Kristian G. Andersen

Speaking of furin - Bob, your old buddy is on the Virological again and it's a pretty nice theory for how the furin site was acquired in bats - just need to add a little extra divergence and there you have it:http://virological.org/t/tackling-rumors-of-a-suspicious-origin-of-ncov2019/384/3

Slack / Private Message Drop, p.7 · original PDF · in context

Typically SARS-like CoVs are cultured in the presence of trypsin (to allow for cleavage of S1/S2), but if trypsin isn't added, there's a *huge* selection pressure for gaining a furin site.

Slack / Private Message Drop, p.23 · original PDF · in context

The example from bovine CoVs (post #6 on the thread on virological) is exactly a 12bp insertion seen in tissue culture creating a furin cleavage site.3.

Slack / Private Message Drop, p.23 · original PDF · in context

Haven't had time to read this yet, but not quite understanding why I'm not seeing Eddie's name on this... https://advances.sciencemag.org/content/early/2020/05/28/sciadv.abb9153

Slack / Private Message Drop, p.45 · original PDF · in context

And yes, there were (short) delays no doubt - but they were inconsequential in the grand scheme of things (my main issue here is that especially in the US is that people can't uncouple the two - i.e.(1) the delay and (2) the consequences from that delay.

Slack / Private Message Drop, p.49 · original PDF · in context

We KNOW we can't predict these kind of outcomes with _*any*_ certainty so we shouldn't even try - especially not when it comes to something this important.

Slack / Private Message Drop, p.60 · original PDF · in context

One thing is to report basedon tweets (which is wrong), another is doing it when the person isn't a subject-matter expert - I find that really problematic, especially for something this important.

Slack / Private Message Drop, p.62 · original PDF · in context

The furin site in SARS2 is exactly the same as it is in some of the HKU1 sequences.

Slack / Private Message Drop, p.69 · original PDF · in context

People have put furin sites into CoVs previously - here's one example from SARS: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111780/

Slack / Private Message Drop, p.70 · original PDF · in context

Nothing has changed in terms of prior risk of lab accident, but the issue is that we're dealing with the fact that WIV has been doing culturing of bat CoVs for over a decade exactly to understand what it takes for these viruses toemerge in humans (in BSL-2).

Slack / Private Message Drop, p.71 · original PDF · in context

A lot of the GOF work on SARS-like CoVs is also from WIV, although there are also other labs that have been doing that (e.g., Baric).

Slack / Private Message Drop, p.71 · original PDF · in context

> But that work isn't exclusively done at the WIV because as you say yourself the Baric lab are doing it No, that work _is_ exclusively at WIV AFAIK.

Slack / Private Message Drop, p.72 · original PDF · in context

All of this is done in BSL-3, so much (much!) less risk of exposure.

Slack / Private Message Drop, p.72 · original PDF · in context

The work in Shi's lab is different - here they are taking bat CoVs and culturing them under BSL-2 in cell lines from different animals - to e.g., understand which ones can infect human cells and what type of mutations that occur inT/C may make them permissive.

Slack / Private Message Drop, p.72 · original PDF · in context

The little details about the furin site - e.g., that it's exactly in the spot where experiments had previously inserted it,the fact that the exact sequence exist in a cat CoV, Shi herself being sketchy with details and considering lab accident, etc.

Slack / Private Message Drop, p.72 · original PDF · in context

These studies are presented each as independent evidence of the pangolin virus RBD, but if all those papers are relying on a third data set - and don't actually have _any_ data from this very critical CoV RBD, then that's an issue.

Slack / Private Message Drop, p.86 · original PDF · in context

For the last month, I have been feeling like I'm one of these guys: https://en.wikipedia.org/wiki/Musicians_of_the_RMS_Titanic

Slack / Private Message Drop, p.87 · original PDF · in context

And yeah - looks like 1977 was a vaccine trial, which is pretty crazy.

Slack / Private Message Drop, p.101 · original PDF · in context

Yeah, everything is basically D614G by now, so that's kinda the virus we need to make sure the vaccine works against - but I'm not really concerned there's a difference between Doug and Dougless here.

Slack / Private Message Drop, p.104 · original PDF · in context

We should alert themto the problem, make it clear that they have divulged private and confidential information from the review process (and implicated high-ranking US officials) in a factually wrong narrative about a scientific study on a sensitive subject.

Slack / Private Message Drop, p.117 · original PDF · in context

We believe that RB is either Reviewer 2 of our paper, or Reviewer 2shared confidential information with RB.

