Edward C. Holmes

Coronavirus US live: intelligence report concludes Covid-19 was not 'manmade or genetically modified' https://www.theguardian.com/world/live/2020/apr/30/coronavirus-us-live-federal-guidelines-social-distancing-expire-trump-cuomo-latest-news-updates?CMP=share_btn_tw&page=with:block-5eab41b68f08f76ffc19f175#block-5eab41b68f08f76ffc19f175

Slack / Private Message Drop, p.2 · original PDF · in context

D614 was associated with a huge epidemic in China that was only controlled through a severe lockdown and don't see any difference in G614.

Slack / Private Message Drop, p.2 · original PDF · in context

That must come from an email that I sent to my press officer who then forwarded to them.

Slack / Private Message Drop, p.5 · original PDF · in context

Reads to me that are pissed off that they were not involved inour paper and so want to get in on the act.

Slack / Private Message Drop, p.5 · original PDF · in context

The Telegraph claim that the WIV deleted files etc.

Slack / Private Message Drop, p.16 · original PDF · in context

I think they missed a brilliant opportunity to use pangolins instead.

Slack / Private Message Drop, p.19 · original PDF · in context

On the debit side I was just sent another (long) piece of conspiracy theory BS: https://medium.com/@yurideigin/labmade-cov2-genealogy-through-the-lens-of-gain-of-function-research-f96dd7413748

Slack / Private Message Drop, p.19 · original PDF · in context

Completely agree about the pangolin RBD.

Slack / Private Message Drop, p.30 · original PDF · in context

Although CGTN is a propaganda organ for the Chinese government, what she said rang true to me.

Slack / Private Message Drop, p.36 · original PDF · in context

There's a mountain of chatter about the pneumonia cases in Wuhan back in December before the disease was officially reported, but there is nothing about the lab.

Slack / Private Message Drop, p.37 · original PDF · in context

Here are the talking points they sent to the journos.

Slack / Private Message Drop, p.48 · original PDF · in context

The last 2 in the natural origins bit have got nothing to do with his paper at all. [shared file(s): Talking points Latinne et al.

Slack / Private Message Drop, p.48 · original PDF · in context

NO country would have imposed a lockdown faster than China.

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

The mistake - which was understandable - is that they (China) assumed that was SARS and hence would be relatively easy to contain as they just had to quarantine the symptomatic cases.

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

"Henceforth, those who would maintain that the Covid-19 pandemic arose from zoonotic transfer need to explain precisely why this more parsimonious account is wrong before asserting that their evidence is persuasive, most especially when, as we also show, there are puzzling errors in their use of evidence." Is this us?

Slack / Private Message Drop, p.51 · original PDF · in context

"To remedy the problem, the researchers are developing their own vaccine, produced by Immunor AS, a Norwegian pharmaceutical company led by Mr Sorensen".

Slack / Private Message Drop, p.51 · original PDF · in context

Could it explain why the furin site is sometimes lost in cell culture?

Slack / Private Message Drop, p.57 · original PDF · in context

Plenty of reasons why traffic could have increased: perhaps they had a special offer at the wet market?

Slack / Private Message Drop, p.64 · original PDF · in context

I was reading Mike's paper to suggest that D614G was under selection to increase the infectivity of SARS-CoV-2, because it was directly related to the furin cleavage insertion, such that it not perfectly adapted to humans on emergence.

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

I'm really struggling to understand why someone would "put" a furin site into a random bat virus they had not previously sequenced and published.

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

My take is that furin cleavage sites are *everywhere* in natural viruses e.g.

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

Also, the Zhou et al. paper never call it a furin cleavage site insertion and I think the alignment in that paper is the optimal one.

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

I also think that focusing on these genetic details - which are not conclusive - is in danger of missing the bigger picture: that bats (and like other wildlife) carry a huge diversity of coronaviruses some of which are closely related toSARS-CoV-2; that coronaviruses link species boundaries all the time; that 4 other CoVs have emerged in humans inthe last 20 years; that furin cleavage sites are common in viruses and come and go all the time; that people have been warning about emerging CoVs for years.

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.

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

I think the bats not roosting in winter argument is nothing because I reckon it went through an intermediate host anyway.

