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vgr's profile
Venkatesh Rao
Venkatesh Rao
Venkatesh Rao
@vgr

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Venkatesh Rao

@vgr

Conversational account. For work follow @ribbonfarm, @breaking_smart, @artofgig. Tweets are 90% vacuous views, apathetically held. Mediocritopian. IKEA builder.

Los Angeles, CA
venkateshrao.com
Joined August 2007

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    1. Venkatesh Rao‏ @vgr Oct 10
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      Next chapter on death toll. Already in the 1920s the best estimate 21.6m, 20x the Russian 1890s epidemic of 1 million. Revised up to 30m by 1990d, but likely still an underestimate especially for Russia and China.

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    2. Venkatesh Rao‏ @vgr Oct 10
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      We circle back to Odessa, this time with an epidemiological lens, to cross check the Russian estimate of 450k/0.2%. Odessa data as a better documented Russian refugee zone suggests 1.2% and 2.7m instead of 450k.

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    3. Venkatesh Rao‏ @vgr Oct 10
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      China was similarly undercounted. Probably 4-9m, though an estimate via different method landed on just 1m. India was likely 18m. So modern estimates are between 50-100m. 2.5-5x initial estimates. This is all extraordinarily shaky. Literally data as plural of anecdotes.

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    4. Venkatesh Rao‏ @vgr Oct 11
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      Next: story of how multiple people converged on conclusion that it was not a bacterium but a virus. One of the first to publish, Rene Dujarric, had himself injected with filtered blood of a patient (thereby eliminating bacterial causes) and getting sick. https://en.m.wikipedia.org/wiki/René_Dujarric_de_la_Rivière …

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    5. Venkatesh Rao‏ @vgr Oct 11
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      His conclusion was flawed because influenza cannot be transmitted via blood apparently. Right answer, wrong method. Other research pair, Nicole and Lebailley, got it right. FUD of pandemic+war.

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    6. Venkatesh Rao‏ @vgr Oct 11
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      So to peek ahead, modern theory is that Spanish Flu was a member of what is known as the H1N1 virus today (Though I did hear alt theory that it was actually a coronavirus)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2391305/ …

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    7. Venkatesh Rao‏ @vgr Oct 11
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      So methods were generally sloppy then, so people believed what they wanted to. Richard Pfeiffer, of the incorrect bacterial theory of influenza, stuck to his theory. Others tried and failed to replicate the filterable infectiousness result.

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    8. Venkatesh Rao‏ @vgr Oct 11
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      Antibacterial methods seemed to work (likely because they addressed secondary infections). All in all, general confusion like today, leading to strong opinions.

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    9. Venkatesh Rao‏ @vgr Oct 11
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      Took till 1930s to confirm viral theory and connect to swine flu. 1950s to figure out origins in species crossover, via a ferret sneezing on a British researcher named Wison Smith.

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    10. Venkatesh Rao‏ @vgr Oct 11
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      So of the 3 kinds of influenza A, B, and C, only A causes pandemics apparently. There’s also a 4th kind added recently. It was hard to prove because viruses can’t be cultured like bacteria, in a Petri dish. Only inside living cells.

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      Venkatesh Rao‏ @vgr Oct 11
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      In 1931 Alice Woodruff and Ernest Goodpasture (solid names) figured out how to grow viral cultures in fertilized chicken eggs. I guess that’s why flu shots are grown in eggs and also why we get flus via birds. Very enlightening factoid.

      11:13 PM - 11 Oct 2020
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      • Pavan Srinath Yer man Brant (((Richard Drake))) pagan poetry 🐲 Walt 🚴🏼‍♂️🏗🗽🌎⚖️🙋🏻‍♂️🚮 Kerry Akshay Buddiga 🇺🇸 Radagast the Brown Death will not release you
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        2. Venkatesh Rao‏ @vgr Oct 11
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          Russian dude Smorodintsev created first attenuated flu vaccine in 1936. Many eggs were needed. https://www.influenza.spb.ru/en/about_institute/history/ …

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        3. Venkatesh Rao‏ @vgr Oct 11
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          Aside: as a baby I had a bad reaction to a Russian-made smallpox vaccine (I’m old enough to have received that) that parents say almost killed me. So I have an extra large badass vaccine scar. As a teenager I used to tell other kids I got it in a knife fight. Some bought it 😎

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        4. Venkatesh Rao‏ @vgr Oct 11
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          The attentuated vaccine was risky since the virus could regain virulence. Russia continued to use the older tech viruses for 50 years. So 1986. Hmm......I wonder 🤔 Inactivated polyvalent vaccines were invented later and by 1944 American troops in WW2 were receiving it.

