Animal origin theory suddenly has a lot more weight behind it

Tegan Taylor: Hi, it's Coronacast, a show all about the Coronavirus, sometimes other nasties but not today. I'm health reporter Tegan Taylor, coming to you from Jagera and Turrbal land. 

Norman Swan: And I'm physician and journalist Dr Norman Swan, coming to you from Gadigal country. It's Tuesday, March 21, 2023. 

Tegan Taylor: And, Norman, I want to play you something, a little trip down memory lane. 

Eddie Holmes: When I was there in 2014, I actually took photographs of these things called raccoon dogs, there are very strange animals that are found in China. And they were there being sold illegally in the western side of the market. 

Tegan Taylor: So that was Professor of Virology at the University of Sydney, Eddie Holmes, I think you've met him once or twice. He was talking to us back at the beginning of last year about a trip he made some years ago to the market in Wuhan, which was thought to be the epicentre of the COVID-19 pandemic. So that was a year ago. 

Norman Swan: Yes, and that was the occasion of a paper that he published in a leading journal called Cell talking about the genomics of the virus and the history of the virus. 

Tegan Taylor: So I'd thought that I hadn't ever heard of raccoon dogs before, but obviously I have, I just blocked it out from my memory. They're very cute. But they're back in the news again this week because some more information has been released from the market. 

Norman Swan: It has and it's been quite dramatic, and there's been a dramatic few days here. So just to set the scene, because we've got Eddie on the line to come in to this week's Coronacast, the market was thought to be the origin of where the first cases were documented in 2019, there was a lot of swabbing that went on, and the market was closed. And, as Eddie said in that grab, there were cages where live animals were being sold, particularly these raccoon dogs, and they've been back in the news. Data were released last year in a paper from China, which was a bit odd, and we'll get Eddie to talk about that, but then a really dramatic release of data happened on the 9th of March. Welcome back to Coronacast, Eddie.  

Eddie Holmes: Hi there.  

Norman Swan: So tell us what was in that paper a year ago from China, because, in a sense, that's where the more recent story kind of began. 

Eddie Holmes: Yeah, well actually it began on January 1, 2020, when they closed this market down. So if your listeners remember, it's a place called the Huanan market in Wuhan, and I went there in 2014, and this was the location of the earliest cases of COVID-19, people who were working there or living right by it.  

So when they had the outbreak, they closed the market and the local public health authorities went in to do an inspection to try and find out what the cause of it was, and critically they swabbed surfaces, so they swapped door handles, benchtops, drains, the cages, gloves, lots of different things. And then when they had those data they tested them for the virus, for SARS-CoV-2. So what we did and what other people did was you take like a physical map of the market. There's an east side of the market and a west side, both these two sides about the size of a soccer field each. And then we plotted where the positive cases were on that map of the market.  

And as you alluded to, in that Cell paper what we found was in the southwestern corner of the market, there may have been 10 or 20 market stalls there, that was where most of the positive samples were. And amazingly, that was where we thought the wildlife was because that's where I took my photograph of animals in cages in 2014. But we couldn't really prove it.  

Now, this is the key thing, as well as doing the testing for the virus, those swab data they had, they also gave you a clue as to what animals or humans were at those particular stalls. So if you take that swab, and you can actually sequence all the genetic material in that swab, so not just the virus, but all the human DNA, cattle DNA, whatever it was. And we knew right from the get-go that this information was actually really key because it could actually tell us…if the market was just a human event, only humans, all that extra DNA in that sample other than the virus would be human. But if there are animals in there, we will see traces of animal DNA. So we knew that was there. And those data (we can discuss this later on) these data were actually available or generated in early 2020, right, so three years later now we are… 

Norman Swan: So they were generated but not necessarily available. I mean, that's key here.  

Eddie Holmes: Yeah, not available. And I think one of the questions is…and you've already heard the World Health Organisation complain about this, and I myself am furious about this, is that these data could have been given out three years ago, right, and the whole last three years would have been different. This is just an extraordinary event.  

So last year, as you mentioned, a Chinese team that did this swabbing, they posted a preprint of a paper online. It didn't have the raw data but it said in this preprint that all that extra genetic material in the swabs was human and there were no animals in there. And many of us were thinking, well, that just can't be right, this is an animal market. For example, they took swabs from a thing called a defeathering machine, sounds pretty gruesome, but that can't just have human DNA on a machine that is used to defeather animals, this can't be true. So people were sceptical. So that preprint sat there, it didn't move, it was never published, and there was no access to the raw data. 

Norman Swan: And what I understand is they tried to publish it in Nature, they asked for the raw data and the raw data never appeared, so the paper never got published. 

Eddie Holmes: Yeah, that's a story that I've heard as well. So then what happened was, and it's all gone so quickly, Norman, my timeline is a bit thrown, but it was only about ten days ago or nine days ago that one of the people I work with who has continually been interested in the market noticed that on a website called GISAID, and that's like a big repository for genome sequences, and so there's 15+ million SARS-CoV-2 genome sequences on that database, they noticed there were these strange sequences that appeared. And we realised that that was these data that we wanted, this key data from the swabs from that original market survey, and it might tell us what animals were there. 

