How we know the COVID-19 coronavirus wasn't made in a lab

• COVID-19 myths have spread just about as quickly as the disease itself.
• One myth in particular just won't go away… that this coronavirus is a man-made bioweapon.
• But by using the virus' genetic sequence scientists have been able to debunk this myth once and for all.
• The answers lie in the spike proteins lining the outside of the virus, its uniqueness and how poorly this virus performed in computer simulations.
• In other words, if you wanted to make a virus you wouldn't have chosen this one.

Following is a transcript of the video.

Narrator: COVID-19 myths have spread just about as quickly as the disease itself, but one myth in particular just won't go away: that SARS-CoV-2, the virus that causes COVID-19, isn't naturally occurring and was actually manmade. In fact, one substantial survey found that almost 30% of Americans believe that this virus came from a lab.

But scientists believe that they can confidently say that the virus wasn't created by humans and the myth going around is nothing more than that, a myth. So how do they know with such certainty? The key is in the virus's genetic code. This is the genomic sequence for SARS-CoV-2.

It was decoded in January 2020, just weeks after the world started to learn of this novel coronavirus. Each of those letters is a genetic building block known as a nucleotide, and when built up, they form an organism's genetic code, which we can use to understand them. Each organism has a different code and a varying amount of nucleotides. A human has about three billion of them, whereas a virus, such as SARS-CoV-2 has about 30,000. Your genetic sequence can give information about your hair, eye color, sex, and lineage. And just like your genes give clues about who and where you come from, scientists can use a virus genome sequence to help explain where that virus originated as well. An ancestry test for viruses, if you will.

Robert Garry: We honed in on the parts of the virus that we thought were unique and that might play a role in the evolution of the virus, but also in the pathogenesis of it. And a couple of things stood out pretty quickly when we starting to compare with the other coronaviruses that have come before.

Narrator: That's Robert Garry, a professor of Microbiology and Immunology at Tulane University. Along with his colleagues, he used the virus sequence to try and understand where SARS-CoV-2 came from. They first looked at the virus's backbone. That's the whole genomic structure, unique to each virus, like a viral template. Simplified, the backbone for SARS-CoV-2 and its 30,000 nucleotides looks a little bit like this.

Each section is responsible for a part of the virus. For example, this one is responsible for the spike proteins you may have seen lining the virus shell. So it may not come as a surprise that to engineer a virus in a lab, you would need to start with a backbone. But to manufacture from scratch the backbone of a virus that can also cause disease is almost impossible.

Garry: I mean, people just don't know enough about what makes a virus pathogenic to be able to assemble that. How you pick amongst all the possibilities to get to that last little bit that's gonna turn it into this worldwide pathogen, which sequences do you think about to put in there?

Narrator: Simply, there is just not enough knowledge about how to make a new virus that would also cause significant devastation, like SARS-CoV-2 has. So creating a new, deadly backbone is pretty much impossible. But there is another way the novel coronavirus could have been created in a lab, and that would be using an existing virus backbone or genetic sequence as a starting point.

With a recycled backbone, two main methods could have been used to create the new virus. They could've either quickly mutated it, or added and deleted parts of the existing virus. But additions and deletions in a virus leave a trace that can be pointed out pretty quickly, a little bit like removing a red brick from a wall and replacing it with a black brick. This is exactly what Maciej Boni, an associate professor at Penn State, looked for.

Maciej Boni: You might see an insertion that looks unusual, and you look out in nature and you see that no other viruses have genetic insertions like that. We did not see any genetic insertions that are not also identified in nature. So there's no evidence suggesting that it was manmade or laboratory created somehow.

Narrator: So what if they went with the other option and mutated an existing virus? This is known as serial passage and acts in a similar way to selective breeding. Scientists are able to mimic evolution, to a degree. By forcing the virus to mutate over and over again into a potentially different form. This can be used to weaken a virus, which is how some vaccines have been made, or to strengthen a virus, say, by making it more transmissible.

