Message 

From: 
Sent: 
To: 
CC: 
Subject: 
Fauci, Anthony (NIH/NIAID) [E] 
1/31/2020 6:25:48 PM 
Jeremy Farrar 
RE:Phone call 
Thanks, Christian. I will keep you posted. 
Best regards, 
Tony 

From: Kristian G. Andersen
Sent: Friday, January 31, 
To: Fauci, Anthon 
Cc:Jeremy Farrar 
Subject:Re: Phone call 

Thanks Tony, 

In addition to Eddie and Bob we have Mike Farzan on board (discoverer of the SARS 
receptor https://www.scripps.edu/faculty/farzan/l, and I believe Jeremy will reach out to Christian Drosten and Ron 
Fouchier in the morning to get their expertise as well. Combined, this group will be able to objectively assess the 
available data and determine whether the genome looks unusual. 

Please let me know if anything changes on your end or if you have any questions. 

Best, 
Kristian 

On Fri, Jan 31, 2020 at 4:38 PM Fauci, Anthony (NIH/NIAID) [E] 

wrote: 
Jeremy: 

I just got off the phone with Kristian Anderson and he related to me his concern about the 
Furine site mutation in the spike protein of the currently circulating 2019-nCoV. I told him 
that as soon as possible he and Eddie Holmes should get a group of evolutionary biologists 
together to examine carefully the data to determine if his concerns are validated. He should 
do this very quickly and if everyone agrees with this concern, they should report it to the 
appropriate authorities. I would imagine that in the USA this would be the FBI and in the UK 
it would be MIS. It would be important to quickly get confirmation of the cause of his 
concern by experts in the field of coronaviruses and evolutionary biology. In the meantime, I 
will alert my US. Government official colleagues of my conversation with you and Kristian and 
determine what further investigation they recommend. Let us stay in touch. 

Best regards, 

Tony 

Anthony S. Fauci, MD 
Director 

REV0000750 


National Institute of Allergy and Infectious Diseases 


National Institutes of Health 
Bethesda MD 20892-2520 

Phone: 
FAX: 
E-mail: [ 
The information in this e-mail and any of its attachments is confidential and may contain sensitive 
information. It should not be used by anyone who is not the original intended recipient. If you have received 
this e-mail in error please inform the sender and delete it from your mailbox or any other storage devices. The 
National Institute of Allergy and Infectious Diseases (NIAID) shall not accept liability for any statements made 
that are the sender's own and not expressly made on behalf of the NIAID by one of its representatives. 

From:Jeremy Farrar 
Sent:Friday, January ' ' • " 

To: Fauci, Anthony (NIH/NIAID) [E] 


Subject:Re: Phone call 
Thanks Tony 
Can you phone Kristian Anderson 

He is expecting your call now. 

The people involved are: 

Kristian Anderson 
https://www.scripps.edu/faculty/andersen/ 

Bob Garry 
https://medicine.tulane.edu/departments/microbiology-immunology-tulane-cancer-center/faculty/robert-f-garry-jrphd 


Eddie Holmes 
https://sydney.edu.au/science/about/our-people/academic-staff/edward-holmes.html 

REV0000751 


From:"Conrad, Patricia (NIH/NIAID) (E]" on behalf of "Fauci, Anthony (NIH/NIAID) [E]" 

Date: Friday, 31 January 2020 at 22:34 
To:Jeremy Farraq 
Subject:RE:Phone call 

Will call shortly ... 

Patricia L. Conrad 
Public Health Analyst and 
Special Assistant to the Director 
National Institute of Allergy and Infectious Diseases 
The National Institutes of Health 

Bethesda, Maryland 20892 

Disclaimer: 
The information in this e-mail and any of its attachments is confidential and may contain sensitive infomation. It should not be used by anyone who is 
not the original intended recipient. If you have received this e-mail in error please inform the sender and delete it from your mailbox or any other 
storage devices. National Institute of Allergy and Infectious Diseases (NIAID) shall not accept liability for any statement made that are sender's own 
and not expressly made on behalf of the NIAID by one of its representatives. 

From:Jeremy Farrar
Sent:Friday, January~ 
To:Fauci, Anthony (NIH/NIAID) [E] 
Subject:Phone call 

Tony 
Really would like to speak with you this evening 

It is 10pm now UK 

Can you phone me on +44 Jeremy 


Wellcome exists to improve health by helping great ideas to thrive. We support researchers, we take on big health 
challenges, we campaign for better science, and we help everyone get involved with science and health research. We are a 
politically and financially independent foundation. 

REV0000752 


Fauci, Anthony (NIH/NIAID) [E] Fauci, Anthony (NIH/NIAID) [E] 
Message 

From: 

Sent: 2/1/2020 10:43:31 AM 
To: Kristian G. Andersen 

Subject: RE: FW: Science: Mining coronavirus genomes for clues to the outbreak's origins 

Thanks, Kristian. Talk soon on the call. 

From: Kristian G. Andersen 


Sent: Friday, January 31, 2020 10:32 PM 

To: Fauci, Anthony (NIH/NIAID) [E) 
Cc:Jeremy Farrar 


Subject: Re: FW: Science: Mining coronavirus genomes for clues to the outbreak's origins 

Hi Tony, 

Thanks for sharing. Yes, I saw this earlier today and both Eddie and myself are actually quoted in it. It's a great article, 
but the problem is that our phylogenetic analyses aren't able to answer whether the sequences are unusual at individual 
residues, except if they are completely off. On a phylogenetic tree the virus looks totally normal and the close clustering 
with bats suggest that bats serve as the reservoir. The unusual features of the virus make up a really small part of the 
genome (<0.1%)so one has to look really closely at all the sequences to see that some of the features (potentially) look 
engineered. 

We have a good team lined up to look very critically at this, so we should know much more at the end of the weekend. I 
should mention that after discussions earlier today, Eddie, Bob, Mike, and myself all find the genome inconsistent with 
expectations from evolutionary theory. But we have to look at this much more closely and there are still further analyses 
to be done, so those opinions could still change. 

Best, 

Kristian 

On Fri, Jan 31, 2020 at 18:47 Fauci, Anthony (NIH/NIAID) [E) 

wrote: 
Jeremy/Kristian: 
This just came out today. You may have seen it. If not, it is of interest to the current discussion. 
Best, 

Tony 

From: Folkers, Greg (NIH/NIAID) [E] 

Sent: Friday, January 31, 2020 8:43 PM 

Subject: Science: Mining coronavirus genomes for clues to the outbreak's origins 

REV0000797 


As part of a long-running effort to see what viruses bats harbor, researchers in China collect one from a cave in 
Guandong. 

EcoHealth Alliance 

Mining coronavirus genomes for clues to the 
outbreak's origins 

By Jon CohenJan. 31, 2020, 6:20 PM 

attaaaggtt tataccttcc caggtaacaa accaaccaac tttcgatctc ttgtagatct ... 

That string of apparent gibberish is anything but: It's a snippet of a DNA sequence from the viral pathogen, dubbed 
2019 novel coronavirus (2019-nCoV), that is overwhelming China and frightening the entire world. Scientists are 
publicly sharing an ever-growing number of full sequences of the virus from patients-53 at last count in the Global 
Initiative on Sharing All Influenza Data database. These viral genomes are being intensely studied to try to understand 
the origin of 2019-nCoV and how it fits on the family tree of related viruses found in bats and other species. They have 
also given glimpses into what this newly discovered virus physically looks like. how it's changing. and how it might be 
stopped. 

"One of the biggest takeaway messages [from the viral sequences] is that there was a single introduction into humans 
and then human-to-human spread," says Trevor Bedford, a bioinformatics specialist at the University of Washington, 
Seattle. The role of Huanan Seafood Wholesale Market in Wuhan, China, in spreading 2019-nCoV remains murky, 
though such sequencing, combined with sampling the market's environment for the presence of the virus, is clarifying 
that it indeed had an important early role in amplifying the outbreak. The viral sequences, most researchers say, also 
knock down the idea the pathogen came from a virology institute in Wuhan. 

In all, 2019-nCoV has nearly 29,000 nucleotides bases that hold the genetic instruction book to produce the virus. 
Although it's one of the many viruses whose genes are in the form of RNA, scientists convert the viral genome into 
DNA, with bases known in shorthand as A, T, C, and G, to make it easier to study. Many analyses of 2019-nCoV's 
sequences have already appeared on virological.org. nextstrain.org, preprint servers like bioRxiv, and even in peer reviewed 
journals. The sharing of the sequences by Chinese researchers allowed public health labs around the world to 
develop their own diagnostics for the virus, which now has been found in 18 other countries. (Science's news stories on 
the outbreak can be found here.) 

When the first 2019-nCoV sequence became available, researchers placed it on a family tree of known corona viruses which 
are abundant and infect many species-and found that it was most closely related to relatives found in bats. A 
team led by Shi Zheng-Li, a coronavirus specialist at the Wuhan Institute of Virology, reported on 23 January on bio Rxiv 
that 2019-nCoV's sequence was 96.2% similar to a bat virus and had 79.5% similarity to the coronavirus that causes 
severe acute respiratory syndrome (SARS), a disease whose initial outbreak was also in China more than 15 years ago. 
But the SARS coronavirus has a similarly close relationship to bat viruses, and sequence data make a powerful case that 

REV0000798 


it jumped into people from a coronavirus in civets that differed from human SARS viruses by as few as 10 nucleotides. 
That's one reason why many scientists suspect there's an "intermediary" host species-or several-between bats and 
2019-nCoV. 

According to Bedford's analysis, the bat coronavirus sequence that Shi Zheng-Li's team highlighted, dubbed RaTG13, 
differs from 2019-nCoV by nearly 1100 nucleotides. On nextstrain.org, a site he co-founded, Bedford has created 
coronavirus family trees (example below) that include bat, civet, SARS, and 2019-nCoV sequences. (The trees are 
interactive-by dragging a computer mouse over them, it's easy to see the differences and similarities between the 
sequences.) 

.....

,..,. 

""'

-

-u 

Bedford's analyses of RaTG13 and 2019-nCoV suggest that the two viruses shared a common ancestor 25 to 65 years 
ago, an estimate he arrived at by combining the difference in nucleotides between the viruses with the presumed rates 
of mutation in other coronaviruses. So it likely took decades for RaTG13-like viruses to mutate into 2019-nCoV. 

Middle East respiratory syndrome (MERS), another human disease caused by a coronavirus, similarly has a link to bat 
viruses. But studies have built a compelling case it jumped to humans from camels. And the phylogenetic tree from 
Shi's bioRxiv paper (below) makes the camel-MER$ link easy to see. 

REV0000799 


.------TGEV 
---MinkCoV 
---Ferret CoV 
----Bat CoV CDPHE15 

.-----Scotophifus ba CoV 512 

.__ ___ PEDV 

----Bat CoV HKU10 
.-----Min/opt ru b t CoV 1 
,,....____ Miniopterus ba CoV HKUB 

'.----Hum n CoV NL63 
.__ ___ Bal NL63-related CoV 
._____ Human CoV 229E 

SADS-CoV 
Rhinofophus bat CoV H U2 
Hu an CoV OC43 

,____ Murine epa itis virus 
---Rat CoV HKU24 
.__ Human CoV HKU1 
oo Human MERS-CoV 
IMl,-----1 Camel MERS-CoV 
100 Plplstreflus bat CoV HKUS 
,._ __ Tylonycteris Ba CoV HKU4 
.....__ Hedgehog CoV 

00 

t SARS-CoV 8J01 

'1 Civet SARS-CoV SZ3 
Ba SARSr-CoV WIV1 
Bat SARSr-CoV SHC014 
Bat SARSr-CoV LYRa11 

Ba SARSr-CoV Rf1 
Bat SARSr-CoV ZC45

117 

Bat SARSr-CoV HKU3-1 
-----Bat SARSr-CoV B 48-31 
taCoV u /WIV0S/201 
CoV u IV02/2019 
100 t CoVtwuh n/WIV04/201 

B t CoV uh IV0 /2019 
taCoV uh n IV07/2019 
tCoV TG13 

97 ,_______ Bat Hp BetaCoV Zhejiang 2013 
-----1----Rousettus bat CoV HKU9 
oo Bat CoV GCCDC1 

,_______ ,av 

Q. 

The longer a virus circulates in a human populations, the more time it has to develop mutations that differentiate 
strains in infected people, and given that the 2019-nCoV sequences analyzed to date differ from each other by seven 
nucleotides at most, this suggests it jumped into humans very recently. But it remains a mystery which animal spread 
the virus to humans. "There's a very large gray area between viruses detected in bats and the virus now isolated in 
humans," says Vincent Munster, a virologist at the U.S. National Institute of Allergy and Infectious Diseases who studies 
coronaviruses in bats, camels, and others species. 

Strong evidence suggests the marketplace played an early role in spreading 2019-nCoV, but whether it was the origin of 
the outbreak remains uncertain. Many of the initially confirmed 2019-nCoV cases-27 of the first 41 in one report, 26 
of 47 in another-were connected to the Wuhan market, but up to 45%, including the earliest handful, were not. This 
raises the possibility that the initial jump into people happened elsewhere. 

According to Xinhua, the state-run news agency, "environmental sampling" of the Wuhan seafood market has found 
evidence of 2019-nCoV. Of the 585 samples tested, 33 were positive for 2019-nCoV and all were in the huge market's 
western portion, which is where wildlife were sold. ''The positive tests from the wet market are hugely important," says 
Edward Holmes, an evolutionary biologist at the University of Sydney who collaborated with the first group to publicly 
release a 2019-nCoV sequence. "Such a high rate of positive tests would strongly imply that animals in the market 
played a key role in the emergence of the virus." 

REV0000800 


Yet there have been no preprints or official scientific reports on the sampling, so it's not clear which, if any, animals 
tested positive. "Until you consistently isolate the virus out of a single species, it's really, really difficult to try and 
determine what the natural host is," says Kristian Andersen, an evolutionary biologist at Scripps Research. 

One possible explanation for the confusion about where the virus first entered humans is if there was a batch of 
recently infected animals sold at different marketplaces. Or an infected animal trader could have transmitted the virus 
to different people at different markets. Or, Bedford suggests, those early cases could have been infected by viruses 
that didn't easily transmit and sputtered out. "It would be hugely helpful to have just a sequence or two from the 
marketplace [environmental sampling] that could illuminate how many zoonoses occurred and when they occurred," 
Bedford says. 


A research group sent fecal and other bodily samples from bats they trapped in caves to the Wuhan Institute of 
Virology to search for coronaviruses. 

Eco Health Alliance 
In the absence of clear conclusions about the outbreak's origin, theories thrive, and some have been scientifically 
shaky. A sequence analysis led by Wei Ji of Peking University and published online by the Journal of Medical Virology 
received substantial press coverage when it suggested that "snake is the most probable wildlife animal reservoir for the 
2019-nCoV." Sequence specialists, however, pilloried it. 

Conspiracy theories also abound. A CBC News report about the Canadian government deporting Chinese scientists who 
worked in a Winnipeg lab that studies dangerous pathogens was distorted on social media to suggest that they were 
spies who had smuggled out coronaviruses. The Wuhan Institute of Virology, which is the premier lab in China that 
studies bat and human coronaviruses, has also come under fire. "Experts debunk fringe theory linking China's 
coronavirus to weapons research," read a headline on a story in The Washington Post that focused on the facility. 

Concerns about the institute predate this outbreak. Nature ran a story in 2017 about it building a new biosafety level 4 
lab and included molecular biologist Richard Ebright of Rutgers University, Piscataway, expressing concerns about 
accidental infections, which he noted repeatedly happened with lab workers handling SARS in Beijing. Ebright, who has 
a long history of raising red flags about studies with dangerous pathogens, also in 2015 criticized an experiment in 
which modifications were made to a SARS-like virus circulating in Chinese bats to see whether it had the potential to 
cause disease in humans. Earlier this week, Ebright questioned the accuracy of Bedford's calculation that there are at 
least 25 years of evolutionary distance between RaTG13-the virus held in the Wuhan virology institute-and 2019nCoV, 
arguing that the mutation rate may have been different as it passed through different hosts before humans. 
Ebright tells Science Insider that the 2019-nCoV data are "consistent with entry into the human population as a natural 
accident." 

Shi did not reply to emails from Science, but her longtime collaborator, disease ecologist Peter Daszak of the EcoHealth 
Alliance, dismissed Ebright's conjecture. "Every time there's an emerging disease, a new virus, the same story comes 
out: This is a spillover or the release of an agent or a bioengineered virus," Daszak says. "It's just a shame. It seems 
humans can't resist controversy and these myths, yet it's staring us right in the face. There's this incredible diversity of 

REV0000801 


viruses in wildlife and we've just scratched the surface. Within that diversity, there will be some that can infect people 
and within that group will be some that cause illness." 


A team of researchers from the Wuhan Institute of Virology and the Eco Health Alliance have trapped bats in caves all 
over China, like this one in Guangdong, to sample them for coronaviruses. 

EcoHealth Alliance 

Daszak and Shi's group have for 8 years been trapping bats in caves around China to sample their feces and blood for 
viruses. He says they have sampled more than 10,000 bats and 2000 other species. They have found some 500 novel 
coronaviruses, about SO of which fall relatively close to the SARS virus on the family tree, including RaTG13-it was 
fished out of a bat fecal sample they collected in 2013 from a cave in Moglang in Yunnan province. "We cannot assume 
that just because this virus from Yunnan has high sequence identity with the new one that that's the origin," Daszak 
says, noting that only a tiny fraction of coronaviruses that infect bats have been discovered. "I expect that once we've 
sampled and sampled and sampled across southern China and central China that we're going to find many other viruses 
and some of them will be closer [to 2019-nCoV]." 

It's not just a "curious interest" to figure out what sparked the current outbreak, Daszak says. "If we don't find the 
origin, it could still be a raging infection at a farm somewhere, and once this outbreak dies, there could be a continued 
spillover that's really hard to stop. But the jury is still out on what the real origins of this are." 

Posted in: 

• Asia/Pacific 
• Health 
• Coronavirus 
doi:10.1126/science.abb1256 


Jon Cohen 

Jon is a staff writer for Science. 

• Email Jon 
• Twitter 
REV0000802 


Disclaimer: Any third-party material in this email has been shared for internal use under fair use provisions of U.S. 
copyright law, without further verification of its accuracy/veracity. It does not necessarily represent my views nor those of 
NIAID, Nm,HHS, or the U.S. government. 

REV0000803 


Message 

From: Pope, Andrew 
Sent: 2/3/2020 9:04:47 AM 
To: 
CC: 
Subject: o ay s a mee Ing in o 
IAID) 
; Kanarek, 
; Logan, Kendall 
Behney, Clyde 
Attachments: Agenda-2019-nCoV.docx; SOW.docx 

Thank you for participating in today's meeting of experts at the National Academies to discuss and identify what data, 
information and samples are needed to understand the evolutionary origins of 2019-nCoV and more effectively respond 
to the outbreak and resulting misinformation. 

Attached for your information are: 
Agenda 
Scope of Work 
A list of participants will be sent along shortly 

Please let me know if you have any questions of problems with connecting. 

"Zoom" Call-in info is as follows (and is included at top of agenda): 

Zoom Dial-in Info: 

Time: Feb 3, 2020 02:00 PM Eastern Time 
Join from PC, Mac, Linux, iOS or Android: 
Telephone: 
Meeting I0:I 
International numbers available: 
Andrew M. Pope, Ph.D. 

Director 
Board on Health Sciences Policy 
Health and Medicine Division 
The National Academies of Sciences, 

Engineering, and Medicine 


--direct 

office 
Find us at nationalacademies.org/HMD 

~000807 


The National Academies of 

SCIENCES• ENGINEERING· MEDICINE 

-000808 


The National Academies of 

SCIENCES • ENGINEERING· MEDICINE 

Expert Meeting 

Rapid Response for Assessment of Data Needs for 2019-nCo V 

Agenda 

February 3, 2020 

2:00 p.m.-3:00 p.m. (ET) 
Keck Center, Room 103 
500 5th St NW, Washington, DC 20001 

Join from PC, Mac, Linux, iOS or Android: 
Telephone: 
Meeting ID: 
International numbers available: 

Meeting Objective: Assess what data, information and samples are needed to understand the 
evolutionary origins of 2019-nCo V and more effectively respond to the outbreak and resulting 
misinformation. 

2:00 p.m. 
2:05 p.m. 
2:15 p.m. 
Welcome and introductions (5 mins) 

ANDREW POPE 

Director, Board on Health Sciences Policy 
National Academies of Sciences, Engineering, and Medicine 

Statement of Work (10 mins) 

KELVIN DROEGEMEIER 
Director 
Office of Science and Technology Policy 

D. CHRISTIAN ("CHRIS") HASSELL 
Senior Science Advisor 
U.S. Department of Health and Human Services 
Perspective from NIH/NIAID (1O mins) 

ANTHONY ("TONY") S. FAUCI 

Director 

National Institute of Allergy and Infectious Diseases 

National Institutes of Health 

11Page 

llllllooosog 


The National Academies of 

SCIENCES • ENGINEERING· MEDICINE 

2:25 p.m. Discussion of Meeting Objective (30 mins) 
2:55 p.m. Delete·mine Next Steps (5 mins) 
3:00 p.m. Adjourn 
21Page 

llllllooos10 


The National A.cade1nies of 

SCIENCES• ENGINEERING • MEDICINE 

Statement of Work 

Rapid Response for Assessment of Data Needs for 2019-nCoV 

February 3, 2020 

Statement of Task: 

In response to a request from OSTP, the NASEM will examine information and identify data requirements that 
would help determine the origins of 2019-nCoV, specifically from an evolutionary/structural biology standpoint. 
NASEM will also consider whether this should include more temporally and geographically diverse clinical 
isolates, sequences, etc. Although a widely-disputed paper posted on a pre-print server last week has since 
been withdrawn, the response to that paper highlights the need to determine these information needs as 
quickly as possible. As part of a broader deliberative process, this review will help prepare for future events by 
establishing a process for quickly assembling subject matter experts for evaluation of other potentially 
threatening organisms. 

Workplan: 

NASEM will hold a meeting of experts to assess what data, information and samples are needed to address the 
unknowns, in order to understand the evolutionary origins of NCoV and more effectively respond to both the 
outbreak and any resulting misinformation. A statement from the National Academies will be prepared and 
published on the Web as a "Based on Science" article that summarizes the status and needs for more and what 
types of data. A more in-depth examination of the issues will be established as a follow up as needed. 

500 Fifth Street, NW, Washington, DC 20001 


M Gmail 


URGENT: Please review by NOON if at all possible ... 

Kristian G. Andersen 
To: Peter Daszak 
Cc: "Pope, Andre 
Tue, Feb 4, 2020 at 9:05 AM 
, "Ralph Barie 
Gigi Gronvall 
I too agree with all that has been said, but would caution against adding language suggesting that the virus might evolve 
(i.e., "mutate" to most people) towards better infectivity or transmission -a lot has been said about that for Ebola and 
other viruses, and it's been driving fear because most people don't fully understand what it means. I'm not arguing that it's 
not something that might well happen -the SARS data beautifully show it -but I would be worried about the message it 
could send. 

Reading through the letter I think it's great, but I do wonder if we need to be more firm on the question of engineering. The 
main crackpot theories going around at the moment relate to this virus being somehow engineered with intent and that is 
demonstrably not the case. Engineering can mean many things and could be done for either basic research or nefarious 
reasons, but the data conclusively show that neither was done (in the nefarious scenario somebody would have used a 
SARS/MERS backbone and optimal ACE2 binding as previously described, and for the basic research scenario would 
have used one of the many already available reverse genetic systems). If one of the main purposes of this document is to 
counter those fringe theories, I think it's very important that we do so strongly and in plain language ("consistent with" 
[natural evolution] is a favorite of mine when talking to scientists, but not when talking to the public -especially conspiracy 
theorists). 

Best, 
Kristian 

On Tue, Feb 4, 2020 at 9:02 AM Peter Daszak wrote: 
I agree with all of the other comments so far sent in, and want to add the following: 

1) In the 3rd paragraph, it's important to add "including further samples from wildlife", and perhaps the rationale for this 
"to identify other viruses closely related to nCoV" 
2) Re. references for #3 that there are current and planned studies underway on the bat origins of CoVs. Here are 
some references to pick from if they make sense: 
Latinne A, Hu B, Olival KJ, et al.; Origin and cross-species transmission of bat 
coronaviruses in China. Nature Communications 2020;1n review. 

Wang N, Li S-Y, Yang X-L, et al.; Serological Evidence of Bat SARS-Related 

Coronavirus Infection in Humans, China. Virologica Sinica 2018. doi: 10.1007/s12250


018-0012-7. 

Hu B, Zeng L-P, Yang X-L, et al.; Discovery of a rich gene pool of bat SARS-related 

coronaviruses provides new insights into the origin of SARS coronavirus. PLOS 

Pathogens 2017;13(11):e1006698. doi: 10.1371/journal.ppat.1006698. 

Zhou P, Fan H, Lan T, et al.; Fatal Swine Acute Diarrhea Syndrome caused by an HKU2related 
Coronavirus of Bat Origin. Nature 2018 

HIGHLY CONFIDENTIAL AND PROPRIETARY ■-0000008 


Cheers, 

Peter 

Peter Daszak 

President 

EcoHealth Alliance 


New York, NY 10001 

Tel. 
Website: www.ecohealthalliance.org 
Twitter: @PeterDaszak 

EcoHealth Alliance leads cutting-edge research into the critical connections between human and wildlife health and 
delicate ecosystems. With this science we develop solutions that prevent pandemics and promote conservation. 

mantha 
Subject: URGENT: Please review by NOON if at all possible ... 
Importance: High 

Many thanks again for your thoughtful participation yesterday. The plans have changed in terms 
of our product. Instead of a "Based on Science" web posting, we are now developing a letter that 
will be signed by the 3 Presidents of our 3 Academies (NAS, Marcia McNutt; NAM, Victor Dzau; 
NAE, John Anderson), in response to a letter from OSTP. We think this will be more appropriate 
and expeditious. 

HIGHLY CONFIDENTIAL AND PROPRIETARY •-0000009 


Thus, given the urgency of the request from OSTP and HHS we ask that you please review the 
attached DRAFT CONFIDENTIAL letter, and let us know if you have any concerns or suggested 
edits. In particular, we 
would like to ask if there might be some additional detail added to the data 
needs that are identified. We think it would be helpful to be a bit more specific, but don’t want to 
go into too much detail either. Your help there would be most helpful. 


Many sincere thanks again for your continued engagement on this important activity! 


Andy 


Andrew M. Pope, Ph.D. 


Director 
Board on Health Sciences Policy 
Health and Medicine Division 
The National Academies of Sciences, 


Engineering, and Medicine 


, direct, office
Find us at nationalacademies.org/HMD 



HIGHLY CONFIDENTIAL AND PROPRIETARY-0000010

To: 
Shore, Caroly 
Pope, Andre 
Tue 2/4/2020 9:10:35 AM (UTC-05:00) 
Kristian Andersen 
TrevorBedford 
Gigi 
To: 
Shore, Caroly 
Pope, Andre 
Tue 2/4/2020 9:10:35 AM (UTC-05:00) 
Kristian Andersen 
TrevorBedford 
Gigi 
Subject: URGENT: Please review by NOON if at all possible ... 
Response Letter DRAFT « Fen4. dOGX 

Many thanks again for your thoughtful participation yesterday, The plans have changed in terms of our product, Instead 
of a "Based on Science" web posting, we are now developing a letter that will be signed by the 3 Presidents of our 3 
Academies {NAS, Marcia McNutt; NAM, Victor Dzau; NAE, John Anderson), in response to a letter from OSTP. We think 
this will be more appropriate and expeditious, 

Thus, given the urgency of the request from OSTP and HHS we ask that you please review the attached DRAFT 
CONFIDENTIAL letter, and let us know If you have any concerns or suggested edits. In particular, we would like to ask if 
there might be some additional detail added to the data needs that are identified. We think it would be helpful to be a 
bit more specific, but don't want to go into too much detail either. Your help there would be most helpful. 

Many sincere thanks again for your continued engagement on this important activity! 

Andy 

Andrew M. Pope, Ph.D. 

Director 

Board on Health Sciences Policy 

Health and Medicine Division 

The National Academies of Sciences, 

Engineering, and Medicine 

direct 
office 

Find us at _nationalacademh.';s.org[t!MQ 

Tire 1'latiomll .Acadcmi~of 

SCIENCES• ENGINEERING 

•MEOIC!NE 
111111>001849 


CONFIDENTIALDRAFT 

February 4, 2020 

[inse1iaddress] 

DearXXX: 

Thank you for your letter regarding the current outbreak of a new respiratory virus, the 2019 
Novel Coronavirus, or 2019-nCoV, which was first detected in Wuhan, China, and has now been 
reported in a growing number of locations worldwide, including the United States. 1The request from 
OSTP is timely given the public health urgency of the outbreak and potential for misinformation. 

In response to your request, we consulted leading expense in the fields of virology, infectious 
disease genomics, genome sciences, epidemiology, immunobiology,

microbiolo&:ir, coronaviruses, 
emerging.infections,biosecurity, and global health, to share their views of whether available genomic 
data on 20 I 9-nCo V are consistent \Vith natural evolution and the data that could help determine the 
origins of 2019-nCoV, specifically from an evolutionary and structural biology standpoint 

Many studies of the genome of 2019-nCoV to berter understand its origin and hO\V it relates to 
viruses found in bats and other speciesa.realreadyunderway."The initial views of the experts-l is that 
the available genomic data are consistent with natural evolution~ and that there is currently no evidence 
that the virus was engineered to spread more quickly among humans. [ask ex.perts to add specifics re 
binding sites?] They also told us that additional genomic sequence data from geographically and 
temporally diverse viral samples, including samples that have been collected prior to the outbreak in 
Wuhan, could be used to clarify the origins of the virus. Understanding the driving forces behind vira[ 
evolution may facilitate the development of more effective strategies for managing the 2019-nCo V 
outbreak international collaboration is more important than ever to overcome these types of global 
challenges. 