Slack / Private Message Drop, p.119 · original PDF · in context

It's the second time I have noticed him being a complete arse - the other time was amplifying that idiotic WaPo WIV story.

Slack / Private Message Drop, p.128 · original PDF · in context

@Eddie Holmes Mostly, I'm just a little confused - because these are big and important questions so we all know that we need to be really careful what we say (especially because of a few prior misfires).

Slack / Private Message Drop, p.136 · original PDF · in context

Iagree it was mysterious - really mysterious - but then some pangolin viruses came around and mystery solved.Clearly not Bayesians.

Slack / Private Message Drop, p.140 · original PDF · in context

Yeah, I thought it was a pretty interesting article - especially the title.

Slack / Private Message Drop, p.145 · original PDF · in context

We need to know frequency and time dependency before we can say *anything* about immunity/vaccines).

Slack / Private Message Drop, p.147 · original PDF · in context

Bob and I are now officially in the same 'Family' as the Grand Wizard of EgoHealth.

Slack / Private Message Drop, p.148 · original PDF · in context

That's the key here - that mouse model is using the human ACE2 receptor, so it'd be a perfect fit - plus the acquisition of furin sites during rapid passage as we discussed in the paper (as is seen for flu).

Slack / Private Message Drop, p.149 · original PDF · in context

Trump going to force through an EUA for _any_ vaccine by end of October is going to be the biggest - and by far most consequential - mistake America will do when it comes to COVID-19.

Slack / Private Message Drop, p.154 · original PDF · in context

The main risk here is that with the EUA, some would demand the vaccine and it'd sideline the clinical trials, causing very significant delays for the development of_actual_ safe and efficacious vaccines.

Slack / Private Message Drop, p.155 · original PDF · in context

Especially the latter point is important when we think about vaccine escape since big and consequential genomic rearrangements can happen really quickly.

Slack / Private Message Drop, p.160 · original PDF · in context

I'm hopeful vaccines will be able to get us to where we need to be immunity wise, just not so sure about natural immunity and how long-lasting it is - but even if it isn't, there's still no doubt that it's already helping to drive down cases in at-risk areas.

Slack / Private Message Drop, p.162 · original PDF · in context

Proposing that all the bat and pangolin sequences are fraudulent and hence SARS-CoV-2 is a lab construct is - well, absurd.

Slack / Private Message Drop, p.163 · original PDF · in context

They put a restriction site INSIDE the furin site so they can follow the viruses over time - it's all very clever.

Slack / Private Message Drop, p.168 · original PDF · in context

I'm not even going to go there - I have no concerns about the bat or pangolin data so simply ignoring all of that is just dumb (well, that data invalidates their findings, so of course, I get it).

Slack / Private Message Drop, p.171 · original PDF · in context

I haven't looked at the pangolin data - I'm not quite sure where the raw data is since I believe it was all uploaded tothe Chinese data portals.

Slack / Private Message Drop, p.178 · original PDF · in context

Only need to assemble one of the remaining pangolin CoVs, which has a huge dataset.

Slack / Private Message Drop, p.184 · original PDF · in context

E.g., they mention that SARS1 has a furin cleavage site in the spike - that's clearly not true and suggestive of them not looking very closely at the literature.

Slack / Private Message Drop, p.189 · original PDF · in context

Presumably though, if these reads are real surely they must be contamination from other sequencing experiments at WIV.

Slack / Private Message Drop, p.197 · original PDF · in context

> Zhang has now been booted out of China CDC and is now full-time in Shanghai.

Slack / Private Message Drop, p.201 · original PDF · in context

The concern here is that we know that type of work was going on at WIV (the EgoHealth stuff), so we certainly can't dismiss it based on this.

Slack / Private Message Drop, p.208 · original PDF · in context

Alina is talking about the pangolin sequences where there's overlap in the data used - as described in Eddie's paper.

Slack / Private Message Drop, p.228 · original PDF · in context

So if those BioSamples were created on, say 12/25, then that's totally what you'd expect - but we're talking two weeks before there was any (official) realization of a novel coronavirus.

Slack / Private Message Drop, p.242 · original PDF · in context

(and one pretty critical thing against the bonkers theories in the paper - wouldn't WIV have been mentioned in theBioSample had the virus come from there....? :man-shrugging:)

Slack / Private Message Drop, p.245 · original PDF · in context

I have a TON of DK reporters asking about this, but haven't found anything official.

Slack / Private Message Drop, p.251 · original PDF · in context

Yup, I have been hearing you saying this for years - for Ebola too.

