December 5, 2024 • 30 mins
The world is full of undiscovered viruses. They’re in the air we breathe, the ground we walk on, and they’re inside our bellies. For this last episode of the season, we’re exploring the mysteries of the microbes that have us surrounded. First we meet Portland State University virologist Ken Stedman, who made a wild discovery that changed what we thought a virus could be. Then, Shiraz Shah from the Copenhagen University Hospital Gentofte explains how viruses that colonize our guts during infancy may affect our health for the rest of our lives.
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Episode Transcript
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Speaker 1 (00:04):
Viruses are in the air we breathe, in the water
we drink. They're in the ground we walk on there,
on our skin, they're in our bellies. They have us surrounded,
and the wild thing is we've only identified a fraction
of them. In other words, not only are we surrounded
(00:25):
and permeated by viruses, we're surrounded and permeated by viral
dark matter, by viruses that we don't even know exist.
Speaker 2 (00:34):
We have lots of viruses in us and we have
no idea what they're doing, and potentially in that dark matter,
there are some answers to the questions on what are
they doing there.
Speaker 1 (00:48):
I'm Jacob Goldstein, and this is Incubation. Today, on our
final episode of season two, we're going out to the
scientific frontier to talk about all the viruses we don't
know about in the world and in our bodies. In
(01:12):
the second half of the show today, I'll be speaking
with a researcher who has recently discovered hundreds of families
of viruses that live inside the human gut, and he's
found a link that suggests some of those viruses could
actually help kids stay healthy. But first I'm going to
talk with Ken Steadman he's a professor of biology at
(01:33):
Portland State University. He studies viral dark matter, which basically
means he goes looking for viruses in wild places. To start,
I asked him, how do you look for a virus
that nobody knows exists?
Speaker 2 (01:46):
A couple of different ways. All viruses that we know of,
by definition, have to have a host that they infect.
What we do is we'll go and collect samples in
the craziest places we can find, usually volcanic hot springs,
and then we bring them back to lab and see
if they infect our favorite microbes that also happen to
grow in these hot springs.
Speaker 1 (02:07):
I've read a little bit about your work at last
in Volcanic National Park in northern California, So tell me
about what's going on there. Tell me about Boiling Springs Lake.
Speaker 2 (02:16):
So, Boiling Springs Lake I like to describe as the
biggest hot spring in the world that nobody has ever
heard of. It's a slight exaggeration. The low temperature in
the lake is about one hundred and thirty hundred and
forty degrees fahrenheit.
Speaker 1 (02:29):
And so what does that mean for finding weird viruses?
Speaker 2 (02:32):
Well, hang on just a second, that's the temperature. I
haven't told you about the pH yet, have I Wait
a minute.
Speaker 1 (02:37):
If you like the temperature, you're gonna love the pH exactly.
Speaker 2 (02:41):
So the pH is about two.
Speaker 1 (02:43):
pH of two means it's it's acidic. It's highly acidic.
So not great for soaking is what you're not great for.
Speaker 2 (02:49):
We've seen people walking up there and they're a swimming
gear and we tell them not a real good idea.
Speaker 1 (02:55):
So you go to this hot, acidic lake and what
what do you do there?
Speaker 2 (02:58):
We just took about two hundred liters worth of water
from the lake and then purified all of the virus
sized particles in it, then determined what their genetic sequences were,
what we call them meta genome, but basically all the viruses,
what genes do they have in.
Speaker 1 (03:17):
So you're basically just what pouring this acid into a
machine and saying, tell me all the genes that are in.
Speaker 2 (03:25):
Here or or less. Yeah. So one of the things
about viruses which makes virus is incredibly unique is they
have what we like to call we call it a
very on it's the virus structure. So the lunar lander
module kind of thing.
Speaker 1 (03:40):
Right, your classic virus looks like a little lunar lander
like a pod, and then little legs coming out right.
Speaker 2 (03:46):
Absolutely, and it's relatively small.
Speaker 1 (03:48):
So what you do is sayge right, that's the classic phase.
That's the thing that lands on the bacterium and then
inserts its genetic material.
Speaker 2 (03:54):
Injects it exactly. But even if you think about no
Sarscobe two virus that causes COVID nineteen also is a
little bag which has genes on the inside of it.
So you break up in the bag and you throw
it into the machine and then it gives you back
hundreds of thousands of sequences in our case now millions
(04:14):
of sequences with the newest technology, so millions of genes,
hundreds of thousands of genes. But they're not genes, they're
gene fragments, they're little pieces. Now, at first you just
want to look at what those little pieces are relative
to known sequences.