The National Academies stand ready to assemble a committee of experts to examine these 
issues in more detail and provide more complete evidence-based advice to you in an expedited manner 
if requested. 

Thank you, again for your commitment to the National Academies a11d our efforts to provjde 
independent, objective analysis; advise the nation; and inform public policy decisions. 

Sincerely, 

1"20 J9 Novd Coronaviros (2019-nCoV) Situation Sumirmry.~Centers forDiscasa Control 1md Prevemion. 3 Feb. 
2020. Jittps://www.cdc.gov/cor<m.ivirus/20 l 9-11CoV/surmm1ry.html#nnchor .... 1580079 l 37454. Accessed 
3 Feb. 2020. 
} (possible add lis1I 
3 Iinsert references! 

~ [possiblyaddbriefexplal1ationthat this does not prcdnde an u11intentional lelease from a laboratorystudyingthe 
evolutionof related cornm1vimsesJ 

llllaoo1eso 


cc: fmsert names] 

Message 

From: 
Sent: 
To: 
Edward Holmes 
2/5/2020 1:23:41 AM 
Garry, Robert F Kristian G. Andersen rambaut-
Subject: Re: Summary -Invitation to edit 

Kristian, can you quickly check those RBD mutations in the pangolin S protein ... 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of S dne IS dne | NSW | 2006 | Australia 

T 
E_ 
On 5 Feb 2020, at 1 :03 pm, Garry, Robert F • wrote: 
https://www.statnews.com/2020/02/04/two-scenarios-if-new-coronavirus-isnt-contained/ 

To your point Ka very good article here about coronaviruses that are endemic in humans (Andrew gets a quote). 

My guess that "quarantines and travel bans will first halt the outbreak and then eradicate the microbe, 
and the world will never see 2019-nCoV again" is unlikely, unfortunately. 

And unfortunately as well I think that we're about to learn that "quarantines and travel bans" are 
really bad for the economy. 


From: Kristian Andersen 

Date: Tuesday, February 4, 2020 at 7:08 PM 
To: Robert Garry 
Cc:Edward Holmes· "rambautQ 
Subject: Re: Summary -Invitation to edit 

External Sender. Be aware of links, attachments and requests. 

That's pretty interesting ... All of which of course happens in humans. I do wonder if there's a scenario in which this thing 
could have been circulating in humans and animals for a while until that perfect little bugger came about and took off. 
Seems a little strange, but definitely not impossible -although, of course, if the O-glycans are somehow involved in the 
infectivity of human cells (as opposed to immunity), then we're swinging back to cell culture. 

On Tue, Feb 4, 2020 at 4:34 PM Garry, Robert F • wrote: 
Another thing about the evolution of the glycans. 
This has happened naturally in other CoV. 

REV0002843 


Not all MHV have an optimal furin site. Those that do have the furin site inevitably also add a 2-3 predicted O-linked 
glycans in or about the cleavage site .. 

Variation on the theme in HKUl, a virus that probably does have intense transmission infecting millions of people each 
year. Here the insert is three Serine residues, which pushes this site to a mucin-like patch (there are already a couple of 
pralines and the SSS is a turn as well) 

Funny thing -not on the attachments, but those strains of MHV and HKU-1 that have a-linked glycans and the furin site 
ALSO have a larger patch -sometimes very large patch -of predicted a-linked glycans at the top of the prefusion form. 
When you see the pattern repeat itself in different viruses you start to believe it. 


From: Robert Garry 

Date: Tuesday, February 4, 2020 at 5:56 PM 

Cc: "rambaut~ 
Subject: Re: Summary -Invitation to edit 

Kristian that's correct about everything he said for the P residue. It's what's shifted me to thinking that the insert of the 
furin site is the result of cell culture passage [or less likely intense transmission in a nonbat host]. Really need to see the 
data from Ron about generating the furim cleavage site on in vitro passage. Really! 

CoV come with or without a furin site. CoV without a furin site are said to be non-cleaved and rely on endosomal 
proteases like cathepsin for entry. However if you infect a virus like SARS in culture in the presense of exogenous 
protease like trypsin its lO0X more effective at entering because the spike gets cleaved and it can enter at the cell 
surface. 

You have to infect flu viruses (the ones without the multibasic cleavage site) in the presence of trypsin, and include 
trypsin in the overlay if you want to get virus spread aka plaques. 

This also contributes to the pathogenicity of -well -highly pathogenic flu virus -different tissues have different 
proteases and are able to "activate" flu to different extents -if the flu v has a furin cleavage site it has a lot more 
choices and can more easily go systemic. 

This is an excellent review on CoV fusion -deals with all the complexities: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397359/ 

Bottom line -I think that if you put selection pressure on a Cov without a furin cleavage site in cell culture you could 
well generate a furin cleavage site after a number of passages (but let's see the data Ron!). It will infect a lot better if it 
can effectively fuse at the cell surface and doesn't have to rely on endosomal cleavage and receptor mediated 
endocytosis .. 

From: Kristian Andersen Date: 
Tuesday, February 4, 2020 at 5:08 PM 

To: Edward Holmes 
Cc: Robert Garry• 
Subject: Re: Summary -Invitation to edit 

External Sender. Be aware of links, attachments and requests. 

REV0002844 


Outside my expertise, but I don't necessarily think that passage in animals would add the glycans. It's more that the 
glycans could suggest some sort of immune system as the glycans often work to 'shield' epitopes. So if the acquisition 
of glycans is adaptive, that would be suggestive of an immune system. 

We didn't write this in the report, but the residues on which the glycans (S, T, and S) are all conserved in the bat virus it's 
the addition of the P that makes it a specific glycan site though (not conserved in the bat, hence not predicted to be 
O-glycans). It's entirely possible that the 'P' works as a flexible residue for the furin cleavage site and by proxy creates 
the (predicted) O-linked glycans. 

I'll let Bob weigh in as well -definitely not my area of expertise. 

K 

On Tue, Feb 4, 2020 at 2:59 PM Edward Holmes rote: 

Agreed. Timing is perfect. 

Bob -a question from Jeremy: 

"Quick question though -why could passage in animals in lab work add the glycans?" 

Any thoughts? 

Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 

School of Life & Environmental Sciences and School of Medical Sciences, 

The University of Sydney I Sydney I NSW I 2006 I Australia 

T 

E 

On 5 Feb 2020, at 9:53 am, Garry, Robert F < wrote: 

Ironically the prevailing theory now in the underbelly if the internet is that the us or other enemy engineered this bio weapon 

and released it on China 

If the public health aspects of this were not bad enough the political fallout would be. 

Good to have cogent science against the bio weapon scenario which is why I favor getting who involved in the "controversy" 

Accidental release is a scenario many will not be comfortable with but it would be irresponsible to dismiss the possibility out 
of hand. 

Sent from my iPhone 

On Feb 4, 2020, at 3:28 PM, Edward Holmes· wrote: 

External Sender. Be aware of links, attachments and requests. 

REV0002845 


Jeremy is passing to Tony and Francis first. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 5 Feb 2020, at 8:12 am, Garry, Robert F 

wrote: 
On the broad topic of O-linked glycans on viruses from China I've attached a model of Alongshan virus, which I know 
Eddie has a particular interest. 

It's instructive to see the mucin-like domains with a high concentration of serines, threonines and pralines. 

This sequence in HKUl CoV is also a mucin like domain: 
481 fassckshkp psascpigtn yrscesttvl dhtdwcrcsc lpdpitaydp rscsqkkslv 

Again several predicted 0-linked glycans (also several at the furin site). 

In the crystal structure Si08 it is disordered because of the a-linked glycans .. 


From: Kristian Andersen 

Date: Tuesday, February 4, 2020 at 2:39 PM 

To: Edward Holmes 
Cc:Robert Garry 
Subject: Re: Sum -
External Sender. Be aware of links, attachments and requests. 

Sounds good Eddie! 

I was on a conference call hosted by the National Academy of Sciences yesterday and a statement about this not being 
"engineering" should be coming out from them -I believe Tony called that meeting. Let's see what comes out of that 
as well. 

The idea of engineering and bioweapon is definitely not going away and I'm still getting pinged by journalists. I have 
noticed some of them starting to ask more broadly about "lab escape" and for now I have just ignored them -there 
might be a time where we need to tackle that more directly head on, but I'll let the likes of Jeremy and Tony figure out 
how to do that. 

K 

On Tue, Feb 4, 2020 at 12:36 PM Edward Holmes • wrote: 
I've just passed to Jeremy. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 

I

The University of Sydney I Sydney I NSW 2006 I Australia 

~I 
REV0002846 


On 5 Feb 2020, at 7:14 am, Garry, Robert F wrote: On 5 Feb 2020, at 7:14 am, Garry, Robert F wrote: 
Another caveat is that I think there is plenty of room for additional discussion amongst the experts. Jeremy's idea (or 
was it Tony's) of a face-to-face under the auspicious of WHO still makes sense to me. 

From: Edward Holmes• 
Date: Tuesday, Februa 
To: Kristian Andersen 
Cc: Robert Garry "rambaut1 
Subject: Re: Summary-Invitation to edit 

External Sender. Be aware of links, attachments and requests. 
Works for me. Should I quickly check with Jeremy to see if he is happy for it to be circulated to the wider group? 

Great job. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 5 Feb 2020, at 7:03 am, Kristian G. Andersen • wrote: 
Did a final pass and I think it looks great. 

Unless others have further comments, I'd say this is ready to go up the chain. Importantly, my assumption is that 
this will not be a document that is meant for public consumption, as that would require much more careful crafting 
and attention to specific wording of key concepts in the document (not really a task I think we could/should take on that 
would be way, way more work). 

K 

On Tue, Feb 4, 2020 at 11:31 AM Garry, Robert F 

wrote: 
Gentlemen -I believe that the document is getting very clean. 
Only a few minor points to address [or not] from my view. 
I believe it is a cogent explanation why concerns were raised. 
If there is a natural explanation for CoV, it needs to be found. A lot of unobserved transmission in animals/humans 

AND as yet unsampled Bat CoV variants (with whole or partial furin sites) must exist. 

Some, perhaps more than a few, will not like it still since it allows that the nCoV may have arisen during cell culture 

passage in a lab (their labs). 

Thanks for the great science ... 

b 

REV0002847 


From: Kristian Andersen 
Reply-To: Kristian Andersen 
Date: Monday, February 3, 2020 at 9:36 PM 
To: Robert Garry 

Subject: Summary -Invitation to edit 

External Sender. Be aware of links, attachments and requests. 

has invited you to edit the following document: 

Error! Filename not specified. 

Summary 

!Error! Filename not specified.lclosing via link to this document as this needs to be safe. Should have a draft of 
the various sections shortly. 

GJ.t§!lhi 
❖i+i 

Google Docs: Create and edit documents online. 
Google LLC, 1600 Amphitheatre Parkway, Mountain View, CA 94043, USA 


not 

You have received this email because someone shared a document with you from Google Docs. 

c:norifiort 

<Alongshan copy.pdf> 

REV0002848 


Message 

From: Edward Holmes 
Sent: 
To: Andrew Rambaut 
External Sender. Be aware of links, attachments and requests. 

CC: Garry, Robert F 
Andersen 
Subject:Re: Summary -Invitation to edit 

Region 6 is the RBD. Could be recombination? Very strange. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
ihe Universw of Sydney | Sydney | NSW | 2006 | Australia 

E 
On 5 Feb 2020, at 9:04 pm, Edward Holmes 

I think we might have dropped the ball with this pangolin virus. I ignored it when I saw it didn't have the furin 
cleavage site. Should now check all the key sites. 
Cheers, 
Eddie 

wrote: 
PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 
T 
E 

On 5 Feb 2020, at 8:44 pm, Andrew Rambaut • wrote: 
I think we need to keep this document live and update it as necessary. Give it a date and version number. 
Andrew 

GARRY0000098 


Sent from my phone. Apologies for brevity or illiteracy. 

On 5 Feb 2020, at 09:23, Edward Holmes· 

wrote: 
Kristian, can you quickly check those RBD mutations in the pangolin S protein ... 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T· 
E 
On 5 Feb 2020, at 1:03 pm, Garry, Robert F 

wrote: 

https:ljwww.statnews.com/2020/02/04/two-scenarios-if-new-coronavirus-isnt-contained/ 

To your point Ka very good article here about coronaviruses that are endemic in humans (Andrew gets a quote). 

My guess that "quarantines and travel bans will first halt the outbreak and then eradicate the microbe, 
and the world will never see 2019-nCoV again" is unlikely, unfortunately. 

And unfortunately as well I think that we're about to learn that "quarantines and travel bans" are 
really bad for the economy. 


From: Kristian Andersen 

Date: Tuesday, February 4, 2020 at 7:08 PM 


"rambaut( 

To: Robert Garry 
Cc:Edward Holmes· 


Subject: Re: Summary -Invitation to edit 

External Sender. Be aware of links, attachments and requests. 

That's pretty interesting ... All of which of course happens in humans. I do wonder if there's a scenario in which this thing 
could have been circulating in humans and animals for a while until that perfect little bugger came about and took off. 
Seems a little strange, but definitely not impossible -although, of course, if the O-glycans are somehow involved in the 
infectivity of human cells (as opposed to immunity), then we're swinging back to cell culture. 

On Tue, Feb 4, 2020 at 4:34 PM Garry, Robert F • wrote: 
Another thing about the evolution of the glycans. 
This has happened naturally in other CoV. 

Not all MHV have an optimal furin site. Those that do have the furin site inevitably also add a 2-3 predicted O-linked 
glycans in or about the cleavage site .. 

GARRY0000099 


Variation on the theme in HKUl, a virus that probably does have intense transmission infecting millions of people each 
year. Here the insert is three Serine residues, which pushes this site to a mucin-like patch (there are already a couple of 
pralines and the SSS is a turn as well) 

Funny thing -not on the attachments, but those strains of MHV and HKU-1 that have a-linked glycans and the furin site 
ALSO have a larger patch -sometimes very large patch -of predicted a-linked glycans at the top of the prefusion form. 
When you see the pattern repeat itself in different viruses you start to believe it. 

From: Robert Garry· 
Date: Tuesday, February 4, 2020 at 5:56 PM 
To: Kristian Andersen , Edward Holmes 
Cc:"rambaut, 
Subject: Re: Summary -Invitation to edit 

-~~----Kristian 
that's correct about everything he said for the P residue. It's what's shifted me to thinking that the insert of the 
furin site is the result of cell culture passage [or less likely intense transmission in a nonbat host]. Really need to see the 
data from Ron about generating the furim cleavage site on in vitro passage. Really! 

CoV come with or without a furin site. CoV without a furin site are said to be non-cleaved and rely on endosomal 
proteases like cathepsin for entry. However if you infect a virus like SARS in culture in the presense of exogenous 
protease like trypsin its lO0X more effective at entering because the spike gets cleaved and it can enter at the cell 
surface. 

You have to infect flu viruses (the ones without the multibasic cleavage site) in the presence of trypsin, and include 
trypsin in the overlay if you want to get virus spread aka plaques. 

This also contributes to the pathogenicity of -well -highly pathogenic flu virus -different tissues have different 
proteases and are able to "activate" flu to different extents -if the flu v has a furin cleavage site it has a lot more 
choices and can more easily go systemic. 

This is an excellent review on CoV fusion -deals with all the complexities: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397359/ 

Bottom line -I think that if you put selection pressure on a Cov without a furin cleavage site in cell culture you could 
well generate a furin cleavage site after a number of passages (but let's see the data Ron!). It will infect a lot better if it 
can effectively fuse at the cell surface and doesn't have to rely on endosomal cleavage and receptor mediated 
endocytosis .. 

From: Kristian Andersen 
Date: Tuesday, February 4, 2020 at 5:08 PM 


To: Edward Holmes· 
Cc:Robert Garry· 
Subject: Re: Summary -Invitation to edit 

External Sender. Be aware of links, attachments and requests. 

Outside my expertise, but I don't necessarily think that passage in animals would add the glycans. It's more that the 
glycans could suggest some sort of immune system as the glycans often work to 'shield' epitopes. So if the acquisition 
of glycans is adaptive, that would be suggestive of an immune system. 

GARRY0000100 


We didn't write this in the report, but the residues on which the glycans (S, T, and S) are all conserved in the bat virus it's 
the addition of the Pthat makes it a specific glycan site though (not conserved in the bat, hence not predicted to be 
O-glycans). It's entirely possible that the 'P' works as a flexible residue for the furin cleavage site and by proxy creates 
the (predicted) O-linked glycans. 

I'll let Bob weigh in as well -definitely not my area of expertise. 

K 

On Tue, Feb 4, 2020 at 2:59 PM Edward Holmes 

rote: 
Agreed. Timing is perfect. 
Bob -a question from Jeremy: 
"Quick question though -why could passage in animals in lab work add the glycans?" 
Any thoughts? 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW 12006 | Australia 

T, 
E 
On 5 Feb 2020, at 9:53 am, Garry, Robert F • wrote: 
Ironically the prevailing theory now in the underbelly if the internet is that the us or other enemy engineered this 
bio weapon and released it on China 

If the public health aspects of this were not bad enough the political fallout would be. 
Good to have cogent science against the bio weapon scenario which is why I favor getting who involved in the 
"controversy" 

Accidental release is a scenario many will not be comfortable with but it would be irresponsible to dismiss the 
possibility out of hand. 
Sent from my iPhone 

On Feb 4, 2020, at 3:28 PM, Edward Holmes 

wrote: 
External Sender. Be aware of links, attachments and requests. 
Jeremy is passing to Tony and Francis first. 
Professor Edward C. Holmes FAA FRS 
The University of Sydney 

GARRY0000101 


On 5 Feb 2020, at 8:12 am, Garry, Robert F 

wrote: 
On the broad topic of O-linked glycans on viruses from China I've attached a model of Alongshan virus, which I know 
Eddie has a particular interest. 

It's instructive to see the mucin-like domains with a high concentration of serines, threonines and pralines. 

This sequence in HKUl CoV is also a rnucin like domain: 
481 fassckshkp psascpigtn yrscesttvl dhtdwcrcsc lpdpitaydp rscsqkkslv 

Again several predicted 0-linked glycans (also several at the furin site). 

In the crystal structure Si08 it is disordered because of the a-linked glycans .. 


From: Kristian Andersen 

Date: Tuesday, February 4, 2020 at 2:39 PM 

To: Edward Holmes 
Cc: Robert Garry 
Subject: Re: Summary -Invitation toe it 

External Sender. Be aware of links, attachments and requests. 

Sounds good Eddie! 

I was on a conference call hosted by the National Academy of Sciences yesterday and a statement about this not being 
"engineering" should be coming out from them -I believe Tony called that meeting. Let's see what comes out of that 
as well. 

The idea of engineering and bioweapon is definitely not going away and I'm still getting pinged by journalists. I have 
noticed some of them starting to ask more broadly about "lab escape" and for now I have just ignored them -there 
might be a time where we need to tackle that more directly head on, but I'll let the likes of Jeremy and Tony figure out 
how to do that. 

K 

On Tue, Feb 4, 2020 at 12:36 PM Edward Holmes· 

wrote: 
I've just passed to Jeremy. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
ih--dney| | Sydney | NSW | 2006 | Australia 

E 

On 5 Feb 2020, at 7:14 am, Garry, Robert F 

wrote: 
GARRY0000102 


Another caveat is that I think there is plenty of room for additional discussion amongst the experts. Jeremy's idea (or 
was it Tony's) of a face-to-face under the auspicious of WHO still makes sense to me. 


From: Edward Holmes 

Date: Tuesday, February 4, 2020 at 2:10 PM 

To: Kristian Andersen 
Cc:Robert Garry "rambaut, 
Subject: Re: Summary -Invitation to edit 
External Sender. Be aware of links, attachments and requests. 
Works for me. Should I quickly check with Jeremy to see if he is happy for it to be circulated to the wider group? 

Great job. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 5 Feb 2020, at 7:03 am, Kristian G. Andersen 

wrote: 
Did a final pass and I think it looks great. 

Unless others have further comments, I'd say this is ready to go up the chain. Importantly, my assumption is that 
this will not be a document that is meant for public consumption, as that would require much more careful crafting 
and attention to specific wording of key concepts in the document (not really a task I think we could/should take on that 
would be way, way more work). 

K 

On Tue, Feb 4, 2020 at 11:31 AM Garry, Robert F 

wrote: 
Gentlemen -I believe that the document is getting very clean. 
Only a few minor points to address [or not] from my view. 
I believe it is a cogent explanation why concerns were raised. 
If there is a natural explanation for CoV, it needs to be found. A lot of unobserved transmission in animals/humans 

AND as yet unsampled Bat CoV variants (with whole or partial furin sites) must exist. 

Some, perhaps more than a few, will not like it still since it allows that the nCoV may have arisen during cell culture 

passage in a lab (their labs). 

Thanks for the great science ... 

b 

From: Kristian Andersen 
Reply-To: Kristian Andersen• 
Date: Monday, February 3, 2020 at 9:36 PM 

GARRY0000103 


To: Robert Garry· To: Robert Garry· 
,··


Subject:Summary -Invitation to edit 

External Sender. Be aware of links, attachments and requests. 
has invited ou to edit the following document: 

Error! Filename not specified. 
Summary 
!Error! Filename not specified.lc1osing via link to this document as this needs to be safe. Should have a draft of 
the various sections shortly. 

GH4iihi.f.i4-i 

Error! 

Google Docs: Create and edit documents online. 

Filename 

Google LLC, 1600 Amphitheatre Parkway, Mountain View, CA 94043, USA 

not 

You have received this email because someone shared a document with you from Google Docs. 

specified. 

<Alongshan copy.pdf> 

GARRY0000104 


Message 


From: Edward Holmes 

Sent: 2/6/2020 2:36:30 AM 

To: 

CC: Andrew Rambaut 
Subject: Re: Summary -Invitation to edit 

From Jeremy. 
"Do you think in the report .... possible to dampen down further the 'conspiracy' idea and make totally neutral? 
Talking with Marion last night and with the WHO meeting next week .... both wondering whether actually publishing this 

sooner, but ruthlessly on the science .... is worthwhile to put that flag down ... " 
Thoughts? 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of S dne S dne NSW I 2006 I Australia 

T 
E 
On 6 Feb 2020, at 11:10 am, Kristian G. Andersen· 

wrote: 
Haha, I got the same email. I assume Andrew probably did too. 
I already said yes. 

Not. 
K 

On Wed, Feb 5, 2020 at 16:05 Garry, Robert F • wrote: 
I'd probably stammer a bit on, "Professor Garry can you assure our audience beyond any reasonable doubt that 
nCo V did not escape from the WIV?" 

From: Edward Holmes • 
Date: Wednesday, February 5, 2020 at 5:46 PM 

To: Andrew Rambaut • 
Cc: Robert Garry , Kristian Andersen· 
Subject: Re: Summary -Invitation to edit 


REV0001890 


External Sender. Be aware of links, attachments and requests. 

I thought I had better say no ... 

Dear Professor Holmes, 

My name is Andrey Kozlov, I'm producer in Russian Broadcasting CompanyNTV. We are making a report on 
false conspiracy theories around new China's coronavirus. I'm looking for an interview opportunity with you 
on this issue. We would like to discuss with you these theories, where they came from, what effect they have 
and etc. Will it be possible for you to meet with our film crew this week? Perhaps, on Thursday or Friday? 
Hope for you cooperation. 

Best regards, 
Andrey Kozlov, 
Producer, 
NTV Broadcasting company 

Cell. 
PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
On 6 Feb 2020, at 9:43 am, Andrew Rambaut • wrote: 
The Sunda pangolin, also known as the Malayan or Javan pangolin, is a species of pangolin. It is found throughout 
Southeast Asia, including Brunei, Cambodia, Java, Sumatra, Borneo, the Lesser Sunda Islands, Laos, Malaysia, 
Singapore, Thailand, Myanmar and Vietnam. 

(wikipedia) 

On 5 Feb 2020, at 22:39, Garry, Robert F • wrote: 
Fascinating-so does this mean they were infected before being smuggled out of Malaysia? 

REV0001891 


_ wrote: _ wrote: 
Date: Wednesday, Febru 
To: Robert Garry 
Cc: Kristian Andersen 
Subject: Re: Summary -Invitation to edit 

External Sender. Be aware of links, attachments and requests. 
Smuggled in. Captured by the anti-smuggling cops in two southern provinces. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E, 
On 6 Feb 2020, at 9:24 am, Garry, Robert F • __ 
SO just info from Wiki but Manis javanica is the Malayian pangolin. 

Chinese pangolin (Manis pentadacty/a) is the one in southern China. 
I guess the ranges overlap some, but is it odd that they got this species? 

From: Edward Holmes • 
Date: Wednesday, February 5, 2020 at 4:12 PM 

To: Robert Garry· 
Cc: Kristian Andersen • Andrew Rambaut < 


Subject: Re: Summary-=-Invitation to edit 

External Sender. Be aware of links, attachments and requests. 
More pangolin viruses on this tree -crazy. 

REV0001892 


PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
On 6 Feb 2020, at 9:08 am, Garry, Robert F • wrote: 
No problem with Marian Koopsman either. 


From: Robert Garry· 

Date: Wednesday, February 5, 2020 at 4:07 PM 

To: Kristian Andersen· 
Cc: Andrew Rambaut , Edward Holmes 
Subject: Re: Summary -Invitation to edit 


Kawaoka is a good guy. Good perspective on GoF research and flu. 

From: Kristian Andersen • 
Date: Wednesday, February 5, 2020 at 4:01 PM 

To: Robert Garryj 
Cc: Andrew Rambaut • , Edward Holmes < 


Subject: Re: Summary -Invitation to edit 

External Sender. Be aware of links, attachments and requests. 

'Ego' is Eddie's genius (he's got many other ... ). 

Yeah, Eddie, good point. Need to nix Barie too then. 

How about Yoshi? He might know some good people in Japan. 

K 

On Wed, Feb 5, 2020 at 13:59 Garry, Robert F • wrote: 
REV0001893 


Subject: Re: Summary -Invitation to edit Subject: Re: Summary -Invitation to edit 
I'm "sure" that Ego was a typo -otherwise well done! 


From: Kristian Andersen· 

Date: Wednesday, February 5, 2020 at 3:58 PM 

To: Edward Holmes· 
Cc: Andrew Rambaut 


External Sender. Be aware of links, attachments and requests. 

EgoHealth people might have some African collaborators they could suggest? 

K 

On Wed, Feb 5, 2020 at 13:57 Edward Holmes 

wrote: 
WHO need geographic breath. Very important for them. 

Thanks for all the suggestions. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney I Sydney I NSW I 2006 I Australia 

T 
E 
On 6 Feb 2020, at 8:55 am, Garry, Robert F 

wrote: 
Yes was just going to suggest Malik Peiris from Hong Kong -brings expertise of Co V and flu. 

Not sure Christian Happi is the right person for CoV. His input would be very general. 

I'm told they had or about to have a meeting on Co V preparedness in Dakar. But not sure who is involved. 

Might be a place to start. 
MERS Co V has been isolated from camels in Kenya, but mostly WIV and outside investigators involved. 

REV0001894 


From: Edward Holmes 

Date: Wednesday, February 5, 2020 at 3:43 PM 

To: Andrew Rambaut • 
, Kristian Andersen< 
-Invitation to edit 
Cc: Robert Garry· 
Subject: Re: Summary 

External Sender. Be aware of links, attachments and requests. 
Thanks. Anyone from Asia? Africa? 
Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 6 Feb 2020, at 8:36 am, Andrew Rambaut • wrote: 
Colin Parrish, Jamie Lloyd Smith, Sara Sawer for zoonotic theory? 

A 
Sent from my phone. Apologies for brevity or illiteracy. 

On 5 Feb 2020, at 21:28, Garry, Robert F 

wrote: 
Drosten, Fazan, Fouchier, Barie and Shi Zheng Ii from WIV -to capture different sides of the various 
scenarios. 

Ab Osterhaus, Linfa Wang, and Peter Diazek to capture the bats. 

George Gao and possibly Steve Harrison for structure. 

Seems like she may be retired but probably has deepest historical perspective on Co V research: 

http:/ /www.ucdenver.edu/ academics/ co lleges/medicalschoo 1/ departments/ImmunologyMicro biology/faculty/ 
departmental/Pages/HOLMESKV.aspx 

Kathryn V. Holmes, Ph.D. 

REV0001895 


12800 E. 19th Ave., RC-1 N 9127 
Mail Stop 8333, Aurora, CO 80045 

Phone: 
E-mail: 
From: Edward Holmes < 
Date: Wednesday, February 5, 2020 at 3:13 PM 

To: Kristian Andersen· 
Cc: Robert Garry 
Subject: Re: Summary -Invitation to edit 

External Sender. Be aware of links, attachments and requests. 
I've asked Tommy to check the metagenomic assembly and to look at the synonymous changes. At face 
value it looks like recombination, which itself raises a whole set of other questions. Just so random that it is 
illegally smuggled pangolins from southern China. 
Jeremy has the green light from WHO. Can you think of good sensible people to be on it? Need gender and 
geographic diversity. 
Best wishes, 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 

The University of Sydney I Sydney I NSW I 2006 I Australia 
T 
E, 
On 6 Feb 2020, at 3:14 am, Kristian G. Andersen· 

wrote: 
Yup, agreed. Need proper biochemistry to really answer this question. 

