Speaker 1: Viruses are in the air we breathe, in the water
Speaker 1: we drink. They're in the ground we walk on there,
Speaker 1: on our skin, they're in our bellies. They have us surrounded,
Speaker 1: and the wild thing is we've only identified a fraction
Speaker 1: of them. In other words, not only are we surrounded
Speaker 1: and permeated by viruses, we're surrounded and permeated by viral
Speaker 1: dark matter, by viruses that we don't even know exist.
Speaker 2: We have lots of viruses in us and we have
Speaker 2: no idea what they're doing, and potentially in that dark matter,
Speaker 2: there are some answers to the questions on what are
Speaker 2: they doing there.
Speaker 1: I'm Jacob Goldstein, and this is Incubation. Today, on our
Speaker 1: final episode of season two, we're going out to the
Speaker 1: scientific frontier to talk about all the viruses we don't
Speaker 1: know about in the world and in our bodies. In
Speaker 1: the second half of the show today, I'll be speaking
Speaker 1: with a researcher who has recently discovered hundreds of families
Speaker 1: of viruses that live inside the human gut, and he's
Speaker 1: found a link that suggests some of those viruses could
Speaker 1: actually help kids stay healthy. But first I'm going to
Speaker 1: talk with Ken Steadman he's a professor of biology at
Speaker 1: Portland State University. He studies viral dark matter, which basically
Speaker 1: means he goes looking for viruses in wild places. To start,
Speaker 1: I asked him, how do you look for a virus
Speaker 1: that nobody knows exists?
Speaker 2: A couple of different ways. All viruses that we know of,
Speaker 2: by definition, have to have a host that they infect.
Speaker 2: What we do is we'll go and collect samples in
Speaker 2: the craziest places we can find, usually volcanic hot springs,
Speaker 2: and then we bring them back to lab and see
Speaker 2: if they infect our favorite microbes that also happen to
Speaker 2: grow in these hot springs.
Speaker 1: I've read a little bit about your work at last
Speaker 1: in Volcanic National Park in northern California, So tell me
Speaker 1: about what's going on there. Tell me about Boiling Springs Lake.
Speaker 2: So, Boiling Springs Lake I like to describe as the
Speaker 2: biggest hot spring in the world that nobody has ever
Speaker 2: heard of. It's a slight exaggeration. The low temperature in
Speaker 2: the lake is about one hundred and thirty hundred and
Speaker 2: forty degrees fahrenheit.
Speaker 1: And so what does that mean for finding weird viruses?
Speaker 2: Well, hang on just a second, that's the temperature. I
Speaker 2: haven't told you about the pH yet, have I Wait
Speaker 2: a minute.
Speaker 1: If you like the temperature, you're gonna love the pH exactly.
Speaker 2: So the pH is about two.
Speaker 1: pH of two means it's it's acidic. It's highly acidic.
Speaker 1: So not great for soaking is what you're not great for.
Speaker 2: We've seen people walking up there and they're a swimming
Speaker 2: gear and we tell them not a real good idea.
Speaker 1: So you go to this hot, acidic lake and what
Speaker 1: what do you do there?
Speaker 2: We just took about two hundred liters worth of water
Speaker 2: from the lake and then purified all of the virus
Speaker 2: sized particles in it, then determined what their genetic sequences were,
Speaker 2: what we call them meta genome, but basically all the viruses,
Speaker 2: what genes do they have in.
Speaker 1: So you're basically just what pouring this acid into a
Speaker 1: machine and saying, tell me all the genes that are in.
Speaker 2: Here or or less. Yeah. So one of the things
Speaker 2: about viruses which makes virus is incredibly unique is they
Speaker 2: have what we like to call we call it a
Speaker 2: very on it's the virus structure. So the lunar lander
Speaker 2: module kind of thing.
Speaker 1: Right, your classic virus looks like a little lunar lander
Speaker 1: like a pod, and then little legs coming out right.
Speaker 2: Absolutely, and it's relatively small.
Speaker 1: So what you do is sayge right, that's the classic phase.
Speaker 1: That's the thing that lands on the bacterium and then
Speaker 1: inserts its genetic material.
