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__ice9's profile
ice9
ice9
ice9
@__ice9

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ice9

@__ice9

I do quantitative things. Sometimes I think about society and economics.

Chicago, IL
Joined January 2017

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    1. ice9‏ @__ice9 15 Sep 2020

      Such research has remained controversial. It is not clear how well it parallels natural viral evolution. For expediency, large selective pressures are applied at particular sites in cell culture. Limited synthetic methods may occasionally be used as a shortcut.

      1 reply . 2 retweets 30 likes
      Show this thread
    2. ice9‏ @__ice9 15 Sep 2020

      Fouchier's landmark paper... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810786/ … https://www.freethink.com/articles/gain-of-function-mutation … ... provoked extensive objections, from basic plausibility to actionability to the risk of artificial pandemics. https://www.cidrap.umn.edu/news-perspective/2014/06/commentary-case-against-gain-function-experiments-reply-fouchier-kawaoka … https://science.sciencemag.org/content/342/6156/311.1 … https://europepmc.org/article/pmc/pmc7119956 … .

      1 reply . 11 retweets 35 likes
      Show this thread
    3. ice9‏ @__ice9 15 Sep 2020

      >"I was intrigued," says Ron Fouchier, in his rich, Dutch-accented English, "in how little things could kill large animals and humans." >It's late evening in Rotterdam as darkness slowly drapes our Skype conversation. >28 Mar, 2020 09:00 AM

      1 reply . 4 retweets 28 likes
      Show this thread
    4. ice9‏ @__ice9 15 Sep 2020

      Be that as it may, the techniques do leave a certain kind of 'fingerprint,' distinct both from natural evolution and from outright biological weapons programs.

      1 reply . 3 retweets 32 likes
      Show this thread
    5. ice9‏ @__ice9 15 Sep 2020

      1) start with a natural strain 2) optionally, hybridize with another strain, simulating co-infection 3) passage, optionally with mutagens, to acquire further specific desired features 4) optionally, edit in small tweaks that did not arise, hand-wave result as plausible in paper

      1 reply . 4 retweets 43 likes
      Show this thread
    6. ice9‏ @__ice9 15 Sep 2020

      5) make up something about how this provides a valuable early warning to prepare for a possible pandemic, shows that such-and-such virus could theoretically gain terrible new capabilities outside of your ever-so-responsible lab, etc. 6) angle for more grant funding.

      1 reply . 3 retweets 50 likes
      Show this thread
    7. ice9‏ @__ice9 15 Sep 2020

      But of course, the real reason: >"I was intrigued," says Ron Fouchier, "in how little things could kill large animals and humans." 'I like playing with invisible transmissible death.' Gain-of-function research should be banned by international law. It has only been 8 years.

      2 replies . 30 retweets 94 likes
      Show this thread
    8. ice9‏ @__ice9 15 Sep 2020

      ice9 Retweeted ice9

      One important point, not addressed in the Yan et al. manuscript-- SARS-CoV-2 still has dN/dS values (including in Spike) vs. related CoVs that are low and in typical ranges for RNA viruses. This argues against extensive positive selection.https://twitter.com/__ice9/status/1306049991652278272?s=20 …

      ice9 added,

      ice9 @__ice9
      Replying to @__ice9 @halvorz
      Yes, dN/dS should be markedly higher in selectively passaged viral strains. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5049878/ … This seems to pose a large unaddressed problem to the argument for substantial gain-of-function work. Reasonable enough.
      1 reply . 4 retweets 29 likes
      Show this thread
    9. ice9‏ @__ice9 15 Sep 2020

      Hence, if the broader claim of lab escape is valid, then it was likely either a mostly natural strain, or one modified chiefly by recombination against one or more other natural strains. Not all samples sequenced are disclosed, making it difficult to exclude either possibility.