REV0001896 


K 

On Wed, Feb 5, 2020 at 07:49 Garry, Robert F • wrote: 
Yeah_ I reread the Barie JV paper and still think some caution is needed. It's a good paper, but nCoV or 
it's progenitor may have found another RBD binding solution that might be as good or better. Argument 
that nCoV is inferior, hinges on nCoV aa501. However, there's a proline at 499 that's not present in SARSv 
or civet v (it is present in pangolin and RaTG 13), which would put in a kink and change a lot. 

From: Kristian Andersen • 
Date: Wednesday, February 5, 2020 at 9:27 AM 
To: Robert Garry· 
Cc: Edward Holmes , Andrew Rambaut 


Subject: Re: Summary -Invitation to edit 

External Sender. Be aware of links, attachments and requests. 
Wait, I have the pangolin sequences -will take a look once I'm in the office. 

K 

On Wed, Feb 5, 2020 at 7:20 AM Kristian G. Andersen· 

wrote: 
Eddie, can you please share the pangolin sequence? I can take a look later today (hopefully -super packed 
calendar). If not today, definitely tomorrow. 

Bob, for the idea about civets not being optimal -take a look at this 
paper: https://www.ncbi.nlm.nih.gov/pubmed/3199643 7 

Once I have had a look, I'll update on Slack -let's try and keep stuff on there so it doesn't get lost. 

K 

On Wed, Feb 5, 2020 at 6:24 AM Garry, Robert F wrote: 
I Worth pointing out -if the crackpot charge comes re cell culture hypothesis -that we are discussing this 
in private amongst experts. 

Clearly and I think correctly our approach has been different than say the flawed nejm paper -see science 
feb3 -about asymptomatic infection -Drosten was on the rushed out paper Tony got tripped up. Public 
error and pretty important. IMO they should retract the paper to send clear message. 

Sent from my iPhone 

On Feb 5, 2020, at 5:18 AM, Edward Holmes 

wrote: 
REV0001897 


External Sender. Be aware of links, attachments and requests. 

The pangolin virus looks like it might fall in roughly the same place on the tree as those new bat virus 
trees I put on Slack. Don't have the seqs of those yet. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 5 Feb 2020, at 9:52 pm, Andrew Rambaut 

wrote: 
Perhaps say we are adding new information? See whether he wants to hold off. I suspect Bethesda will be 
sending it round already? 

I think we need to add a section about the pangolin and possibly something about whether the glycan sites 
are evidence of selection by an immune system? 

A. 

On 5 Feb 2020, at 10:47, Edward Holmes 

wrote: 
The animals are from Guangdong and Guangxi. Seized by customs. Need those Hubei pangolins. 

Should I tell Jeremy to hold on sending the summary out to the group while we investigate more or does 
that really matter? He did say that more wildlife needed to be studied. He's sent it to the Bethesda boys. 
Best wishes, 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney I Sydney I NSW I 2006 I Australia 

T 
E 
On 5 Feb 2020, at 9:34 pm, Andrew Rambaut • wrote: 
REV0001898 


Do we know where this pangolin is from? Guangdong markets? 
A. 

On 5 Feb 2020, at 10:31, Edward Holmes • wrote: 
I've asked Tommy to check for synonymous changes. He's writing a paper. Only got the figure this 
afternoon. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 5 Feb 2020, at 9:25 pm, Andrew Rambaut • wrote: 
Need to look for some synonymous mutations. Perhaps the nCoV progenitor is also in Pangolins (widely 
traded illegally)? 

A. 

On 5 Feb 2020, at 10:22, Edward Holmes· 

wrote: 
I Region 6 is the RBD. Could be recombination? Very strange. 

REV0001899 


Message 

From: Andrew Rambaut 

Sent: 2/7/2020 1:10:22 PM 


To: Kristian G. Andersen 

CC: Edward Holmes Garry, Robert F 
Subject: Re: Stuff 
Don't worry about FOI. Huawei will be feeding all of this directly to Xi Jinping. 

A 

Sent from my phone. Apologies for brevity or illiteracy. 

On 7 Feb 2020, at 21:05, Kristian G. Andersen 

wrote: 
I would argue that any animal being identified would be beneficial to them -otherwise we're all going to point 
fingers at them telling people that they're so shit that they can't even predict the outbreaks of their own making ... 
Too harsh? 
K 
[for a potential future FOIA reader -please note that I can at times be sarcastic and have a knack for bad jokes]. 
On Fri, Feb 7, 2020 at 12:59 PM Andrew Rambaut • wrote: 
No. They will hate it being pangolins. They were saying the had predicted the bats. 

A 

Sent from my phone. Apologies for brevity or illiteracy. 

On 7 Feb 2020, at 20:53, Edward Holmes· 

wrote: 
No, not at all. 
Just Twitter chat. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
REV0002816 


On 8 Feb 2020, at 7:51 am, Kristian G. Andersen 

wrote: 
Is this pangolin stuff the Ego guys? 

On Fri, Feb 7, 2020 at 12:42 PM Garry, Robert F • wrote: 
Shameless. 


From: Edward Holmes 

Date: Friday, February 7, 2020 at 2:18 PM 

To: Robert Garry· 
Cc: Kristian Andersen Andrew Rambaut 


Subject: Re: Stuff 

External Sender. Be aware of links, attachments and requests. 

Entertaining that the Ego Health crowd agree that having a press conference without providing the data is not 
the right way to proceed ... no similarity to Bombali virus then. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 8 Feb 2020, at 2:46 am, Garry, Robert F • wrote: 
Some comments over on the Slack channel, but need that 99% pangolin sequence. 

I agree that the presence of the furin site would all but rule out passage. 

If it's not there (or at least some insert) passage isn't ruled out (data from Fazan or Fouchier critical here). 

Stating the somewhat obvious here: In Kristian's alignment Pangolin337 is essentially the RBD of SARSCoV-
2 save for a single amino acid change (what are the differences at the nucleotide level?), but differs more 
than BaTG 13 elsewhere. May be looking at some mosaicism or recombination event amongst the different 
Pangolin Co V strains that should be "fairly" easy to pick up on. 


From: Kristian Andersen 

Date: Friday, February 7, 2020 at 9:29 AM 

To: Robert Garry 
Cc: Edward Holmes Andrew Rambaut • 


Subject: Re: Stuff 

External Sender. Be aware of links, attachments and requests. 

REV0002817 


"But, does this swing it completely away from the passage idea?" 

No, it does not, however, every little helps. The furin is still peculiar, but if we're discussing whether 
evolution could create a furin cleavage site or not, then, well, we better hit the pub sooner rather than later. 
Now, the presence of the furin site in pangos would nail it, but the absence (as it appears to be) wouldn't really 
tell us much. 

K 

On Fri, Feb 7, 2020 at 2:41 AM Garry, Robert F • wrote: 
Yes indeed 
Would be good to know about the 12 base pair insert 
Would be great to see any insert there. 
If not will be important to fetermine where this pangolin came from 
As Andrew taught [me] they come from all over illegally 
Also don't know obviously if it's 99.0 or 99.8%. If there is a 99% virus there may well be a 99.8% virus 

back in the pangolin's home country. 

Sent from my iPhone 

On Feb 7, 2020, at 4: 11 AM, Edward Holmes 

wrote: 
External Sender. Be aware of links, attachments and requests. 
OK, I've just emailed one of the authors. Let's hope we get a reply. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 

REV0002818 


The University of Sydney I Sydney I NSW I 2006 I Australia 

T 
E 
On 7 Feb 2020, at 8:55 pm, Garry, Robert F 

wrote: 
That is the or at least a key question. 
Sent from my iPhone 

On Feb 7, 2020, at 3:46 AM, Andrew Rambaut • wrote: 
External Sender. Be aware of links, attachments and requests. 
Can we at least get a pers-comm as to whether it has the insertion or not? 
https ://www.nytimes.com/reuters/2020/02/07 /world/ asia/07 reuters-china-health-pangolins.html 
https://www.businessinsider.com/china-scientists-identify-pangolin-as-possible-coronavirus-host-20202?
r=US&IR=T 
A. 

On 7 Feb 2020, at 09:36, Edward Holmes • wrote: 
Jeremy wants us to publish our report somewhere. Thoughts? 

I'll need to update the pangolin stuff again. Not proven of course, but it makes complete sense. We don't 
know what the amino acid sequences of these pangolin viruses that 99% similar to 2019-nCo V will look like, 
but there must be decent chance they have all the key mutations. But, does this swing it completely away 
from the passage idea? 

Things are changing so fast it is hard not be redundant. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 

School of Life & Environmental Sciences and School of Medical Sciences, 


REV0002819 


Begin forwarded message: 

From: Jeremy Farrar· 


Subject: Re: Stuff 
Date: 7 February 2020 at 5:31:44 pm AEDT 

To: Edward Holmes • 
I will be neutral. 

Anyone from China? 

Tomorrow morning fine. 

Any preference for journal? All will take immediately, I can let them know coming if helpful and you have a 

preference 
With revisions -will share with the TC group over the weekend -if OK -got to add the new info 


From: Edward Holmes 

Date: Friday, 7 February 2020 at 06:29 

To: Jeremy Farrar· 


Subject: Re: Stuff 
Tonight? More likely to you tomorrow am. Just need more about the pangomania which is very important. 
Let me know if you need anything else changed. 
Not sure about journal. 
Authors: Kristian, me, Bob, Andrew. You? Or do you want to be neutral? 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 

The University of Sydney I Sydney I NSW I 2006 I Australia 
T 
E 
REV0002820 


On 7 Feb 2020, at 5:26 pm, Jeremy Farrar· 

wrote: 
When can you update? 
Lancet 

Nature 
NEJM 
Will all review immediately, after quick QC, will share with WHO. 
Can I help with any of the editors? 
Who will be authors from your side? 

Andrew Rambaut 

Institute for Evolutionary Biology 
Ashworth Laboratories, University of Edinburgh, Edinburgh, EH9 3FL, UK 

contact -I http://tree.bio.ed.ac.uk I tel· 


The University of Edinburgh is a charitable body, registered in Scotland, with registration number 
SC005336. 

REV0002821 


Message 

From: R.A.M. Fouchier 


Sent: 2/8/2020 2:50:00 PM 

To: 
CC: 

afauci( 

Andrew Rambaut 
Eddie Holmes 
kga19781 
Mike Ferguson 
Subject: Re: [ext] 2019 N-CoV 

I do not understand Andrews argument" The sequence data clearly and unambiguously rules out any form of 
lab construct or engineering of the virus.". Molecular biologists like myself can generate perfect copies of 
viruses without leaving a trace, eg the BamHI site. The arguments for and against passaging and engineering are 
the same if you ask me. 
Ron 

From: Andrew Rambaut 
Sent: Saturday, February 8, 2020 4:16 PM 
To: Jeremy Farrar 
Cc:Eddie Holmes; Christian Drosten; kga19781-; 
p.vallance1 ; collinsf1-; afaud 
m.koopmans Mike Ferguson 
Subject: Re: [ext] 2019 N-CoV 

I agree with Eddie, I think someone needs to lay out the science of this before it gets out of hand ( and causes 
more formal investigations). 

I am of the view that the natural selection hypothesis is the most likely (specifically the non-bat reservoir). And 
as Eddie mentioned this is becoming more likely from day to day with the pangolin story. 

I disagree with Ron that the passaging hypothesis is evidentially equal to the engineering hypothesis. The 
sequence data clearly and unambiguously rules out any form oflab construct or engineering of the virus. It 
doesn't really have anything to say about the relative plausibility of the 3 hypotheses for selection. 

I think we need stronger arguments than an assertion that no lab has done those experiments. We can definitely 
argue that it has nothing to do with RaTG 13 ( or SARS or any other published SARSr virus). The argument that 
we would need to offer this hypothesis for all other outbreaks is not a useful one in this context. 

Is it possible to argue that A) a passaging experiment wouldn't create the features we see? or B) that there are 
logical reasons why someone wouldn't do such an experiment? 

The pangolin virus that was announced in the press conference might solve this issue if it has the furin cleavage 
site insertion which would be all but conclusive for the natural scenario. 

Andrew 

rfgarry1 r.fouchier 
REV0000735 


On 8 Feb 2020, at 20:21, Jeremy Farrar 

wrote: 
The theory of the origin of the has gathered considerable momentum not in social media, but increasingly among some 
scientists, in main stream media, and among politicians. 

The aim of this was to bring a neutral, respected, scientific group together to look at the data and in a neutral, 
considered way provide an opinion and we hoped to focus the discussion on the science, not on any conspiracy or other 
theory and to lay down a respected statement to frame whatever debate goes on -before that debate gets out of hand 
with potentially hugely damaging ramifications. 

With the additional information on the pangolin virus, information not available even 24 hours ago, I think the argument 
is even clearer. 

My preference is that a carefully considered piece of science, early in the public domain, will help mitigate more 
polarised debate. If not, that debate will increasingly happen and science will be reacting to it. Not a good position to 
be in. 


From: Edward Holmes· 

Date: Saturday, 8 February 2020 at 20:11 

, Josie 
, Mike Ferguson 
Subject: Re: [ext] 2019 N-CoV 
Hi Christian, 
I don't know where this story came from, but it has nothing whatsoever to do the HIV nonsense. Please don't associate 

this with that. This is a broader story. 
Ever since this outbreak started there have suggestions that the virus escaped from the Wuhan lab, if only because of 
the coincidence of where the outbreak occurred and the location of the lab. I do a lot of work in China and I can you that 

a lot of people there believe this and believe they are being lied to. Things were made worse when Wuhan lab published 
the bat virus sequence -a bat sampled in a different province for which they have a large collection of samples. 
I believe the aim/question here is whether we, as scientists, should try to write something balanced on the science 

behind this? There are arguments for and against doing this. 

Personally, with the pangolin virus possessing 6/6 key sites in the receptor binding domain, I am in favour of the natural 
evolution theory. 
Best wishes, 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

REV0000736 


THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
I I I

The University of Sydney I Sydney NSW 2006 Australia 

Tl 
El 
On 9 Feb 2020, at 6:52 am, Drosten, Christian I wrote: 
Dear All, 
I am overloaded with nCoV patient-related work and will need a few days before I can work on this text. 
Can someone help me with one question: didn't we congregate to challenge a certain theory, and if we could, drop it? 

This whole text reads as if the hypothesis was obvious, or was brought up by some external source, forcing us to respond. 
Is this the case? It does not seem as if this was linked to the HIV nonsense. 
Who came up with this story in the beginning? Are we working on debunking our own conspiracy theory? 
Christian 

Professor Christian Drosten 

Director, Institute of Virology 
Scientific Director, Charite Global Health 

Charite -Universitatsmedizin Berlin 
Campus Charite Mitte 


Germany 

E-Mail:I 
https:// 
https://globalhealth.charite.de/ 
Von: Jeremy Farrar 

Datum: Samstag, 8. Februar 2020 um 10:45 

An: Edward Holmes 
Betreff: [ext] FW: 2019 N-CoV 
APOLOGIES WITH ALL CORRECT EMAILS 

Kristen, Andrew, Bob, Eddie have reworked the summary and it is attached here. 

REV0000737 


We are pushing to get the sequence data from the reports on the pangolins, but do not have currently, clearly that is 
very important to incorporate. 

Interested in your views 

• Is this reasonably balanced given the data? 
• Is there anything anyone disagrees with? 
• Is there anything more in relation to what would seem to be the two possibilities 
o Nature, Intermediate host, evolution and passage 
• Future data you may have 
• Advice on whether KA, AR, RG and EH should publish this. 
These and other thoughts welcome in confidence. 

Andrew 
Institute for 
Ashworth 
Rambaut 
Evolutionary 
Laboratories, 
Biology 
University of Edinburgh, Edinburgh, EH9 3FL, UK 
contact I http://tree.bio.ed.ac.uk I tel 

The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. 

REV0000738 


Message 

From: 
Sent: 
To: 
CC: 
Subject: 
Jeremy Farr 
Andrew 
• Josie Golding 
; christian.drosten1-; Mike 
Attachments: Summary.Feb7 RF.pdf 

I am not in favor of publishing as is. I fail to see how the last of the three discussed scenarios (passaging) does not fall 
under the category of "laboratory manipulation". There is no evidence that might hint to this scenario and hence it 
should be put aside just like the engineering option. As far as I am aware, no laboratory has worked on passaging the 
pangolin-origin virus, the bat-CoV RaTG13, or another closely related virus or had access to it prior to the outbreak. That 
nCoV-2019 could originate from a SARS-like virus in Chinese labs can also be excluded. This information could be added 
after reference 10 in the manuscript, to provide further argument. 
If we assume passaging as a possible scenario here, we must assume it is also plausible for all outbreaks from the past, 
present and future. This manuscript would be much stronger if it focused on the likelihood of the first 2 scenarios as 
compared to intentional or accidental release. That would also limit the chance of new biosafety discussions that would 
unnecessarily obstruct future attempts of virus culturing for research and diagnostic purposes for any 
(emerging/zoonotic) virus. 

I made some additional comments in the attached pdf, also in line with Andrew's comments. 

With kind regards, 
Ron 

Van: Jeremy Farrar 
Datum: zaterdag 8 februari 2020 om 10:45 

Andrew Rambaut • 
Onderwerp: FW: 2019 N-CoV 
APOLOGIES WITH ALL CORRECT EMAILS 
Kristen, Andrew, Bob, Eddie have reworked the summary and it is attached here. 
We are pushing to get the sequence data from the reports on the pangolins, but do not have currently, 
very important to incorporate. 
Interested in your views 
Is this reasonably balanced given the data? 
clearly that is 
REV0000343 


Is there anything anyone disagrees with? 
Is there anything more in relation to what would seem to be the two possibilities 

o Nature, Intermediate host, evolution and passage 
Future data you may have 
Advice on whether KA, AR, RG and EH should publish this. 
These and other thoughts welcome in confidence. 

REV0000344 


Message 

From: 
Sent: 
To: 
CC: 
Subject: 
kga19781-
collinsf-afauci~-Josie Golding 
christian.drosten-
Attachments: Summary.Feb7_MF.pdf 

Dear Jeremy et al 

I have made some comments and suggestions on the pdf attached. 

I am not an expert on protein O-glycosylation -however, Dr Tabak, who was on the call last weekend, is and if 
I were to consult anyone else on this it would be Henrik Clausen 
https://icmm.ku.dk/english/research-groups/clausen-group/ 

However, from what I do know of general glycobiology, I am not sure one can conclude that an immune 
system would be required to select for O-glycosylation sites. Once an alpha-helix is disturbed by the 
introduction of a praline, adjacent Ser and Thr residues will be (over-)predicted to have O-glycosylation 
potential -hard to know the functional consequences/significance without knowing whether the potential 0sites 
are actually occupied. 

Regards 

Mike 

From:Jeremy Farrar , 
Sent: 08 February 2020 09:45 
Andrew Rambaut 
christian.drosten 
Subject:FW: 2019 N-CoV 
APOLOGIESWITH ALL CORRECT EMAILS 

Kristen, Andrew, Bob, Eddie have reworked the summary and it is attached here. 

We are pushing to get the sequence data from the reports on the pangolins, but do not have currently, clearly that is 
very important to incorporate. 
Interested in your views 

REV0000827 


• Is this reasonably balanced given the data? 
• Is there anything anyone disagrees with? 
• Is there anything more in relation to what would seem to be the two possibilities 
o Nature, Intermediate host, evolution and passage 
• Future data you may have 
• Advice on whether KA, AR, RG and EH should publish this. 
These and other thoughts welcome in confidence. 

REV0000828 


Overview 

Sequencing of 2019-nCoV revealed two notable features of its genome. We investigate these features and 
outline some examples for how the virus may have acquired them. We also discuss some scenarios by 
which these features could hm,e arisen. Analysis of the virus genome sequences clearly 
demonstrates that the virus is not a laboratory construct or experimentally manipulated virus. 

We believe the features discussed, which may explain the infectiousness and transmissibility of 
2019-nCoV in humans, €61:::Hehave~risen through selection and adaptation prior to the initial outbreak. 

The two primary features of 2019-nCoV of interest were: 

• Based on structural modeling and early biochemical experiments, 2019-nCoV appears to be 
optimized for binding to the human ACE2 receptor. 
• The highly variable spike protein of 2019-nCoV has a furin cleavage inserted at the S1 and S2 
boundary via the insertion of twelve in-frame nucleotides. Additionally, this event also led to the 
acquisition of three predicted O linlEed glycan§.__around the furin cleavage site. 
Mutations in the receptor binding domain of 2019-nCoV 

The receptor binding domain (RBD) in the spike protein of SARS-CoV and SARS-like coronaviruses is the 
most variable part of the virus genome. When aligned against related viruses, 2019-nCoV displays a 
similar level of diversity as predicted from previous studies, including to its most closely relate~virus SARS-
like CoV isolated from bats (RaTG13, which is ~96% identical to 2019-nCoV). 

Six residues in the RBD have been described as critical for binding to the human ACE2 receptor and 
determining host range1. Using coordinates based on the Ubani strain of SARS-CoV,they are Y442, L472, 
N479, D480, T487, and Y491 (the corresponding residues in 2019-nCoV are L455, F486, Q493, S494, N501, 
and YSOS). Five out of six of these residues are mutated in 2019-nCoV compared to the closely related 
virus, RaTG13(Figure 1). Based on modeling 1 and early biochemical experiments 2.3, 2019-nCoV seems to 
have an RBD that may bind with high affinity to ACE2 from human, primate, ferret, pig, and cat, as well as 
other species with high receptor homology. In contrast, 2019-nCoV may bind less efficiently to ACE2 in 
other species associated with SARS-like viruses, including r.~1.1.J.J..1..2....i...u· 
1....__ ___

u...i..~LL.l.!,,jL....l,,,il~ _________ 

do we have the pangolin ACE2 sequence/model?
A phenylalanine at F486 in 2019-nCoV corresponds to L4 
experiments the leucine at position 472 mutated to phenylalanine (L472F)4, which has been predicted to 
be optimal for binding of the SARS-CoV RBD to the human ACE2 receptor 5• However, a phenylalanine in 
this position is also present in several SARS-like CoVs from bats (Figure 1). While these analyses suggest 
that 2019-nCoV may be capable of binding the human ACE2 receptor with high affinity, importantly, the 
interaction is not predicted to be optimal1. Additionally, several of the key residues in the RBD of 
2019-nCoV are different from those previously described to be optimal for human ACE2 receptor binding 
as determined by both natural evolution of SARS-CoV and rational designs. This latter point is strong 
evidence against 2019-nCoV being specifically engineered as, presumably, in such a scenario the most 
optimal residues would have been introduced, which is not what we observe. 

1.SAAScoron~NSC01S·MV91998.1 ~WNTRNIOATSTGN~NYKYR~LRHGKLRPFEROISNVPFSPOGKPCT PPAPNCYWPLRllYGFYTTSGIGYQPVRVVVLSFELLNAPAT' 
2. SAAScoranl'tArvsA021 • MV979S6. 1 4WNTRNIOATSTGNYNYKYR~LRHGKLRPFEROISNVPFSPDGKPCT PPAPNCYWPLllrnYGrVTTSGIGYQPVRVVVLSFElLNAPAT' 
J. SAAScoronavl'n;sA001 • MV97984.1 ~WNTRNIOATSTGNYNYK&IRYlRHGKlRPFERDISNVPFSPaGKPCT PPAPNCYWPLROVGFYTTSGIGYOPVRVVVLSFElLNAPAT' 
4. SAAS corof\3'Jir'U~ 8J182-1 l AC869905.1 4WNTRNl0A1STGNYNYKYRYLRHGKLRPFEROISNVPFSPDGKPCT PPA■NCYWPLKDVGFYTTTGIGYQPVRVVVLSF(LLNAPAr· 
s, s.AAScoronaiv\rus8J182a • ACB69860.1 ~WNTRNIDATSTGNYNYKYRYLRHGKLRPFERDISNVPFSPOGKPCT PPA■NCYWPlffllYGFVTTTGIGYQPYRVVVLSFElLNAPAT' 
16.SARS (Oton.MrvsR'M'kfurt 1 • AAP3?.i,97.I ~WNTRNIOATSTGNYNYKYRVLRHGKlRPFEROISNVPFSPOGKPCT PPA■NCYWPLNDYGFYTTTGIGVQPYRVVVLSFElLNAPAT' 
'1.SAAScoroniNtn.lSUtNnl•AYl?4?◄ 
1.l • S pi.ff ~WNTRNIOATSTGNYNYKYRVlLRHGKLRPFERD SNVPFSPDGKPCT PPA■NCYWPLNDVGFVTTTGIGYOPYRVVVLSFELLNAPAT'
• . -..
8.SAAScoron""""HKIJ•'.39649•AllOS483,\ ,wNTRN I OATSTGN'!NYK Y RYil RHGK LR PF [ RD SNVP F 5 P DGK PCT P PA■'ICYWP Ll!IJIIYGF YTTTG GYQP YRVVV LS FELL NA PAT' 

9.Sovo,ea«nere,pC,otory5llnOromo,,clotodc., ~WNTRN I OATSTGNN'NYK Y!!YLRHGK L RP FE RD SNVP F SP DGK PCT P PA■'ICYWP l NIJYG F YTTTG GYQP YRVVV LS FELL NAP AT' 

10,S.W,..ocuto"'Plri!O<y"f"dn>me•r<l.>t<dc... '<WNTRN I OATS TGNVNY K YR Y l RHGK l RP FE RD SNVP F SP DGIC PCT P PA■NCYWP LtlaYG F YTTTG GYQPYRVVV LS FELL NAPA T' 

11.SARS<0<o"'"'""NS.1-MR91Sa6 I ,wNTRN I OATS TGNYNY K YRYLRHGK l RP FE RD SNVP F SP OGK PCT P PA■NCYWP LOYGF YTTTG GYQPVRVVV LS FELL NA PAT' 

12.SARScotonav,ru,MAISboN1 -Af.AI0473.I '<WNTR NI OATSTGNlltNYK YRY LRHGK l RP FE RD SNVP F SP DGK PCT P PA■'<C YWP L lllJYG F YTTTG G YQPYRVVV L 5 F [LL NAPA r' 

13.SARScoro"""'"" .... ,se,oNl ,Af-'10443.1 4WNTR NI OAT STGI\RNY K YR 'liLEIHGK LR PF E RD SNVP F SP DGK PCT PPA■'ICYWP L 'liUIVG F VTTTG G YQPYRVVV LS f El L NAPA, .. 

M.S.V.reocu1<ro,plroto,y ,yn<l,o-r<!atodc. .. '<WNTR NI DAT STGNYNY KY R)'. LUHGK l RP FE RO S NV PF SP DGK PCT PP A■NC YWP ll!IJIY G FY TTT G G YQ P VRVVV LS FE l L NA PAT' 

1S.SARScoronavi,u,E,coNI,"61210781 4WNTRN I OATSTGNYNYK YRS l RHGK LR PF ERO SNVP F SP DGK PCT P PA■NCYWP Llil:IVG F YTTTG GYQP VRVVV LS F Cl LNA PAT' 

16.SAASco,onaviru,Bj302 •Mll0762S.1 '<WNTRN I OATS TGNYNYK YRY L RHGK l RP f ERO SNVPf SP OGK PCT P PA■NCYWP l SDYGF VTTTG GYQPYRVVV LS FE l L NAPAT' 

17.SARSw,or,av,ru,BJ302,AAA07627.1 ~WNTRN I OATS TGNYNY K YR Y L RHGK LR PF E RD SNVP F SP DGK PCT P PA■'ICYWP L SllYG r YTTTG G YQP YRVVV LS FELL NAPAT' 

18.SARScoronav\rusGOO\·MPS\227.l ~WNTRN I DAT S'TGNYN V K YR Y L RHGK l RP FE RD SNVP F SP DGK PCT P PA■NCYWP L 'flll!YG I YTTTG GYQP VRVVV L SY ELL NAP AT' 

19.RhlnolophYs.«lnls<Ofon..,irus•AHX37SSS.1•WNTRN I DA 1 S S-GN F NVK YRS L RHGK LR PF ERO SNVP F SP OGK PCT P PA F NCYWP Lill£iYG F VTHWG GYQP VRVVV l SF ELL NAPAT' 

20 Rh;nolophusalfinlscoronov~u,.IIHX37S69.1 •WNTRN I OATS SGN F•V K YRS LRHGK l RP FE RD I SNVP F SP DGK PCT P PAF NCYWP L&illllVG F VTTIIJG GYQP YRVVV LS F Cl L NAPAT' 

21.BotSARS-•kec,,,oflOvi,u,-AVP78031,1 ~WNTAKlllDmJ-----NY F YRSWR'STK L KP FE RO■S $-------------• -N'GaRTL STVlllFtlP P-YQ'ATRVVV LS FELL NAPA T' 

22.e., SARS-1,k•=-=•AVP78042,1 ,wNTil.KlllOT'G-----av FY R SlfR'!,TK L 1( PF ER o■s so■-------------N'Glfll"H S TVQF P •-YQA TRVVV L SF E LL NAP AT' 

?J.&'l<rorona-,ln,;,QH .. 3300.1 ,wN'SKBI DAK'SGGN F NV■YR■F RIK Ajqil KP FE RD I ST-.i:YQXGSK P Clif!.llTG■NCYl'/'IP l YRVGf Y P g;g.RQP YRVVV LS FE l L NA PAT' 

~;:~~:~t:gm~,~~n~~~Jf~i¾2~:~:~~~-g~~=~~~~~=~~=rn~~~t ~~~ ~ ~g:n:J~~ga~~~ggt~~g~~~~::g■G~g~~~~~~t ~ ~ ~ tt~~~~:j::

. . -. . 

Figure 1 I Mutations In contact residues of the 2019-nCoV spike protein. The spike protein of 2019-nCoV (bottom) was 
aligned against the most closely related SARS and SARS-like CoVs. Key residues in the spike protein that make contact to the 

REV0000829 


ACE2 receptor have been marked with blue boxes in both 2019-nCoV and the SARS-CoV Urbani strain. 

