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I'm Jad Abumrad. This is Radiolab dispatch number. Whatever number we're at, I'm gonna say 14. I'm not sure this dispatch is a little bit more lo fi than than even our others because I don't know.

I just wanted to play you a conversation I had with senior correspondent Molly Webster. She and I check in every Friday morning where she usually just kind of updates me on new research. She's following things she's been interested in and in this case, her research update to me last Friday, which is so interesting.

I'm reporting you are here recording that we decided to record.

OK, we'll talk and then you just tell me to stop whenever. I will tell you to stop it. Why would I tell you that? You know, you'd be the rare person in my life who doesn't.

She told me about a few new studies that she had just read.

These are articles about different individual covid patients from different spots around the world.

And each paper looked at how the virus behaves inside a single human body. One a case study from the UK starts with a man in his 70s coming into a hospital with an immune system that was already pretty low.

Yeah, his immune system was low because he had lymphoma and then was on a drug to try and keep the cancer in check. And that lowers your gut and your immune system. So this man in his 70s, he had a suppressed immune system and he shows up in a hospital because of cancer stuff. And while he's there, they test him and he's positive for sars-cov-2, OK, but he seems relatively fine and he just has like a small cough or something.

And so they send him home. And then thirty five or thirty four days later, on day thirty five, he walks back into the hospital and what had been a cough for the last month had turned into shortness of breath. And they test him again.

And he has coronavirus, which most likely meant that he had coronavirus for the whole month and couldn't get rid of it.

So we test positive for coronavirus and he has like the covid-19 pneumonia kind of settles into your lungs. The crackly cough thing. Yeah, the gray spots on the lungs that they, like, identify in CT scans and stuff. And so they check him into the hospital. And then what basically starts is just a series of trying to treat this man. At the same time, the UK is actually really good about taking samples and genetic sequencing them, as we all know, in a way that America is not doing right now.

And so so over the course of his time in the hospital, and he does eventually end up dying on what they say is day one or two. Oh, wow. Over the course of that time, they sequenced his virus twenty three times.

So basically over the last three and a half months of this man's life, the doctors take snapshots of the virus inside him. You can think of these as a series of stills that capture what the virus is doing, how it is moving. You can take them as mug shots, series of mug shots. Now, at this point, this is going back a year.

There was really only one main version of sars-cov-2 that was out there, or at least in our consciousness.

There weren't all of these variants from South Africa or Brazil or the New York City variant that there's a new one.

Yeah, I do. The New York City was new and now there's a new Oregon variant.

Oh, snap. None of that was on our radar yet. We were just focused on the original. The original like what I call like Oge sars-cov-2. That was the perp that the doctors expected to see on all those mug shots. And they did see it on day one. But then when he went away and came back thirty four days later and proceeded to get sicker and sicker in the hospital, they sequenced again.

And this time they saw something different.

Instead of just one covid virus inside them, they saw pop up like little subpopulations.

They saw a whole bunch of different kinds with enough variation that they look different. Huh. What they noticed is like, oh, there's still the dominant like Oge sars-cov-2 genetic sequence all over this body. But Lurdes, that really small, quiet like subpopulations that are hanging around and at the time they were like, whoa, whoa, whoa. There's all these, like variations. What has this person been infected by, like six different types of this virus and they all happen to get into this person at the same time.

Oh, like, he somehow managed to have six different encounters with six different coronaviruses or like day one, he had a case and then it cleared.

Yeah. And then maybe he got it again and then again and again and again.

So the doctors at that point have a new thought. Maybe this isn't the same infection that he's had the whole time. Maybe these are separate viruses, entirely separate.

But then they realized, no, this is one strain that got in and just keeps changing, changing, changing, changing, changing.

In other words, what the researchers came to understand and they weren't trying to study this.

They were simply trying to save the man's life, is that these subpopulations were one virus rapidly mutating, trying out new forms inside a human body, that when you have a human body that has a compromised immune system, the covid virus will just rapidly experiment that the immune suppressed body is like a playground of sorts because like nothing actually shuts the virus down and it can replicate uninhibited.

This one researcher said that at any point in time when you're like infected with coronavirus, you can have like at least a billion copies of the virus inside of you, one end zone, one billion.

And so that means that every time it replicates, it has a chance to, like, mutate, substitute, delete one little nucleotide.