But for this to work, the existing virus would have to show significant genetic similarity to the new virus. In fact, they would have to be almost identical. Because this process only speeds up viral evolution and has a limit, it's not possible to direct mutations into a completely different form. Yet Garry and his team found that the backbone for SARS-CoV-2 was strictly unique, differing significantly from other coronaviruses.

For example, SARS-CoV, the first SARS, has only about a 79% genetic sequence match to SARS-CoV-2. So it's ruled out. The best candidate is RaTG13, a bat coronavirus with a 96% gene sequence similarity.

Garry: Now, 96% sounds pretty close, but in genetic terms, that's actually a pretty long ways away.

Narrator: To put it in perspective, humans and chimpanzees share 99% of the same genome. And you may have noticed there's still a large difference between the two. For SARS-CoV-2 and RaTG13, that 4% is the difference of about 800 nucleotides, or about 50 years of natural evolution.

Garry: 800 is too big a barrier. You have something that was 99.5% or 99.7% similar, maybe only 20 or 30 nucleotides, you might get away with it, you might be able to manufacture that, doing it in the lab.

Narrator: But it just wouldn't be possible with current knowledge and existing viruses. There's also another part of the gene sequence that helped Garry and his colleagues learn about the natural origins of SARS CoV-2. In particular, this set of nucleotides in the gene sequence. You might remember those from earlier. They're responsible for the virus spike proteins, the pointy, claw-like arms lining the outside of the virus that give it its distinctive appearance, and coronaviruses their name.

Specific viruses, including coronaviruses, use these arms to enter and take over host cells. But this piece of the spike protein helped tell the researchers that this virus originated in nature. This set of nucleotides relates to the receptor binding domain, or RBD. That's the part that latches on to the receptors on targeted cells. As viruses can only survive when inside other cells, this is a vital section that you would have to focus on if you were to make a virus in a lab. Garry and his team found the RBD has evolved specifically to bind to the human cell ACE2, a receptor usually used to help regulate blood pressure.

But it's the way it so successfully binds to the ACE2 receptor that is crucial. You see, when a scientist tests what aspects would make a virus more potent, they run models through computer simulations. But when researchers put this sequence through those simulations, they found that SARS-CoV-2's RBD shouldn't be successful at all and would actually cause poor efficiency in transmission, which we know is not the case.

Garry: Yeah, by working in the lab or working with the computer, trying to figure it out, we just would not have come up with this particular way to have this virus bind to this receptor, a very important part of the whole replication process.

Narrator: In other words, if your goal was to make a virus to infect humans, you wouldn't have chosen this one.

Garry: Basically, what nature has done is come up with a solution for binding that is better than any computer and also way better than what any scientist could come up with.

Narrator: So we know why scientists confidently say SARS-CoV-2 wasn't made in a lab, but that's not the end of the story. It's also been rumored that SARS-CoV-2 was a known virus that was accidentally leaked from a lab. Now, we can't say for certain this isn't the case, but it's highly unlikely. For one, this virus wasn't sequenced before January 2020. And if it was, the world would know because the Wuhan Institute of Virology was specifically looking for something like this in order to protect the world from any outbreaks.

Garry: If they would have come up with a SARS coronavirus that was 76% similar to the original SARS one. I mean, they would have published that as fast as they could. That would have been, at least in the scientific world, very big news.

Narrator: But it's also just statistically highly unlikely.

Garry: So just out in nature there, literally billions of people that are having millions of encounters with these animals. And, you know, we're talking about a handful, a few dozen, maybe, in the whole world are scientists that go out and trap bats. So just on the odds of the thing, it's just a minuscule chance that it was this one scientist that accidentally infected himself in this very sophisticated laboratory setting.

Narrator: So SARS-CoV-2's origin is no longer a mystery. But where and how it jumped in nature, well, that's a question many are still trying to answer.