Furin cleavage site and o linked glycan~ 
An interesting feature of 2019-nCoV is a predicted furin cleavage site in the spike protein (Figure 2). In 
addition to the furin cleavage site (RRAR), a leading P is also inserted so the fully inserted sequence 
becomes PRRA (Figure 2). A proline in this position is predicted to create three flanking O liRl<ed glycan~ 
at S673, T678, and S686. A furin site has never before been observed in the lineage B betacoronaviruses 
and is a unique feature of 2019-nCoV. Some human betacoronaviruses, including HCoV-HKU1 (lineage A) 
have furin cleavage sites (typically RRKR), although not in such an optimal position. 

1.SARscc,onMNSC018·AA\/9799S.1 I Y S TGlllNVF QTOAGC LI GAE HIio.TS YE co IP I GAG I CAS YHT■ 
S S l R STS OKS I VA YTMSL GAGSS I A Y SNNT I A I PTN F S I 
2.SARSccron.MnaA0:21 AAW7Q&i.1 J YSTG1'1NVJ!QTQAGCL IGAEHVIJTSVECO P j GA.GI CASYHTIIISS-1 RSTSQKS I VAVTMSlGA.VSS IAVSNNT I At P'TNI= SI 
3.SARSccro"J\'f,usAOOl,AA\19798◄.I I Y 5 TGN!lillf QTOAGC l 1 GAE HIIQTS YE CO P I GAG 1 CA 5 Y HT S SI RS TS QK 5 VAYTMSL GAQ'.S S 1 A Y SNNT I A I P°IN f S I 
~.S/IRScoron.wirvs8Jl82·12 •AC-OS.1 1 Y 5 TGNNVF QTQAGC L I GAE HVO:T SY ECO P I GAG I CA S YHTIIS■ 
l RS TS OKS VAYTMSL GAllS SI AY SNNT I A I P°IN F S I 
5.SARScoronJVirus8j182.l·ACB69™>.1 I Y S TGNNV F QTQAGC L 1 GAE HVQ I'S YE co P I GAG I CAS YH T■S■ 
l RS TS QK S VA YTMSL GAO:SS 1 A Y SNNT I A IP 1N F S I 
6.SARSccronMttJSfrantfun 1-AAP33697.1 I YS TGNNV f QTOAGC L 1 GAE HVD'TS Y ECO P I GAG I CA 5 YHl S■ 
I RS r 5 OK 5 VAYTMSL GMlSS 1 AV SNNT I A I PTN f 5 I 
7.SARSroron.wiru'IVrboni..1'Y278?41.1 •Spr.. I 'IS TGNNV r QTQAGC L t GA C HVIITS V C CO P I GAG I CAS YtlT■ 
Sal R ST S QK S VA YTMS l GA.U-S.S I AV SNNT I A' PTN F S I 
8.SARScoron,virusHKU,39'349-AOC354U.1 I Y S TGNNVF QTOAGC L I GAE Hl/01'S YE CO P I GAG I CAS VH T■S■ 
I RS TS OKS VAYTMSL GAO.SS I AV SNNT I A IP TN F 5 I 

9. Sev..-eacute,..,.,rato,ys,,n<lromN<iated c,_ I Y S TGJ\INI/F OTOAGC L I GAE HIIDTS YE CO P 1 GAG I CAS VHTIIIS■ 
l R STSOK S VAYTMS L GAUSS 1 AV SNNT 1 A I P°IN F S I 
10.SoYc,.,acutere,p,ratory>'J"d,ome..-,1.ced c. I Y 5 TGNNI/ F QTOAGC L t GAE HVIJTS YE CD P GAG I CA S YHT S■ 
I RS TS OKS VAYTMS L GA,US.S 1 A Y SNNT I A 1 P°IN F S I 
11,SAAScoroM\l[rusNS,I -Ml\91SS6.1 I Y S TGNNVFQTQAGC l 1 GA HIIIIITS YE co P GAG IC A 5 YHT■ 
S■ 
l RS TS QK 5 VAYTMS L GA,tfSS I A Y SNNT I A I P°IN F S I 
,i.S,AAS(QfOnavtirusMAIStxoN1 •AEA1047J.l I r !, TG~NV f-Q-rQAGC LI C::IAt HV&"'rS Y t co P GAG I CA$ YH-r■ 
s•L Rs·, SOK 5 VAYTMS L GA.tl.SS I A Y SNNT I A IP TN f-S I 
13,SAAScO<onaW'USM.AISExoNI-AfA1M43.I f Y 5 TGN~V F QTOAGC L I GAE HIIIJ.T SY ECO P GAG f CAS YHTIIIS■ 
L RS TS OKS 'I AYTMS L GAllSS I A Y SNNT I A 1 PTN F S I 
~;:~s~:o~:;;:r~~)::8T2W18~~~Utdt-t: g::~~~~~ ~~g ~:~ ~~i=~=t ~~~f~~ t~:~1~: ~:

:~rrg=~~~g:;:g~g~ ; g~g: =;1~g~~ ~~~~~i: ~:;1~~ 

16.SAAScorona~rus8J302-MR0762S.1 I Y STGNNVF QTOAGC l I GAE HVO:TS YE co P GAG I CAS VHTaS■ 
L RS TS OKS VAYTMS l GAUSS I A Y SNNT I A IP TN F S I 
17.SAAScotonov.-usBJ302•MR07627.1 I YSTGNNVIQTOAGCL IGAtHVOI SY~CD P GAGICASYHllll~■ 
L RS 1,QKS VAYTMSLGA11SS IAY~NNTIAI P INFS I 
18.SAAScoronov,rusGOOl -AAP51227.1 I Y 5 TGNt.V F Q°IQAGC L 1 GAE HVD'TS YE CO P GAG I CA S YHTRS■ 
L RS TS QK S VAYT'-1S l GMJ'S,5 1 AV SNNT I A IP TN F S I 
19,Ahinolophus.offn1scoronoviru-, N-007SS81 I Y SAGIINV r QTQAGC l I G ..... C HVNA SVC CO P GA.GI CAS Y flT A5al RNTaQt< S I VAYTMS L GA 
■~S I~ VANN S I A IP TN f S 1 
20.Rhlnolophu>•ffn1Scot<>n•¥1rus-AHX3756!>.1I Y S AG■NVF OTQAGC L I GAE HVNA SY ECO P GAG I CAS YHT~S 
■ 
L RllilTliQK S I VAYTMSL GA■-NS 1 A V,\NN S I A I PTN F S I 
21,1™5ARS,l-tco,on.,wvs-AV1'78031,I I Y ATGTNV f OTOAGC l I GAE HVNAS YE CO P GAG I CA S VHT ASIIII RS TS QKA I VAYTMSL GA 
■NS I A ViANNS I A I PTN f S I 
22.Bot SAA.S•lkoco,onawus-AVP7S042.1 I YA GTSI/F QTQAGC l I GAE HVNAS Y ECO P GAG I CA SY HT A 51111 RS I IIQKA I VA YTMSL GA■NS 1 A YANN S I A I PTN F S I 
23.8<'1tcoron"'1,us, OHR63300.1 .y S TG SNVF QTRAGC l I GAE HVNt,15 YE CO P GAG IC AS VIIT:!HJII S. R sa.t1SJ2S I IIAYTMSL GA■NS8A V SNN S I A I P°IN FT I 
2"-EPI_IS-._40ll31ll>Otl'UnnanlRaTG13/,0131-•r S TG S NVF QTRAGC LI GAE HVNNS VE CD P I GAG IC AS YIIHlTNS R s.-a SJJS 1.AYTMSl GA■t!ISaA Y SNN,S I A I PTN FT' I 
25.EPI_IS-._402125Wuh,Mlu-1/2019IM1'1908-9Y S TG SNVF QTRAGC L I GAE HVNMS YE CO P I GAG I CA S Y"1TQTNS P RR AR S A SQS I A YTMS L GAPIJ'ISiat-Y SNN S I A I PTN FT I 

• • ~ I 

Figure 2 I Acquisition of furin cleavage site and O liAked glycaR!t_ The spike protein of 2019-nCoV (bottom) was aligned 
against the most closely related SARS and SARS-like CoVs. The furin cleavage site is marked in grey with the three adjacent 
1=1rediceedo liAIEeel glycan§lln blue. Both the furin cleavage site and o linlEeEl glycaA~are unique to 2019-nCoV and not previously 

seen in this group of viruses. 

While the functional consequence -if any -of the furin cleavage site in 2019-nCoV is unknown, previous 
experiments with SARS-CoV have shown that it enhances cell-cell fusion but does not affect virus entry6• 
Furin cleavage sites are often acquired in conditio!l._selecting for rapid virus replication and transmission 
(e.g., highly dense chicken populations) and are a hallmark of highly pathogenic avian influenza virus, 
although these viruses acquire the site in different and more direct ways7-
9 
• The acquisition of furin 
cleavage sites have also been observed after repeated passage of viruses in cell culture (personal 
correspondence and NASEM call, February 3, 2020). 

A potential function of the three predicted O-linked glycans is less clear, but could create a "mucin-like 
domain" shielding potential epitopes or key residues on the 2019-nCoV spike protein. 

Origin of 2019-nCoV 

As noted at the start of this document, we believe that the origin of 2019-nCoV through laboratory 
manipulation of an existing SARS-related coronavirus can be ruled out with a high degree of confidence. 
If genetic manipulation would have been performed, one would expect that a researcher would ha1o1e 
ttSee one of the several reverse genetics systems available for betacoronaviruse~ However, this is not the 
case as the genetic data clearly shows that 2019-nCoV is not derived from any previously used virus 
backbone, for example those described in a 2015 paper in Nature Medicine10. 

Instead we believe one of three main scenarios could explain how 2019-nCoV acquired the features 
discussed above: (1) natural selection In humans, (2) natural selection In an animal host, or (3) selection 
during passage. 

Adaptation to humans 

As the features outlined above are likely to enhance the ability of the virus to infect humans, it is possible 
that these are indeed adaptations to humans as a host and arose after the virus jumped from a 
non-human host, during the early stages of the epidemic. However, all of the genome sequences so far 
have the features described above and estimates of the timing of the most recent common ancestor of 
the currently sampled viruses support the seafood market outbreak as the zoonotic origin (i.e., in early 
December) and this would afford little opportunity for adaptation to occur. This may be explained by a 
transition to a rapid growth phase in the epidemic when the features arose and from which all current 

REV0000830 


cases are derived. However this would require a prior hidden epidemic of sufficient magnitude and 
duration for the adaptations to occur and there is no evidence of this. We also note that these features 
did not emerge during the SARS epidemic, which involved extensive human to human transmission. 

Selection in an animal host 

Given the similarity of 2019-nCoV to bat SARS-like CoVs, particularly RaTG13, it is highly likely that bats 
serve as the reservoir for this virus. However, previous human epidemics caused by betacoronaviruses 
have involved intermediate (possibly amplifying) hosts such as civets and other animals (SARS) and 
camels (MERS). It is therefore likely that an intermediate host would also exist for 2019-nCoV, although it 
is unclear what that host may be. Given the mutations in key residues of the RBD in 2019-nCoV it seems 
less likely that civets would be involved, although it is impossible to say with certainty at this stage. 
Notably, provisional analyses reveal that Malayan pangolins (Manis javanica) illegally imported into 
Guangdong province contain Co Vs that are extremely similar to 2019-nCoV11. Although RaTG13 remains 
the closest relative to 2019-nCoV across the genome as a whole, the Malayan pangolin CoVs are identical 
to 2019-nCoV at all six key RBD residues. Analyses of these pangolin viruses are ongoing, although they 
do not carry the furin cleavage site insertion. 

For the virus to acquire the furin cleavage site and mutations in the spike proteins that appear to be 
suitable for human ACE2 receptor binding, it seems plausible that this animal host would have to have a 
high population density -to allow the necessary natural selection to proceed efficiently -and an ACE2 
gene that is similar to the human orthologue. Since furin cleavage sites have not been observed in 
sarbecoviruses before, it is unclear what conditions would be required for it to be acquired in the lineage 
leading to 2019-nCoV. 

Selection durin assa e 

Ba glycosylation (0-and N-) can reduce host immune response to antigens -but is there any 
be evidence that neutralising antibodies are made to this region of spike protein? If not, where 
20 would the selective pressure come from? O-glycosylation (if present) could just as easily be 
cul stabilising (or preventing) a secondary structure feature (i.e., not immune system driven). Also 
the note that O-glycosylation predictors tend to over-predict, experimental evidence (mass spec) 
of important. Also, one of the most common functions of glycosylation is to protect the underlying 
bel peptide from proteolysis -i.e., these sites if occupied might actually reduce the efficiency of the 
ro furtin cleavag site. 


ct 

Limitations and recommendations 
The evolution scenarios discussed above are largely indistinguishable and current data are consistent 
with all three. It is currently impossible to prove or disprove either, and it is unclear whether future data 
or analyses will help resolve this issue. Identifying the immediate non-human animal source and 
obtaining virus sequences from it would be the most definitive way of distinguishing the three scenarios. 

The main limitation of what is described here is our clear ascertainment bias. We are looking for features 
or evolutionary aspects that could help explain how 2019-nCoV lead to such a rapidly expanding human 
epidemic, yet the specific features we are trying to find may be the exact features one would expect in a 
virus that could lead to an epidemic of the magnitude currently observed. Before 2019-nCoV 'took off 
and started the current epidemic, it is plausible that many stuttering transmission chains of highly similar 
viruses could have entered the human population, but because they never took off they were never 
sampled. It is extremely important to keep this in mind as any inference about the plausibility of various 
scenarios about the evolution and/or epidemic potential of 2019-nCoV is attempted. 

To further clarify the evolutionary origins and functional features of 2019-nCoV it would be helpful to 
obtain additional data about the virus -both genetic and functional. This includes experimental studies of 
receptor binding and the role of the furin cleavage site and predicted 0-linked glycans. The identification 
of a potential intermediate host of 2019-nCoV as well as sequencing of very early cases, including those 
not connected to the market, could also help refute the passage scenario described above. Even in the 

REV0000831 


light of such data, however, it is not guaranteed that data can be obtained to conclusively prove all 
aspects of the initial emergence of 2019-nCoV. 

REV0000832 


References 

1. Wan, Y., Shang, J., Graham, R., Barie, R. s.& Li, F. Receptor recognition by novel coronavirus from Wuhan: An 
analysis based on decade-long structural studies of SARS.J. Viral.(2020) doi:10.1128/JVl.00127-20. 
2. Letko, M. & Munster, V. Functional assessment of cell entry and receptor usage for lineage B ~-coronaviruses, 
including 2019-nCoV. bioRxiv2020.01.22.915660 (2020) doi:10.1101/2020.01.22.915660. 
3. Hoffmann, M. et al. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the 
cellular protease TMPRSS2 for entry into target cells. bioRxiv2020.01.31.929042 (2020) 
doi:10.1101 /2020.01.31.929042. 
4. Sheahan, T. et al. Mechanisms of zoonotic severe acute respiratory syndrome coronavirus host range expansion 
in human airway epithelium.}. Viral.82, 2274-2285 (2008). 
5. Cui, J., Li, F. & Shi, Z.-L. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbial. 17, 181-192 (2019). 
6. Follis, K. E., York, J. & Nunberg, J. H. Furin cleavage of the SARS coronavirus spike glycoprotein enhances cell-cell 
fusion but does not affect virion entry. Virology350, 358-369 (2006). 
7. Longping, V. T., Hamilton, A. M., Friling, T. & Whittaker, G. R. A novel activation mechanism of avian influenza 
virus H9N2 by furin.}. Viral.88, 1673-1683 (2014). 
8. Alexander, D.J.& Brown, I. H. History of highly pathogenic avian influenza. Rev. Sci. Tech. 28, 19-38 (2009). 
9. Luczo, J. M. et al. Evolution of high pathogenicity of HS avian influenza virus: haemagglutinin cleavage site 
selection of reverse-genetics mutants during passage in chickens. Sci. Rep. 8, 11518 (2018). 
10. Menachery, V. D. et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human 
emergence. Nat. Med. 21, 1508-1513 (2015). 
11. virological.org: 
http:/ /viro logica I .org/t/ncov-2019-spi ke-protei n-receptor-b ind i ng-dom a in-shares-high-amino-acid-identity-witha-
co ro navi rus-recovered-from-a-pa ngo Ii n-vi r a 1-m etage n om ic-dataset/362 (2 O 20 ). 
12. Ge, X.-Y. et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 
503, 535-538 (2013). 
13. Hu, B. et al. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the 
origin of SARS coronavirus. PLoS Pathog. 13, e1006698 (2017). 
14. Zeng, L.-P. et al. Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1 Encodes an Extra Accessory 
Protein, ORFX, Involved in Modulation of the Host Immune Response.}. Viral.90, 6573-6582 (2016). 
REV0000833 


15. Yang, X.-L. et al. Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct 
Progenitor of Severe Acute Respiratory Syndrome Coronavirus.J. Viro/.90, 3253-3256 (2015). 
REV0000834 


Message 

From: Garry, Robert F 


Sent: 2/10/2020 3:51:18 PM 

To: KristianG. Andersen Edward Holmes 

CC: Andrew Rambaut 
Subject: Re: More 

All true. 

But if Lipkin says higher ups are concerned and intel involved it's consistent with all we know too. 

Not surprised Ego krewe (maybe Fouchier too) writing some sort of counter to the white paper with the allusion to 
scenario 3 "passage." Preemptive strike? 

After a brief chat with Kristian after our NIH telecon I have to admit likewise that I don't really know the answers maybe 
someone does. The data we have is just insufficient and even pango99 prob not helping (unless it magically has a 
furin cleavage site, which seems doubtful). I think the key may come from Guangdong. So, China Ag U Researchers 
culturing pangolin virus for undeterminable length of time makes me somewhat nervous. 

From:Kristian Andersen_ 
Date: Monday, February~ 

To: Edward Holmes 
Cc: Andrew Rambaut 
Subject:Re: More 

External Sender. Be aware of links, attachments and requests. 

Having known Bob for more than a decade I feel quite confident that he will make the connection between Butt Lesion 
and a certain Columbia professor. 

I feel less confident that we will always be able to understand the references that Bob might himself be making at 
times ... (note, a postgraduate degree in manga, anime, and comics may be required). 

On Mon, Feb 10, 2020 at 1:27 PM Edward Holmes 

Thanks mate. 
Thermonuclear ego explosion when those two are together. 

You had better explain the butt lesion ref to Bob if he doesn't know. A link to the New York Post article should do it. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 11 Feb 2020, at 8:17 am, Kristian G. Andersen~rote: 
Eddie -lemme know your favorite brand and I'll send you a fresh pair of jocks. 
Can't go wrong with the Grand Wizard of Ego Health and Butt Lesion in the same room. Looking forward to it. 
K 

GARRY0000263 

wrote: 

On Mon, Feb 10, 2020 at 12:56 PM Edward Holmes 

wrote: 
He's about where we were a week ago. He's for escape. 

He also said that Peter Daszak, grand wizard of EgoHealth, and some others were writing a piece saying the Wuhan lab 
were being persecuted. 
I'll talk to Jeremy later. 

Currently, I'm more concerned that I will run out of underpants. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 11 Feb 2020, at 7:52 am, Andrew Rambaut 

wrote: 
We should get him on the group. Will make it more entertaining and balance the German/Dutch a bit. 
A 
Sent from my phone. Apologies for brevity or illiteracy. 

On 10 Feb 2020, at 21:11, Edward Holmes 

wrote: 
Ian Lipkin just called -very worried about the furin cleavage site and says that high ups are as well, inc. intel. Also saw 
the restriction site. 

Actually, he was most vexed that he wasn't part of our discussion group. Classic. I think I'll send the doc. 

I still have no power. Could be a week. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 
The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC0OS336. 

GARRY0000264 


From: Edward Holmes 
Sent: Monday, February 10, 2020 5:06 PM EST 
To: Ian Lipkin 
Subject: Re: Please call me 

I agree. Talking to Jeremy (Farrar) in a few minutes and I’ll get back in touch after. 
It is indeed striking that this virus is so closely related to SARS yet is behaving so differently. 
Seems to have been pre-adapted for human spread since the get go. It’s the epidemiology that I 
find most worrying. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 11 Feb 2020, at 9:01 am, Ian Lipkin 

wrote: 
It’s well reasoned and provides a plausible argument against genetic engineering. It does not 
eliminate the possibility of inadvertent release following adaptation through selection in 
culture at the institute in Wuhan. Given the scale of the bat CoV research pursued there and 
the site of emergence of the first human cases we have a nightmare of circumstantial evidence 
to assess. 

Ian 

On Feb 10, 2020, at 4:33 PM, Edward Holmes 

wrote: 
Hi Ian, 
Here’s the document we wrote a few days ago. Things are moving so quickly that is hard 
to keep up. Comments welcome. I favour natural evolution myself, but the furin cleavage 
site is an issue. I’ll have a chat with Jeremy in a little while to see if can get you more 
directly involved. 
Pangolins. Key observations are that: 

(i) Two sets of pangolins independently collected from different Chinese provinces both 
have CoVs in the same clade as 2019-nCoV. What are the odds? 
(ii) In the receptor binding domain the Guandong pangolins are the closest to 2019-nCoV, 
with 6/6 of the key mutations (only 1/6 in the closest bat sequence). 
Absolutely not proven that the pangolin is the intermediate host, but the points above make 
it a credible choice for additional investigation. 
Agree it might not be clear - very rushed at the end. 
Cheers, 
Eddie 
PROFESSOR EDWARD C. HOLMES FAA FRS 

CONFIDENTIAL TREATMENT 
REQUESTED - NOT FORCIRCULATION / COMMITTEEMEMBERS AND STAFF ONLY LIP-000472 


ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 

The University of Sydney | Sydney | NSW | 2006 | Australia 
T 
E 
On 10 Feb 2020, at 9:08 pm, Ian Lipkin 

wrote: 
When you are back up for air I need to speak on two issues that concern you directly. 
Ian 

On Feb 9, 2020, at 4:14 PM, Edward Holmes 


wrote: 
Ian, sorry, it won’t be today. 
Huge storm in Sydney: no power for 24 hours, flood water 1 cm from house, 

transport buggered. 
I need to sort this out. 
Phone will die soon. 
Professor Edward C. Holmes FAA FRS 

The University of Sydney 

On 10 Feb 2020, at 4:47 am, Ian Lipkin 

wrote: 
Eddie-

Please call me. 
Thanks 

Ian 

<Summary.Feb7.pdf> 


CONFIDENTIAL TREATMENT 
REQUESTED - NOT FORCIRCULATION / COMMITTEEMEMBERS AND STAFF ONLY LIP-000473 


Message 

From: 
Sent: 
To: 
Subject: 
Jeremy Farrar 
2/10/2020 1:26:57 AM 
rosten, Christian 
Many thanks all 

Sydney had a complete power cut over the weekend which has delayed things a little. 

Appreciate not everyone will agree on the next plans but the discussion has been very constructive, thank you. As 
(hopefully) the pangolin data becomes available and can be incorporated a final draft will be completed and shared and 
a decision made among the people who have led the analysis (EH, KA, BG and AR) of next steps. 


From: Marion Koopmans 

Date: Sunday, 9 February 2020 at 20:07 

To: "Kristian G. Andersen" , "Drosten, Christian" 
Jeremy Farrar , Edward Holmes 
Golding 
Subject: Re: [ext] 2019 N-CoV 

Wow .... took off from e-mail for a day ..... 

As mentioned to Jeremy, I would not be in favour of publishing something specific on the lab escape hypothesis, 
because I agree (with Kristian) that this could backfire. Yes, there is speculation in the public domain, triggered by 
several papers, including the rubbish ones. By zooming in on a specific finding that is NOT in the public domain as far as I 
know, I think this will generate its own conspiracy theories. 

So if published, I would suggest zooming out a bit for starters, describing that one of the key challenges is where this 
virus came from, discuss some of the (wild) guesses out there, and then argue step by step what the challenges are in 
inferring this from sequence data, where you do not know exactly what the pool is that you are sampling from, so end 
up interpreting the needle drawn out of a haystack. Here, the many pieces of the discussion that passed by these last 
few days can be included, like rates of evolution and dating of possible origins; examples of cleavage site acquisition 
from other viruses, recombination in coronavirus evolutionary history, possible abrupt changes in spillover events, 
ability to confirm or disproof things in vitro. etc 

And I would leave "lab escape"for the discussion, because putting that in the public domain as a hypothesis in my view 
will be read as "see, they also thought so" 

Marion 

REV0000812 


wrote: wrote: 
On 8 Feb 2020, at 22:15, Kristian G. Andersen• 

wrote: 
A lot of good discussion here, so I just wanted to add a couple of things for context that I think are important -and why 
what we're considering is far from "another conspiracy theory", but rather is taking a valid scientific approach to a 
question that is increasingly being asked by the public, media, scientists, and politicians (e.g., I have been contacted by 
Science, NYT, and many other news outlets over the last couple of days about this exact question). 

To Ron's question, passage of SARS-like Co Vs have been ongoing for several years, and more specifically in Wuhan under 
BSL-2 conditions -see references 12-15 in the document for a few examples. The fact that Wuhan became the epicenter 
of the ongoing epidemic caused by nCoV is likely an unfortunate coincidence, but it raises questions that would be 
wrong to dismiss out of hand. Our main work over the last couple of weeks has been focused on trying to disprove any 
type of lab theory, but we are at a crossroad where the scientific evidence isn't conclusive enough to say that we have 
high confidence in any of the three main theories considered. Like Eddie -and I believe Bob, Andrew, and everybody on 
this email as well -I am very hopeful that the viruses from pangolins will help provide the missing pieces. For now, giving 
the lab theory serious consideration has been highly effective at countering many of the circulating conspiracy theories, 
including HIV recombinants, bioengineering, etc. -here's just one 
example: https://www.factcheck.org/2020/02/baseless-conspiracy-theories-claim-new-coronavirus-wasbioengineered/. 


As to publishing this document in a journal, I am currently not in favor of doing so. I believe that publishing something 
that is open-ended could backfire at this stage. I think it's important that we try to gather additional evidence -including 
waiting on the pangolin virus sequences and further scrutinize the furin cleavage site and O-linked glycans -before 
publishing. That way we can (hopefully) come out with some strong conclusive statements that are based on the best 
data we have access to. I don't think we are there yet. 

Best, 
Kristian 

On Sat, Feb 8, 2020 at 12:38 PM Drosten, Christian I 

OK, I see. We should then introduce references to these informal sources in the beginning of the text. Else it reads a bit 

funny. 

Christian 

Professor Christian Drosten 

Director, Institute of Virology 

Scientific Director, Charite Global Health 

Charite -Universitatsmedizin Berlin 

Campus Charite Mitte 

Chariteplatz 1 

D-10117 Berlin 

Germany 

REV0000813 


E-Mail: christian.drosten@charite.de 
https ://virolog ie-ccm. cha rite .de/ 
https ://g lobalhealth. cha rite .de/ 


Von: Jeremy Farrar 

Datum: Samstag, 8. Februar 2020 um 21:21 

An: Edward Holmes 
Cc:"k a1978 
hristian Dr 
, Mike Ferguson 
Betreff: Re: [ext] 2019 N-CoV 

The theory of the origin of the has gathered considerable momentum not in social media, but increasingly among some 
scientists, in main stream media, and among politicians. 

The aim of this was to bring a neutral, respected, scientific group together to look at the data and in a neutral, 
considered way provide an opinion and we hoped to focus the discussion on the science, not on any conspiracy or 
other theory and to lay down a respected statement to frame whatever debate goes on -before that debate gets out 
of hand with potentially hugely damaging ramifications. 

With the additional information on the pangolin virus, information not available even 24 hours ago, I think the 
argument is even clearer. 

My preference is that a carefully considered piece of science, early in the public domain, will help mitigate more 
polarised debate. If not, that debate will increasingly happen and science will be reacting to it. Not a good position to 
be in. 


From: Edward Holmes 

Date: Saturday, 8 February 2020 at 20:11 

"a.rambaut, 
"r.fouchieri 
<P.Vallancel1 
Subject: Re: [ext] 2019 N-CoV 

REV0000814 


Hi Christian, 

I don't know where this story came from, but it has nothing whatsoever to do the HIV nonsense. Please don't associate 
this with that. This is a broader story. 

Ever since this outbreak started there have suggestions that the virus escaped from the Wuhan lab, if only because of 
the coincidence of where the outbreak occurred and the location of the lab. I do a lot of work in China and I can you 
that a lot of people there believe this and believe they are being lied to. Things were made worse when Wuhan lab 
published the bat virus sequence -a bat sampled in a different province for which they have a large collection of 
samples. 

I believe the aim/question here is whether we, as scientists, should try to write something balanced on the science 
behind this? There are arguments for and against doing this. 

Personally, with the pangolin virus possessing 6/6 key sites in the receptor binding domain, I am in favour of the natural 
evolution theory. 

Best wishes, 

Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 

School of Life & Environmental Sciences and School of Medical Sciences, 

I I I

The University of Sydney I Sydney NSW 2006 Australia 

Tl 
E 

On 9 Feb 2020, at 6:52 am, Drosten, Christian • wrote: 
Dear All, 
I am overloaded with nCoV patient-related work and will need a few days before I can work on this text. 
Can someone help me with one question: didn't we congregate to challenge a certain theory, and if we could, drop it? 

