Transcript of Matt Ridley’s lecture at NIH

This transcript is based on automatically generated subtitles of the Youtube version of the recording.

Jay Bhattacharya’s introduction

[I’d like to welcome] you all to the inaugural lecture in the scientific freedom series.

It’s essential in to study in the study of science to seek truth.

It involves complex scientific questions where uncertainty remains, perspectives differ, and the public conversation can quickly become divided.

There’s value in platforming freedom of discussion within science, where credible voices can examine evidence, ask hard questions, and engage thoughtfully with one another.

My role in this series is not to render judgment or to adjudicate among competing theories. My objective is simple. It’s not to declare definitive truth, but to foster rigorous, open, and non-judgmental discussion. It’s by making room for good faith inquiry guided by evidence, curiosity, and respect.

I recognize that many people may not agree with every perspective shared here. In fact, I guarantee you [we/you?] won’t.

Uh that’s not only expected, but it’s part of the process.

Some of the most important advances in science come from challenges uh to our assumptions.

I encourage listeners to approach these conversations with an open mind and a willingness to hear viewpoints that may not align with their own.

Today’s topic, the origins of COVID-19, is one of those scientific inquiries that has resulted in intense debate, differing interpretations of evidence, and at times deeply held and conflicting perspectives.

It’s important for us that we acknowledge the complexity of the question and the reality that uncertainty still remains.

Some researchers support the hypothesis of natural spillover, similar to what we saw with SARS-CoV-1, where virus crossed from animals to humans. Others have explored the possibility of a lab leak, and that’s the viewpoint you’re going to hear today. An inadvertent spillover from the course of research conducted for different scientific purposes.

These aren’t trivial per distinctions, and they are not easy conversations to have, but they’re necessary for us to advance as scientists and to make good decisions about uh what we should do in science policy going forward.

Uh if the origin stems from a natural spillover, we must deepen our understanding of zoonotic transmission and strengthen surveillance of human animal interface. If a lab-associated incident played a role, we must carefully examine research practices, biosafety protocols, and systems of oversight.

And and and actually, we probably should just do both.

Um

In um either case, the goal is the same: to reduce risk and protect public health.

There’s another dimension that’s equally important. Trust in scientists, public trust in science. Science depends on public trust. The uh uh the the activities that we do, all our all of our work at the NIH is supported by the public. And so, it’s absolutely vital that we maintain this public trust.

Uh many scientists felt hesitant to discuss certain hypotheses, including the one you may hear today, in uh out of concern that doing so could impugn their integrity and uh and harm the the broader scientific enterprise. But nothing could be further from the truth.

The kind of discussion you that we will have today actually advances public trust because it shows models scientists engaging with each other in good faith in ways that advance the interest of the public. We don’t need to show that we agree with one another. We know we what we do need to show is that we are engaged with another one another in good faith, engaging with the evidence uh and advancing our knowledge together.

This lecture series then is a step toward fostering this that kind of dialogue. And in that spirit, I’m absolutely delighted to welcome today’s speaker, Lord Matt Ridley.

Matt Ridley is a British science writer whose work spans evolution, genetics, and the origins of human society. He was educated at Oxford University, where he conducted scientific research on evolution before starting his career as a science journalist at The Economist, serving as a science editor, Washington correspondent, and American editor, then full-time editor. He then served in the House of Lords for a for for a decade or more. Over the past decades, he’s written extensively on evolutionary biology, the role of evolutionary thinking in uh understanding human behavior, culture, and innovation. His books, which include The Red Queen, anyone else uh read The Red Queen by him? I absolutely love that book. If you haven’t read it, please do. Um The Origins of Virtue, Genome, Nature vs. Nurture, The Rational Optimist, The Evolution of Everything has been translated into more than 30 languages and received numerous accolades for science communication.

Um more recently, he turned his attention to the origins of COVID, uh writing a a a a book the bestselling book Viral: The Search for the Origins of COVID-19, which he co-authored with Alina Chan.

In it, he examines competing hypotheses about SARS-CoV-2, first how how it infected first humans, and then he explores the scientific debate around the natural spillover and possible lab leak.

We invited Matt here not because we expect unanimity of views, but because we value thoughtful engagement with complex questions. This exactly the kind of discussion that this series is meant to encourage.

Uh please uh
join me in welcoming Matt Ridley.

[applause] [applause] I see he usually comes out right immediately, but it doesn’t actually work out sometimes. Oh, no, there he is. How are you, Matt? Welcome.

Ridley’s talk

Thank you, Jay.

[opens paper]

Introduction

Opening slide (Book covers)

Ladies and gentlemen, let me say what an enormous honor it is to give this lecture today in defense of scientific freedom, and I pay tribute to Jay Bhattacharya’s courage in championing this issue and indeed in inviting me.

Uh In what follows, I have relied heavily on my co-author, Alina Chan, but if I get anything wrong in the next hour, it’s my fault, not hers.

I’m going to explain why I changed my mind, why I went from dismissing the lab leak hypothesis to concluding that it was not just probably, but almost certainly, correct.

This was not driven by motivated reasoning. Quite the reverse. I am pro-science, pro-biotech, pro-genetic engineering. Indeed, that was one of the topics on which I spoke most often in the House of Lords.

Although I am a professional writer, I do have some relevant expertise in this matter. I have a PhD in biology, I wrote a bestseller on genomics, and I was a member of the Science and Technology Select Committee of the House of Lords.

But even if I had no expertise, as a human being who experienced the pandemic, I and everybody else has a right to investigate this question.

This is not something where scientists should say, “Stay in your lane.”

And I am frankly dismayed by how the WHO, most of the scientific establishment, including some of the NIH, and the science journals, plus most of the mainstream media, and some of the intelligence community, not only failed to investigate this issue properly, but were reluctant even to discuss and debate it.

If a plane crashes, we do our best to find out why and share the lessons.

This thing killed a hundred thousand times as many as a a typical plane crash.

As you will hear, by far the most important discoveries about what happened were made by amateurs working in their own time and on their own dime.

Slide 1 (Why does it matter)

So, it’s worth, I think, starting with the question, why does it still matter six years on?

I think it matters for several reasons. Because we do owe it to those who died to find out why. Uh we need to understand that last pandemic. Uh we need to explain why the virus was unusually infectious for a virus that had just intruded into the human species for the first time.

Uh we need to prevent the next pandemic by learning lessons from the last one.

And importantly, if we shrug our shoulders and say we never know we may never know how this happened, that sends a message to bioterrorists that they can do this and get away with it.

Attribution is deterrence. Not that I’m implying this was an incident of bioterror, but I think the next one possibly could be.

Slide 2 (Talk outline)

In my talk, I’m going to cover the following topics:

• the outbreak,
  
• the market,
  
• the bat viruses,
  
• the connection with Laos,
  
• the lab,
  
• the furin cleavage site,
• the DEFUSE proposal,
  
• and some loose ends.

1. The Outbreak

Slide 3 (1. The Outbreak)

We’re talking about a coronavirus.

Slide 4 (Coronavirus phylogenetic tree)

There are four kinds of coronavirus, alpha, beta, gamma, and delta.
There are four coronaviruses that cause versions of the common cold and are endemic in human species, two alphas and two betas. There are two coronaviruses that have caused brief and lethal outbreaks in human beings in the current century, and there is one that has caused a pandemic. It is a close cousin of SARS. It is in the group known as SARS-like beta coronaviruses, or sarbecoviruses.

What is the natural habitat of sarbecoviruses?

Slide 5 (Horseshoe bats image)

It is the guts of one genus of bats, the horseshoe bats, which live only in the old world, not in the new world, are highly gregarious and tend to live in natural caves.

Slide 6 (How did the virus get from bats to people?)

So, the question we have to ask ourselves is, how did a bat virus get into people?

And ignoring possibilities like frozen food, which are not very plausible, I think there are four plausible routes.

• The first is that it was a repeat of SARS in which an intermediate mammal host caught the virus and that infected people.
  
• The second is that the intermediate host was actually a person who went into a cave and got infected.
  
• The third is that the person was a scientist and
  
• the fourth is that the scientist took the virus back to a lab and did research on it.

Slide 7 (A coincidence of place…)

And the reason we need to take that last possibility seriously at the very start is because of the extraordinary coincidence of place and time.

