. I think the
better comparison is to Norway and Denmark.

------
nikolay
I hear a lot of ideas, which ignore the indications from both China and South
Korea about re-infection. Nobody for sure knows how long the immunity lasts.
Also, people could be asymptomatic/mild-symptom, just because they have a
strong immune response, not because the strain is less deadly. How do you
quantify who is immunosuppressed and who has a well-functioning immune system?

~~~
danieltillett
Yes, but this idea of mine is not one of these ideas.

~~~
nikolay
I read your idea, but it doesn't address the exact points I listed - selecting
a "less deadly" strain and having fingers crossed that immunity persists. So
far, many have insufficient antibody counts and get reinfected. I just saw a
number around 20%.

~~~
danieltillett
There are lots of things we don’t know right now. This is not a reason for not
acting.

If my proposal works we don’t need to worry about immunity persisting because
the dangerous strains will be driven to extinction.

------
yters
South Korea somehow avoided the whole lockdown approach.

~~~
Igelau
Can we confidently say what has or hasn't been avoided by anyone? It seems a
little early to be counting our chickens.

------
_-___________-_
> SARS-CoV-2 (the virus that causes COVID-19) appears to be killing between 1%
> to 3.5% of the people it infects

The article that this text links to discusses case fatality rate, which is
_not_ the percentage of people the virus infects that die. This is a
fundamental and very important difference, especially given that you later
note the percentage of asymptomatic people.

~~~
danieltillett
Nobody knows the true asymptomatic rate, but even if it is 5o% the number of
people that will be killed is massive.

Let’s not get caught up on the final death rate and let’s look at what we can
do right now.

~~~
_-___________-_
The OP literally opens with a misinterpreted statistic. It links to an article
about CFR and claims that the values are IFR instead of CFR. This is not
"getting caught up on something", I'm pointing out a fundamental error.

Most serious estimates of IFR are between 0.1 and 0.6%. The OP should be
edited to either correctly state that COVID-19 kills between 1 and 3.5% of
_identified cases_ , or be updated to use numbers that are not misleading.

~~~
danieltillett
These IFR numbers you quote are also incorrect as there are many people
infected who have not yet had time to die. The best estimate probably comes
from South Korea (they seem to be picking up nearly all cases with their
massive contact tracking and testing) where the death rate is at 1.8% and
trending higher.

~~~
_-___________-_
Then why not link to a study about the IFR in South Korea? My point is that
the claim you make about the percentage of people who are infected that die is
not supported at all by the article that the claim links to, which only
discusses the percentage of confirmed cases that die.

~~~
danieltillett
Because the whole issue of IFR is irrelevant to my argument and the range
provided is wide enough to cover all estimates.

------
sysbin
In theory the idea would work. People being cooperative enough is where I'm
skeptical. I assume anyone in the high risk group would volunteer to receive
the less-dangerous strain and when the incentive of lowering risk of death is
obvious. I speculate young people wouldn't volunteer unless they have a health
issue placing them in the high risk group.

~~~
logicchains
>I speculate young people wouldn't volunteer unless they have a health issue
placing them in the high risk group.

I suspect lots of young people would happily volunteer if it meant their life
could return to normal. Heck, I'd bet even for the current strain, with a
~0.1% risk of death for young people, quite a few people would volunteer to
get it if it meant they could get out of lockdown.

~~~
sysbin
I'm not disagreeing with that opinion. I just haven't observed young adults
taking the lockdown seriously.

I personally work from home (as one of the privileged few being a programmer)
and when I do go outside I take social distancing serious. My health in
general isn't great although I'm not old (early 30s) and which is why I don't
leave my apartment much anymore. I live in a college area and young adults are
still going over to each others apartments and without practicing social
distancing when going out to buy groceries. I'm in Quebec for context. I've
heard it isn't much different in the USA.

Maybe the (possible) solution could work without young people on board.

~~~
logicchains
>I live in a college area and young adults are still going over to each others
apartments and without practicing social distancing when going out to buy
groceries.

That's my point: the young adults don't want to comply with the social
distancing, so if someone said "hey, if you let me infect you with this virus
that has a 1/50,000 chance of killing you, you can no longer get/transmit the
more dangerous strain so you don't have to social distance any more", a lot
would take the offer.

~~~
sysbin
Why wouldn't they just say "no" and continue not social distancing?

~~~
logicchains
They don't want to be fined? I thought in most places with a lockdown they're
fining people who don't follow social distancing requirements.

------
Geenkaas
The Netherlands is testing with plasma from a recovered patient right now:

Source: [https://nos.nl/artikel/2330036-nederlandse-coronapatient-
hee...](https://nos.nl/artikel/2330036-nederlandse-coronapatient-heeft-plasma-
met-antistoffen-ontvangen.html)

NB: I am NOT a microbiologist and do not know how far this is related.

~~~
maxerickson
It's not particularly related.

Plasma contains molecules that contribute to immunity. The donation transfers
those molecules from the donor to the recipient. It doesn't directly confer
any immunity to the recipient, it reduces the amount of virus circulating in
their body, giving their own immune system more time to respond.

------
Gupie
Isn't this just one of many ways to produce a vaccine, so won't it need the
same long term trials for safety and effectiveness that any type of vaccine
needs? Reducing this this time somehow is what I think is needed.

~~~
danieltillett
I address this in the post. The answer is no it is not just another vaccine
approach.

~~~
Gupie
Do you mean this "virus would not be a vaccine from a regulatory perspective"?
In that case it is just another vaccine approach, but one that you alledge
falls outside the current regulations. Do you think the regulations need to
change due to the emergency?

~~~
danieltillett
This is a question that really is unimportant at this point. What matters is
what we can do today.

~~~
postingawayonhn
It's extremely important because it's a question a lot of people are going to
be asking. You'll need a good answer as to why this approach should not be
subject to similar regulations as vaccines otherwise this will go nowhere.

~~~
danieltillett
Is the FDA regulating the spread of the dangerous version?

More seriously there is nothing for the FDA to regulate here. It is a natural
virus spreading in a natural way.

~~~
Gupie
How can you claim it would be spread in a natural way? The intention is to
spread it deliberately.

~~~
danieltillett
Because the attenuate virus we are looking for would be one that can spread
naturally. Of course humans might choose to help it along once it is found by
say hanging out with an infected person. Lots of options here

------
gmanis
Daniel, Why can’t we use the virulent strain but in extremely small quantity?
Like 1/1000 of the typical viral load?

~~~
cjbprime
That's covered by the post: because the person who received the small viral
load will infect others and give them a large viral load.

~~~
gmanis
Thanks. How about a quarantine say 14 days after the small viral load
delivery.

Maybe we can do that to a subset of healthy young population so that they can
go back to work without risking others?

I don’t have much idea about either virology or molecular biology. Just
curious.

------
credit_guy
> "Can’t we just wait for a vaccine?

