Andrew Rambaut

I have not yet heard from you and would ask you to let us know as soon as possible whether or not you will be able to dothis for us.The manuscript abstract appears below.In our paper we describe some unusual characteristics of the regulatory 5' UTR sequences of SARS-CoV-2 that might imply its non-natural origin.

Slack / Private Message Drop, p.3 · original PDF · in context

We are also discussing possible therapeuticimplications of this finding - especially RNA interference and direct knock-out of the unique 5' UTR regulatory sequences of the SARS-CoV-2 virus, which, due to the high replication (and error) rate of SARS-CoV-2 might besuperior to the development of conventional immunogenic vaccines and might be an interesting idea to pursue.```5' UTR apparently has a non-natural origin.

Slack / Private Message Drop, p.3 · original PDF · in context

But I wonder if you'd have time at least to cast your eye over this very brief set of notes (responding to a number of points in the Nature Medicine paper) that I have received from a molecular biologist contact of mine, who has long experience in vaccine development and gain of function research (his comments are in blue): (NATURE MEDICINE ARTICLE IN BLACK TYPE)In theory, it is possible that SARS-CoV-2 acquired RBD mutations (Fig. 1a) during adaptation to passage in cell culture, as has been observed in studies of SARS-CoV11.

Slack / Private Message Drop, p.31 · original PDF · in context

(COMMENTS FROM MOLECULAR BIOLOGIST IN BLUE TYPE) This has two problems in respect of the second half assumption 1. doesnt prove it didn't happen in a petri dish - themixing could have happened naturally in a co-infected pangolin that had two related coronavirus infections at the same time, or in a petri dish where two viruses were infecting the same human cells.

Slack / Private Message Drop, p.31 · original PDF · in context

Both equally possible, latter probably more plausible - how many co-infected pangolins are out there?

Slack / Private Message Drop, p.31 · original PDF · in context

But third scenario they don't touch onmight be the most plausible of all - rather than postulating random recombination between the two viruses - the third possibility is that a researcher deliberately inserted the pangolin spike mutation into bat virus to see what this did.

Slack / Private Message Drop, p.31 · original PDF · in context

New polybasic cleavage sites have been observed only after prolonged passage oflow-pathogenicity avian influenza virus in vitro or in vivo17.Yes if you postulated the virus found these 4 amino substitutions one by one - I agree this is highly implausible.Pluasible scenario is that it got all 4 substitutions all at the same time - ie by recombination event between twoco-cultured viruses which can happen in days OR by researcher deliberately introducing these 4 substitutions all atthe same time which is a very simple process.

Slack / Private Message Drop, p.31 · original PDF · in context

It is the acquisition en masse of these 4 key new residues and nothing in flanking sequences that raises the distinct impression that someone deliberately inserted these 4 residuesin one step - with recombination would expect some variability on either side of these 4 substitutions between bat and pangolin spike sequences - there is absolutely none - all the residues on each side are identical - this is whatis so concerning.

Slack / Private Message Drop, p.31 · original PDF · in context

Subsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described.

Slack / Private Message Drop, p.31 · original PDF · in context

If they did indeed find a bat virus in their stocks with99% identity apart from the polybasic cleavage site then would they be comfortable to disclose this as then the only conclusion was that COVID19 was artificially created in their lab.

Slack / Private Message Drop, p.31 · original PDF · in context

From Jefferson's wikipedia page https://en.wikipedia.org/wiki/Tom_Jefferson_(epidemiologist) : "His views about the effectiveness of influenza vaccines and his outspokenness about them are also controversial;at a 2007 meeting on pandemic preparedness he was shunned by other vaccine researchers and ate alone."He is getting his revenge for being shunned.

Slack / Private Message Drop, p.96 · original PDF · in context

Koonin doing mad stuff again... ```Prediction of the incubation period for COVID-19 and future virus disease outbreaks Ayal B Gussow; Noam Auslander; Yuri I Wolf; Eugene Koonin Research article Abstract: Background: A crucial factor in mitigating respiratory viral outbreaks is early determination of the durationof the incubation period and, accordingly, the required quarantine time for potentially exposed individuals.

Slack / Private Message Drop, p.143 · original PDF · in context

The predictive approach described here can directly help in establishing the appropriate quarantinedurations and thus facilitate controlling future outbreaks.

Slack / Private Message Drop, p.143 · original PDF · in context

Wins a prize for the most gratuitous use of `quasispecies`: "but also describe the emergence of natural SARS-CoV-2 quasispecies with an extended ORF3b gene that may potentially affect COVID-19 pathogenesis".

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

Just saw this - ```In fact, a Chinese BSL-3 lab (the Shanghai Public Health Clinical Centre), which published a Nature article reporting a conflicting close phylogenetic relationship between SARS- 35 36 CoV-2 and ZC45/ZXC21 rather than with RaTG13 , was quickly shut down for "rectification" .

Slack / Private Message Drop, p.167 · original PDF · in context

Obviously RaTG13 isn't the whole story and the nutters' obsession with it ismisplaced (the existence of the pangolins and RmYN02 tell you almost as much). ```Dear Andrew,I was recently contacted by a national fact-checking body, run by Norwegian media outlets.

