Ask HN: How to get Bill Gates's attention? | Hacker News Reader

Ask HN: How to get Bill Gates's attention?

122 pointsdanieltillett87 comments

I have what is possibly a very simple, cheap and quick solution to solving the COVID-19 pandemic. The problem is I am in Australia and only someone like with clout in the USA or Europe like Bill Gates can put it into practice. Any ideas how I can get their attention?

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If anyone wants to know what this possible solution is I have written it up here in non-technical language [0].

0. https://www.tillett.info/2020/04/05/a-solution-to-covid-19/

Edit. HN seems to have put me on the “posting too fast” treadmill so I will have to edit this post.

While effectively the same as a vaccine, it is quite different. Any such attenuated strain identified can be used outside of the regulatory system. This is the real key to the idea.

Edit 2. I am not a crank - well at least I don’t think I am. I have a PhD in microbiology and I have been a professor in microbiology and virology. I now work in the biotech industry. Have a look at the about me section of my blog to check into my background if you care about these things.

This is well written, and passes the "not a crank" test that many will surely apply. Mathematicians get inundated with unsolicited false proofs of famous theorems, and the cranks always give themselves away by various "poker tells" that they are too delusional to control. This is not that; it is a serious proposal, and it escapes being wrongly classified as otherwise.

I am reminded of a famous computer scientist I know, who dropped everything for years because he had an idea about the CD4-CD8 ratio in Aids patients. Aids patients have fewer CD4 cells. Perhaps the body was only sensing the total, and could be triggered to make replacements for the lost CD4 cells if one medically removed CD8 cells. Remind anyone of rebalancing a portfolio during a market crash? I can find no trace of this effort online, so it's not my place to name the researcher. Science does a poor job of recording its failures.

In any case, it didn't work; medicine is very hard. Be prepared for this idea to be wrong, too, despite best intentions.

You might want to summarize this in the submitted post itself to reduce friction for the readers (and thereby maybe increasing the odds of success).

The post is pretty much just a summary, but I will post it here too.

Edit. HN is not letting me reply to people with questions (shaking small fist). If would like me to answer anything then post a question on my blog.

It will in a while. There is a delay (dead time) until a reply link appears which increases the deeper a comment is in a thread. This is to prevent particularily heated discussions where people just fire responses without thinking too much.

HN has a rate limiter for some posters (like me) that will not allow you to post at all after a certain number of posts/day

Why Bill Gates? Or why start with him?

Get a grant from anywhere reputable. You need to work your way up the ladder through a ton of hard work. I don't mean that's how the system should work, but each rung of the ladder will be a signal to the next rung that your idea is worth the opportunity cost of not considering a competing idea.

Waiting for Gates or another almost god-like figure can be an excuse to avoid hard work or the pain of failure. I don't think it matters that this is "in the public interest" instead of purely for personal gain.

If you're right about these strains being out there, I don't think you'd have to do a worldwide search. A local search in any metro area should be successful. Unless I misunderstand your proposal.

Have you looked into my background? I know all about how the how the system works. I am not looking to avoid hard work.

As for why Bill Gates I specifically said I am looking for people with the clout to make this happens - while I am sure Bill would understand my proposal so would lots of other smart people.

I don’t wish to be snarky, but yes you have misunderstood my proposal.

Sorry, no I didn't look at your background at all. My comment was basically reflexive because people are constantly trying to skip the middle steps of getting the attention of super high profile people when I see those incremental steps as the only reason the system can continue to function. But there also has to be ways of escaping the system when very good or novel ideas come around. Like maybe yours.

Wish you the best in your efforts and please don't let comments like mine dissuade you from any possible route to helping get us out of this mess.

> people with the clout to make this happen

You said you are in Australia? The Australian government has the clout to make this happen.

But we don’t have the cases. I am not the Australian government, but if you happen to have the direct line to our PM I will be most happy for you to make a call and set up a meeting.

So you're saying we need to check all the mild cases for that 0.1% chance that they have the attenuated strain. You say that even the mild cases have the dangerous form of the virus most of the time.

