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If you want to be cool then you say "fuck the government, fuck the police". Its a big part of the reason, a lot of people want to show off by breaking rules for street cred.


I'm not sure it's that simple. I think most people breaking the rules just think it doesn't apply to them. Like they're healthy, they're low risk, they're good at following all the other rules ("we won't get close to anyone while we're out, we won't touch anything we shouldn't").

I assume it's a bit like washing your hands after using the toilet. Most people do. I don't think those that don't are saying fuck you to society - they just think "I didn't pee on my hands, there's no mess here".

I guess if something doesn't immediately affect you, it's easy to think it will never affect you and it's not your problem to deal with.


Thing is though the government is not saying don't go out. You have to go to work, (if you're essential). You have to go to the grocery store. And truth be told, you should be exercising to keep up your immunity and overall health. That's all good stuff.

But when you're calling up your friends to go on that errand with you, or to go on that walk, or run, or bike ride with you, that's where I think people are going off the rails. I think the government and public health people probably meant for us to do this stuff alone. So there would be no need to say, "WE won't get close to anyone while we're out". Because you're not out with anyone. Only one family member needs to go to the store. Your bicycling group is still unsafe even if you're keeping 2 meters away from each other. Etc etc.

The question is, does ubiquitous surveillance help alleviate this sort of thing? My suspicion is that it doesn't. I'm thinking this is an education issue. A lot of people still aren't getting it.


There are certainly a group of folks who are just trolls, and intentionally do the opposite of whatever their political opponents recommend. Look at the idiots who modify their trucks to "roll coal". Or people who intentionally burn more energy because they think climate change is BS.


I'm not saying those people don't exist - just that I suspect they are a significant minority when compared to the group I spoke of.


Your overthinking it, imagining that a large part of the population wants to be Jason Bourne. It doesn't matter if 1% will evade this (you and your friends).

But you show exactly the bigger problem: the West is so individualistic, that it will rather have millions of deaths and economic collapse than a bit of privacy infringement over a number of months, again, everybody viewing himself as some sort of secret agent that the government is out to get at all costs.

Asian countries on the other hand understand that some time you need to make some real sacrifices yourself for the greater good.


I grew up in the alps on the countryside and I am thinking about people like my neighbour and my father. Other than them I do understand the reasoning behind contact tracing, while they don't. If they were forced to use such an app they would work against it just out of defiance. And they are by no means special people. They have no idea about computers, they are more or less center conservative or center left.

Especially in the german speaking parts of Europe the scepticism towards government data collection has historical roots that I probably don't have to elaborate on, with people who died from said collection still in living memory. While safety is a fundamental right, it doesn't outweight all the other fundamental rights automatically. These rights need to be balanced even (and especially) in times of crisis.

I think the right way here would be to follow the CCC recommendations, and make it about a voluntary utilitaristic action, rather than enforcing it from the top down. People have to want to do it, just like they did in China. How you will get them there is different in Europe however.


Not a doctor, but I did a crash course in ventilators recently and it has the main features - inspiration/expiration pressure, volume, rate, oxygen %.

UK gov also put out a document with the MVP for a ventilator, and the Tesla one looks like it will cover most of the therapeutic features.

The one thing I would worry about is software bugs in such a rushed project.


Tesla (and SpaceX) has experience with life critical code (running vehicle powertrains independent of the rest of the vehicle subsystems; please save Autopilot critiques for another thread).

A fully validated ventilator is ideal, but if your other option is death, a ventilator that is "less than fully validated" might be preferable.

EDIT: You're right to acknowledge there might be bugs, it's important to quantify risk. You decision based on the risk(s) raised.


Its an important thing to know.


We have recent data from Wuhan.

We have old data from 1918.

This is a white swan, not a black one.

More importantly, the mortality, while much higher than flu, it's still relatively low.

Now imagine a virus as contagious as this one, but with 10% mortality over all age groups. That would be unprecedented and probably cause society meltdown.


> More importantly, the mortality, while much higher than flu, it's still relatively low.

Anecdote: someone was trying to convice me to panic about Coronavirus because "three hundred and [something] people died just today!"