> "No. Apart from the time it will take to develop, trial, and mass produce a
> vaccine (12-18 months), it is unlikely that any vaccine will be practicable.
> The reason why is immunity to respiratory viruses (like corona) doesn’t last
> long – 6 months to 2 years. We would have to keep vaccinating everyone in
> the world every year (or maybe every 6 months if we are unlucky). "

I am not sure I agree with this. I am taking the annual flu shot, along with
all the members of my family. I would be fine with an annual, or semiannual,
coronavirus shot.

~~~
aliased
Poor countries can't afford that.

------
bluefox
Perhaps a first step is to simulate a population where several variations of
the virus exist, and where people set out to get infected by those who are
believed to host a "safe" variation. What is the likelihood that interaction
between the variations and people's mistaken beliefs screw this up?

------
mbreese
From the comments on your site:

> One thing is certain with the current situation is we need to take some
> risks if we are going to solve it quickly.

Looking for quick answers in a crisis is really risky. There is a natural push
to try to get things back to normal as soon as possible, but developing an
attenuated vaccine (even with a potential strain already in existence), takes
a lot of time and testing.

I certainly agree that we should be trying to sequence every variation we can
find in the wild, but even if everything works just right, it will take a lot
of time. I haven’t followed enough of the reports, but how many strains have
been identified thus far?

Another issue is that even just getting the reagents to collect and passage
the virus is difficult as they are all needed for clinical testing. So working
with live (even attenuated) virus is very difficult at the moment. But this
highlights a reason why it is so critical to study these topics when we aren’t
in crisis mode. Much of the current vaccine work has been adapted from earlier
SARS-CoV research.

But this approach of finding a weakened strain (or generating one), is a good
idea to be attempted in parallel. (I’m sure that someone is trying to passage
the virus though a different host to attenuate it as we speak). The first step
is to try and sequence as much as we can from the wild, but this has its own
logistical difficulties. Hopefully there is a research study going on that is
trying to collect as many samples as possible now, so that we can sequence
later when things have calmed a bit (because there is likely going to be a
second round).

I don’t intend to sound so negative on this. I largely agree that this is one
avenue that needs to be studied. And from your background, I know you
understand these risks/concerns. I worry about the larger public though. My
main concern is that this concept can be very risky, especially with an
already scared public looking for quick answers. Seriously, the last thing we
need is people intentionally trying to get infected in the hope of getting a
less lethal strain. This isn’t a cowpox scenario. I guess my hesitation comes
down to me not liking the idea of taking too many risks for the sake of doing
it quick. That’s been known to come back and bite people.

~~~
danieltillett
Not doing something is very risky too. This is a problem with only hard
choices.

------
mirekrusin
Interesting, I wonder if this could explain to some extend different death
ratios that are currently blamed on hospital capacity, age etc. - in other
words, what if Italy has spread of more danerous mutation kind and Japan has
spread of less dangerous one.

~~~
bede
The global sequencing effort makes this reasonably straightforward to study.
While the prevalance of different strains does vary geographically, new
international tranmission events occur _so frequently_ that most places have a
handful of circulating strains already [0]

[0] [https://nextstrain.org/ncov/europe](https://nextstrain.org/ncov/europe)

------
temac
Is there a guarantee it would not associate with other viruses (possibly other
strains, or even something worse?)

And the lack of testing to "save time" actually does not look like a good idea
for a live virus you want to give to the whole earth.

~~~
ruslan
IMHO, he is not going to give new virus to the whole earth, the virus already
exists hence freely speading by itself from host to host. The idea is to speed
up spreading of "good" virus to preempt spreading of a bad one and finally
make the last to extinct.

------
0k
Brilliant && simple. Why nobody is acting on it?

Please correct spelling:

..I now work..

..a number of papers..

Thank you, please spread the word (url).

~~~
danieltillett
No idea why nobody is acting on it - maybe nobody else has thought of it yet.
While the idea of there being attenuated strains out there is nothing radical,
the idea of using them is.

Please everyone if you know someone you think might be able to help make this
happen then spread the word. You are even welcome to steal the idea and claim
it is your own :)

~~~
esfandia
Have you considered sending this as a letter to a medical journal? I know it's
not a "scientific article" per se, but many journals have a section dedicated
to letters. For example, CMAJ (Canadian Medical Association Journal) considers
such letters, and right now they're fast-tracking anything COVID-related:
[https://www.cmaj.ca/](https://www.cmaj.ca/)

Best of luck!

~~~
danieltillett
Yes I have, but the people I am trying to reach are not medical researchers,
but people able to think outside the box.

------
jl2718
This will happen naturally. No need for intervention. The longer it goes the
better.

~~~
danieltillett
This is true, but it might take a few hundred years. I think it would be
better if we try and help the process along.

~~~
jl2718
I'm not sure, but you might be greatly underestimating the rate of evolution
for these virii. Generally it is ~10^9 faster than eukaryote evolution
([https://viralzone.expasy.org/4136](https://viralzone.expasy.org/4136)) and
there are many (10^?) generations that occur in every host. Early selective
pressure for fast replication makes it deadly, but late-stage selective
pressure is to be transmissible through mild symptoms. The end game is that it
becomes part of our DNA.

I might also mention that the virus doesn't really care about us. Mostly it's
interested in infecting our bacteria. That's kind of a joke, but in reality,
it says everything about how to control it.

~~~
danieltillett
We have a pretty good idea how fast corona virus evolve. Yes there will be
selection pressure for it to become less deadly, but this can take a long
time. My proposal is how we can speed up this process.

------
ekianjo
> Singapore and Japan have recently seen this in action where they eased
> restrictions and found the disease came back and they had to reintroduce
> restrictions.

Poorly informed, Japan did not even have restrictions in the first place.

~~~
danieltillett
Yes they did, just not the same as everyone else.

~~~
ekianjo
Closing schools and doing nothing else does not count much in terms of
restrictions.

------
ignoramous
This is genuis if it could be put to work.

Many possible vaccines for covid-19 are discussed in this paper [0] which is
surprisingly accessible. There's a table [1] that depicts categorization of
vaccine candidates and it does mention _attenuated virus_ as a possible
solution, the one in development by Codagenix and The Serum Institute of India
[2] expected in the second-quarter of 2022.

2022 seems to be an eternity away, and the problems, as the paper points out,
with attenuated vaccines are:

1\. Requirement of a much wider phase 3 trial than other vaccine types.

2\. Very time consuming to create such viral strains in the lab.

There are overwhelming advantages working in its favour, though:

1\. Human vaccines using the same platform exist for other diseases.

2\. Existing infrastructure can be used to ramp up trials, approvals,
manufacturing, and administration.

The proposed solution by Dr. Daniel Tillett here makes sense because it turns
those disadvantages on its head-- a substantial number of people might already
have been infected with proven mild inflection and the strain(s) can be
isolated at a much faster clip!

[0]
[https://www.cell.com/immunity/fulltext/S1074-7613(20)30120-5](https://www.cell.com/immunity/fulltext/S1074-7613\(20\)30120-5)

[1]
[https://www.cell.com/action/showFullTableHTML?isHtml=true&ta...](https://www.cell.com/action/showFullTableHTML?isHtml=true&tableId=tbl1&pii=S1074-7613%2820%2930120-5)

[2] [https://seruminstitute.com/news.php](https://seruminstitute.com/news.php)

~~~
danieltillett
I am not sure about the genius part, but it can be done. While a search for an
attenuated virus might fail (there might not be one out there yet), it at
least won’t take long or cost much to look. Let's get started.

------
Tarrosion
Any thought of writing a WaPo, NYT, etc. editorial? With an idea this
potentially impactful and your credentials, seems like you'd have a good shot
of being accepted.