Slack / Private Message Drop, p.260 · original PDF · in context

As for sterilizing immunity - the animal trials for both the J&J and RNA vaccines were promising on this aspect -the Oxford vaccine, not at all.

Slack / Private Message Drop, p.293 · original PDF · in context

Yeah, clearly a lot more cases going around at that time than was appreciated - and obviously not (directly) linked tothe seafood market.

Slack / Private Message Drop, p.301 · original PDF · in context

Totally agree Bob - we have no idea which epitopes are protective and we don't know if e.g., the different vaccines cover the same epitopes.

Slack / Private Message Drop, p.331 · original PDF · in context

I can't quite figure out if pangolin actually assigned it to that lineage - the question was asked earlier, but no reply yet

Slack / Private Message Drop, p.332 · original PDF · in context

Interesting difference between SC1 and SC2 is that it was pretty darn quick in the former - essentially happened right after the jump from intermediate hosts.

Slack / Private Message Drop, p.339 · original PDF · in context

I'm glad Alina is such a great expert on so many important topics - whether it be lab leak detection or whether people should sample from bats or not.

Slack / Private Message Drop, p.358 · original PDF · in context

@Andrew Rambaut I assume - bloody hope! - Pfizer and Moderna already have these cloned and in animals...

Slack / Private Message Drop, p.366 · original PDF · in context

@Andrew Rambaut I hope they're correct that the vaccines will work just fine - I'm certainly less confident making such statements and unwilling to speculate until I have seen some of the UK neut data.

Slack / Private Message Drop, p.367 · original PDF · in context

The vaccines are not going to be distributed in time - not by a long shot

Slack / Private Message Drop, p.373 · original PDF · in context

I'm hopeful that the mRNA vaccines with two doses will provide (near) sterilizing immunity.

Slack / Private Message Drop, p.377 · original PDF · in context

Separately, two vaccine failures en route to our lab - I sure as shit hope these are not B117!

Slack / Private Message Drop, p.399 · original PDF · in context

We have a bunch inbound from Jordan too, but those are failures from one of the Chinese vaccines.

Slack / Private Message Drop, p.400 · original PDF · in context

We also wouldn't see the same from other vaccines - because, again, more complex.I don't know if this holds up...

Slack / Private Message Drop, p.400 · original PDF · in context

I don't know man - enquire about the excellent honorarium first...

Slack / Private Message Drop, p.405 · original PDF · in context

I mean, that post has more views than our Proximal Origin post....

Slack / Private Message Drop, p.407 · original PDF · in context

Definitely too early with L452R and I'm annoyed that they put out a press release with no data and before we could actually get a close look at what's going on.The concern I have is that they mentioned this was found in three skilled nursing facility outbreaks with 100% attack rates - if true, then absolutely concerning, but I don't know how good the data is.

Slack / Private Message Drop, p.414 · original PDF · in context

Eeek will for sure be worse and cross the 4x threshold (I believe) is being used in the flu field to trigger avaccine update.

Slack / Private Message Drop, p.415 · original PDF · in context

However, what's going to be very different here is that we're going to have a gazillion different (partially) vaccine 'resistant' lineages floating around atthe same time because we have sooooo many infections.

Slack / Private Message Drop, p.415 · original PDF · in context

And the model still has to be to drive down transmissions as low as possible - primarily with NPIs, with vaccines also coming in helpful (but the current view is that the vaccines will come in anddo it all - I doubt it).

Slack / Private Message Drop, p.418 · original PDF · in context

@Kristian Andersen Yes - although I prefer the initial drop of R<1 is done by NPIs first, followed by vaccination -not attempt to do the other way around.

Slack / Private Message Drop, p.419 · original PDF · in context

There is little doubt in my mind we'll have to update the vaccine.

Slack / Private Message Drop, p.456 · original PDF · in context

The Moderna paper yesterday (which looks more promising) they literally took the serum at the very peak (a week after the booster) so the data would look better.

Slack / Private Message Drop, p.456 · original PDF · in context

In any case - it sounds like Moderna is already working on an updated design, so that's the right thing to do - I just hope that work gets fast-tracked.

Slack / Private Message Drop, p.456 · original PDF · in context

I don't think most people understand exactly how problematic that is - including vaccine makers and immunologists.

Slack / Private Message Drop, p.462 · original PDF · in context

This is pretty nuts - AZN/Oxford vaccine totally killed by B.1.351.

Slack / Private Message Drop, p.495 · original PDF · in context

It's just a shit vaccine - I'm sure the others won't see this bad a drop (and we have _some_ data on that) and will also prevent severe disease in many cases.