Speaker 2: Injects it exactly. But even if you think about no
Speaker 2: Sarscobe two virus that causes COVID nineteen also is a
Speaker 2: little bag which has genes on the inside of it.
Speaker 2: So you break up in the bag and you throw
Speaker 2: it into the machine and then it gives you back
Speaker 2: hundreds of thousands of sequences in our case now millions
Speaker 2: of sequences with the newest technology, so millions of genes,
Speaker 2: hundreds of thousands of genes. But they're not genes, they're
Speaker 2: gene fragments, they're little pieces. Now, at first you just
Speaker 2: want to look at what those little pieces are relative
Speaker 2: to known sequences.
Speaker 1: Uh huh.
Speaker 2: That the dark matter is going to be, you know,
Speaker 2: those little pieces that don't match anything, and the light
Speaker 2: matter is going to be stuff that does Ninety plus
Speaker 2: percent of the sequences that we got back of our
Speaker 2: hundreds of thousands of sequences didn't match anything.
Speaker 1: And what did you think when you saw that, Oh.
Speaker 2: It's like other environments, other people seemed very similar things.
Speaker 2: So you do this with seawater, you do this with
Speaker 2: things you find in soil. Ninety odd percent plus or
Speaker 2: minus don't match anything.
Speaker 1: Does that mean that we don't know about ninety percent
Speaker 1: of the viruses that are out in the world. Is
Speaker 1: that broadly what that implies?
Speaker 2: That is exactly what it implies.
Speaker 1: And it's not just in a weirdo boiling acid lake.
Speaker 1: How about just in the dirt. If I just went
Speaker 1: into my yard and dug up some dirt and send
Speaker 1: it to somebody who could put it in one of
Speaker 1: your machines. What percentage of the viruses in my backyard
Speaker 1: are known to science?
Speaker 2: Roughly?
Speaker 1: Wow, eighty percent are dark matter are unknown. I love that.
Speaker 2: It's keeps us employed.
Speaker 1: Yeah, so okay, so you get this result back it's
Speaker 1: ninety percent is unknown. What like? And so what you
Speaker 1: just have is like a genetic mess that you don't
Speaker 1: know what to do with, because it's not like each
Speaker 1: little fragment is like, oh, that's a new virus. It's
Speaker 1: just these are weird fragments that we don't understand.
Speaker 2: Yeah, exactly weird fragments if we don't understand. But one
Speaker 2: of the other things that we found is some of
Speaker 2: the fragments that we could actually identify didn't look like
Speaker 2: sequences that we should have found, Meaning not only are
Speaker 2: they different than anythings that's been found before.
Speaker 1: They are like too weird, They're like, wait, that doesn't
Speaker 1: make any sense.
Speaker 2: How could that even be? Exactly did you think you
Speaker 2: had made a mistake of some sort so that the
Speaker 2: machine was broken. We thought that we had absolutely screwed
Speaker 2: up in this case. So we've got genetic material virus,
Speaker 2: you've got RNA viruses, you got DNA viruses, right, So.
Speaker 1: Basically a virus is just like a bag with genetic
Speaker 1: material in it. And there's some viruses have DNA and
Speaker 1: some viruses have RNA. And even though these are like
Speaker 1: two types of viruses, sort of historically evolutionarily, they're like
Speaker 1: really different from each other.
Speaker 2: Right, DNA viruses and RNA viruses we always thought were
Speaker 2: completely different relative to each other. And if you think
Speaker 2: about the evolutionary relationship between between RNA viruses and DNA viruses,
Speaker 2: there basically seems to be almost none.
Speaker 1: Like how big is the gap? Sort of whatever evolutionarily,
Speaker 1: how different are DNA and RNA viruses?
Speaker 2: So the difference between DNA and RNA viruses is probably
Speaker 2: billions of years evolutionarily speaking.
Speaker 1: Okay, I was gonna say, like, it's like as big
Speaker 1: as the difference between mammals and reptiles, but it's way
Speaker 1: bigger than that.
Speaker 2: It's probably more like the difference between you know, bacteria
Speaker 2: and people, bacterian people exactly, much more like that in
Speaker 2: terms of evolutionary difference.
Speaker 1: Wow. Okay, So there are these profoundly different things.