Do you think we could find the attenuated case more easily of we tested immune compromised people that have mild to no symptoms? Because if they did have the dangerous form of the virus, the symptoms wouldn't be mild. So we know that if you have the virus and are immunocompromised and have mild symptoms, it's probably not your immune system that is strong but the fact that the virus strain you have is attenuated?

Or does that not work because the amount of people you can test that have those conditions is just too low to find any?

Yes for this to work you are going to have to screen a lot of people with mild cases to find the very rare mutant that is attenuated. The chance this rare mutating just happens to infect an immune compromised person is low. Just looking through the entire population of mild cases will be much quicker as the limiting factor is not the genome sequencing of the viral strains.

A decent percentage of people are also asymptomatic with most influenza strains. You probably know friends/acquaintance who says they never get the flu in winter, even though it's highly likely they have gotten the virus before, it's just their inflammation response for whatever reason (likely genetic variation) doesn't produce symptoms.

Source: https://www.nhs.uk/news/medical-practice/three-quarters-of-p...

Yes this is true, but it has nothing to do with finding an attenuated strain. I addressed this in my post and yes many people who have a mild symptoms are infected with a dangerous strain, but an attenuated strain will only cause mild symptoms. If you want to find an attenuated strain you have to look in people with mild symptoms.

> If you want to find an attenuated strain you have to look in people with mild symptoms

Shouldn't we be looking at people with no symptoms? I know this is not ideal as we're likely only testing symptomatic people.

Yes we want to test asymptomatic people too. Some countries like Germany and South Korea are doing are better job of testing widely and so they have many more mild/asymptomatic samples that can be screened.

> test asymptomatic people for COVID-19 and then genome sequence the SARS-CoV-2 strain that has infected them with the aim of identifying a virus with mutation(s) in an essential viral gene(s)

But without these essential genes the virus would not multiply / infect people anyway, right? Also, how is it different from inactivated vaccines that are currently being developed ? Also, why cant someone engineer such a virus with appropriate deletions?

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

1. You are looking for partial deletions of essential genes, not full. Many of these deletions are going to weaken the virus, but not cause the virus to not be able to replicate.

2. An inactivated vaccine will have to be given again and again. A live attenuated vaccine can drive the dangerous strains to extinction. Also attenuated vaccines protect those not vaccinated.

3. In theory you could engineer a virus with deletions, but nobody knows what deletions will work. By using natural deletions you know are mild you get around this problem. It also solves the regulatory issue as you are not going to be able to quickly test a lab made strain.

and how would we know that the harmless-virus infection protects against the dangerous strain?

are there already databases of sequenced strains?

and how would the regulatory aspect work? if the harmless individual is no longer infectious, how would people be infected

1. You would check the person’s immune response. With luck they have infect a pool of people in the local area which should give you more data.

2. Yes there are, but we need to look for a quite rare mutant.

3. We would be genome sequencing clinical samples - these would be kept in storage until the data comes back.

It is a good idea, but just like the other dozens of possible vaccines it still needs to go through all trial phases, so it's not quicker than the other vaccines which could 'potentially be deployed today' (RNA etc)

No it doesn’t which is the reason why the idea is more than an idea for another vaccine. Even if it did it, it would be a ecological solution that would mean we could stop vaccinating in the future - a bit like how we were able to stop vaccinating for smallpox once the attenuated viral vaccine drove it to extinction in the wild.

Why would it need less trials than a vaccine? Are there special regulations?

Because it is natural. You don’t need permission from the FDA to catch a natural virus.

Aren’t a lot of vaccines just weakened versions of natural viruses?

Insulin is natural, would not they require testing before it could be used to treat a new disease?

Yes many (most) viral vaccines are weakened versions of natural viruses, but the weakened versions were created in the lab.

Yes insulin is natural, but it needs to be processed and purified via a lab process (if from pigs) or grown up in a vat of cells for the human form.

Wow that’s a huge loophole then. If true you might be on to something. That’s pretty cool.

It’s also sad we have to go to these Herculean lengths to bypass the slowness of the FDA.

Yep. I do think there will be some major changes out of this experience that will change how the FDA and the whole medical system works. Things that were “impossible” before like telemedicine were suddenly able to be implemented.