  $ units
  8 billion / 80yr
  /day
"Actually, three hundred thousand people died today. Probably more, even."


I think a lot of people would be very surprised if you told them how many people die in their country every year.

It's nearly 3 million in the US.


How do you reckon social media will impact your models? Rumors and information - real or fake - has never been easier to spread in the world (Wuhan's data becomes less relevant here). We've already seen calls for defiance of lockdowns in right wing circles. In my country, old videos are being circulated to spread misinformation about the treatment.

Again, our data for all older epidemics is applicable to the epidemic in isolation. But there is no way to accurately model how the epidemic interacts with people simply because the way people live has changed drastically from past epidemics.


Normal cells also use RNA during protein synthesis. Why doesn't remdesivir disrupt that too and kills healthy cells?


There is no RNA cloning machinery in our cells. The RNA is instead copied from the DNA in the nucleus. Viruses like the coronavirus actually bring their own RNA cloning machinery that's assembled by the cell. Remdesivir only blocks the RNA cloning proteins of the virus.


Doesn't that mean that Remdesivir would essentially defeat _all_ RNA viruses? Or is the effectiveness dependent on the exact RNA cloning mechanism used by the virus?


Yes, it was originally invented to treat ebola, but it's thought to have general antiviral properties against RNA viruses.


There are a lot more RNA virus specifically targeting antivirals surprised that most of them are not yet tested.


sounds like we should get on it


According to this radio programme[1] I was listening to at the weekend, scientists have been warning about the potential of coronaviruses to cause a pandemic for a long time, and saying we should work on general antivirals for them. Obviously that didn't happen.

[1] https://www.bbc.co.uk/programmes/m000gvd1


Didn't it? The one we're talking about was developed to fight the last two Coronaviruses.


Yep. This is the same drug they tried to deploy against Ebola, and that's why they think itll be useful for such a wildly different drug virus here as well


I suspect this is to deter Russians from coming home for the Orthodox Easter which is way more important than in the West.


I am a Russian living abroad. I know literally no one coming back to Russia for Easter. It's the first time I even heard of this idea.

Summer or New Year are the times when Russians are more likely to go to visit their relatives and friends.


Do you have any idea why that is? Length of travel? Cost of travel? I'm a Pole living abroad and every year I try to go to visit my family for Easter, it seems like a pretty normal thing to do.


Orthodox Christianity is not a big thing among the current generation of Russian diaspora, so Easter doesn't have any cultural significance to most of them.

Summer is a good time to visit because of the mild climate, and New Years', because it has always been a big holiday, culturally.


Thank you for sharing that! It's amazing that this tradition exists in Poland. Do Poles come to see family for New Year / Christmas?

Oh, and by the way: Russia has state holidays from Jan 1st till Jan 10th (+/-, every year is slightly different), which makes it a lot easier to meet everyone.

Easter does not have any state recognition in Russia, so everyone would be quite busy with their regular errands, I guess.


Yeah, we go home for Christmas too. So per year I'll usually go for Christmas and for Easter. Maybe if the year is really good we'll try to visit at the end of summer too.


The only reason I got home to Slovenia for Easter is, it's a 4-day-weekend in the UK.


same here. what a weird idea


This comment shows how little westerners know about Russia and Russians. Easter is of very little importance in Russia, especially for Russians living abroad.

For religious Russians abroad there are Orthodox churches in almost every country, even in Thailand and Cambodia.


It does sound silly if the food is left to rot on fields.

Maybe we should also subsidize food transportation and storage or something.


It has to be harvested first.


How does one isolate a specific antibody from the blood? Presumably there are thousands (millions?) of different ones in there for all kinds of pathogens.