In all the many thousands of cities in China and the next to the 40,000 food markets in China, this outbreak happened in the very city where research on SARS viruses was occurring more than anywhere else in the world.

That is quite a coincidence.

Slide 8 (and of time)

It’s also a coincidence of time as well as place.

In all the thousands of years of human history, this outbreak happened at the time when research was going on on these kind of viruses for the first time.

Slide 9 (Previous lab leaks)

And lab leaks do happen and have happened. Just to run through some examples of recent and relevant lab leaks,
- there was a global pandemic of flu in 1977 that was derived from an inadequately attenuated influenza virus used as a vaccine.
- There was an outbreak of anthrax in 1979 in the Soviet Union which it took the Soviet authorities 12 years to admit was the result of a leak from a biowarfare lab.
- In Kunming in 2003, hantavirus infected researchers and the person who investigated that case was Shi Zhengli of the Wuhan Institute of Virology.
- The same year in both Taiwan and Singapore, in researchers got infected with SARS while working on them. And again in Beijing the following year, at least twice possibly four times, there was a leak of a virus.

The important thing about those cases is that except for the Taiwan case, they didn’t know how it happened. So these things can happen without anyone knowing that there’s been an accident in a lab.

• In Surrey in England in 2007, foot-and-mouth disease broke out on a farm just down the road from the world’s reference lab for foot-and-mouth viruses. That turned out not to be a a coincidence. A contractor had gone from one site to the other.
  
• And in 2019, just before the pandemic, brucellosis broke out and infected a large number of people in China as a result of a lab leak.
  
• And finally, of course, SARS-CoV-2 has infected people in the lab since the pandemic began, probably many times, but we know of one particularly clear case in Taiwan.

All in all, in the first 20 years of this century, there’ve been hundreds of individuals infected in scores of labs and in many different incidents.

And just before the pandemic, the World Health Organization and organizations like the EcoHealth Alliance were warning that this lab leak risk was getting worse. The threat from lab-enhanced viruses is intensifying and curiously, these warnings have been much quieter since the pandemic. That seems to me curious.

2. The Market

Slide 10 (2. The Market)

Nonetheless, when the outbreak happened, the Chinese authorities immediately assumed they were dealing with a repeat of SARS

Slide 11 (Huanan market photo)

and that the Huanan Seafood Market in particular was where this was happening and they went as far as saying that there was no human-to-human transmission and they continued saying that up until the 20th of January, which turned out to be bad advice.

They In other words, the only way you could get this virus in January, they thought, was from another mammal.

Slide 12 (Wuhan map)

And at first, the evidence does look quite interesting because the cases reported to the World Health Organization from December 2019 do cluster around the market and that’s more true of the ones that had no connection with the market than with the people who had actually been to the market.

But

know that that is largely a case of ascertainment bias because the criterion for whether or not you could even be considered for having this disease in December 2019 were that you had to either have been to the market or to live near the market. So I’m afraid this is purely circular reasoning and it tells us nothing.

Slide 13 (Demaneuf picture)

Besides, we now know that there were at least 73 and possibly as many as 86 cases that were not reported to the World Health Organization from December 2019 and we don’t know the origin of them.

And indeed, according to Chinese government document seen by the South China Morning Post, there were nine cases in November. These have not been shared with the World Health Organization. They could be very important.

Slide 14 (Bloom phylogeny)

Furthermore, the virus that people caught in the market was not the ancestral form of this virus. It was a derived form. It was the B strain of the virus and that’s quite an important piece of influence because it’s very hard to see how that could imply an origin in the market.

Slide 15 (Xiao et al. table)

There were mammals for sale in the market and in other markets in Wuhan, not very many by the standards of markets in southern China where the sale of live wild mammals is much more common, but there were some and they included animals that could be susceptible to this kind of virus.

But it did not include bats. It did not include pangolins. And all of the raccoon dogs for sale, for example, in this market were sourced locally. They had not come from Yunnan, which is where this virus had come from or southern China generally.

Slide 16 (Market map)

It is true that virus was present in the market, not just in people, but also on countertops, doorknobs, in the sewage, and so on.

And those samples tended to cluster in the southwest corner of the market, which is where those mammals were on sale.

Again, that looks suggestive until you find out that the Chinese CDC had prioritized those very areas for sampling. So again, this is almost certainly a case of ascertainment bias of circular reasoning.

And if you look for a correlation in those samples between mammal DNA and virus RNA, you find a negative correlation.

In other words, there is a correlation between the virus and people’s DNA, but there is not a correlation between the virus and any mammal DNA. There is one sample that has both raccoon dog DNA in it and virus RNA in it, but only one read out of 210 million reads in that sample maps to the virus.

That is not strong evidence for mammals being the source of the of the outbreak.

Slide 17 (George Gao)

These were the reasons that led George Gao, the head of the China CDC, to announce in May of 2020, quite early in the pandemic, that he thought the virus was not the source. It was more like a victim.

And it was this press announcement, rather obscure, but I did stumble upon it, that led me to begin to change my mind.

I was gobsmacked by this. I thought it was case closed at that point and I began to go back and look at the evidence more closely.

Slide 18 (animals)

I can’t stress enough how different this is from SARS.

In the case of SARS, infected civet cats and in particular people who handled such mammals were very clear from the start.

In this case, not only were no animal handlers infected of of a relevant kind, but no animal no mammal has ever been found with this virus.

Not one.

That’s not quite true, of course, cuz once the pandemic started, mammals did indeed start catching it, but from us.

There is no case that precedes a human infection.

So there’s no direct evidence today that points to an intermediate animal origin of SARS-CoV-2.

3. The Bat Viruses

Slide 19 (3. The Bat Viruses)

What do we know about this virus?

Slide 20 (Zhou et al.)

Well, when Shi Zhengli first published the sequence of the virus in Nature, she revealed something very important. There were three bat viruses that were closely related, one of them particularly so, RaTG13.

And this is what she said about it. We then found that a short region of the RNA-dependent RNA polymerase gene from a bat coronavirus, which was previously detected in Rhinolophus affinis from Yunnan province, showed high sequence identity to the new virus. We carried out full-length sequencing on this and found it was 96.2% the same.

There’s two features of that passage of text that I need to draw your attention to.

The first is that they clearly imply that they sequenced the bat virus after noticing the similarity between one of its genes and one of the human virus’s genes. That turned out to be false. They had sequenced the bat virus in 2018, the year before the pandemic.

In which case, why did they need to notice just one of the genes being similar? Why didn’t they blast the sequence similarity of the whole genome?

And the other strange thing is that notice the sentence about the previous detection of this virus does not have a reference. Does not have a footnote, does not have an endnote.

I spent several fruitless days trying to track down RaTG13 on the internet. When had they found it? Where had they found it? Under what circumstances?

It did not exist. It was a ghost. It took us more than 6 weeks to to resolve this dilemma.

Slide 21 (Rahalkar & Bahulikar)

And the work that that did so was the result of Manali Rahalkar’s work in India and Rosanna Segreto’s in Norway. And what they noticed was that there was a virus out there that had been described in 2016 that had a 100% similarity to RaTG13, but it had a different name. It was called 4991.

And it later transpired that they had changed the name from 4991 to RaTG13 at the start of 2020. And not before. But hadn’t communicated this fact. Now, whether intended or not, the result of this was to disguise the story of the closest related bat virus and to make it rather obscure at a time when it was quite possible that the pandemic would blow over as only a minor event in China.

So, what is the story of 4991 or RaTG13?

Slide 22 (Map china)

Well, the first thing is it doesn’t come from Wuhan. Doesn’t come from anywhere near Wuhan. It comes from Southwest China in Yunnan. It comes about as far away from Wuhan as the Florida Keys is from where I’m standing today. That’s a long way for a virus to travel. And we know of only one animal that has made that journey from a bat cave to Wuhan. It’s Homo scientificus.

So, what is the story? How had they found this bat virus and what what under what circumstances?

Slide 23 (A New Killer Virus)

Well, we did actually have a report in the scientific literature from 2014 that was around the events that led up to the discovery of that virus.

This article is actually about a different virus, a rodent virus, but nonetheless it’s about the same incident.

