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.
>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.
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.
Maybe in this context, making a "hard choice" is accepting that something like 0.3% of the world population dies? Historically we saw worse and recovered, while trying to engineer something with no guarantee it won't be massively worse, using an unprecedented and more or less unstoppable strategy, might not be the most prudent thing to do. Looks like a good movie plot though.
We don't have that option, unfortunately. In real life we're dealing with hospitals permanently jammed and new covid patients keep dying every 6 months, plus the huge economic costs from keeping hospitals _at_ capacity as opposed to 10x over capacity.
Article [1] is dated Feb 12, and contains the sentence:
"Instead, it [SARS-CoV-2] appears to be no more concerning than the influenza virus." The citation for this claim is an article in Canada's National Post.
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:
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.
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.
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.
> b) You don't identify something harmless by just testing asymptomatics.
True, but I think you are missing part of Daniel's proposal. You don't "just" check for unique variations of the virus in asymptomatic carriers, you also check the sequence for major deletions: We would ideally be looking for a virus strain with a large(ish) deletion in an essential viral gene. This sort of mutation is easy to spot in the SARS-CoV-2 genome data, and because the genetic information has been removed, it makes the virus very unlikely to be able to mutate back into a dangerous strain. Ideally, the strain identified will have infected a number of other people in the local area too so we can know it is safe.
So while you do want to verify that the sequence is not also present in "serious" cases, you are prescreening by a factor that theoretically should correlate to severity. Whether you "need" to do additional testing depends on your assessment of base risk. If you assume that almost everyone is going to be infected with a powerful strain if you do nothing, doing your testing in live cases with a strain you suspect is mild might still be justified. Ideally (as quoted from Daniel) this "testing" might be mostly satisfied by just monitoring those already infected by the original carrier(s) with the same mild strain.
8 and red. Most people don't invert the logic and realize that there is no claim that an odd number can't have a red back. I think confirmation bias accounts for missing the brown.
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.
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.
> 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.
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.
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.
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.
It looks like you need to find someone who can help make your post feel more professional - perhaps Ask HN for help or just directly email one of the clued up people here that are open to cold emails (patio11?).
I almost didn’t read it because the title sounds too generically woowoo, and the domain you are using seemed unprofessional. Then on reading the article, you didn’t give your background, an irrelevant picture of a painting opens the article, and the sidebar of your article topics are all over the shop. Sorry for being so negative: it is much easier to find reasons why something doesn’t feel right, and I’m not a fantastic marketer so I can’t offer you fixes I could predict would help.
It seems like a really good idea (are there others that have suggested it?), but I suspect it needs to be more convincing with a bit of repackaging if you want to push it.
Maybe add comments to those 2 papers with an “elevator pitch” or a request for other relevant info, and link to an improved post, and it should bubble up and find the right people to evaluate it.
Edit: also perhaps get your idea onto the various Covid daily link sites: good ideas should bubble up. Use Twitter to relevant people. Pass the idea to this guy who writes fantastically and has audience: https://medium.com/@tomaspueyo/coronavirus-act-today-or-peop...
> It looks like you need to find someone who can help make your post feel more professional - perhaps Ask HN for help or just directly email one of the clued up people here that are open to cold emails (patio11?).
It would probably have the opposite effect. This way it looks like a probably serious scientist wrote an idea that is probably worth considering on his personal website / blog.
If you give the site the "Hacker News treatment", I suspect that it will immediately look like "somebody with funding is trying to sell me on an idea for some reason". This stuff might work for naive consumers, but naive consumers don't matter here. I am sure that this post is already being shared among experts, and they are the ones who need to decide if this idea has merit or not. Throwing marketing bs at them will probably just hurt the cause.
The site is my personal blog. I thought about writing a more technical level paper, but what I wanted to accomplish is to get this idea in front of a non-scientific audience who can think outside the box (like many of those on HN).
A standard scientific paper will sink without a trace -scientists are just too conservative to take something like this seriously. I hate to say it, but the people who will make something like this a reality are the tech billionaires of this world.
The tech billionaires of this world will not fund anything based on a layman's explanation. They want to fund ideas based on reliable research. The Gates Foundation is staffed with tons of specialists for this reason.
I think that if you really believe your idea has some merit, you should still write a paper. After that you can blog about it for any audience out there and maybe write a follow-up. You're a professional, you know how it works.
I most likely will write such a paper, but the first thing is to get those that can make this happen interested. They are not going to be reading a scientific paper.
This seems like a pretty good idea (good enough that certainly there must already be people working on it) so it seems like if you could find and contact them, maybe you could contribute to their efforts?
Well I hope other are working on it, but I haven’t found much evidence of this so far. HN has a pretty diverse audience including a lot of scientists like me.
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.)
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.
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.
It would only be logical to require a "vaccine-strain" that has the capability for uncontrolled spread to go through much more stringent trials and paperwork than one that is limited by distribution.
The whole argument about attenuated strains being a possible shortcut seems to be a variation of the "natural medicine" fallacy.
Except the experiment has been done for us already by nature. We are not doing the experiment, just observing what has already happened. Sure you would not be able to make a strain of unknown attenuation in the lab and spread it around (this would be very dangerous), but you can use the data that nature has provided us. I am proposing we go and collect that data.
It would probably be helpful to mention that at the start or end of the post. Clear, non-inflated credentials/background with links.
(I sometimes see this in italics at the top)
Sort of a weird ask, but as a real, no shit, virologist, what do you think about changing your messaging to make content more accessible to lazy readers?
I have some half baked ideas about tradeoffs in infection rate and fatality, but I'm worse than a layman, I'm a layman with an opinion.
I'd sorta thought a virus could be real lethal(like ebola) ore real infectious(like a cold) but it's kinda hard to be both at the same time.
it _seems_ like there's a mapping between getting read (infection rate) and convincing people (fatality).
to be super explicit, is messaging a virus? is there a tradeoff in how the message spreads vs how convincing it is?
You've probably got other things to do, but it seems like there's a parallel there, even if imperfect, that's worth looking at. If you got a minute, I'd love to read your thoughts.
Viruses don’t really care about thing like death rate, they just care about how effectively they are spread from person to person (viruses don’t really care about anything, but I am describing how they appear to act if they had a mind).
In general the less deadly viruses spread better as dead people are not able to spread the virus around as well as living people. The general trend is for viruses to become less deadly over time, but it can take a long time for this to happen.
Spread rate would also need to stay in a certain range for a virus to stick around. Spread too fast and there won't be a second wave. The herd immunity effect gives this system some self-balancing properties, but there's surely a tipping point where even that won't help a speeding virus to survive.
> is there a tradeoff in how the message spreads vs how convincing it is?
That doesn't make any sense, viruses that are more fatal don't spread well because dead people are not good spreaders. Very sick people are also less capable spreaders than someone walking around with a persistent cough. Someone who's convinced would be MORE likely to spread a message.
While you do not recommend ZJ01 due to the potential for it to mutate back into the original strain, isn't it also quite dangerous?
That would likely remain a primary concern for many - we musn't cause large scale harm intentionally. And if we don't know what effects a strain has, it makes it ethically difficult to distribute.
From the ZJ01 Medrxiv[1] page you link to:
"We found, in our 788 confirmed COVID-19 patients, the decreased rate of severe/critical type, increased liver/kidney damage and prolonged period of nuclear acid positivity during virus dissemination, when compared with Wuhan."
This just rules our using ZJ01. There are other attenuated strains out there that will have deletion mutations that can’t mutate back. We need to go find them.
Sorry if it's a stupid question, but hypothetically, would we be able to engineer rather than find a harmless strain of coronavirus with the spike protein of SARS-CoV-2?
If I understand correctly, antigens identify the virus by its S proteins. Would we be able to use the same methods <a href='https://www.nature.com/articles/nm.3985'>as in this paper</a> to replace the S protein in a harmless cold-like coronavirus with the S protein of SARS-CoV-2, and would then the resulting immunity defend against SARS-CoV-2?
This is not a stupid question. Yes we could engineer such a strain, the problem would be testing it given we would not be able to predict how dangerous it was.
Well if the regulatory agencies decided that they weren’t going to act then I suspect there would be a grass roots level spread of the strain anyway. This would be the worst way to use such a strain, but I don’t think it would be possible to stop this happening.