Tegan Taylor: Who's the 'they' that hasn't released them until now? And then how do you know that it was the real data when you did see it pop up on that website?  

Eddie Holmes: So, what happened was, 'they' were a team led by the Chinese CDC, Chinese Centre for Disease Control, they were the people conducting the investigation in Wuhan. And if you actually look at the database, they are linked as the people who submitted it there. So when we saw these data, I emailed a colleague of mine in China who was part of that team, a good friend of mine actually. He doesn't work at the Chinese CDC but he was associated with them. And I asked him, I said, are these data important? What's the story? And he wrote back and said basically, 'Yeah, we told them to release the data, please go ahead and analyse them and let me know if you have any questions.' So it was very…it was like the green light for us. So we then downloaded these data and started to analyse what was going on.  

And then I think it was last Saturday morning, like at 3am, my phone was going crazy, so I foolishly kind of looked at what was going on. And my colleagues in the in the US and Europe who were doing this work with me, they had found all this animal DNA in these market samples. Not only that, they found raccoon dogs, and raccoon dogs were one of the key species in our Cell paper we suggested were the intermediate hosts that can host the virus. And also that was the animal, remarkably, that I'd photographed in that market in 2014. And I've sent you these photographs, Norman, there are photographs of these raccoon dogs. And suddenly there it was.  

And again, remember, this is the critical thing, when the market was first described as a potential place where this virus emerged, the Chinese authorities said there was no live animals in the market, no wildlife. Okay, suddenly now we've got not just raccoon, lots of other species like bamboo rats, porcupines, civets, hog badgers (by the way they're very good to look at, the hog badger, I recommend everyone looking at what a hog badger looks like), hedgehogs, it's like a zoo in there. And so we thought, oh my God, this is extraordinary.  

So then I emailed this colleague back in China, I said, 'We found raccoon dog, this is amazing. We want to publish. What are your plans?' And then a few hours later the data was removed.  

Tegan Taylor: Oh! 

Norman Swan: Who removed it?  

Eddie Holmes: Well, extraordinary. So it's not clear who actually removed it. Was it the website? Or was it the people that…the Chinese CDC that put it on the website? We don't really know, but it just disappeared. It was just extraordinary. All the market data suddenly disappeared from that website.  

Norman Swan: But you had downloaded it, so you've got it.  

Eddie Holmes: Yeah, we had downloaded it and we'd put it on a number of different computers around the world. And actually it turns out we weren't the only people, some other people had also seen it and downloaded it, but they didn't have it all. We managed to get all of it downloaded. 

Norman Swan: So the scientific question now of course is; is there a smoking gun? Because the question is; is there an intermediate animal, was there an animal infected and that animal infected humans? And to explain what you've done is that you've taken these samples by where they were collected in the market, and looked at the balance of DNA that you find in the samples. First of all, it was (I mean, to get technical) mitochondrial DNA, which is easier to measure, but then you looked at the DNA in the actual genome itself, and found correlations there. And what you found, you believe, is strong evidence that the animals were infected. Just explain what you found. 

Eddie Holmes: Yeah, so it's DNA and it's RNA. So SARS-CoV-2 is an RNA virus, so RNA makes RNA, there's no DNA in there as well. So we have RNA and there's DNA. So we have two things. The first thing we did is look for mitochondrial DNA, as you described, that's a very good marker for what animals these samples are from. And so if you do that what you find is there's a whole range of animals in this market. I mean, some are quite as you'd expect, for example there was a cattle stall and we found there was some blood there and that turns out to be beef blood. Okay, there were some fish stalls and we found fish DNA, and that was for the Yangtze River carp, and of course Wuhan is on the Yangtze, so fresh fish. Okay, so that's pretty good.  

But then in this one corner what we found was lots and lots of this wildlife DNA. Originally we were told there was no wildlife in the market. So again, raccoon dogs, hedgehogs, porcupines, bamboo rats, civets, marmots. Now, the key thing, the really important thing is not only was there lots of these animal DNA in there, but they were often more common than the human DNA. 

Norman Swan: And just to explain, before you go on, you also found virus there. 

Eddie Holmes: Yeah, and virus, these are all virus positive samples. And this is the most remarkable thing of all, Norman, so when I took my photographs, and they're pretty rubbish photographs, my wife was always telling me how bad they are, and I was just taking them because I thought these are kind of weird things to see. In that stall that I took a photograph of I saw raccoon dogs and I saw ducks, raccoon dogs on top of webbed feet you can see in these photographs, so raccoons on top of ducks. And you look at the DNA in that stall, and it turns out it's raccoon dog and there's a lot of duck. And very little human.  

And there's one particular sample, it's from a cart right next to this stall, and this cart has the virus in it, it has that SARS-CoV-2, it's there. There is lots and lots of sequence from raccoon dogs in that cart, plus a few other animals too. But there is no human genetic material in that sample. None. 