But it wasn’t until May of 2020 when a young Indian named The Seeker found a medical thesis from Kunming Hospital that gave us the details of this story.

Six men had gone into a disused copper mine on a mountainside in Mojiang County in Southern Yunnan to shovel bat guano out, probably with a view to reopening the mine. They had got sick, badly sick with pneumonia. Three of them died. Three of them eventually recovered.

And this was a case that led virologists all over China to get very interested. Samples from the men’s lungs were sent to Wuhan and were found to be positive with antibodies for SARS.

And that led to the conclusion that these men were probably the first and only occasion where human beings had caught a sarbecovirus directly from a bat.

Slide 24 (Fieldwork photo)

Which would be a very interesting story in its own right. And that led the Wuhan Institute of Virology to mount a number of expeditions to the site about seven over the next 2 years uh e- in order to sample the bats in the mine shaft. And you can see them here dressed in full PPE and handling live bats in a keep net.

Uh we’d like to know more about this site. But journalists and others who’ve tried to get there since the pandemic began have been turned away often very firmly. And there has been nothing published, literally nothing, about research from this site ever since. We’ve had no uh uh no reports of whether or not there are still infected bats there or something. Which seems a little strange, to put it mildly.

Slide 25 (The mysteries of 4991)

So, these are some of the things we need to know about 4991 or RATG13.

• Why did they change its name?
  
• Why did they not cite their own 2016 paper in which they described the RdRp gene from it?
  
• Uh why did they mislead us about the date on which they’d sequenced its genome?
  
• Why did they omit a connection with a human disease?
  
• And why did they claim, wrongly as it turned out, that there was no more sample after we finished the genome sequencing?

Slide 26 (Babar phylogeny)

In the summer of 2020, two uh op- sleuths is a good word. Uh two sleuths, one called Babar, one called Francis Francisco de Asis, uh spotted in a genetic database that there were eight other viruses that had apparently come from the same site and were closely related to RaTG13.

We eventually were This was eventually confirmed to us by Shi Zhengli and her colleagues. Yes, we found nine viruses all together in our expeditions to that mine, not uh not eight.

Slide 27 (Yu Ping phylogeny)

Which means that the Wuhan Institute of Virology was working with the nine closest relatives to SARS-CoV-2 when the virus was detected in December 2019.

Uh The Seeker eventually found a thesis, the way he does, um about these viruses. It was in which they are described as lineage 4, Ping Yu’s MSc thesis, uh and which shows their relatedness and includes 4991. And that was published at the end of 2019, which is how we know they hadn’t yet changed the name.

But when Ping Yu’s thesis was published as a paper in Infectious Genetics and Evolution, lineage 4 was omitted altogether. That may have been because they were saving it up for a later publication or something, we don’t know. But it does mean that we didn’t know that they had lineage 4 in their possession at all or what they were doing with it.

4. The Laos Connection

Slide 28 (4. The Laos Connection)

Then in 2021, there was a complication in this story.

Slide 29 (Latham map)

Because the Pasteur Institute found a virus in Laos that was more closely related to SARS-CoV-2 than RaTG13, 96.8% rather than 96.1 or 2%.

Well, that seems to change the story. But it doesn’t necessarily because neither of these viruses is the ancestor of SARS-CoV-2. They’re not close enough to be the progenitor. But they are representatives of the group from which this virus is derived. And besides, the fact that they come from a different country doesn’t necessarily change anything because

Slide 30 (email Laos)

the Wuhan Institute of Virology was receiving viruses from Laos via the EcoHealth Alliance, as shown by both emails and research reports, and indeed genetic databases.

Slide 31 (Genbank record)

This one shows Peter Daszak depositing a uh of coronavirus at the Wuhan Institute of Virology from Laos. So, viruses were crossing international borders here uh without report, which is of itself quite interesting.

Slide 32 (Shi’s interview in SciAm)

When the outbreak happened, Shi Zhengli gave an interview to Scientific American and she said, “I have never expected this kind of thing to happen in Wuhan.”

What did she mean by that? She meant that they had been sampling bats in the vicinity of Wuhan in Hubei province extensively over preceding years and had never found these kind of sarbecoviruses there.

So, they’d also been sampling human beings in Wuhan and had not found SARS-like antibodies in them.

So, no wonder she worried, could they have come from our lab? She eventually concluded that they had not.

But we’ll have to see whether that’s plausible.

5. The Lab

Slide 33 (5. The Lab)

What was going on in Shi Zhengli’s lab at the Wuhan Institute of Virology?

Slide 34 (Photo Shi / Daszak)

Well, here she is with Peter Daszak of the EcoHealth Alliance in her laboratory. Peter Daszak was funneling uh millions of dollars from the US taxpayer to the Wuhan Institute of Virology to support her research. And this is one of the NIH grants that covered that. Understanding the risk of bat coronavirus emergence.

The work was intended to Shi Zhengli had begun, obviously, by tracking down the origin of SARS. But the next step was to identify other uh sarbecoviruses that might cause pandemics. And then also to study them closely in the lab. This project did not receive universal support from virologists.

Indeed, Andrew Rambaut on the 21st of November 2019, just as we now know the pandemic was starting, uh wrote on Twitter that “The more we look, the more new viruses we find. The problem is we have no way of knowing which may be important or which may emerge. There is basically nothing we can do with that information to prevent or mitigate epidemics.” So, he’s saying the benefit of this research may not be very great. And Peter Daszak replied to him, “That’s not true. We’ve made great progress with bat SARS-related coronaviruses, identifying more than 50 novel strains, sequencing spike protein genes, identifying the ones that bind to human cells, using recombinant viruses and humanized mice to see SARS-like signs.” So, live infectious experiments. So, as well as the benefit being small, according to Rambaut, the risk is suddenly sounding like it might be quite high. Is the risk-benefit ratio really right here?

Slide 35 (Daszak at TWiV)

A few weeks later, still not knowing that a pandemic was brewing in Wuhan, Peter Daszak gave an interview to Vincent Racaniello in which he explained more detail what they were doing in the lab. “Coronaviruses are pretty good. You can manipulate them in the lab pretty easily. The spike protein drives a lot about what happens. You can get the sequence. You can build a protein. We work with Ralph Baric at the University of North Carolina to do this, insert into the backbone of another and do some work in the lab.”
“So, if you’re detecting viruses in bats, but you can’t grow those viruses cuz they’re not in a good enough state to get them into the lab and grow them, then you can at least extract their sequences and from that synthesize their spike gene and stick the spike gene like a cassette into another virus that you can grow, and then you’ve got a chimeric virus that you can test on cells in the lab.”

Slide 36 (Baric)

Now, Ralph Baric had invented these techniques and had collaborated with the Wuhan Institute of Virology to to do this work. It would be nice to know what he knows. The University of North Carolina has steadfastly refused to share his emails and is fighting in the courts over that. And he himself has not given any evidence to Congress in open session.

But he is going he has gone on the record to say of the lab leak as a theory about the origin of COVID, “you can’t rule that out.”

Slide 37 (EHA report)

We do know what some of these experiments achieved. This is a tardy report from the EcoHealth Alliance that was eventually filed, which shows one experiment in this slide where they took the spike gene from a virus called SHC014 and put it into the backbone of a virus called WIV1, and the result was a three-fold increase in the death rate of mice and a 10,000-fold increase in the viral load in brains and lungs of humanized mice.

That is gain of function.

There’s absolutely no uh dodging that. Of course it is gain of function. But this experiment is on a virus that is very closely related to SARS, not to SARS-CoV-2. So, it’s not It’s not the experiment that could have led to this pandemic.

However, what what other viruses were they doing these experiments on?

Slide 38 (FdA graph)

And the answer is we don’t know. We know which viruses they were working on up until 2016, but we do not know which ones they were working on in later 2016, ’17, ’18, and ’19.

So, it’s possible that they were working on ones that were more closely related to SARS-CoV-2 by then, that were in lineage four.

Slide 39 (database)

We probably would know if we could see their viral pathogen database, which they maintained and kept open to outsiders up until suddenly they closed it at 2:00 a.m. on the 12th of September 2019, couple of months before the pandemic started, and they’ve never shared with it since.