Typically, you first test the blood to see if there are any antibodies in that blood of interest. E.g., collect blood sample, harvest serum from blood by coagulation and centrifugation, apply serum to surface coated with COVID protein(s), wash away unbound material, detect whether antibodies to serum have bound to surface coated with COVID proteins. If yes, then this is a blood sample of interest. You could also test for neutralizing antibodies in parallel/before/after/instead in a viral replication assay. Once you have identified the blood as containing what you want, you then harvest more and collect mature B cells. Mature B cells each produce one antibody. You isolate the B cells by limiting dilution and/or immortalize them by fusion with a special type of cell to make a hybridoma to isolate clonal populations of single cells that are maintainable. Then you test each clonal population for whether it produces the antibody of interest, isolate the nucleic acid that encodes that antibody and put it into a cell type suitable for manufacturing. There are other ways to do it, but the above is fairly standard. It is laborious and easy to mess up and takes time (1 to 2 months) to do correctly. Any step can go wrong and require starting over.


> You isolate the B cells by limiting dilution and/or immortalize them by fusion with a special type of cell to make a hybridoma to isolate clonal populations of single cells that are maintainable. Then you test each clonal population for whether it produces the antibody of interest

Do people actually still do it this way? I would have thought that you would use more targeted approaches where you use an antigen to fish for cells of interest before culturing. There are a few such techniques described here:

https://www.frontiersin.org/articles/10.3389/fimmu.2019.0169...

Naively, i would have thought you could do something with affinity columns or magnetic beads, too - coat beads with antigen, then use those to extract B cells expressing a matching surface immunoglobulin.


Magnetic bead filteration is commonly used to filter immune cells, but they are expensive. I used to work for a lab that did this on a daily basis. Common problems with it were getting enough cells to run the assays, and the process of extraction is damaging to the cells. So you need a lot of starting material and then after that they don't stay alive for very long. You can treat and freeze after isolation but thawing only decreases the amount of healthy cells.


Here’s a noob question. The coronavirus is made out of a whole bunch of proteins. Have we fully mapped out all the protein structures and corresponding DNA code?

The antigen is also a protein, I assume the DNA sequence for it is well known. Right?

How far are we in terms of tech to print custom proteins from arbitrary DNA sequences?

Is understanding protein folding and protein to protein interaction the holy grail of making massive improvements in molecular biology? What are the big unsolved problems?

Like if we know the virus’s DNA and it’s 3D protein architecture, we can solve for antigen proteins in a computer that outputs possible DNA sequences and we can manufacture them the next day in a protein printer. How far away are we to that future?


Protein folding is part of it. The other is finding which parts are antigenic to the immune cells. Epitope mapping is a common method to screen small bits of the proteins to see if any are hits for immune cells to recognize and kill. There are algorithms that can take the RNA/DNA, predict proteins, and then guess a percentage of those that may be important. But you still need to synthesize those in mass quantities and start testing each. Once you have candidates you then test them in mouse models (typically) to see if they actually provide an immune response. If interested check out the iedb. https://www.iedb.org/


"Have we fully mapped out all the protein structures and corresponding DNA code [of the COVID-19 virus]?"

Yes

"The antigen is also a protein, I assume the DNA sequence for it is well known. Right?"

Yes

"How far are we in terms of tech to print custom proteins from arbitrary DNA sequences?"

Generally that is something a first year graduate student can accomplish.

"Is understanding protein folding and protein to protein interaction the holy grail of making massive improvements in molecular biology? What are the big unsolved problems?"

There are too many unsolved problems to count. There have been great advances lately in de novo prediction of protein folding and to a lesser extent protein:protein interactions. But even if you had perfect knowledge of all that, you still can't just like design the perfect vaccine.

"Like if we know the virus’s DNA and it’s 3D protein architecture, we can solve for antigen proteins in a computer that outputs possible DNA sequences and we can manufacture them the next day in a protein printer. How far away are we to that future?"

We (the world) accomplished that within a couple of weeks of identifying the COVID virus.


Honestly I think I learned more from this one comment that most of my biology classes. :D

Any materials you can recommend for complete novices in industrial biology processes?


> It is laborious and easy to mess up and takes time (1 to 2 months) to do correctly.

Sounds like a manual software testing. What are the chances of automating entire process? Whenever I see bio/chemists working it seems very manual job. I assume someone already tried it, but perhaps only for specific area rather than making universal robot?


