Ask HN: How to get Bill Gates's attention?
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?
88 comments
[ 1.6 ms ] story [ 98.9 ms ] thread0. 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.
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.
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?
Th...
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...
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.
Insulin is natural, would not they require testing before it could be used to treat a new disease?
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.
It’s also sad we have to go to these Herculean lengths to bypass the slowness of the FDA.
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.
Source: https://www.nhs.uk/news/medical-practice/three-quarters-of-p...
Shouldn't we be looking at people with no symptoms? I know this is not ideal as we're likely only testing symptomatic people.
Do you have reasons to think biotech's are not currently putting the same methodology into place for their upcoming vaccine?
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...
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.
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
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.
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.
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.
You said you are in Australia? The Australian government has the clout to make this happen.
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.
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?
[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 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.
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.
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.
No subsequent vaccine, even an effective one, would be tolerated.
It's not worth getting wrong.
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...
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.
- 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.
[†] 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.
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.
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.
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
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
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
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.
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...
Good luck
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.
Edit. Don’t get me wrong. I’m on your side. I just want to figure out if it’s feasible.
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?
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.
http://www.overcomingbias.com/2020/03/variolation-may-cut-co...
I'd like to sign up for it either way, assuming medical supervision.
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.
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.
(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)
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 :(