Chinese virology researcher released something claiming it SARS-2 might even be genetically-manipulated after all? ZC45 and/or ZXC21 backbone. Claims that the RaTG13 genome was a concocted cover-up. I’m still assessing the sub-claims, but I think she makes some pretty cogent-sounding arguments for it.
(That the RaTG13 sequence could have been concocted is something I kinda wish I’d thought of earlier.)
See here for my further thoughts on this.
EDIT: After assessing, I’m not finding the GMO claims convincing. The RaTG13 story does seem to have something weird going on, and there’s several people and papers that note weird inconsistencies (See the further thoughts, I don’t have a simple explanation.).
Chinese virology researcher released something claiming that SARS-2 might even be genetically-manipulated after all? After assessing, I’m not really convinced of the GMO claims, but the RaTG13 story definitely seems to have something weird going on.
Claims that the RaTG13 genome release was a cover-up (it does look like something’s fishy with RaTG13, although it might be different than Yan thinks). Claims ZC45 and/or ZXC21 was the actual backbone (I’m feeling super-skeptical of this bit, but it has been hard for me to confirm either way).
https://zenodo.org/record/4028830#.X2EJo5NKj0v (aka Yan Report)
Looks like something fishy happened with RaTG13, although I’m not convinced that genetic modification was involved. This is an argument built on pre-prints, but they appear to offer several different lines of evidence that something weird happened here.
Simplest story (via R&B): It looks like people first sequenced this virus in 2016, under the name “BtCOV/4991”, using mine samples from 2013. And for some reason, WIV re-released the sequence as “RaTG13″ at a later date?
(edit: I may have just had a misunderstanding. Maybe BtCOV/4991 is the name of the virus as sequenced from miner-lungs, RaTG13 is the name of the virus as sequenced from floor droppings? But in that case, why is the “fecal” sample reading so weirdly low-bacteria? And they probably are embarrassed that it took them that long to sequence the fecal samples, and should be.)
A paper by by Indian researchers Rahalkar and Bahulikar ( https://doi.org/10.20944/preprints202005.0322.v1 ) notes that BtCoV/4991 sequenced in 2016 by the same Wuhan Virology Institute researchers (and taken from 2013 samples of a mineshaft that gave miners deadly pneumonia) was very similar, and likely the same, as RaTG13.
A preprint by Rahalkar and Bahulikar (R&B) ( doi: 10.20944/preprints202008.0205.v1 ) notes that the fraction of bacterial genomes in in the RaTG13 “fecal” sample was ABSURDLY low (“only 0.7% in contrast to 70-90% abundance in other fecal swabs from bats”). Something’s weird there.
A more recent weird datapoint: A pre-print Yan referenced ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337384/ ), whose finding (in graphs; it was left unclear in their wording) was indeed that a RaTG13 protein didn’t competently bind their Bat ACE2 samples, but rather their Rat, Mouse, Human, and Pig ACE2. It’s supposedly a horseshoe bat virus (sequenced by the Wuhan lab), so this seems hecka fishy to me.
(Sure, their bat samples weren’t precisely the same species, but they tried 2 species from the same genus. SARS-2 DID bind for their R. macrotis bat sample, so it seems extra-fishy to me that RaTG13 didn’t.).
((...oh. According to the R&B paper about the mineshaft, it was FILTY with rats, bats, poop, and fungus. And the CoV genome showed up in only one of ~280 samples taken. If it’s like that, who the hell knew if it came from a rat or bat?))
At this point, RaTG13 is genuinely looking pretty fishy to me. It might actually take evidence of a conspiracy theory in the other direction for me to go back to neutral on that.
I’m not finding the Protein-E sequence similarity super-convincing in itself, because while the logic is fine, it’s very multiple-hypothesis-testing flavored.
I’m still looking into the ZC45 / ZXC21 claim, which I’m currently feeling skeptical of. Here’s the paper that characterized those: doi: 10.1038/s41426-018-0155-5 . It’s true that it was by people working at “Research Institute for Medicine of Nanjing Command.” However, someone on twitter used BLAST on the E-protein sequence, and found a giant pile of different highly-related SARS-like coronaviruses. I’m trying to replicate that analysis using BLAST myself, and at a skim the 100% results are all more SARS-CoV-2, and the close (95%) results are damned diverse. …I don’t see ZC in them, it looks like it wasn’t uploaded. Ugh. (The E-protein is only 75 amino acids long anyway. https://www.ncbi.nlm.nih.gov/protein/QIH45055.1 )
A different paper mentions extreme S2-protein similarity of early COVID-19 to ZC45 , but that protein is highly-conserved. That makes this a less surprising or meaningful result. (E was claimed to be fast-evolving, so its identicality would have been more surprising, but I couldn’t confirm it.) https://doi.org/10.1080/22221751.2020.1719902
I think Yan offers a reasonable argument that a method could have been used that avoids obvious genetic-modification “stitches,” instead using methods that are hard to distinguish from natural recombination events (ex: recombination in yeast). Sounds totally possible to me.