The reason they give for not allowing us access to that database, which would exonerate them in a flash if it has no relevant viruses in it, the reason they give is because they don’t want people hacking it. But if you share data, you don’t have to worry about people hacking it. So, I don’t understand that excuse.

Slide 40 (NIH renewal)

We do know, however, from a grant renewal document to the NIH from the EcoHealth Alliance that there was a plan to broaden the range of viruses they looked at.

To move away from ones that were very close cousins of SARS to ones that are 10 to 25% different.

The reason for this is because the ultimate aim of this project is going to be to produce a vaccine that will work against any kind of sarbecovirus.

Now, it’s interesting cuz SARS-CoV-2 is 24% different in the spike gene from SARS. So, this is exactly the kind of virus they were moving to take seriously from this point on.

6. The Furin Cleavage Site

Slide 41 (6. The Furin Cleavage Site)

When the sequence first appeared, it alarmed a number of Western virologists.

Slide 42 (KGA’s photo)

Kristian Andersen wrote to Anthony Fauci at the urging of Jeremy Farrar on the 31st of January 2020 to say that “I should mention that after discussions earlier today, uh Eddie Holmes, Bob Garry, Mike Farzan, and myself all find the genome inconsistent with expectations from evolutionary theory.” What did he mean by that?

Slide 43 (Chan & Zhan alignment)

He meant that in the middle of the spike gene of SARS-CoV-2, there is something that sticks out like a sore thumb. A feature called a furin cleavage site that massively increases the the ability of this virus to be infectious in human beings because it enables it to use a human enzyme called furin to cleave the spike and facilitate entry into and out of cells.

But what’s so clear is that this is not a mutation. It is an addition. It is an insertion. 12 extra nucleotides, four extra amino acids have been added, and this is clear by aligning the sequences with other viruses.

This is the first and only discovery of a furin cleavage site in a sarbecovirus ever made out of many hundreds.

It’s quite striking.

And you’d think that it would indeed alarm and interest everybody who saw it.

Slide 44 (Zhou et al. alignment)

But when Shi Zhengli published the sequence in Nature, she didn’t mention it. She doesn’t use the words furin or furin cleavage site in the paper at all.

And her diagram of the first half of the spike gene stops just before it would appear.

As Alina Chan has put it, this is like describing a unicorn and not mentioning the horn.

Slide 45 (alignment)

That diagram stops there. But the end of the S1 section of the spike gene is there. Why not go on to the S1/S2 boundary? And as you can see, the uh the furin cleavage site has two arginine residues in it. That’s why it’s good at attracting uh furin.

And they are coded for by CGG.

Well, that’s unusual because these kind of viruses do not use CGG for arginine very often at all. It’s the rarest codon to use, and yet here are two of them next to each other, and this is the only occurrence of two CGG codons next to each other anywhere in any sarbecovirus genome that we’ve found so far.

No wonder David Baltimore, when he first saw this, said this could be the smoking gun.

He later wrote back from that under pressure from colleagues, but that’s what his first thought was.

Well, maybe Shi Zhengli wasn’t interested in furin cleavage. Maybe that wasn’t her thing.

Slide 46 (furin screenshots)

I’m afraid it was.

She’d spent a lot of time, as had Ralph Baric, in the months and years leading up to the pandemic, interested in how much furin cleavage could enable you to grow viruses that you couldn’t otherwise grow, and was a a a limiting step in in how well viruses infected.

Here is a paper that she published in 2017 on a rodent virus, where she draws attention to a very similar furin cleavage site. And here’s a paper published by her colleague Shibo Jiang, in which he inserts a furin cleavage site into a gene.

Albeit not a viral gene, but an antibody gene.

A 12 nucleotide sequence.

Slide 47 (FIPV)

And here’s a virus that they do mention in their Nature paper, a cat virus, coronavirus, which has exactly the same furin cleavage site. So, they would know that the sequence PRRA R would create a furin cleavage site if inserted.

Slide 48 (Email KGA)

Now, as I say, the news of the furin cleavage site alarmed many Western scientists when they first saw it, and that letter from uh Kristian Andersen to Anthony Fauci uh resulted in a flurry of activity.

Uh for a while we weren’t able to read the emails, but then we did. And uh this is what Fauci said to Farrar, “I just got off the phone with Kristian Andersen. He related to me his concern about the furin site mutation in the spike protein of the currently circulating virus. I told him as soon as possible, he and Eddie Holmes get a group together, examine the data, and if necessary, report it to the FBI and MI5.” Quite right, too. That’s the right response.

And indeed, later that day, a meeting was convened between Fauci, Farrar, Collins, Vallance in the UK, and a bunch of virologists including Andersen and others.

And the upshot of that meeting was that they agreed that they would write something about this, and that Andersen would be tasked with drafting it. Uh and after the meeting, Farrar and Andersen and and uh Holmes all still thought it was quite likely as a hypothesis that the furin cleavage site had been inserted.

But some time over the next few days, they changed the line they were going to take in this article they were drafting, and eventually ended up writing something that ruled out a lab operation altogether.

What had changed?

Kristian Andersen is on the record as saying that he’d had a good look at RaTG13 for the first time and this convinced him it was different.

But that’s not really plausible because he had been uh tweeting about RaTG13 a week before.

Slide 49 (Farrar)

True, by the end of that week, there was indeed uh a possible excuse for why we they could start to rule out a lab leak and that was the news from Jeremy Farrar to uh to Francis Collins that reports were coming out of a 99% similar virus in a pangolin.

The missing link.

And Collins quite rightly replied, “Very interesting. Does it have the furin cleavage site?”

And the answer was no, it does not. And nor is it 99% similar. Once we saw the whole sequence, it’s only 90% similar. It’s not the missing link.

Slide 50 (Pangolins)

I won’t go into the pangolins in any detail cuz they’re a red herring, but it’s important to note that the effect of this announcement was to throw a lot of us off the off the scent for a while.

Whether that was its purpose, I can’t say.

But as a before he published his paper ruling out a lab leak, Kristian Andersen knew that the pangolins didn’t help. Unfortunately, pangolins don’t help clarify the story.

Slide 51 (PO)

The paper appeared in March of 2020, preprinted in February.

The proximal origin of SARS-CoV-2 and it said, “We do not believe that any type of laboratory based scenario is plausible.”

And in a press release from Scripps, Andersen went further and said it rules out laboratory manipulation.

Now, I was misled by this paper. This was what led me to go and say to colleagues who were asking about this in Parliament in the UK, “No, no, it’s been ruled out. It wasn’t a lab leak. There’s good evidence it’s been ruled out.”

But I hadn’t read the paper very carefully and when I did, I found the arguments rather flimsy. I mean, the main argument was that the fit of the receptor binding domain to the human ACE2 receptor was good but not perfect.

And if people had done it, they’d have made it perfect.

I’m not sure that’s a very rational argument.

Slide 52 (KGA)

But it was only many, many months later that we found out that Kristian Andersen had not changed his mind after all.

He said on the 17th of March, “We do not believe any type of laboratory based scenario is plausible.”

On the 1st of February, he thought it was friggin’ likely.

On the 2nd of February after the meeting, he still thought natural or escape were both options.

And on the 16th of April, a month after publishing the paper, he’s still not fully convinced, can’t fully rule it out, and thinks the furin site could still have been inserted.

Now, I’m sorry, but where I come from, publishing a scientific paper that says the exact opposite of what you think in private is not good scientific practice.

But those of us who have written to the editor of Nature Medicine requesting that this article be retracted or corrected have not even had the courtesy of a reply.

Slide 53 (Slack screenshot)

We do have quite a good explanation of what had caused them to change their line if not their mind.

And it comes in an exchange between Andrew Rambaut and Kristian Andersen.

“Given the shit show that would happen if anyone seriously accused the Chinese of even accidental release, my feeling is we should say that given there’s no evidence of a specifically engineered virus, we cannot possibly distinguish between natural evolution and escape, so we are content with ascribing it to natural processes.”

And Andersen replies, “Yep, I totally agree. That’s a very reasonable conclusion, although I hate when politics is injected into science. It’s impossible not to.”

Now, you can’t read that exchange and come to any other conclusion that the decision to write the paper the way they did was political rather than scientific.