Well that is interesting, for a SW developer point of view :)

Do you have reasons to think biotech's are not currently putting the same methodology into place for their upcoming vaccine?

No idea. Someone has to be the first person to have thought of any idea and maybe it is me (unlikely). I personally don’t care about this, I just want to see the idea acted upon.

Here is the post for those who don’t want to follow the link.

Like nearly everyone on the planet I am worried about COVID-19. SARS-CoV-2 (the virus that causes COVID-19) appears to be killing between 1% to 3.5% of the people it infects and has a R0 (i.e. how many new people each person infected goes onto infect) of between 2.5 to 3.9. Left to run wild, the virus will likely kill tens of millions of people worldwide.

The governments of the world have implemented strict population isolation protocols to try and limit the spread of the virus, but the economic cost of this is extremely high. A vaccine for COVID-19 is 12 to 18 months away (at best).

We are stuck in a diabolic situation where the only way to prevent the economy sliding into a slump deeper than the Great Depression is to consign many tens of millions of people to an early grave. Is there a way out?

SARS-Cov-2 Viral Diversity

SARS-CoV-2 like all viruses mutates (changes) overtime. Many of these genetic changes are small (single nucleotides) that are not important to the replications or transmission of the virus from person to person, but they can be used to identify the origin of the virus. DeCODE genetics has been testing Icelanders for COVID-19 and genome sequencing the SARS-CoV-2 strains isolated. They have found two very important pieces of information:

1. More than 50% of the people infected with SARS-CoV-19 are asymptomatic (i.e. they have no illness). 2. They can identify the geographical origin of the strains by the genetic differences (mutations) between the different strains.

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.

If we can find one of these non-pathogenic viral strains out in the wild we could give it to everyone in the world and solve our diabolic problem. This non-pathogenic strain would act much like the live attenuated (oral) polio vaccine.

How do we find the attenuated SARS-CoV-2 strains?

This hypothesis is worthless if we have no way of finding any of these non-pathogenic SARS-CoV-2 viral strains. Luckily there is a quick and cheap way to find these strains if they exist – test asymptomatic people for COVID-19 and then genome sequence the SARS-CoV-2 strain that has infected them with the aim of identifying a virus with mutation(s) in an essential viral gene(s). This approach is cheap (a couple of hundreds of dollars a virus strain) and quick (a week or less). With almost no effort or cost we could sequence a few thousand viral strains from asymptomatic people until we find a virus strain with the right mutations to make it harmless and which is in effect an attenuated vaccine. We would know that this strain can still reproduce in people and lead to immunity, but not make people seriously ill.

What viral mutations are we looking for in a good non-pathogenic viral strain?

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.

Has this ever been done before?

Yes. The polio, measles, rubella, mumps, and chicken pox vaccines are all live attenuated viruses. Even something as dangerous as smallpox was controlled in the 18th century using a variation of this idea called Variolation. The idea was the doctor would deliberately infect you with a less harmful strain of smallpox to make you immune to the more deadly strains of smallpox. Of course, they didn’t know how this approach worked in the 18th century, but it was still very effective and millions of people were saved from dying from smallpox by it.

What are the risks?

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.

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.

Q & A

I have been getting a few questions on this post so I thought I would address them here.

How do you know there is an attenuated viral strain out there?

I don’t. I am hypothesising that there is one (or more) based on the known mutation rate of coronaviruses and the number of cases. Coronaviruses mutate continuously (this is why companies like deCODE can tell the geographical origin of different strains) as the molecular machinery for replicating their RNA genome is not very accurate. When you combine this with the millions of mild cases out in the world, the odds are on our side that there is at least one person infected with a strain that has a mutation that makes the virus less dangerous (attenuated). We just need to look for this strain – luckily the tools we need to use (genome sequencing) are now cheap and quick. What would have been impossible 20 years ago can now be done in a week.

Aren’t most people who have mild/asymptomatic cases infected with the 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.

My argument is coming from the other direction. While almost all mild cases of COVID-19 are caused by a dangerous strain of SARS-CoV-2, an attenuated strain of SARS-CoV-2 will only cause mild disease. If you want to find an attenuated strain you need to look at mild cases even though >99.9% of the people you check will be infected with a dangerous strain. What we want to find is one of the rare natural viral mutants that is attenuated. Where you will find such a mutant is in people with a mild form of the disease.