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        5. Venkatesh Rao‏ @vgr Oct 11
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          Jonas Salk apparently worked on the early flu vaccine in 1940s. Alexander Fleming helped prove viral origin in 1918. This story has interesting cameos.

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        6. Venkatesh Rao‏ @vgr Oct 11
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          Viruses weren’t actually seen till after 1943 when the electron microscopes were invented. Spinney compares them to Higgs boson before then. Quasi mythical and not entirely believed in.

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        7. Venkatesh Rao‏ @vgr Oct 11
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          The H and N of HxNy naming scheme refer to Haemaggluttinin and Neuraminidase, which help virus break into and out of cell apparently. Now you know. This is what the villain of this story looks like btw. Bastard.pic.twitter.com/BqFQmdjgb9

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        8. Venkatesh Rao‏ @vgr Oct 11
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          Because flu viruses are single strands of RNA, they are not as stable as DNA and make lots of replication errors. This is why they drift 2% a year and vaccines have to be updated every covfefe. Shit, viruses are liek twetes. Taht’s why their hard to fihgt

          1 reply 0 retweets 17 likes
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        9. Venkatesh Rao‏ @vgr Oct 11
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          So pandemics apparently happen when 2 different virus strains meet cute in a human cell and have virus sex. Results in novel immune resistant strain. Especially bad if human and animal flus meet. You get human-adapted alien virus.

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        10. Venkatesh Rao‏ @vgr Oct 11
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          This is awful. I’m never taking off my mask or going near animals again. How did we ever think we could win this arms race long term? It’s like our microbial interface is full of fast adapting little trumps crossing the wall from bird snot.

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        11. Venkatesh Rao‏ @vgr Oct 11
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          Anybody think about how Trump’s wall idea is just a country scale mask against people he thinks of as diseases? Some 4d irony there that I don’t have the energy to unpack. Wear masks, don’t build walls.

          1 reply 0 retweets 18 likes
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        12. Venkatesh Rao‏ @vgr Oct 11
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          So flu equilibriums last about a human lifespan. Once populations get “immunologically naive” another pandemic can happen. 1968 Hong Kong flu was possibly 1890 Russian flu, and 2009 H1N1 was apparently 1918 Spanish Flu.

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        13. Venkatesh Rao‏ @vgr Oct 11
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          There’s an eerie echo here in outbreaks of totalitarianism. Despite “never forget” culture re Holocaust, 2010s had become immunologically naive to perils of totalitarianism. Even though Trumpism mind flu is an attentuated strain, it’s descended from Hitlerism mind flu of 1933.

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        14. Venkatesh Rao‏ @vgr Oct 12
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          There are apparently 18 kinds of H and 11 kinds of N. So you could potentially have a flu called H18N11 🤔. And that’s not even counting strains. We should just give up and stop living in dense cities. This doesn’t seem very winnable long term. Yeah I’m a bit defeatist.

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        15. Venkatesh Rao‏ @vgr Oct 12
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          Ok that’s 13 chapters done. Next one ominously titled “beware the barnyard.” Bedtime horror story resumes tomorrow. Try not to pet bats and ferrets and chickens ok.

          2 replies 0 retweets 7 likes
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        16. Venkatesh Rao‏ @vgr Oct 12
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          Footnote to tonight’s notes... defeatism here is not just me. I’ve heard a popular theory that the century of gains against infectious disease was entirely based on temporary victories. Individual battles are won but the war overall gets harder and we are steadily losing ground.

