Disclaimer: I know essentially nothing about US legislation, scientific ethical frameworks, etc. as I am not American. I just read the paper and have some background in genetics.
tl;dr: No, this is classic gain-of-function research as far as I can tell
From the paper, I can see two vaguely plausible arguments for why this isn’t gain-of-function research:
SARS-CoV is already (obviously) already capable of infecting human cells. Using SARS-CoV as a vector to test other spike proteins’ ability to infect humans doesn’t increase the number of hosts
Prior to the chimeric testing referred to, it seem like the authors did not expect the altered spike protein used (SHC014) was likely to successfully infect human cells; host-range regions were different from SARS-CoV, and it was unable to enter human cells when in a pseudovirus (which, as I understand it, are not fully replication-competent, making an outbreak unlikely)
However, neither of these arguments really holds water in my opinion. The first seems the strongest—my main concern is that introducing a different spike protein could plausibly increase transmissibility or pathogenicity, but I don’t know enough about that topic specifically to confidently evaluate that claim. If anybody does know I’d be interested to hear (for instance, do any SARS-CoV-2 variants have spike mutations?).
As to the second point; if you didn’t think it was plausible that SHC014-MA15 (the chimeric virus) would be capable of infecting human cells… why did you do the test in the first place?
I think this should probably be merged with cognitive reduction, which is more general and (I think?) encompasses this one
From the old LessWrong Wiki Discussion Page:
Phyg and Phygish
“Phyg” and “phygish” are used a lot. I’m looking for recommendations on how to define them without putting this page in the wrong Google index. --R claypool 15:03, 10 August 2012 (UTC)
What counts as jargon?
I’ve recently had an addition or two of mine removed form the jargon file that I disagree with. So let me explain why I’ve been adding them.
I’m happy to take the definition of jargon to be “the language, especially the vocabulary, peculiar to a particular trade, profession, or group”
Now, I’m a reasonably well-read lay-person, but every so often, when I’m reading a discussion in comments, I’ll come upon a word that I have to go look up on wikipedia to understand it before I can figure out what the commenters are talking about.
I consider most examples of this happening to mean that they’re using a word that is jargon. In most cases—the words I’ve not understood were philosophical jargon… ie you have to have studied at least a solid base of philosophy to understand what they mean without reaching for the dictionary.
I’d consider words such as utilitarianism, consequentialism and deontology to be good examples of such philosophical jargon. I might guess at what I think they might mean—but to be sure—a definition (and link to a better explanation) is a good idea to have on hand… and therefore I added them to the jargon file.
The reason being that: if a complete newbie (such as myself) doesn’t understand them… then so will other newbies—and we are excluded unnecessarily from the conversation.
My argument is in favour of allowing these words in the jargon file for this reason.
Content of this article
Should this article be a list of Jargon with short descriptions or just repeat the contents of Category:Jargon? MrHen 16:42, 23 April 2009 (UTC)
Random idea: Make this article a list of Jargon with short descriptions, and transclude the contents of this article onto the category page. The reason for duplicating the content on the category page is because when browsing through the category trees, users will often end up on the category page, rather than the article page. --PeerInfinity 17:40, 23 April 2009 (UTC)
Unclear and hard to use
Unless there’s overwhelming objection, I’m going to merge the acronyms list to this article and reformat it more like a list of short definitions for the newbie, like most jargon lists I’ve seen. (Certainly it shouldn’t be spread over two pages as it is now, with this page not actually providing any explanations at all.) This should be a single-point info list for n00bs—David Gerard 09:38, 17 April 2011 (UTC)
No objections, so I’ve done this. Do of course feel free to fix any of my quick definitions you don’t like—David Gerard 18:49, 21 April 2011 (UTC)
Hmm, ok. I think both courage and evolution I found more difficult because they’re less well-defined clusters in postspace (compared to self-deception and superstimuli). I’m glad you found the feedback helpful.
I’ve also edited gears-level and spaced repetition. I think they’re probably C and B class respectively, but I’m still very unconfident about that. Gears-level in particular I’m not sure if it might not just be better to point to Gears in Understanding, as it’s pretty well-written and is pointing to an odd (& specific) concept.
