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. trongly believe we have just tried to get on For Tony's benefit a revised draft of the email to Jon is pasted below. 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 > wrote: ta 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-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 @sydney.edu.au On 28 Jul 2020, at 4:54 pm, Jeremy Farrar < @wellcome.ac.uk> 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?