“SARS-CoV-2 could always pick up a mutation that could just change the game,” Pardis Sabeti, a Harvard computational geneticist explains in this video exploring the basics of how viruses evolve as they infect more people, and how more infectious variants may be selected for. Sabeti and others use math and genetics to monitor new variants and provide insight into viral origins and spread. 

“One of the things that a lot of people feel complacent about is that [Covid-19] seems to affect people that are mostly elderly … or, you know, mostly not them,” she says. “But at any point this virus could change and affect them. It can become more lethal. It could become more lethal to our children. It can evade our vaccines. And so it’s one of those things where you just don’t want to give it a minute to change in a way that’s particularly bad.”  

It’s clear, she says, that “the best thing we can do is to get the infection rates to zero so that the virus has no opportunities to mutate and change.”


This video is part of Reset: The Science of Crisis & Recovery, an ongoing series exploring how the world is navigating the coronavirus pandemic, its consequences and the way forward. Reset is supported by a grant from the Alfred P. Sloan Foundation. Watch more videos from Knowable Magazine.

Video Transcript:

Newscaster: “Researchers have identified a new double mutant variant of the virus.”

Pardis Sabeti (computational geneticist, Harvard University): “We’ve long known that these viruses mutate. So SARS-CoV-2 could always pick up a mutation that could just change the game.”

Newscaster: “As more contagious variants continue to spread, younger Americans are feeling the brunt of this latest surge.”

Pardis Sabeti: “One of the things that a lot of people kind of feel complacent about is that it seems to affect people that are mostly elderly or, you know, mostly not them. But at any point a virus could change and affect them. It can become more lethal, it can become more lethal to our children, it can evade our vaccines. And so it’s one of those things where you just don’t want to give it a minute to change in a way that’s particularly bad.”

Newscaster: “The World Health Organization just declared this a global health emergency.”

Pardis Sabeti: “Right when the outbreak hit, we were in a really good position, because we caught this virus early, and we had a head start, and even though the virus is moving quickly we kind of had never gotten this kind of data this fast out into the world.”

Newscaster: “This now makes the first coronavirus death confirmed in the US.”

Pardis Sabeti: “Looking back now, it’s so frustrating to see that we did lose all of that lead.”

Newscaster: “Doctors say they have now detected the first two cases of the variant which originated in the UK.”

Pardis Sabeti: “The virus mutated again and again and again as it was expected to do, and we might not have seen the worst of it.”

Monitoring mutations

Pardis Sabeti: “I’m a computational geneticist. My lab develops new technologies in genomics and then uses those to track infectious diseases. We are actively working in a number of states in the US, doing sequencing and identifying variants. The way that we identify a virus is that you take a sample wherever the virus is shedding. We see it in our nasal passages and we see it in our saliva. You can take that and you can basically access the genome of the virus in the sample, and there’s a lot of molecular tools like PCR, which is just a way of amplifying that part of the virus and seeing that it’s present.

“We can just take it a step further and not just amplify and say is it there or not there, but read out exactly what the genome of the virus that’s there is. And that gives us much more information about what version of the virus are we seeing, how is it related to other versions.

SARS-CoV-2: Evolution

Pardis Sabeti: “With microbes in general, we really get to see evolution in real time. In a year, you can just see generations and generations of things happening. And what we’ve seen is what we expect to see — that the virus keeps picking up mutations that make it better or spread more easily and evade therapies and those are the ones that are going to keep propagating.

SARS-CoV-2: The virus

Pardis Sabeti: “SARS-CoV-2 is a very big virus as viruses go. Coronaviruses in general, they’re very big genomes — they’re 30 kilobases — and so that’s a lot of information that they’ve got, and a lot that can change that we need to understand and deconstruct and decode. They are also RNA genomes so we know that those mutate fast relative to other organisms, and so we have to be mindful and watching what they’re doing all the time.

“One of the things I think is interesting about Covid is it has forced an entire collective, an entire generation of scientists to look at it, and to study it and to generate a lot of data. I think that’s one of the things that’s special about it, is just the number of eyes that have been on it.”

SARS-CoV-2: Decoding the genome

Pardis Sabeti: “A genome is this long kind of code, where there’s four letters that are strung together in this way, and a lot of times if you can decipher that there’s a lot of information there.

“So mathematics becomes really, really important in deciphering this. We use a lot of statistical tools to mine the data of the 30,000 bases of the SARS-CoV-2 genome. In the hundreds of thousands of genomes have been sequenced, you can find patterns using mathematics.

So my lab, one of the big things we do is we build algorithms to mine this data and to look for patterns. You can trace the origin, you can date when the virus likely entered the population, you can get a sense of how it’s transmitting and whether or not it’s coming in from multiple infections from the environment or if it’s likely that the disease is spreading from person to person in a close amount of time.”

Tracing the origin: Learning from Ebola

Pardis Sabeti: “In the case of Ebola, for a long time into the outbreak, people believed that Ebola was being transmitted from the environment. Around the world, all the messaging was don’t touch monkeys, don’t touch bats, don’t touch fruit that might be touched by those animals. It was really always thinking — assuming — that every case was coming from the environment. It didn’t really make sense with how quickly it was spreading.

“Our data was pretty strongly indicating that this was transmitting from human to human, that they were all — all of the viruses descended from one likely original infection that probably entered the human population once, and was from there transmitting from human to human. So that was like a kind of thing that was revelatory for Ebola, and since then we have a better understanding that that’s a pretty common phenomenon can happen. In SARS-CoV-2, it’s similar that we can see that all of the cases that we’re looking at originated from one common ancestor, suggestive of one long transmission chain.

“You know there’s a question of, could it infect animals and come back out and infect humans, and that’s possible, but that we know that the primary mode of transmission is from human to human.

“When you give a virus more opportunities to transmit from human to human than ever before, you’re going to see a lot of changes. Most of those changes don’t really matter — like most mutations are probably detrimental or just get cleared out — but when you give it that many chances, it will stumble upon things that help it, and when those things emerge, they’re more likely to reproduce and pass on. The fewer the viruses are out there, and the fewer those viruses transmit, the less mutations we’re going to see. It’s a pretty kind of direct correlation between the number of infection cycles you have, the number of opportunities you have for new mutations to arise, and so the best thing we can do is to get the infection rates to zero, so that the virus has no opportunities to mutate and change.”