7. The Defuse Proposal

Slide 54 (7. The Defuse Proposal)

In September 2021, a document was leaked to the press that should have been made available from the very start, the DEFUSE proposal. Lots of people knew about its existence and chose not to tell us about it.

Slide 55 (Defuse cover)

It’s a very important document. It was an application from Peter Daszak on behalf of the EcoHealth Alliance, the Wuhan Institute of Virology, and a number of other groups for $14 million from DARPA to investigate defusing the threat of bat-borne coronaviruses.

Slide 56 (FCS in Defuse)

And it stated halfway through the text that they were interested in furin cleavage sites and that they were interested, if they couldn’t find one, in putting one into a sarbecovirus for the first time.

“We will introduce appropriate human-specific cleavage sites and evaluate growth potential in monkey cells and human airway epithelial cultures.”

Slide 57 (Defuse draft diagram)

Now, some people have said, “Oh, no, they weren’t they were talking about putting it in at the S2 site, not at the S1/S2 junction.” No, the diagram makes quite clear that they’re interested in both sites.

Slide 58 (Defuse draft)

And when we saw an earlier draft of the document, we were even more shocked because we found Peter Daszak reassuring Shi Zhengli in a in a marginal note that although she he says the work will be done in North Carolina, a lot of these assays can be done in Wuhan.

And the reason for that is because the biosafety level two nature of the work on SARS-CoV-2 in Wuhan makes our system highly cost-effective.

Much cheaper to do it in Wuhan.

And Ralph Baric replies, “China might be growing these viruses under BSL-2. US researchers will likely freak out.”

Slide 59 (Wild West email)

Did they freak out? Here they are freaking out.

Anthony Fauci, “Serial passage in ACE2 transgenic mice.”

Jeremy Farrar, “Exactly.”

Francis Collins, “Surely that wouldn’t be done in a BSL-2 lab.”

Jeremy Farrar, “Wild West.”

Slide 60 (time again)

Let me remind you of the timeline again.

Of all the gin joints and all the towns in all the world, this virus walks into the one city where this kind of research is happening the year after someone has proposed to put a furin cleavage site into a sarbecovirus for the very first time.

That’s quite a coincidence.

8. The Loose Ends

Slide 61 (8. Loose ends)

Now, a few loose ends and then I’ll wrap up. I’m sorry I’ve gone on so long.

Slide 62 (items)

There’s a mutation in the human version of the virus that happened very early in the pandemic. It stabilizes furin cleavage. It’s a response to furin cleavage. It implies that the furin cleavage site was new. Had not been in that virus forever.

Chinese government banned the sale of ex-laboratory animals in markets during 2020.

Three key lab workers, according to US intelligence, I can’t verify whether this is true or not, fell ill. They included Ben Hu, who was in charge of these chimeric virus experiments, and Ping Yu, who as we saw was the the person who described lineage four.

The man who developed a COVID vaccine very early in the pandemic in China died, reportedly by falling off a roof.

Conclusion

Slide 63 (conclusion)

To summarize, ladies and gentlemen, in 2017-18, in Wuhan and nowhere else, the Wuhan Institute of Virology shifted their priority to 20% divergent viruses from SARS, sequenced at least one lineage four sarbecovirus, proposed to insert a furin cleavage site into a sarbecovirus for the first time, proposed infecting human cells and humanized mice with such viruses at a low biosafety level.

And the following years, in Wuhan, a lineage four sarbecovirus appeared with a newly acquired furin cleavage site in the very same city, leaving no trace in any animal in the markets or anywhere else, and the Wuhan Institute of Virology misled the world, whether intentionally or not, about the name and date of sequencing of certain relevant viruses, and took their database offline.

Slide 64 (Peer-review)

Now, I’m often asked, “If you think you all this is important, why haven’t you published it in the peer-reviewed literature?” Believe me, we’ve tried.

We’ve submitted papers saying all this again and again. They’re always turned down by gatekeeping referees who want to be able to say, “You haven’t published this in the peer-reviewed literature.”

That’s a circular argument again.

And on that note, ladies and gentlemen, I’ll end.

Slide 65 (Acknowledgements)

I would just like to acknowledge the many, many people, this is not an exhaustive list, who have contributed to this knowledge. Most of it didn’t come from me. It came from these people.

Thank you very much.

[applause]

Q&A

Question 1

Jay Bhattacharya

Uh thank you for that uh that lecture. Um we’re going to make room for questions and those of you who’d like to ask questions, please line up at the the mics um provided. Uh but I thought I would I would take the the opportunity just to get to ask you the first question if you you don’t mind.

Um and that has to do with the stakes of the debate. Uh I I I mean, I have a position and I and I think largely agrees with your position, but I know there are scientists who disagree with with both of us. Um, uh how much does it matter who’s right in this debate? Uh, because it seems to me that that’s one of the reasons why we’re seeing such difficulty getting a scientific debate going on is because people think the stakes of this debate are so high that uh that if you’re right then we should not be doing virology at all. That’s one version of the of the of the of the of the this the I think the imagine stakes. But in fact, it seems to me the stakes are not quite that high. Right? The if if the stakes could be that we just do virology much more carefully. We ban dangerous gain-of-function, but we allow many many other parts of virology to to continue which is an essential part of scientific investigation into human disease. Um, so what I would love to hear your thoughts about what what the stakes actually are in this debate.

MR

Well, I think quite a lot of scientists feel that they have to do their best to resist this conclusion because the the result could be a loss of public license for science altogether which would be catastrophic. And I agree, it would be catastrophic. Uh I think the vast majority of science benefits humankind and I wouldn’t want to see it stopped because of one mistake that might have been made. But I don’t think as you imply that the stakes are quite that high or at least were quite that high. If if at the start they had gone with what Kristian Andersen apparently wanted to do which was say, “Look, this is a possibility and we need to take it seriously.” Then I think the damage could have been confined to one small corner of virology and the rest of biotechnology and the rest of biomedicine and the rest of science would be untainted. But as it is, the way it’s gone on these last 6 years, it’s now harder and harder to um confine the damage to one small set of experiments, dangerous gain-of-function experiments which as I say had relatively small benefit, potential benefit, and relatively large risk. Um that’s I think the problem and I you know, I can sympathize with people who think if we admit it now, we’re going to lose social license to do science altogether. But I still think that it’s vital to I mean, the truth is just too important to take that line.

JB

Yeah, I I I agree. Agree with that. Um the uh the the the the uh the returns to doing science are so tremendously high. We can cure diseases that were I mean, you know, when I when I was a medical student, I thought would never be cured. Sickle cell anemia and uh and uh you know, we can get improvements in cystic fibrosis. We have so many um huge investments, many which come out of this institution that you that you’re speaking at. And so to to me, I would love to see a way to to one, to uh have the truth out whichever way it ends up. I mean, I as you know, I’m convinced that your your your presentation is correct, but as as as if but others may disagree. Um but two, uh to be able to to take action to make sure this sort of thing never happen again while nevertheless protecting our ability to do the kind of science I know you also support.

MR

Well, I I I think it we have made the world a more dangerous place by failing to solve this problem. And by that, I mean if if you’re in Pyongyang or Tehran and you want to bring the Western world to the to its knees, you’ve just had a demonstration of just how cheap that could be. You wouldn’t even need a very dangerous virus, just a highly infectious one. Uh and uh you could destroy the Western economy almost altogether. Um and therefore the message and and by the way, the World Health Organization would shrug and say, “I’m afraid we weren’t able to find out and we didn’t get enough cooperation from the Chinese.” That’s that’s a pretty clear message to the bad actors in the world that this is a way to go and I I hate to say this cuz it sounds like I’m sort of recommending it to them. Of course, I’m not. I’m I’m just saying that I think we we we do need to take that into account as well. By the way, just a little footnote on that um spare a thought for the people who sell mammals in markets. Nobody really minds too much about throwing them under a bus saying, “Well, I think it was you guys who did it.” You know, they’ve got a livelihood to make, too. Uh you see what I mean? So either way this goes, there is harm to certain people’s livelihoods. Uh we have to make sure we get to the truth without worrying about that. Yeah.

JB

Absolutely. So in that spirit, why don’t we open up for uh questions? That’s why don’t we start on the left since there’s two folks over there. And if you have a question, please line up at the provided mic microphones.