I don’t think we will get to that point. If we collect good data from the natural spread of any attenuated strain then I think the regulatory authorities will allow its use on the basis of this data.
I hear the phrase "peer review" thrown around so much it's reaching semantic satiation. I get that it's the way respected science gets done, but it's also the laziest possible critique because you're literally asking for someone else to think about it for you.
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.
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?
I don’t see that any regulatory authority would approve something that is capable of spreading, regardless of the possible benefits: it would violate medical ethics. Reread the Belmont Report.
There are many teams all over the world that are looking for less deadly (and more deadly!) strains to guide development of therapies. They’re too busy right now to post on message boards or speak to reporters. It’s however extremely unlikely that a less deadly strain will become the therapy, although it could be the basis of a therapy (but I think this too is unlikely).
All the attenuated live viral vaccines spread. This is one of the reasons they are so effective since they keep herd immunity up. For example, every kid that gets the live polio vaccine spreads it around to their peers and parents.
Can you point me to sources supporting that claim? I searched myself, and what I found says that our knowledge is limited to the polio vaccine:
"Little attention has been given to vaccine transmission, possibly because transmission is rarely measured and largely unknown in humans except for the oral polio vaccine. Whether transmission is indeed rare for other live vaccines, or has merely gone unnoticed, is not clear – polio vaccine transmission is accompanied by evolution to high virulence, creating problems that draw attention to transmission."
This is a difficult topic to research these days due to the anti-vax/anti-anti-vax noise. :(
It doesn’t appear that horizontal transfer is absurd, and while I’m not immediately seeing a large body of evidence that it happens all the time, it does seem to be generally accepted that it occurs.
The polio vaccine actually went to the inactive form to reduce the risk of polio from one of the vaccine strains reverting to wild type and infecting others. It is still less effective at achieving herd immunity than the live version because of the lack of viral spread.
Don't be hard on yourself; it happens. It's hard to withstand hours of engagement with internet commenters. The worst comments make a much deeper impression than everything else, just as getting stung by a bee is more memorable than seeing a butterfly.
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?
The sequencing is not the important thing here, but the search for strains with gene deletions and contact tracing everyone in the area to find more cases to prove the strain is attenuated. As far as I know nobody is doing this.
You’re fairly hard to get in contact with directly. Would you mind sending me an email? I don’t think I’ll be a your “middle hop”, but I’ll try. My email is lyndsy@<my_HN_username>.com
My username here is my real name, and I should be easy to find. It’s also my username on Twitter, Keybase, and most other popular platforms.
It was there, but I put it right at the bottom so at least only people who read the entire post would find it. I am at least a lot easier to get in contact with than anyone with the political clout to make this happen.
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
It is not hard to do the sequencing to find candidate attenuated strains (you are just looking for strains with deletions in key genes). The more difficult part is all the contact tracing in the area around where the strain is first found to check if the strain really is attenuated.
The ideal outcome is you find a strain with a deletion and you then test everyone in the area and you find 10,000 more people infected with the strain that have only a mild case and none of these people are in the hospitals. This strain would be very valuable to have.
Are they not? That seems like a pretty obvious experiment to do.
For reference: I have a family member in virology. He reports that everyone he knows is now working on covid, mostly because if they don't they can't come to work on anything. The biggest problem is finding subjects that will produce a paper of any kind. I really don't think research bandwidth is the issue here.
I guess I have to repeat the question as its converse: is there any evidence that this is not happening? If it isn't, let's figure out the right people to pressure and not just discuss it on HN. And if it is, maybe we should let the experts do their work without pretending to have had their ideas for them?
If you know anyone working on my idea please let me know as I will update my blog post. Nothing would please me more than to learn that someone is already doing this on a serious level.
> how would they know someone is asymptomatic? afaik they are mostly testing people who have symptoms
There was literally a paper published yesterday (or the day before) on a blanket screen done on a population in germany to get some data on the undercount of asymptomatic cases. It was front page news on all the mainstream news sites...
I gotta be honest. This whole discussion has an "amateur hour" vibe. I have a hard time believing that professional academics in a long-established and very competetive field really failed to remember how the measles vaccine worked.
It's not that I think this is a bad idea, just that (1) it's almost certainly someone else's idea already, (2) is therefore probably harder to do than presented and (3) is thus not the magic bullet people are looking for.
To wit: stay the fuck home. Maybe someone will save us. They probably won't. We beat this with isolation or we wait for a vaccine.
I think what you are missing here is what is the novel part of my idea and what is the conventional. It is not novel to think of an attenuated vaccine, what is novel is to look for an attenuated strain in a pandemic using genome sequencing. I hope someone else has thought of this, but so far I haven’t seen any evidence of this.
Waiting for vaccine is not a good option. This is a situation with only hard choices.
To assess the diversity and spread of the virus it appears. To the best of my knowledge nobody is systematically looking for a natural attenuated strain by genome sequencing. If you are then please get in contact with me.
"Waiting for a vaccine" is mostly a strawman. We're being asked to wait 2-3 months for the outbreaks to reach a size where they can be contained by testing, tracing and quarantine. But that only works if people take this seriously and honor the lockdowns.
Even if this would work in rich countries, this is not a realistic option for people in poor countries. They do not have the money to wait in isolation for the next 3 months.
We’re also likely to see convalescent sera available shortly, and neutralizing antibodies available in several months. Those, along with more widely available testing, will help us tread water until we develop a good drug or vaccine.
Robin Hanson has been covering variolation: http://www.overcomingbias.com/2020/04/variolation-test-desig... and part of the issue is that the FDA is poorly equipped and set up to respond to a pandemic. One obvious solution is to cut through the bureaucracy and make emergency exceptions, but no one with political power in the US seems to know this, or understand it.
There's a lot of differences in risk appetite (and actual risk) from state to state.
Maybe the feds could allow states to get a waiver from FDA regulations if they want to try things like variolation.
This would still require someone at the federal level to stick their neck out a little, but (I think) a lot less than if they were to propose something like this as a federal policy.
We've got a federal system, let's make some use of it.
Alternatively, if this approach actually works, all the countries in the world that can appropriately adapt their regulations will survive, and the ones that choose not to won't.
It's the "figure out if it actually works" part that is going to take most of the time for any potential prophylactic option for COVID-19. The bureaucratic overhead in this particular case is not going to be the inner loop.
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.
>What we really want is a strain that has infected a whole lot of people and all of them have had a mild case
How about 10 to 50 million ?
I live in Nigeria. Between December and late February, many people in Nigeria and Ghana report experiencing symptoms similar to those that could be caused moderate COVID-19 infection. These included, fever, diarhoea, cough, sore throat, malaise.
Many physicians and scientists I know think it we may have had a mild outbreak of the disease. If so, was this reduced severity due to a mild strain of the virus or to other factors ? It warrants investigation.
Your proposal and the theory underlying it make a lot of sense.
I would really like to be able to dig deeper into this.
1. Age is not the main factor at play here.
While the median age is lower than Italy's there are still a lot of elderly people in Nigeria. On an age and population adjusted basis, Nigeria has nowhere near the number of cases and deaths as Italy.
2. The demographic profile and phylogenetic makeup of Nigeria is similar to Cameroon which has experienced more cases and deaths than Nigeria in both absolute numbers and on a pro-rata basis. This makes some of us believe we are dealing with two different circulating strains in both countries.
3. It definitely is the case that testing is not adequate but a highly susceptible affected population would soon be revealed by the number of symptomatic cases and, (more to the point), deaths. Both indices have remained relatively low
If you are part of a cluster of a viral infection and you suspect Covid, then look for Anosmia as a symptom.
Anosmia is reported in 30%+ of Covid cases. Flu/cold viruses can cause Anosmia but it obviously isn’t common since you don’t hear about it and it isn’t given in lists expected symptoms.
Within a sample of 10 people that have Covid, you have an expected number of people that would have Anosmia.
Beware of false information https://www.nationalgeographic.com/science/2020/04/lost-your... because AFAIK the journalist has incorrect thinking: “flus and colds are a common cause of Anosmia” DOESN’T mean that “Anosmia is a common symptom” (the abstract they reference is poorly written, still poor journalism IMHO).
