I feel like I have a context for understanding electrons and protons. I have read A Brief History of Time. What do I read next in order to have this article not sound like mumbo jumbo?

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."

I have this gut feeling it's pretty high, at least in the tech industry. I don't believe this is problematic but it feels like a taboo topic. If use is common we should be better about talking openly about it.

Are there any good books that are full of more rules of thumb like these?

Otherwise, cool. I signed up.

Do repo cleaning tools such as https://rtyley.github.io/bfg-repo-cleaner/ leave the original commit's SHA-1 ID intact?

Recently I've had to work with XML config files for a tool called Oozie, which is a data pipeline scheduling tool within the hadoop/spark ecosystem, and it has been soul crushingly tedious for me. Everything feels verbose and opaque, the documentation seems to prioritize enumerating every possible configuration option over providing minimum viable configs for common use cases.

JSON configs often just feel more simple and developer friendly. I'd say this has less to do with technical differences between JSON and XML and more to do with how "modern" software systems have been designed to be more ergonomic for developers/administrators and these modern systems happen to be more likely to use JSON.

It's also fun to hear non-technical people at work talk about "Jason files".

The reason is (the potential for) self driving cars. Once/if there is mature self driving tech, they can eliminate the cost of having to pay human drivers. When you consider Uber in that light, as long as they don't run out of money before self driving maturity, then their high valuation makes sense.

This may seem obvious to some but this fact has been entirely absent from every conversation I have heard about the valuation of uber's IPO ( looking at you Marketplace's "Make Me Smart" ;). It seems like it is taboo to point out that Uber needs to eventually eliminate all their human drivers from the equation.

Capitalism would explain the difference between a tech worker's pay and a teacher's pay as based on skill and worker scarcity, not on who works the hardest.