Speaker 2: So we sequenced a bunch of DNA put into our machine,
Speaker 2: you know, said hey, get some DNA sequences, and then
Speaker 2: some of those proxially a couple of thousand sequences that
Speaker 2: actually match. Something in those sequences were things that look
Speaker 2: like RNA viruses in terms of their sequence.
Speaker 1: But it's DNA that you're But we sequenced DNA.
Speaker 2: Yeah, but we and when I say we, mostly a
Speaker 2: graduate student working in our group, Jeff Deemer. He then
Speaker 2: started to try and put some of these pieces together.
Speaker 2: What he found was those pieces that looked like RNA
Speaker 2: viruses were connected genetically to sequences that looked like DNA viruses.
Speaker 1: Okay, and connected like physically like that they were physically
Speaker 1: almost like the one piece of a chain of genetic
Speaker 1: material exactly.
Speaker 2: And then what we did is we went back to
Speaker 2: the samples that we collected from Boiling Springs Lake, and
Speaker 2: instead of pouring them into the machine to get the sequences,
Speaker 2: we then made many many copies of whatever this piece was.
Speaker 2: And this piece was to show that were actual connected
Speaker 2: to each other. So there are these what we're now
Speaker 2: calling cruci viruses that appear to have evolved by DNA
Speaker 2: viruses and RNA viruses coming together.
Speaker 1: Okay, so we thought these were like totally different kinds
Speaker 1: of viruses, but now you have discovered this new kind
Speaker 1: of virus that's kind of like a cross between the
Speaker 1: two of them. Right, what does that mean? Like, what
Speaker 1: does it mean for how we think about RNA viruses
Speaker 1: and DNA viruses.
Speaker 2: It means that there's communication between them, and there's this recombination.
Speaker 2: So it's not billions of years of evolutionary difference, which
Speaker 2: is what we thought. Now it looks as if they
Speaker 2: can be exchanging genetic information with each other, which is
Speaker 2: really kind of revolutionary in terms of thinking about virus
Speaker 2: evolution and what it means is. We always thought DNA
Speaker 2: viruses evolved like this and RNA viruses evolved like this,
Speaker 2: But if they can exchange genes with each other, that
Speaker 2: kind of throws a lot of what we think about
Speaker 2: virus evolution kind of out the window. Turns out that
Speaker 2: these viruses in and of them els are just so
Speaker 2: different from any other virus anybody's ever seen before, in
Speaker 2: terms of their shape, in terms of their genes, what
Speaker 2: is in them?
Speaker 1: So you and your colleagues found this, this crucivirus in
Speaker 1: the boiling acid Lake. I know that since then a
Speaker 1: number of other of these cruciviruses have been found. So
Speaker 1: just give me the landscape. Give me what we know
Speaker 1: so far of like where are they, what are they doing, etc.
Speaker 2: We do not know what they're doing. Crucy virus has
Speaker 2: been found in boiling Springs Lake, Antarctic lakes, in deep
Speaker 2: sea sediments off the coast of Greenland, in Korean air samples,
Speaker 2: isopods off the coast of Oregon, monkey feces, in dragonfly guts,
Speaker 2: soil just outside the lab at Portland State University. Basically
Speaker 2: anywhere that we have looked, we've found these crucy viruses.
Speaker 2: Very low amounts of them, but seem to be very ubiquitous.
Speaker 2: So where are the everywhere?
Speaker 1: Love it?
Speaker 2: What are they doing? We don't know.
Speaker 1: Are they in my body right now?
Speaker 2: Probably in your body right now.
Speaker 1: So these things are all around us, all over the world,
Speaker 1: possibly in our guts, and nobody knows what they're doing.
Speaker 2: That is exactly correct. I love it me too.
Speaker 1: So what do we know about like what they're doing.
Speaker 2: We're trying to figure out what they infect. We think
Speaker 2: they're infecting microbial EU carry out, So things like fungi
Speaker 2: or protus, these paramesia things you know swimming around in lakes.
Speaker 1: Are there are those things? Also? Are there also organisms
Speaker 1: like that in our bodies?
Speaker 2: There definitely are?
Speaker 1: Is that part of the microflora?
Speaker 2: Yeah, we have. We have a euchreytic microflora. Mostly these
Speaker 2: are going to be fungi, some kinds of yeats, et cetera.