Edited the courage tag, think it’s C-class (Not sure if it needs integrating somehow with the groupthink and/or heroic responsibility tags? certainly some things in each of these don’t fit under the others but there is a fair amount of overlap at present)
Edited self-deception & superstimuli, think they’re now C-class (self-deception in particular, I’d like somebody who’s actually read Elephant in the Brain to have a look over it, because it seems relevant but I’m not overly familiar)
Edited evolution and think it’s now B-class
I’d imagine publication bias priors are helpful, especially with increasing specificity of research area, and especially where you can think of any remote possibility for interference.
Just as an example I’m familiar with (note this is probably a somewhat more extreme example than for most research areas due to the state of pharmacological research): If you see 37 RCTs in favour of a given drug, and 3 that find no significant impact (i.e. 93% in favour), it is not unfounded to assume that the trials actually performed are roughly equal in favour and against, and that there may be a missing 34-odd studies.
A 2009 analysis found that this was almost exactly the case (the studies registered were 36:38 in favour of the drug; one positive RCT went missing before publication. Along with twenty-two non-significant studies that were missing altogether, and a further 11 which were so poorly analysed as to appear significant.
(Bad Pharma, by Ben Goldacre, is a pretty sound resource for this topic in general)
I’ve updated the Heuristics and Biases tag again btw. I don’t think it’s A-grade based on “I’d like to see more work done on it”, but I think it’s about as good as I personally am going to be able to get it. I’d really like somebody (yes you, fellow user reading this) to have a read through and make any adjustments that make sense and/or make it more comprehensive.
re: fallacies, I thought about it, and I think they’re actually used pretty similarly, at least here on LW. Planning fallacy could easily be described as a bias generated by an ‘imagine your ideal plan going correctly (and maybe add, say, 10%)’ heuristic. At the very least, there’s plenty overlap. Really what I envisioned for that section was making the point that a heuristic can be good (or just ok), because that was something that I didn’t realise for a long time.
OK. So you see the grading as being more of a “neglected-o-meter” in the sense that it describes the gap between how a tag currently is and how it would be in an ideal world? (i.e. a more important tag would have a higher bar for being A-grade than a less important one?)
I think that makes more sense than an absolute-quality stamp, but I think the tag grading post as is currently written should make that clear (if it is the case)-- currently it implies almost the opposite, at least as I read it. For instance phrases like “It covers a valuable topic” in A-grade, and “tagged posts may not be especially good.” in C-grade. To me these read as “quality/importance of topic and of posts are as important for grading as description”.
I think actually the way you’re describing tags now is more useful (for e.g. directing peoples attention for improving tags), but I’m not sure if it came across that way (to me) in the initial post. I would be interested to hear how other people read it.
This all seems like really helpful advice, so thanks! Multiple-pass reading is something I’ve made previous attempts at but need to find a way to properly remember to implement, especially for longer things (like, say, books).
I generally timebox specialist reading that has a near-term goal—reading for university or for a specific paper. The big problem for me personally is that, as a jobless university student, there is definitely a temptation (worsened by lockdown and summer holidays) to let more generic reading expand until it fills my the spare time in my day with little structure. I think your comment has really helped me highlight that as an issue, so thanks.
Well around half of them are sources I’m currently using to write a paper, and some of the rest I’m reading in preparation for next year of university. But I think I probably could benefit from a little of what you outlined.
I’ve edited the Heuristics and Biases tag. I think it’s probably A-grade (I’m still getting a handle on exactly what an A-grade tag should feel like though, honestly).
That said, I’d like it if somebody could check the specifics of the three definitions, because I’m actually not completely sure, and check that it scans ok.
For sure! I figured the team wouldn’t have missed this, just wanted to give my two cents. For what it’s worth I think the tagging system is actually really nicely implemented already; I feel like a kid in a candy shop with all these posts that were just thoroughly inaccessible to me until now.
I’ve edited the Effective Altruism tag pretty heavily, and I now believe it qualifies as A grade.