But I thought the whole deal with the coronavirus I mean, you and I did a story about this is that unlike the other RNA viruses, which are super sloppy, the coronavirus actually catches its own mistakes pretty well and doesn't mutate that much.

So it doesn't actually mutate that fast, but it still does just mutate. And every time it replicates, there is a chance that mutation can set in and hence evolution can happen. Right, because if you change part of your genetic code. You have a chance to, like, have new characteristics that let you survive in the world in a different way. And so if it's in the body and it's allowed to replicate a billion times with really nothing to stop it, every time it replicates, you throw the dice and something can happen.

So getting back to this guy, the researchers note is that he's got all of these different subpopulations of sars-cov-2 viruses, different kinds inside of them. But most of the new variants, they're not really doing much.

They don't have much dominance. Like if you actually look at the numbers, I think it's something like I may be making this up, but I don't think I am. But it's something like the original genetic virus is almost at one hundred percent dominance. And every every other little subpopulation is like less than two percent.

But then she says the doctors start to give this guy treatments.

So he gets the hospital day thirty five, day forty one. They do a round of Ramdisk severe.

That's one of the few drug treatments available against the virus, day 50 for they do another round of Ramdas severe and then on day sixty three they give them convalescent plasma from a donor. And this is like the blood you take from the body of a person who has successfully fought off Kobie two. And you put it in a person who's struggling to mount an antibody defense system to like take the virus down.

The thought is and this is also a story we've done the antibodies in the survivors blood will help you fight off the virus.

So day six to three, guy gets infusion of plasma and then on day sixty five, they give them another batch of convalescent plasma. So they're like giving treatments. And then as they're giving treatments, they're taking samples and genetically sequencing them. And what they see is that by the time they check his. Samples in the eighties, like eighty two or day eighty one. The different subtypes have like exploded really, and and there are like very noticeable changes in the coronavirus inside his body.

More on that after the break.

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This is Radiolab. I'm Jad Abumrad. Today, we are in Molly Webster territory.

Actually, we are in the middle of a recording of her Ani's weekly meeting, where she was telling me about some papers that have just come out that show how the sars-cov-2 virus behaves inside a single human body.

I also just want to say before we rejoin, we join that conversation.

God bless the man in the U.K. and the human beings who are at the center of these case studies papers kept their identities secret.

Of course, we will obviously do the same.

But in a few of these cases, not all these people passed away and they allowed doctors to study them in the final months of their life so that we could all learn something about the nature of this enemy. So endless gratitude to those people.

OK, so before the break, Molly was explaining that in this this man in the U.K. with a compromised immune system, the doctors first noticed that there were all of these variants of the coronavirus popping up, all these different subpopulations, which were basically kept in check for a while.

But then as soon as the doctors started trying to treat the patient with drugs and convalescent plasma, those subpopulations just explode.

And there are like very noticeable changes in the coronavirus inside his body. They see like these deletions that they call deletions that sixty nine and seventy. And then there's this other mutation at something called seven ninety six. It's very it's very wonky, like all based on like amino acid positioning, OK. And suddenly that that virus variant is dominant. Huh. And the OGE sars-cov-2 virus variant has become a quiet subpopulation.

Weird. So. OK, help me unpack with that.

I don't quite know how to how to here that does that mean that whatever it was in the plasma or whatever antibody army came in from the donor obliterated Jesus, but it somehow allowed for this little subpopulation to just bloom, essentially.

So what they say is like, oh, my gosh, we added in all of these antibodies and we've just witnessed. How sars-cov-2 might try and get around those antibodies, so they basically witnessed evolution happening right in front of them. Yes. Is that is that the way to say it? That is right.

And in the example you just gave, where there was a mutation in 60 or 70 or whatever it was, what does that actually do for the virus?

So the sixty nine 70 deletion on its own makes the virus twice as efficient at infecting cells. Really, and they think that's because it can clamp on more tightly to your cells.

And so if you have that variation, you bind more tightly, which means like when you inject your genetic material, it all gets inside and the cell can't shake you.

OK, so we're only in stage one here. So they see this scary mutation bloom in this one patient, this poor man. And then Molly says, as they kept trying to treat the man and then test him to measure the effect of those treatments. They saw this kind of real time evolution just continue and escalate. They see all of these different populations come and go, rise, fall.