~~~
omosubi
Is that where decision makers are looking right now? I don't ask this to be
snarky, but it seems that they post so many op-eds that it would get buried

------
socialist
At the end we'll all figure out "immunity" is the best defense. Miracles only
happen when common sense takes over.

------
TuringNYC
Dear @danieltillett - Thanks for the thoughtful piece.

You noted on your post "live attenuated (oral) polio vaccine" but later wrote
"Apart from the time it will take to develop, trial, and mass produce a
vaccine (12-18 months), it is unlikely that any vaccine will be practicable."

So how do you imagine this solution being administered if not as a vaccine? Is
the solution a Pox Party
([https://en.wikipedia.org/wiki/Pox_party](https://en.wikipedia.org/wiki/Pox_party))
with someone verified to have the harmless strain?

~~~
danieltillett
A pox party would work. Given the strain will be infectious like the dangerous
strains it is not going to be too hard to spread it around.

You can look at it from the other perspective - once identified it would be
impossible to stop people spreading it around on their own. Let’s say one of
you friends got infected with this “safe” strain you would quickly head over
to their home for a cup of tea and a good chat.

~~~
barbs
Much like the dangerous virus can mutate to a less harmful version of itself,
isn't there a risk that the benign version could mutate back to a (more)
dangerous form if spread this way?

~~~
danieltillett
Not if you select a strain with the right mutation.

------
m348e912
I'm late to the comment party but I wanted to say our hope might just be
better treatment (and not a vaccine). Covid-19 doesn't have to fatal as long
as hospitals _don't_ use their standard protocol. Here's what I mean:
[https://www.evms.edu/media/evms_public/departments/internal_...](https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf)

~~~
danieltillett
There is a large percentage of the world’s population that can’t access any
hospital, let alone get treatment.

~~~
m348e912
Does this treatment you can't get include vaccinations? I'm not sure what
you're getting at. Anyway, hydroxychloroquine is on the list of World Health
Organization Model List of Essential Medicines.[0] It's a widely available
drug that can be found even in remote parts of Africa and India where malaria
is prevalent.
[0][https://apps.who.int/iris/bitstream/handle/10665/325771/WHO-...](https://apps.who.int/iris/bitstream/handle/10665/325771/WHO-
MVP-EMP-IAU-2019.06-eng.pdf)

------
z3t4
So we need a DIY genome sequence kit. Where can I find a practical guide? What
do I need?

~~~
danieltillett
No we just need the samples and use the instruments we already have.
Sequencing the viruses genome is not a complex problem technically.

------
Robotbeat
This is the same thing as a vaccine (but without doing the safety due
diligence). IMHO as a not-medical-professional, we’d be better off with just
using one of the (dead) vaccine candidates early than with a _slightly_
attenuated live virus.

We actually started clinical trials of the Moderna mRNA vaccine in humans a
month ago. We may have some early safety data. Better that than intentionally
exposing people.

~~~
danieltillett
No it is not. There is still safety data, it has just been done by nature and
not by jabbing people in the arm with some experimental vaccine.

~~~
Robotbeat
No, the safety data is not well controlled in this case. There are lots of
ways to administer a vaccine, it doesn't have to be injection.

Look up the history of vaccination. Starting in the late 18th Century, people
used to do this exact thing for early vaccinations: they found a naturally
occurring, less pathogenic strain (for instance, cowpox[1] in the days of
smallpox), and intentionally exposed people. This is exactly the same thing as
a vaccine except less controlled and, ultimately, much less safe.

.

[1]The root of "vaccine" is "vacca," i.e. Latin for "cow," for this reason.

~~~
danieltillett
Safety data can be gained from epidemiology studies. There is more than one
way to work out if a treatment is safe and effective.

~~~
Robotbeat
Epidemiological studies are much poorer than clinical trials. I’d rather have
low-N but well controlled clinical trials than nebulous epidemiological
studies.

~~~
danieltillett
Of course, but in this pandemic we shouldn’t let the perfect be the enemy of
the good. Waiting for the perfect vaccine to be developed will have a very
high cost. There are no easy options here.

------
ajnin
The idea of voluntarily infecting the entirety of the population with a virus
to prevent economic downturn seems a very dangerous idea to me. The purpose of
society is to ensure the well-being of the people. It is not economic growth.

Furthermore, I see a few problems with that idea :

\- it seems very hard to create a truly harmless virus. Viruses still destroy
cells to replicate, they cause immune system response, inflammation, what
would happen to weak or immunocompromised people ?

\- if immunity through vaccines lasts 6 to 24 months, why wouldn't this be the
case here too ? You'd still need to develop a vaccine or keep infecting people
with new strains of this virus

\- why would the deadlier strain disappear ? Unless you also engineer the mild
strain to be much more infectious, both strains would still spread equally in
the population. Presumably the milder strain would be less symptomatic so it
would in fact spread less

\- it's not demonstrated in what way economic downturn would be more harmful
in the end. Economy is a means not an end.

~~~
DCKing
> The purpose of society is to ensure the well-being of the people. It is not
> economic growth.

"Growth" is not the issue, but economic prosperity and stability is immensely
important with respect to the well-being of the people. Economic downturns
also reliably cost lives in a huge amount of different ways.

I'll consider this idea to be pretty whack until people smarter than me think
it's a good idea. But I hope we can come to terms that it's worth discussing
taking _some_ health risks to limit economic downturns. "People's lives" vs
"the economy" is a false dichotomy.

------
ineedasername
The author doesn't address how widespread the testing would need to be to
accomplish this. What sample size is needed? Does it need to be geographically
diverse? Does the human population tested need to be genetically diverse?

Also: Why is this faster than other methods of vaccine development already
underway? Once developed, wide-scale manufacture & deployment is an enormous
logistical challenge completely separate from R&D. Can this use existing
vaccine manufacture & distribution channels?

It's difficult to really assess the viability of this plan without it taking
into account many of these details. To my moderately-informed-outsider
thinking (which lets face it, is the crowd the author was targeting by posting
here on HN) it may suffer from the "ideas are easy, execution is hard"
problem, because execution details apart from the actual R&D side are lacking.
I'd like to hear more from the author on the topic though.

~~~
danieltillett
I actually do address the numbers needed in the post. Yes you would want to
sample as widely as possible in the ideal world, but more important is just
getting the right samples.

The reason why this would be faster is the process of looking for the strain
and identifying it as safe would generate data that would allow the regulatory
authorities to approve its use.

Manufacturing would not be the limiting factor here.

~~~
ineedasername
I read the whole article through. Now I have done so twice. Maybe I have a
blind spot, maybe I misunderstand something, but I don't see where you address
the number of tests needed. Certainly you don't address the need (or lack
thereof) for geographically & genetically diverse testing.

Your background also does not appear to contain detailed experience within the
manufacturing and deployment side of vaccines, so I hope you'll forgive me if
your lack detail on that end isn't mitigated by simply saying "Manufacturing
would not be the limiting factor here" without further explanation.

You say you'd like to get this proposal in front of influential people, but
why would Bill Gates assume the logistics are fine, not a problem, without you
specifically addressing the issue?