I would appreciate any references to data showing how uncommon Anosmia is in cold/flu patients (I did look, but didn’t look hard).
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.
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.
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 ?
0.1% would be great. That's the mortality of the regular flu and we have ramped up the hospitals to cope already so the 0.1% severe cases would be better handled. That would be much better than we manage the flu. It would also make it actually possible to take risk groups and isolate only those for a longer time without crashing the economy. It would be the opposite of the flu where vaccination is focused on risk groups.
Agreed. But for the heard immunity one does not have to go and vaccinate/expose to an attenuated strain of virus the whole population. Even getting a majority of say under 50yo immunized should have a big effect.
These are special times. In reality it does not matter if this 0.1% +70yo will die after vaccination since the mortality rates in this age group infected with the wild type are bigger by about two orders of magnitude.
But out of concern to human rights it will make sense not only to exclude any immunocompromised people but also make it voluntary to the groups where mortality rates are at certain level.
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.
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.
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.).
I just forwarded your information and article to the producers for the top shows at Fox News. Let's see if they move on it and get in touch.
I've also done the same for CNN producers.
It'll be interesting to see who responds, if any. My standard advice still holds: Don't hold your breath. Sadly. All of these people are far more interested in ratings than things that matter.
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.
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.
This is all described in the post. I have updated it to make it a little clearer (based on feedback). If you missed it the first time around you might get it now.
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.
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.
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.
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.
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.
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.
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.
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.
> 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?
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.
Daniel, can you please elaborate on this: "Unregulated spread by individuals is a solution" ? How do you envision it ? Virus is not an open source software, you cannot just "make your own copy" without a physical contact. :)
It is ‘a’ solution, but in my opinion not a good one. There are a number of ways this could happen, the easiest is just to send people to the area where it was first found and look for people infected. It is technically very easy to test any sample to make sure it is the right strain.
Even if you can’t get the strain it would not be technically very complex to recreate the virus from scratch once you know what deletion you need.
A modification of the standard RT-PCR tests can be used to identify if someone has the correct strain. This really is just a matter of making a different set of primers.
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?
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].
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.
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.
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.
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.
Well this is what many countries and scientists are already doing. It’s just not working as virus is unpredictable and it might infect some but not others.
The best way to find a solution is still try to understand how it acts on different types of people and if they have underlying previous conditions what changes it does, this takes time and I believe that’s the reason there isn’t any cure except by chance in a short time.
Are they already doing that? Is there somewhere I can find the statistics broken out by strain? Or even a list of identifiers of the known strains?
From what I've seen, it's been published in some news articles and such that there "might be" different strains. Haven't seen anything particularly solid yet.
Covid-19 is not mutating like other viruses, but it acts differently on different people, and very problematic for people with pre-existing conditions. Also in some cases again not proven it also infected heart muscles, now it’s not clear yet that it’s due to pneumonia or covid-19. In China they tried plasma from recovered patients and that also didn’t yield very good results. Also in some studies they find a correlation between BCG vaccine and low mortality (again not proven).
The issue with covid-19 is that it’s proving to be much harder to understand than other viruses in spite of not mutating like flu virus. Hopefully by more studies we can increase the chances of developing some cure or may be with so many efforts someone discover cure by chance.
Well it’s not mutating the virus they found in initial cases is still the same as the one at present in Patients in Europe and USA.
The premise of article is actually not novel, it’s the way vaccines are made. Smallpox way of developing vaccine in crude way without scientific understanding was done in the early years, now we have come very far.
This virus is really novel that’s the reason novel corona virus (covid-19). Scientists and research community are frantically searching for a vaccine or treatment plan to manage it. So far there is a very limited understanding. Hope can find some way to treat it, otherwise only solution left is relying on herd immunity.
The premise of using an attenuated virus as a vaccine is not novel, but the idea of using genome sequencing to find an attenuated strain and showing through epidemiology that it is safe does seem to be novel.
Even if it doesn’t pan out I think it is worth trying.
I don't know if all [corona]viruses move this way but it seems covid illness evolution goes in waves. high symptoms, 2 days ok, high symptoms, 2 days ok, ... repeat a few cycles
It's pretty confusing when symptoms are below a critical threshold and you don't have a test yet.
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%.
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].
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.
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.
Is my translation incomplete, or did that German study use a test with unreported sensitivity (but >99% specificity)? 15% could be closer to a lower bound, if so.
On top of that, other research indicates some folks might be recovering without developing antibodies at all (they could be clearing the infection with only their innate immune systems). In that case we couldn't be totally sure about the upper bound anytime soon:
We are really more interested in mild cases, not asymptomatic cases. The evidence seems to be that most asymptomatic infections go on to show some symptoms at a later date.
They didn't really say asymptomatic or mild case, but presumably people with (strong) symptoms would have gotten a test and already be in the official statistics.
The next study that is currently being prepared will include antibody-tests, but it seems logistics and which test to use is not a trivial matter.
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?
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.
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?
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 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.
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.
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.
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.
Ah, so you first check for a candidate and then check a (somewhat random) group of people infected with that candidate for severity. That sounds sensible. Thanks for updating a stranger from the internet!
> There are no stupid questions, just stupid politicians.
politicians aren't stupid, they just play a different game and it looks really dumb from the outside. for them, their moves make sense, they're pros at it.
anyway, you've done very well to find yourself on the top 30 of HN. the smarter press reads this directly. the less smart press reads it a few days later after it spreads through the net via reddits, facebooks, etc. hopefully it's a matter of time a good headline will find its way to pair of eyes in the right place at the right time.
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.
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.
Lets solve this issues once we find the right attenuated strain. Personally I think these sort of social problems will be overcome once we compare with the alternative of sitting around waiting for a vaccine.
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.
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.)
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.
I understand the metaphor you’re using, but for the sake of clarity I feel compelled to explain that there is a big difference: ankle-spraining significantly increases in likelihood with each subsequent instance. So “spraining ‘em all” even once would literally result in long-term degradation and increased frequency of injury. They would take less to heal, but would also get injured so often that the aggregated result would be worse than before.
Sadly joints tend to work a bit differently from the immune system (with some exceptions).
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.
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.
> 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?"
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.
There are dozens of ways the attenuated strain could be spread. You could do anything from going door to door sticking an infected swab up people’s noses to one of your contagion parties (they would be fun).
Actually once a safe strain was identified it would be impossible to stop people spreading it on their own. People would test to make sure they had the safe strain and then invite everyone they knew around for tea and scones.
Everyone they knew would need screening for the asymptomatic deadly strain first, or there would be a risk of everyone at the party catching the wrong strain.
> It seems like you'd need to manually administer this strain to millions of people.
Yes, but this doesn't seem too hard. Just have some infected people spit in a cup, and mix it into large vats of raspberry jam and people can then just spread it on their toast on one morning.
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
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.
And anyways, the harsh lockdowns currently implemented are basically forcing the virus to evolve into being asymptomatic.
Currently, anyone with even mild flu-like symptoms stays home
My understanding (not an expert) is that there is a difference depending how much of an initial dose of the virus you get. If it is very small then your immune system has more time to respond before the virus replicates to dangerously large numbers, whereas if your initial dose is large then you are starting with a large number of virus particles that replicate too fast for your immune system to respond.
Yes, that is the discussion I have heard, that healthcare workers without proper PPE get larger doses than those with the right gear and are more likely to fall ill. Same effect applies to the average person in public when exposed to an infected person who may not be showing systems - even imperfect PPE reduces their initial dose and increases their odds of having a less severe infection.
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/
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.
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.
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.
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.
> 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%.
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.
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.
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.
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]
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) was started on October 13, 2015."
They don't seem to elaborate on what the hell they mean by the valley of death.
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!
Flexible funding allows one to keep the proceeds even if the goal is not met in the allotted time. Kickstarter offers only an all-or-nothing payout for projects (unless something changed the last time I checked).
You'd have to sample many thousands of people who either have no symptoms or got sick. If the strain only exists in people with no symptoms then there's a good chance it's not deadly or at least less deadly than the other strains.
Of course you might find the best strain you can find exists in 100% of asymptomatics and 20% of the dead. That would indicate your strain has some non-zero death rate.
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.
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.
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.
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.
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.
> 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.
> 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.