Speaker 1 (04:31):
Uh huh.
Speaker 2 (04:32):
That the dark matter is going to be, you know,
those little pieces that don't match anything, and the light
matter is going to be stuff that does Ninety plus
percent of the sequences that we got back of our
hundreds of thousands of sequences didn't match anything.
Speaker 1 (04:45):
And what did you think when you saw that, Oh.
Speaker 2 (04:48):
It's like other environments, other people seemed very similar things.
So you do this with seawater, you do this with
things you find in soil. Ninety odd percent plus or
minus don't match anything.
Speaker 1 (05:01):
Does that mean that we don't know about ninety percent
of the viruses that are out in the world. Is
that broadly what that implies?
Speaker 2 (05:09):
That is exactly what it implies.
Speaker 1 (05:11):
And it's not just in a weirdo boiling acid lake.
How about just in the dirt. If I just went
into my yard and dug up some dirt and send
it to somebody who could put it in one of
your machines. What percentage of the viruses in my backyard
are known to science?
Speaker 2 (05:26):
Roughly?
Speaker 1 (05:29):
Wow, eighty percent are dark matter are unknown. I love that.
Speaker 2 (05:35):
It's keeps us employed.
Speaker 1 (05:38):
Yeah, so okay, so you get this result back it's
ninety percent is unknown. What like? And so what you
just have is like a genetic mess that you don't
know what to do with, because it's not like each
little fragment is like, oh, that's a new virus. It's
just these are weird fragments that we don't understand.
Speaker 2 (05:56):
Yeah, exactly weird fragments if we don't understand. But one
of the other things that we found is some of
the fragments that we could actually identify didn't look like
sequences that we should have found, Meaning not only are
they different than anythings that's been found before.
Speaker 1 (06:16):
They are like too weird, They're like, wait, that doesn't
make any sense.
Speaker 2 (06:20):
How could that even be? Exactly did you think you
had made a mistake of some sort so that the
machine was broken. We thought that we had absolutely screwed
up in this case. So we've got genetic material virus,
you've got RNA viruses, you got DNA viruses, right, So.
Speaker 1 (06:33):
Basically a virus is just like a bag with genetic
material in it. And there's some viruses have DNA and
some viruses have RNA. And even though these are like
two types of viruses, sort of historically evolutionarily, they're like
really different from each other.
Speaker 2 (06:48):
Right, DNA viruses and RNA viruses we always thought were
completely different relative to each other. And if you think
about the evolutionary relationship between between RNA viruses and DNA viruses,
there basically seems to be almost none.
Speaker 1 (07:07):
Like how big is the gap? Sort of whatever evolutionarily,
how different are DNA and RNA viruses?
Speaker 2 (07:14):
So the difference between DNA and RNA viruses is probably
billions of years evolutionarily speaking.
Speaker 1 (07:23):
Okay, I was gonna say, like, it's like as big
as the difference between mammals and reptiles, but it's way
bigger than that.
Speaker 2 (07:31):
It's probably more like the difference between you know, bacteria
and people, bacterian people exactly, much more like that in
terms of evolutionary difference.
Speaker 1 (07:41):
Wow. Okay, So there are these profoundly different things.
Speaker 2 (07:45):
So we sequenced a bunch of DNA put into our machine,
you know, said hey, get some DNA sequences, and then
some of those proxially a couple of thousand sequences that
actually match. Something in those sequences were things that look
like RNA viruses in terms of their sequence.
Speaker 1 (08:03):
But it's DNA that you're But we sequenced DNA.
Speaker 2 (08:06):
Yeah, but we and when I say we, mostly a
graduate student working in our group, Jeff Deemer. He then
started to try and put some of these pieces together.
What he found was those pieces that looked like RNA
viruses were connected genetically to sequences that looked like DNA viruses.
Speaker 1 (08:29):
Okay, and connected like physically like that they were physically
almost like the one piece of a chain of genetic
material exactly.
Speaker 2 (08:38):
And then what we did is we went back to
the samples that we collected from Boiling Springs Lake, and
instead of pouring them into the machine to get the sequences,
we then made many many copies of whatever this piece was.
And this piece was to show that were actual connected
to each other. So there are these what we're now
calling cruci viruses that appear to have evolved by DNA
(09:02):
viruses and RNA viruses coming together.
Speaker 1 (09:04):
Okay, so we thought these were like totally different kinds
of viruses, but now you have discovered this new kind
of virus that's kind of like a cross between the
two of them. Right, what does that mean? Like, what
does it mean for how we think about RNA viruses
and DNA viruses.