And if I can't get answers to the questions I've raised after 1 full reading,
one slightly faster reading, and an exchange with the author himself, then if
I were a person of any influence I would not devote limited time to this
proposal. Presumably you posted here to get such attention. Presumably you
would engage a bit more and answer in greater detail if you knew I were
someone who could help advance this in some way. (I'm not-- I have access to
researchers in academe but no influence) But I don't see you getting the
attention needed, not without a proposal that moves beyond the R&D phase _in
significant detail_

Personally I find the lack of logistical details beyond the R&D and sequencing
side of things indicate that your own business interests have you focusing on
that end of the project to the detriment of other factors that need to be
taken into consideration. Please note that I'm not saying you're doing this
for the money: Only that your current area of professional endeavor is the
area of the problem where you have focused your proposal, and the areas where
it's lacking are not bolstered by your simple assertion of "they are are not a
problem."

You have posted to an audience that is not automatically going to know how
your R&D could be logistically deployed, but also an audience that knows ideas
are easy, and execution is hard. If you wish to have your proposal widely
accepted here, if you wish people here with connections to those who could
influence anything, these are things you need to address.

~~~
danieltillett
I address the number issue here.

 _With little cost we could sequence a few thousand viral strains, or even
tens of thousands of strains, from positive test sample from asymptomatic and
/or mild case until we find a virus strain with the right mutations to make it
harmless and which could work like a vaccine._

The manufacturing issues are not really my strength or extremely relevant to
the idea, but this involves a live virus so you just need to grow it up in
large scale cell cultures. We have the infrastructure for this in place in the
biotech industry. One of the positives of SARS-CoV-2 from the perspective of
my idea is how contagious it is - you only need a small number of viral
particles to achieve an infection. This makes the scaling much easier.

The bigger issue at this point is finding the attenuated strain strain.

~~~
ineedasername
You address how many viral strains could be obtained, you don't address how
many people have to be tested to obtain that many strains. Since you would
need to find asymptomatic people, and current testing prioritizes only those
with relevant symptoms, you would need to test many, many people to obtain
enough asymptomatic occurrences. You do not provide an estimate for that
number. Or if my assumption is wrong, then please take it as a sign that
people without your specific expertise may come away with the same
assumptions.

I don't necessarily expect you to answer all my questions: I offer them, and
hope you take them in the spirit in which they are intended, which is as a
sort of peer-review process (Though I am certainly not your peer in these
matters: I mention that as an analogy) because I believe you do have a
compelling idea, but I believe for it to gain much traction there are details
that must be filled in, and others that must be spelled out more plainly for
outsiders to your field that don't have your knowledge.

I certainly appreciate you engaging with me and indulging my curiosity, and
questions that perhaps seem to have obvious answers to someone with more
expertise in the field than I have.

Thank you.

~~~
danieltillett
In some countries they are doing a better job of testing the mild/asymptomatic
cases (Germany, Singapore, South Korea are all examples). Even the USA these
days is detecting plenty of positive mild cases.

We can use the the swab samples sitting in the testing facilities to do the
genome sequencing.

Your response is quite common so I am writing a follow on post mon how this
idea can be done in practice.

~~~
ineedasername
And to the extent we can rely on info from the US administration, Dr. Fauci
commented (with some hedging) that Fall may bring widespread testing of the
population at large for antibodies, which could be co-opted for this purpose
as well.

I hope your proposal, and others proposing similar steps, win through. We need
massively parallel efforts pursued. Not just to solve this current crisis, but
to improve our overall global ability to rapidly reply to the next such
problem. Best of luck to you.

------
projektfu
Isn’t such a mutation just one SNP away from returning to virulence?

~~~
pacaro
No. TFA makes clear that they are not looking for a SNP, but rather a
deletion. In a comment further up, they suggest a deletion on the order of
several hundred base pairs

------
david_w
He leaves out "developing a treatment" as an option. Why?

~~~
danieltillett
Because it is a discussion about another topic and I wanted to keep the post
short. Treatments are good, but this will not solve the problem.

------
elcomet
The best would be to find a mutation that cannot jump from human to human .

Otherwise it could be dangerous if it mutates again to a more dangerous virus,
even if not the original coronavirus (as you said we choose a mutation with a
deletion).

~~~
danieltillett
No. A major part of the value would be the host to host transmission as it
would get herd immunity into those people not directly given the virus. Only a
transmissible virus strain can drive the pathogenic strains to extinction too.

Large deletion mutations don’t back mutate in practice.

------
weakstrain
The author is thinking that reversing a deleted zone mutation is hard, but it
could be that a simple mutation of the weak strain make it deadly, so my
question is: can you guarantee that a new mutation is not going to make this
strain deadly?, also the more people with the new strain of the virus, the
more the bad mutation could happen.

So I suggest looking for a strain for which we have a mean of killing the
virus, that is a weak virus for which we have a general vaccine for expected
mutations, if that is possible.

~~~
dpratt71
There are no guarantees in life, but the reason we don't have global pandemics
constantly is that mutations that make a virus as dangerous as SARS-Cov-2 are
quite rare.

~~~
jfoster
There actually has been quite a lot of pandemics over the past 100 or so
years. Covid-19 has yet to eclipse at least 3 of them. (1918, 1957, 1968)

------
hb4ch
> We found, in our 788 confirmed COVID-19 patients, the decreased rate of
> severe/critical type, increased liver/kidney damage and a prolonged period
> of nuclear acid positivity, when compared with Wuhan.

So how are we gonna deal this increased liver damage then, if we are actually
gonna use this less pathogenic branch of the virus as a quasi-vaccine?

Is there way to reengineer this virus so that it would be less kidney/liver
damaging?

------
aliased
Very interesting post. One way to get this talked about more widely is to
somehow get it in front of Trump.

------
beagle3
IIRC this idea is the origin of the word “vaccine” - from vache, French for
“cow” - people used to intentionally get infected with cow pox 300 years ago,
and it would confer protection against smallpox. On phone so hard to check and
link.

------
lucas_membrane
>> The polio, ... vaccines are all live attenuated viruses.

IIRC, the USA came very close to eliminating polio by switching between live
virus vaccines and killed-virus vaccines several times.

------
carlob
I see one potential drawback to this (as opposed to a vaccine), and that is
the impossibility to protect immunodeficient subjects: if you have an
effective vaccine you can be fairly certain that people with leukemia or full
blown AIDS can be protected by herd immunity when surrounded by people who
have been vaccinated. In this case it's not clear to me whether this would
work. I have to say I'm no virologist, but I find the fact that this milder
strain can still propagate on its own some kind of a double edged sword.

Maybe someone who knows more about this than I do could comment.

~~~
jseliger
Right now it is also impossible to protect immunodeficient subjects, but herd
immunity could help. I don't think the author ever says, "We should do this
and only this in lieu of a vaccine."

The argument is, "This can be done now, or soon, while a vaccine will take 12
- 18 months, if not longer."

~~~
carlob
It's not quite the same ethically: for all of this to work you should make
this attenuated virus spread faster than the more deadly ones, so there is a
positive act to be made which goes directly against the Hippocratic oath (do
no harm).

Immunodepressed subjects right now are protected by isolation and by the fact
that right now a smallish percentage of the general population is an
asymptomatic carrier, if we were to start spreading this actively those
variables would change.

------
sharken
It is commendable to search for solutions to the Corona virus.

But the author is doing himself a disservice by saying that tens of millions
of people worldwide will die.

And why is it a bad thing to have to be vaccinated on a yearly basis, poor
African countries have not been hit hard that is a fact.

The areas being hit the hardest can afford to be vaccinated yearly and is
accustomed to it with the yearly flu shot.

Other than that, keep up the good work !