Tegan Taylor: The implication there is that the virus has come via the animal and not via a human that was already infected. 

Eddie Holmes: Yes, correct. So that's the implication. Now, we can't prove that. Because we've not found the animal that carries the virus, this is an association, but it's a pretty…I mean, I don't think it's a smoking gun but I think the gun is pretty well loaded, right? So we've got the virus, we have lots of animal, lots of animal genetic material and no human.  

Okay, so if it came from humans, let's say humans had contaminated the crime scene, you'd expect some fingerprint of humans to be there in this forensic analysis, but they're just not there at all, and you have lots of the animal stuff instead. So that's a very strong suggestion that it actually comes…this virus was in the animal, not the human. 

Now, the key thing is this, that when they closed this investigation, they did not actually sample the wildlife themselves. It was a chaotic thing, you can imagine this thing's going on, this outbreak was happening, people were very nervous, the authorities came in. But what I've heard a number of times from people in China is that the local vendors, the stall vendors were allowed to remove their animals from the market without being tested. The Chinese CDC did not test any live raccoon dogs or any live civets, they found carcasses in freezers they looked at, they did not test the live animals. So we've lost the record, we've lost the source, we won't get the live animal now, because they failed to detect it, failed to sample it back in 2020.  

And the problem I think we now have is this is three years, over three years after the events that took place. And so the chances now of finding the source population, let's say it is raccoon dog, the source population of raccoon dogs that actually have the virus, that's gone. But the virus would have got in to that population, would have burned through it pretty quickly, like we've all had Covid, and it would have just died out. So we won't find that animal now, it's just too late. 

Tegan Taylor: The timing of this is interesting because only a couple of weeks ago we were hearing the tide sort of seemed to be turning in favour of maybe it was a lab leak after all, and then now this data has gone up and then come down again.  

Eddie Holmes: The US has had a variety of agencies looking look into this. So the Department of Energy released their report saying it had low confidence it was a lab leak. The FBI said they had moderate confidence, I think. There's also a number of other ones that have said it's most likely natural, like the CIA and a few others. So it's been debated in the US, but they're looking at what they're calling intelligence data and I don't know what that is. But my guess is it's not particularly compelling. The key evidence they would need to have was evidence of the virus in this lab, this lab is about 30 K away in Wuhan, evidence of that virus in that lab before the pandemic. If you have that, then I'm willing to believe it's out of a lab. If they had those data, that would be high confidence, it would really be quite the smoking gun. But the fact that the agencies in the US disagree on the value of the data they've got suggests to me it's not particularly strong and open to different interpretations. So I wouldn't put much store in that. There's also a massive political battle going on as well. So I think we should stick to the science and the science to me has always been pretty clear that this is most likely natural, most likely it's a zoonotic jump, like has happened many times.  

And in this case now, this looks so much like SARS-1 that emerged in Guangdong in 2002, that was In animal markets, civets and raccoon dogs were involved, we now have an animal market and there are raccoon dogs and civets involved, and it's a very similar virus. So think of it this way, if it came from a lab, what are the odds that all of what I've just told you—we found a market, the right animals that were involved in SARS-1—what's the chance that happened by chance? It seems to be extraordinarily unlikely. 

Norman Swan: So where does it go from here, Eddie? I mean, is this the dead end? 

Eddie Holmes: I don't think this story will ever end, Norman, I suspect you'll be doing Coronacast in ten years and we'll be talking about it again then. I hate to predict the future. But it's become so tense and so debated that I think it'll go on. I think, hopefully, most people in the kind of middle…and we put the data out there, people can analyse it themselves, we have not left it…we've not put too much comment up there, hopefully most people will see what this really does look like. There will always be people who disagree, it's absolutely clear that's going to happen, so we're not going to convince everyone. You know, maybe there'll be twists and turns in the future.  

Sadly, I don't think we'll get much more out of China. I think there's now a political imperative for them not to have the pandemic start in their country. For national pride they're pushing an 'anywhere but China' kind of policy, so I don't think we'll get more from them. I think it will rumble on but I think this is a very decisive turn of events that should hopefully change people's minds.  

And again, the question we need to ask ourselves is…well, I think there's a number questions, one is this wildlife trade, it is dangerous, this is very clear from this and other outbreaks. But two, why have we waited so long for these data? My group does this sort of work every day, literally every day, it's not that hard to do. So I'm just…you know, I'm baffled why it's taken so long.  

Norman Swan: Well, let's hope the poor Chinese scientists who put this up on the GISAID database didn't get into too much trouble. 

Eddie Holmes: That is an interesting question and we will watch in the next few days what happens. 

Norman Swan: Eddie, thank you very much for joining us on Coronacast.  

Eddie Holmes: My pleasure. 

Tegan Taylor: Professor of Virology at the University of Sydney, Eddie Holmes. And I think that might be it for us today, Norman.  

Norman Swan: It might be, and we'll see you next week.  

Tegan Taylor: See you then.