Question 2

Question

So uh Matt, all the issues that you face to peer review do you think that uh an emerging model like the one that we see for the journal eLife where you have publication and then after publication, you have open peer review do you think that would be a better model for this particular case?

MR

Uh yes, I do. I think uh I I don’t spend much time trying to publish things in the peer-reviewed literature, so I’m not great expert on it. But it does seem to me that the problem of of power review and gatekeeping, you know, in other words, keeping out people you don’t like from the peer-reviewed literature and uh ushering through people you do like into into journals has become a significant problem in science, not just in this area but in lots of areas. And I think it largely derives from the asymmetric anonymity. Uh if the reviewer can be anonymous uh but the uh author of the paper is not anonymous, then I think that that creates a big part of the problem. Um it does seem to me in an age when publication can be instant and there’s an enormous uh you know, we’re drinking from a firehose of information on the internet every day anyway, that there’s no reason not to allow people to just put things out there and have uh the peer review happen in open session with people tearing your paper apart um uh in in front of the whole world. I think the only people who would suffer from that are the those who make a fortune out of publishing these um journals that um uh rely on uh the the existing kind of peer review.

JB

Actually, can I ask a follow-on to that question cuz I think that’s such an interesting point. So um there’s been an uh as you know, and you pointed out in your talk uh an enormous fight over that proximal origins paper and and whether Nature should or should not retract that paper. Um and um let me ask again a question about the stakes. Right? Um does the editor of Nature get to decide what’s true about proximal origins?

MR

Well, strictly speaking, it’s Nature Medicine in this case, but I don’t know whether that I don’t know whether that comes under Nature. I don’t really know. Um Uh this does seem to me to be a a problem. If you walk down street in America or Britain or anywhere else and you ask your friends, what do you think happened? They all say it came out of a lab. Come on, of course it did. Don’t be ridiculous. Um if the one area that where that hasn’t budged is large is large chunk of the scientific establishment, but and in particular, Nature and Science and Cell which are publishing one side of this argument but not the other. And uh and and that you know, that they don’t seem to be bothered by the fact that the rest of the world thinks it was a lab leak. If they really thought they were wrong, ifthey really thought the rest of the world was wrong on that uh you know, they get out there and debate it and so on and get and have the conversation. Instead of which, they want they seem to want to use their privileged position as the premier journals to defend one side of an argument but not engage in it with the other side. And that doesn’t feel to me right. There’s too much power with these journal editors.

JB

Yes. I mean, I think this is partly why I I’ve been so interested in introducing replication as the standard of scientific truth. I mean, I’m not introducing it. This is what all we scientists believe are the standard scientific truth, right? Independent people looking at the same question come to the same conclusion. That’s always been our standard of truth. Whether or not top editors of top journals decide one way or the other is in a sense truly beside the point.

MR

Yeah, I think I mean, science scientists like anyone else are prone to confirmation bias. They look for evidence that supports their theory, not evidence that that that that uh combats it. Um and and you can’t expect them not to. That’s human nature. But what kept science honest in its heyday was the fact that Professor A loved tearing Professor B’s paper to shreds. I mean, that that in a sense is the sort of uh is the gold standard of science as opposed to everything else.

JB

Okay. Next question, please.

Question 3

Question

So I have um two questions. What is the epidemiological evidence proving the lab leak theory? And in the name of gold standard science which we’re all dedicated to, can you describe in detail the experiments that you personally performed to support your lab leak theory? Thank you.

MR

Um the the second uh question is [clears throat] very easy to answer which is that I I have performed no no experiments at all. I’m not an experimental scientist. Um

the first question, what is the epidemiological evidence for a a lab leak? Uh and there is no direct epidemiological evidence, I think, that could distinguish between a lab leak or a zoonotic jump um definitively.

However, I personally think that the fact that we had a virus extremely well adapted to infectivity in human beings is unusual for one that has jumped from an animal, but would be expected for one that has spent a lot of time in cell cultures.

Ebola and SARS and Nipah and Hendra and these other zoonotic zoonotic infections can be very lethal, but not very they’re not very infectious to start with. They get infectious once they get a hold on on the human species.

This one was extremely infectious and fairly mild from the start. That’s very unusual, I think, for a zoonotic jump.

And therefore, that is epidemiological evidence suggesting that it might have

The other one piece of evidence that crucial, of course, is that the phylogeny of the virus is very clearly suggest that it did start in Wuhan and nowhere else. That that that the the the evidence on that is pretty strong.

JB

Can Can I do a follow up to that question also? Um What is the nature of the evidence that would definitively definitively establish as a lab cuz it currently seems to me that there is no lab experiment that could, in principle even, distinguish between the two definitively. Uh or even direct epidemiological evidence short of uh the kind of epidemiological evidence you get from looking at lab notebooks, for instance, to definitively establish.

MR

I think we’re unlikely to find a smoking an absolutely definitive dispositive smoking gun inside the genome of this virus. As I said, we found some extremely surprising and suggestive things, but they don’t completely answer it. [JB It seems to me the nature}

an account of a of an an experiment with a chimeric lineage for sabecovirus that was 98 to 99% similar to this in Wuhan in 2019, then I think we’re home and dry, but I don’t know whether we will ever find that.

JB

It seems to me that the the key piece then of that the the case you’re making then is not lab evidence directly, not epidemiological directly, and not even just forensics directly. It’s it’s the combination of the three.

MR

It’s very much a combination of you know, it’s the good old Bayesian thing. You add up probabilities till you get to a a final result. And and it it feels I mean, a better analogy might be trying to prove a court case. You know, you’re you’re putting before the jury all the evidence and the other side is putting their evidence before the jury and the jury has to make up their mind. And I’m pretty sure that if this was put before a jury that at the moment the lab leak would win the case.

JB

Next Next question, please.

Question 4

Question

Hi, thank you for the lecture. This is a really interesting subject. Um I’m thinking about a related topic in the spirit of the academic freedom lecture series. Artificial intelligence research is advancing rapidly. Um there’s currently no regulations on deep learning or artificial intelligence research. Uh despite that that opens up a lot of opportunities for um for harms, dangers they’re being warned about by some experts in the field. Synthetic biology is connected to that, whether you had um a case of bioterrorists or even uh misaligned superintelligence connected to a self-driving lab or something like that. Um so, I wonder if either of you have thought about this subject as something where the scientific community, maybe even NIH in particular, uh should be thinking about how to approach um the dangers of research or if it could even be the topic for a future academic freedom lecture.

JB

Thank you. That’s a great suggestion for a future academic lecture. I’ll absolutely do [laughter] that.

MR

Yeah, I agree. And I I will I will look forward to reading it and and I don’t claim to be an expert on that that area, except I would say one thing, which is that I’m not sure that the people having the artificial intelligence debate currently have talked to you guys enough, have talked to biomedical scientists and evolutionary biologists enough, because, for example, this idea that, you know, you tell an artificial intelligence to make everything into paper clips and brook no argument and eventually take over the entire world and kill people if necessary to get to your paper clip manufacturing goal, um that argument, you know, that that that a a dangerous AGI could take over the world. We we face that all the time. They’re called viruses or great white sharks or something. All sorts of things that want to do damage to us, but they have competition. They have competition from other species, and the same will be true of artificial general intelligence. There will be competing AGIs in an evolutionary ecosystem. And so, telling the AI guys, start talking to some evolutionary biologists fast. Thank you.

JB

Next question, please.

Question 5

Question

Yeah, no thanks. Thanks for a wonderful lecture. And and my question to you, I mean, my my point, yes, is that we need to understand that we’re scientists. That’s what we do, actually. So, if we give up on that, we better do something else. I think that it’s in the nature of what we do. But that same need to understand actually is what’s driving my question to you, you know, because we have to make decisions of what we fund or not. And so, there’s always this argument and counterargument. In the gain-of-function, the counterargument of why you would want to actually promote research is if you find yourself in a situation with a pandemic or an epidemic, you want to be able to provide the tools to counteract it, which was the argument that has been put forward. So, how do we the those that are providing resources to others judge these elements? I mean, to what extent any type of knowledge, if taken outside of the context, can be have malevolent applications? And so, but but we have a responsibility of thinking about it. It’s not that because it’s an inevitability, we’re not going to do it. So, so I’m curious to see what you’re thinking in terms of of course, we’ve created these committees that evaluate and determine is this appropriate or not? But that requires cooperation. And are we currently in a state where we are going to be able to get that cooperation, particularly where science has no boundaries?