~~~
banachtarski
You’re ignoring the fact that this virus Is an order of magnitude more lethal
than the flu, and I would guess that most individuals in poorer countries skip
the vaccine altogether.

~~~
sharken
It has only been proven lethal for very old and people with chronic illnesses.

Those people should stay at home and practice distancing.

~~~
CathedralBorrow
Are you just igoring news that fly in the face of what you're stating here?
Have you looked at the current state of NYC?

~~~
sharken
My wording could be better I admit and yes I have looked at the NYC numbers
that show 86% of deaths are due to underlying illnesses, source:
[https://eu.usatoday.com/story/news/health/2020/04/07/new-
yor...](https://eu.usatoday.com/story/news/health/2020/04/07/new-york-
coronavirus-deaths-data-shows-most-had-underlying-illnesses/2960151001/)

Being old and having underlying illnesses is by far the biggest reason for
deaths in NYC, with Hypertension and Diabetes being among the top risk
factors.

Worryingly, in Sweden in the capital Stockholm, around 15% of the staff caring
for the elderly have had Corona virus.

------
torbjorn
I sent this article to a vaccine researcher I know, here are his comments (I
have his permission to share this):

TLDR the virus mutates too quickly for this to be safe.

" There are many ways to make vaccines, and the oldest one is to take the
wild-type pathogen, and either ‘break’ it (‘attenuate it’), or find an example
in nature that’s messed up and can’t cause disease.

The initial smallpox vaccine was cowpox: Close enough to human smallpox that
it elicited protective immune responses, but too maladapted to humans that it
couldn’t thrive in us, and would be caught by the slow-walking cops of our
immune system.

The strategy used for many of the 1950s/60s-era vaccines was to isolate the
disease-causing pathogen, then in a laboratory force it to grow in
progressively more-messed-up circumstances. This would drive evolution of the
pathogen to mis-adapted freaks. For example, the mumps isolate was from the
daughter of the Merck scientist (Maurice Hilleman), and he grew it in cow
cells, then lizard cells, then insect cells (or somesuch, I don’t know
exactly). By the end of the process, the thing could still infect humans, but
just BARELY.

Nowadays, with molecular biology, we can rationally design the ‘attenuations’,
and do knock-outs or modifications.

Which brings me to low-virulence wildtype isolates of SARS-CoV-2 (S2): The
root problem here, as with HIV, is it’s a super-fast-evolving RNA virus. Sure,
a particular isolate might be low-virulence NOW, but give it a few weeks on a
cruise ship and – viola! – nasty bugger ahoy!

When SARS-CoV-1 broke out, years back, it had a high lethality and freaked out
the public health experts at the time (in fact, we were writing proposals to
get into the research, but then it got contained). At that time, efforts were
initiated to make a vaccine, based on the observation that all that was needed
with the Bcell production of ‘neutralizing antibodies’. This is the long
standard, matching most existing vaccines. So it was a low-weight lift, for
vaccine developers (relatively easy-peasy). The project got pretty far along,
but then stopped when SARS-CoV-1 disappeared as a threat.

When MERS, then SARS-CoV-2 came along, they resurrected the previous,
promising design, based on a slow-evolving vector. But in the case of S2, they
discovered that the targeting receptor usage of S2 was significantly
different, so the design required a significant re-tune. Even so, the Chinese
(I think) did it, injected the first people several weeks back, and I don’t
think it works well (too early for formal reports).

S2 is nasty, as HIV is. It is using evolution against us. And because its
hypermutable (like the influenza viruses), it’s going to be nearly impossible
to make one vaccine that works cycle after cycle. It will continue to evolve,
but the subsequent cycles will probably have lower lethality than this first
pass (which was completely novel to the human immune system, so we had no
‘herd immunity’ protection). Going forward, it will be hard for highly-
virulent forms to transmit if they kill their hosts too quickly, which will
select for less-virulent forms.

The trick is to stay alive during this pass. The only mechanism we have to do
this is to not get infected. The only way to do that is to not expose
ourselves to infected people, or the things they’ve touched.

We’re back to how things were in the 1800s. Better than no science, but about
the same as post-epidemiology/cell-theory-of-disease (1890s)

But as I said, this vaccine should be RELATIVELY easy to develop. It doesn’t
have to be perfect, it just has to blunt viremia (so that the global pneumonia
it causes in your upper/lower respiratory system doesn’t cause aveoloar
collapse. In other words, even working a little bit will probably massively
lower the death count.

But even an easy-peasy vaccine will take 18 months. There’s just no getting
around that, unless you want to inoculate 5 billion people with something that
might make the pandemic worse."

~~~
danieltillett
Can you ask this person to write to me directly as I think they have missed
what is novel about my proposal and have instead focused on what is not.

------
snowwrestler
The idea that naturally mild strain of the coronavirus would provide a durable
benefit, but a human-created vaccine would not, seems to me like an idea that
needs a lot more explanation. The mechanism of immunity should be the same
between those two.

~~~
perlgeek
The main argument here is that finding a mild strain (and having it tested
implicitly by virtue of it infecting many humans) could be faster than
developing a human-created vaccine.

I don't have any credentials in this field, but IMHO we should attack the
problem from all possible angles, including the search for a natural, less
harmful strain.

~~~
snowwrestler
He says:

> Apart from the time it will take to develop, trial, and mass produce a
> vaccine (12-18 months), it is unlikely that any vaccine will be practicable.
> The reason why is immunity to respiratory viruses (like corona) doesn’t last
> long – 6 months to 2 years. We would have to keep vaccinating everyone in
> the world every year (or maybe every 6 months if we are unlucky). This just
> isn’t going to work in the real world (especially poor countries) and is one
> of the reasons we don’t have a vaccine for the coronavirus strains that
> cause the common cold. Unless we can drive the current dangerous SARS-CoV-2
> strains to extinction we are going to have a problem with this disease
> indefinitely.

Every one of these objections also applies to a less harmful strain.

For example, one reason vaccines don't confer durable immunity to many
respiratory infections is because the infectious agents change over time,
migrating away from the vaccine response. Well, by the same token, a less
deadly strain of such an infectious agent would also change over time at the
same rate.

On the other hand if we think a naturally occurring strain would provide
stable immunity over a long time, then a human-created vaccine would also be
stable for a long time.

There is nothing magical about naturally occurring strains. They work in the
body exactly the same way vaccines do. (Which is of course why vaccines work
in the first place.)

~~~
danieltillett
The “magical” part is nature has run the experiments we aren’t yet ready to
run with vaccines. Time really is an important issue.

~~~
snowwrestler
Nature may have run enough experiments to know that the less deadly strain is
as safe as a vaccine, but she won't just tell us that. We would have to
discover it for ourselves with the same scientific method we use to
interrogate vaccine candidates. Which BTW is the time-consuming part... we
already have some candidates.