Slack / Private Message Drop, p.495 · original PDF · in context

Fact is, in six months, that vaccine will be totally irrelevant.

Slack / Private Message Drop, p.496 · original PDF · in context

Pretty key data from Tulio - people infected with B.1.351 have neutralizing activity (at similar levels to non-B.1.351) against B.1.351 and non-B.1.351.Bodes well for vaccine updates. [shared file(s): Screen Shot 2021-02-17 at 11.00.59.png]

Slack / Private Message Drop, p.520 · original PDF · in context

I have little doubt that the virus will escape our vaccines relatively quickly, meaning we will still continue to see cases - there's no herd immunity here.

Slack / Private Message Drop, p.531 · original PDF · in context

That scenario may seem like doom, however, it's possible that via vaccination and (re)infections there will beenough immunity to protect against severe disease.

Slack / Private Message Drop, p.531 · original PDF · in context

it's nicely spotted, since it's the only mutation unique to SC2 in the RBD - we should have picked this up earlier.

Slack / Private Message Drop, p.536 · original PDF · in context

Mink farming is typically also associated with other farming - creating risks of further epizootics.

Slack / Private Message Drop, p.539 · original PDF · in context

One question to the FOIA though - I _do_ think we need to make the reviews public as the emails make the Nature connection clear.

Slack / Private Message Drop, p.547 · original PDF · in context

It's unbelievable how dumb some US politicians are - even the very very very basic facts of what GOF is, they didn't bother to check.

Slack / Private Message Drop, p.551 · original PDF · in context

I'm interested to see what happens when P.1 / B.1.351 hit London and battle it out with B.1.1.7 - especially as vaccine coverage is going up.

Slack / Private Message Drop, p.553 · original PDF · in context

I read this channel and see (1) a rat looking thingie rolled up in a bamboo stick, and (2) socks with a furin cleavage site on them - made in China.We have come a long way since we started this channel, gentlemen.

Slack / Private Message Drop, p.599 · original PDF · in context

Twitter is on fire with scientists pushing for the lab leak theory too.

Slack / Private Message Drop, p.615 · original PDF · in context

Civil - but a lot of the stuff he discussed about the WIV research was naive (e.g., not realizing that pseudotyped viruses don't constitute a risk, not knowing many of these viruses are replication incompetent, etc.).

Slack / Private Message Drop, p.616 · original PDF · in context

That one is an inactivated vaccine so if that has 2P, then definitely lab leak!

Slack / Private Message Drop, p.618 · original PDF · in context

Yes, as we said, we considereda lab leak a very real and serious possibility, no, that does not change our conclusions [add new stuff from WHO report].

Slack / Private Message Drop, p.620 · original PDF · in context

He really is - and I mean, a PhD student teaching one of the most prominent statisticians (at Harvard...) the basicsof statistics is pretty, well, ballsy.

Slack / Private Message Drop, p.623 · original PDF · in context

The combo of being anti-lab leak, spot on when it comes to the science, while also playing bluegrass and being fromFort Worth, Texas, I don't know man...

Slack / Private Message Drop, p.625 · original PDF · in context

Beijing is simply not interested in allowing us to find the answers to those very pertinentquestions._

Slack / Private Message Drop, p.651 · original PDF · in context

This figure from the report is pretty interesting - breeding of putative intermediate hosts all around Wuhan. [shared file(s): Screen Shot 2021-03-29 at 7.50.43 PM.png]

Slack / Private Message Drop, p.656 · original PDF · in context

That line that bisects the cluster is the main river - WIV is South-East of that river, Huanan market North-West

Slack / Private Message Drop, p.657 · original PDF · in context

Yeah, I get the sense that the Chinese are trying to deflect as much as possible away from the market, not being concerned with the lab leak because they know it didn't come from there.

Slack / Private Message Drop, p.657 · original PDF · in context

All the cases south of the river are unrelated to the market - but in university housing around WIV as far as I can see.

Slack / Private Message Drop, p.658 · original PDF · in context

See how this starts North (right where Huanan market is) of the Yangtze river and then moves South (where WIV) is.This is exactly the same pattern we see from the confirmed case data.

Slack / Private Message Drop, p.662 · original PDF · in context

And in terms of contaminants - many of these show up frequently, especially things like the Human mastadenoviruses

Slack / Private Message Drop, p.676 · original PDF · in context

I'm pretty convinced the obfuscation has to do with this though - they could care less about a lab leak, but if this is aresult of wildlife farming and borderline illegal activities, then that's a problem domestically and internationally.