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

Are you saying they deliberately inserted the furin cleavage site?

Slack / Private Message Drop, p.73 · original PDF · in context

Strictly confidentially, I literally (2 mins ago) just got an email that says: "Recently, we isolated a pangolin-Cov that ishighly related with SARS-CoV-2 (https://www.nature.com/articles/s41586-020-2313-x).

Slack / Private Message Drop, p.73 · original PDF · in context

We further found that the infected pangolins showed similar CT scans with COVID-19 patients (please see the attachment, a and b are virus-positive pangolins, while c is virus-negative).

Slack / Private Message Drop, p.73 · original PDF · in context

No one gives a shit and now we are seeing loads of pangolins with frothy lungs.

Slack / Private Message Drop, p.74 · original PDF · in context

Notable that HKU1 does have a furin cleavage site but NL63 doesn't.

Slack / Private Message Drop, p.74 · original PDF · in context

Sorry to keep going, but HKU1 is really interesting in this context: (i) has an furin cleavage site (RRKRR) in the right spot; (ii) causes human and has spread (it turned up in Australia; (iii) betacoronavirus; (iv) closest relative is MHV but that is way distant.

Slack / Private Message Drop, p.74 · original PDF · in context

I hear there may be more pangolin viruses.

Slack / Private Message Drop, p.75 · original PDF · in context

I was worried about conclusion being made on whether people use/don't use face masks.

Slack / Private Message Drop, p.75 · original PDF · in context

Oh, I don't disagree with the conclusion at all (I completely agree that face masks are hugely important), but the analysis is dire.

Slack / Private Message Drop, p.75 · original PDF · in context

A pangolin is the obvious animal you'd have in the lab.

Slack / Private Message Drop, p.76 · original PDF · in context

Also, many of the points are stupid/wrong: (i) why anyone would have a pangolin virus in the lab is beyond me and obviously idiotic.

Slack / Private Message Drop, p.76 · original PDF · in context

That Viruses paper on the pangolin virus, which does not even describe the sequence, was published online in Oct. 24th 2019.

Slack / Private Message Drop, p.76 · original PDF · in context

It's obviously not credible tohave read this, got the pangolins and the viruses and done the leaky experiments in this timeline; (ii) the WIV is not the only lab with closely related bat viruses - obviously RmYN02 comes from a different lab; (iii) I don't see that 4amino acid insertion and no flanking changes is at all problematic, particularly as these insertions are so commone.g. in H7N7 AIV the sequence went from PEIPKGR (low path) to PEIP*KRRR*R (high path).

Slack / Private Message Drop, p.76 · original PDF · in context

Alas, the involvement of WHO will upset some people but Idon't know what else is feasible; (iii) to me, the pangolin story is crucial: the RBD looked 'anomalous' but then a littleof sampling of an animal what we would never have expected found it was there in nature; (iv) yes, there are some new data points but it is also very clear that we really need better sample of nature to sort this out.

Slack / Private Message Drop, p.78 · original PDF · in context

Doubtless there will be more bat viruses out there that fill in key positions, but if random animals like pangolins are in the mix (and these were smuggled into China from elsewhere) only god or George Gao knows what else is out there.

Slack / Private Message Drop, p.78 · original PDF · in context

In basements all over the world people will be looking at Google Maps and drawing straight lines between the fish market and the China CDC head office in Beijing.

Slack / Private Message Drop, p.82 · original PDF · in context

Had a quick look...if Alina is suggesting that the pangolin RBD came from humans she's totally mad (look at the synonymous diversity). 100% clear that that RBD is out there in nature.

Slack / Private Message Drop, p.85 · original PDF · in context

The two pangolin papers in Nature (different groups) both show the same RBD in the animals from Guangdong.

Slack / Private Message Drop, p.85 · original PDF · in context

But the pangolin sequence is only 'highly identical' at the amino acid level.

Slack / Private Message Drop, p.85 · original PDF · in context

I've just emailed Tommy if he can assemble the same RBD without the Liu et al. data and/or if it has been Sanger sequenced.

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

I've also asked if they can assemble the same RBD without the Liu et al. data and/or if it has been Sanger sequenced.