This matters because if someone were to do anything to promote or help others
infect themselves with the strain... that person or company could face
significant civil liability if the strain turns out to not be safe for
everyone. Even one wrongful death suit can ruin your day.

Vaccine liability is "manually managed" via federal legislation. Encouraging
people to have infection parties is not.

~~~
danieltillett
Yes we use the scientific method of epidemiology - has been working since John
Snow used it to determine that there was a cholera problem with the Broad
Street Pump [1].

I am not encouraging anyone to do anything other than look for a natural
attenuated strain. This point seems to be missed time and time again.

1\.
[https://en.wikipedia.org/wiki/1854_Broad_Street_cholera_outb...](https://en.wikipedia.org/wiki/1854_Broad_Street_cholera_outbreak)

~~~
snowwrestler
If you're proposing an investment of effort to find new information, it's
absolutely fair game to ask what we will do with that information--how we will
benefit from it.

a) We find a naturally attenuated strain and do nothing to promote or spread
it.

b) We find such a strain and treat it like a vaccine candidate with all the
testing.

c) We find such a strain and treat it like a vaccine candidate but without all
the testing.

If someone does a) or b) they are on solid legal and scientific ground, but
arguably have not created any new benefit beyond what is already happening to
develop a vaccine.

Whoever does c) would certainly deliver a benefit in terms of speed... but if
they cause any unexpected harm, would be exposed to legal liability.

I guess my fundamental question is whether the hard part of developing a
vaccine is attenuating the virus or proving such attenuation is safe.
Epidemiology can help us find natural versions of the former, but it can't
help us with the latter.

Epidemiology cannot satisfy a question of safety. It can only identify risk
factors, as John Snow did with the water pump. If your idea succeeds, at best
we will be able to say "this strain seems to be a low risk factor for serious
illness or death in this population." Then what?

The critical moment for cholera was to run an experiment: remove the pump
handle and see what happens. But in the case of vaccines or vaccine-like
strains, we are not talking about an experiment to _remove_ a risk factor, we
are talking about _spreading_ a risk factor after properly qualifying its risk
as low. That is much harder to do. The only way is to run a bunch of
experiments.

~~~
danieltillett
No matter what is done or not done there is risk. This is the nature of this
problem. I am of the belief that the more options you have the better. If
there is an attenuated strain out that has infected a large number of people
we should look for it. What we do with it if we find it is a political
question, not a scientific one.

------
ineedasername
I'm always skeptical simple solutions proposed to solve complex problems.
Unintended consequences or unanticipated roadblocks are often an issue.

In this case, the author _might_ under estimate the logistics involved in
getting this done. At a minimum, the author does not adequately address the
logistical challenges of this endeavor in the context of already challenging
testing environments. The "quick & cheap" aspect of this is therefore a claim
without support.

It might be a promising line of endeavor, and we should pursue multiple
parallel initiatives, but the resources needed to pursue this are highly
correlated with the resources needed to perform many of the other initiatives
that are also promising. There is a bottleneck. Why should this take
precedence over other already promising lines of inquiry?

~~~
the-pigeon
I don't think this is a very simple solution at all.

It's really just a different vaccine approach and this isn't the first person
to suggest it. It's been talked about online since February if not before.

Not to say I don't think it's a viable idea and I do think it needs more
visibility. As the author states this has worked for other diseases.

~~~
ineedasername
The author proposes it as "quick & cheap" and leaves out nearly all logistical
considerations. To my thinking, that is an overly-simple proposal.

~~~
danieltillett
Something can be quick and cheap without being easy. The proposal is far from
easy.

The post leaves out a lot of technical details that the average non-scientist
doesn’t need to know.

------
jbermudes
I'm glad people are realizing that all this social distancing is merely a
pause button on the virus. Once we press play on society, exponential growth
will happen again and we will have effectively rolled back the clock until we
reach herd immunity through things like the OP's suggestion.

At least this next time we'll hopefully have more PPE.

~~~
Taek
I'd much rather live in a world where everyone is required to wear masks all
the time than live in a world where we are all told to stay home all the time.

I believe it's also well established that any measures taken to slow the
spread of a new virus will always result in fewer total deaths, in that sense
quarantining is much more effective than just being a pause button.

~~~
grey-area
This is a false dichotomy. Masks or gloves as worn by ordinary people are
nowhere near effective enough to mean lockdowns could end. They're very
effective in clinical settings with proper ppe head to toe and procedures for
taking them off outside the dirty ward, but there's no way most people can
stick to those, nor keep their houses/shops clean enough.

 _I believe it 's also well established that any measures taken to slow the
spread of a new virus will always result in fewer total deaths_

In the sense that they prevent a healthcare system being overwhelmed yes, in
any other sense no, they are very much just a pause button for the spread of
the virus, not a cure.

~~~
drtillberg
We wouldn't insist that people 'stop breathing' to prevent the spread of
coromaviris. It's only somewhat different to insist that we all stop living
and working.

Masks and gloves, plus generally keeping 6ft apart and routinely testing and
contact tracing/quarantining infected individuals... what's the effective rate
there? 95%? The modern medical establishment would move heaven and Earth, and
incur thousands of dollars per person to get that last 5%. Most of us
routinely ignore them in this regard, with respect to our own personal health,
as we live our daily lives.

There just isn't a lot of evidence for the case that the choice is shutting
the economic or killing millions.

~~~
pinkfoot
> There just isn't a lot of evidence for the case that the choice is shutting
> the economic or killing millions.

Which is why we have models, no?

~~~
_-___________-_
Yes, although reality seems to be disagreeing with the models more and more.
You have countries in southeast Asia with community transmission but no
lockdown, and countries in Europe with the military enforcing a strict
lockdown, and the latter are far worse off in terms of hospital admissions and
deaths per capita than the former.

~~~
pinkfoot
Did the European countries not get their transmissions before they implemented
a lockdown?

My understanding is it takes 1 - 3 weeks to see the effect of a lockdown?

------
czep
Finding an attenuated strain that spreads as easily but is less deadly does
sound like our best hope. Such a strain would "crowd out" the deadly strain,
effectively blocking it from causing harm.

If life was a Star Trek episode, Picard would be saying "Make it so" right
about now.

~~~
TeMPOraL
"Captain's log, stardate 73740.9. The Enterprise has taken on board a
distinguished Federation virologist, dr. Daniel Tillett, to help him with his
search for a less harmful strain of the virus that's currently ravaging
several planets in Federation space. The doctor is confident that such an
attenuated strain could be used to swiftly end the ongoing pandemic."

I would watch that episode. Hell, I'd watch any new episode; unfortunately,
the only proper Star Trek we've had since Enterprise stopped airing is The
Orville.

~~~
throwanem
And then it turns out similar to "Ethics", where the virologist's work is
questionably founded and potentially quite dangerous, we get a Picard speech
about how sacrificing some to save others is wrong, Data and Crusher
technobabble up a treatment that doubles as a vaccine, the photogenic kid gets
saved at the bottom of the fourth act, Admiral Nechayev and Picard fence a
bit, credits.