Speaker 2 (09:20):
It means that there's communication between them, and there's this recombination.
So it's not billions of years of evolutionary difference, which
is what we thought. Now it looks as if they
can be exchanging genetic information with each other, which is
really kind of revolutionary in terms of thinking about virus
(09:41):
evolution and what it means is. We always thought DNA
viruses evolved like this and RNA viruses evolved like this,
But if they can exchange genes with each other, that
kind of throws a lot of what we think about
virus evolution kind of out the window. Turns out that
these viruses in and of them els are just so
(10:01):
different from any other virus anybody's ever seen before, in
terms of their shape, in terms of their genes, what
is in them?
Speaker 1 (10:11):
So you and your colleagues found this, this crucivirus in
the boiling acid Lake. I know that since then a
number of other of these cruciviruses have been found. So
just give me the landscape. Give me what we know
so far of like where are they, what are they doing, etc.
Speaker 2 (10:27):
We do not know what they're doing. Crucy virus has
been found in boiling Springs Lake, Antarctic lakes, in deep
sea sediments off the coast of Greenland, in Korean air samples,
isopods off the coast of Oregon, monkey feces, in dragonfly guts,
soil just outside the lab at Portland State University. Basically
(10:50):
anywhere that we have looked, we've found these crucy viruses.
Very low amounts of them, but seem to be very ubiquitous.
So where are the everywhere?
Speaker 1 (11:01):
Love it?
Speaker 2 (11:01):
What are they doing? We don't know.
Speaker 1 (11:03):
Are they in my body right now?
Speaker 2 (11:06):
Probably in your body right now.
Speaker 1 (11:09):
So these things are all around us, all over the world,
possibly in our guts, and nobody knows what they're doing.
Speaker 2 (11:17):
That is exactly correct. I love it me too.
Speaker 1 (11:23):
So what do we know about like what they're doing.
Speaker 2 (11:26):
We're trying to figure out what they infect. We think
they're infecting microbial EU carry out, So things like fungi
or protus, these paramesia things you know swimming around in lakes.
Speaker 1 (11:40):
Are there are those things? Also? Are there also organisms
like that in our bodies?
Speaker 2 (11:46):
There definitely are?
Speaker 1 (11:47):
Is that part of the microflora?
Speaker 2 (11:49):
Yeah, we have. We have a euchreytic microflora. Mostly these
are going to be fungi, some kinds of yeats, et cetera.
But there are many other of the And again this
is something which has been not very well studied, so
you kind of put in environmental viruses have not been
well studied. These microbial EU carry outs have not been
(12:11):
very well studied. So you put those two together, extremely
poorly studied.
Speaker 1 (12:16):
Very dark. It's very dark matter.
Speaker 2 (12:20):
Very dark matter, but at the same time really exciting
because there's so much to discover.
Speaker 1 (12:25):
Like why does microbial dark matter matter?
Speaker 2 (12:29):
Besides being cool, I think it's an area where we
can make discoveries. There's so much we don't know. We
have lots of viruses in US and we have no
idea what they're doing, and potentially in that dark matter
there are some answers to the questions on what are
(12:50):
they doing there? So I think that that's a very
important thing to think about.
Speaker 1 (12:55):
Not just how are they making us sick, but how
are they keeping us healthy? How might they get out
of balance at times and contribute in indirect ways to sickness?
Certainly seems plausible. We know that happens with the bacteria
in our gut.
Speaker 2 (13:08):
Yeah, I think that that's a very reasonable thing to
think about. And then just in a larger ecological sense,
you know, understanding the ecology. There's still so much that
we don't know. I think understanding that virus' role in
not just us, but also in life on our planet.
I think understanding that dark matter will really help us
(13:31):
understand what's going on with all of these different pirates.
Speaker 1 (13:44):
I appreciate your time. It was a fun conversation.
Speaker 2 (13:46):
Yeah, it was fun conversation for me too. I learned things,
So thank you for that good.
Speaker 1 (13:54):
Ken Stedman is a biology professor and extreme virologist at
Portland State University. His work and his team's work are
expanding our idea of what a virus can be in
a minute, discovering hundreds of kinds of new viruses that
(14:14):
live in the human gut. I'm going to go out
on a limb and say the most underrated viruses are phages.
(14:36):
Phages are the viruses that infect bacteria. They're the most
abundant biological entity on Earth and their killers.
Speaker 3 (14:45):
Every other bacterium on Earth gets killed by a virus
every day.
Speaker 1 (14:50):
Actually, that's wild to think about.