Can’t we just wait for the vaccine?

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

Isn’t social distancing and quarantining solving the problem?

Yes and no. Yes countries like South Korea and Australia have shown that through mass screening and social distancing you can keep a lid on the disease, but this leaves the population susceptible to a new outbreak. 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. I don’t think many people want to live for years with cycles of restrictions, easings and further outbreaks.

Wouldn’t the use of such an attenuated strain just be a vaccine?

Yes in one way, but it is a little more subtle. Assuming we can find an attenuated strain, then how to best use it a separate question. Giving it deliberately to lots of people would change the ecosystem for the dangerous strains of the virus. The dangerous strains would find it dificult to spread through the community as many (most) people would have already been infected (and hence immune) with the attenuated strain. Overtime the dangerous strains would become rarer, and the attenuated strains more common, until eventually the dangerous strains would go extinct and we would just be left with the mild version. While we would not be able to get rid of this mild strain, it would just be another of the hundreds of viruses out there causing common colds. The idea is at its base is really to replace the dangerous strains with a less dangerous strain that we can live with.

Nice idea, but it would likely have problems with regulators. I am not a doctor, but these are my thoughts.

Yes, there are "non-pathogenic" strains. I'm pretty sure that my mild symptoms that encouraged me to self-isolate a week earlier than the government lockdown were the result of one of those strains.

However, SARS-1 had long-term consequences for those who were infected in the past [1]. I think that the risks of these sequelae are the reason why prevention is recommended instead of herd immunity. It's possible that the mild strains of COVID-19 will be so prevalent in the environment that I won't be able to avoid them completely, but pursuing eradication is possible (e.g. smallpox, rinderpest) and will probably be the focus of much public health attention in the decades to come.

Edit: You're right that a live attenuated vaccine like polio can mutate back into a dangerous form, and this has been a problem for eradication efforts. Therefore vaccinated people should self-isolate for 2 weeks to find out whether it will mutate.

Also, as you say, "immunity" might not last for life. Perhaps as little as a few months. Isolate for 2 weeks every 3 months, and risk the vaccine mutating to a more dangerous form? I don't think that's a practical solution. I do agree that the non-pathogenic strains should be researched heavily, as a source of clues for developing a vaccine, it just won't be as simple as infecting people on purpose with a different strain.

[1] https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndr...

> The major risk is the virus we think is safe is not 100% safe.

IANAD, but IMHO you cannot just sequence the virus in asymptomatic people - you have to sequence a randomized, sizable % of the whole positive population, including mild or severe cases, and the dead too. Only then you'll be able to "paint a picture" of the different strains' effects on humans and slap some confidence data to each identified strain. Your idea definitely looks promising though.

That was my thought as well - basically, how do you know if the strain doesn't kill if you don't check for severe and lethal cases linked to the same strain? I understand the part about looking for specific mutations, and assuming they would indicate the "usual" complications with the deadlier strains would not be present, but mutations are not exactly predictable, right? If they don't cause the sympthoms of the current deadly strain - they may be causing something else completely, which could be as deadly a little bit later down the line - isn't this a reasonble concern, @danieltillett?

I'm no expert in this field, hence my dumb question: lets assume we find such an attenuated strain and "infect" people with it such that they could all build the anti-bodies for it. Couldn't the dangerous strain still mutate itself over time in a way where the anti-bodies for the attenuated strain wouldn't help anymore or is this rather considered unlikley (since the virus then would have to become fundamentally different)? In other words, would we then end up with the possibility of similar mutations as with the seasonal flue where this "vaccine" with an attenuated strain would have to be renewed periodically? In any case, thanks for working on this!

There are no dumb questions with this problem. What I think you are asking is if the dangerous strains could mutate enough that an immune response to the selected attenuated strain no longer work. The answer is yes this could happen, but if it does we just repeat the process of finding a new attenuated strain.

First get this validated by a medical authority. Find the best one you can.

