ngela Rasmussen studies the interactions between hosts and pathogens and how they shape disease. Before the pandemic, she worked on the emerging viruses that cause Middle East respiratory syndrome (Mers), Ebola, dengue and avian flu. Then, when Covid-19 erupted, the American virologist, who works at the University of Saskatchewan in Canada, was drawn into the debate over where it came from. She has been among the most vocal scientists on Twitter defending a “natural” origin, as opposed to a lab leak. Last month, she and 17 co-authors published findings in Science that they feel should silence all rational critics on the question.
There’s really no explanation other than that the virus started spreading in the human population at that market
In the Science paper, which started life as a preprint in February before going through peer review, you say that the Huanan seafood wholesale market in Wuhan was the “early epicentre” of the Covid-19 pandemic. To be clear, are you saying that the Huanan market was the origin of the pandemic?
That is what the research heavily implies. We are not able to pinpoint the exact spillover event, the exact animal from which the virus crossed into humans, but there’s really no other explanation for what our analysis shows. And that is that there weren’t any Covid-19 cases in Wuhan or anywhere else prior to these early cases that we looked at, which are all strongly associated with the market.
What does your paper add that is new?
Nobody disputes that there were a lot of early cases associated with the market. The question was, could the virus have come from elsewhere and just been amplified at the market? First, we did a lot of detective work to see if there was a geographical relationship between those early cases. Their geospatial coordinates had been available but nobody had conducted that kind of analysis before. Importantly, when we excluded the early cases that had a direct link with the market – meaning the patient had been there – the association with the market became even stronger. That’s consistent with the virus acquiring the capacity for human-to-human transmission at the market, so that people who hadn’t been there started catching it from those who had. It radiated out like ripples on a pond.Second, we have known since June 2021 that many species of live animal were on sale at Huanan. We obtained plans of the market, and legal and business records regarding what species were sold at the various stalls, and we cross-referenced these with data from the Chinese Center for Disease Control and Prevention (CCDC) about swabs taken from surfaces in the market in early 2020, that tested positive for Sars-CoV-2 – the virus that causes Covid-19. These positive samples clustered in the part of the market where the live animals were sold; they came from cages, carts and equipment that had been in contact with those animals. That wasn’t widely known.
By a crazy coincidence, in 2014 one of my co-authors, Edward Holmes, had taken a picture showing one particular stall where live raccoon dogs – which are susceptible to Sars-CoV-2 – were kept in cages stacked on a cart. He took the photo while being given a tour of the market by Chinese scientists who considered it to be at high risk of viral spillover. That stall later produced five samples positive for Sars-CoV-2.
Finally, we showed that many of the species on sale at the market are susceptible to infection by Sars-CoV-2. We were the first ones to put all this evidence together, and to say that when you look at the whole picture, there’s really no explanation other than that the virus started spreading in the human population at that market.
There was a companion paper to yours in the same issue of Science. What did that show?
In the early cases the virus already existed in two distinct lineages, A and B – though confusingly, B was the older of the two. Until February this year it was thought that only lineage B was present at the Huanan market, but then a group led by George Gao, the former head of the CCDC, showed that lineage A was there too [this paper is undergoing peer review]. The companion paper, by Jonathan Pekar of the University of California San Diego and colleagues – which I wasn’t involved with – reconstructs their family tree to show that they probably reached humans as a result of two separate spillover events within a couple of weeks of each other.
Now, if the virus had escaped from a lab, somebody would have had to get infected with lineage B in the lab, go to the market and infect people there without having infected anyone along the way, and then somebody else would have had to do the exact same thing with lineage A a few weeks later. It’s not impossible, but a simpler explanation is that the virus was brought to the market in an animal, from where it spread to other animals, diverging in the process. The two lineages then spilled over separately into humans.
No meaningful further studies will happen without Chinese collaboration, and this debate has damaged the chances of that
One of the criticisms of your paper is that you remain vague on “upstream events” – that is, how the virus got to the market in the first place.
That is one thing we don’t know. We do know that the live animal trade uses a common supply chain. Animals are gathered from all over the place, including far-off parts of China, and brought to the market. There may well have been other spillover events upstream, but the other thing to keep in mind about the market is that it’s an environment where human-to-human transmission can be established and sustained – because there are many animals housed in close contact with each other, and many humans milling around them. Spillover events in remote, sparsely inhabited areas are more likely to be dead ends because there are too few susceptible human hosts. We also know that when a related coronavirus, Sars, emerged in China 20 years ago, it was linked with the live animal trade.
Have you ruled out that a lab leak caused the pandemic?
I don’t think you could ever completely rule it out, but we have demonstrated pretty conclusively that it came from the market.
Could more be found out?
Yes. We’re still trying to establish the susceptibility to Sars-CoV-2 of the various species that were on sale at the market. I’d like to see information about the farms where the animals were raised, and any samples taken from those animals before the farms and the market were closed, and the animals culled. These might allow us to identify the intermediate host – the animal from which the virus likely jumped to humans. I’d be curious to see human serology data too, to find out if people working in the live animal trade in 2019-20 had elevated levels of Sars-CoV-2 antibodies in their blood.
It is possible that this information exists and we’re not being given access to it, and this is one of the hardest things to discuss with people who support the lab leak theory. If you look at it from the Chinese government’s point of view, though, it’s actually worse if this came from the market. After Sars they were supposed to have cracked down on the live animal trade, so it’s hugely embarrassing for them if the same thing happened again – especially in a city where world-class coronavirologists work. One thing is clear: no meaningful further studies will happen without Chinese collaboration, and this debate has damaged the chances of that.
Some scientists who defend a natural origin have been accused of conflicts of interest, generally because they have collaborated with Chinese scientists including researchers working at the Wuhan Institute of Virology – the institution most often named as the source of a hypothetical lab leak. Do you have a potential conflict of interest?
I have never collaborated with the Wuhan Institute of Virology. I’ve never had grants to work in China, and I’ve never been to China. I have nevertheless been accused of a conflict of interest, for work I have done on Mers and Ebola that was funded by the US Department of Defense. Some of the wilder conspiracy theories implicate US biodefence.