The fact that the early SARS-CoV-2 samples were already quite adapted to human ACE2 and didn’t have the rapid-evolution you’d expect from a fresh zoonotic infection is something a friend of mine had previously noted, probably after reading the following paper (recommended): https://www.biorxiv.org/content/10.1101/2020.05.01.073262v1 (Zhan, Deverman, Chan). This fact does seem fishy, and had already pushed me a bit towards the “Wuhan lab adaptation & escape” theory.
Some things I think help are:
Personal fit to the particular job demands (which can include some subset of: lots of people-time, navigating conflict, frequent task-switching, personal initiative, weighing values (or performing triage), etc.)
Personal investment in appropriate values, and a lasting commitment to doing the role well.
Having it be fairly clear what they’re biting off, what resources they can use, and what additional resources they can petition for. Having these things be actually fairly realistic.
(Minimum expertise to thrive is probably set by needing to find someone who will advocate for these things well enough to make them clear, or who can at least learn how to. Nebulous roles can be navigated, but it is harder, and in practice means they need to be able to survive redefining the role for themselves several times.)
Having some connections they (and others) respect who will help support what (and how) they’re doing, lend some consistent sense of meaning to the work, and people who will offer reliable outside judgement. Quite possibly, these things come from different people.
(Public opinion is often too noisy and fickle for most human brains to learn off of it alone.)
For roles that require the buy-in of others, it’s helpful if they have enough general respect or backing that they will mostly be treated as “legitimate” in the role. But some roles really only require a small subset of high-buy-in people.
Also, some sort of step-down procedure.
Extracted from a FB thread, where I was thinking about burnout around nebulously-defined community leader roles, and what preparedness and a good role would look like. Parts of this answer feel like I’m being too vague and obvious, but I thought it was worth making the list slightly more findable.
I’ve seen some presentations about how to do style-matching off of GitHub repos to pretty-confidently ID anonymous coders. While set-up requires a sizable amount of compute and data, the results have gotten quite impressive. There are ways to work against this (stuff that deliberately obscures your coding style, usually by rewriting your code), but they’re not that well known. And a similar thing can be done with writing style and writing samples.
Staying anonymous against high-effort attempts to discern your identity has gotten very hard, and is only likely to get harder.
At some point, all you can do is guard against the low-effort ones.
A quiz and a day’s wait before adding a new user is another option. Make it something that a regular lurker who read the rules would be able to pass easily, but a rando couldn’t. SCP wiki did something like this, it seemed to help with quality control.
Rotate through 3 different quizes, or scramble the quiz order sometimes, if you want to make automated sign-ups annoying for mobs and spammers. Have the web people track the number of sign-up-quiz fails (it’s a nice metric for “is there a mob at the doorstep”).
(Edit: Ah, someone already proposed a more-elaborate variant using GPT-X. Simple quizes with a few mild gotcha-questions should be enough of a screen for most cases, though.)
A proposal I think I haven’t seen posed is giving new members a “trial period.” If an average (or randomly-selected) post doesn’t have a karma score of at least X by the end of the period (or if it dips below Y at any point), they’re out and their stuff is deleted. Ban them from handing out karma until after the trial, or this quickly breaks. This probably still has weird incentive consequences that I’m not seeing, though...
...it does mean having a bit of an evaporative-filter for quality-ratings, and it means links to crappy posts turn into deadlinks in just a matter of time.
I did specify long-term, which for me meant time-frames of around a year to a decade out. Honestly, I suspect you’re largely right about the short-term.
Well, except I might be more optimistic about vaccination efforts. Effective vaccination pushes in the past give me some hope.
Also, the mutation rate is a good bit lower than the seasonal flu. SARS-CoV-2′s point-mutations per year is around 28 substitutions, which is about 1⁄2 as many as the flu. Or around 1⁄3 the rate, at ~1.1e-3 subs per site per year, compared to flu’s 3.3 subs per site per year. (Different genome lengths, hence the different answers.)
It’s kinda weird to me how limited the options seem to be for flashcards and annotation/marginalia. While plenty of things perform the core functionality, I haven’t seen anywhere near as many interesting experiments with these formats as I have with outliners.
And for flashcards particularly? You’d think it’d be the simplest damn thing to program!
I’m not much of an index card person, but there seem to be a lot of people who swear on elaborate index-card set-ups. That I haven’t seen more of them implemented as software confuses me too.