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

The similarity between the RBD and the Guangdong pangolins from the Liu et al. study alone was noted on Virological in late January.

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

How can Liu et al. have possibly known what the human RBD would have looked like? https://virological.org/t/ncov-2019-spike-protein-receptor-binding-domain-shares-high-amino-acid-identity-with-a-coronavirus-recovered-from-a-pangolin-viral-metagenomic-dataset/362

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

GD/1/2019 (Xiao), which is assembly from NGS SRA data of their pangolin samples, plus confirmation with PCR amplicon sequencing (Sanger/NGS unknown). 4.

Slack / Private Message Drop, p.88 · original PDF · in context

Their RDBs are all highly similar (almost identical), and so I think this somehow proves that this RBD sequence is real.

Slack / Private Message Drop, p.88 · original PDF · in context

Yes, as you said, some other papers are very nasty, they just down the pangolin sequences from GISAID and do some analysis and published, and without mentioning the source or citing the original papers.

Slack / Private Message Drop, p.88 · original PDF · in context

And if we except that it suggests that the WIV do not have other bat viruses that could have led to SARS-CoV-2 through experimental manipulation.

Slack / Private Message Drop, p.94 · original PDF · in context

As I said above, all this suggests to me is that the only interesting virus they have at the WIV is RaTG13 and not another that they were secretly working on that gave riseto SARS-CoV-2.

Slack / Private Message Drop, p.95 · original PDF · in context

Completely stupid comments about the Guangdong pangolin CoV...that it may have come from humans.

Slack / Private Message Drop, p.100 · original PDF · in context

Also, there is not one Guangdong pangolin CoV.

Slack / Private Message Drop, p.100 · original PDF · in context

She also completely forgets thatt the Guangxi pangolin CoV is also closely related to SARS-CoV-2.

Slack / Private Message Drop, p.100 · original PDF · in context

I didn't realise until the other day that the 1977 H1N1 outbreak was *not* a lab escape but a shonkyvaccine trial.

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

Like this (paywalled, but the by-line says it all): https://www.telegraph.co.uk/news/2020/06/27/lockdown-social-distancing-could-make-immune-system-weaker-says/

Slack / Private Message Drop, p.108 · original PDF · in context

Feb 9 from Jeremy, sent to all "We now have (and we will get more) the pangolin data (Eddie has) we think we cantie this up even tighter with the next iteration and make a conclusive statement which will then be the go to scientific statement to refer to.Eddie and I have just come off a call with the National Academy of Medicine in the US - who the White House has asked to produce a report on this...."

Slack / Private Message Drop, p.111 · original PDF · in context

In addition, they completely fail to note that it was Clare that suggested Nature Medicine!!

Slack / Private Message Drop, p.113 · original PDF · in context

Kristian contacts me to say that he has spotted some strange things in the issue - specifically the furin cleavage site and restriction sites - that we was concerned about.

Baric Transcribed Interview (Redacted), p.149 · original PDF · in context

In early Feb we had spotted some features in the SARS-CoV-2 genome that at the time appeared unusual - particularly the furin cleavage site and the receptor binding domain. 2.

Baric Transcribed Interview (Redacted), p.149 · original PDF · in context

It is worth pointing out that the senior author on our paper - Bob Garry - has published a significant number of papers on coronaviruses, including on the SARS spike protein, and even commented on this on the virological.org website prior to the call taking place (https://virological.org/t/analysis-ofwuhan-coronavirus-deja-vu/357).

Baric Transcribed Interview (Redacted), p.149 · original PDF · in context

Importantly, our study was an evolutionary study based on genomic information, which is the only way to investigate the origins of SARS-CoV-2 - we believe all the authors on our paper have a strong demonstrated record in answering exactly those types of questions for a multitude of viruses. 3.

Baric Transcribed Interview (Redacted), p.149 · original PDF · in context

We have attached our first draft of what would eventually become our paper from Feb 7, which was circulated to everyone on the call.