Next, send your idea and medical validation to the Bill and Melinda Gates foundation. You're not contacting Bill, you're contacting his foundation. Their doctors will look at your idea and can present it to Bill on the next scheduled call.

No one should contact that terrorist eugenics organization. They're diabolical.

I sent this to someone at the Bill & Melinda foundation. If they contact you let us all know.

I read somewhere that Bill Gates is very active on social media e.g. Reddit and Twitter. Here is one of the AMAs he did on Reddit: https://www.reddit.com/r/IAmA/comments/5whpqs/im_bill_gates_...

A recent AMA related to covid-19. There are references to his team and adviser: https://www.reddit.com/r/Coronavirus/comments/fksnbf/im_bill...

His Reddit handle is: https://www.reddit.com/user/thisisbillgates His Twitter handle is: https://twitter.com/BillGates His blog is: http://www.gatesletter.com

If you search, you will also easily find his email address online. He has multiple email addresses as per online searches.

HTH

Yes in an ideal world I should just be able to write to Bill and he will have the time to consider my proposal seriously. In the real world the only way to get the attention of someone like Bill is to have someone he takes seriously bring it to his attention. Hence the post here.

In the last AMA on Reddit he did provide information about the people to whom he listens. I am posting the link to the AMA again here: https://www.reddit.com/r/Coronavirus/comments/fksnbf/im_bill...

Dr. Trevor Mundel[0], who leads the Gates Foundation’s global health work, and Dr. Niranjan Bose[1], Bill Gates' chief scientific adviser.

[0] https://www.gatesfoundation.org/Who-We-Are/General-Informati...

[1] https://www.linkedin.com/in/niranjan-bose-014b00

And does anyone happen to know these two individuals well enough to be able to introduce the idea to them? The whole problem is like getting a warm intro to a VC.

Sounds like these people would be much more likely to see a message and would be plenty capable of passing it on to Bill if they see merit in it.

Yes to get to someone like Bill will be a two jump exercise.

I have heard of a healthtech startup in Cambridge, UK that is supported by Bill and Melinda Gates Foundation. The company is simprints(https://www.simprints.com). Contact the founders of that company. One of them is Alexandra Grigore (https://www.linkedin.com/in/alexandra-grigore-8aa20186)

Chinese researchers on findings of a less deadly strain, preprint March 10:

https://www.medrxiv.org/content/10.1101/2020.03.10.20033944v...

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. To investigate the underlining mechanism, we isolated one strain of SARS- CoV-2 (ZJ01) in mild COVID-19 patient and found the existence of 35 specific gene mutation by gene alignment. Further phylogenetic analysis and RSCU heat map results suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 strains of viruses worldwide (C/T type) based on the base (C or T) at positions 8824 and 28247. ZJ01 were both T at these two sites, becoming the only TT type currently identified in the world. The prediction of Furin cleavage site (FCS) and the sequence alignment of virus family indicated that FCS may be an important site of coronavirus evolution. ZJ01 had mutations near FCS (F1-2), which caused changes in the structure and the electrostatic distribution of the S protein surface, further affecting the binding capacity of Furin. Single cell sequencing and ACE2-Furin co-expression results confirmed that Furin level was higher in the whole body, especially in glands, liver, kidney and colon while FCS may help SARS-CoV-2 infect these organs. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 (the source of FCS sequence-PRRA) caused influenza, further showing potential in differentiating into mild COVID-19 subtypes.

Yep this is exactly the sort of mutant we want to look for, but ideally we want a strain with a gene deletion not just point mutations to lessen the chance of back mutations. It does prove that there are less pathogenic strains out there, there just needs to be an effort put into finding them.

Can you put the desired action and the solution in the first sentence, then back it up in the rest of the post?

The post has an academic style, and academia optimizes for writing articles, not for the articles to be read or impact the world.

If you rub a lamp and a genie appears, better get to the point.

You're most likely not going to get a response from an email or a tweet. To get his attention, put in some legwork.