We we have found less deadly strains (I link to one paper in the post that found one - still too deadly) and we have found strains with large (and small) deletions. What we haven’t done is go specifically looking for strains with exactly the properties we want (yet at least).
There is no need to create any viral mutants in the lab (and all the difficulties this will involve), just use what is already out there in the community. We just need to go and look for them.
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?
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.
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...
Anyway unproven but may be a way forward if the results prove good.
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?
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.
It probably won't be known at first, but we're talking a timescale of months to work out things like that. Things could be back to normal by the end of the year if we start now-ish. That is not blind hope either, it's just simple math.
They know which parts of the RNA express the spike protein that our antibodies recognise. If the spike protein is not affected, then the virus should still be good for training our immune system to respond to.
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...
(preprint https://www.biorxiv.org/content/10.1101/2020.03.22.002386v3....). 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.
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
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.
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.
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.
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.
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.
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)
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.
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?
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.
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.
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?
By doing an end run around the regulations. Actually even if you were to follow all the vaccine regulations by choice this would still be faster as it would have already been tested in human. Nature has run the trials for us.
I don't see the point of this. Nature has most certainly not established the long-term effects of this virus, seeing as it has only been spreading in humans for a short while.
Skirting the regulations is pointless, because the important thing is the intent of the regulations. If it were just a problem with the regulations, we could also just change the regulations and give the untested vaccine.
Plus, if you want to argue from a pure legal background, this approach would probably still run into trouble, as in most countries it would be highly illegal to infect people on purpose.
If we wait for the long term we will all get infected and we will all be broke. We need to think differently.
I am not arguing that we should infect people on purpose. If people chose to become infected on their own by hanging out with those infected with an attenuated strain then that is a very different legal question.
Personally I think the result would be the regulatory agency would just rush the use through based on the epidemiology data gathered in the search for the attenuated strain.
Here's what I have trouble reconciling: You say that this attenuated virus would spread automatically -- just like a virus -- and yet no one would be infected on purpose, only if people "chose to become infected on their own by hanging out with those infected with an attenuated strain".
How much agency do I have in whether I get infected or not? It seems strange to me if it depends on the genetic makeup of the virus.
If you were to deliberately go and hangout with someone you know is infected with the attenuated strain then a lot, if you catch it because your neighbour did this then none.
This discussion is really a distraction as I don’t think a “grass roots” spread would be the way any such strain would be spread. I think the regulatory agencies would look at the data collected from the natural spread and use this to approve the strain for use.
Well, in principle it does sound like a possibly "vaccine", but without the long-term testing I still don't see how we can be sure we have found this attenuated strain. Personally, I am youngish (30s) and healthy, so I would probably fall into the core group of those that "should" be infected. But given the choice, I don't think I'd do it, because even now, three months after this virus became big, there is still huge uncertainty about its lethality (even among young people), the number of severe cases (possibly causing long-term long tissue), and how this virus behaves in the long-term: how long would immunity even last? [seems unclear now]. There were also reports from China, and now South Korea, about possible reinfections or reactivations. Under these circumstances, I'd rather pass and keep to social distancing/masks etc. until a better solution comes along or the safety of an attenuated strain has actually been proven through a large scale, controlled trial.
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.
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.
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.
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.
"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.
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.
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.
> Government guidance is that people who are over 70, have an underlying health condition or are pregnant, are strongly advised to limit social interaction
What's interesting is that 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?
Just before I get into discussing this idea, I'm curious how sure you are about it. The way you describe it it's pretty much a simple solution that just needs implementing.
How do you know exactly what the outcome would be?
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?
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%.
> 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.
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.
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.
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.
>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.
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.
>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.
The whole approach requires young people to not take the lockdown seriously. They will be the people who spread around the less dangerous strain of the virus.
Would anyone have a choice? Surely once a few people are infected it will start spreading on its own. Even if people who are infected were instructed to isolate there will be a certain level of non-compliance, particularly at scale.
That doesn't matter. The reason why everything is closed is hospital capacity. That impacts everybody. If you had a car accident you may not get all the help you need.
14% of people may need hospitalisation and you want to focus your efforts on that group. There is almost no young people there.
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.
I am in an open source Christmas lights community that sources pixels from China. About a month and a half ago one of the Chinese vendors posted that the PRC is full steam ahead on Plasma therapy. He also stated his elderly father had gotten covid and was recovered within 24 hours.
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.
Something else to think about: This post implies that this solution would be implemented in some thoughtful and publicly-known way. We should consider the possibility that some organization (government or otherwise) could do this regardless of whether society accepts this as a solution. It's possible that this is already in the process of being implemented right now. Maybe better to ask for forgiveness than permission...
I'm a layman to this topic but it makes total sense that we should be pursuing this approach. At some point, it needs an influential person to back it and help remove the red tape. I think it could be done though. Probably just needs money first to find the right mutation and that would be the lure for an influential person.
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?
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.
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
> "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.
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?
> 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.
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.
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]
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.
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 :)
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/
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) 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.
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.
> 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.
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!
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.
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.
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
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) with someone verified to have the harmless strain?
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.
Thanks for the thoughts @danieltillett. I'm sorry you are not getting more traction on the idea. I'd sign up for this if I had this!
IANAL but I did run an infection detection medical diagnostics startup for 3yrs that I co-founded. Since we're on HN, perhaps here is how you might get traction (note, i'm just throwing this out move-fast-and-break-things-style for the sake of brainstorming):
1. Form a company, announce the idea bigtime! (Incorporate overseas for liability protection?)
2. Sell a sequencing service that tells you the strain you have -- offer no medical advice. Not a diagnostic for medical purposes, more like 23&me (does this get around regs?)
3. Offer a free matching service to find locals with the strain, perhaps with an app to validate their strain, etc. (some incentive for the customer?)
Note this isn't legal advice, but it would be awesome if someone with the correct background could provide feedback on this approach.
As for my startup, we sold overseas in easier reg jurisdictions -- we were never able to break into the US market.
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?
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_...
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-...
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.
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.
Epidemiological studies are much poorer than clinical trials. I’d rather have low-N but well controlled clinical trials than nebulous epidemiological studies.
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.
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.
> 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.
The reason why you need economic growth is to ensure the well being of your people, you talk about them as they are not interlinked when they very much are.
Other countries (some that may not care about the well being of their citizens) will be quite happy to take your place hierarchy and exert their influence over the world as they see fit, which may well be to the detriment to your nation (and nation is comprised of its people).
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.
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.
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.
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.
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.
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.
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.
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
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).
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.
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.
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.
> 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?
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.
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.
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."
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.
> But the author is doing himself a disservice by saying that tens of millions of people worldwide will die.
We're officially at almost hundred thousand dead now, most places on Earth haven't reached peak infections yet, and it's an open secret that deaths are being underreported everywhere. I can easily see tens of millions of dead in few weeks.
OP didn't say that, he said without depression-causing economical restrictions this is going to be a likely headcount. I.e. right now there is a difficult choice between killing the economy and killing millions of people.
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.
Sorry but are you an epidemiologist or virologist? The armchair advice you're giving very much belies what established experts in the field are saying. It also ignores all the cases of respiratory and cardiac complications in not just the elderly. Is "very old" equivalent to "older than 20" for you?
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.
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."
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.
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.
> 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.)
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.
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.
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.
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.
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?
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.
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.
It's not a pause button, it's a playback speed button that slows down the contamination.
Remember #FlattenTheCurve.
What is true is that it would take waaaay longer to reach herd immunity this way.
Another thing that people usually get wrong is the her immunity concept: from what I understand, it doesn't mean we ALL need to be infected. We just need to be enough, so the virus can't spread anymore.
At that R0 herd immunity will be probably achieved when at least 70% of the population is infected. So it’s not all, but we are still speaking of about 5.5 billion people globally...
Statistically a disease reaches herd immunity if everyone except 1 / R0 are infected.
For a disease with R0 of 3 (such as covid) this would be 66%. To explain: If two out of three are immune then a disease which usually infects three people will run out of steam.
Isn't this why there is a 1918-related flu outbreak every generation and why bubonic plauge used to recurved every generation because there aren't immune?
What about people born after that point? As immune people die over time from other causes, and as people are born without immunity, the percent of the population with immunity from having had it falls.