Speaker 2: But there are many other of the And again this
Speaker 2: is something which has been not very well studied, so
Speaker 2: you kind of put in environmental viruses have not been
Speaker 2: well studied. These microbial EU carry outs have not been
Speaker 2: very well studied. So you put those two together, extremely
Speaker 2: poorly studied.
Speaker 1: Very dark. It's very dark matter.
Speaker 2: Very dark matter, but at the same time really exciting
Speaker 2: because there's so much to discover.
Speaker 1: Like why does microbial dark matter matter?
Speaker 2: Besides being cool, I think it's an area where we
Speaker 2: can make discoveries. There's so much we don't know. We
Speaker 2: have lots of viruses in US and we have no
Speaker 2: idea what they're doing, and potentially in that dark matter
Speaker 2: there are some answers to the questions on what are
Speaker 2: they doing there? So I think that that's a very
Speaker 2: important thing to think about.
Speaker 1: Not just how are they making us sick, but how
Speaker 1: are they keeping us healthy? How might they get out
Speaker 1: of balance at times and contribute in indirect ways to sickness?
Speaker 1: Certainly seems plausible. We know that happens with the bacteria
Speaker 1: in our gut.
Speaker 2: Yeah, I think that that's a very reasonable thing to
Speaker 2: think about. And then just in a larger ecological sense,
Speaker 2: you know, understanding the ecology. There's still so much that
Speaker 2: we don't know. I think understanding that virus' role in
Speaker 2: not just us, but also in life on our planet.
Speaker 2: I think understanding that dark matter will really help us
Speaker 2: understand what's going on with all of these different pirates.
Speaker 1: I appreciate your time. It was a fun conversation.
Speaker 2: Yeah, it was fun conversation for me too. I learned things,
Speaker 2: So thank you for that good.
Speaker 1: Ken Stedman is a biology professor and extreme virologist at
Speaker 1: Portland State University. His work and his team's work are
Speaker 1: expanding our idea of what a virus can be in
Speaker 1: a minute, discovering hundreds of kinds of new viruses that
Speaker 1: live in the human gut. I'm going to go out
Speaker 1: on a limb and say the most underrated viruses are phages.
Speaker 1: Phages are the viruses that infect bacteria. They're the most
Speaker 1: abundant biological entity on Earth and their killers.
Speaker 3: Every other bacterium on Earth gets killed by a virus
Speaker 3: every day.
Speaker 1: Actually, that's wild to think about.
Speaker 3: It really sucks for them.
Speaker 1: Shiraz ali Sha studies the phages that live inside people.
Speaker 1: Your researcher on a project called COPSAC, the Copenhagen Prospective
Speaker 1: Studies for Asthma in Childhood. The project is following hundreds
Speaker 1: of kids from birth into childhood to try to understand
Speaker 1: the causes of asthma. Shiraz focuses on the human virum,
Speaker 1: the universe of viruses that live in the human gut
Speaker 1: and he told me that studying the viroom from birth
Speaker 1: is really important.
Speaker 3: In the first year of life, the baby has an
Speaker 3: immune system that has not yet matured, so it does
Speaker 3: not know how to distinguish friend from foe. What happens
Speaker 3: in the first year of life is that the immune
Speaker 3: system is still trying to get to know what is
Speaker 3: it supposed to attack and what is it not supposed
Speaker 3: to attack. And it seems that there's more and more
Speaker 3: evidence showing that if you are not exposed to a
Speaker 3: diverse array of good bacteria in the body and on
Speaker 3: the body within the first year of life, then the
Speaker 3: immune system is not properly trained, and then you're way
Speaker 3: more prone to chronic inflammatory or immune diseases in the future,
Speaker 3: like asthma like asthma, like allergy like asthma, even stuff
Speaker 3: like depression and anxiety, inflammation linked heart disease, most definitely cancer,
Speaker 3: most definitely diabetes, most definitely yes.
Speaker 1: So okay, so now you're getting into some of what
Speaker 1: you study, right, tell me about your work on this.
Speaker 3: So this is a place called COPSAC Copenhagen Perspective Studies
Speaker 3: for Asthma in Childhood.
Speaker 1: It's a place where they're trying to understand how asthma
Speaker 1: works in kids.