This whole text reads as if the hypothesis was obvious, or was brought up by some external source, forcing us to 
respond. Is this the case? It does not seem as if this was linked to the HIV nonsense. 
Who came up with this story in the beginning? Are we working on debunking our own conspiracy theory? 
Christian 

REV0000815 


Professor Christian Drosten 

Director, Institute of Virology 
Scientific Director, Charite Global Health 

Charite -Universitatsmedizin Berlin 

Germany 

E-Mail:! 
https://virologie-ccm.charite.de/ 
https ://g lobalhealth. charite.de/ 

Von: Jeremy Farrar 
Datum: Samstag, 8. Februar 2020 um 10:45 

Betreff: [ext] FW: 2019 N-CoV 
APOLOGIES WITH ALL CORRECT EMAILS 

Kristen, Andrew, Bob, Eddie have reworked the summary and it is attached here. 

We are pushing to get the sequence data from the reports on the pangolins, but do not have currently, clearly that is 
very important to incorporate. 

Interested in your views 

• Is this reasonably balanced given the data? 
• Is there anything anyone disagrees with? 
• Is there anything more in relation to what would seem to be the two possibilities 
Campus Charite Mitte 


REV0000816 


o Nature, Intermediate host, evolution and passage 
• Future data you may have 
• Advice on whether KA, AR, RG and EH should publish this. 
These and other thoughts welcome in confidence. 

REV0000817 


Message 

From: Garry, Robert F 

9:16:27 PM
Sent: 2/11/2020 
To: 

CC: 

Subject: Re: A few thoughts on the summary 

Edward Holmes 
Yes very interesting -publish! 
I predict Kristian will soon have some better dN/dS data to add productively to the mix as well. 
Stay agnostic ... hope Ian can as well. 

From: Edward Holmes 
Sent:Wednesday, February 12, 2020 2:57 AM 
To: Garry, Robert F 
Cc:Kristian G. Andersen • Andrew Rambaut 
Subject:Re: A few thoughts on the summary 


External Sender. Be aware of links, attachments and requests. 
See my comments on Slack. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
ihe Universw of Sydney | Sydney | NSW | 2006 | Australia 

E 
On 12 Feb 2020, at I :47 pm, Garry, Robert F < wrote: 
Virologica Sinica 
February 2018, Volume 33, Issue 1, pp 104-1071 Cite as 

Serological Evidence of Bat SARS-Related Coronavirus Infection in Humans, China 

"The virus may have been circulating for a longer period and in a larger population than we postulate based on 
molecular assays. This could be tested using banked sera once we have specific assays." 

SAmples in South China seropositive, but those from Wuhan seronegative. 

GARRY0000272 


From:Kristian G. Andersen 
Sent:Wednesday, February 
To: Edward Holmes· 
Cc:Garry, Robert F Andrew Rambaut 
Subject:Re: A few thoughts on the summary 
From:Kristian G. Andersen 
Sent:Wednesday, February 
To: Edward Holmes· 
Cc:Garry, Robert F Andrew Rambaut 
Subject:Re: A few thoughts on the summary 
External Sender. Be aware of links, attachments and requests. 

Yup, all good -as long as we don't have to inspect his arse. 
On Tue, Feb 11, 2020 at 6:06 PM Edward Holmes·

• 

wrote: 
PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The Universi of S dney| | Sydney | NSW | 2006 | Australia 

T· 
E 
On 12 Feb 2020, at 1 :00 pm, Garry, Robert F 

wrote: 
No problem from me ... 

From:Edward Holmes 
Sent:Wednesday, Febru r 
To: Kristian G. Andersen Garry, Robert F < ; Andrew Rambaut 
Subject:Fwd: A few thoughts on the summary 

External Sender. Be aware of links, attachments and requests. 

From Ian about the Feb 7 summary. 

Think we should add him as an author. Safety in numbers. In his own mind he brings a lot of gravitas ... plus 
because he is involved in the GOF I think it add weights. Happy to be over-ruled though. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T -----


E 

Begin forwarded message: 

From: Ian Lipkin· 


GARRY0000273 


Subject: A few thoughts on the summary 
Date: 12 February 2020 at 1 :40:21 am AEDT 
To: Eddie Holmes 

Eddie-
Call me whenever you wish. 

Ian 

Adaptation to humans 

1. Animals in the Wuhan wildlife market may not be the zoonotic origin of the outbreak. It's also possible that an 
infected human involved in the wildlife trade transmitted the virus to people in the market. This might explain why 
the environmental sampling revealed more viral sequences on the West (seafood) than the East (terrestrial) side of 
the street. I don't see a way to test this possibility; nonethless, we could mention it. 
2. The virus may have been circulating for a longer period and in a larger population than we postulate based on 
molecular assays. This could be tested using banked sera once we have specific assays. 
Selection during passage 

1. Are we suggesting that the furin cleavage site evolved from de novo mutations or through recombination? 
On Feb 10, 2020, at 4:33 PM, Edward Holmes· wrote: 

<Summary.Feb?.pdf> 

GARRY000027 4 


Message 

From: 
Sent: 
To: Kristian G. Andersen 
Subject: RE: Interest in commentary/hypothesis on SARS-CoV-2 origins? 

Dear Kristian, 
Yes please! It sounds possibly like a Perspective. I would love to take a look and consider whether it might be suitable for 
Nature. 
All the best, 
Clare 

From: Kristian G. Andersen 
Sent: 12 February 2020 23: 
To: Clare Thomas 
Subject: Interest in commentary/hypothesis on SARS-CoV-2 origins? 


Dear Clare, 

I can only imagine you must be crazy busy at the moment! I wanted to reach out to you to sec if there would be 
interest in receiving a commentary/hypothesis piece on the evolutionary origins of SARS-Co V-2? There has 
been a lot of speculation, fear mongering, and conspiracies put forward in this space and we thought that 
bringing some clarity to this discussion might be of interest to Nature. 

Prompted by Jeremy Farrah, Tony Fauci, and Francis Collins, Eddie Holmes, Andrew Rambaut, Bob Garry, Ian 
Lipkin, and myself have been working through much of the (primarily) genetic data to provide agnostic and 
scientifically informed hypotheses around the origins of the virus. We are not quite finished with the writeup 
and we still have some loose ends, but I wanted to reach out to you to see if this might potentially be of interest? 
We see this more as a commentary/hypothesis, as opposed to a more long-form Letter or Article. 

Best, 
Kristian 

Kristian G. Andersen, PhD 

Associate Professor, Scripps Research 
Director of Infectious Disease Genomics, Scripps Research Translational Institute 
Director, Center for Viral Systems Biology 

The Scripps Research Institute 

10550North Torrey Pines Road, SGM-300A 
Department of Immunology and Microbial Science 
LaJolla, CA 92037 

p: 
c: 
t 
e: 
Assistant: 
REV0002849 


DISCLAIMER: This e-mail is confidential and should not be used by anyone who is not the original intended 
recipient. If you have received this e-mail in error please inform the sender and delete it from your mailbox or 
any other storage mechanism. Springer Nature Limited does not accept liability for any statements made which 
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Please note that Springer Nature Limited and their agents and affiliates do not accept any responsibility for 
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the e-mail and attachments (if any). 
Springer Nature Limited. Registered office: The Campus, 4 Crinan Street, London, Nl 9XW. Registered 
Number: 00785998 England. 

REV0002850 


Message 

2/13/2020 8:47:54 AM 
Kristian G. Andersen 
From: Clare Thomas 

Sent: 

To: 

Subject: RE: Interest in commentary/hypothesis on SARS-CoV-2 origins? 

Dear Kristian, 
Ok that sounds great. Thanks so much. 
All the best, 
Clare 

From: Kristian G. Andersen 


Sent: 13 February 2020 16:33 
To: Clare Thomas 
Subject: Re: Interest in commentary/hypothesis on SARS-CoV-2 origins? 

Sounds great Clare. We'll work out a few more of the details and share with you a draft so you can get a sense 
of whether this would be of interest and would also give you a chance to provide suggestions for things to 
incorporate. 

I'll be gone for the rest the week, but I assume we'll have this ready early/mid next week. 

Best, 
Kristian 

On Thu, Feb 13, 2020 at 2:34 AM Clare Thomas 

wrote: 
Dear Kristian, 

Yes please! It sounds possibly like a Perspective. I would love to take a look and consider whether it might be suitable 
for Nature. 

All the best, 

Clare 

From: Kristian G. Andersen 


Sent: 12 February 2020 23:09 
To: Clare Thomas 
Subject: Interest in commentary/hypothesis on SARS-CoV-2 origins? 

Dear Clare, 

I can only imagine you must be crazy busy at the moment! I wanted to reach out to you to see inhere would be 
interest in receiving a commentary/hypothesis piece on the evolutionary origins of SARS-Co V-2? There has 

REV0000266 


been a lot of speculation, fear mongering, and conspiracies put forward in this space and we thought that 
bringing some clarity to this discussion might be of interest to Nature. 

Prompted by Jeremy Farrah, Tony Fauci, and Francis Collins, Eddie Holmes, Andrew Rambaut, Bob Garry, 
Ian Lipkin, and myself have been working through much of the (primarily) genetic data to provide agnostic 
and scientifically informed hypotheses around the origins of the virus. We are not quite finished with the 
writeup and we still have some loose ends, but I wanted to reach out to you to see if this might potentially be 
of interest? We see this more as a commentary/hypothesis, as opposed to a more long-form Letter or Article. 

Best, 
Kristian 

Kristian G. Andersen, PhD 

Associate Professor, Scripps Research 

Director of Infectious Disease Genomics, Scripps Research Translational Institute 
Director, Center for Viral Systems Biology 

The Scripps Research Institute 

10550 North Torrey Pines Road, Department 
of Immunology and Microbial Science 
La Jolla, CA 9203 7 

t: ({T}( G Andersen 
e: 
w: \,rw\v.andersen--lab.com 
REV0000267 


Assistant: 
DISCLAIMER: This e-mail is confidential and should not be used by anyone who is not the original intended 
recipient. If you have received this e-mail in error please inform the sender and delete it from your mailbox or 
any other storage mechanism. Springer Nature Limited does not accept liability for any statements made which 
are clearly the sender's own and not expressly made on behalf of Springer Nature Ltd or one of their agents. 
Please note that Springer Nature Limited and their agents and affiliates do not accept any responsibility for 
viruses or malware that may be contained in this e-mail or its attachments and it is your responsibility to scan 
the e-mail and attachments (if any). 
Springer Nature Limited. Registered office: The Campus, 4 Crinan Street, London, Nl 9XW. Registered 
Number: 00785998 England. 

REV0000268 


Message 

From: Edward Holmes 
Sent: 2/16/2020 2:38:46 AM 
To: Garry, Robert F 

External Sender. Be aware of links, attachments and requests. 

Subject:Re: Paper 

CC: 
Andrew Rambaut 
Kristian 
G. Andersen 
Oh yes, the reviewers are easy ... I think this is a slam dunk. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
On 16 Feb 2020, at 7:36 pm, Garry, Robert F 
Yeah I know and that's a good choice for him. 
So, as you know when you submit you'll need to suggest reviewers to include and exclude. Seems easy -there 

are some natural choices for both lists. Nature commentaries are peer reviewed iirc but I'm guessing they'll 
push this as fast as possible. 
Sent from my iPhone 
On Feb 16, 2020, at 2:29 AM, Edward Holmes· 

External Sender. Be aware of links, attachments and requests. 

I agree, and I offered, but he wants to remain independent. 

wrote: 
wrote: 
PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
GARRY0000306 


On 16 Feb 2020, at 7:24 pm, Garry, Robert F 

wrote: 
No problem either count 
Jeremy has been amazing leader-should be author 
Sent from my iPhone 

On Feb 16, 2020, at 2:18 AM, Edward Holmes 

wrote: 
External Sender. Be aware of links, attachments and requests. 

Ah. I so, I can submit on his behalf. 
Jeremy wants to add something to the acknowledgments. 
Just seen this: no GISAID acknowledgment as far as I can tell: 
https://www.tandfonline.com/doi/full/10.1080/204 77724.2020.1725339 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The Universi of S dne S dne I NSW I 2006 I Australia 

T 
E 
On 16 Feb 2020, at 7:14 pm, Garry, Robert F • wrote: 
One thing -I'm not sure when Kristian is returning to the connected world. Monday is a federal holiday. 
Sent from my iPhone 

On Feb 16, 2020, at 12:44 AM, Edward Holmes· 

wrote: 
External Sender. Be aware of links, attachments and requests. 

Thanks Bob! 
Sorry about the typo. I'll let Kristian fix that one. 
Cheers, 
Eddie 

GARRY0000307 


PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
On 16 Feb 2020, at 5:05 pm, Garry, Robert F 

wrote: 
Looking fine! Congrats all. 
Minor: last sentence first paragraph covid-9 to covid-19 
Sent from my iPhone 

On Feb 15, 2020, at 10:46 PM, Edward Holmes· 

ote: 
External Sender. Be aware of links, attachments and requests. 

All, attached is what I propose is the final version of this paper. I've just given it a final wash-and-brush-up. 
Looks great I reckon. 
Can you please check your names, affiliations and acknowledgements. 

I'll pass to Jeremy to see ifhe has any final comments and wants to be acknowledged. 
This needs to go to Nature on Monday in somebody's time zone. Kristian I'll let you deal with this. You may 
need to provide more contact details. Figure also attached separately. 

Cheers, 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney Sydney | NSW | 2006 | Australia 

T 
E 
On 16 Feb 2020, at 12:09 pm, Garry, Robert F • wrote: 
I formally agree. 

GARRY0000308 


Any guy that helps discover Jingmen tick viruses and Wuhan cricket virus must be trusted. Very important. 
Going to dinner with my wife so will put down the phone. 
Did I mention the Jingmen tick viruses have pretty spectacular mucin like domains? Would not have looks at 

Co Vs otherwise. 

Sent from my iPhone 

On Feb 15, 2020, at 6:26 PM, Edward Holmes· 

wrote: 
External Sender. Be aware of links, attachments and requests . 

•

I will send through a final version that everyone can formally agree to later today. I'll also pass to Jeremy. 
Kristian can then do the formal submission, although I'll probably ping a copy to Magda and Clare anyway. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The Universi of S dne S dne NSW I 2006 I Australia 

T 
E 
On 16 Feb 2020, at 11 :22 am, Ian Lipkin· 
Congratulations. It's a timely and well reasoned review. 
Ian 

On Feb 15, 2020, at 7:15 PM, Edward Holmes· 

Fab. 

Just need to sort out author order. Kristian 1st and probably should correspond as he's chatted with Clare? Bob, 
I was thinking you might go last? I'd be nervous about putting my name there as I am amateur on the specific 
virological stuff we discuss. I feel I have only contributed to the writing. I don't mind Andrew going last either. 

wrote: 
wrote: 
PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 

GARRY0000309 


On 16 Feb 2020, at 11 :03 am, Andrew Rambaut 

wrote: 
I am done. Added in all the references (I think). 
A. 

On 16 Feb 2020, at 00:01, Edward Holmes 


Right, I need to get this finalised. Can I suggest that people stop editing the Google Docs version within the 
next hour (noon Sydney time) and I'll finish everything in normal Word. Need to draw a line under this very 
soon. 

Thanks! 

Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
Andrew Rambaut 

Institute for Evolutionary Biology 
Ashworth Laboratories, University of Edinburgh, Edinburgh, EH9 3FL, UK 

contact -
I http://tree.bio.ed.ac.uk I tel • 

The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. 

<Andersen.Nature Perspective.docx> 
<Andersen.Figure 1.pdf> 

GARRY000031 0 


Message 

From: Edward Holmes 


Sent: 2/16/2020 3:06:49 PM 


To: 

CC: Ian Lipkin Andrew Rambaut 
Subject: Re:Paper 
Garry, Robert F 
Just got this from Francis Collins. 

"This is really well done, and I would argue ought to be made public ASAP (Jeremy sent it this morning). 

Francis" 

I'll submit and send to Magda/Clare this morning. If they ok we can then put on bioRxiv and perhaps 
Virological.org as well? 
Cheers, 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E. 
On 17 Feb 2020, at 9:52 am, Garry, Robert F 

wrote: 
Important to get this out. 
https:ljwww.washingtonpost.com/politics/2020/02/16/tom-cotton-coronavirus-conspiracy/ 


From: Edward Holmes· 

Date: Sunday, February 16, 2020 at 4:14 PM 

To: Robert Garry 
Cc:Ian Lipkin 
Andrew Rambaut 

Subject: Re: Paper 

External Sender. Be aware of links, attachments and requests. 

I'll quickly check with Magda first. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

REV0002837 


On 17 Feb 2020, at 9:06 am, Garry, Robert F < wrote: On 17 Feb 2020, at 9:06 am, Garry, Robert F < wrote: 
Sounds correct to me. 


From: Edward Holmes· 

Date: Sunday, February 16, 2020 at 4:04 PM 

To: Robert Garry, 
Cc:Ian Lipkin • Andrew Rambaut 
Subject: Re: Paper 

External Sender. Be aware of links, attachments and requests. 

All, I assume this needs to go on bioRxiv right? That's the Nature policy for all COVID-19 papers. We also meant to send 
to WHO. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 17 Feb 2020, at 7:57 am, Garry, Robert F 

wrote: 
Thanks Eddie! 
Yes the NAID pies are nice. 
The fusing SARS-CoV-2 pie is maybe not the prettiest one, but for me a clear indication that the polybasic site is 

functional. 

You can observe this with flu v if you concentrate and treat with trypsin or some proper peptides. The virions fuse with 
each other. 
Looks to me like SARS-CoV-2 gets at least partly activated coming out of the cells. 
b 


From: Edward Holmes· 

Date: Sunday, February 16, 2020 at 2:50 PM 

To: Robert Garry· 
Andrew Rambaut 

Subject: Re: Paper 

External Sender. Be aware of links, attachments and requests. 

Great pies. Let's see what Nature say. I will get the paper out the door today. 

REV0002838 


Cheers, 

Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of S dne IS dne | NSW | 2006 | Australia 

T 
E 
On 17 Feb 2020, at 4:54 am, Garry, Robert F • 
Maybe Kristian can sell them on this version? 
Or maybe not. 


From: Robert Garry· 

Date: Sunday, February 16, 2020 at 8:21 AM 

To: Ian Lipkin Andrew Rambaut 
Eddie Holmes 

Kristian Andersen 
Subject: Re: Paper 
They might need a cover. © 

Seriously though NIH Took some pies that Tony would love to see on the Nature cover: 
https:ljwww.flickr.com/photos/niaid/albums/72157712914621487 
<image001.png> 
This one is actually VERY pertinent to our story BTW -notice that there are several fusing virions. 
We've actually seen the same thing with fusion peptides that activate FluV. 
SARS-CoV-2 is "activated!" 


From: Ian Lipkin 

Date: Sunday, February 16, 2020 at 5:46 AM 

Andrew Rambaut 
Eddie Holmes· 
Subject: Re: Paper 
REV0002839 


wrote: wrote: 
External Sender. Be aware of links, attachments and requests. 

Our audience includes the general public and policy makers as well as the scientific community. Once the paper is 
accepted we should ask Nature how it and we can promote broad visibility. At minimum we will need a short, powerful 
press release that hits the high points: who reviewed the data, what we considered, what we concluded, what needs to 
be done. 

Ian 

On Feb 16, 2020, at 5:58 AM, Andrew Rambaut • 

Just catching up on all this. Bob -you definitely should go last author. Without your expertise and knowledge (and your 
rummaging around the literature), we wouldn't have been able to write this. Happy to go second and Eddie can go 
second senior. 

Andrew 

On 16 Feb 2020, at 00:20, Garry, Robert F • wrote: 
Andrew should go last -he did the bulk of the heavy lifting. 

1 Tulane University, School of Medicine, Department of Microbiology and Immunology, New Orleans, LA, USA 
2 Zalgen Labs, LCC, Germantown, MD, USA 

I have to list the latter because of the US Col rules. 


From: Edward Holmes 

Date: Saturday, February 15, 2020 at 6:15 PM 

To: Andrew Rambaut 
Cc:Robert Garr • 
Ian Lipkin 

Subject: Re: Paper 

External Sender. Be aware of links, attachments and requests. 

Fab. 

REV0002840 


Just need to sort out author order. Kristian 1st and probably should correspond as he's chatted with Clare? Bob, I was 
thinking you might go last? I'd be nervous about putting my name there as I am amateur on the specific virological stuff 
we discuss. I feel I have only contributed to the writing. I don't mind Andrew going last either. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 

I I I

The University of Sydney I Sydney NSW 2006 Australia 

T 
E 

On 16 Feb 2020, at 11:03 am, Andrew Rambaut wrote: 
I am done. Added in all the references (I think). 

A. 

On 16 Feb 2020, at 00:01, Edward Holmes • wrote: 

Right, I need to get this finalised. Can I suggest that people stop editing the Google Docs version within the next hour 
(noon Sydney time) and I'll finish everything in normal Word. Need to draw a line under this very soon. 
Thanks! 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of S dne S dne NSW 2006 Australia

I I I I 

T


E! 

REV0002841 


contact -I contact -I 
Andrew Rambaut 

Institute for Evolutionary Biology 

Ashworth Laboratories, University of Edinburgh, Edinburgh, EH9 3FL, UK 

I I

http://tree.bio.ed.ac.uk tel 

The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. 

Andrew Rambaut 

Institute for Evolutionary Biology 

Ashworth Laboratories, University of Edinburgh, Edinburgh, EH9 3FL, UK 

I I

http://tree.bio.ed.ac.uk tel

contact -I 


<Suggested cover v2 redl.pdf> 

REV0002842 


Message 


From: Edward Holmes 

Sent: 2/16/2020 6:59:20 PM 

To: 
CC: Andrew Rambaut Ian Lipkin 
Subject: Re:Paper 

All came together very quickly in the end. Jeremy Farrar and Francis Collins are very happy. Works for me. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E. 
On 17 Feb 2020, at 1 :53 pm, Kristian G. Andersen· 

wrote: 
Pure coincidence. The no-shower-since-Thursday will serve as evidence in case you need proof.. .. 
Great job lads!! 
K 
On Sun, Feb 16, 2020 at 6:48 PM Edward Holmes· wrote: 

Well, that's suspicious ... he comes back 15 minutes after I submit? A natural phenomenon? I'm not sure we 
can exclude the hypothesis of deliberately engineered responsibility shirking. 
Anyway, it's done. Sorry the last bit had to be done without you ... pressure from on high. 
Fair point about bioRxiv. I've asked Nature what they want. Virological will work. 
More rattlesnakes to come mate .... 
Cheers, 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
REV0002858 


On 17 Feb 2020, at 1:41 pm, Kristian G. Andersen 

wrote: 
Gentlemen, it seems I should go to the desert more often ... Only had three rattlesnake encounters, one near death 
experience, and one running out of gas on the highway (with 1/4 left in the tank ... it's a Jeep thing ... ), so 
all in all, pretty mellow. Fun though. 

I'm still on my way back so not caught up yet -lemme know what's needed from me? 
Eddie, bioRxiv is only for primary research and not this type of paper, so no need to submit. 
Bob, pangolins ... not me. But good idea. 
Onwards. 
K 

On Sun, Feb 16, 2020 at 4:35 PM Edward Holmes· 

wrote: 
Added (attached). 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T-
On 17 Feb 2020, at 11: 16 am, Andrew Rambaut 

wrote: 
The pangolin metagenomic data seems to have come ultimately from this paper: 
https:/ /www.ncbi.nlm.nih.gov/pubmed/31652964 
We should cite it. 

A. 

On 16 Feb 2020, at 23:12, Garry, Robert F 

wrote: 
Sounds good ... 

From: Edward Holmes I 
Date: Sunday, February 16, 2020 at 5:06 PM 

To: Robert Garry· 
Cc:Ian Lipkin• , Andrew Rambaut 
REV0002859 


Subject: Re: Paper 

External Sender. Be aware of links, attachments and requests. 

From: Edward Holmes 
Date: Sunday, February , a : 
To: Robert 
Just got this from Francis Collins. 

"This is really well done, and I would argue ought to be made public ASAP (Jeremy sent it this morning). 
Francis" 
I'll submit and send to Magda/Clare this morning. If they ok we can then put on bioRxiv and perhaps Virological.org as 

well? 

Cheers, 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sidney Sidney | NSW | 2006 | Australia 
T 
E 


On 17 Feb 2020, at 9:52 am, Garry, Robert F · wrote: 
Important to get this out. 
https://www.washingtonpost.com/politics/2020/02/16/tom-cotton-coronavirus-conspiracy/ 

, Andrew Rambaut 

Subject: Re: Paper 

External Sender. Be aware of links, attachments and requests. 

I'll quickly check with Magda first. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 17 Feb 2020, at 9:06 am, Garry, Robert F • wrote: 
REV0002860 


Sounds correct to me. 


From: Edward Holmes 

Date: Sunday, February 16, 2020 at 4:04 PM 

To: Robert Garry, 
Cc:Ian Lipkin , Andrew Rambaut 
<a.rambaut@ed.ac.uk> 
Subject: Re: Paper 

External Sender. Be aware of links, attachments and requests. 

All, I assume this needs to go on bioRxiv right? That's the Nature policy for all COVID-19 papers. We also meant to 
send to WHO. 

Professor Edward C. Holmes FAA FRS 
The University of Sydney 

On 17 Feb 2020, at 7:57 am, Garry, Robert F 

wrote: 
Thanks Eddie! 
Yes the NAID pies are nice. 
The fusing SARS-CoV-2 pie is maybe not the prettiest one, but for me a clear indication that the polybasic site is 

functional. 

You can observe this with flu v if you concentrate and treat with trypsin or some proper peptides. The virions fuse 
with each other. 
Looks to me like SARS-CoV-2 gets at least partly activated coming out of the cells. 
b 

From: Edward Holmes, 
Date:Sunday, February 
To: Robert Garry 
Cc:Ian Lipkin 
Andrew Rambaut 

Subject: Re: Paper 


External Sender. Be aware of links, attachments and requests. 

Great pies. Let's see what Nature say. I will get the paper out the door today. 
Cheers, 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

REV0002861 


ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T-
E! 
On 17 Feb 2020, at 4:54 am, Garry, Robert F • wrote: 
Maybe Kristian can sell them on this version? 
Or maybe not. 

Andrew Rambaut 
Subject: Re: Paper 
They might need a cover.© 

From: Robert Garry 
Date:Sunday, February 
To: Ian Lipkin Kristian Andersen· 
Eddie Holmes• 
Seriously though NIH Took some pies that Tony would love to see on the Nature cover: 
https://www.flickr.com/photos/niaid/albums/72157712914621487 
<imageO0l.png> 
This one is actually VERY pertinent to our story BTW -notice that there are several fusing virions. 
We've actually seen the same thing with fusion peptides that activate FluV. 
SARS-CoV-2 is "activated!" 


From: Ian Lipkin 

Date: Sunday, February 16, 2020 at 5:46 AM 

Andrew Rambaut 
Subject: Re: Paper 

External Sender. Be aware of links, attachments and requests. 

Our audience includes the general public and policy makers as well as the scientific community. Once the paper is 
accepted we should ask Nature how it and we can promote broad visibility. At minimum we will need a short, 

REV0002862 


powerful press release that hits the high points: who reviewed the data, what we considered, what we concluded, 
what needs to be done. 

Ian 

On Feb 16, 2020, at 5:58 AM, Andrew Rambaut 

wrote: 
Just catching up on all this. Bob -you definitely should go last author. Without your expertise and knowledge (and 
your rummaging around the literature), we wouldn't have been able to write this. Happy to go second and Eddie can 
go second senior. 

Andrew 

On 16 Feb 2020, at 00:20, Garry, Robert F 

wrote: 
Andrew should go last -he did the bulk of the heavy lifting. 

1 Tulane University, School of Medicine, Department of Microbiology and Immunology, New Orleans, LA, USA 
2 Zalgen Labs, LCC, Germantown, MD, USA 

I have to list the latter because of the US Col rules. 


From: Edward Holmes 

Date: Saturday, February 15, 2020 at 6:15 PM 

Ian Lipkin 
Subject: Re: Paper 

External Sender. Be aware of links, attachments and requests. 

Fab. 

Just need to sort out author order. Kristian 1st and probably should correspond as he's chatted with Clare? Bob, I was 
thinking you might go last? I'd be nervous about putting my name there as I am amateur on the specific virological 
stuff we discuss. I feel I have only contributed to the writing. I don't mind Andrew going last either. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

REV0002863 


THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
On 16 Feb 2020, at 11:03 am, Andrew Rambaut 

wrote: 
I am done. Added in all the references (I think). 
A. 

On 16 Feb 2020, at 00:01, Edward Holmes· 

wrote: 
Right, I need to get this finalised. Can I suggest that people stop editing the Google Docs version within the next hour 
(noon Sydney time) and I'll finish everything in normal Word. Need to draw a line under this very soon. 

Thanks! 

Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of S dne S dne | NSW | 2006 | Australia 

T 
E 
Andrew Rambaut 
Institute for Evolutionary Biology 
Ashworth Laboratories, University of Edinburgh, Edinburgh, EH9 3FL, UK 

contact -http://tree.bio.ed.ac.uk tel

I I 


The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. 

REV0002864 


Andrew Rambaut 

Institute for Evolutionary Biology 

Ashworth Laboratories, University of Edinburgh, Edinburgh, EH9 3FL, UK 

contact -http://tree.bio.ed.ac.uk I tel 


<Suggested cover v2 redl.pdf> 

Andrew Rambaut 

Institute for Evolutionary Biology 

Ashworth Laboratories, University of Edinburgh, Edinburgh, EH9 3FL, UK 

contact -I http://tree.bio.ed.ac.uk I tel 1 


REV0002865 


From: Jeremy Farrar 
Sent: Monday, February 17, 2020 10:42 AM EST 
To: Ian Lipkin 
Subject: Re: Connections COVID-19 

Yes I know and in US - why so keen to get out ASAP. 
I will push Nature 

On 17 Feb 2020, at 16:41, Ian Lipkin 

wrote: 
Jeremy, 
Thanks for shepherding this paper. Rumors of bioweaponeering are now circulating in China. 

