Ep 105: Follow the data: the search for COVID’s origin (with Alina Chan)

On this episode, we talk with Alina Chan, postdoc at the Broad Institute of MIT and Harvard and co-author with Matt Ridley of Viral: The Search for the Origin of COVID-19. SARS-CoV-2 could have plausibly jumped into humans in Wuhan via one of two paths. The first is zoonotic transfer from wild bats to humans, possibly via an intermediate animal host. The second is some kind of lab accident: researchers working on a SARS-CoV-2-like virus accidentally became infected with it and then transmitted it to others in Wuhan. Although early discussions among virologists reached the consensus that the origin was almost surely zoonotic, more recent discussions have started to take the lab-leak theory seriously. Unfortunately, we still lack conclusive evidence in support of either hypothesis. And, as public leaders have co-opted the investigation for nonscientific reasons, the subject of COVID’s origin has become practically taboo.

Alina’s approach is to “follow the data,” leaving no stone unturned, and we believe that it is our responsibility as scientists to do the same. We talk to Alina about her book, as well as the many new things that have been revealed about COVID’s origins since its 2021 publication. Towards the end of the chat, we discuss the implications of what we’ve learned about SARS-CoV-2 for how we should prepare for and deal with future pandemics.

We hope that this episode inspires you to seek the best possible explanation of COVID origins. Please write to info@bigbiology.org and tell us what you think, and share with friends and family. 


Cover photo: Keating Shahmehri

  • Marty Martin 0:08

    Welcome to season six of Big Biology.

    Art Woods 0:10

    Honestly, I never thought we'd even get to season three, who would have imagined that anyone would want to listen to us for so long?

    Marty Martin 0:16

    To start season six, we're taking a risk we're covering a topic that has become taboo in the last few years partly because so many politicians and crackpots have co-opted it.

    Art Woods 0:26

    But also because it matters so much because of how it's changed our lives.

    Marty Martin 0:29

    We're talking, of course, about SARS-CoV-2, the virus that killed millions, if not tens of millions of us, caused many long-term physical disabilities, shutdown our schools and compromised our kids’ development, shuttered our businesses and sort of broke our social networks.

    Art Woods 0:43

    And of course, the pandemic is far from over. A new variant is spreading now, and although we're better able to protect people from the virus's worst effects COVID continues to kill.

    Marty Martin 0:53

    Our focus today is the SARS-2 virus, specifically its origins. We’ve chosen to tackle this topic to do our small part to try to get back some of the trust that we scientists loss it's like 2019.

    Art Woods 1:05

    Our read is that too many scientists and too many policymakers who are supposed to make science-based decisions just didn't stick to the scientific method.

    Marty Martin 1:12

    Too often, too few people spoke plainly and simply said, "We don't know," when we didn't know.

    Art Woods 1:19

    Take for example, masks. Initially, we didn't need them. The virus was said not to be transmissible in the air, so masks were of course superfluous. The truth was, we'd let national repositories of masks and other PPE run low, and we were hedging our bets to have enough masks for medical workers should the worst happen,

    Marty Martin 1:36

    Not long after, when it became clear just how fast the virus spread. Masks became imperative, mandated for everyone, anywhere lots of people were present. Not only were they now in fact, protective, they were so important that no one was to go into public without one so as to block transmission.

    Art Woods 1:53

    But just a while later, they became unnecessary, or at least optional again, after George Floyd was murdered in the summer of 2020. People gathered in huge groups to protest and to seek social change, some wore masks during the protests, but many didn't. And many experts said that was okay.

    Marty Martin 2:09

    During that period, mask policy was truly bizarre. You had to wear one on all planes, trains, and buses. But if you were traveling to participate in a protest, you could lose the mask once you reached your destination, even at a giant crowd of people.

    Art Woods 2:22

    And it was always okay to take off masks in restaurants and on planes when you were eating.

    Marty Martin 2:26

    Yeah, how was that supposed to work?

    Art Woods 2:28

    In a nutshell, we could have done better. Public Health must of course balance science with other concerns. But always we have to remain honest, we could have said what we did and didn't know and probably kept much more of the public trust.

    Marty Martin 2:40

    So consider this episode as an effort to try to get back some of that trust so we scientists can play our best role when the next pandemic comes, which it will.

    Art Woods 2:49

    Today we speak with Alina Chan about the origins of SARS-CoV-2. Alina is a postdoc at the Broad Institute of MIT and Harvard.

    Marty Martin 2:56

    In early 2020, Alina and colleagues found some molecular evidence that SARS-2 was pre-adapted to humans, which led her to start investigating whether the virus could have come from a lab instead of a spillover from wildlife at a wet market, which was the prevailing hypothesis then.

    Art Woods 3:10

    Alina's study attracted the attention of Matt Ridley, the author of several biological books, and a former member of the UK House of Lords. In late 2021, they published Viral: The Search for the Origin of Covid-19, which is an exhaustive treatment of what was then known about COVID origins.

    Marty Martin 3:26

    Today we talk with Alina about that book, but also the many new things that have been revealed about COVID origins since the publication.

    Art Woods 3:32

    Many experts think that Alina is one of the last people we should host on this topic. She's become one of the faces of the lab leak hypothesis, but you can read in her book and you will hear on the show today that her position is simply "follow the data."

    Marty Martin 3:45

    Alina, like others is not yet ready to accept that SARS-2 came from a raccoon dog or some other animal in the Huanan market between an obdurate Chinese government and the lack of any virus positive samples ever been found in animals in that market or the supply chain, there's more to learn here.

    Art Woods 4:00

    First, the Wuhan Institute of Virology-

    Marty Martin 4:02

    or the WIV-

    Art Woods 4:03

    has been collecting and studying thousands of bat samples for years. Second, research conditions in the Wuhan labs were commonly unsafe. And third, an inventory of samples held by the WIV disappeared from the internet in early 2020. And is yet to resurface.

    Marty Martin 4:18

    Now to be clear, most all human infectious diseases-

    Art Woods 4:21

    HIV flu, smallpox, MERS, SARS, one etc.

    Marty Martin 4:25

    Have a zoonotic origin. So it's totally reasonable that SARS two came from some wild animal or its handler in the market.

    Art Woods 4:31

    But it's also reasonable that the COVID pandemic was started by a research-related incident. And we have to figure this out using every scientific tool at our disposal. And even if the outcome is politically or culturally unsavory.

    Marty Martin 4:44

    As someone who's worked for more than a decade and a biosafety level three facility, with viruses, but not corona viruses, trust me, these are tough, complicated research projects. Accidents happen even to the most seasoned lab workers. But is it possible that someone at WIV unknowingly worked with a frozen in bat sample that had SARS-2 in it? If you sample just 100 bats in nature, you can find as many as 30 viruses now to science, maybe one of those was SARS-2?

    Art Woods 5:09

    And if so many mammal species around the world are known now to get infected with SARS-2, including deer, mice, tigers, minks and more. Why wasn't SARS too widespread and the Huanan market, assuming that all mammals there too could be infected with it?

    Marty Martin 5:22

    Critically, we, like many others do not now favor any particular origin story. We have a strong agenda though, but a wholly scientific one. We want no reasonable hypothesis to be off limits, and we hope for a thorough investigation, even though it'll likely take years and a lot of luck to come up with a dispositive explanation.

    Art Woods 5:41

    Finally, before we hear from Alina, we want to thank Andy Dobson, Eric Bortz, and especially David Quamman for sharing their perspectives on this critical topic. It was David's article in The New York Times magazine a few weeks ago that motivated us to produce this episode.

    Marty Martin 5:54

    David, thanks for the time and the energy that went into that piece, and Andy and Eric, thanks for talking to us about your thoughts on COVID origins.

    Art Woods 6:00

    We hope this episode inspires you to seek the best possible explanation of COVID origins. Please write to info at Big biology.org. And tell us what you think about it, and share it with friends and family.

    Marty Martin 6:09

    But most importantly, please keep supporting the scientific mindset that'll eventually inform us about COVID's origins and position us better for the next zoonotic event.

    Art Woods 6:18

    I'm Art Woods.

    Marty Martin 6:19

    And I'm Marty Martin.

    Art Woods 6:20

    And this is Big Biology.

    Marty Martin 6:32

    Alina, thank you so much for joining us on Big Biology today. Our main focus is going to be the origins of SARS-CoV-2, the virus that causes COVID-19. But before we get into that science, we want to talk about how you came to be so invested in it. In 2021, you and Matt Ridley published the book Viral and now you're working at the Broad Institute at MIT and Harvard. Your work has been in bioengineering. But well, you're not working on SARS in the way that you have been working on it now. So how did you come to take the role that you do?

    Alina Chan 7:01

    Yeah so rewind back to late 2019, early 2020, I was a postdoc at the Broad Institute of MIT and Harvard. And I was working in the field of gene therapy. So in this group that I still work in, I and the team of people, we develop delivery vehicles to descend gene therapies into patients. And so one quite famous example of this is the treatment of pediatric spinal muscular atrophy. So this is treated with a gene therapy, a delivery vector that was essentially discovered 10 years, just 10 years before the FDA approved this treatment. So that speaks to the speed at which people can find novel viruses. So this is a virus, but it just doesn't cause disease. So it's a non pathogenic virus, discover it, and then turn it into a gene therapy, use it to deliver a gene treatment that saves lives that helps to delay the progression of these rare and really terrible genetic diseases.