I think the idea is that once there is herd immunity, the virus has no way to propagate and ends up disappearing w/o vectors. However, that would require global immunity.
The whole idea of herd immunity in this context is fucking nonsense. No self-respecting epidemiologist would even bring it up this early into a pandemic.
Herd immunity is the last resort for the immunocompromised or unvaccinated, not the foundation for public health policy.
The point of social distancing is to bring the number of cases down to a point where other measures are possible, such as test-and-trace. Social distancing is step 1, not the whole process.
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.
"where everyone is required to wear masks all the time"
And this is what bothers me with such laws. No it does not make sense to wear masks all the time. (even assumed only outside) When I am running alone in the forest I do not need a mask. While driving a car alone, or with a partner, I do not need a mask. So the law should be, wearing masks all the time in populated public spaces.
"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"
And this is only true if you look only isolated at the virus and do not take into account the various big side effects of a lockdown. Because you will get deaths from: suicide, domestic violence, other diseases, because staying home is not really good for the immune system and general health. Also this only takes into account the rich world. In india staying home is also required, but this is a really serious death risk, if your home is a metal barrack in the slums, with no AC, meaning you just get cooked. Before you starve to death, because you have no income anymore.
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.
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.
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.
"fewer total deaths"
Yes, but not fewer total infections. You save lives by spreading out the infections over time, reducing strain on the healthcare system.
> I'd much rather live in a world where everyone is required to wear masks all the time
A properly fitting mask is uncomfortable. It hurts your nose, it hurts your ears. If you wear spectacles they fog up. People don't tolerate them, and so they fiddle with the mask, taking it off and putting it back, or dropping it under their chin.
Here's what happens when you wear a mask for a couple of shifts at work.
(I am not a professional, so what I write below might be wrong)
Having more time to develop a vaccine or effective treatments is essential, it doesn't have to be herd immunity. Plus in countries where covid19 rate is low enough, social distancing can be helpful for finding and isolating clusters to suppress the epidemic.
Of course, there are two ways out of this, herd or vaccine. The above is a variation of herd that may result in less deaths.
The real problem is that waiting until a vaccine is just not even remotely realistic for so many reasons that it's not even funny. We could end up causing more indirect deaths with social isolation than we could possibly imagine, worst case being a huge collapse in the economy results in a large regional or global conflict.
Indeed, CDC's numbers for March indicate that social isolation is reducing non-ncovid-19 deaths by twice as much as sars-cov-2 is adding them. That's short term, so not what GP was talking about, but very significant numbers nonetheless.
How many suicides? Guys losing their businesses that they put everything into. Can't even go fishing without their fellow man ratting them out to Big Brother.
"How did it end?
The most popular theory of how the plague ended is through the implementation of quarantines. The uninfected would typically remain in their homes and only leave when it was necessary, while those who could afford to do so would leave the more densely populated areas and live in greater isolation.
Improvements in personal hygiene are also thought to have begun to take place during the pandemic, alongside the practice of cremations rather than burials due to the sheer number of bodies."
This isn't really correct, and the proof is that most of east asia is relaxing restrictions right now without experiencing another exponential outbreak.
Testing, tracing and quarantine of infected people does work. It requires a bunch of infrastructure that we don't have yet (and in many places still aren't building, which is beyond frustrating). It also requires that the baseline level of the outbreak be small enough that you can catch most of the cases, which thus requires the continued lockdowns until we get back to that level. But it does work.
A country without other options might be more interested in the idea? I imagine that many first world countries would be too worried about the potential liabilities.
On second thoughts perhaps the idea wouldn’t work in countries that don’t have an effective lockdown. Could the infection wave of a less dangerous genotype overtake the number of infections of the more dangerous genotype before the population has been mostly infected already?
Yes if we act soon as we can spread the less dangerous version faster than the normal human-to-human spread of the dangerous version. For example if we were to send a postcard infected with the less dangerous version to 10 million people it would get out ahead of the dangerous version spreading normally.
good luck, we could have completely eliminated HIV by now but corporate profits are more important than that so the vast majority of the population who has the virus doesn't get the medication they need to not transmit it.
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.
"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.
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.
Perhaps, but that's Star Trek. It wasn't always obvious how the episode would end.
> Pretty wild to count Enterprise as "real Trek", but not Discovery.
Why? TNG, DS9, VOY and ENT, together with movies from TMP to NEM, form a certain coherent whole - both artistically, with themes, styles, pacing, and story-wise with a shared universe. Both Discovery and Picard, as well as JJ's movies, depart from that significantly. The style is different, the pacing is different, the stories and ethics are different (arguably much more shallow).
The Orville, though it was meant as a TNG-era Star Trek parody, seems much closer in pacing, style and ethics to that core TNG-era trek than Discovery.
> TNG was seminal and I loved it growing up too, but let's be real, it's showing its age quite badly these days
How so? Remastered version holds up pretty well today, I'd say.
I mean, yes, Berman/Braga era Trek has a fairly consistent style both visually and thematically because that's how they wanted it, but to privilege that style as "real" (or "proper", as you have it) requires considerable justification as yet not provided. Even from that era, First Contact not only used a largely horror/action-movie style then unprecedented in Trek, but went far out of its way to cast doubt on the Federation's - and the TNG era's - doctrinaire self-congratulation about its "more evolved" ethical ideal, in the shape not only of Picard's desire to exact vengeance upon the Borg, but also of the lack of self-awareness that blinded him to it very nearly unto catastrophe. Was First Contact therefore less "real"?
And if we're going to talk about ethics, we could do a lot worse than to talk about the Picard series's accidental but very real point that Picard's own moral absolutism and blind righteousness is as much of its time, as contingent, as any other ethic, and when taken out of a context where it's able to be effective, it does as much harm as any other, too. The point isn't explicitly made, because Kurtzman and Chabon are a couple of hacks just like Berman and Braga were, but it's easy to draw from the text on the basis of an almost trivial engagement - Picard's quixotism managing to ruin just about everyone it touches, and the writers having to fall back on a Bond-villain plot to try to make him come out looking good, is enough all by itself for that.
That's the kind of thing I mean when I talk about TNG showing its age. The remasters look pretty good, sure. But the Trek fandom has ever qualified their shows as especially worthy not for the quality of their visuals, but for that of their ideas. From that perspective, a lot of TNG, and of its era more generally, struggles today.
> but to privilege that style as "real" (or "proper", as you have it) requires considerable justification as yet not provided
It's arguably the largest consistent body of work in the entire Star Trek franchise, the one that was the peak of its popularity, the one that fleshed out the universe and is most recognizable. Also somewhat unique compared to other science fiction, which I can't say about post-ENT installations.
> Was First Contact therefore less "real"?
Nah, I consider it real because - besides mostly staying thematically and stylistically consistent - in terms of storyline, it critiqued the "ethically more evolved" humanity; it shown shades of gray of an otherwise mostly white object, instead of making it black with occasional lighter tones, like post-ENT installments do. It's the same defense I'd give DS9. It's still the same utopian world, the same beacon of hope - just not a perfect utopia.
(Also: throughout TNG/DS9 and the movies, the Federation did feel like an actual character in the movies. ENT was leading up to it, and it portrayed humanity growing up towards the TNG-era utopia. This aspect seems completely missing from Discovery/Picard; both the Federation and Starfleet seem to exist there just to have a flag and an icon to slap on things.)
Unlike JJ movies, I'm not considering DIS and Picard as completely bad. I've noticed and appreciated the point about Picard brought up in his eponymous series, as much as I appreciated the concerns of Klingons in DIS - their point about Federation being a cultural threat to them would fit perfectly fit TNG-era Trek, and add further depth to their race. And I tried to be fair to both DIS and Picard, to watch them without biasing myself against them - but they really don't fit the whole in my eyes. They stand out as something totally different in almost every way.
> But the Trek fandom has ever qualified their shows as especially worthy not for the quality of their visuals, but for that of their ideas. From that perspective, a lot of TNG, and of its era more generally, struggles today.
I've been rewatching TNG (and DS9) quite recently, and the way I feel, it's the concerns that aged, not the ideas. I.e. TNG (and DS9) cover themes that were the concern of society of the 80s and 90s, which seem less relevant today, but I don't feel like the way of thinking of the characters has aged badly.