Pretty wild to count Enterprise as "real Trek", but not Discovery. And hey,
TNG was seminal and I loved it growing up too, but let's be real, it's showing
its age quite badly these days.

~~~
carapace
I saw a few clips of ST:Discovery and nearly had an apoplexy. When the ship
spins (rolls) on its longitudinal axis and disappears (using the "spore
drive"...) I pretty much lost my mind for a moment.

Then it reappears with a flash _that illuminates the nebula in the
background_. There are no clouds in space. Nebulas are big, really big. It
would be light-years away. But the ship's photo-backwash lights it up like a
flash bulb! I know Star Trek isn't hard sci-fi, but that's pathetic.

And the "spore drive"!? Who thought that up? (I know about mycorrhiza and all
that, I'm not ignorant) The universe is pervaded by invisible intangible
cosmic fungus? That somehow enables FTL teleportation? And keeps people alive
in limbo after they die? That might be Lovecraft but it's not Roddenberry.

And they named the "astromycologist" character after the real guy!? (Paul
Stamets) Did they _ask_ him? That's just so weird.

To me it feels like it's made to mock Star Trek fans. Watching it (just for
about ~4 minutes) made me feel like the network and producers are just mocking
me. (And not in a good way. I _love_ Galaxy Quest, because it's obviously made
with love and, yes, respect for the show(s) it mocks. When Sigourney Weaver
loses it and starts ranting about how it's a dumb episode, nobody would design
a space ship with giant crushers and fire spouts... Yeah, it's awesome!)

Discovery is more cartoonish than the actual cartoon. (
[https://en.wikipedia.org/wiki/Star_Trek:_The_Animated_Series](https://en.wikipedia.org/wiki/Star_Trek:_The_Animated_Series)
)

I gotta agree that _The Orville_ carries the torch forward far far better than
these new Star Trek shows & movies.

~~~
logfromblammo
The spore drive is a correctly-formatted and notarized petition to Juffo-Wup.

The flash does not originate at Discovery and propagate outward as light, but
begins before the ship appears, from a diffuse source, constructively
interferes at Discovery's normal-spacetime discontinuity, and generates a
holographic illusion between the observer and the nebula that just appears to
be a flashbulb reflection.

Every Star Trek problem may be resolved by sufficient application of
technobabble (a.k.a. [TECH] in the script). It's space opera. Apply the MST3K
rule. (It's just a show; I should really just relax.)

The space-mushroom dimension is the same as the gate network from Stargate
SG-1, or the wormhole-traversal tech and Leviathan starburst from Farscape.
It's the plot conceit that allows the cast to instantly move from one set to
another without any of the boring and unremarkable travel time. The exact
nature of the instant-transport is dependent on the dramatic series plot arcs
that the show-runners came up with in case they ever got past the pilot
episode. The cool CGI visual effect used to signal to the viewer that sci-fi
is happening now is flawed. Not everyone can pull off the Stargate-opening
vortex.

Discovery and Picard are very much darker than pure Roddenberry, in that they
portray The Federation as something far short of a perfectly ethical Utopia.
In my opinion, this is a decision that allows for a far wider range of
character development. An imperfect Starfleet can employ a monstrous starship
captain that murders to keep its secrets. Klingons can be more than just a
racial stereotype to be used as a script proxy for 1960s Russia (and the
language has already been constructed, so might as well use it).

~~~
TeMPOraL
> _In my opinion, this is a decision that allows for a far wider range of
> character development._

This may be the core disagreement, I (and I'm guessing GP) don't like this
decision. Star Trek was an unique word in sci-fi (at least on-screen sci-fi)
_because_ of that bright idealism, that utopia. "An imperfect Starfleet can
employ a monstrous starship captain that murders to keep its secrets"[0], and
done regularly, this makes the show just another run-of-the-mill sci-fi.

(I do like how Klingons were fleshed out as a species in DIS, though; it's my
favorite aspect of the show.)

There's plenty of sci-fi shows and movies. Star Trek, in its TNG to ENT era,
was unique in terms of positivity and optimism. I miss that, because (with the
possible exception of the Orville) there's nothing like that anymore.

\--

[0] - To the extent that Sisko once facilitated murder to keep a secret
hidden, this infamous DS9 episode works precisely because it's a one-off
situation that's in a stark contrast with the overall behavior of the
character and setting of the show.

~~~
carapace
Bingo! Take away Roddenberry's vision of a better future and you've got
Babylon 5, eh? Like I mentioned in a sib comment, it turns out that this was a
tension going right back to the original series. It's hard to write!

(You like the Klingons? To me they seemed derivative of (LotR) Orcs but I
haven't spent time to really know.)

> I miss that, because (with the possible exception of the Orville) there's
> nothing like that anymore.

I've been thirsty as hell for some good (video) sci-fi for a while now and
have been looking and (IMO) you're correct.

[https://en.wikipedia.org/wiki/List_of_science_fiction_films_...](https://en.wikipedia.org/wiki/List_of_science_fiction_films_of_the_2010s)

(And don't get me started on the blurring of the "sci-fi" genre. Superhero
movies are not sci-fi. Sharks attacking are not sci-fi even if they have
lasers on their heads, or six heads, or swim through ice. Fast & Furious isn't
sci-fi. Harry Potter isn't sci-fi. (WTF Sy-fy channel!?) Zombies aren't sci-
fi. Nor vampires, nor bigfoot, nor giant animals. Godzilla isn't sci-fi. I'm
just ranting... ignore me. Swords and magic: not sci-fi. ...okay I think I'm
done...)

~~~
TeMPOraL
> _Take away Roddenberry 's vision of a better future and you've got Babylon
> 5, eh?_

I'd wish! I find B5 to be great in a different way than Star Trek. It has one
of the deepest and most interesting stories I've ever seen explored in sci-fi
on the screen. I wish there was another show like this. Alas, it seems that if
you take away a vision for a better future, the shows you get today are
cookie-cutter action flicks. They're sometimes fun to watch, but I don't feel
enriched in a way I felt after Star Trek or B5.

> _(You like the Klingons? To me they seemed derivative of (LotR) Orcs but I
> haven 't spent time to really know.)_

Not initially, and not from the looks - though the series did manage to
(spoiler alert) turn them into what you'd expect to see in TNG in the latter
seasons.

What I liked about the Klingons in DIS is that they didn't feel like space
brutes who value violence and hate the Federation for no reasons. In DIS, they
had a good reason, that resonates with people today - cultural imperialism.
They went to war with the Federation because they felt it's the only way to
protect their cultural identity, as they perceived UFP to be a civilization
that conquers in times of peace, through slowly infusing everyone with their
views and values. The DIS Klingons have seen that as a threat to the survival
of their species' identity. And put that way, it's a very believable as a
justification for conflict.

> _And don 't get me started on the blurring of the "sci-fi" genre. (...)_

In complete agreement (though I liked Iron Man 1; it was more serious than
other MCU movies, and also scratched my tech porn itch). My additional
complaint is the pressure put on inter-character drama and general "character
development". As I often repeat, if I wanted to watch the deep emotional
struggles of people and their relationships, I'd pick _literally any other
literal /movie genre_. Sci-fi (and to some extent fantasy) is unique, because
it can get away with extensive world building and exploring ideas that are
hard to explore otherwise. It serves as a real-life holodeck simulation. And
I'd prefer my sci-fi to focus on that.