    So we're going to talk a lot about your book Viral. And just as kind of set the stage for that you evaluate a variety of different hypotheses for the origins of SARS-CoV-2, super interesting sort of data brought to bear on the various ideas. Just to sort of give, I guess, the punchline away, you're going to come down reasonably strongly on the side of the lab leak hypothesis, even though you're not sure about that. We're gonna get into all the details of that. But I just wanted to ask, like, right here at the very beginning, how has writing that book changed your life and the way you're interacting with the scientific community?

    So by the time I decided to write this book, while the search for the original COVID-19, I had spent more than a year looking into this question of how the pandemic began. And so what one of my friends had advised me about that, at the time was that you've tweeted so much, and I think I had made like, thousands of tweets, in the past year, about the original COVID-19, they say it's time to put it all down in one place, because you know, time erodes, like tweets. So no one's really gonna go back unless there's an investigation or something, to look at thousands of tweets. So I agreed with them. It was really, I think, my goal to write the book, like the one book, that people in the future read about the origin of COVID-19. So this book, it's incredibly balanced. And actually, many people have told me that the best argument for natural origin is in Viral, because we don't make up straw men. We don't over interpret data. We just lay out all the evidence and we make the strongest case we can for natural origins v.s. lab origins. And this one has an incredibly long citation list. I think it might be one of the books or the longest citation list you can see so that readers can actually go to the sources of all the information and facts and like developments cited in the book.

    So I'd say how it changed my life. It is that it cemented me as public enemy number one for those scientists, experts, others who are trying to downplay a lab origin for whatever reason. I think the book might be one of the worst things to happen to them, besides evidence emerging towards pointing to a lab leak, or the intelligence agencies changing the shifting towards a lab leak. I think Viral is probably one of the top three things, the worst things to happen to them, because it lays out all of this argument for a lab origin in a very approachable way. For a layperson, you don't have to be a scientist to understand this. And it's quite clear that as you get to the end of the book, and more developments appear, that more evidence is piling up for a lab origin of COVID-19. No one knows for sure, that this is scientific consensus, actually, that we just don't know. And both lab and natural are possible. But in my view, there's certainly more circumstantial evidence for a lab origin than a natural origin. At this point.

    Art Woods 10:43

    Yeah yeah. I felt just my compliments to the book because it did feel like a very balanced and fair treatment-

    Alina Chan 10:49

    Oh thank you.

    Art Woods 10:50

    of different hypotheses. And you know, it felt like it had integrity, because you guys were pursuing the data and the sources, instead of coming in with preconceptions. So that was nice to see. One other comment about all the citations and the, you know, the support at the end, so I was reading this book on my Kindle. And you know, on a Kindle, you don't really know when a book is going to end. And it ended much earlier than I thought it was going to, based on the percentage that I'd read through. I think it's because there's this giant section of notes and references at the end

    Marty Martin 11:19

    There's so much more to go so much more to learn.

    Art Woods 11:21

    Oh, wait, wait, wait, it's over?

    Marty Martin 11:25

    I mean, just to comment on the writing in the book, too. It is incredibly approachable. I mean, trying to cover something so fraught, something so complex and complex, even to biologists, because there's a lot of molecular biology, there's epidemiology, there's socio-political interaction. I mean, there's so many so much dimensionality to it. And yet, you still make it easy to read. I mean, it just, you know, is quickly processed. So that was really present.

    Alina Chan 11:50

    I have to attribute that mostly to Matt Ridley. He's the, you know, established-

    Marty Martin 11:55

    He has practice, right? Yeah

    Alina Chan 11:57

    A lot of practice, yeah.

    Art Woods 11:59

    One follow up question, just on this topic. So you know, you just characterized yourself as public enemy number one for some subset of people. So is that affecting the kinds of things that you're going to be able to do in your career and the sorts of collaborations that you establish? I mean, is that having, like consequences for you?

    Alina Chan 12:15

    I mean, so go back to early 2020, I certainly was not aware of this faction of scientists who were trying to downplay a lab origin. At the time, maybe I was too naive or idealistic. I just thought that all scientists wouldn't want to approach this objectively, to find the truth. And so what I became famous for in 2020, and there's a whole Boston Magazine article on me by Rowan Jacobson, it lays out that I attracted so much attention from journalists and the public, not because I said it came from a lab, but because I left the door open for a lab origin. So I said, both natural and lab have to be considered, no matter how likely or unlikely, and that was enough in 2020 to draw all this attention, both positive and negative to me. And so this faction of scientists who tried to shut down, prematurely shut down, investigation to lab origin or or consideration of a lab origin, their emails were only released, via private exchanges, were only released in 2021. And that's when I became aware that, hey, there are all these powerful scientists who don't want a lab origin to be talked about, to be considered. And so I think at that point, yes, my panic level went up slightly. And I have to say, it's not pleasant. It's not the kind of situation a junior scientist wants to find themselves. Not even a senior scientist doesn't want to find themselves in the situation.

    Marty Martin 13:34

    Nobody? Sure, yeah. But there's a level of vulnerability, understandably, so we want to be really careful. In fact, I think it's important to point out that there was and is efforts by non-scientists to represent things in a particular way. So I understand that, you know, there's sort of an arms race of a kind, where maybe there's some good intentions to mitigate not so good intentions coming from another place. So can you say something about what you know, or what you expect the motivations to have been for the scientists to not really give the lab leak very much credibility?

    Alina Chan 14:08

    So I think that certainly different reasons why different scientists would not want the lab leak hypothesis to be properly considered. The most direct one is when you have been collaborating or funding the scientists in Wuhan who might have accidentally started the pandemic. So if you are amongst their collaborators or funders this has backlash for you as well. No matter where you are around the world, because you have shared ideas, you have encouraged them, you have given them money to do it. And so there is arguably a sense of blame that might be cast on them. If this was found to be a lab leak, it would destroy their legacies, their reputations, their safety. So for that small group of scientists who collaborate and funded with the Wuhan Institute of Virology, specifically, there is that direct consequences for them.

    And so if we look at the people with further relationships, like less strong relationships with the Wuhan lab, we're thinking about, perhaps scientists who have advocated quite strongly for some risky virological experiments to be done. So these are scientists who are not out to cause trouble. But they do think that it's important for scientists in the lab to do experiments that help them see how a virus can get better and better at infecting human cells or jumping from species to species. And the motivation for this is to understand how future outbreaks might happen. And in the labs that developing vaccines therapeutics diagnostics to test for and prevent and to tackle these emerging outbreaks. So for this group of scientists, they've spent many years advocating for these risky experiments, what happens when one of those risky experiments starts a pandemic when millions of people are dead? You know, so here, even though they're not directly connected to the WIV, the Wuhan Institute of Virology, they still have the sense of blame, I guess that the public might point at them and say you encouraged this work, you say it was a risk worth taking, and now millions of people dead, because of that risk. So there are those folks as well.

    And then there are people who are even more distanced from the whole thing. But they see that if a lab origin is investigated seriously, and perhaps even confirmed to be true, it would lead to both geopolitical and even within-country political chaos. So unfortunately, the US now it's devolved into this situation where it feels like if lab origin has won, the Republicans have won. And if it's natural, then the Democrats have won. This is totally bizarre to me, as a non-American, as a Canadian looking in on this, it's just like, why? Because, because the origin of this pandemic has nothing to do with anybody's political identity. You know, like whether it came from a raccoon dog at the market or a lab accident, you being a Democrat or Republican, it didn't matter.

    Art Woods 16:53

    Yeah, we just want to know.

    Marty Martin 16:55

    I mean, that's true. We all want to know, and we could see it that way as scientists, but when it was co-opted by politicians, you know, that's how we ended up in that scenario, it became a flag. And now winning the flag, the science is actually inconsequential. So it is an issue of winning versus understanding. It’s just playing with different games, yeah. So I wonder, let's one more question, and then let's go to what we know about the origins itself. To what extent do you think that the culture of academia has anything to do with this? So you know, you talked about the various different potential classes of motivations of the people that took the roles that they did, but those of us that are active scientists, I mean, we all know that there's an enormous pressure to publish a lot in prominent places, to do so quickly, to get grants, to get collaborators. I mean, did that play a role? Or how do you think about that?

    Alina Chan 17:49

    I mean, of course, so it's only natural for all scientists to want to publish in prestigious journals. But that wasn't the only factor here. So in recent months, the private exchanges between the authors of a very famous paper called proximal origin that has been cited thousands of times in the media, to downplay lab origin, their private messages have been subpoenaed by congress and released on the Internet. And so in these private messages, you can see that they are struggling with doubt. So they convened in early 2020. And initially many of them believed it was more likely that it came from a lab. But over time, they were really freaking out about the potential consequences of making this public of making their doubts public. And within a month, they had sort of psyched themselves into saying that we don't have to raise the lab leak hypothesis, we can just say that nature has everything it needs to make this virus. And they emailed the lead author of proximal origin, emailed the journal, where it was eventually published in Nature Medicine, they said to the editor, let's edit this paper, so it makes it clear that this virus does have a natural origin. So they put out this paper, published in March 2020, with the intent to make it clear to the public that it was natural. But in the background, they continue to worry. So this lead author continued to worry even a month after publication, worrying that the evidence was not strong against a virus being manipulated in the lab, being cultured in the lab and escaping into the wild, so he continued to worry. So I think that it wasn't just about publishing in a big journal, for these scientists. It wasn't just the adrenaline of you know, most scientists having, you know, this excitement of publishing in a big journal. It wasn't just that. For them, they were grappling with questions of what happens if we tell the public that even we the top like, experts in this area, are worried about our lab origin?