I'd argue that First Contact's critique of Federation ideals is uniquely pointed because it aims that critique specifically at Picard, who is constantly shown to be the conscience of the Federation, the one who insists on those ideals even when others argue that the exigencies of the situation demand compromise. His character mirrors Worf's in that way - just as Worf values Klingon ideals far more highly than the other Klingons we see, Picard does the same with the ideals of the Federation. It might be part of why they get along so well, but it's also worth considering that Worf's idealism is founded on detachment - he's able to indulge in it because he's in a position where he almost never has to deal with the messy realities that make idealism so difficult to sustain.
One wonders whether the same might be true of Picard. Unfortunately, we don't get a chance in B&B-era Trek to see how he reacts to the test of the Dominion war, but his behavior in First Contact is nonetheless telling. If even "the conscience of the Federation" so signally fails to live up to the ideal - if it's only the desperate intervention of someone from a time universally regarded in Picard's own as a cesspool of cruelty and horror that saves him from his own mad, vengeful hatred - does that tell us something about the merit of the ideal? If even the person who most exceeds all others in following its guidance can so signally fail, are we wrong to question its value as a guide for those less uniquely exceptional?
I can't disagree that Discovery and Picard are very different from what's gone before. But, then, the TNG-era works were very different from TOS, too. Where we differ, I think, is that I don't see anything wrong with that - indeed, I don't see how it could be any other way. The works are made in the context of, and in dialogue with, their times - as you yourself note with regard to TNG and DS9. These are very different times from those in which the earlier shows were made, and it would be much more of a surprise to see new Trek shows try to ignore that difference than to see them embrace it.
"Infinite diversity in infinite combinations." It's a worthy ideal, and an apropos one to see expressed in the same series of TV shows and movies whose own originator codified it.
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!)
So...you're upset to see space opera played straight in your space opera? Have you forgotten entirely about S1 of TNG, or just chosen to ignore it? DS9 is "not Roddenberry", too, what with its most universally acclaimed episode being about Sisko deliberately subverting his own principles and those of the Federation to suborn all manner of criminality, not excluding several murders, in order to deceive a neutral party into entering the war as a Federation ally. Is DS9 awful, too?
To be honest, I don't get the mockery angle at all. I mean, you're talking about a show whose first season not only has antimilitarism as a major through-line in the way Lorca's story plays out, but concludes with a war being ended by a couple of people having a conversation about why more fighting sucks for everyone, and implementing a clever technobabble-driven plan to bring about peace. There's a lot I don't love about Discovery - most of its second season, for a start - but come on, what could possibly be more Star Trek than that?
> So...you're upset to see space opera played straight in your space opera?
No, I like space opera too. I'm upset that ST has become Buffy the Vampire Slayer in Space. (Don't get the wrong idea, I like Buffy too.)
> Have you forgotten entirely about S1 of TNG, or just chosen to ignore it?
You'll have to clue me in to what specifically you're referring to, I re-watched it last year but I don't want to guess at what you mean.
> DS9 is "not Roddenberry"
I agree. DS9 was, in part, created specifically to explore "not Roddenberry" directions in the ST universe.
There's a book, I can't find it at the moment, and I don't remember the title, but it's all excerpts from interviews with cast and crew. That's it. It's amazing.
Anyhow, I bring it up because, reading it, it became clear what, for me anyway, is the crucial defining aspect of ST that differentiates it from other sci-fi franchises: In ST, people in the future have gotten over their bullshit. They are emotionally mature, guided by reason and rationality and their higher values. That's the key difference (from say, Star Wars or Farscape or Firefly...) People in the future pretty much have their shit together.
Now this is something that some of the writers don't get. You find them complaining in their own words that Gene won't let them write an episode involving interpersonal drama between bridge crew. (Apparently this is really hard for some writers. No judgement intended.) It wasn't until after he died that Berman/Braga started to relax that.
Now to me, this is wrong (for ST) for two reasons:
First, it makes sense to me that these folks who fly around the galaxy in machines that can destroy worlds would have to be level-headed to use them w/o destroying themselves.
Second, and more importantly, that's a huge part of what made ST so endearing and appealing in the first place: the deep and abiding love that Kirk/Spock/McCoy (most obviously) and the rest of the crew (less obviously) feel for each other.
I mean, when Spock tells McCoy that he would also wish him to be present at his Pon farr, oh man, my eyes well up with tears.
When it comes down to it, the characters in the "real" ST (if I may) treat each other like members of a healthy family do, and that's wonderful to see (in any context, not just space operatic sci-fi.)
That's also the source of the "moral" superiority of Star Fleet: they actually are good guys. (And Vulcans don't lie.) You erode that and you've got Spaceballs.
> To be honest, I don't get the mockery angle at all. I mean, you're talking about a show whose first season not only has antimilitarism as a major through-line in the way Lorca's story plays out, but concludes with a war being ended by a couple of people having a conversation about why more fighting sucks for everyone, and implementing a clever technobabble-driven plan to bring about peace. There's a lot I don't love about Discovery - most of its second season, for a start - but come on, what could possibly be more Star Trek than that?
I've only seen ~4 minutes so I can't speak to the good things about the show, feeling mocked was my subjective response (I don't think the ST:D folks sat down and twirled their mustaches while contemplating how much they despise ST fans, hey?)
It was things like how the Klingons are space orcs; the Romulan guy looks like space Legolas the elf. The people wearing hoodies (why does everyone in space wear hoodies these days?) The gay guys are the only ones married? Why does the female lead have a masculine name? It seems like they're trying to tick the diversity boxes without actually rattling anybody's cages (and I say that as a SJW, pro-diversity.) The rolling spaceship is ridiculous, the flash illuminating the nebula was just idiotic. The whole thing feels superficial and lazy despite obviously being the result of a lot of hard work by a lot of skilled, talented people. Maybe they're just pandering to the tastes of a younger audience (with whom I am out of touch.)
Let me see if I can sum it up... Lord of the Rings and Game of Thrones seem similar, yeah? But LotR is about Good vs. Evil whereas GoT is about aristocrats being really really shitty to each other. They are both entertaining, but I wouldn't let my kids watch the latter.
I mean, don't get me wrong, what you describe as the good in Trek is something I also appreciate. The trouble is that, TOS aside, I don't see it where you do.
The reason I called out TNG S1 earlier was because it lacked absolutely nothing in terms of space-opera absurdity by comparison with Discovery, and so it's odd to me that you should abhor the one and disregard the other. But I'd also mention it in this connection because the Roddenberry-driven performances of its characters don't read as "members of a healthy family", as you describe, but rather mostly as just flat and lifeless in affect. The interpersonal stuff just reads off, like a stage play put on by disinterested actors not directed very well. As we see later in the same series, that's certainly not the fault of any lack on the part of the main cast, whose relationships become more believable, rather than less, as the show goes on. The major change is the one you cite: Roddenberry no longer exercising creative control. I think it's reasonable to consider that that change lay behind the improvement of character and relationship portrayals that I describe - especially considering that, as you also note, many of the people who made the show have said exactly the same.
Consider, too, that while the idea for TOS was his and a lot of the development was as well, he did not exercise anything like the same degree of absolute authority over that show as he did over S1 of TNG. I agree with you that TOS's characters were lively and that their friendships were obviously close, deep, and warm, and I think it's interesting that they were so in an environment much more similar to TNG's later seasons than to its early ones.
(As a side note, if you haven't read Diane Duane's The Wounded Sky, from the Pocket Books TOS novel series, I can strongly recommend it. Of all the portrayals I've seen of the relationships among the TOS main characters, in and out of canon, this is the only one I find myself always coming back to specifically for the sake of that portrayal. I'm told that "Where No Man has Gone Before" from TNG S1 was meant to be an adaptation, but God alone knows how; they're nothing alike, especially in that that episode's characters are exceptionally flat even in comparison with the standard set by that season.)
With regard to your comments on the supposed superficiality of Discovery, I feel it necessary to note that this is a judgment you've formed, and which you apparently hold quite firmly, on the basis of about four minutes of what I gather to be trailers and promos, and not on the basis of any true engagement, however adversarial, with the show itself. I find it difficult to understand how any judgment so formed could be anything other than superficial in its own right, considering that you have by your own account barely scratched the surface. It may be worth considering whether a more sustained investigation is worth your while. If nothing else, it can only enable you to better substantiate your arguments for why the show is bad!
