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  • Alex Cloherty

Where did the virus come from? Part II

This week on Microbial Mondays, we are looking at the other side of the coin. Last week, I asked, could COVID-19 have come from the wild - i.e. is it of a "natural origin"? Today, I ask, what is the evidence for a lab-leak origin for SARS-CoV-2?


In the interest of full disclosure, it was a little harder to find solid scientific literature to support this theory, because most top virologists still think that a natural origin is the more likely of the two explanations, although many also acknowledge now that there is no concrete evidence to totally eliminate the possibility of a lab leak. I think scientists are also cautious of getting caught up in the swirling cesspit of social media-driven conspiracy theories on this topic. And understandably so. There are a lot of non-scientifically backed theories stemming from ideas like, "SARS-CoV-2 spreads so fast that it must have been engineered to do so". But, nature is often stranger than fiction, so I don't give much weight to those assertions. To further complicate things, it can be easy to get bogged down in all the pseudoscience on the internet, when trying to form an educated opinion. But having said that, I do think it is important to evaluate what we do know as fairly, and dispassionately as possible. So here goes.


Well, to start off, this wouldn't be the first time there was a lab leak. Although many highly infectious diseases do spill over to us from different animal hosts, accidents do happen. Accidents like the mini-outbreak in 2004, when two researchers caught the first SARS coronavirus while working in a lab in Beijing, and spread the disease to seven other people before the outbreak was contained. So, lab leaks are definitely possible, although this example does demonstrate that when successfully identified, they can be effectively contained pretty quickly.


So, yes, in theory, COVID-19 could have very well come from a lab. And of note, even the former director of the USA's Centers for Disease Control and Prevention (CDC) thinks it's likely Amongst those who believe it was a lab leak, there seem to be two different factions: one asserting that SARS-CoV-2 was collected, studied, and leaked by accident, and the other arguing that, more nefariously, it was designed and released either by accident or on purpose.


The first theory, that SARS-CoV-2 was collected for study and leaked by accident has the most weight to it, in my opinion. Virology labs usually specialize in viruses that occur around them - that is exactly why I wanted to come to Amsterdam to study HIV. Historically, Amsterdam was a hotspot for the HIV-1 virus, so many of the top labs studying the virus are in and around this Dutch city. As I wrote last week, Southeast Asia is a geographical hub for coronaviruses, so I don't think there is anything innately suspicious about there being a lab in Wuhan that specializes in coronaviruses. it also totally makes sense that the lab in Wuhan was studying bat coronaviruses, because bats have long been known to be a potential source of viruses that jump into humans and cause disease. Since 2012, the lab in question had been collecting bat feces to study the coronaviruses within it - exactly because the bat poop was a potential source of risk for future virus outbreaks in humans, as one of their own publications warned. Put this together with the fact that the Wuhan lab in question doesn't seem to have always been following proper safety protocols according to Prof. Dr. W. Ian Lipkin, an expert in the field at Columbia University and NIAID Center for Research in Diagnostics and Discovery Director, and you can see how there could have been an accident. Maybe the bat feces collected by the researchers at the Wuhan lab in question was infectious, employees got sick, and they spread it throughout the community. It could have all been a terrible mistake.


Let's now jump to the other faction of lab-leak proponents. One common, and somewhat scientifically grounded, piece of evidence brought forth is that the SARS-CoV-2 virus includes some weird-looking genetic sequences. So weird, "that it must have been created with intention" according to some. And, some people have suggested that, perhaps it was created with RaTG13, a bat coronavirus that has 96.2% the same genetic material as SARS-CoV-2, as a backbone. Already in March 2020, a paper published in the highly respected scientific journal Nature walked through this theory. Those scientific sleuths found a total lack of signatures of genetic manipulation left behind in the viral genome, and situated SARS-CoV-2 within the evolutionary realm of other coronaviruses. Their main conclusion was that the genome of the SARS-CoV-2 virus makes sense if the virus would have evolved in an animal that if: 1) that animal had a high population density, which would allow for rapid evolution of the virus as it spread throughout the population, and 2) that animal had an ACE-2 gene (the doorbell that SARS-CoV-2 rings to enter our cells) that is similar to the human one. The authors acknowledge that it is still possible that the virus could have been artificially "bred" in a lab, but that this is very unlikely due to features of the virus that typically only evolve if the virus is fighting against real immune systems.