I’ve also edited the Epistemic Modesty tag, and think it’s now C or B grade.
I’d also like it if the X-risk and S-risk tags are consistent with one another—I propose that “S-risks (Risk of astronomical suffering)” and “X-risks (Existential risk)” is the best format.
Are there any plans to implement tagging of whole sequences? I understand that tagging the first post in a sequence has a similar effect, but it might be more productive in some instances to have, for instance Slack and The Sabbath as the top link under the slack tag, rather than the individual posts from this sequence appearing in an order based on relevance.
Obviously that then creates issues about whether you want posts that appear in sequences to also appear individually or not, and whether you want all sequences to be taggable or not, and so on. I’m not sure if these issues outweigh the benefits; even just on an admin-only basis, it seems like a helpful feature if we expect a significant user base who don’t read the tag descriptions (the other place it might otherwise make sense to put sequence links).
(Other examples where this seems to me it might be more useful than the current method: Philosophy of language & A Human’s Guide To Words, Group Rationality & The Craft And The Community. I imagine there are more)
This is true, and a mistake on my part (they don’t bother with IFR in medical school, likely because it’s not as relevant for day-to-day medicine as CFR). I’ll update the post to try to explain the difference. Thanks a lot.
To your first point: my intuition is that ACE2 is far too small for the genome to pass through itself. ACE2 is an enzyme that’s bound to the membrane—it actually just cleaves angiotensin 1 to angiotensin 2 (hence ‘angiotensin cleavage enzyme, ACE2). It does pass through the membrane, but it’s not really a ‘channel’—it is simply localised to the cell membrane, and acts on substances extracellularly.
Enveloped viruses can enter cells in many ways (principles of virology chapter 5 is really excellent for this, if you’re interested). It seems that SARS-CoV (the original outbreak) enters cells primarily how it is implied above—simple, direct membrane fusion mediated by the ACE2 receptor. There is some speculation that it may under some circumstances be endocytosed (taken into the cell in a separate sphere of membrane) and then break free of the endosome (the bubble) in a pH-dependent way. Obviously this is further complicated by the fact that this is SARS-CoV-2 that we’re really interested in, so I thought it would be best to leave it blank. You’re right in thinking this process is similar to SER budding, though.
To your second point: I wasn’t actually sure! I’ve done some research, but honestly I’m still not as confident about this as about the rest. As far as I can tell, for most viruses nucleocapsid shedding is either mediated by substances or organelles inside the cytoplasm—ribosomes in particular, apparently, bind to the capsids of some viruses and destabilise them—or is part of the process of receptor binding. Some viruses, for instance, seem to be able to leave their nucleocapsid behind with their envelope so it coats one side of the cell membrane.
Sorry I can’t give a better answer, hope it helps!
What sources are governments using for decision-making?
The biggest impacts seem to me to be via influencing government. The UK government, for instance, is still very reticent to enforce widespread testing or mandatory quarantine. Their ‘quarantine guidance’ for households with symptoms looks like this, which seems patently foolish for a number of reasons.
Influencing governments’ decision making is high-impact and potentially tractable via getting modelling and trial data to them. The UK Government publish their ‘scientific basis for decision making’ but it appears to be weeks out of date and unreferenced.
With that in mind, how do we get better decision-making information into government? What theory of change can we find for influencing policy makers? I believe this should be primarily targeted towards larger organisations and researchers who can have more direct influence, but may be useful for individuals as well.
Primarily or exclusively due to the thread:
Bought a pulse oximeter
Copper tape on phone, laptop hand-rests, and doorknobs and light switches (due to living in shared student accommodation) -- including recommending others do the same; two or three people I know have taken me up on this advice.
Bought, and take daily, vitamin D pills
More careful with packages (treat external packaging as if it is infective)
Gathered enough food/medicine to be able to quarantine and look after self if required
Due to ‘seeing the smoke’ due mainly to LW posts (would likely have done otherwise, but much later)
Came home to my parents to lower risk from being in a city
Properly educated myself on the virus and the outbreak
Self-quarantined, including minimising contact from my parents until 15 days asymptomatic living here