There might be two different types and they rise and fall together. And then there's somewhere like a virus variant A is in there. D won't survive. I have this like a little part of the paper. Cut out. I'm just going to read it to you. Yeah, it is. Patterns in the variant frequency suggests competition between virus populations carrying different mutations, viruses with the mutation deletion pair spike letters seven ninety six sixty nine 70 rose to high frequency during convalescent plasma therapy, but were then outcompeted by another population in the absence of therapy.

Specifically, these data are consistent with a lineage of viruses with the MSP two five one three T and already P r d RPV one five seven L variant, which was dominant on day sixty six but was outcompeted during therapy by the mutation deletion variant. That's seven ninety six and sixty nine seventy. With the lapse in therapy, the original strain which had acquired and fifteen and one seven seven three s and the spike y two hundred h t to forty. I regain dominance followed by the emergence of a separate population with the spike w sixty four GP three three zero s variant.

That's like one paragraph from the paper. So those are all different like subpopulations of coronaviruses that are kind of duking it out in this one guy.

This all happened in that one body, in that one patient in the UK. This is just from that paper.

Dang. How many different Korona tribes are we talking about? Let's see.

Let's just see if we can do a quick count. So this five one, why seven ninety six, sixty nine, seventy to forty two hundred eighty three thirty s w sixty four g i five 13 t v one five seven L and one seven seven three s. So something like at least ten different populations rose and fell. Viruses have state like these virus variants have existed in different parts of the body. Some of them exist all over globally, some exist in different parts of the body, and they're all having different types of battles with the things you're putting inside, and then they're all having different types of battles with each other.

And they're seeing this in a single human. Yes, a single person. I don't know why, but this is completely blowing my mind.

Well, because one of the one of the scientists described it as like.

You can see a single body, a single patient as like a battleground or a training ground where the fuckin scary look, if you know what it's like, if you can look in and follow the action, it's almost like The Truman Show. But rather than us being in The Truman Show, you're looking in you're looking into The Truman Show like watching the world change and be manipulated. And you're like, now I want to make it rain now. Now I will cause a tornado and I'm going to see, like, how the world.

That how this world reacts, that it's just like a whole microcosm inside one person in that passage you read it said that the the different populations of coronavirus are competing. Are they fighting?

How are they fighting? It's all about real estate, really. It's like, can you get in a cell? How fast can you get in a cell and how quickly can you replicate in that cell? If you think about the body, there is a limited number of cells for the virus to infect. And so if it wants to make lots of different types of itself and I'm saying wants like it has like a wish, if it wants to make different types of itself, all of those different variants are fighting for the same real estate.

Huh?

Like, there's there there's there's one paper about a patient who had had Corona, who is immune suppressed, had coronavirus for at least 70 days, asymptomatic. Eventually it cleared their system, but they saw the virus mutating inside this one person. There's something that medicine can witness. I think it's not even like learn. It's like actually like what what we can witness is, in a sense, everything that is happening out in the wild.

But like in one place will be, oh, yeah, I just did a big jump.

You just made a jump gate, which is which is which is where my mind was going, which was it.

OK, so if we if we zoom out just a bit and we look at this one body and we see that these via these variations, these different populations that are rising and falling and competing for real estate, is there anything that they are seeing in these single human cases inside of these single immunosuppressed people that is mirroring?

What we're seeing out in the world in terms of all the different variants that are floating around in South Africa and Brazil and all that, so that's where it gets really spinny.

That's that's where it gets really tricky. Is that. These patients end up being like a blueprint, like with them, you could see what the virus might do in the future and to break that down, what they saw happen inside those bodies were the formation and creation of mutations that then appeared out in the wild six months later in the UK variant, the South African variant and the Brazil variant that we're all like running scared from five months before a scary virus variant showed up in the wild.

They saw it inside a person.

OK, ok, OK.

If they're seeing these mutations dominate in immunocompromised bodies before they dominate in the wild, does that tell them that they started in immunocompromised bodies and then got out into the wild?

Well, so that's an interesting question. So so with this specific case studies that were written up, uh, whatever happened inside the body never left the body because the because the patient was in hospital the whole time and closed down.

But the thought now is based on two of these case studies and a few others that have come out, is that probably at least the UK variant, that B one one seven came out of an immunocompromised body because they said that variant has like a significant mutations in it, and in order to get that in the wild, it would take many, many months. And if you were genetically sequencing like they do very frequently in the UK, you would see the tracings of that change start to happen.