Slack / Private Message Drop, p.176 · original PDF · in context

Because it would be an absolute tragedy if in our eagerness, we were to boost the nutjobs - the anti vaxxers,dangerous obsessives who campaign against the whole concept of vaccination and who would risk further millionsof lives.

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

Would be good to get out the bit about pissing off the Chinese Authorities!

Slack / Private Message Drop, p.232 · original PDF · in context

Looks like it could be a handy outgroup for the SC2, pangolin, RaTG13 clade

Slack / Private Message Drop, p.253 · original PDF · in context

So definitely could be associated with a change in virus behaviour.

Slack / Private Message Drop, p.342 · original PDF · in context

Just sent to Bob and me (plus Christian Drosten, Trevor and Guy Hoelzer). ```Gentlemen, It appears that the mutations in the spike protein that causes PCR failure for that part of the Taqpath assay will befound to have induced a PCR selection bias, and thus contributed to the spread of the virus without increasedpathogenicity.Specifically, there will be more false negatives in tests of people with any variant with new variation in the primer target sequences, especially the 8 variants Andrew reported in the spike protein coding region.

Slack / Private Message Drop, p.356 · original PDF · in context

See second report here HKU-3-3 is a SARS-CoV-2 precusor, at least from the perspective of the spike protein.http://ipaknowledge.org/covid-19-and-sars-cov-2-research.phpAlso available herehttps://www.researchgate.net/publication/340769150_Motif_Pathogenicity_Typing_SARS-CoV-2_Coronavirus_May_Contain_a_Unique_Likely_Pathogenic_Protein_Motif_Signature_Also_Found_in_a_Natural_Isolate_from_2005```

Slack / Private Message Drop, p.356 · original PDF · in context

James thinks he is on to something that explains everything: ```Evolutionists in the know: Australia, S Korea, China all use the Beijing test - no spike protein per their protocol? https://www.health.gov.au/sites/default/files/documents/2020/06/post-market-validation-of-the-beijing-genomics-institute-bgi-sars-cov-2-real-time-pcr-platform.pdfIf so, that might explain the discrepancies... concluding that "we never could have gotten our arms around this because variants" will not fly."Not knowing enough to exclude primer sites that are evolutionarily labile" - yes, I'd buy that.IF Oz, S.

Slack / Private Message Drop, p.359 · original PDF · in context

If these constellations have no effect on vaccine elicited immunity then boy will we have dodged a bullet.

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

As you know, it is typical that GISAID receivessuch an alert when a novel strain appears, as in 2009, when GISAID was advised by the US CDC of H1N1p, and in2013, when the China CDC gave GISAID a heads up on the HPAI H7N9, and on numerous other occasions when itseemed an outbreak could occur.

Slack / Private Message Drop, p.421 · original PDF · in context

@Kristian Andersen Daszak's involvement in the WHO investigation is like "having Donald Trump run the investigation of Russian hacking of the 2016 election."