    Marty Martin 19:47

    Yeah.

    Alina Chan 19:48

    Yeah. Okay. Well, let's at this point, we haven't actually laid out the alternative hypotheses. So let's do that now and touch briefly on the evidence for and against each one. Maybe let's frame this in terms of three possible hypotheses, what we would call the bio weapon hypothesis, the lab leak hypothesis and the spillover, the natural hypothesis that you've been talking about. Let's just start with the bioweapon hypothesis because I think that one is going to be fairly easy to pass over. There's been some talk in the press about whether or not the virus was engineered in some way by the Chinese military as a way of starting a pandemic, or disabling one population or another, what's the evidence for and against that?

    So I think that some people had these suspicions, because the Wuhan Institute of Virology, which I'll call the WIV, has some PLA research going on in there. And it's known to be an institute that carries out classified research projects. So some of these like thesis, like graduate thesis, in that Institute, can be sealed for up to two decades. So it's not your regular like university here in the states where you just defend publicly and then go off and live your life. Like people, there are some students and trainees in this institute, whose projects cannot be talked about for like two decades, even after like their thesis is written. So because of this, this institute, and its relation to the PLA, that's why people I think, had this fear that the virus had been developed as a bioweapon.

    And furthermore, one thing that happened in the early days of the pandemic is that this general, this military General Chen Wei, was sent into commandeer the WIV. So I think that stoked a lot of fear in people that there was something untoward happening in that lab. And that's why this general had been sent in to take charge. To my knowledge, I don't think that there is evidence that this is a bioweapon. Again, I do admit that it's difficult when you don't have access to the lab records and to the knowledge of activities happening in that building. But this virus, if you look at its characteristics, one would not predict these characteristics to be something useful as a bioweapon. And it's not like you took a particularly lethal strain of Ebola, or anthrax and like developed it in lab, this, this looks to me very much like, if we had come from the lab, it looks very much like a natural SARS-like virus that was discovered in some animal that didn't seem to be causing very much disease, but was potentially enhanced in the lab. And that's why it reached some pandemic potential.

    Marty Martin 22:24

    So if it was a bio weapon, what kinds of things might it have? I mean, what would be the signatures of SARS-CoV-2, as a bio weapon that we would look for?

    Alina Chan 22:34

    So I think this argues that scientists know how to engineer precisely how to engineer a virus.

    Marty Martin 22:42

    That's where I was going- it's not so easy, right?

    Alina Chan 22:44

    Yeah, someone would have to be highly brilliant. And I would say that actually, it's not scientists don't have that mastery over biology yet, even though it's making huge leaps and bounds, is that I think, most lab outbreaks are actually accidental. And I think most people can agree that they're mostly accidental, they're not intentional. And so there is this argument from people who insist that this pandemic started in the market, they say, there's no way that scientists would have engineered the virus to precisely be able to cause a pandemic like this. And I would say that's not the argument that most lab leakers are making. Most "lab leakers" with quotation marks are saying that this is an accident, this isn't an experiment gone wrong, that someone might have thought it's a de-risk experiment, someone might have taken this virus and then thought this is doesn't look like it's causing some good disease in people or animals, it's fine for me to play around with this, to put in some features and understand how it could get better at infecting human cells and it accidentally leaks out of the lab and causes a pandemic, this is not the virus engineered to cause a pandemic.

    Art Woods 23:58

    So we want to turn more detail to the data and the observations that might support this view of a lab leak accident. But maybe before we do that, let's just spend a minute on taking seriously the zoonotic origins, the spillover idea, and just make the case that you do very well in the book that is like substantial evidence that it could have been a zoonotic transmission, you know, somewhere in Wuhan, maybe at the Hunan seafood market. So what's the evidence for that kind of origin?

    Alina Chan 24:26

    So if you're looking at a natural origin that actually two branches of this, so the first one is the most commonly perceived one, which is that there is an ancestral bat virus version of this pandemic virus, it's in bats, and it jumps through different intermediate animals. So something like a civet or raccoon dog, let's say, into people, and that the spillover might have happened at the Huanan seafood market in Wuhan, where they've been known to be the sort of animals susceptible to COVID-19 being sold on occasion in that market.

    The second branch is where a human person is exposed to these viruses, whether from a bat or another intermediate animal, outside of Wuhan, and then travels to Wuhan, and there that person starts an outbreak. So the person could be a wildlife traderm, that's why they went to the market in the middle of Wuhan, and then they started a super spreader event. So that's the second scenario, both are considered natural spillover hypotheses.

    So I'd say that the main evidence for a natural origin has to do with one of the earliest outbreaks being detected at the market, at this market in the center of the city. People who argue for the market hypothesis say: "What are the odds that one of the earliest clusters would be at the market? And not let's say at the hospital, or like a library or school or an elderly care home?"

    Art Woods 25:47

    Why wasn't it anywhere else in Wuhan?

    Alina Chan 25:49

    Yeah, yes. Why wasn't anywhere else in Wuhan? Why was it at this market? So I would say that there is still a plausible pathway that this is true, although it has to explain several pieces of evidence that don't really point towards this natural origin right now at that market. One of it is that the key evidence for natural origin that was very easily found for SARS in the 2003 outbreak, and most other multiple outbreaks have not been found for SARS-CoV-2, for the COVID-19 causing virus. So in the case of SARS 2003 and MERS, people, the investigators very quickly tracked down intermediate hosts. So they tracked down the animal sources of this virus that the earliest cases had been exposed to. Many of the index cases, so the patients arose or the earliest patients, in SARS and MERS had been identified as handling these animals so they like waitresses, chefs, like people, who vendors who delivered the animals from market to restaurants, so these people were directly in contact with these animals. So there's very strong evidence that the viruses, SARS and MERS, were jumping from these animals to the people in that profession. But in the case of COVID-19, SARS-CoV-2, those animals have failed to emerge, have failed to be found or reported.

    And this is despite lots of sampling of mammals in the market, right?

    Yes, exactly. And SARS-CoV-2 also is now recognized to be highly transmissible across multiple species. So it just jumps from species to species, like out of control. So the thought is, are the Chinese authorities powerful enough to cover up all of that to go down the entire supply chain and to stem, to stop any more outbreaks of this highly transmissible animal virus? For me, I think it's less probable. So to lay out what the zoonosis proponents are saying right now, they're saying that this explosively transmissible virus that jumps from species to species like nothing, evolved in a very brief period right before it emerged in Wuhan, jumped into people two times at the market, and then disappeared completely. So for me, that seems fairly unlikely. But I think it's still plausible, it's still on the table, it still deserves to be investigated.

    Marty Martin 28:04

    So two things I want to follow up on what you just said, let's start with the latter one first two times, they're two different lineages say more about that and how it plays into the zoonotic event.

    Alina Chan 28:15

    So one piece of evidence then makes the market less likely as the ground zero of the pandemic, is that all of the early patients from that market had what is called the "B lineage" of the virus, so they were all infected by this B lineage of the virus. Another early lineage of the virus that was circulating in the city in Wuhan was the A lineage virus. So even though we call these two, A and B lineages, these two viruses are only separated by two mutations, so only two letters of nearly 30,000 letters in the genome are different. And the A lineage, these two letters are closer to the bat, ancestral virus, then in the B lineage, and that's why most scientists will look at these two sequences and say B must have come later than A, because the odds of a virus emerging in the human going backwards two times, and precisely towards the band ancestral virus is very improbable. So when you see that at the market, or the early cases, only were infected by the B lineage, it suggests to you that someone later on in the pandemic had gotten the B lineage, gone into the market, and started the outbreak at that market. Because people with A lineage were not linked to the market. Several of them had been exposed quite early. There's one family that was exposed at the end of December 2019, never went to the market, traveled back home to different parts of Chin, and then that's where they realized that they had COVID and were found to have lineage A.

    So from the point of view of the zoonosis proponents, this is a piece of evidence actually against the market being the place of origin. So how could they possibly argue and turn this around? So later, the Chinese CDC Released data from the surface samples collected at the market. These were samples taken later in 2020. So like way after the outbreak had reached out of control and assuming they found that a single surface sample in the market had an A lineage sequence, so the zoonosis proponents use this single sample from like the sofas on the market to say that: "Aha, this means that the a lineage was also at the market and it must have also jumped from an animal to a human." So, here they are using some pretty fast reasoning, rather than the more common sense, like idea that another sick person carrying the A lineage, were just in the market, and contaminated it.

    Art Woods 30:40

    Was coughing all over the place. Yeah.

    Alina Chan 30:42

    Yeah, so this whole market actually was the size of more than nine NFL fields.

    Marty Martin 30:46

    Oh, wow. I didn't realize it was that big, okay.