Speaker 3: Exactly, Okay, and so and so. The way that they
Speaker 3: do this is basically, they have a bunch of kids
Speaker 3: that were born in twenty ten and they've been following
Speaker 3: them since the moms got pregnant and today they're like
Speaker 3: fifteen years old.
Speaker 2: Right.
Speaker 3: What they're doing is they're recording as much data on
Speaker 3: these children as possible as humanly possible, like where do
Speaker 3: they go to date hair, how many siblings do they have,
Speaker 3: but also blood tests, you know, which chemicals do they
Speaker 3: have in their bodies in their pee, what bacteria do
Speaker 3: they have in their poop, in their lungs, et cetera,
Speaker 3: et cetera. So we have like jigabtes upon jigabat also
Speaker 3: their own genes, their own genomes we also have.
Speaker 1: And so, just to be clear, it's the idea of
Speaker 1: doing all this and starting before the child is even born.
Speaker 1: Is the question they're trying to answer, why do some
Speaker 1: people get asthma and others don't?
Speaker 3: Exactly Because even though asthma is such a common childhood
Speaker 3: kind of disease, it's very poorly understrue. And this is
Speaker 3: not only the case for asthma. It's also the case
Speaker 3: for all the other chronic diseases basically that kill adults,
Speaker 3: like cancer, heart disease, diabetes, you know, chronic respiratory disease,
Speaker 3: multiple scrosis, you know, all of these. And so maybe
Speaker 3: by collecting all of this data on the children, we
Speaker 3: can start predicting based on the data, who's going to
Speaker 3: get which disease, and based on that, maybe we can
Speaker 3: figure out, Okay, if we do this, this and this,
Speaker 3: maybe we can avoid that and that and that chronic disease.
Speaker 3: Every time the kids visit us, and they do so
Speaker 3: once a year, we take as money samples as we
Speaker 3: possibly can.
Speaker 1: Right, So you have this whole poop library going over
Speaker 1: the kid's whole lifetime that you can sort of examine
Speaker 1: over time. Yes, and how many kids are in this cohort?
Speaker 3: So we have two horts and what I'm going to
Speaker 3: talk about today. The data is from the corps AC
Speaker 3: twenty ten cohorts. So they were born in twenty ten.
Speaker 3: They're like fourteen years old now, right, And the twenty
Speaker 3: ten cohort is seven hundred kids.
Speaker 1: So the cohort you're following is seven hundred kids who
Speaker 1: were born in twenty ten. You're coming into this as
Speaker 1: a person who has been studying viruses that attack bacteria
Speaker 1: for purposes here, and so when you get there.
Speaker 2: What do you do?
Speaker 3: I get there and then my boss he basically explains
Speaker 3: me some of the studies that they've been doing on
Speaker 3: the bacteria in the gut so far. And one of
Speaker 3: the major studies that they did just like one year
Speaker 3: before I came was that they found that in one
Speaker 3: year old, when you're basically still a baby, the bacteria
Speaker 3: that you have in your gut when you're a baby
Speaker 3: end up determining whether or not you get asthma as
Speaker 3: a five year old. And I was like, what, I mean,
Speaker 3: how is that even possible? And so what the general
Speaker 3: picture is that if you have only a few different
Speaker 3: bacteria in your gut when you're one year old, then
Speaker 3: you have much higher risk of getting asthma as a
Speaker 3: five year old, right, But if you have like loads
Speaker 3: and loads of different bacteria in your gut when you're
Speaker 3: one year old, then you're much more protected from asthma
Speaker 3: as a five year old. And so basically that that
Speaker 3: got me thinking, Wow, that means that most bacteria are
Speaker 3: actually good for us. I mean, there are few bacteria,
Speaker 3: maybe one hundred species in total that can cause infection,
Speaker 3: But the total number of bacteria in nature is like
Speaker 3: one hundred million species at least, So those other one
Speaker 3: hundred million are not causing. It's just one out of a
Speaker 3: million bacterium.
Speaker 1: That is bad and the other one in a million
Speaker 1: gives him a bad name, and so go on.
Speaker 3: So I was thinking, Okay, if that's the case for bacteria,
Speaker 3: then what about viruses. What if it's the same for viruses.