Speaker 3 (14:53):
It really sucks for them.
Speaker 1 (14:55):
Shiraz ali Sha studies the phages that live inside people.
Your researcher on a project called COPSAC, the Copenhagen Prospective
Studies for Asthma in Childhood. The project is following hundreds
of kids from birth into childhood to try to understand
the causes of asthma. Shiraz focuses on the human virum,
(15:17):
the universe of viruses that live in the human gut
and he told me that studying the viroom from birth
is really important.
Speaker 3 (15:24):
In the first year of life, the baby has an
immune system that has not yet matured, so it does
not know how to distinguish friend from foe. What happens
in the first year of life is that the immune
system is still trying to get to know what is
it supposed to attack and what is it not supposed
to attack. And it seems that there's more and more
evidence showing that if you are not exposed to a
diverse array of good bacteria in the body and on
(15:48):
the body within the first year of life, then the
immune system is not properly trained, and then you're way
more prone to chronic inflammatory or immune diseases in the future,
like asthma like asthma, like allergy like asthma, even stuff
like depression and anxiety, inflammation linked heart disease, most definitely cancer,
most definitely diabetes, most definitely yes.
Speaker 1 (16:09):
So okay, so now you're getting into some of what
you study, right, tell me about your work on this.
Speaker 3 (16:14):
So this is a place called COPSAC Copenhagen Perspective Studies
for Asthma in Childhood.
Speaker 1 (16:19):
It's a place where they're trying to understand how asthma
works in kids.
Speaker 3 (16:23):
Exactly, Okay, and so and so. The way that they
do this is basically, they have a bunch of kids
that were born in twenty ten and they've been following
them since the moms got pregnant and today they're like
fifteen years old.
Speaker 2 (16:34):
Right.
Speaker 3 (16:34):
What they're doing is they're recording as much data on
these children as possible as humanly possible, like where do
they go to date hair, how many siblings do they have,
but also blood tests, you know, which chemicals do they
have in their bodies in their pee, what bacteria do
they have in their poop, in their lungs, et cetera,
et cetera. So we have like jigabtes upon jigabat also
their own genes, their own genomes we also have.
Speaker 1 (16:54):
And so, just to be clear, it's the idea of
doing all this and starting before the child is even born.
Is the question they're trying to answer, why do some
people get asthma and others don't?
Speaker 3 (17:06):
Exactly Because even though asthma is such a common childhood
kind of disease, it's very poorly understrue. And this is
not only the case for asthma. It's also the case
for all the other chronic diseases basically that kill adults,
like cancer, heart disease, diabetes, you know, chronic respiratory disease,
multiple scrosis, you know, all of these. And so maybe
by collecting all of this data on the children, we
(17:28):
can start predicting based on the data, who's going to
get which disease, and based on that, maybe we can
figure out, Okay, if we do this, this and this,
maybe we can avoid that and that and that chronic disease.
Every time the kids visit us, and they do so
once a year, we take as money samples as we
possibly can.
Speaker 1 (17:44):
Right, So you have this whole poop library going over
the kid's whole lifetime that you can sort of examine
over time. Yes, and how many kids are in this cohort?
Speaker 3 (17:52):
So we have two horts and what I'm going to
talk about today. The data is from the corps AC
twenty ten cohorts. So they were born in twenty ten.
They're like fourteen years old now, right, And the twenty
ten cohort is seven hundred kids.
Speaker 1 (18:02):
So the cohort you're following is seven hundred kids who
were born in twenty ten. You're coming into this as
a person who has been studying viruses that attack bacteria
for purposes here, and so when you get there.
Speaker 2 (18:17):
What do you do?
Speaker 3 (18:18):
I get there and then my boss he basically explains
me some of the studies that they've been doing on
the bacteria in the gut so far. And one of
the major studies that they did just like one year
before I came was that they found that in one
year old, when you're basically still a baby, the bacteria
that you have in your gut when you're a baby
end up determining whether or not you get asthma as
(18:39):
a five year old. And I was like, what, I mean,
how is that even possible? And so what the general
picture is that if you have only a few different
bacteria in your gut when you're one year old, then
you have much higher risk of getting asthma as a
five year old, right, But if you have like loads
and loads of different bacteria in your gut when you're
one year old, then you're much more protected from asthma
(19:01):
as a five year old. And so basically that that
got me thinking, Wow, that means that most bacteria are
actually good for us. I mean, there are few bacteria,
maybe one hundred species in total that can cause infection,
But the total number of bacteria in nature is like
one hundred million species at least, So those other one
hundred million are not causing. It's just one out of a
million bacterium.