    Alina Chan 30:49

    Yeah, it's huge. And it was right next to the busiest, like metro hub, like subway hub, in Wuhan. And it's flanked by three of the central hospitals. And it was just a short walk from the Wuhan CDC. So this is very centrally located market. It's not like out there in this like rural area or suburbs. It was like right smack in the central district, the most populous district with the most elderly people. So this whole place completely spattered with viruses by the time the CDC and other investigators went in to collect samples.

    Marty Martin 31:19

    Okay. And one other thing to follow up from what you said a minute ago, I think a piece that I haven't heard emphasized enough, it's not just that there wasn't much virus found, or there was a virus found in the animals at the market, the supply chains, I mean, the many, many different people, the many, many different species, the many different places. I don't know how much that was chased up. But if you have more information, I would love to hear about it, but not finding SARS, in all of those other places that must have, you know, gotten the animals to bring to market in the first place. That seems to be incredibly strong evidence, too. So do we know any more about that? Do we know about the magnitude of effort to look for buyers?

    Alina Chan 31:58

    Yeah. So we're getting conflicting reports about how much of a search was done? I mean, certainly, the position that I think it's the most logical is that this the origin of COVID-19 has huge national security implications for China. There's no doubt in my mind that they would have done everything to find out where this virus came from this cause as a country like that, you just cannot risk leaving it alone. You can be like, oh, let's let them do whatever they want, we don't want to find out. You need to find out so you can shut it down and prevent these things from happening again, like consider that China has locked down so many of its major cities, like to the point where people are rioting in the streets, you know, they cannot afford to let the origin of a virus like this remain a mystery to the authorities. So they, I think that they must have done everything they could to find out.

    But put that aside, there are a few conflicting reports here. So naturally, the Chinese investigators said that they did follow up. They said that they went through this through the supply chain, they went through farms, zoos, like markets searching for the virus, and they said they came up empty. But those who argue against that say that there were farms that were shut down, reportedly, without testing, so no one even came to collect samples, they just shut those homes down. And they say that the search wasn't extensive enough and that the wildlife trade is so huge that you need to sample very aggressively to find this virus. But my counter to that is that this virus is so hyper transmissible, you know how can you stamp it out? You've seen when it exploded in mink farms around the world, how difficult it was to stamp it out? And now it's just everywhere in the wild deer population in the States. So how likely is it that without testing without finding the source, you managed to shut it down? I don't know. So is this certain that there's no intermediate host? No, it's not certain. But we can say that there's no evidence that the search has been performed, and no evidence has been found or reported.

    Marty Martin 33:51

    Okay.

    Art Woods 33:52

    There's this interesting thing that you bring up in the book about ascertainment bias and sort of where the local authorities in Wuhan were initially looking for the virus. And you had an interesting exchange with Michael Warby about this on the AAAS podcast as well. And let me see if I can just articulate how I understood it. It's that very early on when the earliest cases started rising, the authorities essentially, like focused on the ones that they had prior knowledge had been associated with the market. And so rather than looking more broadly across the city, they of course, found early cases associated with the market, because that's where they looked. Is that what happened?

    Alina Chan 34:28

    Yes, that's exactly what happened. So to make things clear, for people who are new to this, there are these famous Science papers now by Warby and some of the proximal origin authors, saying that the Huanan seafood market is the epicenter of the pandemic. And the data they used to support this comes entirely from the Chinese CDC. But these authors, they admitted in their papers, as well, that they didn't have access to the actual data. So what they have is just dribs and drabs, they didn't have access to the methods. So as scientists this is crucial if you don't know how data was collected, you don't know how incomplete or how biased it is. So it's very problematic that they went out with such a strong statement that the market was the epicenter when they didn't have access to the complete data or the methods.

    But what emerged quickly enough from the Chinese CDC, just looking at the reports in early 2020, so back when any, like cover up or anything about the origins was still like not coordinated at least. So in early 2020, and 2021, and even 2023, the people who investigated the early cases in Wuhan have all come out and said, like it was because we saw this small cluster, they had seen four cases for early cases linked to the market. And after that, everyone assumed it was just as one happening again, they just thought it was 2003 SARS again. So they focus their search entirely on that market, anyone with links visited worked at the market, the three hospitals surrounding the market. So if you follow that, if you'd only look for patients, and those three hospitals, the pattern would obviously be a radial pattern like dispersing out from that area, and also the district of the market. So using these criteria, that's why all of the cases are either linked to the market could live very far away, but linked to the market. Or if a unlinked to the market, they look like they're radiating out of the market, because of this search method.

    Art Woods 36:33

    You had some interesting points about expectations for how rapidly the virus would evolve or not, depending on how new it was in human populations. And my understanding is that, you know, if it were a zoonotic event, the virus is, you know, in some way pre-adapted or adapted to circulating in whatever animal host it came from, it jumps into a new host, humans, that's going to be a different kind of cellular machinery and immune system. And that should impose very hard selection on early lineages of the virus. And as a result, you should see quite rapid evolution. So did we see rapid evolution of those early samples of virus?

    Alina Chan 37:10

    No. So what we're seeing here is we're thinking about the conventional way of thinking about spillover, especially informed by the first SARS and or the MERS outbreaks, is that scientists, experts in that field had made this assumption that these viruses are not immediately adapted to the human host. So when they're circulating in bats, or the intermediate animals, they have to gain some adaptive mutations, mutations that are advantageous for them just to jump into humans, and to cause transmission and infection. And so in the case of SARS, and MERS, you can see it plain as day, like you can see these viruses they're trying many times they're circulating, definitely amongst camels or civet cats, things like that. They're trying many times to jump into humans, and eventually they do and it's picking up many adaptive mutations during the jump and after spreading in humans to get increasingly optimized for causing human infection and spreading between humans. But for SARS-CoV-2 with the COVID-19 virus that is completely missing. So in the early phase of the outbreak, there was only a single mutation that was considered adaptive, that is the D614G mutation. And today, it's widely understood that this mutation arose in response to the emergence of a furin cleavage site in the virus. So we can talk a bit more about this feature, but this furin cleavage site is a gain of function feature. It's a feature that transforms a normally weak attenuated virus into a pandemic level virus once it one that's capable of spreading wildly amongst humans and other animals.

    Marty Martin 38:39

    Okay, and we do want to come back to the into its role in transmission and everything. I think that's a great way to turn to the ideas of lab leak

    Art Woods 38:47

    I mean, maybe we'll get to this in the next section. But I think you know what you just said Alina raises the question of what happened, so that there was not a lot of early evolution in the virus in humans in Wuhan. So that implies that it was associated with humans or associated with human cells earlier than that.

    Alina Chan 39:06

    So what the strongest zoonosis proponents are saying, and this is in those Science papers from 2022, by the proximal origin authors, they're saying that this pandemic virus was so well adapted for human transmission, that it required zero mutations to cause two separate outbreaks at the market. So they're saying that both lineage A and B jumped at the market and immediately caused the outbreak. So in their paper, they say like no adaptation was required, this virus was ready to cause a pandemic. And so that is their position. They see this well adaptiveness of the virus not as evidence for a lab origin but they see it just as a, as more reasoning for natural origin. So they've argued that it's because the virus is so well adapted and has this furin function feature, that's why it calls a pandemic, a natural pandemic. So they in their minds, they have, they have sort of thrown the lab leak origin off the table. They're insisting that any evidence even for adaptiveness points towards a natural origin.

    Marty Martin 40:02

    That's really confusing, because it seems that it works for either one of the hypotheses. I mean, there's so many viruses, so many species of bats. I mean, this particular mutation, as we're going to talk about, this particular mutation may be likely for these viruses, but the idea of pre-adaptation, I don't see how this particular thing is convincing in either way, you could come up with explanations for either one, this is evidence for either one of them, depending on where you want to start.

    Alina Chan 40:27

    Exactly. That's what I said in 2020. And that's why I've continued to say. I said, from the very beginning, I said that we don't know how this adaptation happened. We don't know if it happened in the wild. We don't know if it happened in humans. We don't know if it happened in the lab. But we have to investigate to find out how. But what the zoonosis proponents, the extreme ones, they're like: "We know how it happened. They're like it must have happened in they said in 2020, it must have happened in humans. And then there they're saying '22 must have happened in animals." But no matter what they're saying it didn't happen in the lab. So that's their stance.

    Marty Martin 41:00

    Okay, well, let's walk through the big picture about the lab leak multiple alternatives, and then go back into the furin cleavage site. So there's a lot of different ways that we could approach this. I think one of the things that I really like about your book, and your take on this, in general, is that you're always laying all the possibilities on the table. Now, in this particular case, unless you want to spend about four hours going through all the alternatives, we might want to winnow them to the most likely, and instead of laying out all of the different ways that lab leak might have happened, let me just ask you to do one of my favorite concepts steel man, the argument against the lab leak. What's the best set of ideas for why it isn't a good explanation?