And, sure, I wouldn't let my kids watch Game of Thrones, either, if I had any. But that doesn't make it a bad show. To be sure, there's a vast sufficiency of traits which do make it a bad show! But it being inappropriate for children is not among them.
> The reason I called out TNG S1 earlier was because it lacked absolutely nothing in terms of space-opera absurdity by comparison with Discovery, and so it's odd to me that you should abhor the one and disregard the other.
Oh there is a lot of silliness in TNG (Data can't get the hang of contractions!?) but, and this is entirely subjective, to me it seemed in line with the rules or framework that TOS established. What I mean is, other than the holodeck, most of the technology was the same. Of course, the TOS tech is "magical" already: there are no teleporters, warp drives, etc., and we can't diagnose disease by waving rotating salt shakers over people. But somehow the rolling effect preceding "spore drive" offended me in a way that "going to warp" doesn't.
When I say "offended" I don't mean "oh my opinion is different". I mean that scene broke me. I was gibbering in the corner.
Ah, here's the exact clip that triggered a kernel panic in my brain: 'Discovery Spore Jumps to the Second Red Signal | Star Trek Discovery "New Eden"' https://www.youtube.com/watch?v=7-3WKobwcxQ
Oh God. I forgot about the rotating dongle on the ship...
Anyway, it starts off bad, hard to take, and then just keeps getting worse and worse, and the the jump... https://youtu.be/7-3WKobwcxQ?t=232
Whaaaaaat?
It's like watching "Team America" but with real people playing the parts of the puppets, in space, with goofy special effects and way too much production value.
(But it's not space. Just as the ship arrives the background is illuminated as if there is atmosphere (it's not the background nebulas like I thought, just open space. Whew! That's something.))
Sorry, sorry...
(Like I said, maybe I'm just too old...)
> But I'd also mention it in this connection because the Roddenberry-driven performances of its characters don't read as "members of a healthy family", as you describe, but rather mostly as just flat and lifeless in affect. The interpersonal stuff just reads off, like a stage play put on by disinterested actors not directed very well. As we see later in the same series, that's certainly not the fault of any lack on the part of the main cast, whose relationships become more believable, rather than less, as the show goes on. The major change is the one you cite: Roddenberry no longer exercising creative control. I think it's reasonable to consider that that change lay behind the improvement of character and relationship portrayals that I describe - especially considering that, as you also note, many of the people who made the show have said exactly the same.
Granted, but they (the characters) don't really get into interpersonal conflicts, eh? Consider Lt. Barclay and how he is treated as his character develops. Off the top of my head, that's about as close as you get to drama. Or when Riker meets his duplicate, or his father. There is some drama. (I'm reminded that Spock and his father are also at odds in TOS.)
So I seem to have convinced myself that you're right: already in TNG the cracks in the utopian "healthy family" milieu are showing.
It's not that I don't enjoy TNG, or DS9 or the others, despite the drift from utopia. FWIW, it's the utopia I miss.
In re: The Wounded Sky I'll pick one up. Thanks for the advice!
> With regard to your comments on the supposed superficiality of Discovery, I feel it necessary to note that this is a judgment you've formed, and which you apparently hold quite firmly, on the basis of about four minutes of what I gather to be trailers and promos, and not on the basis of any true engagement, however adversarial, with the show itself.
You're right. Some trailers, a few minutes of the beginning of s1e1, and the clip I linked above. I wouldn't call it a judgment, more like a visceral reaction. But as you read above, it's pretty firm and consistent.
> I find it difficult to understand how any judgment so formed could be anything other than superficial in its own right
Oh it is, I didn't dig too deep, although it does come from my core. Part of it is that I take sci-fi way too seriously. I identify as a sci-fi fan.
But you're right! Without "a more sustained investigation" I can, at best, only be projecting my own BS onto it, eh? And like I said, it's obvious that a lot of work and talent went into it. It's kind of crass to dismiss it like I've been doing. I'll try to watch that clip again and get over myself. Cheers!
> And, sure, I wouldn't let my kids watch Game of Thrones, either, if I had any. But that doesn't make it a bad show. To be sure, there's a vast sufficiency of traits which do make it a bad show! But it being inappropriate for children is not among them.
Ha! Well met.
G.R.R.M. once said that he thought LotR would be better if Gandalf didn't come back, but I think he was just trolling. ;-)
Oh, I don't know; I think I can see what he means. The change would give additional point to the major theme of mortals taking on the burden of looking after themselves - of deciding their own course among the wonders, terrors, and banalities of the ever-unfolding future, instead of any longer relying on gods, demigods, and immortals to do so.
(If that's a theme you appreciate in LotR, then you may be interested to know it is also the theme closest to the heart of Babylon 5, and around which its story entirely revolves...)
Thanks for this response! And for what it's worth, I miss utopia, too - or utopianism, anyway. Blame the postmodernist insistence on engaging in dialogue with a work, if you like, or the wide contrarian streak in my nature; when I see something presented as if without cracks, I insist on looking for them all the harder, and always end up finding them, too.
Sometimes I wish I didn't; life would seem simpler that way, for sure. But Leonard Cohen was right: there is a crack in everything. That's how the light gets in.
> Oh, I don't know; I think I can see what he means. The change would give additional point to the major theme of mortals taking on the burden of looking after themselves - of deciding their own course among the wonders, terrors, and banalities of the ever-unfolding future, instead of any longer relying on gods, demigods, and immortals to do so.
Also, is that a theme of LotR? It's been a while since I read them but I thought the theme was pretty clearly just "stick it Sauron", no? Am I a philistine?
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).
> 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.
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.
(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...)
> Take away Roddenberry's vision of a better future and you've got Babylon 5, eh?
There's a hell of a take! Whatever Roddenberry's virtues, I don't recall him ever having the gumption to write a story in which the heroes go to war against the gods because the gods aren't doing it right.
(It's a very Klingon thing to do, though, unless Worf was joking about that.)
Fair, and thank you! Fwiw, I'd have aimed the shot at the 2003 Battlestar Galactica instead, where it is very much deserved. Wild that Ronald Moore, who wrote so much of what's best in TNG, could also produce something that's so grim for the sake of grimness...
I personally loved the reimagined BSG in its own way (different from my feelings for Star Trek or B5). I only wish they'd explored the hybrid utterings angle further, there was a lot of space for some out-there (and possibly Lovecraftian) ideas.
> 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.
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...
> 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.
...and it lead me down a rabbit-hole. It seems all the good sci-fi these days is being done as shorts by mostly independent filmmakers and posted to youtube. Here are some I found last night:
ENT was pretty dark, too, you know. If we're not going to talk about "In the Pale Moonlight"'s argument that violating an ideal in a small way might be justifiable, if not respectable, to preserve it in the large, then can we talk about how Archer, in "Dear Doctor", refused to hand over the cure Phlox had developed for the Valakian plague, thus consigning an entire species to extinction, because the then-inchoate Prime Directive ideal meant more to him than saving the lives of millions of fellow sentients? Sure, the show portrays this as an uncomplicatedly virtuous choice, without the nuance that Michael Taylor brought to "In the Pale Moonlight". But I don't see why I need to take that portrayal at face value, when the supposed virtue in question is that of refusing to save millions of lives.
I think the core disagreement here may instead be that, where you see the Federation portrayed as a true utopia, I don't. I agree that in the B&B era it claims to be so, and that the claim is also often made on its behalf, but that's not the same thing at all. I think it's less interesting and less worthwhile to take those claims at face value, in spite of all the evidence to the contrary, than to take them as a stepping-off point for a discussion of how utopian ideals are no less susceptible to failure in practice than any other sort of absolutism, and how, while idealism is certainly not lacking in value, it cannot alone serve as the foundation for a mature sense of morality.
Granted that this is a difference of interpretation. But, then again, we're talking about how we choose to appreciate works of art. In that context, what isn't?
I give ENT a pass because it my mind it works as "humanity halfway from now to TNG-era UFP". Taking baby steps both outwards and inwards. It was dark, particularly across the Xindi angle, but not that dark relative to everything else.