Speaker 3: What if the only viruses that we know about are
Speaker 3: the ones that cause disease and there are loads of
Speaker 3: other viruses that are actually good for us. That's what
Speaker 3: I was thinking back then. But the funny thing is
Speaker 3: that this other guy called Dennis Nielsen, who is a
Speaker 3: professor at copenha University because he's an expert at figuring
Speaker 3: out which viruses are in a sample, he basically said, Okay,
Speaker 3: you guys found this thing with bacteria, why don't we
Speaker 3: look at the viruses in the gut and maybe we
Speaker 3: can find something similar or even cooler. And so when
Speaker 3: I started copsack, this data set is already in the
Speaker 3: pro being generated. Dennis has taken seven hundred fecal samples
Speaker 3: extracted viral particles, and then he has basically put them
Speaker 3: through a sequencer and we're getting in sequences from each.
Speaker 1: Child's sequences, meaning genetic sequences that allows you to determine
Speaker 1: what viruses. Yeah, exactly, So you get there in twenty seventeen,
Speaker 1: and another researcher is already just starting to look for
Speaker 1: what viruses are in the fecal samples of these kids
Speaker 1: in the study. How do you get involved to what
Speaker 1: do you do?
Speaker 2: What happens back then?
Speaker 3: What people used to do when they got gut VIRAM
Speaker 3: data is that they would then take all the DNA
Speaker 3: sequences that came out of that and they would then
Speaker 3: blast it. Is what it is called against a public
Speaker 3: database of viruses, viruses that scientists have already discovered and
Speaker 3: know about, so that you can figure out which viruses
Speaker 3: are in those samples. The problem is that most of
Speaker 3: the viruses in the human gut at that time were
Speaker 3: unknown to science by I love it. So by doing
Speaker 3: that exercise, you're only going to get like a list
Speaker 3: of contents of maybe ten virus, whereas the actual diversity
Speaker 3: in each sample is going to be like maybe ten
Speaker 3: thousand or maybe a thousand or something.
Speaker 1: Right, But the problem is you don't know what you're
Speaker 1: looking for, right, You just have this random strings of
Speaker 1: genetic material, and if you're trying to find newly discovered viruses, well,
Speaker 1: how do you even do that? In fact, how do
Speaker 1: you do it?
Speaker 3: So what we first do is we assemble all the
Speaker 3: sequences like a piece of a puzzle and get extended
Speaker 3: so that you get larger and larger fragments of DNA
Speaker 3: that must have come from the same virus.
Speaker 1: You have this weird set of little chains and you
Speaker 1: need to put together like, ah, here is a virus
Speaker 1: and here is a different virus.
Speaker 3: Yeah, exactly, And so that's then what happens. Now we
Speaker 3: got a bunch of DNA sequences from each child, so
Speaker 3: that then what I do is I annotate all the
Speaker 3: protein coding genes on these strands of DNA, so that
Speaker 3: I know which proteins are encoded on each DNA fragment,
Speaker 3: and by looking at those proteins, what they encode, what
Speaker 3: kind of functions those protein code, I can start making
Speaker 3: qualified guesses in terms of Okay, this one a virus
Speaker 3: and this one must not.
Speaker 1: Are you like actually looking at sequences and like look
Speaker 1: at like at like one looks at jigsaw puzzle pieces
Speaker 1: on a table.
Speaker 3: Yeah, I guess you could say. I mean, I can
Speaker 3: look at the protein coding genes that are encoded on
Speaker 3: each cluster, and I manually look through ten thousand clusters
Speaker 3: of sequences, and out of those ten thousand, around three
Speaker 3: hundred of them were the ones that I could confidently
Speaker 3: say were viruses and they correspond to viral families.
Speaker 1: So when you're saying you're manually looking through ten thousand,
Speaker 1: is that like years of work?
Speaker 3: Yeah, it took five years, actually four years.
Speaker 1: Yeah, And so you do this work, you spend four
Speaker 1: or five years going through this data. How many viruses
Speaker 1: do you find that live commonly in the human gut, in.
Speaker 3: The children who we looked at? And that's all we
Speaker 3: can really say anything about. There are ten thousand species
Speaker 3: of viruses distributed in around two hundred and fifty viral families.