(It does seem like it would be a good use of flashcards to set up a rudimentary priority queue, or stack. Possibly with added randomness. I’m honestly a little surprised it doesn’t allow that.)
I think this is a good question. Here are some probable components of programmability...
Did it surface most of its actual functionality to users?
A couple different settings: Closed proprietary cloud software, API (how friendly or permissive is it?), downloadable open-source...
How easy (and safe!) it is to call relevant utility functions?
Do you need to close the software to edit it? Did they merely surface the functionality, or did they also leave functions that were highly-exposed, labeled, well-documented, and easy to use? How well do they adhere to various standards, and therefore benefit from skill-transfer? Is it easy to screw up? To revert? What’s the learning curve like?
I really wish there was better flashcard and annotation/marginalia software out there! It’s kinda weird to me how limited the options seem to be for both. While plenty of things perform the core functionality, I haven’t seen as many interesting experiments with it as I have with, say, outliners.
While writing this post, I developed a vague suspicion that there’s something in-between Annotator and Flashcard that could be pretty valuable if someone actually implemented it. This seems as good a place as any to describe it. (And if someone has already done it, or wants to do it, cool!)
Annotators and Flashcards are both often tracking an underlying dictionary-ish data-type, and a lot of flashcards seem to originate from textbooks. I have a suspicion that there should exist a good standardized-format notetaker that goes something like… this?
TextCards: 3 linked items
A bounded section of highlighted textbook (Any size, from a section to entire chapter. Sometimes discontinuous.)
An index-card laconic description (or answer)
A title (or question)
Sometimes, it could be used to pose standard quiz-questions (the highlighted section is just the part of the book the quiz came from, the title is the question, the description is an answer). But where it might really shine is in “Summarize Chapter X” questions; it encourages you to write along as you read the text, and if you miss something on a quiz, you can click right to the sections you were originally summarizing.
When rendered as marginalia, the small titles (until click) should make that experience more tolerable for frequent-margin-users. (Marginalia asyncing with the page seems like a really common problem, otherwise.)
For convenience, adding something that swipes all of the questions from a highlighted section of the text to form the front end of flashcards (that you then answer) seems pretty nice. For well-formatted answer-sections, you might even be able to get it to pair the two (but you’d probably need to highlight where to look). Additionally, it wouldn’t be that hard for it to track which chapter’s questions you’re doing poorly on -and therefore what chapters you should re-read- if it knows where in the book you swiped them from. Bonus points if you can sort and cross-link notes by title, folder, tags, overlapping highlights, and/or order in text.
Presumably this is usually harder than I think it should be, because PDFs are just awful (I’ve dragged tables from PDFs before; I feel so sorry for Tabula!). But HTML books and ebooks don’t have that problem, and often simulate a textbook-like structure.
At minimum it’s oversimplified. That’s why I called it a parable.
I appreciate the nuance in your comment even as it is. But I’m curious about the facts/narratives you have that disagree with it?
(My personal strongest murphyjitsu was that “space program defunding” was more complicated than this. If you know more about that than I do, I’d be curious to hear about it.)
A long time ago, you could get the biggest positive visual impact for your money by generating art, and if you wanted awe you could fund gardens and cathedrals. And lo, these areas were well-funded!
The printing press arrived. Now, you could get massive numbers of pamphlets and woodcuts for a fraction of the price of paintings. And lo, these areas were well-funded!
Then tv appeared. Now, if you wanted the greatest awe and the biggest positive visual impact for your money, you crafted something suitable for the new medium. And in that time, there were massive made-for-tv propaganda campaigns, and money poured into developing spacecraft, and we got our first awe-inspiring images of Earth from the moon.
Some even claim the Soviet Union was defeated by the view through a television screen of a better life in America.
And then we developed CGI and 3D MMORPGs. And lo, the space program defunded, as people built entire cities, entire planets in CGI for a tiny fraction of the cost!
I didn’t downvote it, but I did find the writing style mildly grating. (Relatedly: I cannot exceed your set-point of smug, it is over 9000 :) )
To be clear: I think the underlying point was pretty good, and I mostly had issues with the delivery. I still feel it was probably something worth writing, although I also think I’m not the target audience for this particular bit of advice.
Some of it was probably a tone thing, which I won’t go into. But here are some things that seem tractable:
My experience of it was a bit better as soon as I switched out almost all the “You”s for “I”s. I have something of a distaste for the… puppety-feeling where someone seems to be trying to put words into my mouth, that don’t fit with my actual experience. This set it off pretty badly. There are a lot of specifics, and it’s clearly your personal account; own it.*
This got really stark for me at around...