    Alina Chan 41:44

    So I'd say that it's only possible to steel men an argument against a highly engineered form of the virus leaking from a lab, because there's just no way and even the top experts admit this, even the proximal origin author admitted there's no way to distinguish between a natural virus that went through the wildlife trade and jumped into a person in Wuhan versus a natural virus that was collected by scientists, brought back to the city and then leaked from the lab. There's no way unless you can, you know, magically, we would like the recordings of history in your mind, there's no way to distinguish those two pathways. It would require an investigation, right, like talking to people interviewing them collecting historical facts. So that's the only way. The science cannot distinguish which pathway it took for this natural virus. So a steel man argument that's been made against an engineered version of the virus leaking from a lab is Wuhan. Is because no one outside of that lab in the public ever heard of this virus, the precursor of this pandemic virus being collected or studied in that lab. So there's no such proponents, they insist that unless you can find evidence that this precursor, that a version of the pandemic virus was being studied in the lab before the detected outbreak, then you have no proof. Then you can't say that the scientists ever had it in their hands, they had to have this in their hands to cause an outbreak. That's what you're saying.

    Art Woods 43:04

    This is the so-called dispositive evidence?

    Alina Chan 43:06

    Yes. So unfortunately, this steel man is not very strong. It's very brittle actually, because the fact is that this institute, engaged in a lot of classified research. And based on the publicly available publications and data from that lab, at least in late 2019. Most of the things they published were from viruses they had collected before 2016. So that leaves at least two or three years, we don't know what new samples or viruses are collected. We don't really know what experiments they have done. And some of them say that well, what about the people who work closely with them? Shouldn't they know all of the viruses that they have in the collection? And unfortunately, the answer is no. So there is an organization called the EcoHealth Alliance that's based in New York City. They have been longtime collaborators with the Wuhan Institute of virology, since the first SARS outbreak, that's when they joined forces and started this whole, I guess, campaign to define natural viruses in the world, understand how they could jump into people, to prevent future outbreaks. This EcoHealth Alliance had been collaborating with them and sending money from the States to this lab in Wuhan. But at the end of the day, they did not have access to the database that had been amassed at this Wuhan lab, even though money had gone through to this Wuhan lab, they did not have access. So when the pandemic started this, this database had gone missing. And with they didn't share with anybody, they made them all sorts of excuses, things like upgrading database, things like we're being hacked, so that's why we can share the database with you. And so even the closest collaborators don't know what viruses, what samples have been taken like comprehensively by the Wuhan scientists.

    Art Woods 44:48

    So in that database, there are probably there's probably information about the viruses that were collected between 2016 and 2019. And in that list, there might be something that's more closely related to SARS-CoV-2, or very, very closely related, if we could only have a look at that data?

    Alina Chan 45:02

    Yes.

    Art Woods 45:02

    Yeah. Okay. Yeah.

    Marty Martin 45:04

    So I don't I've never done this kind of research myself, but I do have samples in freezers that are in the midst of being investigated. So I mean, yeah, it's understandable that even if there's lots of people trying to figure out what's in these samples, that doesn't happen, instantaneously. Yeah. So I wanted to get into the sort of the mechanics of how these viruses get studied. And, you know, methodology where lab leak might be plausible, but I want to go back really quickly to one thing that you said in terms of the interaction between the EcoHealth Alliance and the WIV. This database, is it the case that the database is still not available? And do we know anything about the timeline there or have there been promises made about when access might be granted?

    Alina Chan 45:49

    So in 2019, I'd say that the Chinese scientists were very excited about showing all the work they've done over the past decade, and hunting down these viruses, looking for novel viruses in bats, in the wildlife trade, and even amongst sick people. So they went to rural areas, people in the wildlife trade, looking for people with illnesses, like undiagnosed illnesses and collecting samples from them and bringing it back up to Wuhan. So they were really proud of this work, you know, they really, I think they saw themselves on a mission to prevent future pandemics from nature. So it wasn't like they were trying to downplay the work they were doing. And so by early, mid-2019, they had put online this database describing more than 22,000 samples collected for pathogen discovery. But in September 2019, it was just taken offline. And then there was no more external access to this database, even though that there are hints that internal access continued through like early 2020. But since 2019, no more external author access. So if someone had had access, they could have gone in and checked, like, how many samples did they collect in like 2016 to 2018, let's say, and from where, and from what types of animals, and what types of viruses did they find in the samples? So this even if it didn't give a real time, insight into what was happening in the lab, certainly would have given a much more updated perspective than what was in the public scientific literature.

    Marty Martin 47:15

    Mmhmm okay. So I think a lot of what we've been talking about so far is the WIV, the Wuhan Institute of Virology, but there's another research entity, that maybe I mean, at least in the recent past has gained a little bit more attention. So maybe let's also include what we're learning about the, what is colloquially called the Chinese CDC. It's right next to the Huanan market, you mentioned it just a minute ago. But in particular, I want to ask you about the conditions, the research conditions that we know to exist in these places. In the book, you wrote about a lot of the research with these viruses that were discovered in that period, the research about which we know, happening under were called biosafety level two conditions. I don't know how much we want to get into the weeds or you want to share the details about the difference between three versus four versus two versus all of these things. But what can you tell us about the practices that are known to have happened in the lab, other leaks that may have happened, rates at which they were disposing of biohazards training protocols, these kinds of things? What are the details that we do know in one or both places about the pathways by which escape might have happened?

    Alina Chan 48:20

    So I'd say that when news of this novel Coronavirus, emerged in early 2020 Most people were thinking holy cow, it must have escaped from that high biosafety BSL four lab they thought there must be some top secret research happening in that super-safe lab and it broke out, because it was so stealthy and transmissible. But as others, including myself, said that looking deeper, and looking through all the publications and videos and photos from the WIV, we soon realized that the biosafety conditions at which these live sounds like viruses had been handled when not that high. Were actually, some would say the lowest level of biocontainment that is in a lab, at BSL two, this is where they studied the life and recombinant so like engineered viruses. And so that shocked a whole bunch of virologists on this one, one of the proximal origin authors saw that and they said that's screwed up, you shouldn't be studying these viruses and BSL two, another virologist said I can't believe they did something so stupid.

    Marty Martin 49:16

    And I think one key thing maybe to mention there, because I've done a lot of work myself into BSL three, the difference between two and three, in three, and especially four, the precautions you take with the way that it looks in the movies wearing the Tyvek suit and multiple gloves and all of this protection, that's three, and four is even more involved. But two is basically working in a hood with the air flow controls such as exposure is low, but really the transmission of an airborne pathogen in that context, there's effectively no protection or minimal protection just to, you know, give some somewhat of an image of what the difference is.

    Alina Chan 49:48

    Yes, and BSL two is very variable around the world. So it's not like it's one standard, uniform lab that's shipped to every country. Now every institute even sets up their own BSL two and sets up their own best practices and like policies, so these are two, as far as I know, most of them do not have any enforceable protocol where if you get sick with a random like cold or something, you have to report or take samples. No, that doesn't happen at BSL two. In fact, I've seen a lot of shoddy practices at BSL two, it's not even thinking about foreign countries, it's about things I've seen in North America

    Marty Martin 50:21

    In general, yes.

    Alina Chan 50:22

    That there are parts of the experiments that sometimes are done outside of the hood of the cabinet where you're slightly more protected. But actually, that cabinet protects your work. It doesn't protect you. But it's not built to protect you. It's built to protect your work. And there's so many things that can happen just splashes like aerosolization of things that can happen at BSL 2. People using their gloves, on doors and on your cell phones. I've seen people touching the experiments with the gloves, then reaching into the pocket and bringing the phone up to their ear. There are lots of things that have been at BSL two. But I also want to point out one thing is that there is photographic evidence of these scientists when they're collecting viruses, not wearing proper PPE. So there are photos of them with no gloves, no masks, just handling the bats. And I would say that it's not because they are terrible people who don't mind causing a pandemic, it is because these virus hunters had spent so many years collecting samples, that their level of cautiousness had dropped.

    Art Woods 51:23

    Yeah, they sort of forget about the risk. Yeah.

    Alina Chan 51:26

    There's simply no way to have a bio containment condition when you're sampling for viruses in a cave, right. You're surrounded by hundreds of thousands, or maybe even millions of bats flying everywhere, pooping, dropping on you, like biting you, unless you suit up, you know. And that makes it very difficult for you to move around and to crawl into these tight spaces, so there were conditions when they just went out there without PPE to take samples.

    Marty Martin 51:49

    And I mean, again, from personal experience trying to do this research, when you are wearing all of this equipment, remember that the average bat that they're working with is very tiny, the more gloves and the more coverage you have on, the less dexterity you have. And it's not to say that you want to trade off risk of exposure by having no gloves on versus risk of exposure, because you're trying to handle equipment with a tiny bat in the hand. But these things are particularly difficult. Not all of the bats, of course, will be infected, if you're working with 100, maybe it's one maybe it's far less, it's not to excuse negligence of safety protocols, but at the same time, there is a complexity that happens here that would make some sense of the pictures that you were talking about.

    Alina Chan 52:28

    Yeah, that's actually a snippet of an interview in David Quamman's book Spillover, where he is on a trip with one of these EcoHealth scientists in China looking for SARS-like viruses in a bat cave.

    Marty Martin 52:38

    I remember this part of the book, yeah.

    Alina Chan 52:40

    And he suddenly realizes- I'm not wearing any PPE, I'm not wearing any protective equipment, but we are hunting for SARS-like viruses. So he asked his EcoHealth like guy and he says: "Hey, why aren't we wearing any, you know, masking gloves, that kind of thing?" And the guy says: "Well, it's kind of like wearing a seatbelt. And my assessment is that on this trip, we don't need it. So I don't tell anybody to wear it." So it's just subjective, like just on that day.