Speaker 1: So so you discover all these new viruses, does that
Speaker 1: mean you get to name them?
Speaker 3: Super good question? So this is and this is this
Speaker 3: was actually a huge issue for us. So now we're
Speaker 3: finding two hundred and fifty new viral families. How are
Speaker 3: we gonna present this in a paper?
Speaker 1: Right? It can't just be like a b C. You're
Speaker 1: gonna write out a letter Earth exactly.
Speaker 3: And so a lot of different suggestions were on the table.
Speaker 3: Pokemon was one of them.
Speaker 1: Did you have a Pikachu in mind? That's the first question?
Speaker 3: Who gets to me exactly like Pikachu veradee? You know,
Speaker 3: Charmander Verde, et cetera, et cetera. And then a colleague
Speaker 3: of mine, Jonathan, who's the third author of this paper,
Speaker 3: he suggested, why not just name them after the kids?
Speaker 1: Are the kids in the study? The kids? Who's who's
Speaker 1: whose poop had the viruses in it?
Speaker 3: Exactly? So we shuffled all the names and then we
Speaker 3: just distributed them over the two undred and fifty viral families.
Speaker 3: So what are some of the names Christian Verde, Ucas Verde,
Speaker 3: Josephinea Verde.
Speaker 1: Yeah, So you do this work, you identify all of
Speaker 1: these previously undiscovered viruses that live in the guts of
Speaker 1: these kids. Do you then start to try and understand
Speaker 1: the health implications of different virmes et cetera.
Speaker 3: That was the entire purpose of this exercise, right, So
Speaker 3: those bacterial phages which were also by far most of
Speaker 3: all the families.
Speaker 1: The viruses that infect in bacteria.
Speaker 2: Okay, exactly.
Speaker 3: Those bacterial phage families can be divided into like two
Speaker 3: broad categories. They are the virulent bacteriophages and the temperate bacteriophages. Right.
Speaker 3: The virulent bacteriophages they just kill the bacteria, okay, whereas
Speaker 3: the tempered bacteriophagies they integrate themselves as prophages on the
Speaker 3: bacterial DNA.
Speaker 1: So first you look at the viruses that infect bacteria,
Speaker 1: and then you divide those into two categories, and you say,
Speaker 1: there's the viruses that just destroy the bacteria, and there's
Speaker 1: the viruses that infect the bacteria but don't destroy it.
Speaker 3: Exactly.
Speaker 1: Does that tell you anything clinically?
Speaker 2: Yeah?
Speaker 3: So Christina who was the first author of that paper
Speaker 3: that came out in Nature Medicine earlier this year, she
Speaker 3: found that it was the temperate bacterial phages that were
Speaker 3: predictive of later asthma. For some reason, the children that
Speaker 3: end up developing asthma by age five, they had way
Speaker 3: more temperate phages by pacteriophages in their gut at age one.
Speaker 1: Uh huh. And so the key data set is you're
Speaker 1: looking at the virum of the kids at age one
Speaker 1: and trying to understand is it predictive of asthma by
Speaker 1: age five? And what answer do you and your colleagues
Speaker 1: find to that question.
Speaker 3: What we find is that there are more temperate phages
Speaker 3: in the kids who end up developing asthma later. Then
Speaker 3: we look at the temperate phages specifically, and look, we
Speaker 3: look at which families of temperate phages are predictive of disease.
Speaker 3: And then what we find, which is kind of surprising
Speaker 3: and funny, is that nineteen of the two hundred and
Speaker 3: fifty families we had in total two hundred and thirty
Speaker 3: of the more tempered nineteen of them. If you look
Speaker 3: at the amounts of those nineteen families in the children,
Speaker 3: you can actually distinguish between kids that end up developing
Speaker 3: asthma as five year olds or not. And what's interesting
Speaker 3: is that the kids that develop asthma as five year
Speaker 3: olds have less of these nineteen families than the healthy ones.
Speaker 2: Aha.
Speaker 1: So, so is it right that these nineteen families of
Speaker 1: viruses seem to maybe be protective against asthma? Like having
Speaker 1: more of these of these particular viruses is correlated with
Speaker 1: a lower risk of asthma exactly. That's very interesting. Now
Speaker 1: I get nervous that even though it passes some set
Speaker 1: of statistical tests, this is going to be a fluke finding.