1- Create a website: http://IhaveaCOVIDsolution.com , On the website, outline your idea, why it would work, put a personal video of a story etc.. 2-Email the website to everyone who knows Bill. Track if he opens it for free with Email Tracking, Scheduling, Templates & Attachment Tracking. 3-If he doesn't open it, tweet it to him. 4-A week later, follow up on your email 5-Find where many of his followers (on Twitter) hang out, which hashtags do many use. Post your website and use that hashtag. Or, tweet each of them individually. 6-Find posts on Quora about Covid-19 solutions, post your idea (for free) and post your website. 7-A week later follow up again with Bill. Also, reach out to other Gates foundation Execs. Reach out to Melinda or Microsoft execs(ex-Msft friends also) and get ignored (will toughen you up). Maybe 1 of them will want a phone call. Find Bill's address, write him a hand-written letter and send the website URL as well.

At some point, he will either:

Answer, quick email from him. Best case a phone call. His publicist will say "Thanks, Bill will look at your ideas." You'll never hear from them again

Maybe he won't answer, but at some point you'll get someone to respond and perhaps become a client to your solution.

Check out the Mercatus Center's 'Fast Grants' program: https://fastgrants.org/

They're giving $10k - $500k grants to fight covid-19, and decisions are made within 48 hours.

Press Release: https://www.mercatus.org/features/mercatus-emergent-ventures...

I have already applied there. I don’t actually want any money just collaborators to make this happen.

While possible, the notion that asymptomatic[†] cases are due to a separate less-pathogenic strain is both indeed a possibility researchers are thinking about, and yet also not (a priori) the only or perhaps most probable explanation for the wide variance in clinical outcomes we see. Other important, perhaps dominant, factors include heterogeneity in people's immune responses to virus--common in other conditions--and (possibly) a dose-dependence (e.g. if you are exposed to a high viral load e.g. by intense or prolonged exposure, some reports (but far too few for definiteness yet) are that clinical outcomes may be poorer). Though there are different COVID strains in circulation (see the amazing data tracking of https://nextstrain.org/ncov), with regards to the proposed hypothesis: there is no evidence that these strains show any difference in virulence (see e.g. the perspective of Francois Balloux at UCL: https://twitter.com/BallouxFrancois/status/12395362423558225...). Many groups are attempting to scale up environmental genomic testing for COVID (see again the nextstrain site).

[†] Note that currently, researchers are rather vigorously debating the true proportion of asymptomatic cases (or distinguishing them from pre-symptomatic cases)--we need more widespread e.g. antibody-based testing to answer this more confidently than we can by indirectly fitting coarse time-series to simplified models.

This is likely to run into some hiccups.

When we exterminate species of animals, microbes that inhabit them jump species. It's how they survive.

One of the things that fosters antibiotic resistance is that bacteria mutate at a higher rate in hostile environments.

Different people with different genetics react differently to the same things.

I am not trying to rain on your parade. I'm trying to take you seriously and share my thoughts. I'm sure we all want a solution.

I think we need to up our game on other things. I don't know how to get traction on that. We already know a lot of things that help and we are just not doing a very good job of getting everyone to understand and comply.

If we did, people might dismiss the success as "luck" anyway. Humans have a terrible track record of not knowing how to count the disasters that didn't happen but should have.

Best of luck. I see in comments someone forwarded it to the Gates Foundation. I would be happy to learn I'm wrong and this works.

Summary of the idea from the link in the sibling comment, partially in the words of the author (edited by me):

[There might be] 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.

[If there are and] we can find one of these non-pathogenic viral strains out in the wild we could [use it] much like the live attenuated (oral) polio vaccine.

The submitter seeks help to test this hypothesis.

I would add that the hypothesis can be checked very quickly and cheaply by genomic sequencing.

I can afford the cost of all the sequencing, what I need is access to a large number of samples from people infected with mild cases of COVID-19. My best estimate is you would need to look at north of 5000 samples to find a strain with the right sort of gene deletion.

What about reaching out to the mods of https://Reddit.com/r/Covid19Positive ?

For all our sakes, I wish you the best of luck with this idea. I'm sorry I don't know how to help you but your idea sounds promising and it's super invigorating to see high agency people try to implement their solutions to our problems! :)

Presumably you are asking for

- Website where people who fit criteria can register

- some form of triage (symptoms checking, contact tracing)

- Then collection. Presumably people will need to supply mucus samples, and have those samples collected safely. This sounds difficult and seems like the expensive and hard to scale part. But I can imagine a fleet of drivers with some training being able to collect and store samples in "proper" equipment. This is well out of my expertise.

