COVID Transmissions for 5-27-2021

Revisiting the origins of SARS-CoV-2

May 27, 2021

Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.

It has been 557 days since the first documented human case of COVID-19. In 557, a people called the Avars came to Europe and began fighting the Byzantine Empire. To this day, there is still debate over where they came from.

There is also debate over where SARS-CoV-2 came from, and it isn’t a group of people with culture, language, and history. That debate continues, and I’d like to update you on where I stand on it today.

Bolded terms are linked to the running newsletter glossary.

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Revisiting the origins of SARS-CoV-2

Earlier this month, a science journalist named Nicholas Wade wrote an extremely long article making the argument that SARS-CoV-2 may have originated in a lab, and that this possibility should be taken seriously as more than a conspiracy theory. He accused many prominent scientists who had denied a lab origin of political games, and in my opinion, the nature of the article he wrote is such that it doesn’t deserve to be linked here. Under the guise of a sober evaluation of science, he wrote something more akin to a hit piece. Having read it, in my opinion, it misrepresents the arguments for a natural origin of the virus while over-representing arguments for a laboratory origin.

It also—I believe inappropriately—represents experimental modification of viruses as a dangerous prospect, despite zero evidence that any such modification has ever caused any human disease anywhere.

That said, the piece has reignited debate over the origins of SARS-CoV-2, which was fanned further by a Wall Street Journal piece providing an unconfirmed US intelligence report that 3 staffers at the Wuhan Institute of Virology (WIV) were hospitalized with a respiratory illness in November 2019. This report has its own problems—not least of which is the fact that respiratory illnesses are very common in the autumn, and people in China often seek hospital care more readily than elsewhere, both of which are things that are mentioned in the WSJ article itself.

Still, President Biden has requested a detailed intelligence report on the origin of SARS-CoV-2, and so I think it is important to revisit this question here in a more sober context. First, I want to call your attention to a two-part piece that I wrote last August, for this very newsletter, about the argument against laboratory origins for SARS-CoV-2. I believe that many of these arguments remain valid, but I do have some modifications to make. Here is my prior work, for those who wish to read it:

Part 1: https://covidtransmissions.substack.com/p/covid-transmissions-for-8-20-2020

Part 2: https://covidtransmissions.substack.com/p/covid-transmissions-for-8-27-2020

At this point I think it’s important for me to tell you all that I think much of the media discourse on the origins of the virus has departed the realm of science. This has become a political issue, and where science is entering this debate is in supporting preexisting agendas. This type of scientific just-so storytelling is not my jam. I do not wish to presuppose anything when it comes to infectious disease origins, and I do not have an agenda. I want to pick this idea apart instead, and see where the evidence may lead us.

Now, I think it is important to lay out a distinction here between several possible “lab origins.”

Made in a lab and accidentally leaked: This is the idea that the virus was deliberately engineered in a laboratory setting, either using intentional design of new elements, combinations of existing known sequences, or directed evolution
Experimented with in a lab and accidentally leaked: In this concept, SARS-CoV-2 is a natural virus that was sampled in the field and then taken to the Wuhan Institute of Virology to be studied
Sampled in the field and leaked during transfer of the sample to the lab: Here, SARS-CoV-2 is a natural virus that was sampled from animals in the field by researchers associated with the Wuhan Institute of Virology, and during its transfer to that lab, was released into the city of Wuhan

I want to be clear that the first option is still one that I consider to be beyond the realm of reasonable possibility. For the reasons laid out in my original pieces linked above, I believe that the feat of creating a virus like this is beyond current technology, especially given the absence of molecular markers of laboratory passage. As explained in my prior writing, there natural virus immune evasion-related sequences that typically evolve away in the laboratory setting in because they are not needed. If indeed this virus was the product of laboratory passage, I would expect that early sequences would lack these immune evasion sequences, and that overtime we would have seen them reappear in virus variants. This has not happened. These sequences were present in the early genomes sampled, and they continue to be present. So I just don’t see how, using current technologies, this virus could have been engineered somehow and then accidentally released. I firmly believe that anyone telling you otherwise has an agenda, because there is no evidence whatsoever supporting this hypothesis.