Speaker 1: You know, It's going to be due to random chance.
Speaker 1: And so what I really want you to do is
Speaker 1: go run this test on some other kids at age one,
Speaker 1: make your prediction, and have it come true by age five.
Speaker 1: Is that a reasonable thought?
Speaker 3: That is super reasonable, I have to say, Jacob. And
Speaker 3: this is also something that Nature and Medicine asked us
Speaker 3: to do, and we said, well, nobody else has virum
Speaker 3: data for so many children. Unfortunately, such a cohord does
Speaker 3: not exist. You know, COPSAC twenty ten is one of
Speaker 3: the most deeply phenotype cohorts in the world, so we
Speaker 3: were not able to replicate it in another cohort.
Speaker 1: Yeah. Yeah, So you have this finding that a certain
Speaker 1: family of virus seems to be protective against asthma. Are
Speaker 1: you able to understand anything about what causes a kid
Speaker 1: to have or not have this apparently protective family of
Speaker 1: viruses in their gut?
Speaker 3: Super good question. I don't know. I think it has
Speaker 3: a lot to do with different environmental factors that end
Speaker 3: up determining for random reasons, which viruses end up in
Speaker 3: the guts of these children.
Speaker 1: I mean, when you say you don't know, does that
Speaker 1: mean there's no way in your data set to investigate
Speaker 1: the question?
Speaker 3: There definitely is, and this is what we're doing is
Speaker 3: ongoing basically, right. So what we do see is that
Speaker 3: there's a huge correlation in, for example, where the kids live,
Speaker 3: whether they live in a rural environment or like a
Speaker 3: city environment. Okay, the ones that really live in a
Speaker 3: rural environment have a much more diverse, you know, ecosystem
Speaker 3: in the gut. In terms of the bacteria. We haven't
Speaker 3: looked at the viruses directly yet, but we have an
Speaker 3: intuition that the same might apply for viruses as well. Also,
Speaker 3: there's there are huge, you know, kind of links to
Speaker 3: the diet, the kind of food that you eat, whether
Speaker 3: it's very processed food or whether it's like whole foods.
Speaker 3: Whole foods are generally associated with way way higher diversity.
Speaker 3: So if you want to increase your chances of having
Speaker 3: the good viruses in your gut, then it's a good
Speaker 3: idea to live you know, rurally or at least spend
Speaker 3: some time in nature. It's a good idea to eat
Speaker 3: whole foods instead of process foods, et cetera.
Speaker 1: Okay, so that's based on what we know about bacteria
Speaker 1: and what you suspect is true also for viruses. Let
Speaker 1: me ask you this, when you think about the future,
Speaker 1: what do you hope we know about the virme in five, ten,
Speaker 1: twenty years that we don't know now.
Speaker 3: I'm hoping in the future that we have a much
Speaker 3: better overview in terms of what kinds of chronic diseases
Speaker 3: are caused by deficits in which viruses, but also in bacteria,
Speaker 3: so that we can prevent maybe ten twenty thirty years
Speaker 3: from now, we can prove event a lot of time
Speaker 3: diseases that cause a lot of problems today that those
Speaker 3: can just be prevented by giving babies viruses or bacteria
Speaker 3: or even adults.
Speaker 1: Thank you so much for your time. It was great
Speaker 1: to talk with you.
Speaker 3: Good to talk to you too.
Speaker 1: Shiraz Shaw is a senior researcher at the Copenhagen University
Speaker 1: Hospital ghenth HOFTA. Thanks to both of my guests today,
Speaker 1: Shiraz Shah and Ken Steadman. Incubation is a co production
Speaker 1: of Pushkin Industries and Ruby Studio at iHeartMedia. It's produced
Speaker 1: by Kate Furby and Brittany Cronin. The show is edited
Speaker 1: by Lacey Roberts. It's mastered by Sarah Buguer, fact checking
Speaker 1: by Joseph friedman Or. Executive producers are Lacey Roberts and
Speaker 1: Matt Romano. I'm Jacob Goldstein. Thanks very much for listening
Speaker 1: to this season of Incubation. I hope we'll be back
Speaker 1: next year with Season three.