Lab-leaks and affinis excrement - or, how a scientist thinks.

So, where did the virus come from?

To start us out on this journey back through time, to even before December 2019, when the first COVID-19 cases were detected, I want to drop a knowledge bomb about how science works. To be a scientist, you have to learn to think in a pretty unique way. You must be dispassionate about your results, as little influenced as possible by your social beliefs, and willing to change your mind.

Being a scientist is also not the same as being a Sherlock. All the mighty force of Sherlock's deductive reasoning would simply not cut it in a lab (although to be fair, Sherlock also uses abduction - “Once you eliminate the impossible, whatever remains, no matter how improbable, must be the truth.”).

In science, we do use some deductive reasoning. "Deductive reasoning is a form of logical thinking that uses a general principle or law to forecast specific results" - i.e. hypothesis-based science. Based on what we already know, we form a hypothesis, or an educated guess, about what will happen. But what is key to science, is that we don't stop at a hypothesis. We then spend years testing it.

But, equally or maybe even more important in science is the lesser-discussed inductive reasoning. "Inductive reasoning is a form of logical thinking that uses related observations to arrive at a general conclusion." In science, this means gathering huge amounts of data in an dispassionate, objective way, and then (again dispassionately) analysing the data to see what generalizations can be formed. Of course, having some bias is an unavoidable side-effect of the human condition, but we do our very best to avoid it.

Most of the science that I do involves both deduction and induction. To build up a scientific story, I usually start with induction (gathering a lot of data and just seeing what I see), and then based on that data, I form a hypothesis. That hypothesis then allows me to forecast specific results that I expect to see in the next phase of the project (deduction). I then carry out experiments to test that hypothesis. The whole process will take years of work before myself and my fellow scientists will be convinced that my story is "true", or at least as close to the truth as possible.

So, now that you've had a primer on scientific thought, lets jump in to the real topic of this post. As of now, in June 2021, can we confidently say where SARS-CoV-2 (the virus that causes COVID-19) comes from?

Let's start with the theory that SARS-CoV-2 crossed over to humans from an animal. To prove that SARS-CoV-2 had such a so-called "natural origin", we would need to identify the animal from which that jump occurred, or at least an animal virus that is extremely similar to SARS-CoV-2. A whole lot of effort has been put into identifying an animal point of origin, but so far with no complete success. At first, scientists suspected that civets, due to their role as a host in the first SARS outbreak of 2002-2004, or pangolins, because they are hosts for distant cousins of SARS-CoV-2, could be the culprits. However, since early 2020 a torrent of scientific studies have found no evidence that either civets or pangolins are at fault for handing over SARS-CoV-2 to us. From this gross lack of evidence, we can induce that either a different animal host, or a lab leak is more likely.

So, let's go to a different animal host. After the focus on civets and pangolins, bats were next identified as a likely source of the virus - because they can give us loads of viruses, including Nipah virus, Hendra virus, and the closely related first SARS coronavirus and MERS coronavirus. Notably, the WIV, that infamous-in-the-media lab in Wuhan, was the first to publish that a bat coronavirus named RaTG13 (Ra for Rhinolophus affinis, the horseshoe bat from which this virus was isolated) has 96.2% the same genetic material as SARS-CoV-2.

Let's pause there. I see this 96.2% waved around a lot. To put this in perspective, that is about the same amount of genetic material that humans share with Chimpanzees. On the higher end, humans have about 99.9% genetic similarity to each other. On the lower end, we share about 85% of our genes with cows. Of course, this is not a perfect comparison - animals and animal evolution are different from viruses and viral evolution. But it gives you some perspective on how over 95% similarity doesn't necessarily mean a perfect match. In the world of coronaviruses, that 4% dissimilarity between SARS-CoV-2 and RaTG13 corresponds to about 50 years of evolution between them. In human terms, they are cousins, not siblings.

Nonetheless, RaTG13 has long been our best lead on an animal source for SARS-CoV-2. After the initial publication from Wuhan about the relatively close relatedness of this bat coronavirus to SARS-CoV-2, the lab later published an addendum explaining how they found it. They had gone back into their freezers to compare SARS-CoV-2 to samples collected from bats, rats, and musk shrews in or around an abandoned copper mineshaft in Mojiang County, Yunnan Province, China. Between 2012 and 2015, they sampled bats once or twice a year and collected over a thousand samples, which together contained almost 300 different coronaviruses. RaTG13 was one of those. In fact, RaTG13 was already discussed in a 2016 publication that included the warning:

"Additionally, the surveillance identified two unclassified betacoronaviruses, one new strain of SARS-like coronavirus, and one potentially new betacoronavirus species. Furthermore, coronavirus co-infection was detected in all six bat species, a phenomenon that fosters recombination and promotes the emergence of novel virus strains. Our findings highlight the importance of bats as natural reservoirs of coronaviruses and the potentially zoonotic source of viral pathogens."

Or, in plain language: "we found SARS-like coronaviruses in bats. Several bats. This could be bad news for our future selves."

Importantly, that very same mineshaft was also associated with a severe pneumonia-like illness that infected six miners in 2012. Three of them died. Recently, a Master's thesis that described the outbreak and illness in detail was unearthed in the near magical depths of the internet. This thesis described how, in April 2012, the miners were tasked with clearing bat poop (also called guano) from the copper mineshaft. After about two weeks of work, they developed breathing problems, coughs, and fever, resulting in hospital admission. Half of them died, half survived.

The thesis hypothesized that a coronavirus from horseshoe bats (the same species that RaTG13 originated from) probably caused these pneumonia cases. However, researcher Dr. Shi Zheng-li, also known as the "Batwoman" and an expert on bat viruses who now runs the side-eyed Wuhan institute, later concluded that that causative virus was more likely to be the Mojiang paramyxovirus, a totally different virus family as compared to coronaviruses. In support of this, researchers have since tested blood samples taken from the miners for antibodies against SARS-CoV-2. The results were negative, meaning that the miners' immune systems didn't recognize SARS-CoV-2 and therefore probably did not succumb to COVID-19.

More recently, though, a report posted to a scientific hub for papers that have not yet been peer-reviewed (so take it with a grain of salt, it's not been extensively vetted yet like academic papers published in journals are), identified another bat coronavirus, RmYN02, a coronavirus in bats in southern China, might be more closely related to SARS-CoV-2 than RaTG13. There is about 40, rather than the 50 with RaTG13, years of evolution between RmYN02 and SARS-CoV-2. But, 40 years still makes RmYN02 merely a cousin to SARS-CoV-2, rather than a mother or a sister.

Looking at the region, a bat-poop source of the coronavirus could make sense. Why? Because aside from bats inhabiting mine shafts, bat guano is also a commonly used fertilizer in many countries in South East Asia and beyond. You can even buy "Chinese organic bat guano" on Alibaba. And, coronaviruses have been detected in bat guano fertilizer collected in Thailand, so it wouldn't be too big of a logical jump to assume that the same could happen in China.

Altogether, the story up to this point tells us two things: that bats are definitely important sources for severe pneumonia-like illnesses, including coronaviruses, and that if SARS-CoV-2 has a natural origin, it probably does come from bats. However, I do not see enough evidence to say with 100% certainty that COVID-19 came from the Horseshoe bat.

And with that, that's all I've got for you in regards to the natural origin theory. In full fairness, next week on Microbial Mondays we'll be flipping viewpoints and assessing the alternative theory: could SARS-CoV-2 have come from a lab leak? Tune in next week for an analysis of the evidence.

Until next time - did you dig up more scientific evidence online for or against the natural origin theory? Let me know in the comments!

~ Alex