    Marty Martin 53:03

    And there's plenty of people that go on vacation walking in caves and things, you know, if you're going to collect bat samples, or take the bat guano off the floor, then you're going to suit up. But if you're just walking across that same floor, your risk is really not all that different. In one case you're on vacation. In the other case, you're doing research.

    Alina Chan 53:18

    Exactly these scientists, they were looking at the tourists walking in their flip flops, and they think: "Why do I have to be suited up?"

    Marty Martin 53:24

    Exactly.

    Alina Chan 53:25

    And so they eventually started catching these bats and bringing them back to the lab as well. And there's videos of these two at the WIV, like they even filed patents on how to build cages for breeding these bats.

    Art Woods 53:36

    Speaking of that, you know, we're imagining these scientists studying these viruses, culturing them. They must be cultured in animals or cell lineages, so what are those animals? What are the cell lineages? Just draw the picture for us.

    Alina Chan 53:48

    Okay, so you;re this virus hunter, you've collected these tens of thousands of pathogen samples, now what? So you shipped them all back up to the lab? And you first want to find out how many of these samples have the viruses that you're interested in? So certainly, almost every sample has pathogens in them, because you're collecting it from wild animals, but how do you find the viruses that you are specifically interested in? So you run a quick DNA or RNA test to search for the genetic material, a very highly conserved part of the virus type you're interested in. And so they will do this routinely for SARS-like viruses that would go to track how many of these samples have a SARS-like virus in them. And when they found such samples, they would try to grow the virus out of them. And initially, they were quite clumsy with it. But over a decade, this lab built up some like unparalleled levels of resources and a pipeline for isolating these viruses. So they would, they had this range of different cells in the lab from primates, from humans, from bats, from pigs, and they would put the samples from wildlife samples onto the cells to see if they could get viruses from there. And sometimes at first try they couldn't. So they had to do this thing where they thoroughly passage those viruses through cell lines. So they would posit multiple times through cell lines. And eventually, they would see that cell death was occurring, that meant that the virus had been found. So virus had been grown. And so this very routine practice actually is capable of causing adaptation.

    So you've just taken a bat virus, or let's say, you've collected a wildlife sample from a bat or raccoon dog even. And you've taken it to the lab. And you've just done this thing where you've passed it several times over cells to try and encourage it to be able to grow to infect cells. So by like five passages or something, that virus has picked up many mutations, adaptive mutations that weren't apparent in the wild, and they showed us very clearly for one case, where they were tracking a swine virus. So something that was infecting farmed pigs, is that initially, it couldn't grow in primates, like monkey cells, but by the time they pass it through five times over these cells, they could see cell death. So that virus had adapted to be able to grow out in the lab. So there's nothing inherently nefarious about this process. It's just something that is done in these labs to be able to grow the virus and to study it in the lab.

    Art Woods 56:04

    And to be clear that's a potential explanation for why there was not a lot of early evolution in the SARS-CoV-2 lineages that were found in Wuhan, that they had been previously passed, done this serial passage technique.

    Alina Chan 56:16

    Yes. And unfortunately, this process can cause the virus to become adapted to different species in the lab of the cells, to be able to latch on to receptors on these cells and to enter and to replicate, to use the machinery in these host species.

    Marty Martin 56:30

    Right okay. Well, this is a good time to go back to what we had promised to talk about the furin cleavage site, maybe say a little bit about the sort of degrees of confidence that we have, or the given your expertise and what you know, from the literature, what's the more likely scenario? That through a passage this adaptation happened or through something more active, you know, a researcher finding this particular gene and intervening it somehow within another existing virus. I mean, which one of those is more technically plausible, which one of those seems more likely based on the records?

    Alina Chan 57:05

    So the furin cleavage site is a feature in the spike of SARS-CoV-2, and it helps the virus to infect cells. So it's a way to activate the spike. And it's the reason why the SARS-CoV-2 virus can infect so many different cells in your body, wherever the cells are producing furin, that's where the virus spike can get activated, to grow, to allow entry into the cell and to infect and grow and cause disease. SARS- CoV-2 is the only SARS-like virus of dozens have been studied and found so far that has such a feature. And so the question is, did this emerge naturally? Or was it put in the lab? Or did it result from that manipulation? So on the natural side of things, there are scientists arguing that there are furin cleavage sites in other coronaviruses, for example, MERS has such a furin cleavage site feature, so not the exact same sequence, but it also has a furin cleavage site at that spot in the spike. So they say if nature can produce this, why do we need to say that it came from a lab? But on the lab side of things, the most striking piece of evidence is that in 2018, this Wuhan scientists, alongside the US collaborators, had said we're going to put exactly this feature into cells, like viruses in the lab. So they don't give you the sequence but they say exactly this furin cleavage sites, we're gonna find them in the wild, we're gonna look at sequences were found in the wild, take those furin cleavage sites, perhaps optimize them for humans, and then put them into cells like viruses in the lab, they also don't name the cells like viruses in the lab, and we don't know what they had in the collection. For me and others, this striking coincidence that in 2018, the scientists said they're gonna do this furin cleavage site insertion, and then less than two years later, a SARS-like virus with a furin cleavage site is rampaging in their city.

    Art Woods 58:45

    Yeah the timing is suspicious at the least. Yeah.

    Alina Chan 58:47

    It could have been any pathogen, it could have been any city, it could have been any year that the pandemic started. But it was precisely a SARS-like virus with a novel furin cleavage site in Wuhan city, two years after the scientists there proposed putting furin cleavage sites into SARS-like viruses.

    Art Woods 59:03

    Yeah and as I understand it, this information came out from a grant proposal, I think, to the NIH, right. There was a collaboration between- oh DARPA okay. And and it was it was not funded that that research proposal, right, and yet, the suspicion is that some of the work was done anyway>

    Alina Chan 59:20

    Yes. So most scientists don't write grants that have, that just describe experiments that haven't been done. So you don't want to appear foolish in front of your your grants managers or-

    Art Woods 59:31

    You want to know that you can do them.

    Alina Chan 59:32

    Yeah you want to have some level of assurance. So at least part of the, you know, the plan must have been the risk, must have been tested preliminarily to see is this even feasible. At the end of five years, you don't want to show up and be like, oh, all of these ideas were really ambitious, but bad. We didn't get anything done. So there are even some labs that write proposals where like all the work has been done. Just about to publish it. Yeah, they just want money.

    Marty Martin 1:00:01

    Yeah, it's a cycle. You have all of the data, we call them as scientists, we call them preliminary data, right? So these are the data for the not-quite-finished studies that justify more money for bigger studies or a follow up or something like that.

    Art Woods 1:00:13

    And sometimes your preliminary data gets published in Nature.

    Marty Martin 1:00:15

    Sometimes your preliminary data is the end of the story. Yeah, I think that's what it is. But that just adds, I mean, again, it's one of those pieces of color from a lot of conversations about this particular part of the story that I haven't heard a lot about that I don't think is percolated into the public so much. I mean, it's not like when a grant isn't funded, that means the research was never done. I mean, there's at least a timeliness about this preliminary thing we were just talking about. But big entities like this have funding coming in from many different places, there are many different parties involved all over the world, in this case. Facets of this could happen, you know, not independent of whether the money comes, you may need that money to take it over the finish line. But any successful competitive scientist like to say, would have to have done parts of this to justify so much money coming back to finish the work.

    Alina Chan 1:01:02

    Plus popping these cleavage sites and do novel viruses had become increasingly trendy amongst virology. I don't mean to say that they will all be risking pandemics, but they were doing it to study viruses. They were doing it to understand how viruses can be made to grow in different cells and in human cells in the lab. So it was just a thing that was increasingly done. It wasn't something that was like taboo, that was obviously like dangerous, obviously too expensive to do. And in fact, the WIV itself had recently been co-authors on a paper where a furin cleavage site had been put into a MERS-like virus spike. So for them, this was just a natural progression. They've been talking amongst them and their US collaborators, they've been talking nonstop about cleavage sites and spikes of coronaviruses for like five years by that point. So for them, this was just a natural progression. It wasn't something that was particularly new, or particularly unapproachable, or expensive.

    Art Woods 1:02:04

    So let me just zoom out here and say it sounds like it's some high level this there's two possibilities here. One is that the furin cleavage site got in naturally, somehow is a natural recombination event and it spread, you know, either by zoonotic event or by a lab accident. Another possibility that also is firmly within the lab leak sort of realm hypothesis is that the furin cleavage site was engineered. Of those two, what do you think the odds are of the engineering hypothesis being correct?

    Alina Chan 1:02:31

    I think the only way to tell is to look through all of the lab records, which are completely off access now, or to look to the communications between the Wuhan scientists and their partners internationally. So surprisingly, that has still not been done, because the idea to put furin cleavage sites into SARS-like viruses actually came from a US collaborator. So it's possible that one scientists, if they did it by themselves, to carry on the idea by themselves in their own lab, with their own resources easily done is that they might have talked to some of their collaborators in the States just to bounce some ideas off them. Again, this wasn't a thing that was like military or like, particularly seen as taboo,

    Art Woods 1:03:08

    Scientists talking to each other, yeah.