Complete automation would be tricky. We are dealing with a lot of starting and intermediate materials that need to be precisely incubated under demanding and entirely sterile conditions. You need incubations at liquid nitrogen temperatures (for storing cell lines), -80 C, -20 C, 4 C, room temp, 30 C, 37 C, 37 C 5% CO2, etc. THen you need a way to go to and from each of these environments and a way of sterilizing in between steps. I'm not saying it's impossible, but it seems difficult.


IIRC the virus was isolated last year, so wouldn't at least some antibodies have been identified by now? Or, it's just very common to have to start over?

Is it unusually difficult for this coronavirus? eg I've heard it's unusually large.


Antibodies have been identified by now. They are being tested as we speak. Coronavirus is not more difficult than any other target really. It just takes time.


It sticks to a virus protein, so you can use that virus protein to find it!


Is synthetisizing antibodies a thing? Is it hard? If so, why?


They're far too large and complex to be synthesized from scratch, that is simply not possible.

They are produced in various biological systems, with nature doing the synthesis. As far as I understand you can scale that up reasonably well with some effort.


To add to this, you don't even need to know what the antibody looks like, or even if it exists. Very simplified example: It's possible to grow a dish of cancer cells (because they divide quickly and are immortal, e.g HeLa cells), "purify" away everything that isn't protein (cell lysis), then run the proteins through a gel that separates them by size (Western blot). Comparing these to a control will show you which proteins enabled survival, which gives you your candidates for sequencing and further tests.

However, right now we have humans synthesizing large amounts of antibodies that are proven to work (because the humans creating them survived and cleared the virus). It may ultimately be faster to isolate antibodies from the serum and engineer cell cultures (through adding DNA to them, "recombinant DNA") to create more of those antibodies, resulting in much stronger synthesis of a single antibody (so-called "monoclonal antibody drugs").

It's nearly certain that both of these are happening many times over around the world right now. All of the science here was already in lab use the first time I worked in a bio lab in 2003, and nowadays we have methods that didn't exist then (such as CRISPR for DNA manipulation and fast sequencing of both nucleic acids and proteins).


It's too large and complex to do now but I bet we'll be able to do that sort of thing by 2040.


The reason it's not researched much is because giving someone an antibody will not confer immunity - it will only treat the immediate virus.

It has value, but there are usually better treatments available that more broadly fight a variety of viruses and don't need to be so specifically customized as an antibody.


I suppose testing would be easier for a cure (compared to a vaccine)? Given that only the "adapter" needs to be specialized, I was wondering why there don't seem to be any approaches based on antibody mass-production....


I have a friend who runs a company which genetically engineers cells to make chemicals for a living. This doesn't seem like 2040-era science fiction.

Indeed, I'm not sure it's out-of-scope for 2020-era technology.


What is the said company ?


Ginko Bioworks.

Apparently it's grown quite a bit since I've spoken to my friend. When we last checked in, it was a little startup. Now, it's a $2.4 billion dollar operation. I guess my friend is probably worth a few hundred million right now.


Maybe even by 2030 if the coronavirus causes an expansion of research. Which it'll likely do.


I'm ok with Google having this data. I'm not ok with governments having it.


Why? At least with government you have theoretical recourse at the polls. With a megacorp you can’t do shit if you don’t like what they’re up to.


Right, you can't do shit... except not turn on location history, which as this page says, is off by default.


In this case the government wouldn't have that information either.


Governments can just ask for it and Google has to give it to them. [1][2] In fact the US Government has decided it is easier to have the service providers collect data for them and then just get it when needed instead of them separately trying to "archive" data.

[1] https://www.justice.gov/archive/ll/highlights.htm

[2] https://en.wikipedia.org/wiki/United_States_Foreign_Intellig...


Why? Google has enough power to fuck with your life and no oversight whatsoever.


Google doesn’t have armies or overzealous attorney generals (and lackeys) willing to ruin lives for their stupid conviction rate. I wouldn’t have believed police officers lie on a ticket if it hadn’t happened to me.


No, instead they have armies of overzealous AI bots making decisions without any human oversight.

That's far more scary to me, but you know, you do you.



I'm not ok with Google or anyone having this data as I can't realistically or easily opt out or remove my data.


Google appears to be best-of-industry in making the data they have about you both extractable and deletable.


Let's just say I'm the polar opposite.


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