Baric Transcribed Interview (Redacted), p.149 · original PDF · in context

This was critical and as Eddie wrote in an email to everyone on the call on Feb 9th: "Personally, with the pangolin virus possessing 6/6 key sites in the receptor binding domain, I am in favour of the natural evolution theory." and Rndrew Rambaut replied to this stating: "I am of the view that the natural selection hypothesis is the most likely (specifically the non-bat reservoir).

Baric Transcribed Interview (Redacted), p.149 · original PDF · in context

The truth is that we had a range of views among us, our paper included the pangolin data that was not available at the time of the call, and we circulated drafts of our document to everyone. 7.

Baric Transcribed Interview (Redacted), p.149 · original PDF · in context

Indeed, the great irony is that 99.9% of the feedback we have received on our paper - including death threats - are people accusing us of dismissing the lab escape theory too quickly.

Baric Transcribed Interview (Redacted), p.149 · original PDF · in context

We have all the documentation to back up what happened and he'd look like a total knob for trying to suppress discussion of lab origins.

Slack / Private Message Drop, p.115 · original PDF · in context

The email makes several serious allegations, including details about a confidential and private meeting involving senior US andUK officials/scientists on a topic that is highly sensitive but ultimately led to our "Proximal Origins" paper that wesubmitted to Nature some months ago.

Slack / Private Message Drop, p.120 · original PDF · in context

Clearly, individual B is either Reviewer 2 of our paper, or Reviewer 2 shared confidential information with them.

Slack / Private Message Drop, p.120 · original PDF · in context

It does not appear that individual B knew that you discussed the paper directly with Nature Medicine, nor does it appear that the person knew who the handling editor was at that journal (Joao).We are very sorry to have to bring this to your attention, but given how serious a matter this is, we feel we have nochoice as our scientific reputations are being judged.Please let us know if you have any questions.

Slack / Private Message Drop, p.120 · original PDF · in context

The story here is that the outbreak in Victoria was due to an escape from hotel quarantine from return travellers.There's even an inquiry going on that the moment.

Slack / Private Message Drop, p.134 · original PDF · in context

But the hotel quarantine thing is huge in Australia.

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

I think the one from the Wuhan Institute of Virology has a leak.

Slack / Private Message Drop, p.139 · original PDF · in context

In other news I think he's confused Bart for Homer: https://www.newyorker.com/magazine/2020/08/31/did-pangolins-start-the-coronavirus-pandemic

Slack / Private Message Drop, p.144 · original PDF · in context

She seems to seriously think that humans gave a SARS-CoV-2-like virus to pangolins....which obviously raises more questions than it resolves.

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

Just had my first freedom of information journo request....

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

Apparently, the Wuhan Institute of Virology were manipulating sun spots in the lab.

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

HKU-1) more often have furin sites and seem to be more often rodent associated.

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

True, but I don't see how a passage in a mouse model would produce a virus so well adapted to humans and with that RBD.

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

Fair point about ACE2, but the RBD is very different to SARS-CoV.

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

To me, if the furin cleavage site is active in cell culture then it is also likely to be active in evolution.

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

Perhaps, but the official numbers from China are clearly large underestimates.

Slack / Private Message Drop, p.152 · original PDF · in context

My original statement on the vaccines said: "SARS-CoV-2 is in the evolutionary slow lane for an RNA virus.

Slack / Private Message Drop, p.161 · original PDF · in context

This is good news because it means that the virus will find it just a bit harder to 'escape' from any future vaccines or antiviral drugs if and when they are developed".

Slack / Private Message Drop, p.161 · original PDF · in context

The accusations at the end that RmYN02 and the pangolin sequences are fraudulent seems like defamation to me (and I'm on these papers).

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

Let me make this very clear: the Guangdong pangolin viruses have been sequenced multiple times by multiple groups.

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

Plus there are Pangolins from Guangxi that have been sequenced.

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

There is nothing wrong with the pangolin sequences.

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

Inspector Clouseau's argument is that Guangdong pangolins are a single outbreak - and she's right about that - and then she seems to think that Guangdong pangolins may have gotten their viruses from humans which is just crazy.

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

She also persistently claims that all the pangolin sequences were all derived from the one in the Viruses paper (pre-pandemic of course) which is untrue: there's aseparate assembly in Tommy's paper.