First, you just end up being an asshole pretending to be honest
First, you just end up being an asshole pretending to be honest
...which instantly broke my immersion. My experience of being painfully honest with myself, and then others, was radically different.**
It probably also could have used more short paragraphs, and some variety in presentation. Some of the goals you’ve acted on and then forgotten, such as Real Analysis or Mandarin, could have been better-presented as single bullet-points after going into only 1 of them in-depth. The Etsy section could have used a header, and been broken into more than 1 paragraph. That kind of thing.
*A lot of bad advice on persuasive essay writing encourages the formation of habits like this. One cannot list the number of times one has been told to make that unnatural substitution of “One,” where “I” would have been better, and more honest. Teachers who do this are just… wrong. Technical writing is a real thing, but this way of teaching it is crap, and can ruin otherwise-decent writers.
** My experience was close to painful self-consciousness (for self-honesty), and weird social penalties (for honesty with others). Real honesty is often distinctly un-charming, but in my case… bluntness leaned closer to “overly-invested*** eccentric” than “asshole.” If it had been framed as a self-account, this jarring wouldn’t have been an issue.
*** Exhibit A: This overgrown write-up.
I’ve personally found that just stapling shut the outer edge of the first fold on either side of a surgical mask results in a mask that mostly sucks to my face when I breathe in. It doesn’t stick well when I breathe out, though.
This is much easier to implement than fancy adherents; all it takes is 2 staples and a stapler, or a needle and thread. It struck me as a plausible 80-20. (Well, less than 80%. Obviously, this is no N95.)
(It might only work for some face-shapes, though.)
This generates a new problem, which would also apply to taped/glued solutions:
The front is made of a softer fabric than N95s. After an hour of wear, it will suck to my lips if I breathe in with my mouth. And since it doesn’t stick on out-breaths, air still gets out the sides and sometimes the top. I don’t know how much additional risk this presents, but I would be curious to hear someone weigh in.
(It also has uncomfortably-high humidity, but that’s even more true of N95s.)
Late Edit: Pangolins with this viral infection have been found from both Guangxi and Guangdong provinces.
Despite the virus being characterized in pangolins, after looking into this, I now think it is basically incorrect to think of this as primarily a “pangolin virus.” The pangolins were a dying canary in a coal mine, and probably caught it from something else that serves as the real reservoir species for this nCOV precursor*.
These pangolins were being smuggled when they were captured by the authorities in Guangxi. They were dying of probably several diseases; they had lesions in their skin, intense congestion, and were in generally atrocious condition when they got sequenced for viruses. They turned up positive for all manner of things (herpes out the wazoo, but also a sendai virus which was most closely related to the sequence of a human-taken sample, a paramyxovirus, and yes, several coronaviruses).
Here’s the original article on the pangolins whose virome they sequenced, and the article noting its relatedness to nCOV.
Given that so many of the pangolins died, the pangolins look more like a highly-susceptible secondary species, than a mostly-asymptomatic primary reserve species* to me.
* GD/PIL or GD/P2S is thought of as a possible nCOV progenitor, alongside bat-virus RaTG13. GD/PIL’s receptor-binding motif (RBM) in particular is identical to SARS-2′s, although nCOV otherwise appears more closely related to RaTG13.
** On educated priors, I think the true reservoir is probably rats, bats, or (less likely) humans in the Guanxi, Hunan, and/or Hubei province.
Personally, I assign >90% on either rats (strong priors + skin lesions) or bats (strong priors + simplest story). But these were exotic animal smugglers; there is a small chance that the original reservoir species could be any animal.
I think it’s probably a virus that was merely identified in pangolins, but whose primary host is probably not pangolins.
The pangolins they sequenced weren’t asymptomatic carriers at all; they were sad smuggled specimens that were dying of many different diseases simultaneously.
I looked into this semi-recently, and wrote up something here.
The pangolins were apprehended in Guangxi, which shares some of its border with Yunnan. Neither of these provinces are directly contiguous with Hubei (Wuhan’s province), fwiw. (map)
True, and I’ve seen lab work cultivate something similar.
(I’m pretty sure this particular skill is the inverse of programmer-style “laziness,” funnily enough. In one field, seeing repetition is reassuring. In the other, it can be evidence that your code is not as elegant and modularized as it could be.)
I always thought you’d automatically learn the gait if you just did the work often enough, though. It’s definitely a coping skill, but I read its origins as more cultivated than culturally-induced or taught.
It mostly follows the natural incentive gradients of the work. This can be in contrast to things like separation of self and client in psychology, which seems to feel actively un-natural for many people. Of course, there’s something of a spectrum here, with heavy individual variation.
Thanks! Sounds like a promising lead.