Putting that aside, I want to comment further on the other two scenarios. I do believe there has been some new information that changes my perspective on the likelihood of these situations being the case. I commented in my original pieces that extremely high security precautions were taken at the WIV. It has now become clear that this is less true than originally reported.

Last year, it was reported and widely thought to be true that all natural samples collected from bats were studied in Biosafety Level (BSL) 3 or 4 conditions at the institute. BSL 3 and 4 conditions are highly restrictive and include infection control measures that are generally adequate to prevent the transfer of infectious agents to laboratory researchers. They are not perfect, and there have been examples of lab accidents. None have ever caused a pandemic.

However, it has become recently apparent that some work was conducted at the WIV under BSL2 conditions. BSL2 is still restrictive, but much less restrictive. Limited personal protective equipment is worn, though infectious agents are still worked with in isolation from the wider laboratory environment. These are the conditions under which seasonal influenza viruses are studied. I think it is possible for researchers to become infected in the course of sloppy work in a BSL2 setting.

This opens the door to the possibility that either in transfer to the lab, or during work being conducted at the lab, a natural virus was released that infected researchers there and spread to the rest of the city. While this opens the door to that possibility, it does not represent evidence that this actually happened. At this time, no one has any evidence that this actually happened. I think that’s important to emphasize here.

But, science is a business of possibilities and hypotheses. Let’s consider these two options as hypotheses, and understand how we might test them.

In both of these cases, the virus is a natural pathogen that exists somewhere in the world outside of the WIV. This means that every single fact we know about it is still true: it is a bat virus, and it contains sequence elements that appear to also originate from another species. This means there is either an undetected bat ancestor that has evolved to look more like coronaviruses from other species, or that the ancestor of SARS-CoV-2 passed through some intermediate host. The WIV has sampling programs that collect viruses from various animals, but as I understand it, they primarily focus on the isolation of coronaviruses from bats. If we identified the intermediate host, the nature of this host might immediately answer the question. If it is not an animal that the WIV was actively sampling from, then I think the hypothesis has been tested and it’s clear that the virus most likely wasn’t introduced to humans through laboratory sampling activities.

However, if it is an animal for which there are records of WIV sampling activities, matters become more complicated. In that case, it will be hard to distinguish between an origin from non-lab activities vs an origin from lab activities. The argument will be one of probabilities, and non-lab interactions with animals are certainly more common than laboratory-drive interactions with animals. We will need to turn to other evidence at that point.

The other evidence that I would turn to here is epidemiological evidence. If the WIV is the origin of the virus, we would expect early cases of COVID-19 to cluster around the WIV. In a general sense, the epicenter of the outbreak being in Wuhan suggests to many people that there is clustering around the WIV. However, Wuhan is a city of 11 million people. Fewer than 100,000 people there were identified as having COVID-19, though probably this is an underestimate. It probably isn’t an underestimate by more than a factor of 10, though. A relatively small share of the people in Wuhan actually got the virus, which is a good thing for the purposes of contact tracing. It should be possible to figure out, from information on the epidemiology, if these people are associated with the WIV, or if the cluster nearby to the WIV, or something similar. If that is the case then it should be pretty apparent to any outside investigator if a lab origin is possible. So far, no outside investigator with access to the epidemiological information has suggested that it points to a laboratory origin. But, none have said that it rules out such an origin, either.

On the other hand, the epidemiological information does appear to restrict the possibilities for a laboratory origin. As I have mentioned before, there is evidence of substantial epidemiological clusters of COVID-19 in Hubei province outside of the city of Wuhan as far back as November. For more on that, I recommend you read Question 4.4 of this document, by a grad school friend of mine, Dr. Jim Duehr: https://drive.google.com/file/d/1kAHSEx9-eIyVIahczH8itHaUm9jI9WX7/view. It supplies substantial references. In fact, the “first documented human case of COVID-19” that I reference in the beginning of this newsletter each day is a case from outside of Wuhan, which Jim references in his document.