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

The pangolin viruses were Sanger sequenced here and this paper clearly shows that these animals are sick: https://www.biorxiv.org/content/10.1101/2020.06.22.164442v1

Slack / Private Message Drop, p.179 · original PDF · in context

The pangolin viruses from the Viruses paper were first assembled in that Virological post.

Slack / Private Message Drop, p.179 · original PDF · in context

But fucking Alina has managed to sow doubt by linking it to those dodgy pangolin papers.

Slack / Private Message Drop, p.179 · original PDF · in context

On that subject the following..."Are mouse and cat the missing link in the COVID-19 outbreaks in seafood markets?"...has just come up on bioRxiv.

Slack / Private Message Drop, p.179 · original PDF · in context

I thought it was 'Taming of the Pangolin'.

Slack / Private Message Drop, p.181 · original PDF · in context

Those furin cleavage sites are definitely out there in nature.

Slack / Private Message Drop, p.186 · original PDF · in context

I've also passed it onto the state health officials who ought to know about the dangerous misinformation that's going around.

Slack / Private Message Drop, p.192 · original PDF · in context

They are not really thinking lab origins, more the wildlife trade/wet market angle.

Slack / Private Message Drop, p.194 · original PDF · in context

Notable that Rhinolophus sinicus bats are in Hubei and have a range of ACE2 receptors. [shared file(s): Journal of Virology-2020-Guo-e00902-20.full.pdf]

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

That's the original sequencing report from mid-late December where the commercial company first found reads for 'SARS'.

Slack / Private Message Drop, p.200 · 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

This chat was all over social media in China.

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

And yet there is no chat about nothing from WIV.

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

That cleavage site paper is really interesting...a key point is that the polybasic insertion is selected against in Vero cells: that journalist from the NYT (Nicholas Wade) was trying to argue with me that passage in Vero cells was a way that the polybasic insertion could occur...clearly the conspiracy theorists have been discussing this.

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

@Kristian Andersen Do you believe the data that "bat SARSr-CoV RBDs showed a higher binding affinity to human ACE2 than to R. sinicus ACE2s".

Slack / Private Message Drop, p.212 · original PDF · in context

Dear Edwards, It would be appreciated if you would help me with the following questions on viral evolution.

Slack / Private Message Drop, p.220 · original PDF · in context

Any suggestion and comment on this is appreciated.Sincerely yoursHassan

Slack / Private Message Drop, p.220 · original PDF · in context

With that in mind, I wantedto reach out to see if you had any suggestions of recent graduates, post-docs, or other colleagues who has strong background in genomics, bioinformatics and virus evolution analysis that might be interested these opportunities.We greatly appreciate your help.

Slack / Private Message Drop, p.222 · original PDF · in context

Or was God in on what was happening at the WIV?

Slack / Private Message Drop, p.223 · original PDF · in context

In this paper they clear show the pangolins are sick and they Sanger sequenced the spike protein.

Slack / Private Message Drop, p.230 · original PDF · in context

I don't see anything nefarious in here at all (how the fuck can you fake the CT scanof a pangolin lung - Tippex?).

Slack / Private Message Drop, p.230 · original PDF · in context

The paper got decent reviews at Nature Microbiology but the Chinese authorities are not letting them publish it because of the loss of face the first time around.

Slack / Private Message Drop, p.230 · original PDF · in context

Chan has used Twitter to make increasingly strong claims about the origin of SARS-CoV-2, in particular that it may be of lab rather than natural origin.Of course, Dr.

Slack / Private Message Drop, p.234 · original PDF · in context

Tommy Lam says he has more sero-positive pangolins.

Slack / Private Message Drop, p.236 · original PDF · in context

Tommy also says that Ian Wilson has shown that the Guangxi pangolin virus binds well to human ACE2.

Slack / Private Message Drop, p.236 · original PDF · in context

They are a commercial company that have nothing to do with Wuhan.

Slack / Private Message Drop, p.241 · original PDF · in context

WIV do their sequencing in-house I think.

Slack / Private Message Drop, p.241 · original PDF · in context

That time-line makes zero sense with any known timeline, the epidemiological history of the outbreak, nor what was on Chinese social media.

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