~~~
carapace
In re: B5, I've a confession to make. I never watched it. I've seen a few
episodes, of course, but I was homeless at the time it ran and I've just never
gotten around to it since. I should probably go order the DVD set right now,
eh? I know a teeny bit about the story and characters, and I've heard that it
was written as a single super-arc, which sounds awesome.

Those Klingons sound more interesting than what I was afraid they were like.

> My additional complaint is the pressure put on inter-character drama and
> general "character development". As I often repeat, if I wanted to watch the
> deep emotional struggles of people and their relationships, I'd pick
> literally any other literal/movie genre. Sci-fi (and to some extent fantasy)
> is unique, because it can get away with extensive world building and
> exploring ideas that are hard to explore otherwise. It serves as a real-life
> holodeck simulation. And I'd prefer my sci-fi to focus on that.

I couldn't have put it better myself. So much this. And I find it doubly
exasperating because there's so much written science-fiction to draw on, going
back decades! Where is the movie/mini-series of "Moon is a Harsh Mistress"?
...oh!
[https://en.wikipedia.org/wiki/The_Moon_Is_a_Harsh_Mistress#F...](https://en.wikipedia.org/wiki/The_Moon_Is_a_Harsh_Mistress#Film)

> In 2015, it was announced that Bryan Singer was attached to direct a film
> adaptation, entitled Uprising, in development at 20th Century Fox.

I wonder if that's still happening?

I think "The Legacy of Heorot" would work really well as a movie.

I know it's kind of a cliche (and more work than it seems) but I kind really
want to start a sci-fi production house... just a little one. Y'know?
Specializing in hard sci-fi mostly, but not neglecting the other, uh,
dimensions worth exploring.

------
hebrox
Could we already start with this? There are almost no deaths in young people,
so how about we send the youth to a Corona Summer Camp for a week or 3?

[https://www.worldometers.info/coronavirus/coronavirus-age-
se...](https://www.worldometers.info/coronavirus/coronavirus-age-sex-
demographics/)

~~~
rvnx
How much % of young people end up in ICUs or hospital ? The numbers are always
elusive about that.

~~~
hebrox
According to CDC :

Age group (yrs) 0–19 (123 cases) Hospitalization 1.6–2.5 ICU admission 0 Case-
fatality 0

[https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm](https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm)

~~~
rvnx
Thanks a lot!

------
remote_phone
This entire article is a waste of time from the beginning.

The “two strain” theory was debunked the very next day as bad science.

[http://virological.org/t/response-to-on-the-origin-and-
conti...](http://virological.org/t/response-to-on-the-origin-and-continuing-
evolution-of-sars-cov-2/418)

I can’t believe that a month later, this bad science is still being
circulated, by a purported PhD and former professor.

~~~
danieltillett
I can’t believe you think I am arguing for the “two strain” theory. My
proposal has absolutely zero to do with two strains.

~~~
Retric
"As of 2nd March 2020, there are 111 nonsynonymous mutations that have been
identified in the outbreak, these have been catalogued here in the CoV-GLUE
resource 504 and can be visualised in Figure 1. At current, there is no
evidence that any of these 111 mutations have any significance in a functional
context of within-host infections or transmission rates."

The proposal requires identifying new strains among symptomatic and asymptotic
people, find strains that only occur with asymptomatic people, start infecting
people with that strain, verify they are at lower risk. Then scale this up to
ever larger populations.

If we knew of a less dangerous strain then sure you can start down that path.
However, at this point there is significant evidence such a strain does not
exist due to the extremely slow mutation rate, making this mostly wishful
thinking.

~~~
danieltillett
Of course there may not be a strain with the right mutations out there, but
should this be a reason for not looking. Nobody has been systematically
looking for less dangerous strains (that I know of). My proposal is we look
given it will be quick and cheap.

------
aazaa
> Aren’t most people who have mild/asymptomatic cases infected with a
> dangerous strain?

> Yes. Almost all (>99.9%) of people who are infected (and have a mild case)
> are infected with a dangerous strain of the virus, they just happen to have
> an immune system that can control the virus well. With COVID-19 a mild case
> does not mean you are infected with an attenuated strain – for most people
> with a mild case if they happen to infect a person with preexisting
> conditions or who is old, that person will be at a high risk of dying. A
> mild case does not equal a harmless strain.

Even if the weak-strain hypothesis holds water (which remains to be seen), the
proposal is predicated on something that's physically impossible to do. Test
large numbers of people. Hundreds of millions or even billions.

Then, given those tests, find the weak strains.

That's also the minimum needed to "re-open" the country.

If we could test 20-30% of the population, we'd be in great shape. But we
can't and may not ever be able to.

Even if you can test that many, you've got to prove that the weak strain is
harmless. Then you've got to figure out how to administer doses safely.

So the solution must work within those parameters. And the only practical
option is a vaccine.

> The major risk is the virus we think is safe is not 100% safe. While we can
> use community spread of the identified strain to estimate how safe it will
> be (i.e. if it has infected 1000 people and none have got seriously ill then
> we should have a pretty good idea that it is safe), but our knowledge will
> be incomplete. We can of course spend the next few years testing and
> trialling, but if we do this by the time any strain is shown to be 99.999%
> safe (not even the polio vaccine is 100% safe) we will have all got COVID-19
> and the world’s economy will be a smoking ruin.

This guy is absolutely bonkers, or pulling a Swift.

He's proposing the (forced?) infection of a large portion of the population
with a live virus that has been through none of the safety protocols
established over many decades of catastrophic failures.

This is not how drug testing works. This is not how public health works. This
is not how you assess safety. This is not ethical.

This is tech bro medicine at its absolute worst.

------
papermachete
This is a repost since last time you asked how to reach Bill Gates.

~~~
dang
I invited danieltillett to repost
[https://news.ycombinator.com/item?id=22798626](https://news.ycombinator.com/item?id=22798626).
My reason is to build up a body of community reactions to the idea, that can
serve as a basis for deciding whether to promote it further. I don't know Bill
Gates, but I do know some people inside YC who are hard at work on this
problem, and maybe they know someone who knows someone, etc.

If it's just a repetition of the previous thread, I'm sorry. Repetition isn't
good and that wasn't my intention.

~~~
saagarjha
I know you often do so anyways, but perhaps these kinds of reposts deserve a
comment explaining their circumstances.

~~~
dang
I don't think this would add much value, because it would attract attention
away from submissions to the meta-business of their provenance on HN.

I'm wary of adding bookkeeping facilities for that reason generally.

~~~
saagarjha
Fair enough; just thought I'd mention it because the lack of such bookkeeping
seems to attract attention as well.

~~~
dang
It certainly does. It's a perennial sore spot, understandably. I just fear
that trying to eliminate that pain would cause more pain.

------
AbrahamParangi
The author should test this idea on himself and demonstrate skin in the game.

~~~
danieltillett
I am more than happy to be exposed to an attenuated SARS-CoV-2 strain, but
first we have to find one. My idea is how we can find one.

~~~
op00to
I think it would be pretty easy for you to find a strain. Start licking subway
poles, then see what happens! Just kidding. Stay safe. ;)

~~~
_-___________-_
If the virus managed to stay alive on a subway pole for very long, it's
probably not very attenuated, no?

------
meroes
There's multiple people here suggesting everyday people spread a possibly less
lethal strain, in ways that will likely spread every other contagious disease
they also had.

I think this post needs to be removed now