- testing / sequencing (lab based). This you seem confident on.

Is this a good idea - I don't know. Is it possible - yes it seems quite doable. Does it need billg? I doubt it. Plenty of people have cash and now have motivation.

Good luck.

You could reach out to companies like https://lifeomic.com/ ? If they can't help directly, they might be able to steer you in the right direction?

Good luck

So I'm no expert in medical sciences, but have some basic knowledge. Here's what I think:

You're basically proposing a form of vaccination. Essentially everyone knows that a vaccine would be the way out of this mess. There's loads of research on Vaccines for Covid-19 right now. Your idea isn't exceptionally surprising, as you write yourself it's close to how some of the early vaccines worked.

I am reasonably convinced researchers into vaccines right now turn every stone to look for possible ways to make a vaccine as fast as possible. They probably got the idea already and if it's a feasible path someone is working on it.

That said making a vaccine still faces some basic challenges that every medicine faces: You want to be pretty sure that a) it works and b) it has no massive surprising sideeffects. Given that you want to give it to potentially almost everyone on the planet, you want to be really sure.

> Given that you want to give it to potentially almost everyone on the planet, you want to be really sure.

This is why I have a hard time with the current crisis. We are in what is now universally called a "global health crisis".

Measures are being taken to help prevent the virus that are incredibly costly for the economy, which will cost hundreds of thousands of jobs, and that will indirectly kill thousands of people.

Yet when it comes to vaccines and treatment tests, we use the usual approach, tests on a very very small number of patients, regulator validation that takes months to process, x phase trials where each phase needs to be tested x times. All these are very fine in a normal situation and help prevent mistakes, but extraordinary times require extraordinary measures.

You don't need to be "really sure" that your vaccine is good, you just need it to be better than the status quo. If we can identify one strain that is indeed less deadly than the average of the virus, it's good enough. You sure are going to kill people, but in a crisis mode, if that allows you to save more, it should be a tradeoff we are willing to make.

I hear you. I hope we overhaul the fda when this is over.

"Some of you may die, but it's a sacrifice I am willing to make" - Lord Farquaad, Shrek (2001)

Regardless of the ethical dilemma, it's a politically untenable position. Vaccine-derived poliovirus [1] affected less than 800 people, compared to 6.5 million if vaccination was not pursued. [2] However, even such few cases were exploited by false teachers (anti-vax, religious groups) to oppose the vaccination efforts entirely. [3] China's economy is recovering already. Although the economic consequences of the lockdown are serious, it's not worth jeopardising trust in public health authorities.

[1] https://en.wikipedia.org/wiki/Polio_eradication#Vaccine-deri...

[2] http://polioeradication.org/polio-today/polio-prevention/the...

[3] https://en.wikipedia.org/wiki/Polio_eradication#Opposition_t...

If you give people a vaccine that doesn't work, or worse a vaccine that does more harm than good (or appears that way), then you explode the anti-vax movement into the rule rather than the exception.

No subsequent vaccine, even an effective one, would be tolerated.

It's not worth getting wrong.

Variolation is a good idea with or without attenuated virus. That just improves on it.

http://www.overcomingbias.com/2020/03/variolation-may-cut-co...

I'd like to sign up for it either way, assuming medical supervision.

This suggestion is not really variolation. Real variolation involved infecting a person with an attenuated strain of smallpox, not just a low dose. While the idea by Robin might help to build herd immunity relatively safely those infected will still be a hazard to the vulnerable around them and it won’t lead to a long term solution.

Post your solution on or blog or github with a permissive license. If your solutions is worth anything Bill Gates will come to you.

He did: https://news.ycombinator.com/item?id=22810925

By reading 'The art of computer programming' (Knuth) from cover to cover :) He'd be more than willing to listen to you then (according to his own words, ironically printed on the backcover of my copy of TAOCP).

Seems overly complex. Why not just inject live virus into people's glutes? At dose low enough to trigger a response hopefully not enough to cause pathogenesis.