Since that Nature paper was published, the focus has moved on to a part of the SARS-CoV-2 virus called a 'furin cleavage site' - basically a piece of the virus that is necessary for getting into human cells. Indeed, a Nobel Laureate was quoted as saying, “When I first saw the furin cleavage site in the viral sequence, with its arginine codons, I said to my wife it was the smoking gun for the origin of the virus. These features make a powerful challenge to the idea of a natural origin for SARS2,” Why is the furin cleavage site suspicious? Well, it's been argued that one very small chunk of it is relatively unusual for wild viruses, but not so unusual in genetically modified viruses.


However, not everybody agrees with that last statement. And indeed, that same nobel Laureate later qualified and clarified his opinion in a letter to the highly respected Scientific journal Nature, saying, that natural evolution is still a valid hypothesis in regards to the origin of SARS-CoV-2, but that “there are other possibilities and they need careful consideration, which is all I meant to be saying”. And, other experts like Kristian G. Andersen, who co-authored that March 2020 Nature paper in support of natural evolution of SARS-CoV-2 have vehemently argued against the suspect nature of the furin cleavage site. On Twitter, Andersen argued and explained that the evolution of the furin cleavage site is pretty straight-forward, and not unlikely to happen when a virus is jumping from one host to another. He also contends that while SARS-CoV-2 may be the first of its close cousins to have this sequence, other related coronaviruses like MERS also have furin cleavage sites - so it's not by any means impossible that SARS-CoV-2 evolved this molecular signature naturally. He says, "There is nothing mysterious about having a "first example" of a virus with an [furin cleavage site]. Viruses sampled to date only give us a teeny-tiny fraction of all the viruses circulating in the wild. Fragments - such as the [furin cleavage site] - come and go all the time." In other words, we still know so little about "wild" viruses, that we really can't convincingly say that this sequence is really unusual.


So, could these strange molecular signatures come from bioengineering, or from evolution? At the moment we cannot fully say either way. But it is important to remember that just because some of these features look odd at first sight, doesn't mean that they couldn't have evolved naturally. I mean look at the platypus. Evolution comes up with some pretty weird looking stuff without any human intervention at all. But on the other hand, although it is not uncommon for it to take years to find an animal origin for infectious diseases, the lingering absence of absolute proof of a batty culprit lends more weight to this theory.


But now, let's side-step to the last lingering question tied up within the lab-leak theory: if the virus was leaked, was it on purpose? Here, I can confidently say there is no scientific evidence to clear that up. This steps into the realms of politics. I'll still give my (unqualified, but well-read) two cents, though. On one hand, the investigation into the origins of the virus has been rather unfruitful, and China hasn't been terribly cooperative. Some of the main results from the WHO's investigation, as WHO director general Tedros Ghebreyesus eventually put it (more eloquently) in a press release, were that the investigation wasn't good enough, that the possibility of a lab-leak was not given sufficient consideration, and that China wasn't as cooperative as it could have been. So, many ask, why would China stonewall if they didn’t have something to hide? But, on the other hand, if the Chinese were going to release a virus, why would they do it right next to their institute for virology? And in their own city? If one is going to put in all of the effort to deliberately bioengineer a weapon that will shock the world for over a year, surely one could have planned a less suspicious location to do it, right?


In the end, there is only circumstantial evidence for a lab leak. This doesn't mean that it didn't happen, but it also doesn't mean that it did. If this was a criminal case, the police would probably need to continue to gather evidence before going to trial if they would have any hope for conviction.


Taking into account last week's post on the possibility of natural origin, and today's on the possibility of a lab leak, what do I, as a scientist, think happened? I think that there is simply not enough evidence, at least not any that's available to the public, to say either way. But, I also think that there are other important questions, after "where did it come from?"


We also need to ask, "Whether it came from animals in the wild, or from a lab, how do we prevent this from happening again?" And, "How can we improve public understanding of science, so that if this happens again people will have the right knowledge to react appropriately?" Because, although I have heard conflicting opinions from top virologists about where the virus probably originated from, they all agree on one thing: this won't be our last pandemic.


Until next time, as they say over at Freakonomics - Take care of yourself, and if you can, someone else too.


~ Alex


PS. On a totally different note, you may have noticed that there are no advertisements on this site. So far, I've paid for this platform out of my own pocket, from my PhD salary - "to keep it that way", as the podcasters and bloggers say these days. Today, I'm launching my Patreon page. If you like my articles, and want to support me, you can do it that way, as a Fan of Fungus, an Algae Enthusiast, or a Bacterial Benefactor. It'll help pay for keeping the site live and add-free. And maybe keeping me caffeinated, too. Cheers!


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