      2 replies . 2 retweets 34 likes
      Show this thread
    10. ice9‏ @__ice9 15 Sep 2020

      ice9 Retweeted

      As Twitter has apparently suspended the account of the author, and I am not particularly interested in censorship as a response to controversy, my account will be set protected for a bit. https://twitter.com/kacper_fronc/status/1306067175493398528?s=20 …

      ice9 added,

      This Tweet is unavailable.
      2 replies . 1 retweet 48 likes
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      ice9‏ @__ice9 15 Sep 2020

      ice9 Retweeted ice9

      Further intrigues-- This grant proposal is nearly a verbatim description of a program of optimizing southern Chinese bat CoVs by ACE2-binding-based methods to gauge the risk of human transmission from nature.https://twitter.com/__ice9/status/1306100230773968897 …

      ice9 added,

      ice9 @__ice9
      Replying to @scottleibrand @ChanaMessinger @ciphergoth
      This grant abstract is 100% consistent with the idea that someone may have been swapping RBDs between a large pool of undisclosed natural southern Chinese bat CoV strains. https://grantome.com/grant/NIH/R01-AI110964-06 …
      10:21 pm - 15 Sep 2020
      • 14 Retweets
      • 68 Likes
      • pbear👽🐻🎹 fine Bassaces CoWIVd 🦇 ros mac Winning Emergence agent furkly 🅾🅻🅳🅾 Janice Kinase
      2 replies . 14 retweets 68 likes
        1. New conversation
        2. ice9‏ @__ice9 15 Sep 2020

          The project scope would have involved large numbers of strains closely related to SARS-CoV-2, handled systematically, likely without individual sequence disclosures-- and the dates align as well, mid-2019 to mid-2020 anticipated work. Further discussion: https://www.independentsciencenews.org/commentaries/a-proposed-origin-for-sars-cov-2-and-the-covid-19-pandemic/ …

          1 reply . 10 retweets 36 likes
          Show this thread
        3. ice9‏ @__ice9 16 Sep 2020

          ice9 Retweeted Steven Hebert

          Article discussing the collapse of the pangolin papers, mainly focusing on work by @Ayjchan Also discusses some of the same unusual attributes of SARS-CoV-2 mentioned in the Yan paper cited at the top of this thread. Consistent with the grant language.https://twitter.com/talentpharmNYC/status/1304131865423622146?s=19 …

          ice9 added,

          Steven Hebert @talentpharmNYC
          A fantastic article about the work of @Ayjchan to investigate the origins of #COVID19 and the challenges of following the science, not the political orthodoxy. Well done @rowanjacobsen and @BostonMagazine https://www.bostonmagazine.com/news/2020/09/09/alina-chan-broad-institute-coronavirus/ …
          2 replies . 5 retweets 20 likes
          Show this thread
        4. ice9‏ @__ice9 16 Sep 2020

          ice9 Retweeted

          Article on synthetic virology-- Example reconstruction of infectious SARS-CoV-2 virions from sequence data within about one week of work. https://twitter.com/K_G_Andersen/status/1306037078602383360?s=20 … Of course, this one does not prove anything about the origin of any given virus. Merely an available technology.

          ice9 added,

          This Tweet is unavailable.
          1 reply . 7 retweets 27 likes
          Show this thread
        5. ice9‏ @__ice9 16 Sep 2020

          ice9 Retweeted Alina Chan

          In attempting to confirm my procedural impressions of the grant work above, from descriptions by others closer to the subject matter, I encountered a very close match to the nature of the work I had suggested was involved. This strengthens the claim.https://twitter.com/Ayjchan/status/1297150935744090112?s=20 …

          ice9 added,

          Alina ChanVerified account @Ayjchan
          The Ecohealth NIH grant description can be read here. To predict spillover potential of novel CoVs, they would sequence genomes, isolate viruses, clone spikes into other CoV genomes, test ACE2 binding & infection of different cell lines and humanized mice https://grantome.com/grant/NIH/R01-AI110964-04 …
          Show this thread
          2 replies . 9 retweets 33 likes
          Show this thread
        6. ice9‏ @__ice9 17 Sep 2020