Ian 

On Feb 17, 2020, at 10:28 AM, Jeremy Farrar 

wrote: 
When you have been able to update with the extra sentence and data can you forward on to 
me - keep that WHO see ASAP. 

On 17 Feb 2020, at 12:09, Garry, Robert F 

wrote: 
This also means less concern about the Baric scenario where another mutation could 
kick SARS-CoV-2 into another gear. Binding already optimal. 

Sent from my iPhone 

On Feb 17, 2020, at 4:51 AM, Andrew Rambaut 

wrote: 
External Sender. Be aware of links, attachments and requests. 

Fixed. 

On 17 Feb 2020, at 10:47, Edward Holmes 


wrote: 

Hang on…should be " recent binding studies indicate” not indict. One of the new 
edits. 

CONFIDENTIAL TREATMENT 
REQUESTED - NOT FORCIRCULATION / COMMITTEEMEMBERS AND STAFF ONLY LIP-000615 


PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
On 17 Feb 2020, at 9:44 pm, Garry, Robert F 

wrote: 
Looks great! 
Sent from my iPhone 

On Feb 17, 2020, at 4:41 AM, Andrew Rambaut 


wrote: 

External Sender. Be aware of links, attachments and requests. 

OK. Here is the version with all the changes and the updated references. As 
I manually changed the numbers (adding reference 7 and incrementing all 
numbers above 6) I would appreciate a check. 
I also simplified Bob's text below. 
I am going to start formatting this in virological so let me know if you spot 
any issues. 
A. 

On 17 Feb 2020, at 10:25, Garry, Robert F 


wrote: 

Another better version: 
While these analyses suggest that SARS-CoV-2 may be capable of 
binding the human ACE2 receptor with high affinity, the interaction is 
not predicted to be optimal1. Additionally, several of the key residues in 
the RBD of SARS-CoV-2 are different to those previously described as 
optimal for human ACE2 receptor binding6. In contrast to these 
computational assessments recent binding studies indict that SARSCoV-
2 binds with high affinity to human ACE2 (insert ref). SARSCOV-
2 spike does not appear to have an artificial sequence designed in 
the laboratory. An artificial sequence would have used interactions 
predicted to be optimal for interaction with its receptor. Instead the 

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SARs-CoV-2 spike appears to be the result of selection on human or 
human-like ACE2 permitting another optimal binding solution to arise. 
This is strong evidence that SARS-CoV-2 is not the product of genetic 
engineering. 

From: Andrew Rambaut 
Sent: Monday, February 17, 2020 10:23 AM 

Subject: Re: Connections COVID-19 

External Sender. Be aware of links, attachments and requests. 

OK. I will add that. I am editing the document now. 
Andrew 

On 17 Feb 2020, at 10:20, Garry, Robert F 

While these analyses suggest that SARS-CoV-2 may be capable of 
binding the human ACE2 receptor with high affinity, the interaction 
is not predicted to be optimal1. Additionally, several of the key 
residues in the RBD of SARS-CoV-2 are different to those 
previously described as optimal for human ACE2 receptor binding6. 
In contrast to these computational assessments recent binding studies 
indict that SARS-CoV-2 binds with high affinity to human ACE2 
(insert ref). SARS-COV-2 spike does not appear to have an artificial 
sequence designed in the laboratory would have been designed for 
optimal binding and used interactions predicted to be optimal. 
Instead it appears to be the result of selection on human or human-
like ACE2 permit another optimal binding solutions to arise. This is 
strong evidence that SARS-CoV-2 is not the product of genetic 
engineering. 

From: Garry, Robert F 

Sent: Monday, February 17, 2020 10:02 AM 

put the "While these" back 

From: Edward Holmes 
Sent: Monday, February 17, 2020 9:49 AM 
To: Garry, Robert F 
Cc: Kristian G. Andersen ; Andrew Rambaut 

To: Garry, Robert F 
Cc: Eddie Holmes ; Kristian G. Andersen 
; Ian Lipkin ; Jeremy Farrar 
wrote: 
To: Edward Holmes 
Cc: Kristian G. Andersen ; Andrew Rambaut 
; Ian Lipkin ; Jeremy Farrar 
Subject: Re: Connections COVID-19 
CONFIDENTIAL TREATMENT 
REQUESTED - NOT FORCIRCULATION / COMMITTEEMEMBERS AND STAFF ONLY LIP-000617 


; Ian Lipkin ; Jeremy Farrar 
Subject: Re: Connections COVID-19 

External Sender. Be aware of links, attachments and requests. 

Ok. Pass a draft to me and I’ll give it a quick read through. 
No way I can stay up to your levels... 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

On 17 Feb 2020, at 8:47 pm, Garry, Robert F 

agreed - i'm up - who needs to sleep 
will take very quick swing at it now - yes a sentence or two will 
likely do 
15 minutes i'll be back 

From: Edward Holmes 
Sent: Monday, February 17, 2020 9:45 AM 

Subject: Re: Connections COVID-19 

External Sender. Be aware of links, attachments and requests. 

Bob, if you or someone else wants to add a sentence now that’s ok (refs. 
will need to change as well), but we must get it out today. Things are 
moving/changing so rapidly that we are always going to be out of date. We 
need to draw a line somewhere. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
wrote: 
To: Garry, Robert F 
Cc: Kristian G. Andersen ; Andrew Rambaut 
; Ian Lipkin ; Jeremy Farrar 
T 
CONFIDENTIAL TREATMENT 
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E 
On 17 Feb 2020, at 8:39 pm, Garry, Robert F 

New preprint not affect any of the other three scenarios for selection on a 
human or human like ACE2, but a stronger still argument against 
bioengineering imo. 

Sent from my iPhone 

wrote: 
On Feb 17, 2020, at 2:50 AM, Edward Holmes 
wrote: 
External Sender. Be aware of links, attachments and requests. 

All, 
We have the green light to preprint. 
Kristian - even though bioRxiv deals with primary research papers I still 
feel we should send it there. 
Andrew - I think you can put this in Virological and do some precision 
tweeting. 
Very interesting to see the new ACE2 paper. 

Best wishes, 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

Begin forwarded message: 

From: Clare Thomas 
Subject: RE: Connections COVID-19 
Date: 17 February 2020 at 7:07:01 pm AEDT 

Hi Eddie, 

T 
E 
To: Edward Holmes , Magdalena 
Skipper 
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Thanks for this. I agree that you should deposit the preprint asap. I can 
see it in our system so I’ll send it for expedited review today. 

If the refs are positive it will likely need revising as it already seems out 
of date. See the preprint below, for example, which appeared on 
Saturday and which says that SARS-CoV-2 binds with higher affinity to 
ACE2 than SARS-CoV. And of course if the second pangolin paper 
surfaces that would also affect the conclusions, if their press release is 
to be believed. 

https://www.biorxiv.org/content/10.1101/2020.02.11.944462v1 

Anyway, thanks again for sending this and I’ll try to return a decision 
soon. 

All the best, 

Clare 

The University of Edinburgh is a charitable body, registered in Scotland, with registration 
number SC005336. 

<Andersen.Nature Perspective.Final_v2.docx> 

<Andersen.Nature Perspective.Final_v2.docx> 

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From: Garry, Robert F 
Sent: Monday, February 17, 2020 12:37 PM EST 
To: Jeremy Farrar; Kristian G. Andersen 
CC: Andrew Rambaut; Eddie Holmes; Ian Lipkin 
Subject: Re: Connections COVID-19 

Ian suggested a press release – it’s very appropriate under the circumstances. Who will draft? 

From: Jeremy Farrar 
Date: Monday, February 17, 2020 at 11:35 AM 
To: Kristian Andersen 
Cc: Andrew Rambaut , Robert Garry , Eddie 
Holmes , Ian Lipkin 
Subject: Re: Connections COVID-19 

External Sender. Be aware of links, attachments and requests. 

Reason I ask about when to post is to coordinate press briefings etc etc ….to make sure the key 
messages are reasonably reported… 

From: Jeremy Farrar 
Date: Monday, 17 February 2020 at 18:32 
To: "Kristian G. Andersen" 
Cc: "a.rambaut@ed.ac.uk" , "Garry, Robert F" , 
Edward Holmes Ian Lipkin 
Subject: Re: Connections COVID-19 
No preference – whatever you all think best. 
When do you plan to post? 

From: "Kristian G. Andersen" 
Date: Monday, 17 February 2020 at 18:30 
To: Jeremy Farrar 
Cc: "a.rambaut@ed.ac.uk" , "Garry, Robert F" , 
Edward Holmes , Ian Lipkin 
Subject: Re: Connections COVID-19 

The bioRxiv unfortunately does not accept perspectives/reviews/comments - only original research 
papers so this, per standard policies, can't go on there. For that reason, my preference is to keep this on 
Virological and use that as the channel for dissemination, but if there's a need to try and bypass normal 
bioRxiv policies I can definitely reach out to Richard and John to ask them. I'm leading their efforts for 

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better screening of outbreak-related preprints and have another email out to them so can definitely 
bring it up. Jeremy, what's your preference? 

K 

On Mon, Feb 17, 2020 at 9:22 AM Jeremy Farrar 

wrote: 
Thank you 
Any idea when likely to be released on pre-print server? 
Is tomorrow OK? 
Thinking about the publicity of it…. 

From: "Kristian G. Andersen" 
Date: Monday, 17 February 2020 at 18:11 
To: Jeremy Farrar 
Cc: "Garry, Robert F" , 
Edward Holmes , Ian Lipkin 
Subject: Re: Connections COVID-19 
Sure, attached. 
K 
On Mon, Feb 17, 2020 at 9:02 AM Jeremy Farrar 

Sorry to micro-manage/microedit! 
But would you be willing to change one sentence? 
From 

It is unlikely that SARS-CoV-2 emerged through laboratory manipulation of an existing 
SARS-related coronavirus. 

To 

It is improbable that SARS-CoV-2 emerged through laboratory manipulation of an existing 
SARS-related coronavirus. 

wrote: 
From: 
Date: Monday, 17 February 2020 at 17:56 
To: "Kristian G. Andersen" 
Cc: Jeremy Farrar , "Garry, Robert F" , 
Edward Holmes , Ian Lipkin 
Subject: Re: Connections COVID-19 
CONFIDENTIAL TREATMENT 
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Sorry. This is the final version (v2.2). 
Sent from my phone. Apologies for brevity or illiteracy. 

On 17 Feb 2020, at 16:52, Kristian G. Andersen 

wrote: 
Just corrected a few more typos - but yes, I believe this is the final version for now. I'm sure 
Nature will have plenty of edits. 

K 

On Mon, Feb 17, 2020 at 8:47 AM Jeremy Farrar 

wrote: 
Andrew – is this the ‘final’ draft, pending any changes at Nature – with the additional 
information? 

From: 
Date: Monday, 17 February 2020 at 17:08 
To: Jeremy Farrar , "Garry, Robert F" , 
Edward Holmes , "Kristian G. Andersen" 
, Ian Lipkin 
Subject: Re: Connections COVID-19 
Dear all, 
I think this is now the same version as on Virological. First author's name corrected, 'SARs' 

corrected. Figure updated (and legend corrected). 
Andrew 

On 17 Feb 2020, at 15:28, Jeremy Farrar 

wrote: 
When you have been able to update with the extra sentence and data can you forward on to 
me - keep that WHO see ASAP. 

On 17 Feb 2020, at 12:09, Garry, Robert F 

wrote: 
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This also means less concern about the Baric scenario where another mutation could kick 
SARS-CoV-2 into another gear. Binding already optimal. 

Sent from my iPhone 

External Sender. Be aware of links, attachments and requests. 
On Feb 17, 2020, at 4:51 AM, Andrew Rambaut wrote: 

Fixed. 

On 17 Feb 2020, at 10:47, Edward Holmes 


wrote: 

Hang on…should be " recent binding studies indicate” not indict. One of the 
new edits. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
On 17 Feb 2020, at 9:44 pm, Garry, Robert F 

wrote: 
Looks great! 
Sent from my iPhone 

On Feb 17, 2020, at 4:41 AM, Andrew Rambaut wrote: 

External Sender. Be aware of links, attachments and requests. 
OK. Here is the version with all the changes and the updated references. As I 
manually changed the numbers (adding reference 7 and incrementing all 
numbers above 6) I would appreciate a check. 

I also simplified Bob's text below. 

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I am going to start formatting this in virological so let me know if you spot 
any issues. 

A. 

On 17 Feb 2020, at 10:25, Garry, Robert F 

wrote: 
Another better version: 

While these analyses suggest that SARS-CoV-2 may be capable of 
binding the human ACE2 receptor with high affinity, the interaction 
is not predicted to be optimal1. Additionally, several of the key 
residues in the RBD of SARS-CoV-2 are different to those 
previously described as optimal for human ACE2 receptor binding6. 
In contrast to these computational assessments recent binding 
studies indict that SARS-CoV-2 binds with high affinity to human 
ACE2 (insert ref). SARS-COV-2 spike does not appear to have an 
artificial sequence designed in the laboratory. An artificial sequence 
would have used interactions predicted to be optimal for interaction 
with its receptor. Instead the SARs-CoV-2 spike appears to be the 
result of selection on human or human-like ACE2 permitting 
another optimal binding solution to arise. This is strong evidence 
that SARS-CoV-2 is not the product of genetic engineering. 

From: Andrew Rambaut 
Sent: Monday, February 17, 2020 10:23 AM 

Subject: Re: Connections COVID-19 

External Sender. Be aware of links, attachments and requests. 

OK. I will add that. I am editing the document now. 

Andrew 

On 17 Feb 2020, at 10:20, Garry, Robert F 

While these analyses suggest that SARS-CoV-2 may be capable 
of binding the human ACE2 receptor with high affinity, the 
interaction is not predicted to be optimal1. Additionally, several 
of the key residues in the RBD of SARS-CoV-2 are different to 
those previously described as optimal for human ACE2 receptor 

To: Garry, Robert F 
Cc: Eddie Holmes ; Kristian G. 
Andersen ; Ian Lipkin ; Jeremy 
Farrar 
wrote: 
CONFIDENTIAL TREATMENT 
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binding6. In contrast to these computational assessments recent 
binding studies indict that SARS-CoV-2 binds with high affinity 
to human ACE2 (insert ref). SARS-COV-2 spike does not appear 
to have an artificial sequence designed in the laboratory would 
have been designed for optimal binding and used interactions 
predicted to be optimal. Instead it appears to be the result of 
selection on human or human-like ACE2 permit another optimal 
binding solutions to arise. This is strong evidence that SARSCoV-
2 is not the product of genetic engineering. 

To: Edward Holmes 
Cc: Kristian G. Andersen ; Andrew Rambaut 
; Ian Lipkin ; Jeremy Farrar 
Subject: Re: Connections COVID-19 
From: Garry, Robert F 
Sent: Monday, February 17, 2020 10:02 AM 

put the "While these" back 

From: Edward Holmes 
Sent: Monday, February 17, 2020 9:49 AM 

Subject: Re: Connections COVID-19 

External Sender. Be aware of links, attachments and requests. 

Ok. Pass a draft to me and I’ll give it a quick read through. 

No way I can stay up to your levels... 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

On 17 Feb 2020, at 8:47 pm, Garry, Robert F 

agreed - i'm up - who needs to sleep 

To: Garry, Robert F 
Cc: Kristian G. Andersen ; Andrew Rambaut 
; Ian Lipkin ; Jeremy Farrar 
T 
E 
wrote: 
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will take very quick swing at it now - yes a sentence or two will 
likely do 
15 minutes i'll be back 

From: Edward Holmes 
Sent: Monday, February 17, 2020 9:45 AM 

Subject: Re: Connections COVID-19 

External Sender. Be aware of links, attachments and requests. 

Bob, if you or someone else wants to add a sentence now that’s ok (refs. 
will need to change as well), but we must get it out today. Things are 
moving/changing so rapidly that we are always going to be out of date. We 
need to draw a line somewhere. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

On 17 Feb 2020, at 8:39 pm, Garry, Robert F 

New preprint not affect any of the other three scenarios for selection on a 
human or human like ACE2, but a stronger still argument against 
bioengineering imo. 

Sent from my iPhone 

On Feb 17, 2020, at 2:50 AM, Edward Holmes 

wrote: 
All, 

External Sender. Be aware of links, attachments and requests. 
We have the green light to preprint. 

To: Garry, Robert F 
Cc: Kristian G. Andersen ; Andrew Rambaut 
; Ian Lipkin ; Jeremy Farrar 
T 
E 
wrote: 
CONFIDENTIAL TREATMENT 
REQUESTED - NOT FORCIRCULATION / COMMITTEEMEMBERS AND STAFF ONLY LIP-000650 


Kristian - even though bioRxiv deals with primary research papers I still 
feel we should send it there. 
Andrew - I think you can put this in Virological and do some precision 
tweeting. 

Very interesting to see the new ACE2 paper. 

Best wishes, 

Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
Begin forwarded message: 

From: Clare Thomas 
Subject: RE: Connections COVID-19 
Date: 17 February 2020 at 7:07:01 pm AEDT 

To: Edward Holmes , Magdalena 
Skipper 
Hi Eddie, 

Thanks for this. I agree that you should deposit the preprint asap. I can 
see it in our system so I’ll send it for expedited review today. 

If the refs are positive it will likely need revising as it already seems out 
of date. See the preprint below, for example, which appeared on 
Saturday and which says that SARS-CoV-2 binds with higher affinity to 
ACE2 than SARS-CoV. And of course if the second pangolin paper 
surfaces that would also affect the conclusions, if their press release is 
to be believed. 

https://www.biorxiv.org/content/10.1101/2020.02.11.944462v1 

Anyway, thanks again for sending this and I’ll try to return a decision 
soon. 

All the best, 

CONFIDENTIAL TREATMENT 
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Clare 

The University of Edinburgh is a charitable body, registered in Scotland, with registration 
number SC005336. 

<Andersen.Nature Perspective.Final_v2.docx> 

<Andersen.Nature Perspective.Final_v2.docx> 
<Andersen.Nature Perspective.Final_v2.2.docx> 

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Message 

From: 
Sent: 
To: 
CC: 
Subject: 
Clare Thomas 
3/4/2020 11:44:43 PM 
RE: Decision on Nature submission 2020-02-02583 
Dear Kristian, 
It looks like it's set up with you as the CA with your gmail address as the contact info kga1978@gmail.com. 
I can see whether my assistant can merge the account with your other one: andersen@scripps.edu. I'll ask her to get in 

touch with you once she's done it. Alternatively you can just submit directly to Nature Medicine and if Joao needs to see 

the reports again I can send them to him by email. 
I am indeed drowning in COVID-19 papers. Never been so busy. I cancelled my participation in the conference that Eddie 
is at, in part because I just don't have time to move from my desk ... (sorry to miss you, Eddie). 

I am sure you're frantically busy as well. 
All the best, 
Clare 

From: Kristian G. Andersen 


Sent: 05 March 2020 02:06 
To: Clare Thomas 
Cc: Edward Holmes 
Subject: Re: Decision on Nature submission 2020-02-02583 

Dear Clare, 

We're just about to send our manuscript over to Nature Medicine, which has been much improved due to some 
recent data. I just wanted to share the new material with you so you're in the loop. 

Since the original manuscript was submitted under Eddie's account, would it be possible for you to please 
transfer everything over to my account so I can start the process of getting this to Nature Medicine? Eddie is in 
transit at the moment, so I think it'll be difficult for him to get this transferred in time. If you're not able to 
transfer to my account, don't worry -we'll figure it out. 

Thanks again for giving us the opportunity -we thought this would have been a very good piece for Nature 
given the massive interest, but Nature Medicine (if accepted) will be a good audience too. 

I hope you're not drowning in COVID-19 papers! 

Best, 
Kristian 

REV0002620 


On Thu, Feb 20, 2020 at 9:56 AM Kristian G. Andersen· 

wrote: 
Yeah, no worries Clare -it's a tricky topic and I understand. And thanks for reaching out to your colleagues much 
appreciated. 

Best, 
Kristian 

On Thu, Feb 20, 2020 at 9:54 AM Clare Thomas • wrote: 
Dear Kristian, 
Ok, thanks for clarifying. I am sorry we could not return a more positive decision at Nature but I wish you all the best 

with publishing it elsewhere and I'm glad we could get you some other options at Nature Research, if that interests 
you. 
All the best, 
Clare 

From: Kristian G. Andersen 
Sent: 20 February2020 17:48 
To: Clare Thomas 
Subject: Re: Decision on Nature submission 2020-02-02583 

Thanks Clare for letting me know so quickly. I'll discuss with the other authors to see what the best path 
would be -just one thing to make clear though, reviewer 2 is unfortunately wrong about "Once the authors 
publish their new pangolin sequences, a lab origin will be extremely unlikely". Had that been the case, we 
would of course have included that -but the more sequences we see from pangolins ( and we have been 
analyzing/discussing these very carefully) the more unlikely it seems that they're intermediate hosts. They 
definitely harbor SARS-Co V-like viruses, no doubt, but it's unlikely they have a direct connection to the 
COVID-19 epidemic. Unfortunately none of this helps refute a lab origin and the possibility must be 
considered as a serious scientific theory (which is what we do) and not dismissed out of hand as another 
'conspiracy' theory. We all really, really wish that we could do that (that's how this got started), but 
unfortunately it's just not possible given the data. 

Thanks again for considering our manuscript and while we had of course hoped for a better outcome, we 
understand the decision. 

Best, 

Kristian 

On Thu, Feb 20, 2020 at 8:52 AM· 

wrote: 
20th February 2020 

Dear Kristian, 

Thank you for submitting your manuscript entitled "The Proximal Origin of SARS-CoV-2" to be considered 
for publication in Nature. We've now obtained two ref reports on the paper (appended below) and I've had 
the opportunity to discuss them with our chief editor Magdalena Skipper. In the light of the advice received I 
am afraid we have decided that we cannot offer to publish the Perspective in Nature. 

REV0002621 


While the Perspective is interesting and timely one of our referees raised concerns (also emphasised to the 
editors) about whether such a piece would feed or quash the conspiracy theories. But more importantly this 
reviewer feels, and we agree, that the Perspective would quickly become outdated when more scientific data 
are published (for example on potential reservoir hosts). 

I did, however, take the liberty of consulting with my colleagues at Nature Medicine, Nature Ecology and 
Evolution and Nature Microbiology and I am happy to say that all three journals were interested in 
publishing a revised piece in some form. 

Nature Medicine are interested in publishing it either as a Comment or a Correspondence. If you would like 
to pursue this option, please transfer the submission to Nature Medicine using the link provided below. Feel 
free to reach out to Joao Monteiro, chief editor, at joao .. monteiro@us.nature.com if you want to discuss the 
transfer process or have questions. 

Nature Ecology & Evolution would be interested in considering the manuscript as a Comment article. They 
would like to work with you to address the reviewers' concerns and restructure the manuscript to focus more 
on the plausible evolutionary scenarios. If this option is of interest, you can also use the link below to 
transfer, and please feel free to get in touch with Patrick Goymer (p.goymer@nature.com) to discuss it 
further. 

Finally, Nature Microbiology would similarly be interested in considering a revised manuscript that 
addresses the main concerns from the referees as a Comment article. Should you be interested in this option, 
please use the link below to transfer and please feel free to contact Nonia Pariente 
(nonia.pariente@nature.com; who is currently out of the office but will be back on Feb 24th) and Paula 
Jauregui (paula.jauregui@nature.com) to discuss further. 

I am sorry that we cannot be more positive on this occasion. We hope that our decision does not discourage 
you from submitting your work to us in future as we remain interested in publishing key developments in 
this area ofresearch. We hope that you will find our referees' comments helpful. 

With best wishes, 

Clare 

Clare Thomas 
Senior Editor 
Nature 

Referees' comments: 

Referee #1 (Remarks to the Author): 

Anderson presented a timely manuscript to share their points of view about the origin of SARS-CoV-2. 
There are several rumors about the origin of this virus. However, these "hypotheses" are entirely based on 
very limited, if any, scientific evidences. 
This reviewer sees most of the arguments raised by the authors are valid and convincing. However, the 
authors might want to consider these minor suggestions: 

1.The sections for the RBD and cleavage site of Spike protein basically have summarized the existing 
findings from other recent publications. The authors might want to spell out that these two sections are 

REV0002622 


review summaries. In addition, the author can present these two sections in a more condense format and save 
some space for something else (also see points 6 and 7 below) 

2. Fig. 1. This figure has 6 aligned sequences, but with only 5 sequence titles. The order of these titles are 
also not correct. 
3. Lines 170 -174. It is correct that no adaptive mutation has been found in the spike ofMERS-CoV. 
Deletions in other ORF regions, however, were detected in some human MERS-Co V viruses (PMID: 
26981770). In addition, the 29nt deletion of human SARS-CoV (PMID: 12958366) was suggested to have 
effects on host adaptation. The authors should also consider these findings. It is premature to say that this 
would not happen in SARS-CoV-2. 
4.Line 194. The accident at Singapore occurred in a BSL3, not BSL2, containment. 

5. Line 194. Laboratory escapes of SARS occurred in Singapore, China and Taiwan (PMID: 16830004). 
6.There are two recent reports about coronaviruses in pangolins 
(https://www.biorxiv.org/content/10. l 101/2020.02.13.945485vl .full.pdf; 
https://www.biorxiv.org/content/l0.l 101/2020.02.08.939660v2.ful1.pdf). The authors might want to 
comments on these. 

7. Optional: Can the authors share their views on the possibility of having a lab escape of a natural 
coronavirus? This is also one of the hypotheses that have been extensively discussed. The reviewer 
understand that this is entirely a different topic, but any insights are welcomed. 
Referee #2 (Remarks to the Author): 

This is a perspective discussing evidence against a hypothetical lab origin of SARS-Co V-2. The paper 
addresses suboptimal composition of ACE2-binding sites in the RBD, 3 predicted O-linked glycosylation 
sites and a furin cleavage site in the glycoprotein that was speculated upon before. 

The paper is itself interesting, but unnecessarily speculative. It's not clear why the authors do not refute a 
hypothetical lab origin in their coming publication on the ancestors of SARS-Co V-2 in bats and pangolins. 
The tree showing diverse pangolin viruses has kindly been made available by some of the authors in 
GISAID. Once the authors publish their new pangolin sequences, a lab origin will be extremely unlikely. It is 
not clear why the authors rush with a speculative perspective if their central hypothesis can be supported by 
their own data. Please explain. 

Another critical aspect of this text is the complete lack of referencing to a potential debate on a hypothetical 
lab origin. Who said this, why is this considered a problem? There are indeed a few apparently uninformed 
statements claiming the virus may be a Chinese bioweapon, but is this really problematic on a larger scale? 
The central reason for issuing this text must be exhaustively referenced and discussed. 

The authors state that a predicted polybasic cleavage sites is unique to SARS-CoV-2 in SARS viruses. Who 
knows how many out of thousands undiscovered bat ancestors also acquired such a motif, the sampling bias 
in descriptions of remote bat viruses is dramatic. This should be discussed. Also state clearly that this site is 
only predicted so far and that experimental evidence for its biological function and its potential impact on 
pathogenesis are required. 

The predicted O-linked glycosylation sites are mysterious. What do the authors imply with those sites? In 

REV0002623 


silico prediction of O-linked glycosylation sites is not robust and whether these sites indeed exist requires 
experimental validation. Even if those sites exist, why are they relevant? This is not addressed at all. If the 
authors assume these sites constitute part of a glycan shield, they should say so and weigh their assumption 
carefully. 

Finally, the main argument against a hypothetical lab origin seems the required reconstruction of a backbone 
of a bat virus of unknown pathogenesis. It does not seem feasible that any scientist would disembark on such 
an uncertain endeavor. This difficulties of coronavirus reverse genetics should be stated clearly. 

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REV0002624 


Message 

From: medicine@us.nature.com [medicine@us.nature.com] 

Sent: 3/5/2020 1:03:48 PM 
To: 
CC: medicine@us.nature.com; springernature.com 

Subject: Decision on Nature Medicine submission NMED-LE102233-T 

5th Mar 2020 

Dear Kristian, 

Thanks for working with us to improve your Letter for publication. i'm delighted to tell you that your 
manuscript NMED-LEl 02233-T has been accepted for publication in our Correspondence section, and that it 
has been scheduled for publication in our April print issue. Please note that are fast-tracking the online 
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All the best, 
Joao 

Joao Monteiro 
Chief Editor 

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REV0002761 


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REV0002763 


Message 

From: 
Sent: 
To: 
CC: 
Edward Holmes 
3/5/2020 5:24:59 PM 
Clare Thomas 
Subject: Re: Decision on Nature submission 2020-02-02583 

Thanks Both! 
Sorry if I confused things. 
Sorry to miss you Clare! It was a really good meeting and largely free of coronavirus stuff I had some nice 

conversations with the Nature staff that attended ... who have already sent me papers to review! 
Cheers, 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E: 
On 6 Mar 2020, at 2:08 am, Kristian G. Andersen· 

wrote: 
Hi Clare, 

Yes, sorry -I was confused. Eddie started the process and that emailed a link to me so we should 
be good. Thanks again. 
COVID-19 will be a marathon, not a sprint, so hopefully we'll all get some time to breathe soon 

;). 

Best, 
Kristian 

On Wed, Mar 4, 2020 at 11 :45 PM Clare Thomas • wrote: 
Oh, I was looking at my emails backwards ... I see you've already done it(::;') 

From: Clare Thomas 
Sent: 05 March 2020 07:45 
To: 'Kristian G. Andersen' 

REV0000258 


Cc: Edward Holmes 
Subject: RE: Decision on Nature submission 2020-02-02583 

Dear Kristian, 

It looks like it's set up with you as the CA with your gmail address as the contact info 

I can see whether my assistant can merge the account with your other one: I'll 
ask her to get in touch with you once she's done it. Alternatively you can just submit directly to Nature 
Medicine and if Joao needs to see the reports again I can send thern to him by email. 