Interestingly, like, oh, there's a change here. That's change one, there's a change here that's changed, too. There's a change here. That's change three. But everyone said one day they woke up and there was a new virus with like eight significant changes, which makes them think of it like that all happened in one hidden place and then, like, burst onto the scene.

So that's so funny, because that's that was the the experience of consuming the news was like, oh, you know, Kokabee, too.

And then, like, I remember hearing that, like, it doesn't mutate that much. Okay, great. I'm glad to hear that.

And we've got these vaccines coming in. Yeah.

And then suddenly, like, literally on a Tuesday, everyone's like, oh, snap.

There's a very, very we've got to do that. And I'm like, wait, what where did that come from? Well, scientists have the same reaction. And what they're saying is in these like immune suppressed patients where you're where you can witness the virus trying to adapt and where you can, like, step by step, see how it interacts with each treatment you give it, you can actually have a clue to, like how the virus might change in the future.

Because if it's if but there's that's so weird. It's like seeing the future. It is.

It is like this one guy called a crystal ball. Another guy called it the harbinger of what's to come in the virus like the wild.

Yeah. The idea is at some level, the virus can change a lot of ways, but at another level it can only change so many ways. And so if you watch it mutate like a million, two million, three million, four million, five million times inside a person's body, and you see which variants dominate this like a pretty good chance that like, OK, if the virus ever rolled the dice out in the wild and it landed on this mutation, this mutation would take hold and thrive.

So it's very possible it's going to hit the same mutations in different places independently and we might be able to see that in advance inside one person. Yes. Yeah, you know, it's what I. What I what I'm struck by, yeah, it's really it's it's interesting to hear the story right now. You know, because it's it's. It's from one moment to the next, it's really hard to know whether to feel optimistic or pessimistic, right? Right.

You know, it's like and kind of the story you're telling and it's weird to, like, look outside and see like, oh, it's sunny, like spring is coming, like the vaccines are rolling out. We might actually get to go have. Dinner with friends again and everybody's like in this kind of like a normal normal life is returning with the story you're telling me is like.

Is it? The virus is crafty. But then maybe so are we. I don't know, it's weird to juxtapose what you're saying against that sense of like optimism that's out in the world, because what I'm hearing is that simultaneously this virus is figuring us out. And we're figuring it out. Yeah, and maybe we're turning the corner or maybe we're just in the first chapter of a very long story, you know.

Yeah, like I. I think I keep having a having a lot of visuals like myself, and I would say my community are probably at the lowest ebb. I've seen them act in the last year, but also with with a whole bunch of, like, hope. Just starting to like Glymour, I keep thinking of that midnight in the Garden of Good and Evil statue, do you know what that is?

It's like the little girl and she has her hands up by her shoulders with her palms, like up to the sky. And it's like good and evil are like weighted on each side like that.

Feels like this moment in COGAT to me, where you're feeling like optimism and pessimism, you're holding like hope and just like utter exhaustion like on both shoulders.

Yeah. Wow, yeah, that's that's exactly it. Senior correspondent Molly Webster. This episode would not be possible without the counsel and the interviews with Ravi Gupta and Jonathan Lee, thank you both so, so much. Huge thanks to them. And thanks again to Molly and to you for listening. I'm Jad Abumrad. We'll be back with you again next week. Hi, my name's Facebook, I'm calling from Bonn, Germany, that was created by Jad Abumrad and edited by Foreign Wheeler, Lulu Miller and Nossa.

I'll co-host Susie Luxemburg, now executive producer Dylan CASIS, our director of sound design. I'll stop. And Simon Adler, Jeremy Bloom, Becca Bressler, Rachel Kucik, David Gabal, Matt Kielty and in The Kyun, Sakari Arion Wack Walters' and Molly Webster with help from Cima Olia, Sarah Finback, Johnny Mones and Karenni on our fact checkers, De-Anne Kelly and Emily Kreger.

Oh, yeah. This episode is sponsored by a new podcast called Now What's Next for Morgan Stanley? It's filled with stories of people trying to adapt to and look beyond the global crisis. We're facing chefs, entrepreneurs, health care workers, grounded world travelers. There's even an astronaut. Their stories are unique and their outlooks are optimistic. Listen to now what's next, wherever you get your podcasts.