          ice9 Retweeted OneOfMany258

          ... they just came right out and said it.https://twitter.com/OneOfMany3421/status/1306671434790510595?s=19 …

          ice9 added,

          OneOfMany258 @OneOfMany3421
          Replying to @R_H_Ebright @__ice9 @Ayjchan
          They where doing some funky stuff with Sars in 2019 pic.twitter.com/x7OF9WjBnq
          7 replies . 28 retweets 114 likes
          Show this thread
        7. ice9‏ @__ice9 17 Sep 2020

          ice9 Retweeted tweetstamp.org

          Thread: https://twitter.com/PeterDaszak/status/1197631383470034951?s=19 … Stamps: https://twitter.com/tweet_stamp/status/1306673528121503744?s=19 …https://twitter.com/tweet_stamp/status/1306673603736416258?s=19 …

          ice9 added,

          tweetstamp.org @tweet_stamp
          Replying to @__ice9
          🐤🔏🎫 https://tweetstamp.org/1197633459646275590 …
          1 reply . 2 retweets 20 likes
          Show this thread
        8. ice9‏ @__ice9 17 Sep 2020

          ice9 Retweeted Richard H. Ebright

          Further discussion here also: https://twitter.com/R_H_Ebright/status/1253132609238024195?s=19 … Systematic gain-of-function studies against hACE2 and humanized model animals using recombinant methods to modify Spike across dozens of novel undisclosed bat CoVs had recently begun at WIV at the time of the outbreak.

          ice9 added,

          Richard H. EbrightVerified account @R_H_Ebright
          Replying to @R_H_Ebright @lumiere2016
          "We will test this hypothesis by asking whether novel viruses encoding spike proteins with the highest receptor-binding affinity have the highest ability to infect human cells in culture and to infect laboratory animals."
          2 replies . 11 retweets 38 likes
          Show this thread
        9. ice9‏ @__ice9 17 Sep 2020

          I have also gone to the trouble of submitting each pdf in the thread at their source to the Internet Archive. https://web.archive.org/web/20200917193618/https://www.ecohealthalliance.org/wp-content/uploads/2016/02/Ge-et-al-Bat-SARS-like-CoV-that-uses-ACE2-Nature-2013.pdf … https://web.archive.org/web/20200917193719/https://www.ecohealthalliance.org/wp-content/uploads/2016/02/Li-et-al_Science_Bats-as-reservoir-for-SARS.pdf … https://web.archive.org/web/20200917193758/https://www.ecohealthalliance.org/wp-content/uploads/2018/03/Virologica-Sinica-SARSr.pdf … Published and available elsewhere, of course, but hopefully a useful combined collection.

          1 reply . 3 retweets 37 likes
          Show this thread
        10. ice9‏ @__ice9 17 Sep 2020

          ice9 Retweeted ice9

          Minor note-- The gain-of-function studies disclosed in papers and grants associated with the WIV's bat CoV research do not imply the design of a particular single 'candidate' strain. Past work developed several, reporting on various characteristics.https://twitter.com/__ice9/status/1306694599453429761?s=19 …

          ice9 added,

          ice9 @__ice9
          Replying to @poiThePoi
          If the gain-of-function theory of the origin of SARS-CoV-2 is correct, then it likely wasn't even 'special' in any sense, but rather merely one of a large number of experimental recombinant strains being created and screened to analyze the potential risks of bat CoVs to humans.
          3 replies . 3 retweets 20 likes
          Show this thread
        11. ice9‏ @__ice9 18 Sep 2020

          ice9 Retweeted Alina Chan

          Meanwhile, evidence from the RaTG13 sequencing datasets strongly implies that southern Chinese bat CoV full genome sequencing had been ongoing without disclosure of the results to international databases for at least two years prior to the outbreak.https://twitter.com/Ayjchan/status/1306993218408587267?s=19 …

          ice9 added,

          Alina ChanVerified account @Ayjchan
          These amplicons revealed that RaTG13 had been sequenced in 2017 & 2018, which threw everyone for a loop because we all thought that RaTG13 had only been full genome sequenced AFTER COVID-19 broke out. Acknowledgements: @babarlelephant @franciscodeasis https://twitter.com/Ayjchan/status/1279761424919732224?s=20 …
          Show this thread
          1 reply . 9 retweets 32 likes
          Show this thread
        12. ice9‏ @__ice9 18 Sep 2020