I am indeed drowning in COVID-19 papers. Never been so busy. I cancelled my participation in the 
conference that Eddie is at, in part because I just dorl"t have time to move from rny desk ... (sorry to 
miss you, Eddie). 

I am sure you're frantically busy as well. 

All the best, 

Clare 

From: Kristian G. Andersen 

Sent: 05 March2020 02:06 

To: Clare Thomas 

Cc: Edward Holmes 

Subject: Re: Decision on Nature submission 2020-02-02583 

Dear Clare, 

REV0000259 


We're just about to send our manuscript over to Nature Medicine, which has been much 
improved due to some recent data. I just wanted to share the new material with you so you're in 
the loop. 

Since the original manuscript was submitted under Eddie's account, would it be possible for you 
to please transfer everything over to my account so I can start the process of getting this to 
Nature Medicine? Eddie is in transit at the moment, so I think it'll be difficult for him to get this 
transferred in time. If you're not able to transfer to my account, don't worry -we'll figure it out. 

Thanks again for giving us the opportunity -we thought this would have been a very good piece 
for Nature given the massive interest, but Nature Medicine (if accepted) will be a good audience 
too. 

I hope you're not drowning in COVID-19 papers! 

Best, 

Kristian 

On Thu, Feb 20, 2020 at 9:56 AM Kristian G. Andersen· wrote: 

Yeah, no worries Clare -it's a tricky topic and I understand. And thanks for reaching out to 
your colleagues -much appreciated. 

Best, 

Kristian 

On Thu, Feb 20, 2020 at 9:54 AM Clare Thomas < wrote: 

Dear Kristian, 

REV0000260 


Ok, thanks for clarifying. I am sorry we could not return a more positive decision at Nature but I wish 
you all the best with publishing it elsewhere and I'm glad we could get you some other options at 
Nature Research, if that interests you. 

A!I the best, 

Clare 

From: Kristian G. Andersen 
Sent: 20 February 2020 17:48 
To: Clare Thomas 
Subject: Re: Decision on Nature submission 2020-02-02583 

Thanks Clare for letting me know so quickly. I'll discuss with the other authors to see what 
the best path would be -just one thing to make clear though, reviewer 2 is unfortunately 
wrong about "Once the authors publish their new pangolin sequences, a lab origin will be 
extremely unlikely". Had that been the case, we would of course have included that -but the 
more sequences we see from pangolins (and we have been analyzing/discussing these 
very carefully) the more unlikely it seems that they're intermediate hosts. They definitely 
harbor SARS-CoV-like viruses, no doubt, but it's unlikely they have a direct connection to the 
COVID-19 epidemic. Unfortunately none of this helps refute a lab origin and the possibility 
must be considered as a serious scientific theory (which is what we do) and not dismissed out 
of hand as another 'conspiracy' theory. We all really, really wish that we could do that (that's 
how this got started), but unfortunately it's just not possible given the data. 

Thanks again for considering our manuscript and while we had of course hoped for a better 
outcome, we understand the decision. 

Best, 

Kristian 

On Thu, Feb 20, 2020 at 8:52 AM· 

wrote: 
20th February 2020 

Dear Kristian, 

Thank you for submitting your manuscript entitled "The Proximal Origin of SARS-CoV-2" 
to be considered for publication in Nature. We've now obtained two refreports on the paper 
(appended below) and I've had the opportunity to discuss them with our chief editor 
Magdalena Skipper. In the light of the advice received I am afraid we have decided that we 

REV0000261 


the link the link 
cannot offer to publish the Perspective in Nature. 

While the Perspective is interesting and timely one of our referees raised concerns (also 

emphasised to the editors) about whether such a piece would feed or quash the conspiracy 
theories. But more importantly this reviewer feels, and we agree, that the Perspective would 

quickly become outdated when more scientific data are published (for example on potential 
reservoir hosts). 

I did, however, take the liberty of consulting with my colleagues at Nature Medicine, Nature 
Ecology and Evolution and Nature Microbiology and I am happy to say that all three 
journals were interested in publishing a revised piece in some form. 

Nature Medicine are interested in publishing it either as a Comment or a Correspondence. If 
you would like to pursue this option, please transfer the submission to Nature Medicine 
rovided below. Feel free to reach out to Joao Monteiro, chief editor, at 
if you want to discuss the transfer process or have questions. 

Nature Ecology & Evolution would be interested in considering the manuscript as a 
Comment article. They would like to work with you to address the reviewers' concerns and 
restructure the manuscript to focus more on the plausible evolutionary scenarios. If this 
option is of interest, you can also use the link below to transfer, and please feel free to get in 
touch with Patrick Goymer o discuss it further. 

Finally, Nature Microbiology would similarly be interested in considering a revised 
manuscript that addresses the main concerns from the referees as a Comment article. Should 
you be interested in this o tion lease use the link below to transfer and please feel free to 

contact Nonia Pariente ( who is currently out of the office but 
will be back on Feb 24th) and Paula Jauregui to discuss 
further. 

I am sorry that we cannot be more positive on this occasion. We hope that our decision does 
not discourage you from submitting your work to us in future as we remain interested in 
publishing key developments in this area of research. We hope that you will find our 
referees' comments helpful. 

With best wishes, 

Clare 

Clare Thomas 
Senior Editor 
Nature 

Referees' comments: 

Referee #1 (Remarks to the Author): 

Anderson presented a timely manuscript to share their points of view about the origin of 
SARS-CoV-2. There are several rumors about the origin of this virus. However, these 
"hypotheses" are entirely based on very limited, if any, scientific evidences. 
This reviewer sees most of the arguments raised by the authors are valid and convincing. 

REV0000262 


However, the authors might want to consider these minor suggestions: 

1.The sections for the RBD and cleavage site of Spike protein basically have summarized the 
existing findings from other recent publications. The authors might want to spell out that 
these two sections are review summaries. In addition, the author can present these two 
sections in a more condense format and save some space for something else ( also see points 
6 and 7 below) 
2. Fig. 1. This figure has 6 aligned sequences, but with only 5 sequence titles. The order of 
these titles are also not correct. 
3. Lines 170 -174. It is correct that no adaptive mutation has been found in the spike of 
MERS-Co V. Deletions in other ORF regions, however, were detected in some human 
MERS-CoV viruses (PMID: 26981770). In addition, the 29nt deletion of human SARS-CoV 
(PMID: 12958366) was suggested to have effects on host adaptation. The authors should also 
consider these findings. It is premature to say that this would not happen in SARS-CoV-2. 
4.Line 194. The accident at Singapore occurred in a BSL3, not BSL2, containment. 

5. Line 194. Laboratory escapes of SARS occurred in Singapore, China and Taiwan (PMID: 
16830004). 
6.There are two recent reports about coronaviruses in pangolins 
(https:/ /www.biorxiv.org/content/10.1101/2020.02.13.945485vl .full.pdf; 
https://www.biorxiv.org/content/10.1101/2020.02.08.939660v2.full.pdf). The authors might 
want to comments on these. 

7. Optional: Can the authors share their views on the possibility of having a lab escape of a 
natural coronavirus? This is also one of the hypotheses that have been extensively discussed. 
The reviewer understand that this is entirely a different topic, but any insights are welcomed. 
Referee #2 (Remarks to the Author): 

This is a perspective discussing evidence against a hypothetical lab origin of SARS-Co V-2. 
The paper addresses suboptimal composition of ACE2-binding sites in the RBD, 3 predicted 
O-linked glycosylation sites and a furin cleavage site in the glycoprotein that was speculated 
upon before. 

The paper is itself interesting, but unnecessarily speculative. It's not clear why the authors do 
not refute a hypothetical lab origin in their coming publication on the ancestors of SARS-
Co V-2 in bats and pangolins. The tree showing diverse pangolin viruses has kindly been 
made available by some of the authors in GISAID. Once the authors publish their new 
pangolin sequences, a lab origin will be extremely unlikely. It is not clear why the authors 
rush with a speculative perspective if their central hypothesis can be supported by their own 
data. Please explain. 

Another critical aspect of this text is the complete lack of referencing to a potential debate on 
a hypothetical lab origin. Who said this, why is this considered a problem? There are indeed 
a few apparently uninformed statements claiming the virus may be a Chinese bioweapon, but 
is this really problematic on a larger scale? The central reason for issuing this text must be 

REV0000263 


exhaustively referenced and discussed. 

The authors state that a predicted polybasic cleavage sites is unique to SARS-Co V-2 in 
SARS viruses. Who knows how many out of thousands undiscovered bat ancestors also 
acquired such a motif, the sampling bias in descriptions of remote bat viruses is dramatic. 
This should be discussed. Also state clearly that this site is only predicted so far and that 
experimental evidence for its biological function and its potential impact on pathogenesis are 
required. 

The predicted O-linked glycosylation sites are mysterious. What do the authors imply with 
those sites? In silico prediction of O-linked glycosylation sites is not robust and whether 
these sites indeed exist requires experimental validation. Even if those sites exist, why are 
they relevant? This is not addressed at all. If the authors assume these sites constitute part of 
a glycan shield, they should say so and weigh their assumption carefully. 

Finally, the main argument against a hypothetical lab origin seems the required 
reconstruction of a backbone of a bat virus of unknown pathogenesis. It does not seem 
feasible that any scientist would disembark on such an uncertain endeavor. This difficulties 
of coronavirus reverse genetics should be stated clearly. 

**If you wish to transfer your manuscript to Nature Medicine, you may use our manuscript 
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REV0000264 


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REV0000265 


Message 

From: 
Sent: 
To: 
Joao Monteiro 
3/5/2020 10:17:45 AM 
Kristian G. Andersen Edward Holmes 
Subject: RE: Interest in "Proximal Origins of hCoV-19"? 

Thanks, Kristian. 

Our Editorial Assistant, Sarah will send you the copyright assignment form. Please return it to her today if possible. 
Otherwise we are good to go. 
Joao 

From: Kristian G. Andersen 


Sent: Thursday, March 05, 2020 12:29 PM 

To: Edward Holmes 

Cc:Joao Monteiro 

Subject: Re: Interest in "Proximal Origins of hCoV-19"? 

Hi Joao, 

Just to let you know the manuscript has been transferred over -NMED-C102233-T. 

Please let me know if you need anything else or have any questions. 

Best, 
Kristian 

On Wed, Mar 4, 2020 at 7:04 PM Edward Holmes 

wrote: 
Excellent, many thanks. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney I Sydney I NSW I 2006 I Australia 

T 
E 
On 4 Mar 2020, at 7:02 pm, Kristian G. Andersen· 

wrote: 
Yup, links work -all good, I'll get this done in the morning. 
K 

On Wed, Mar 4, 2020 at 7:01 PM Edward Holmes 

wrote: 
Ok! I started the transfer process but I've just aborted. 

REV0000279 


Kristian -can you just check that the link works. 
Cheers, 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 

I I I I

The University of Sydney Sydney NSW 2006 Australia 

T 
E, 
On 4 Mar 2020, at 6:59 pm, Kristian G. Andersen 

Ah, I have the email -I see the link. I'll update a few things and get this transferred over -should be 
completed tomorrow morning. 
K 
On Wed, Mar 4, 2020 at 6:57 PM Joao Monteiro 

Hi, 
If you are listed as corresponding author, you can just go ahead and transfer the paper using the link in the 
decision letter from Nature that you received. You may also be able to make Kristien a corresponding author, 
if you have access to your account. 
Sent from my iPhone, please excuse the brevity. 

On Mar 4, 2020, at 9:54 PM, Edward Holmes I 
Apologies! I'm in LAX now and will be for a few hours. 
Please let me know what I need to do get this resolved. 
Best wishes, 
Eddie 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 

I I I

The University of Sydney I Sydney NSW 2006 Australia 

wrote: 
wrote: 
wrote: 
T 
E, 
REV0000280 


On 4 Mar 2020, at 4:33 pm, Kristian G. Andersen 

wrote: 
Once I have clarity on HCoV-19/SARS-CoV-2 I have all the edits in. 
As for the previous submission -that's actually under Eddie's account -are you able to 

transfer it over to mine (krisandersen)? Otherwise, I'll forward all the material to Eddie and 
then he can transfer -I believe he's en route to Sydney at the moment. 
K 

On Wed, Mar 4, 2020 at 3:32 PM Kristian G. Andersen· wrote: 

Great, thanks J oao -I can incorporate. 

A couple of specific comments: 

• "Proximal" is included since we're talking about the most recent origin -not deeper 
origins ( e.g., in bats). I have heard from a number of people that they really like that 
bit, so I was hoping to keep it? 
• The naming of the virus is tricky and I'm hoping to push back a little here -but of 
course will do whatever you prefer. The name "SARS-CoV-2" was chosen by ICTV 
without consulting any Chinese authorities or any of the people involved in its 
discovery. The WHO -while they now acknowledge SARS-CoV-2 as the official 
name of the virus, they refuse to use it because of stigma and other issues. HCo V-19 
was suggested by a number of leading Chinese scientists involved in the discovery of 
the virus to (a) avoid stigma, and (b) make it more consistent with the name of the 
disease. https:/ /v.1ww.thelancet.com/j ournals/lancet/article/PIIS0 140-6736(20)304 l 90/
fulltext. Again, we'll of course do whatever you think is best, but my personal 
opinion (shared by my co-authors) is that HCoV-19 is more appropriate than SARSCoV-
2. 
<Screen Shot 2020-03-04 at 3.30.34 PM.png> 

On Wed, Mar 4, 2020 at 3 :22 PM J oao Monteiro wrote: 

Hi Kristian, 

Thanks for the quick reply. I have added a couple notes to the file, for you to review plus some 
stylistic edits. Once you're done, can you transfer the submission from Nature to our system and 
upload the files to include the revised finalized version, t:he point-by-point response and the figure 
file separately, please? The main text should be an editable word doc. 

L.MK if you have any questions. I'll be on and off for the next hour or so. If you can turn this back to 
me before end of the week, would be fab. 
REV0000281 


ATB 
Joao 

From: Kristian G. Andersen 
Sent: Wednesday, March 04, 2020 5:56 PM 
To: Joao Monteiro 
Subject: Re: Interest in "Proximal Origins of hCoV-19"? 

Hi Joao, 

Please find attached a version cut to the suggested size. Please let me know if you have any 
questions or if you need anything else. 

Best, 

Kristian 

On Tue, Mar 3, 2020 at 5:27 PM Kristian G. Andersen wrote: 

Hi Joao, 

Thanks for getting back to me. Sounds good -we'll cut it to size and get back to you asap 
(hopefully tomorrow). 

K 

On Tue, Mar 3, 2020 at 11 :02 AM Joao Monteiro wrote: 

Hi Kristian, 

Thanks for sending the files and sorry about the delay to respond. 

REV0000282 


We're interested in the piece, though I must it has grown significantly since the version I saw in 
consultation with Nature. Our plan was going to pursue publication within our Correspondences 
section, given the tone and overall type of discussion in the piece. I could offer M2200 words, and 
up to 30 references, so you'd need to trim this back down more or less the size of the Nature 
version, while retaining the major changes in response to the reviewers. 

Does this sound a reasonable plan to you? I believe that using this route, we could move ahead 
with publication fairly quickly. 

Please let me know. 

All the best, 
Joao 

From: Kristian G. Andersen 
Sent: Saturday, February 29, 2020 7:22 PM 
To: Joao Monteiro 
Subject: Re: Interest in "Proximal Origins of hCoV-19"? 

Hi Joao, 

Sorry for the delay in getting this over to you. I have attached the manuscript (PDF + 
Word), figure, and the response to the questions raised after our first submission. 
Please let me know if you have any questions or if you want me to submit this via your 
formal submission system. 

Best, 

Kristian 

On Thu, Feb 27, 2020 at 9:17 PM Kristian G. Andersen 

wrote: 
Hi Joao, 

REV0000283 


Sounds great. I need to get a few final edits in to make our conclusions a little less open 
ended (to make clearer that this does have a natural origin), but I'm hoping to get that 
done tomorrow in the AM. I' 11 send it over to you as soon as that's done. 

K 

On Thu, Feb 27, 2020 at 18:53 Joao Monteiro· 

wrote: 
Hi Kristian, 

Thanks for reaching out. Yes, we are very interested in the comment, and since it's been 
already peer reviewed, we were hoping to. I've ahead with fairly quickly. I'm at a 
conference right now, back to the office tomorrow. In the meanwhile, could you send 
me the revised version you're working on? I can work in that fri. The editorial side, so 
that when you transfer, we can move ahead with accepting it straight away. 

All the best, 

Joao 

Sent from my iPhone, please excuse the brevity. 

On Feb 27, 2020, at 7:34 PM, Kristian G. Andersen 

wrote: 
Dear Joao, 

I believe Clare over at Nature might have mentioned our commentary on 
the proximal origins of the hCo V-19 virus last week. We have been 
incorporating some critical changes to the reviewer's comments so I just 
wanted to reach out to you to see if you're still interested in having a look 
at this manuscript? We're still incorporating a few changes but will have 
all of this wrapped up shortly as we're on a tight deadline -the media 
interest in this has been enormous and hasn't slowed down (we have 
refrained from commenting until formal publication). The public interest 

REV0000284 


has also been very high, with more than 65,000 reads of the blog post 
version over the last week. 

Best, 
Kristian 

Kristian G. Andersen, PhD 

Associate Professor, Scripps Research 

Director of Infectious Disease Genomics, Scripps Research Translational 
Institute 
Director, Center for Viral Systems Biology 

The Scripps Research Institute 

10550 North Torrey Pines Road, Department 
of Immunology and :Microbial Science 
La Jolla, CA 9 203 7 

p: 

c: 


t: (q)K G Andersen 
e: 


w: W\V\v.ande.rsen--lab.com 
Assistant: : 


REV0000285 


Message 

From: Chris Emery 


Sent: 3/17/2020 1:21:41 PM 
To: Kristian Andersen Gmail Forward 

FW: COVID-19 preprint of interest -now published
Subject: 

You probably know this, but the paper is live. Press release is up here: https://www.scripps.edu/news-and-events/pressroom/
2020/20200317 -andersen-covid-19-coronavi rus. htm I 


From: "Coleman, Amanda (NIH/NIAID) [C]" 

Date: Tuesday, March 17, 2020 at 1:15 PM 

To: "Shabman, Reed (NIH/NIAID) 

Cc:"Brown, Liliana (NIH/NIAID) [E]" 

Subject: RE: COVID-19 preprint of interest -now published 

[E]" • 
Thanks so much, Reed. I'll let the Office of Communications know. 

Thank you, 

Amanda Coleman [C] 

From:Shabman, Reed (NIH/NIAID) [El 


Sent:Tuesday, March 17, 2020 3:01 PM 

To: Coleman, Amanda (NIH/NIAID [C] · 
Cc:Brown, Liliana (NIH/NIAID) [El 
Subject:RE: COVID-19 preprint of interest -now published 

Hi Amanda, 

Following-up on this email chain. The paper, The proximal origin of SARS-CoV-2, is now online at Nature 
Medicine. Disregard my note if you have already heard from Chris at Scripps, but just wanted to close the loop. 

Reed 

Link: https://www. nature. com/ articles/ s41591-020-0820-9#Ackl 

From:Shabman, Reed (NIH/NIAID) [El 
Sent:Wednesday, February 19, 2020 3:30 PM 
To: Coleman, Amanda (NIH/NIAID 
Cc:Brown, Liliana (NIH/NIAID) [El 
Subject:RE: COVID-19 preprint of interest 

Hi Amanda, 

I reached out to Kristian and team and copied his response below in italics. As you can see from his note, the text is 
submitted to Nature. Kristian suggests that the Office of Communications can communicate directly with Chris Emery 
(copied here). 

REV0002496 

• Chris Emery• 
[C] 

Thanks, 

Reed 

Yes, it's been submitted for peer review (in Nature) and we are holding off on giving further comments to the media until 
it's been through that and published. Chris Emery from our communications department (cc'd here) is taking the lead on 
creating a press release I summary in lay language, as well as a Q&A with questions the public and policy makers might 
have -Wei/come is involved as well to help out. If there's interest on NIA/D's side, I'm sure Chris and the team would 
welcome coordination/collaboration, so if you can please reach out to him directly. 

Best, 
Kristian 

From: Coleman, Amanda (NIH/NIAID) [C] 
Sent:Wednesday, February 19, 2020 1:21 PM 
To: Shabman, Reed (NIH/NIAID) [El 
Cc: Brown, Liliana (NIH/NIAID) [El 
Subject:RE: COVID-19 preprint of interest 

Hi Reed -The Office of Communications asked if we could alert them if this paper is accepted in a peer reviewed journal. 
Do you know if the authors have submitted it to a journal? 

Thank you, 

Amanda Coleman [C] 

REV0002497 


Kristian G. Andersen 
3/31/2020 8:59:49 PM 
Kristian G. Andersen 
3/31/2020 8:59:49 PM 
Message 

From: 

Sent: 

To: Michael Farzan 

Subject: Re: Furin ... 

Hey Mike, 
Still chugging along here in SoCal. .. As per our previous conversations, I thought this was pretty interesting: 
http://virological.org/t/identification-of-a-common-deletion-in-the-spike-protein-of-sars-cov-2/451 
Not quite sure what to make of it -but definitely interesting! 
K 

On Mon, Feb 17, 2020 at 9:26 AM Kristian G. Andersen 
Hey Mike, 

Thanks -I was actually in the desert when that got pushed out, so a Little rushed IMO. But pressure from the 
higher ups to get it out. 

Thanks for your comment on the structure/binding -this is actually really important. We have been discussing 
that bioRxiv paper this morning since it appears to show that -2 does indeed bind as well -or better -than -1. 
There is other data to suggest that too, but good to know that this isn't gospel! 

Four pangolin sequences just dropped as well -unfortunately these are similar to the previous and not similar 
in the RBD. I'm starting to think that one pango that stands out might not actually be correct. Hopefully more 
to come! 

Cheers, 

K 

wrote: 
On Mon, Feb 17, 2020 at 9: 17 AM Michael Farzan 

wrote: 
Yep. 

Hey just saw your review. Nice! 

Fyi: Jason McClellan's otherwise gorgeous S-protein structure includes a probably wrong assertion that the SARS2 S 
protein binds with "20-fold" higher affinity than that of SARSl. This is almost certainly wrong, and based in thei paper 
on an apples to oranges comparison. I suspect that will be in the press soon but thought I would mention it in case 
you were asked, "the jury is still out on that conclusion". 

From:Kristian G. Andersen 


Sent:Sunday, February 16, 2020 9:45 PM 
To:Michael Farzan 
Subject:Re: Furin ... 

HIGHLY CONFIDENTIAL AND PROPRIETARY FARZAN-0000102 


Hey Mike, 

Yup, one of the pangolin sequences have a very similar RBD (the others are more like bat and further from 
human still). It's not the elusive "99% pangolin" though as that sequence was never published nor was a study 
produced -I think they might have spoken a little too soon. The one that's onJine and close in the RBD is from 
merging a couple of metagenomic datasets and is very incomplete, so I'm not quite sure what to make of it. I 
really hope they'd come up with the 99% sequence -that'd be cool! 

Cheers, 

Kristian 

On Sat, Feb 15, 2020 at 9:42 AM Michael Farzan wrote: 


Hi Kristian, you probably know this by now but the RBM of the 99% panglolin-derived virus is virtually 
identical to SARS2 but the furin-site 4-aa insertion is missing. Mike 

From: Michael Farzan 

Sent: Thursday, February 6, 2020 11 :07 PM 
To: Kristian G. Andersen 
Subject:RE: Furin ... 

Hey Kristian, 

It's a bit complicated but here is the best I can find. 

There are two MHV variants A59 and BHK. BHK is lab adapted and has extended host range, and no 
longer is cleaved in the producer cell by furin. It also appears to be independent of the murine ( or human) 
CEACAM receptor, relying on heparan sulfate. 

The furin site has not changed in BHK, rather two amino acids immediately downstream account for the 

phenotype. 

https://jvi.asm.org/content/79/22/14451?ijkey=709aa5da9513e80f42db103ecl9b539edlcc350b&keytype2=tf 
ipsecsha 

Virus-Cell Interactions 

HIGHLY CONFIDENTIAL AND PROPRIETARY FARZAN-0000103 


Drosten, Christian 
Andrew Rambaut 
; collinsf( 
Drosten, Christian 
Andrew Rambaut 
; collinsf( 
Message 

From: Jeremy Farrar 


Sent: 2/8/2020 1:27:14 PM 
To: 
CC: 

Subject: Re: [ext] 2019 N-CoV 

We now have (and we will get more) the pangolin data (Eddie has) we think we can tie 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 .... 


From: "Kristian G. Andersen" 

Date: Saturday, 8 February 2020 at 21:16 
To: "Drosten, Christian" 
Cc:Jeremy Farrar· 

Josie 
Mike Ferguson 


Subject: Re: [ext] 2019 N-CoV 

A lot of good discussion here, so I just wanted to add a couple of things for context that I think are important -and why 
what we're considering is far from "another conspiracy theory", but rather is taking a valid scientific approach to a 
question that is increasingly being asked by the public, media, scientists, and politicians (e.g., I have been contacted by 
Science, NYT, and many other news outlets over the last couple of days about this exact question). 

To Ron's question, passage of SARS-like Co Vs have been ongoing for several years, and more specifically in Wuhan under 
BSL-2 conditions -see references 12-15 in the document for a few examples. The fact that Wuhan became the epicenter 
of the ongoing epidemic caused by nCoV is likely an unfortunate coincidence, but it raises questions that would be 
wrong to dismiss out of hand. Our main work over the last couple of weeks has been focused on trying to disprove any 
type of lab theory, but we are at a crossroad where the scientific evidence isn't conclusive enough to say that we have 
high confidence in any of the three main theories considered. Like Eddie -and I believe Bob, Andrew, and everybody on 
this email as well -I am very hopeful that the viruses from pangolins will help provide the missing pieces. For now, giving 
the lab theory serious consideration has been highly effective at countering many of the circulating conspiracy theories, 
including HIV recombinants, bioengineering, etc. -here's just one 
example: https://www.factcheck.org/2020/02/baseless-conspiracy-theories-claim-new-coronavirus-wasbioengineered/. 


As to publishing this document in a journal, I am currently not in favor of doing so. I believe that publishing something 
that is open-ended could backfire at this stage. I think it's important that we try to gather additional evidence -including 
waiting on the pangolin virus sequences and further scrutinize the furin cleavage site and O-linked glycans -before 

REV0000722 


publishing. That way we can (hopefully) come out with some strong conclusive statements that are based on the best 
data we have access to. I don't think we are there yet. 

Best, 
Kristian 

On Sat, Feb 8, 2020 at 12:38 PM Drosten, Christian • wrote: 
OK, I see. We should then introduce references to these informal sources in the beginning of the text. Else it reads a bit 
funny. 

Christian 

Professor Christian Drosten 

Director, Institute of Virology 
Scientific Director, Charite Global Health 

Charite -Universitatsmedizin Berlin 
Campus Charite Mitte 


Germany 

E-Mail: 
https://virologie-ccm.charite.de/ 
https :/lg lobalhealth. cha rite .de/ 


Von: Jeremy Farrar· 

Datum: Samstag, 8. Februar 2020 um 21:21 
An: Edward Holmes 
Cc:"kga1978( 
"rfgar 
"P.Val 
Betreff: Re: [ext] 2019 N-CoV 

The theory of the origin of the has gathered considerable momentum not in social media, but increasingly among some 
scientists, in main stream media, and among politicians. 

The aim of this was to bring a neutral, respected, scientific group together to look at the data and in a neutral, 
considered way provide an opinion and we hoped to focus the discussion on the science, not on any conspiracy or 

REV0000723 


other theory and to lay down a respected statement to frame whatever debate goes on -before that debate gets out 
of hand with potentially hugely damaging ramifications. 

With the additional information on the pangolin virus, information not available even 24 hours ago, I think the 
argument is even clearer. 

My preference is that a carefully considered piece of science, early in the public domain, will help mitigate more 
polarised debate. If not, that debate will increasingly happen and science will be reacting to it. Not a good position to 
be in. 


From: Edward Holmes 

Date: Saturday, 8 February 2020 at 20:11 


Subject: Re: [ext] 2019 N-CoV 

Hi Christian, 

I don't know where this story came from, but it has nothing whatsoever to do the HIV nonsense. Please don't associate 
this with that. This is a broader story. 

Ever since this outbreak started there have suggestions that the virus escaped from the Wuhan lab, if only because of 
the coincidence of where the outbreak occurred and the location of the lab. I do a lot of work in China and I can you 
that a lot of people there believe this and believe they are being lied to. Things were made worse when Wuhan lab 
published the bat virus sequence -a bat sampled in a different province for which they have a large collection of 
samples. 

I believe the aim/question here is whether we, as scientists, should try to write something balanced on the science 
behind this? There are arguments for and against doing this. 

Personally, with the pangolin virus possessing 6/6 key sites in the receptor binding domain, I am in favour of the natural 
evolution theory. 

Best wishes, 

Eddie 

REV0000724 


PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney | Sydney | NSW | 2006 | Australia 

T 
E 
On 9 Feb 2020, at 6:52 am, Drosten, Christian • rote: 
Dear All, 
I am overloaded with nCoV patient-related work and will need a few days before I can work on this text. 
Can someone help me with one question: didn't we congregate to challenge a certain theory, and if we could, drop it? 