I mean, it's like TNG was #EEE, ENT went down to #AAA, but everyone else (including post-ENT Trek) seems to be made at #555 or below. There's a gap, and I'd love if someone was making more idealistic shows these days.
> where you see the Federation portrayed as a true utopia, I don't.
I used to, then I rewatched the whole series as an adult and it changed my mind a bit. But then, I probably used the wrong word. I don't see the Federation as a perfect, flawless utopia. Just a vision of a world as close to utopian as you can get without breaking your suspension of disbelief. A world that works much better than the real one, and not just because of matter replicators and near-infinite energy availability. A word where the baseline for humans is much higher than it is now. And maybe it's unrealistic, it's too out-there, but every time I watch it I feel inspired to do better, be better. It's not something I usually get from other shows; they're all too focused on.
> than to take them as a stepping-off point for a discussion of how utopian ideals are no less susceptible to failure in practice than any other sort of absolutism, and how, while idealism is certainly not lacking in value, it cannot alone serve as the foundation for a mature sense of morality
That's fair, but again - while I love talking about this, I think our media culture spends too much time talking about all the ways ideals fail and high standards don't work, and too little time about what good ideals or values could be and how to make them work.
There's a certain positivity about TNG-era Star Trek that I feel, that I try to refer to, but continuously fail to express in words.
EDIT:
And I forgot one thing: the curiosity of space, the exploration angle. I know that a lot of astronomy in Star Trek is bunk, and a lot of what was accurate at the time of filming didn't age well, but there was a way in which TOS and TNG made people curious about space. I got similar vibes from a few StarGate: SG-1 episodes as well. I don't see any of that in modern shows - just as if familiarity with real and sci-fi astronomy was table stakes these days. It works for me, but I wonder how the young audience, not exposed to TOS/TNG, responds to modern shows.
> Star Trek was an unique word in sci-fi (at least on-screen sci-fi) because of that bright idealism, that utopia.
What utopia? Outside of the crew of the Enterprise itself in TOS and TNG (most of the time, when not under malevolent outside influence, abd even then there are some exceptions), neither Starfleet, the Federation outside of Starfleet, nor the galaxy outside of the Federation (in roughly descending order of proximity to utopia) were portrayed as without flaws in any version of Trek.
> Star Trek, in its TNG to ENT era, was unique in terms of positivity and optimism.
Usually, this claim is made for the TOS to TNG era (or, more specifically, the era when Gene Roddenberry was directly involved). While, as noted above, it's flawed even then, it really doesn't work for DS9, VOY, or ENT.
Maybe instead of "utopia" I should've said "as close to utopia as you can get without shattering your suspension of disbelief". The world was designed as a reachable utopia, and in my eyes, the vision didn't decay fast enough when Roddenbery left the scene to be lost by the time of ENT.
> While, as noted above, it's flawed even then, it really doesn't work for DS9, VOY, or ENT.
Compared to what? Relative to pretty much every other show, I think it worked really well. The baseline is still visibly much more idealistic than everything else (including post-ENT Star Trek).
> The baseline is still visibly much more idealistic than everything else (including post-ENT Star Trek).
Picard, specifically, seems to differ from late TNG or DS9 not so much in the degree to which the Federation is or is not a utopia, but in that the focal characters are (at least initially, the arc if season one seems to have most of them evolving in the direction of more conventional ST focal characters) in places that would only have been occupied by non-focal characters.
(“Starfleet is doing bad things because it's upper echelons have been infiltrated by outsiders with an agenda that is, at least in chosen methods if not goals, anthithetical the the ideals towards which the Federation strives” is not inconsistent with the degree of idealism in TNG.)
Well, they were working on it innit? The Federation was young (I'm talking about TOS here strictly) and working hard to prove itself to the galaxy. And they met people who were further along than themselves (like the Organians.)
> 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.
Every Star Trek series does that. TOS and TNG tend to portray the focal crew as perfectly ethical taken together (though not always individually), but often as being in antagonistic relationship with their superiors in Starfleet and/or the civilian leadership of the Federation for precisely that reason.
It's true that many of those struggles reflect bureaucratic indifference, incompetence, and narrow-mindedness more than active malevolence (excluding when it is due to outside influence/infiltration), but that's pretty much true of Picard (the series) as well.
I think what I liked about the TNG-era Star Trek was that, as often that there was an "antagonistic relationship with their superiors in Starfleet and/or the civilian leadership of the Federation", they also as often get along. The Federation was a government that worked. That was the baseline assumption. The show demonstrated it, the characters believed it. They were proud of being a part of it, and not just because of some ill-conceived patriotism.
Related to that is the baseline assumption of competence. Characters in Star Trek, especially ones from the Federation, were always assumed to be extremely competent and good at working together; everyone valued excellence. Sure, they were exceptions, but they were that - exceptions, around which a story or a joke could be built. I miss that world of excellence in other shows.
Just take a trip through time and stop it that way, if you could.
(I'm not even talking about the inconsistency between traveling faster than light and not moving backwards in time, I'm talking about repeated in-universe demonstrations of time travel mastery)
Of course, the writer's tortured "ethics" might require that everyone has to keep the last couple months of awful memories.
IIRC, it’s only about 30Kb of information, and the vast majority of that is shared with similar viruses in the same family.
Assuming there’s a reliable way to remove segments of the genome (I’m not a biologist, so I’m not sure if that’s practical), it doesn’t appear to be an impossible problem to solve.
Users need to follow the rules regardless of how right they are or feel they are. And of course there's the side benefit that if you turn out to be wrong, you at least won't have been a jerk about it.
"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.
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.
> This entire article is a waste of time from the beginning.
The moment I read that I lost my interest in his comment. Anything he is going to write afterward would not matter. He didn't gave sufficient reasons either why he thinks the article is a waste of time. We can safely ignore his opinion. Anyone who is directly reading GP's comment please read the article and decide for yourself.
The articles author doesn't claim there are two strains. He claims there are many mutations. The link shared by the parent notes, "As of 2nd March 2020, there are 111 nonsynonymous mutations that have been identified in the outbreak". This seems to agree with the original article.
The article seems to work within the current findings of many mutations and different mutations have varying degrees of impact on people.
"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 premise that there is an "asymptomatic strain" is still theoretically possible but unsubstantiated, despite ongoing investigation.
> "I can’t believe that a month later, this bad science is still being circulated, by a purported PhD and former professor. "
That strikes me as a bit harsh, given that the posted article doesn't actually rely on two-strain to make its case, just the idea of functional variants possibly being out there somewhere. MacLean's rebuttal didn't definitely exclude the possibility that there's some functional variants out there somewhere, we just don't know, haven't seen it in anything we've catalogued so far.
Science is often about calibration. I wouldn't say a search for functional variants is completely worthless. That's why researchers continue to look at variants. On the other hand, completely agree it's overselling to pitch this as a silver bullet for the whole crisis though. Research can be important even when it doesn't solve for everything.
> The premise that there is an "asymptomatic strain" is still theoretically possible but unsubstantiated, despite ongoing investigation.
He doesn’t seem to be arguing that a previously unidentified “asymptomatic strain” - or the effects of such - is currently known. If I understand his reasoning, he’s saying that it’s theoretically possible that a milder strain might exist, and that in order to find and isolate that strain (if it exists) we would need to be blanket testing people in outbreak areas, partitioning those samples by outcome, then sequencing the positive tests.
Once you have a set of sequences from positive tests from people who were and remained asymptomatic, then you can isolate the variants that lead to that and begin testing to see if any of those variants consistently present no (or very limited) symptoms AND confer immunity to the pathogenic strains of 2019-nCoV.
> I was planning to go through all of his replies to other posters and debunk them one-by-one.
If you disagree strongly with someone, there are much better tools you can use like the down-vote button. Down-voted posts are harder to read and especially bad contributions get collapsed out of view.
Going out of your way to hound someone would only lower the S/N ratio here, which is not why we are all here; intellectual curiosity is why we keep coming back here not witch hunts.
> 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.
I invited danieltillett to repost 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.
That's a bit uncomfortable because I thought it deserved the flag, but knowing that this has been mod-reviewed means that flagging probably doesn't serve a constructive purpose.
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'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...
[2] New blood tests for antibodies could show true scale of coronavirus pandemic https://www.sciencemag.org/news/2020/03/new-blood-tests-anti...