MR

Um I’m going I’m going to go out on a slight tangent in answering this and I might might not give you a very good answer therefore. And that is to say that I do think there’s a a possible lesson that we need to be trying to learn here um that lab-leaked pandemics might look different from uh natural pandemics in terms of particularly how infectious they are from the start and therefore whether uh things like lockdowns would work.

Uh in other words, if it happens again that there is an outbreak somewhere in the world, one of the questions to ask really early is has this been in human cells in on the lab bench for a few months? Cuz if so, we going to have a real trouble confining it and cutting it off and using social isolation and NPIs.
Whereas, if it’s literally just come out of a pig that ate a mango that was dropped by a fruit bat um uh the week before, probably we’re going to be much more successful with isolation and that kind of tactic. So, the the public health tactics of managing an outbreak ought to be taking into account the mode of origin. Not not, you know, in a black and white way, but as a possible influence. That probably goes well beyond my expertise and I might well get shot down by someone, you know, possibly by him.

JB

I’m not I I will never shoot you down. I’ll never do that. Although, maybe we can have a discussion about about lockdowns at some point.

Actually, I wanted I wanted to bring that that that question, a fantastic question, to to to sort of a lift it up a little bit more and ask what responsibility do scientists have, right? So, like the the story I love to hear to tell about the about the the launch of the nuclear age. Enrico Fermi does this experiment on a squash court in the University of Chicago of all places and he starts a nuclear chain the the world’s first nuclear chain reaction started by human in on a squash court literally in the middle of Chicago. And before he does this, thank God, he’s a great mathematician. He does a calculation of the likelihood that the that the chain reaction can be contained. And decides that it can be. And then he does the experiment. Socially responsible thing to do before he launches the nuclear age. Um shouldn’t we scientists always do that calculation?

MR

Yeah, and and in Los Alamos they did take seriously the possibility that the first test of a nuclear explosion would ignite the nitrogen in the atmosphere. And they did the calculations and showed that it was it would not before they did it. And rightly so. So yeah, the there needs to be precautionary calculation going on in these occasions.

JB

All right, next question, please.

Question 6

Question

Yeah, thanks for the talk. I wanted to try pushing back just a little bit on the point about intelligence intelligence agencies. As you said, we know that a number of intelligence agencies have looked closely at this. Like you, I would love that research and conclusions and evidence to reach the public someday. I hope it will. But I think maybe you can make a small argument from what we know about the intelligence conclusions against the lab leak theory.

So for example, you mentioned the three sick researchers. There’s these allegations that three researchers at Wuhan Institute of Virology who were very involved in these experiments got sick and I think November 2019.

And if true, this is evidence you know, some some possible evidence at least partially in favor of a lab leak.

But if you were an intelligence agency and you had rock solid evidence that that had happened, that those identities were correct and confirmed, that they were severely ill and so on. Wouldn’t that make you almost certain in the lab leak scenario? And we know that the US intelligence agencies have been pretty ambiguous about this. Most of them reached only a tentative conclusion.

If I remember correctly, the FBI had only moderate confidence in a lab leak. So doesn’t that suggest that maybe they didn’t have such strong evidence after all?

MR

Yes, I think you’re absolutely right that if they were absolutely certain they had COVID, then of course they would be 100% certain that it was that. But people get colds and flus all the time. So that what they don’t know is exactly what they had. They just think it’s intriguing presumably hat I mean they say they were sick enough to be treated in hospital. Ben Hu has gone on the record as denied that and said he was not sick that that fall. The problem here is that I’m not party to the evidence. I don’t know how they got it. They don’t want to to tell how they got it because that would presumably compromise some human intelligence source that they have or something like that. So I think none of us can be quite sure how good that evidence is, which is why it was just one loose end that I I felt I couldn’t not mention, but I don’t myself find it to be part of a strong part of my argument.

JB

Can I follow up on that question? By the way, this this period of like pushing back is fantastic. This is what this uh the this forum is supposed to be about, not to not we all just agree with each other. Um

So let me let me follow up with that question on on um the nature of our cooperation with states that hide evidence around this. Right? Um uh For the longest time, the the West has cooperated extensively with Chinese scientists. Uh and it was extensive like extensive and very fruitful collaboration. Um Let’s go back again back to now to the Cold War. Um the the Cold War one of the major issues in the Cold War was that scientific collaboration. And in fact, there were two scientific worlds all throughout the Cold War. The Soviet bloc and and the Western bloc. And in part because the thought was that there was no no way to do fruitful collaboration that wouldn’t result in exploitation of scientific knowledge developed in the in the West. And where where are we on that? In in your view given the evidence that you’ve shown in your your your your long thought on this on this issue cuz seems to me international collaboration is a very very important fruitful tool for the advance of science. And yet if there are if it’s not possible to have that collaboration without a worry that well on crucial scientific questions like this one, you’re not going to be able to get collaboration from the Chinese authorities. What what should be the right policy? I mean I can tell you that we’re still thinking about that. I don’t think we’ve made a full decision on that. But what where’s the UK on that and how how are you thinking about that?

MR

Well, I think that question is well above my pay grade actually. But [laughter] But some some some some general thoughts.

On the one hand I would like to see politicians and all others who are collaborating with China make this part of the conversation. I mean we do that for human rights. Why don’t we do this for this issue too? Look saying at every meeting, yes, we would love to collaborate with you on something. Please could you be a little more cooperative in sharing information about what happened in Wuhan in 2019. That might be a start and I see no evidence that that is happening. Even though there are many many institutions in America and in Europe that are heavily dependent on Chinese collaboration. And it’s just an interesting thought experiment to think if we were dealing with say, I don’t know, Indonesia or Brazil here. We’d have been a lot tougher in terms of insisting that they open the books and help us understand what had happened. And for some reason we are much too frightened to be a bit aggressive on this issue with China. And you know, I have colleagues in UK Parliament who make a big song and dance about Hong Kong, about the Uyghurs, about human rights in China, but they don’t include this on their list and I find that frustrating cuz I think it’s as important if not more so.

JB

Thank you for that. Next question.

Question 7

Question

Yeah, thanks. In the spirit of respectfully pushing back. Uh you brought up the furin cleavage site, but my understanding is that there’s plenty of evidence to suggest that it naturally occurs very often, particularly between the S1 S2 junction like you were you’re talking about in many coronaviruses, naturally occurring coronaviruses and in many other viruses that infect humans. And actually there’s an evolutionary advantage to having these furin cleavage sites. So you brought that up as a smoking gun. Can you explain that given that it’s naturally occurring, why it’s still a smoking gun?

MR

Yes. Furin cleavage sites naturally occur in MERS-like viruses, merbecoviruses. Most of them in many other coronaviruses, many other kinds of viruses. Never in sarbecoviruses. That’s the point. That that’s the this distinction is often missed. People say, “Oh, you don’t Of course you get furin cleavage sites in coronaviruses.” Yes, but we’ve never seen them in sarbecoviruses before.

And there seems to be a good reason for that. Remember I said that this virus’s natural habitat is the guts of rhinolophus horseshoe bats, not the lungs, the guts. It’s an enteric virus in bats. And in those tissues and using the receptors it does in there, cleavage is a disadvantage. Cleavage actually makes the virus less able to invade the cell. That’s the hypothesis. I’m not saying that’s a proven fact, but that’s the hypothesis. So furin cleavage sites are selected against in bat guts and selected for in human lungs. That that’s the argument as to why we’ve never seen a sarbecovirus with a furin cleavage site. It’s hard to put a number on how many we’ve looked at. And the proximal origin paper said, “Don’t worry, we’re going to find one in a sarbecovirus soon.” Well, 5 years on, we still haven’t found one. But it’ll it’s something like 800 different strains of sarbecovirus have been looked at and still not one with a natural furin cleavage site in it.

JB

Next question, please.