This whole text reads as if the hypothesis was obvious, or was brought up by some external source, forcing us to 
respond. Is this the case? It does not seem as if this was linked to the HIV nonsense. 
Who came up with this story in the beginning? Are we working on debunking our own conspiracy theory? 
Christian 

Professor Christian Drosten 

Director, Institute of Virology 
Scientific Director, Charite Global Health 

Charite -Universitatsmedizin Berlin 
Campus Charite Mitte 


Germany 

E-Mail: 
https://virologie-ccm.charite.de/ 
https ://g lobalhealth. charite.de/ 


Von: Jeremy Farrar 

Datum: Samstag, 8. Februar 2020 um 10:45 

An: Edward Holmes· 
REV0000725 


Betreff: [ext] FW: 2019 N-CoV 

APOLOGIES WITH ALL CORRECT EMAILS 

Kristen, Andrew, Bob, Eddie have reworked the summary and it is attached here. 

We are pushing to get the sequence data from the reports on the pangolins, but do not have currently, clearly that is 
very important to incorporate. 

Interested in your views 

• Is this reasonably balanced given the data? 
• Is there anything anyone disagrees with? 
• Is there anything more in relation to what would seem to be the two possibilities 
o Nature, Intermediate host, evolution and passage 
• Future data you may have 
• Advice on whether KA, AR, RG and EH should publish this. 
These and other thoughts welcome in confidence. 

REV0000726 


Message 
From: 
Message 
From: 
Sent: 7/28/2020 4:23:46 AM 

To: Kristian G. Andersen 
CC: Garry, Robert F External Sender. Be aware of links, attachments and requests. 
Andrew Rambaut 
Subject:Re: Teleconference 
All, I've spoken to Jeremy and he wants a little more of the time-line incorporated, which helps make or case 
stronger. Also happens to be true. He's also agreed to be cc' d on the reply to Jon which is great because he will 
be able to confirm. 

So, I've edited the draft email to Jon accordingly (Kristian, I've moved some sentences around). 

Jeremy's comms person at Wellome also had some suggestions and I'll forward that in a sec. 

Cheers, 

Eddie 

Hi Jon, 

Here are the facts: 

1. On Jan 27 Jeremy Farrar called one of us (Eddie) to say that some rumours were coming out of 
the US that the virus may be a lab escape and could he determine whether this had any scientific 
credibility. By coincidence, on Jan 31 Kristian independently contacted Eddie to note that there was 
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. At this stage we thought it was wise to ask for additional opinion on this, so a conference call was 
rapidly arranged for Feb 1 (Feb 2 Eddie's time). There were indeed other coronavirus experts on the 
call, chosen by Jeremy and Eddie. It is worth pointing out at this point 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/Uanalysis-of-wuhan-coronavirus-deja-vu/357). 
3. Clearly, some people on the call were very strongly of the opinion that the possibility of a lab 
escape was implausible and gave reasons why it should be dismissed (although there was also some 
initial confusion about whether we were referring to the crazy HIV origins theory that had just been 
touted -obviously we were not). Some of those comments we agreed with, others we did not. 
GARRY0000600 


4. A take-home message from the call was that we should investigate further and write a scientific 
paper to clearly set-out the background on the topic and our findings. Indeed, one the of emailed agenda 
items for discussion after the call was: "Advice on whether KA, AR, RG and EH should publish this". 
Hence, we eventually wrote up our findings as a scientific (peer reviewed) paper. Critically, drafts of 
this paper were sent to all the people on the call, including those with the information that has been 
emailed to you. We have attached our first draft of what would eventually become our paper from Feb 
7, which was circulated to everyone on the call. As you can see, it is essentially the basis of our final 
study and people on the call commented on it. 

5. Very shortly after the call, the pangolin data came out. 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." 

With Andrew Rambaut replying: 

"I am of the view that the natural selection hypothesis is the most likely (specifically the non-bat reservoir). And as 
Eddie mentioned this is becoming more likely from day to day with the pangolin story." 

6. Hence, it is completely and utterly false to claim that we (i) all thought it was a lab escape, (ii) that 
we were corrected ("schooled") in our views by the coronavirus experts on the call, and (iii) then 
submitted a Nature paper without anyone else knowing about it. 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. 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. 
7. We also categorically deny that we were "spreading the rumor" that the virus was human 
engineered. As you can see from point 1 this did not come from us. Indeed, at the time, there were 
indeed rumours -which persists to this day -that SARS-CoV-2 was an engineered virus, but these 
certainly did not come from us. As you know, the White House OSTP asked for expert opinions on 
this question too (spurred by the HIV nonsense preprint), and Kristian was part of that panel 
(https://www.the-scientist.com/news-opinion/lab-made-coronavirus-triggers-debate-34502). Our study 
directly addressed these rumors in a scientific way by considering that a lab escape could have 
occurred. We did not dismiss this possibility out of hand, but we scientifically investigated it. 
8. We strongly reject the idea that we should not have raised nor discussed the possibility of lab 
escape: as scientists we have to present all the data and discuss it openly. That's what we did. To not 
have considered or mentioned the possibility of a lab escape would have been negligent. Is the 
person who emailed you seriously suggesting that we should not have discussed these issues? 
Wouldn't that be a cover-up? 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. Can you imagine if we had not mentioned -or considered -it all as suggested by some 
"coronavirus experts"? 
To is, this clearly appears to be a case of sour grapes based on half-truths that lack the full history, 
gossip, and likely stimulated by your recent (great) article with quotes from us on the questions you 
raised with Dr. Zhengli. It's telling that the person who emailed you is anonymous. We have 
absolutely no problem with people knowing that our views on this issue have evolved as more data 
have appeared -and continues to evolve to this day, should more data become available. That's 

GARRY0000601 


science. And it's the only way to do it well. Indeed, we have told our history of thinking on this to many 
people: the way we set this up was a study of alternative hypotheses equally weighted priors, which 
we tested -our posterior clearly favors the hypothesis that this is a natural virus. As far as we can tell 
we are only 'guilty' of following the proper scientific method -but maybe we offended an ivory tower 
"coronavirus expert" in the process. It likely won't be the last time. 

Best, 

Eddie and Kristian 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 

~I I | The University of Sydney | Sydney I NSW 2006 Australia 

On 28 Jul 2020, at 6:21 pm, Andrew Rambaut wrote: 

I agree -most likely Ron doing the leaking. Whoever it was that talked to the emailer was indignant that 'noncoronavirus-
experts' were involved. I can't see any of the others having this sort of pompous, arrogant view of 
the world. Marion approached me well after this to help analyse the Dutch data. Christian I have worked with 
before on MERS. I doubt even that Ron was that bothered -probably just told the story to whoever it was and 
misremembered or 'enhanced' it for effect. 

A 

On 28 Jul 2020, at 03:58, Edward Holmes wrote: 
Pohlmann as on it and very good. Christian was also v. interested in the furin cleavage site (I've other emails). 
Despite this, I'm I 00% sure it is Ron who leaked it -he was the most angry -and I still think it was like Barie 

who emailed Jon Cohen. 
I just thought "I would conclude that a follow-up discussion on the possible origin of 2019-nCo V would be of 
much interest" was very interesting. 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 

I I

The University of Sydney I Sydney I NSW 2006 Australia 

GARRY0000602 


On 28 Jul 2020, at 12:54 pm, Kristian G. Andersen 

wrote: 
Interesting -I don't actually remember this from Ron. Was Stefan Pohlmann on the call too? Surely he knows 
Ralph very well. 

On Mon, Jul 27, 2020 at 7:47 PM Edward Holmes 
Ron thought it was useful at the time. 


PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The Universi of S dne S dne | NSW | 2006 | Australia 

T 
E 
Begin forwarded message: 

From: "R.A.M. Fouchier" 
Subject: Re: Teleconference 
Date: 2 February 2020 at 7:30:12 pm AEDT 

To: Jeremy Farrar 
"rfgar 
Franci 
Goldin 
, "Kristian 
Dear Jeremy and others, 

This was a very useful teleconference. Given the evidence presented and the discussions around it, I would conclude 
that a follow-up discussion on the possible origin of 2019-nCoV would be of much interest. However, I doubt if it needs 
to be done on very short term, given the importance of other activities of the scientific community, WHO and other 
stakeholders at present. It is my opinion that a non-natural origin of 2019-nCoV is highly unlikely at present. Any 
conspiracy theory can be approached with factual information. I have written down some of the counter-arguments. It 
is a bit long (below) but wanted to share it with you anyway. 

GARRY0000603 


Thanks for organizing this on such short notice, 
Kind regards 
Ron 

Ron's notes: 
An accusation that nCoV-2019 might have been engineered and released into the environment by humans (accidental 
or intentional) would need to be supported by strong data, beyond reasonable doubt. It is good that this possibility was 
discussed in detail with a team of experts. However, further debate about such accusations would unnecessarily 
distract top researchers from their active duties and do unnecessary harm to science in general and science in China in 
particular. At present, the arguments that nCoV-2019 could have emerged from an animal source is much stronger than 
other possibilities. 

Observations about the genome that were inferred to be suggestive for a non-animal origin: 

1. HIV-like sequences in the spike protein. 
2. Level of mutations in the spike protein region. 
3. Presence of a furin cleavage site in the middle of spike 
4. BamHl restriction site at the end of the spike sequence 
5. An F-to-Y substitution in the receptor-binding domain of spike 
6. Potential O-linked glycan sites protecting the cleavage site of spike 
1. The biorxiv publication by Prashant Pradhan and colleagues from Delhi ("Uncanny similarity of unique inserts in 
the 2019-nCoV spike protein to HIV-1 gp120 and Gag") has already been heavily debated on biorxiv and virological.org. 
The similarity between the inserts in 2019-nCoV spike and sequences of HIV-1 is accidental. These are very short insert 
sequences that are highly similar to many Genbank entries. Such similarities are explained by pure chance alone. 
2. Andrew Rambaut analyzed the level of mutations in the spike region of SARS-CoV with that of its closest bat 
virus relative and of 2019-nCoV and its closest bat virus relative. The level of mutations between the two pairs of 
viruses was in the same range. Thus, this level of mutations can arise under circumstances of natural emergence. 
3. Bat coronaviruses generally do not have a furin cleavage site in the spike protein. Some human coronaviruses 
do have a furin cleavage site in spike, which must have evolved naturally. As animal reservoir and spill-over hosts are 
highly under-sampled, the presence of a furin cleavage site in spike in such species is unknown. When coronaviruses 
jump host barriers, this frequently involved adaptation of cleavage sites that may be targeted by various proteases. 
Given the presence of furin-like sites in human coronavirus and the mutation of protease cleavage sites upon 
coronavirus host-jumps in general, a natural origin of the furin site is certainly not impossible. 
4. The BamHI restriction endonuclease site evolved due to a single (silent) nucleotide substitution as compared to 
the closest relative bat virus genome sequence. Restriction sites of 6 nucleotides can be found in every sequence, all 
over the genome, when 1 of the 6 positions is allowed to vary. We now find BamHI, next time it might be one of the 
plethora of other 6-nucleotide sequence motifs. This can be explained by pure chance. 
5. The F-Y substitution in the spike receptor binding domain was observed in mouse-adapted SARS-CoV and in 
2019-nCoV. It is generally absent in bat coronaviruses. This substitution is associated with host adaptation in mice. It 
may point to (natural) host adaption of 2019-nCoV (in mice, humans or unknown hosts) as well. It is possible that 
scientists would like to test the effect of F-Y because it was found in a mouse adaptation experiment. However, the 
logical way to test it would be in the original (SARS-CoV) virus backbone. There is no other reason to insert the F-Y 
substitution in an engineered virus. 
6. It is unclear if the potential O-linked glycosylation sites 1) are used during glycosylation; 2) have a functional role 
for the spike protein; 3) were present in the ancestral virus from the original host. This is not an argument in the 
discussion on the origin of 2019-nCoV. 
Additional arguments: 

A. All focus is on spike. Spike is a highly variable protein in general, crucial for host adaptation and under strong 
natural selection. 
GARRY0000604 


B. The virus backbone (beyond spike) is not an indicator of a human source of 2019-nCoV emergence. The virus 
itself has not been described or characterized previously and no reverse genetics system has been described for this 
virus. Any scientist wanting to investigate spike function (e.g. to study protease cleavage or the receptor-binding 
domain) would have used a well-characterized reverse genetics system that is already available (making accidental labescape 
unlikely). Anyone with malicious intend would have used a well-characterized virulent strain (SARS-CoV, MERSCoV) 
described and characterized (by others) in the literature. 
C. The patterns of mutations we observe in the receptor-binding domain and the protease cleavage sites of spike 
are typical for host-switched naturally evolving viruses. We can infer it for the naturally evolved human coronaviruses, 
we have seen it for the natural zoo noses of SARS-CoV and MERS-CoV. Convergent (parallel) evolutionary events are 
common in virology. Also for influenza, we see the same mutations emerge during the pandemics of 1918 (HlNl), 1957 
(H2N2) and 1968 (H3N2), in the 2013 zoonotic H7N9 virus and e.g. an epizootic in seals in 2014 (HlON7). Regardless of 
the divergent subtype, we see identical substitutions in the receptor-binding domains, identical substitutions in 
polymerase, and non-identical substitutions with identical phenotypic consequences (e.g. stability) in the genome. The 
fact that we (think we) see recognizable traits in spike does not mean it must be man-made. 
D. We do not know the source of 2019-nCoV. There is "~30 years of evolutionary gap" between 2019-nCoV and the 
closest bat virus relative. These 30 years may have been in any host. We have no idea what might have happened (in 
evolutionary sense) between BatCov/RaTG13 and 2019-nCoV. We should rest our case until we have a close relative of 
2019-nCoV. 
Van: Jeremy Farrar


Datum: zaterdag 1 februari 2020 om 21:59 
Aan: "Fauci, Anthony (NIH/NIAID) [E]" • , Patrick Vallance 
sie Golding 
Onderwerp: Re: Teleconference 

Thank you to everyone for joining. 

There is clearly much to understand understand in this. This call was very helpful to hear some of our current 
understanding and the many gaps in our knowledge. I do not believe this is a question of a binary outcome, it is more a 
question of "What are the evolutionary origins of 2019-nCoV, important for future risk assessment and 
understanding of animal/human coronaviruses". 

I do know there are papers being prepared, there will media interest and there is already chat on Twitter/WeChat. 

We on this call are not the only ones with scientific expertise in this area and this was an ad hoc group that came 
together to air some thoughts. It is clearly not the sole group to take this forward, that will need a broader range of 
imput and a respected international body to ask an expert group to explore this, with a completely open mind. In order 
to stay ahead of the conspiracy theories and social media I do think there is an urgency for a body to convene such a 
group and commission some work to -(draft) "To understand the evolutionary origins of 2019-nCoV, important 
for this epidemic and for future risk assessment and understanding of animal/human coronaviruses". 

In other words a completely open minded and neutral question bringing in the best minds, and under the 
umbrella of a respected international agency 

GARRY0000605 


I hope that is a reasonable approach, please send any thoughts or suggestions. 

Once again, thank you for making time over a weekend and for such an informed discussion on a complex 
issue. 
Thank you and best wishes Jeremy 

From: Jeremy Farrar 


Date: Saturday, 1 February 2020 at 15:34 
To: "Fauci, Anthony (NIH/NIAID) [E]" • Patrick Vallance· 

Cc:"Oros Marion Koopmans· 
"r , Edward Holmes 

"s 

A 
<rfgar 
Subject: e econ erence 


1st February (2nd Feb for Eddie) 
Information and discussion is shared in total confidence and not to be shared until agreement on next steps. 

Dial in details attached. 
Please mute phones. 
I will be on email throughout -email Paul or I Paul if any problems 
If you cannot make it, I will phone you afterwards to update. 

One Hour 

6am Sydney 
8pm CET 
7pm GMT 
2pm EST 
11am PST 

(Hope I have the times right!) 

Thank you for the series of calls and for agreeing to join this call. 

Agenda 

• Introduction, focus and desired outcomes -JF 
• Summary-KA 
• Comments -EH 
• Q&A-AII 
• Summary and next steps -JF 
GARRY0000606 


Kristian Anderson 

Bob Garry -I have not been able to contact Bob. Please forward if you can. 

Christian Drosten 

Tony Fauci 

Mike Ferguson 
Ron Fouchier 
Eddie Holmes 

Marion Koopmans 

Stefan Pohlmann 

Andrew Rambaut 
Paul Schreier 
Patrick Vallance 

The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. 

GARRY0000607 


Message 

From: Jeremy Farrar 


Sent: 7/28/2020 12:36:51 AM 

To: Edward Holmes 

CC: Kristian G. Andersen Fauci, Anthony (NIH/NIAID) [E] . 
Subject: Re: The authors who wrote the paper saying that SARS-CoV-2 is not human engineered first tried convincing 
Anthony Fauci of the opposite. 

Thanks Eddie. 
I will recheck emails and phones, I will try and do that today. 
I think it really starts on the 8/9 th January and the calls you and I had with China and the original sequence. 

And others were also on those calls -Francis Collins, Mike Ferguson, Patrick Vallance. 
I would suggest we get the sequence of events absolutely right before replying. 
Best wishes Jeremy 


From: Edward Holmes 

Date: Tuesday, 28 July 2020 at 08:30 

To: Jeremy Farrar 
Cc: "Kristian G. Andersen"······••■ "Fauci, Anthony (NIH/NIAID) [E]" • 
Subject: Re: The authors who wrote the paper saying that SARS-CoV-2 is not human engineered first tried 
convincing Anthony Fauci of the opposite. 

Hi Jeremy, 

Here is the exact time-line which I have now checked. 

1. Jan 26. You call me (I was in Switzerland) to talk about some concerns coming out the US that the 
virus might be a lab escape. Patrick Vallance might have been on that call, I can't recall. You later forward 
me an email from Marc Lipsitch and others containing some comments from Richard Ebright. I take a 
quick look at the sequence and say that I saw no evidence for lab escape in SARS-CoV-2 because it's 
pattern of variability was the same as in RaTG13. 
2. Jan 31. 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. Given our conversation earlier 
that week, I called you and informed you of Kristian's findings. We then decided to have a broader 
discussion with key parties on this ASAP. I think Kristian told Tony at this point but he can confirm. You 
and I then decided that Ron Fouchier, Christian Drosten and Marion Koopmans would be good to include. 
Christian also wanted Stephan Pollmnan involved. 
3. Feb 1 (6 am on Feb 2 for me). We have the conference call and then start an email chain about how we 
should deal with this. Writing it up for a paper was on the agenda and discussed. I have all the emails on 
this. 
For Tony's benefit a revised draft of the email to Jon is pasted below. 

REV0000711 


I can't for the life of me see what we have done wrong here. I strongly believe we have just tried to get on 
top of a very vexing question as quickly and openly as possible. 

Cheers, 

Eddie 

Hi Jon, 

Here are the facts: 

1. 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. At this stage we thought it was wise to ask for other expert's opinions on this, so a conference call was arranged. 
There were indeed other coronavirus experts on the call. 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). 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. Clearly, some people on the call were very strongly of the opinion that the possibility of a lab escape was ridiculous 
and listed reasons why it should be dismissed out of hand (although there was also some initial confusion about whether 
we were referring to the crazy HIV origins theory that had just been touted -obviously we were not). Some of those 
comments we agreed with, others we did not. A take-home message from the call was that we should investigate 
further and write a scientific paper to clearly set-out the background on the topic and our findings. Indeed, one the of 
emailed agenda items for discussion after the call was "Advice on whether KA, AR, RG and EH should publish this". 
4. We eventually wrote up our findings as a scientific (peer reviewed) paper. Critically, drafts of this paper were sent to 
all the people on the call, including those with the information that has been emailed to you. We have attached our first 
draft of what would eventually become our paper from Feb 7, which was circulated to everyone on the call. As you can 
see, it is essentially the basis of our final study and people on the call commented on it. 
5. Very shortly after the call, the pangolin data came out. 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). And as Eddie 
mentioned this is becoming more likely from day to day with the pangolin story." 

6. Hence, it is completely and utterly false to claim that we (1) all thought it was a lab escape, (2) that we were corrected 
("schooled") in our views by the coronavirus experts on the call, and (3) then submitted a Nature paper without anyone 
else knowing about it. 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. We categorically deny that we were "spreading the rumor" that the virus was human engineered. At the time, there 
were indeed rumours -which persists to this day -that SARS-CoV-2 was an engineered virus, but these certainly did not 
come from us. As you know, the White House OSTP asked for expert opinions on this question too (spurred by the HIV 
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nonsense preprint), and Kristian was part of that panel (https://www.the-scientist.com/news-opinion/lab-madecoronavirus-
triggers-debate-34502). Our study directly addressed these rumours in a scientific way by considering that a 
lab escape could have occurred. We did not dismiss this possibility out of hand, but we scientifically investigated it. 

We strongly reject the idea that we should not have raised nor discussed the possibility of lab escape: as scientists we 
have to present all the data and discuss it openly. That's what we did. To not have considered or mentioned the 
possibility of a lab escape would have been negligent. Is the person who emailed you seriously suggesting that we 
should not have discussed these issues? Wouldn't that be a cover-up? 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. Can you imagine if we had not mentioned -or considered -it all as suggested by some "coronavirus 
experts"? 

This clearly appears to be a case of sour grapes based on half-truths and likely stimulated by your recent (great) article 
with quotes from us on the questions you raised with Dr. Zhengli. It's telling that the person who emailed you is 
anonymous. We have absolutely no problem with people knowing that our views on this issue have evolved as more 
data have appeared -and continues to evolve to this day, should more data become available. That's science. And it's 
the only way to do it well. Indeed, we have told this to many people: the way we set this up was a study of alternative 
hypotheses equally weighted priors, which we tested -our posterior clearly favors the hypothesis that this is a natural 
virus. As far as we can tell we are only 'guilty' of following the proper scientific method -but maybe we offended an 
ivory tower "coronavirus expert" in the process. It likely won't be the last time. 

Best, 

Eddie and Kristian 

PROFESSOR EDWARD C. HOLMES FAA FRS 

ARC Australian Laureate Fellow 

THE UNIVERSITY OF SYDNEY 

Marie Bashir Institute for Infectious Diseases & Biosecurity, 
School of Life & Environmental Sciences and School of Medical Sciences, 
The University of Sydney I Sydney I NSW I 2006 I Australia 

T 
E 
On 28 Jul 2020, at 4:54 pm, Jeremy Farrar· 

wrote: 
Thanks for forwarding this and the other emails. 

I would like to get the sequence of events absolutely right from the start. Eddie the start goes back to the calls you and I 
had on the 8/9th January. 
Can we get that sequence of events right and agreed before a substantive reply goes back to Jon? 
Jeremy 

On 28 Jul 2020, at 02:07, Kristian G. Andersen 

wrote: 
Dear Tony, 

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I am sorry to be contacting you, as I know you have critically important priorities, including developing a vaccine for COVID-19.We just 
received the email below from Jon Cohen (from Science) about our conversations back in February investigating the origins of SARS-CoV


2. As you know, we considered the theory that SARS-CoV-2 could have been a lab escape and therefore did what any good scientist should 
do -investigate likely hypotheses and let the data decide. As you know, the data strongly suggests that this is a natural virus and clearly this 
person gets a lot of things wrong about how this all played out. 
We need to reply back to Jon, which would have to include confirming that this meeting did indeed take place with you and Jeremy 
present. Please let me know if you have any comments or concerns in this regard. 

At the very end of this email, I have added a draft email that Eddie put together. I have a few clarifying points that I will add and then Eddie 
and I will reply back to Jon. 

Again, sorry to take up your time -please let me know if you have any comments, questions, or concerns. We are planning to email Jon 
tomorrow afternoon. 

Best, 
Kristian 

Kristian G. Andersen, PhD 

Professor Scripps Research

I 

Director oflnfectious Disease Genomics I Scripps Research Translational Institute 
Vice President I Viral Hemorrhagic Fever Consortium 
Principal Investigator Center for Viral Systems Biology

I 

Principal Investigator West African Emerging Infectious Disease Research Center

I 

The Scripps Research Institute 

10550 North Torrey Pines Road, 
Department of Immunology and Microbial Science 
La Jolla, CA 92037 


----------Forwarde~ 
From: Jon Cohen·Date: 
Mon, Jul 27, 2020 at 3:02 PM 
Subject: Re: The authors who wrote the paper saying that SARS-CoV-2 is not human engineered first tried convincing 
Anthony Fauci of the opposite. 

To: Kristian G. Andersen· , Edward Holmes 


Here's what one person who claims to have inside knowledge is saying behind your backs ... 
Jon 

On Jul 25, 2020, at 7:22 AM, ofu8Iedu8z <ofu8Iedu8z 

wrote: 
[EXTERNAL EMAIL] 

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Hello Jon 

Given your recent mentions of the origin of SARS-CoV-2 I thought you might be interested to hear the bizarre back-story 
of the paper "The proximal origin of SARS-CoV-2" (https://www.nature.com/articles/s41591-020-0820-9). 

In summary, four of the authors managed to organize a conference call with Anthony Fauci and others, after quietly 
raising the alarm (or "spreading the rumor", as Jeremy Farrar apparently put it) that the virus WAS in fact human 
engineered. On the call were two world-class virologists who actually work on coronaviruses, who set them straight in 
great detail. That seemed to be the end of the affair. 

But, incredibly, Andersen et al. turned around and submitted the Proximal paper to Nature with the exact opposite 
claim, i.e., that the virus was NOT human engineered. They used (without acknowledgment, of course) all the arguments 
provided by the coronavirologists on the initial call in which they had tried to raise the human-engineered alarm. 

I don't think it would be too hard to verify all this, if you feel like digging a little. If you're wondering if this could all 
possibly be true: ask yourself how this group of authors, none of whom work on coronaviruses, could have such detailed 
arguments about why SARS-CoV-2 was not human-engineered. The answer is that they couldn't (and didn't) -they were 
schooled by the coronavirus experts on the call. 

For the phone conference, Anthony Fauci called in Jeremy Farrar (Director of the Wellcome Trust). Farrar asked the 
coronavirus experts to join the call to listen to the claims. The call took place on a Saturday in early February (either the 
1st or 8th, I'm not sure but I could probably find out). On the call making the claim were: Kristian G. Andersen, Andrew 
Rambaut, Edward C. Holmes, Robert F. Garry, but not Ian Lipkin. 

The coronavirus experts listened for a while and both quickly concluded that the reasoning was completely flawed, that 
the non-coronavirus virologists had no idea what they were talking about, and that the human-engineered claim was 
totally wrong. One of the coronavirus experts was entertaining guests that day and told the people on the conference 
call that they wanted to give their opinion and then go back to the guests. So they told them it was nonsense, gave them 
a list of reasons why, and got off the call. The other coronavirus expert stayed on the call, gave a similar opinion and the 
morning afterwards sent a detailed list of the reasons why the claim was certainly wrong. 

After the paper with the exact opposite claim was received at Nature, senior editor, Clare Thomas sent it out for review 
to some of the best people in the world ... Not surprisingly, this happened to include a very close colleague of one of the 
experts who had been on the conference call. You can perhaps imagine the shock. Thomas was quickly appraised of the 
situation and Nature rejected the paper. It was then sent to Nature Medicine, where it was soon published. 

One author on the paper was not on the conference call: Ian Lipkin. It's not clear how much of the back-story he is aware 
of. It might be worth giving him a call to ask, in case you feel like investigating. If his co-authors left him in the dark as to 
what actually happened and he's worried about the possible fallout he may want to help. 

I apologize for mailing you without revealing my name (at least for now). I work in the field and have heard this story 
from two people who were on the initial call with Fauci. I'm not keen to be personally involved, but I find the situation so 
outrageous, hypocritical, and shameless that I also find I can't keep silent. It doesn't change anything with respect to 
knowledgeable thinking about the origin of the virus, of course, but it's a pretty ugly situation that I (obviously) think 
should be exposed. 

-----EMAIL REPLY DRAFT----


Hi Jon, 

Here are the facts: 

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1. 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. At this stage we thought it was to wise ask for some other expert opinion on this, so a conference 
call was arranged. There were indeed some coronavirus experts on the call who we chose. 
3. Clearly, some people on the call were very strongly of the opinion the possibility of a lab escape 
was ridiculous and listed reasons why it was unlikely (although there was also some initial confusion 
about whether we were referring to the crazy HIV origins theory that had just been touted -obviously 
we were not). Some of those comments we agreed with, others we didn't. There as a long email 
discussion about what the data said. A take-home message from the call was that we should go away 
and write something to clearly set-out the background science on the issue. 
4. So, we eventually wrote up a paper. Critically, however, drafts of this paper were sent to all the 
people on the call, including those that have leaked out the information. I've attached here the draft of 
the document from Feb 7 that was circulated to everyone. As you can see, it is essentially the basis 
of the document and people on the call commented on it. 
5. Very shortly after the call the pangolin data came out. This was critical. As I 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." 

6. Hence, it is completely and utterly false to claim that we all thought it was a lab escape, we were 
corrected in our views by the coronavirus experts on the call, and then submitted a Nature paper 
without anyone else knowing about it. 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. 
I also strongly reject the idea that we should not have raised nor discussed the possibility of lab 
escape: as scientists we have to present all the data and discuss it openly. That's all we did. To have 
not mentioned the possibility of lab escape would have been negligent. Is the person who emailed 
you seriously suggesting that we should have not discussed these issues? Wouldn't that be a coverup? 
Indeed, the great irony is that 99.9% of the feedback I've had on the paper -including death 
threats -are people accusing me of dismissing the lab escape theory too quickly!! Can you imagine if 
we had not mentioned it all? 

This is clearly just case of sour grapes based on some half-truths. It's telling that the person who 
emailed you is anonymous. I've absolutely no problem with people knowing that my views on this 
issue have evolved as more data have appeared. That's science. Indeed, I've told this to many 
people: the way see it is that we set-up an hypothesis and then tested it. As far I can tell we are only 
'guilty' of following the proper scientific method. 

Hope this helps. 

Eddie 

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<Summary.Feb7.pdf> 

REV0000717