It is actually extreme simple. You suggestion of injecting virus into people’s gluts is a vaccine, just one that is unlikely to work well and be dangerous as well. I have explained why vaccines are not the answer.

It might be a lower risk to innoculate in the the glute then getting a primary infection in the lung first. We do not know yet and that's what vaccine trials are for. We know that the spike protein is probably the target though. That protein and fragments can be amplified and expressed and tested as vaccines.

Your search for a live attenuated strain would probably take 18 months minimum and probably longer. You need widespread testing and sequencing which are both in short supply. You also need outcome data. You would also need a sufficient sample size and then hope that your predicted attentuated cohort is say not just all young people.

Sars-Cov2 mutation rate is <26bp per year. https://nextstrain.org/ncov/global?l=clock

No it won’t take long. We already have the samples (they are what has been sent in to labs) and with modern genomic tools you could sequence 100,000 samples for under a million dollars in a couple of weeks at most.

The mutation rate is just an average - anyway we are looking for one specific mutation and in the 6 months SARS-CoV-2 has been around there has been plenty of time for the right mutant strain to have arisen.

It doesn’t matter who the cohort is - all that matters is the strain has the right mutation.

Robin Hanson and other public intellectuals are engaged in ongoing debates about variolation, with several variations on that theme.

https://www.youtube.com/watch?v=DFnP5TK61aI

https://marginalrevolution.com/marginalrevolution/2020/04/wh...

http://www.overcomingbias.com/2020/04/reply-to-cowen-on-vari...

I know your proposal is not exactly that, but it has some overlap with those ideas. I'd recommend joining those discussions on those blogs.

If yours significantly improved the safety of their proposals, it would be a welcome addition to those discussions.

Note though that it shares some obstacles with widespread vaccinations, in that safety and efficacy testing is the major delay, not the chemistry.

We could alternatively do low dose variolation on the young with technology today, with infectious strains administered through a cut on the shin to encourage lower severity progression. We might lack implementation capacity and social will to try very experimental approaches. If so, "found strain" vaccination will face similar capacity issues while also introducing new questions about safety and effectiveness and requiring significantly more research.

So I'm not sure it's a silver bullet, or how it fares against existing proposals, but seems an avenue worth exploring in parallel, and raising first with others generating policy ideas in this space.

N.b.- Tyler Cowen has a foundation that is actively providing grants or prizes for work on COVID-19, he's not Gates, but not just some random blogger either.

This is a great idea! But why it would be any faster than a vaccine. We already have vaccines, the slowness is testing them. Wouldn’t this method need just as much testing?

Because it is a natural virus. You don’t need approval from the FDA to be infected with a natural virus.

Do you have a source? That seems pretty wild if true.

Has the FDA given approval for any of the millions of people to be infected with the dangerous strains?

I don’t think that’s the same thing.

Edit. Don’t get me wrong. I’m on your side. I just want to figure out if it’s feasible.

But to deploy this at scale, you need to

1. Prove it works (is there data that provides lasting immunity to all other strains?) 2. Prove it is safe (e.g. is it mild/asymptomatic across all populations?)

Both of those things take time to fully vet. What's the difference between rolling the dice with a live strain vs. one of the half dozen vaccines already in development?

No you don’t ;)

If you are stuck in the “every approach has to be tested to conventional FDA standards” then yes. If you are able to look outside the box for a little then you will realise that you don’t. This is not a problem that is going to be solved by old thinking.

or people could just start infecting each other

Well spotted ;)

Did you get the email we sent you? It contained a repost invite for https://news.ycombinator.com/item?id=22798626. I worry that it might have gone into a spam hole.

(I apologize for hijacking the thread. By the way, invited reposts are related to the re-upping system described here: https://news.ycombinator.com/item?id=11662380)

Hi Dan I have only just got up (it is early morning here in Australia) so I haven’t had a chance to check my work emails yet.

Do you happen to know someone who knows someone that someone like Bill will take seriously? I did apply to the fast grant program, but I suspect it got thrown in the bin as I am industry not academia these days.

Edit. Just checked and no email even in my junk mail folder :(

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