          Also, direct evidence that the backbone in these studies was not always a pseudovirus or SARS-CoV, even in 2008. This paper did the reverse: generate synthetic consensus Bat-SCoV, swap in SARS-CoV RBD, test in cells and mice. https://www.pnas.org/content/105/50/19944 … Grant merely generalized.pic.twitter.com/JGGVlZyhj0

          1 reply . 4 retweets 18 likes
          Show this thread
        13. ice9‏ @__ice9 18 Sep 2020

          Likewise, the 2015 Baric and Shi paper (includes researchers at WIV by 2019) used mouse-adapted SARS-CoV as a backbone instead of ordinary SARS-CoV. https://www.med.unc.edu/orfeome/files/2018/03/a-sars-like-cluster-of-circulating-bat-coronaviruses-shows-potential-for-human-emergence.pdf … Fully synthetic recombinant virus used for an emergence study. The grant extended this specific work.pic.twitter.com/XKUPyPg7tW

          2 replies . 6 retweets 25 likes
          Show this thread
        14. ice9‏ @__ice9 18 Sep 2020

          The grant described screening a new sample of apparently >50 SARS-like CoVs vs. human ACE2 and testing recombinants in humanized mice. Note emphasis on pathogenicity in all of these papers. The backbone matters (e.g. SARS is deadlier in part because of better IFN suppression).

          3 replies . 7 retweets 32 likes
          Show this thread
        15. ice9‏ @__ice9 18 Sep 2020

          Hence, to properly understand potential emergence harms from this broader sampled set in humanized mice, the most logical approach is using both backbones and RBDs drawn from the set. Fully synthetic methods and whole-genome sequences were already available, as shown above.

          1 reply . 3 retweets 22 likes
          Show this thread
        16. ice9‏ @__ice9 18 Sep 2020

          The goal? Likely to assess human emergence risk from the Mojiang Yunnan cave. 6 miners were infected; 2 died. Shi lied, claiming fungal infection: https://www.scientificamerican.com/article/how-chinas-bat-woman-hunted-down-viruses-from-sars-to-the-new-coronavirus1/ … But a translated thesis proves it was a bat CoV: https://www.independentsciencenews.org/commentaries/a-proposed-origin-for-sars-cov-2-and-the-covid-19-pandemic/ …pic.twitter.com/7m3EhP7Hjo

          1 reply . 8 retweets 34 likes
          Show this thread
        17. ice9‏ @__ice9 18 Sep 2020

          This cave also yielded: RaTG13. In spite of initial doubts, the latest analysis linked above via @Ayjchan strongly suggests RaTG13 is indeed real. And RaTG13 is the closest known match to SARS-CoV-2, >96%.

          1 reply . 2 retweets 19 likes
          Show this thread
        18. ice9‏ @__ice9 18 Sep 2020

          So the "bat woman of China," who contributed to the hunt for SARS and this covered-up CoV of the Mojiang miners ('threat for human emergence' it already happened) had a grant for systematic recombination studies-- including further Yunnan samples. Wuhan is 1900 km from Yunnan.

          1 reply . 4 retweets 27 likes
          Show this thread
        19. ice9‏ @__ice9 18 Sep 2020

          96% similarity between RaTG13 and SARS-CoV-2, grant funding for recombinantly optimizing hACE2 binding over this class of CoVs and infecting humanized mice, undisclosed existence of the full RaTG13 sequence and likely others since at least 2017, 4 separate cave sampling trips,

          2 replies . 4 retweets 36 likes
          Show this thread
        20. End of conversation

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