Question 8

Question

Thank you for a tremendously well-organized and compelling narrative. One of the things that was most disheartening to me during the pandemic itself was the scientific community’s embrace of the conspiracy theory jargon that went on. And I’m wondering if you can talk a little bit about the sociology of a science and the responsibility of scientists to combat this whole idea that a perfectly valid hypothesis, alternative hypothesis is a conspiracy theory.

We’re also fighting against this kind of disinformation language that’s being very commonly used to squelch alternative ideas.

And what is our responsibility as scientists to work against this happening again to us?

MR

Yes, thank you. It’s a it’s an issue I wrestle with and have done for many years. I’ve been a science journalist ever since I joined The Economist as science correspondent in the mid-1980s. And this question has always been there.

How do you take mavericks seriously enough to not miss the genius?

And how do you not do so in such a way that you end up listening to cranks? And it’s very I I I know no rules of thumb that enable me to say this guy’s a crank, that guy’s a maverick genius. Um yes, in some cases it’s very obvious, you know, which side of the line people fall on, but I do find it hard to be absolutely sure in certain gray areas. Uh and I want to remain open-minded, but not so open-minded that my brains fall out, as someone once put it. Um uh and uh so in in this case I took the view that it was unlikely that it came out of a lab because the people who knew more than I did about virology were saying so. Um and I also my prior was we’re not that good at designing viruses yet. Well, I was out of date. We are that good. We are able to swap spike genes into um viruses very precisely and create viruses with much higher infectivity. Um so, I was wrong on on that.

But but when it it in this in 2020 when Facebook literally censored anyone mentioning a lab leak, and so did Reddit. But Twitter didn’t quite. But it downplayed it a lot. It was very hard to have a conversation as a journalist or writer or politician, as I was at the time, uh about this. Um and it was described as a debunked conspiracy theory by people like the New York Times. Now, and even when I thought it wasn’t right, that theory, I I knew that was going too far. It wasn’t a conspiracy theory. It’s a logical possibility. There’d been lab leaks before. So, it’s this feels to me like one that wasn’t difficult to say no, it’s not a conspiracy theory. It’s a theory. Let’s look at it. The evidence might be against it, but we mustn’t label it in this cheap and uh really misleading way.

JB

Thank you for that question. Next question, please.

Question 9

Question

Thank you for putting this on. Uh I’m here to be open-minded, but uh some people uh have laughed at the notion of talking about this, uh scientists and people in the general public, and I just wanted to know what you thought about that. And uh what could be done about that, perhaps, uh for scientists and the general public?

JB

So, let me let me let me take that question. That So, the question, I guess, is uh there are people in the general public and also scientists who think that maybe this question ought not to be discussed, especially on a stage like this at this at the Temple of All Science, the NIH. Right? Um I mean, I I should I should say I I just strongly reject that.

Right? I I think that if we can’t ask and have reasoned conversations on this topic that is at the I believe at the heart of a lot of the public distrust in science, that the future of uh public support for science is is very dim. We absolutely have to have these conversations where in in in in a in a sense, wherever they lead, if we are to to restore public trust in science. Um Yeah.

MR

Yeah, can can I add that that um I I I live in Britain. Britain is a leading biomedical nation, probably second only to America and China now, I don’t know. But, you know, it’s it’s got a terrific track record. Um and I’m a fellow of the Academy of Medical Sciences, uh and I’m not a fellow of the Royal Society, but I wrote to both the Royal Society and the Academy of Medical Sciences saying, “Please, please hold a debate about the origin of this virus that is killing millions of people.” And the reply I got from the Royal Society said, “No, we only have debates about scientific issues.”

Um and the reply I got from the Academy of Medical Sciences said, “It’s too controversial an issue.” Well, I thought the whole point of debates was controversial issues. Um but my the argument I’d made to them was Britain doesn’t seem to actually have skin in this game. It’s not got the problem which America has got that it seems to have funded some of this stuff. [laughter] Um and well, through the Welcome Trust, maybe that’s not quite true, but um uh and therefore we could, you know, suddenly here’s an opportunity, it’s a geopolitical opportunity to be an honest broker and say, “We’re going to put a lot of money into this and we’re going to hold proper debates and we’re going to really try and get to the bottom of this.” Um so, uh it it it but it seems to me extraordinary that people didn’t want it discussed.

JB

Next question, please.

Question 10

Question

Um thank you. I had two questions. Um the first is what’s your theory on how the virus got from the lab to the wet market? Um because to play a little devil’s advocate, I appreciate the um coincidental nature of it being next to the market, but it’s also coincidental that it happened at where the hotspot was the market So, I guess how do you comport the two, and if you had a theory on that?

And then the second question, I was intrigued by one of the examples that you gave of a lab leak, I think in Russia involving anthrax, and you mentioned that it took 12 years for us to realize it was a lab leak. How did we realize that?

MR

Both good questions. Um in terms of how it got to the market from the lab, if that’s what happened, um I obviously don’t know, and I’m not going to speculate on exactly who walked into the market at when they did. But, I think it’s important to realize that quite a lot of the early cases had not been to the market. So, it’s the the the market could have amplified the epidemic anyway and still been nowhere near the very beginning. It could have been a month before it reached the market, but the market was still somewhere where it got noticed for the first time, and it and it took off. Um uh so, uh the you know, a market like that, an undercover market with not great ventilation, huge numbers of people um coming in and out every day is a an excellent super-spreader opportunity for a virus is is all one needs to know, in a way. So, that it’s not mysterious that it really took off in the market, even if it had nothing, you know, so I’m not saying that it had to be a bunch of laboratory white mice that were taken down to the market to be sold as pets or something like that, you know, that and I and I don’t want to go into speculative theories of that kind.

As for the anthrax outbreak, it’s a really interesting story, actually, because Western suspicions that there had been anthrax deaths in Sverdlovsk, 66 of them, I think, um uh were presumably coming from intelligence, were aired, and the Soviets said, “No, no, no, no, no. It’s It’s food poisoning.” And they said, “If you like, send some scientists over and we’ll show them around.” And an international group of scientists went to Sverdlovsk and did a tour of the city and came away saying, “No, the the the Russians are right. This was probably just food poisoning.” And it was 12 years later when the wall came down and the Soviet Union collapsed, and scientists came to the West and said, “You know what? We left the the cap off a filter or we left the filter off a pipe one day, we we sent a plume of anthrax over a suburb, uh and this is what happened.” And And so, without the collapse of the Soviet Union, we wouldn’t probably know to this day what had happened there. And I think that’s quite an interesting point.

Question 11

Question

Um Hello. Um Matt Sbevel. Um I tried to say hi earlier, but you were backstage. Anyway, um it uh it was a great lecture, and I applaud the NIH for having this discussion. Um if we sort of pull back a little bit, there’s clearly you’ve made an argument that politics was involved in making decisions about what should and shouldn’t be done as science, uh and the implication is that somehow we could extract politics from science, and then we would have a better, purer science. And I mean, one would be naive to say that. We need public dollars to support science, and those public dollars come from the public who elect politicians who give us money to do science. So, politics is in science. And we’re seeing it in this country, you know, very prominently, uh play out right now. And so, I’m sort of appealing to you as a visitor looking at this country and seeing how we do this business for guidance and advice, because the NIH is wrestling with us, and you know, in the in the spirit of pushing back, you know, I work at the NIH. I see the influence of politics on my own laboratory here every day, in a way that is dramatically different than it was, you know, 4 years ago or 5 years ago. And I think a lot of that is the consequence of a kind of mismatch between what science is and what the public understands, and it’s out of that mismatch that you had all of these scientists make sort of essentially false statements, but it’s because they knew that they couldn’t work without dealing with contending with the fact that politics is in science. So, that you know, I buy all the story. Lab leak, fine. Shouldn’t have lied about it, fine. We still can’t get rid of politics in science unless you can tell me how.

MR

No, Bevel, you’re absolutely right. And and of course politics will always be there and it’s always going to be a part of the story. Um that doesn’t make it right and that doesn’t I think excuse going a long way into being political in a situation where there are extremely high stakes. That’s what feels to me different about this. Um or if you like, just to put it another way, yes, there’s politics in science, doesn’t mean I can’t look for the truth as well. But thank you for your question.

JB

And thank you all for your participation and for your engagement. Please welcome join me in congratulating Matt Matt Ridley for this amazing lecture.

[applause]