It is difficult to reconcile these clusters with the idea of a laboratory origin, when the outbreak within the city itself only began to gain steam in December. Is it reasonable to suppose that the virus was released in a laboratory accident in Wuhan in November, traveled outside the city to rural areas to cause disease in those areas later in November, and then traveled back into the city somehow to cause a large outbreak in December?

This does seem convoluted, to me, but then again, it’s not strictly impossible. For such a situation, I would want to see meaningful supportive evidence establishing a timeline for how it might have happened. No such evidence has been forthcoming, but that doesn’t mean we won’t find it. Without evidence, though, I can’t say this is what happened. It seems to me more likely that, with clusters appearing outside the city in November, even if there was an outbreak at the WIV in November too, there must have been some other source for this virus. Viruses do not teleport large distances of miles from their origin points. For the virus to be in many places at once, it had to travel there somehow, and so I feel there must be some prior origin point.

The nature of that prior origin point could be pretty complicated. There are many ways that people interact with bats in the world. They are sometimes hunted as a food source. They are sometimes interacted with by people exploring caves, or by people out hiking at night. Bat droppings (“guano,” technically) are a rich source of fertilizer and are often sold for this purpose. Bat guano can contain coronaviruses, as reported in this 2013 paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739538/

Interaction with wild bats is not unique to China. Many cases of rabies in the US originate with people who interact with bats. Likewise, I found a US website advising gardeners on how to use bat guano as a fertilizer. We should not pretend that this is a uniquely Chinese problem, or that Chinese people engage in some kind of widespread unusual behavior like biting the heads off of live bats. That’s something that Westerners like Ozzy Osbourne do.

My point is that there are many ways that people might have exposed themselves to SARS-CoV-2, either through bats directly or through an intermediate host. Right now the closest ancestor that we have found is a virus that diverged from SARS-CoV-2 about 40-70 years ago. There is a lot of potential for intermediate lineages there that we haven’t detected yet. It’s hard to say for sure how the SARS-CoV species entered humans this time, but it may have come directly from bats, or more likely, passed from bats into an intermediate host that then interacted with humans.

One of the criticisms of this hypothesis is that we have not yet identified that intermediate animal, but, I don’t think that’s very reasonable as a criticism. It took time to definitively identify the intermediate host of SARS-CoV-1 as a specific species of civet, and in that case we had a clear origin point for the virus in the form of a live animal market. There was speculation as to that host relatively quickly, with some supporting evidence too, but definitive identification took time and was a matter of meaningful debate.

We do not have a clear sense of the origin point of SARS-CoV-2, so it is hard to trace what animals may have been involved. Early reports suggested that pangolins may have served as an intermediate, but this is based on genetic evidence rather than epidemiological: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860928/

It wouldn’t be the first time we’ve been unclear on where a virus came from when it first entered humans. Ebola viruses are thought to originate in bats too, though we are not at all sure that this is the case. We also suspect that they enter humans through a primate intermediate host, but there are a great many options for primate intermediates. It would not be at all unusual if we fail to identify the intermediate animal that brought SARS-CoV-2 into humans from bats—if there even is such an animal.

All this having been said, I think that there is more possibility that SARS-CoV-2 is a natural virus that was released in a lab accident of some kind, but this possibility is still more remote than a natural spillover event happening in the wild, involving an interaction between people and animals. Neither possibility has definitive evidence, but the epidemiology I have seen and the nature of human-animal interactions point to an origin outside Wuhan followed by later introduction to the city.

This is, by the way, the position that the WHO investigation into the matter also established. Laboratory release was considered the least likely option, but not an impossible one. A natural, in-the-wild human-animal interaction was considered more likely, and based on the evidence that I have at hand now, I have to say I agree. However, I’m open to the possibility that more evidence could change the picture. We shall see if that happens.

For now, the evidence available makes me believe a laboratory was not involved, and that is where I will leave things.

What am I doing to cope with the pandemic? This:

Celebrating my wife’s birthday

Yesterday was my wife’s birthday! We went to a restaurant that we love that was closed for most of the pandemic and recently reopened.

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