Slack / Private Message Drop, p.680 · original PDF · in context

This is not going to end well for George... https://www.washingtonpost.com/world/asia_pacific/china-vaccine-efficacy-not-high-gao/2021/04/11/dafe3ab6-9a8f-11eb-8f0a-3384cf4fb399_story.html

Slack / Private Message Drop, p.692 · original PDF · in context

Finally had some time to read the pangolin paper in Frontiers.

Slack / Private Message Drop, p.696 · original PDF · in context

I have an unhealthy habit of refreshing the epi curve from Israel, which has been a huge success for vaccines.

Slack / Private Message Drop, p.707 · original PDF · in context

I love to think of the Grand Wizard and myself as the Natural Origin Police.

Slack / Private Message Drop, p.713 · original PDF · in context

Suuuuuure._"Step two is something like Operation Warp Speed for the pandemics of the future.

Slack / Private Message Drop, p.732 · original PDF · in context

With the crop ofvaccines in India and B.1.617 I'm concerned, but I don't really know what to make of it - people are _much_ too quick to dismiss both the variant and breakthroughs though (with no data).

Slack / Private Message Drop, p.739 · original PDF · in context

For those tinfoil hats saying we never seriously considered a lab leak, I just found this old beauty from May of last year...

Slack / Private Message Drop, p.748 · original PDF · in context

Now, put that CCP award next to it and we have a perfect setup.

Slack / Private Message Drop, p.756 · original PDF · in context

The PHE names are indeed bad - I always have to cross-reference back to the table also displaying the pangolin names (but as you say, we need to label constellations, not necessarily lineages).

Slack / Private Message Drop, p.761 · original PDF · in context

All the data we have so far supports a natural origin - the only one missing is the intermediate host.

Slack / Private Message Drop, p.770 · original PDF · in context

The authors are correct that both hypotheses are possible, but current evidence points to a natural origin for SARS-CoV-2, as the WHO and others have concluded._ _Unfortunately, the letter suggests a false equivalence between the lab escape and natural origin scenarios.

Slack / Private Message Drop, p.782 · original PDF · in context

To this day, no credible evidence has been presented to support the lab leak hypothesis, which remains grounded inspeculation.

Slack / Private Message Drop, p.782 · original PDF · in context

Appreciate Mike reaching out though - I'm pretty darn sure he must have been the one telling the others that that was going to be necessary.

Slack / Private Message Drop, p.782 · original PDF · in context

Very interestingly, I talked to Jon earlier today (more on that later) and he mentioned that in the very early days of HIV, Mike was convinced that it came from the polio vaccine - i.e., lab derived...https://en.wikipedia.org/wiki/Oral_polio_vaccine_AIDS_hypothesis

Slack / Private Message Drop, p.782 · original PDF · in context

Making demands for investigations and data that are clearly outside the mandate, power, or resources of the WHO - instead of supporting work already in progress - will necessarily make it even harder to support future joint missions to perform thecritically important task of uncovering what led to the emergence of SARS-CoV-2.

Slack / Private Message Drop, p.785 · original PDF · in context

I'm pretty certain this letter is going to look especially dumb about a year from now.

Slack / Private Message Drop, p.789 · original PDF · in context

The only thing we're missing is an intermediate host - that may or may exist - or even existed.

Slack / Private Message Drop, p.791 · original PDF · in context

Now, we have never tested any of the COVID-19 vaccines in a scenario where we're fully back to normal, spending a ton of time indoors with a lot of other people - e.g., a big office full of people talking all day...

Slack / Private Message Drop, p.808 · original PDF · in context

I can guarantee you that if H1N1 had been worse, the lab leak theory of its origin would also not have gone away.

Slack / Private Message Drop, p.818 · original PDF · in context

One bat virus spike protein into a BAC clone of another bat virus - AND the paper even shows those viruses don't infect cells better thanwildtype.

Slack / Private Message Drop, p.821 · original PDF · in context

Yup, we'll see relief in the short term and vaccination can definitely be the end game - however, only if we think about this as being a global problem and not a national one.

Slack / Private Message Drop, p.823 · original PDF · in context

I also think we're seeing _some_ evidence for post vaccination infections in clusters - i.e., super spreading.

Slack / Private Message Drop, p.823 · original PDF · in context

(Although I don't know what the hell is up in the Seychelles - example of a lot of unvaccinatedpeople coming in, followed by high levels of social interactions, with a lot of post vaccination infections.

Slack / Private Message Drop, p.823 · original PDF · in context

Also - remember to mention the solution being vaccination as you suggested - will help combatstigma.

Slack / Private Message Drop, p.839 · original PDF · in context