          2 replies 0 retweets 16 likes
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        17. Venkatesh Rao‏ @vgr Oct 12
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          Well, let’s get back to this grim fairy tale. The story of crossover. Apparently duck guts are the natural reservoir of flu viruses and that’s been known since the 1970s. I’ll never look at ducks the same. Wonder what species stores coronaviruses 🤔

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        18. Venkatesh Rao‏ @vgr Oct 12
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          They used to think flus needed to go from birds to humans by way of pigs (which would make the French origin hypothesis the likeliest for various reasons) but H5N1 in 1997 in Hong Kong showed it could jump direct. Could that have happened in 1918? 🧐

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        19. Venkatesh Rao‏ @vgr Oct 12
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          After partial sequencing from rare preserved samples in the late 90s, researchers managed to get better permafrost-preserved samples from Alaskan mass graves. In 2005 Ann Reid and Jeffrey Taubenberger finally sequenced the full genome after 9 years of detective work. 👏👏👏

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        20. Venkatesh Rao‏ @vgr Oct 12
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          Damn 87 years later. Gotta love the deep historical detective work. They resurrected the virus in the lab and showed it was very bird-like. No pigs needed in transmission chain.

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        21. Venkatesh Rao‏ @vgr Oct 12
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          1918 flu was exceptionally good at blocking interferon, which is the immune system’s first responder that blocks virus protein synthesis. This is like a SIM card hack to get around sms-based 2FA or something.

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        22. Venkatesh Rao‏ @vgr Oct 12
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          If this first line fails, second line defense kicks in, immune cells and antibodies. Blood flow increases to infected cells, nearby cells are killed to prevent spread... this is inflammation. Like a control burn around a forest fire I guess?

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        23. Venkatesh Rao‏ @vgr Oct 12
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          The immune cells released cytokines to do this stuff. If this response is overzealous you get a cytokine storm, which seemed present in 1918 based in reports. Replicated in lab rats after the sequencing.

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        24. Venkatesh Rao‏ @vgr Oct 12
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          Note that we’re already into the story past the point GWB got missionary about this stuff in 2004 or so. In 2011 they figured out that the virus mutated slightly by the second wave to adapt better to humans, which is why it was deadlier. Could happen with SARS-Cov2 as well.

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        25. Venkatesh Rao‏ @vgr Oct 12
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          Btw it seems like H1N1 identifies a class of viruses based on H-N topology. Not a specific strain. I guess the genus/species type Linnean binomial nomenclatureisctoo coarse for viruses.

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        26. Venkatesh Rao‏ @vgr Oct 12
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          So the mutation was possibly favored by wartime conditions on the western front. Normally viruses get more moderate to spread better but if everybody is dying faster from bullets, the more aggressive strains might be favored. Also mustard gas is mutagenic so might have nudged it.

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        27. Venkatesh Rao‏ @vgr Oct 12
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          So if there’s a second winter wave if Covid and there’s a civil war after the election, we have a mutated worse strain to look forward to. Yay. This story just gets relentlessly gloomier as a precedent for 2020.

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        28. Venkatesh Rao‏ @vgr Oct 12
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          More detective work. Drift rates in the virus suggest the North American origin story is most likely. Research by Michael Worobey of U. Arizona in 2014 showed 7 of 8 1918 H1N1 genes resembled flu genes found in North American birds.

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        29. Venkatesh Rao‏ @vgr Oct 13
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          This is fascinating. Apparently horses rather than birds used to be the main flu reservoir. There’s a chance mechanization/cars and the retreat of horses from human life made birds the reservoir. Very circumstantial evidence but I like the story.

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        30. Venkatesh Rao‏ @vgr Oct 13
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          There is some tricky inside baseball here about 8th gene and the W shaped mortality curve. I’m not going to try and follow the intricacies here. But the level of detail that detective work uncovers is astounding. I didn’t know flu research was so broad deep. Good work Science!™

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        31. Venkatesh Rao‏ @vgr Oct 13
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          2 more flu epidemics in 20th century, 1957 Asian flu H2N2 and 1968 Hong Kong flu, H3N2, both share a lot of genes with H1N1. Apparently humans gave the flu to pigs, not the other way around. Swine flu should be called long pig flu.

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