Slack / Private Message Drop, p.428 · original PDF · in context

```Dear Permanent Missions to the United Nations in New York: Phase III vaccine trial participants are in the process of losing their immunity and will become individual superspreaders once they become infected.

Slack / Private Message Drop, p.434 · original PDF · in context

I warned you about the vaccines causing mass amounts ofdeaths, but you did not listen, so now your leaders must face the consequences of those deaths.I will fix this mess for you, but you must give me absolute power.

Slack / Private Message Drop, p.434 · original PDF · in context

This version includes my first fifteen official acts and my first most wanted list, with China President Xi Jinping listed at #2.Every day you do not appoint me is another day that your leaders will be morally responsible for the deaths that will occur.Sincerely,Brady L.

Slack / Private Message Drop, p.434 · original PDF · in context

If it was in fact a lab origin then there was SC2 progenitor in WIV or where-ever and there has been aconspiracy to hide that fact.

Slack / Private Message Drop, p.493 · original PDF · in context

Or it could be adescription of the new genomes and what they mean for natural origins.

Slack / Private Message Drop, p.517 · original PDF · in context

This would be an explosively political hypothesis given all the anti-lockdown stuff going on.

Slack / Private Message Drop, p.530 · original PDF · in context

From what I am hearing it is difficult toculture SARS-CoV-2 from many samples so I would imagine sampling bats (say) you would be just hoping for RNA rather than infectious virus.

Slack / Private Message Drop, p.575 · original PDF · in context

The reality is of course that ifwe found evidence of lab origins or whatever we would be straight down to Nature/Science with it.

Slack / Private Message Drop, p.579 · original PDF · in context

If there are any concerns about the dataset or how the data align with the reported claims, we would also appreciate input on whether the issue could be addressed via aCorrection or whether it has substantial implications for the reliability and/or validity of the article's conclusions.

Slack / Private Message Drop, p.723 · original PDF · in context

Refers to this paper: RE: "Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)?" (https://doi.org/10.137 1/journal.ppat. 1008421)

Slack / Private Message Drop, p.724 · original PDF · in context

I would be interested what Jesse would say if you just posted the list of scientists working at WIV and ask which ofthese people he thought might have deliberately leaked the virus.

Slack / Private Message Drop, p.811 · original PDF · in context

In essence the "lab-capture-escape" scenario is just a very specific conjecture about the exact nature and route of a zoonotic spillover.

Slack / Private Message Drop, p.909 · original PDF · in context

Perhaps we should try to get the point by point evidence document together ASAP and we can then give it to all the people involved that we know will appreciate having it (Fauci, Farrar, Vallance etc.)?

Slack / Private Message Drop, p.926 · original PDF · in context

Public discourse and Twitter in particular surrounding "lab leak" has become increasingly toxic.

Slack / Private Message Drop, p.955 · original PDF · in context

The data just shows there were other haplotypes in Wuhan in January which we knew already - we also now that some aren't associated with the Huanan market.

Slack / Private Message Drop, p.962 · original PDF · in context

The novel disease is detected and characterized only when physicians see a lot of people coming at the same time withatypical symptoms.

Slack / Private Message Drop, p.977 · original PDF · in context

It isunpredictable and the chain of events is of societal nature not ofbiological nature.

Slack / Private Message Drop, p.977 · original PDF · in context

I guess the rules are different in Australia but it might begood to coordinate as my requests are:• All correspondence between you and me from 2019-2021 (my admin has said we narrow this to only those about the lab-escape stuff because they make it clear that is what they are interested in).A second request asking for:• All documents about the "Proximal Origins ..." research project (I am not sure how we will deal with that as it wasn'ta research project).

Slack / Private Message Drop, p.980 · original PDF · in context

I guess they would have seen an ACE-2 binding RBD and thought that is the one to try an FCS in?

Slack / Private Message Drop, p.1000 · original PDF · in context

But first round will be way more consequential as all progeny would have the insert and the spike proteins would have the FCS.

Slack / Private Message Drop, p.1014 · original PDF · in context

However, given these emails about the Feb call have already been released by NIH and UK Gov in highly redacted form, I don't know if it would be possible for them to coordinate releasing more details from those emails unilaterally.Or just the interactions with Kristian (who is not FOIable)?

Slack / Private Message Drop, p.1017 · original PDF · in context

> The University of Edinburgh recently turned down an Freedom of Information request from The Telegraph asking to see Prof Rambaut's replies, claiming "disclosure would be likely to endanger the physical or mental health and safety of individuals".

Slack / Private Message Drop, p.1050 · original PDF · in context

I ask this because it seems that line was adopted very early on, particularly by your co-author Kristian Andersen (Feb 4), and perhaps before there was sufficient evidence for thinking this couldn't have been the case.>> - Were you aware, while you were on that call, that Anthony Fauci had historically funded research at the Wuhan Institute of Virology?>> - Contrary to much rhetoric, I see that the idea that the virus escaped from a lab _is_ considered in your proximal origins paper ("_We must therefore consider the possibility of a *deliberate or inadvertent* release ofSARS-CoV-2"_).

Slack / Private Message Drop, p.1058 · original PDF · in context

All of our conclusions were written in our published and peer-reviewed papers (i.e., in Nature Medicine and then updated in Cell late last year).

Slack / Private Message Drop, p.1058 · original PDF · in context

All of the emails show the establishment ofthe hypotheses we later outlined in the Proximal Origins paper with the assessment of these based on the available evidence.

Slack / Private Message Drop, p.1058 · original PDF · in context

As I say in that email - the missing part ofthe picture was the intermediate host between the ultimate origins in wild bats and the human population in Wuhan.My opinion on the likely origins were exactly the same then as those published in the Nature Medicine paper and have remained the same.

Slack / Private Message Drop, p.1058 · original PDF · in context

Looks good - my only quibble (other than calling the sequence file format a 'fasterfile') is with the timeline of the pangolin genome with the RBD in it.

Slack / Private Message Drop, p.1077 · original PDF · in context

DQ says: > "What the email shows," Andersen said later, on Twitter, in response to criticisms, "is a clear example of the scientific process.[i] They were considering possibilities, lab leak included, engineered virus included, natural spillover included, and they hungered for more data that might support or negate one or another.

Slack / Private Message Drop, p.1077 · original PDF · in context

Then came the pangolins.We had the first pangolin sequence very early Feb (it was posted on virological on 31st Jan) and then Tommy's one very shortly after.

Slack / Private Message Drop, p.1077 · original PDF · in context

So the pango RBD was in our very early drafts.

Slack / Private Message Drop, p.1077 · original PDF · in context

Seems like they have also given Fox News the tip-off: ```Good morning, Could you please comment on the letter you were sent this morning by Republican members of the House of Representatives asking for clarification on why you originally suspected the COVID-19 virus was possibly man created before then suggesting otherwise in the Nature Medicine report entitled, "The Proximal Origin of SARS-CoV-2." Do you still hold the belief the virus was naturally occurring?

Slack / Private Message Drop, p.1083 · original PDF · in context