    Alina Chan 1:03:09

    Yeah, it's shocking that none of that has been investigated. And furthermore, when the pandemic started, these US collaborators who were aware of this plan did not tell the public. So they did not tell the public that oops, like two years ago, we told our WIV collaborators, that it would be interesting to pop some furin cleavage sights into SARS-like viruses, none of them came forward that. It was only in late 2021, that this research proposal was leaked to the public.

    Art Woods 1:03:35

    Right, another point is, you know, if this engineering process is what happened, then there must be records of something very, very close to SARS-CoV-2 existing in the WIV, right. And yet, there's been no viruses apparently disclosed or discovered that are, you know, more than 2 or 3% different than SARS-CoV-2, right, which is still pretty distant, right for a virus 3 or 4% is a long ways away in evolutionary time.

    Alina Chan 1:04:00

    Yes. So, at the time that the SARS-CoV-2 outbreak was detected, the closest relative was in the possession of the WIV. And this was a sample that was collected in 2013, from a mine where people had sickened with an unresolved respiratory illness. So there are some pieces covering this incident. One of them is a medical thesis by the doctor who treated these patients. And their conclusion was, it was most likely a SARS-like virus from a bat that caused these patients to sicken. And half of them died. So three out of six died. They did not diagnose them early enough to collect samples that would have allowed them to track the viruses. But according to these theses, there are two of them a medical thesis and a doctorate thesis, from the actual Chinese CDC directors lab, saying that samples have been sent to the WIV from these patients and that antibody tests had found antibodies against SARS.

    So I mean that you know, the fact that this story wasn't revealed by the WIV on their own initiative in early 2020 to the public, I think it made a lot of people very distrustful of them that how much are they not telling us. And furthermore, as more close relatives of this pandemic virus were found by other groups, some were found in Laos, so a Southeast Asian country bordering South China, where that mine had been located, actually. The EcoHealth Alliance denied ever going down to Laos with the WIV to collect samples from there. But then just upon checking the public literature, you could see that actually, they started doing that they had been collecting samples from Laos several years before the pandemic even. So, there's this track record of them sort of reacting to the public, or not sharing information that is reasonably important to understand, until forced to.

    Art Woods 1:05:42

    But so that 2013 virus, and I think we're talking about, what RaTG13 is that it?

    Alina Chan 1:05:48

    Yes.

    Art Woods 1:05:49

    Was say 96ish percent similar to SARS-CoV-2 and the one from Laos, the collections from Laos, were like 97%, similar to SARS-CoV-2, but that's still a long ways from 99.99% similar to-

    Alina Chan 1:06:04

    Yes, exactly, so the RaTG13 is like 96.2%, and the Laos virus is 96.8%. So these two are still fairly diverged from the pandemic virus, but you still need to understand whether a 99% match had been collected by the WIV in between 2016 and 2019, and worked with.

    Art Woods 1:06:26

    So they may know that they have that in their collection, or were dealing with it, but it's just never been disclosed.

    Alina Chan 1:06:30

    Yes. So there is this striking interview published in the Scientific American, where Shi Zhengli, she's the scientist leading that lab in the WIV that's collecting all these bad virus samples. She says that when she first heard about the outbreak, she thought, how could this have happened in Wuhan? They never expected such an outbreak to happen in Wuhan in Central China. Because these SARS-like viruses were mostly found in South China or Southeast Asia. So for her, for something to happen in her city was shocking. She said she ran back to her lab and went through all her records, she couldn't sleep for nights, until she realized that she said it wasn't from her collection. So she didn't see any trace of that virus in her collection, that's when she was relieved. So again, this idea that even the top experts in precisely this virus type did not expect it to be emerging in their city in Central China. So it's clearly not conspiracy theory, like they themselves thought it was more likely that it might've come from their lab.

    Marty Martin 1:07:25

    So the other lab that I mentioned once, I mean, where does the Chinese CDC this research place that was so close to the Huanan market? Where is it now stand in this story? It sounds like everything we've been talking about so far really points more at WIV, except what you just said about the director of this part of the research looking and it's not in our collections? Do we know anything? Do we have ideas about what the role of the CDC was?

    Alina Chan 1:07:50

    So in the early days of the pandemic, actually, one of the earliest people to say that the virus might have come from a lab was Chinese scientists. So there were two Chinese scientists and one who put up this online report or preprint, saying that pointing to this Wuhan CDC, and also the WIV. So they they pointed at the Wuhan CDC which had just released actually a promotional video of their scientists going out and collecting these bat viruses, in which he said that he was all suited up, but he said that he had been exposed several times like bats urinating on him biting him, that kind of thing. And then he would quarantine himself, because he knew that it was a chance exposure that could lead to outbreak. And so they pointed out to this Wuhan CDC that had just in 2019, relocated, took several months relocating across the city to just a few, like maybe even like two blocks from that market from the Huanan Seafood market. So it's just in the center of Wuhan city, is what it means. So they said, rather than the market, it might have come from that then.

    Today, though, I would say that because that Wuhan CDC much be sampled bats in the Hubei Central China area, I don't think that they would have had collected the precursor to SARS-CoV-2, which I think most scientists would tell you most likely came from South China or Southeast Asia up into Central China. So it's not that it came from a bat in Central China, and infected animals and then people in Wuhan is that there must have been the South China or Southeast Asian ancestral bat virus that slowly made its way up into Wuhan city eventually. So I don't think that Wuhan CDC is a particular focus for me right now. I mean, they are located very close to the Huanan market. But again, both of these sites were right smack in the middle of the city. And if since we understand that the outbreak had been widespread by then, by late December, is it really shocking that it would be all over the market? And if they had gone into like the hospitals and even the subway station and taken swabs there, I'm pretty sure they would have picked up the virus then? So for me, the location is not so strong as much as the city of Wuhan out of all of the other thousands, possibly tens of thousands of other dense human hubs in China and Southeast Asia.

    Marty Martin 1:09:59

    Okay, okay. There's so much to talk about we have, we don't want to keep you for several more hours.

    Alina Chan 1:10:03

    You could write a book.

    Marty Martin 1:10:04

    Yeah you could write a book. Let's zoom out and start to talk about what we can do better next time, because I think there's just sadly no way that there's not another next time of some form. In this particular case, though, how do you think we get to closure or as close as we're ever going to get to closure in this scenario? I think in the end of the book, you almost appeal to Chinese scientists or other folks in China that were involved, and maybe were reasonably worried about talking about what's going on. So do you imagine that's going to happen soon? Or do you think that information that we've not had is going to come out by some mechanism in the near future?

    Alina Chan 1:10:48

    So like I mentioned earlier, I believe that this question of how the pandemic started is too important to China, the Chinese government to leave a mystery. I think it's reasonable to believe that there are people in China who know exactly how this started. So they may not have like physical proof of it, but I think there are people who know and so it's just a matter of time before that truth comes out. It could be next year, it could be 10 years from now, it could be like 50 years from now, people just don't know. But this matter where you have 20 million excess deaths, due to the pandemic is too big to just forget to just like, let it be. And I know that a lot of people today have this feeling like this must be the last pandemic of my lifetime, you know. A lot of people like this will never happen again in my lifetime. But we have no guarantees of that, because whether it came from the wildlife trade, or from a lab, those two activities are still largely going on and proliferating. In fact, for the lab research, especially due to the pandemic, there's been so much more funding and interest in tracking down novel infectious diseases tracking down novel pathogens. So there are a growing number of laboratories around the world, again, with varying standards of biosafety, all going out there taking samples from animals and sick people and bringing them back to the lab for study. And so I'm not that optimistic I don't think that this is the last pandemic or outbreak or major outbreak we'll see in our lifetimes. And I think it's important to take action.

    But herein lies the problem is that you have to battling factions. So on the one side, you have people who say this must have come from a raccoon dogs are on the market. And so we need even more virus hunting, we need even more virus manipulation, we need even more gain of function, like research in labs, so that we can prevent these natural outbreaks. And then on the other side, you have people who are saying, hey, this probably actually likely or plausibly came from exactly that type of research. So you should be banning them or should be restricting them or like offshoring their research into like remote islands where there's like, you know, a month's worth of quarantine, so that these two factions battling, and unless the origin of COVID-19 is revealed to a reasonable degree, I don't think that they will reach a like consensus, there won't be any way to move forward. There have not been actions taken to effectively combat the wildlife trade, or the proliferating virus research, like risky virus research. On that point, I just want to be super clear that virology like 99.9%, like fantastic, good essential work, but they're just like, very niche group of scientists like very, super niche, only a few labs around the world are doing this type of work, where they are unintentionally or otherwise enhancing these natural viruses, and that might bring them to be able to cause human outbreaks.

    Marty Martin 1:13:36

    Yeah. Well, one of the arguments that I know has been made about the WIV continue to do gain of function research and these kinds of things is that it's going to help us. Like I think one of the original motivations of EcoHealth Alliance, and the collaboration with the WIV, was to produce a vaccine that was protective against all sorts of SARS. So we had SARS-1 and then SARS-2, this was worked on before SARS-2, but in principle, there'd be a SARS vaccine to protect against anything that could ever emerge.

    Art Woods 1:14:04

    Right. That's a super noble goal, right?

    Marty Martin 1:14:05

    Yeah, it's a very noble goal. And it's quite likely that of things to emerge, these viruses would be in that set. I mean, we've been talking about that once the first SARS was was discovered. But is that really justifiable? I mean, especially in the case of the innovation that was mRNA vaccines, I mean, and the rapidity that those were brought to market relative to the traditional way of developing vaccines. Is that reasonable now or is that not really going to be part of the control mitigation of the next pandemic?

    Alina Chan 1:14:36

    I think we've kind of seen from this pandemic, how resistant people are to vaccines.

    Marty Martin 1:14:40

    For very different reasons.

    Alina Chan 1:14:44

    Maybe lofty, but less practical goal. I guess it's this idea of creating a pan-coronavirus vaccine and delivering it to people in time that you could delay or to stop a pandemic completely. But I think that although, there's some scientific basis to it. I think it's been kind of always sold. So this idea that you can stockpile these pan-coronavirus vaccines and then give them to who, the military? Like, how are you going to put it down on all the health care workers around America, even like? I think most of them will just boycott.

    Marty Martin 1:15:17

    At least in the near future, yeah.

    Alina Chan 1:15:20

    I can see from a scientific level that this is very interesting and you know, noble, but from a human level, having lived through this pandemic, it seems like it's not going to work. Like what works is like building secure channels for information, for information to flow internationally. And incentivizing whistleblowing, incentivizing good journalistic investigations. And there's, there's some things in the scientific community that can be done too. So one thing we've seen is that there are many of these organizations, funding organizations, database organizations, journals, that they have a very closed door policy about what information they have. So even the scientists sending in information about human to human transmission, and the journal was like, I can't do anything because this is the property of the scientists. But I think we have to rethink this for this specific field on infectious diseases is that no, it's not, it's no longer the property of the scientists that there is a moral obligation to release it in real time. So a lot of these have to be changed to prepare us for the next pandemic. And I think a lot of it is building public trust as well. And that is one thing that's taken a major hit, like major, major hit in this pandemic. So this idea that we're going to vaccinate all these healthcare workers or military people with like pan-coronavirus vaccines upon the news drop of a novel pathogen?

    Art Woods 1:16:37

    It just seems like pie in the sky, right?

    Alina Chan 1:16:39

    Yeah, it's just like, not reasonable, I think. Yeah.

    Art Woods 1:16:43

    So we've touched on some aspects of this, but you know, if you were made the director of CDCs around the world, let's say the American and Chinese CDCs, what, you know, what, what would you do to make this sort of virology research safer?

    Alina Chan 1:16:59

    I mean first thing is moving them out of major cities. A lot of scientists say that, but if you move them all the major cities, then no one wants to do this work anymore, and we won't be able to recruit talent. But I think that's utterly untrue, because a lot of the top scientists are no longer physically doing the experiments themselves, they have very skilled technicians doing the work. So you could build these very high security, high biosafety facilities with strong quarantine and testing measures in a remote area, like, ideally a place that's, you know, in an island, where there's no cars driving in and out, like, there's very reduced chances of exposure, rather than right now, where you have them in the middle of the city, sure you have procedures for them to decontaminate, but the person can literally get exposed in some way due to accidents, and walk on the streets into the nearest like coffee shop or bar. If you want to do the gain of function research, do it in a very high containment condition. So I think that this is not a high, this is not an unreasonable request for the public to make when their lives are at risk.

    Art Woods 1:18:02

    Would you prohibit gain of function research?

    Alina Chan 1:18:05

    No, I don't think so. Because the thing that when you prohibit this type of research, it just goes underground. So that's my same idea with with journals, publishing the sort of work is that I'm not saying that they should never publish their work, but they should set some very strong criteria for publishing this work, which is that you will not publish work that describes things, sequences that were not published within a month of sequencing, let's say. So if you instituted such a policy, then people would have to very quickly share sequences they found online, or at least in into some international confidential database so that we don't have this problem now, where we're like, oh, we don't know what viruses they collected in the past three years. So I think that there are things that can be done to make this work more safe and more transparent.

    Art Woods 1:18:58

    Well, we're getting to the end. We want to ask you first. So what's next for you on this topic? You know, are doing research on this in the lab, are you thinking of writing another book that follows up on additional information that's come out since Viral appeared? What's next?

    Alina Chan 1:19:12

    So when I had written Viral, and it was released in November 2021, I had thought that that point, okay, now, a bipartisan commission is going to be initiated, and there's gonna be a fair, credible investigation of how this started and how it was responded to. That didn't happen. 2022 arrived, I thought okay, this is the year, it didn't happen. And then 2023 arrived. And again, it didn't happen. So I have to say, I'm not now no longer very hopeful that such a commision will happen. But what is happening, at least is that there is a select subcommittee that is, of course led by the Republicans, and they are pulling out all sorts of information from different parties and although I don't agree with their strategy, I do think that dribs and drabs of things are coming out. So even if it doesn't point us exactly at lab origin, even if it doesn't give us certitude, at least they are asking questions and trying to get information. So for example, one one bill that was passed, like the COVID origins bill, I think, of 2023. It asked the intelligence community as a director of national intelligence to release all information about what they know, connecting the web to the original COVID-19. Unfortunately, the DNI decided not to do that. So they put out this really extremely brief, like, report, most of it was just like summaries and like legends, they told us barely anything. But what this means is that there is stuff that's not in the public domain yet. And I think seeing is how the FBI and the Department of Energy, so these are the two agencies have arguably the strongest scientific expertise, they actually have scientists in there to help like interpret this data and evidence, that they are both leaning towards the lab now, I think it's likely we're gonna find out a lot more. I think there's information here in the US, either that hasn't been found or is private, that eventually the public will learn about.

    Marty Martin 1:21:06

    Okay, so last question, Alina, if you could ask anyone, at any point involved in the story one question, what's the thing that you would most one answered?

    Alina Chan 1:21:15

    Anyone?

    Art Woods 1:21:18

    Yeah, this is a superpower.

    Alina Chan 1:21:20

    I mean, wouldn't I just go straight to the one scientist and ask them if it came from the lab?

    Marty Martin 1:21:24

    I kind of expected you to say that I mean, is another way to say that, that having access again to this database, and the opportunity to dig into it, that would be about the most valuable thing we could have now?

    Alina Chan 1:21:38

    Yes, I think that if there was a way to, to find the 2019, or early 2020 version of these databases, and lab records, that's where you would get evidence either ruling out or confirming a lab origin of COVID-19. But we clearly might never have access to that. So I think getting the personal testimony from these collaborators as well, maybe not in the public hearing, but just calling them into a private interview and saying, just tell us when you know, you know, this sort of thing. Like, we understand that in early 2020, a lot of people thought this was just gonna go away, like the first SARS outbreak in 2003. But now we are stuck with this virus that will never leave humanity. All of us are just getting serially vaccinated and boosted into infinity. And like just new variants coming every year. And even our children have to be vaccinated, like it's just like this is fine, but it's too much to have happen again. And we need to know how it happened. So anyone who has vital information, like what are you waiting for?

    Art Woods 1:22:39

    Yeah, this has been a really great conversation, Alina.

    Marty Martin 1:22:42

    Yes, it has.

    Art Woods 1:22:43

    Thank you so much for walking us through all of these details and writing the book, it was really, really eye opening for me. Before we go, is there anything else you'd like to say? Any thing that we didn't cover?

    Alina Chan 1:22:53

    Yeah I would say that there's something I want to say about gain of function research and assessing risk of these experiments is that this proposal from 2018. What it shows us is not just that scientists had the idea to put furin cleavage sites into cells like viruses is that these top scientists, were not able to accurately assess the risk of this work. So fast forward to today, if anyone is submitting a grant to the NIH or DOD saying I want to put furin cleavage sites in the SARS-like viruses, I don't think they will get funded because people like this is a pandemic risk. But then 2018, before the pandemic started, these top experts in the world studying SARS-like viruses, didn't think that this experiment was too risky to be worth doing. So what that means for people today is who can you trust to accurately assess risk? Who out there can actually tell you this experiment is likely to start a pandemic? I think this is a really tough question to ask. And it has implications for like hundreds of millions, potentially billions of dollars, how it's spent on this type of research, as well as preventing and responding to these outbreaks. That's the future-facing question that's on my mind.

    Marty Martin 1:24:04

    But Alina, again, thank you so much for your time to talk about things, thank you for the effort that's gone into, you know, initially writing the book, and then having the interest and passion to make sure that the public knows about this kind of thing. Like you say, at your career stage, that's especially impressive and risky. And I just think it's fantastic that you've done that.

    Alina Chan 1:24:28

    Thanks for inviting me on Big Biology.

    Marty Martin 1:24:43

    Thanks for listening to the show. If you like what you hear, let us know via X, Facebook, Instagram, or just leave a review wherever you get your podcast and if you don't, we'd love to know that too. Write us at info at bigbiology.org

    Art Woods 1:24:56

    Thanks to Steve Lane who manages the website and Ruth Demree for producing the episode.

    Marty Martin 1:24:59

    Thank as well to Dayna de la Cruz for her amazing work on Instagram and X. Keating Shahmehri produces the fantastic cover art.

    Art Woods 1:25:06

    Thanks to the College of Public Health at the University of South Florida and the National Science Foundation for support.

    Marty Martin 1:25:11

    Music on the episode is from Poddington Bear and Tieren Costello.

    Transcribed by https://otter.ai

Big Biology