Speaker 1 (19:18):
That is bad and the other one in a million
gives him a bad name, and so go on.
Speaker 3 (19:24):
So I was thinking, Okay, if that's the case for bacteria,
then what about viruses. What if it's the same for viruses.
What if the only viruses that we know about are
the ones that cause disease and there are loads of
other viruses that are actually good for us. That's what
I was thinking back then. But the funny thing is
that this other guy called Dennis Nielsen, who is a
professor at copenha University because he's an expert at figuring
(19:47):
out which viruses are in a sample, he basically said, Okay,
you guys found this thing with bacteria, why don't we
look at the viruses in the gut and maybe we
can find something similar or even cooler. And so when
I started copsack, this data set is already in the
pro being generated. Dennis has taken seven hundred fecal samples
extracted viral particles, and then he has basically put them
through a sequencer and we're getting in sequences from each.
Speaker 1 (20:09):
Child's sequences, meaning genetic sequences that allows you to determine
what viruses. Yeah, exactly, So you get there in twenty seventeen,
and another researcher is already just starting to look for
what viruses are in the fecal samples of these kids
in the study. How do you get involved to what
(20:32):
do you do?
Speaker 2 (20:32):
What happens back then?
Speaker 3 (20:33):
What people used to do when they got gut VIRAM
data is that they would then take all the DNA
sequences that came out of that and they would then
blast it. Is what it is called against a public
database of viruses, viruses that scientists have already discovered and
know about, so that you can figure out which viruses
are in those samples. The problem is that most of
the viruses in the human gut at that time were
unknown to science by I love it. So by doing
(20:56):
that exercise, you're only going to get like a list
of contents of maybe ten virus, whereas the actual diversity
in each sample is going to be like maybe ten
thousand or maybe a thousand or something.
Speaker 1 (21:05):
Right, But the problem is you don't know what you're
looking for, right, You just have this random strings of
genetic material, and if you're trying to find newly discovered viruses, well,
how do you even do that? In fact, how do
you do it?
Speaker 3 (21:19):
So what we first do is we assemble all the
sequences like a piece of a puzzle and get extended
so that you get larger and larger fragments of DNA
that must have come from the same virus.
Speaker 1 (21:28):
You have this weird set of little chains and you
need to put together like, ah, here is a virus
and here is a different virus.
Speaker 3 (21:36):
Yeah, exactly, And so that's then what happens. Now we
got a bunch of DNA sequences from each child, so
that then what I do is I annotate all the
protein coding genes on these strands of DNA, so that
I know which proteins are encoded on each DNA fragment,
and by looking at those proteins, what they encode, what
kind of functions those protein code, I can start making
(21:57):
qualified guesses in terms of Okay, this one a virus
and this one must not.
Speaker 1 (22:01):
Are you like actually looking at sequences and like look
at like at like one looks at jigsaw puzzle pieces
on a table.
Speaker 3 (22:08):
Yeah, I guess you could say. I mean, I can
look at the protein coding genes that are encoded on
each cluster, and I manually look through ten thousand clusters
of sequences, and out of those ten thousand, around three
hundred of them were the ones that I could confidently
say were viruses and they correspond to viral families.
Speaker 1 (22:23):
So when you're saying you're manually looking through ten thousand,
is that like years of work?
Speaker 3 (22:29):
Yeah, it took five years, actually four years.
Speaker 1 (22:31):
Yeah, And so you do this work, you spend four
or five years going through this data. How many viruses
do you find that live commonly in the human gut, in.
Speaker 3 (22:47):
The children who we looked at? And that's all we
can really say anything about. There are ten thousand species
of viruses distributed in around two hundred and fifty viral families.
Speaker 1 (22:57):
So so you discover all these new viruses, does that
mean you get to name them?
Speaker 3 (23:05):
Super good question? So this is and this is this
was actually a huge issue for us. So now we're
finding two hundred and fifty new viral families. How are
we gonna present this in a paper?
Speaker 1 (23:16):
Right? It can't just be like a b C. You're
gonna write out a letter Earth exactly.
Speaker 3 (23:20):
And so a lot of different suggestions were on the table.
Pokemon was one of them.
Speaker 1 (23:24):
Did you have a Pikachu in mind? That's the first question?
Speaker 3 (23:27):
Who gets to me exactly like Pikachu veradee? You know,
Charmander Verde, et cetera, et cetera. And then a colleague
of mine, Jonathan, who's the third author of this paper,
he suggested, why not just name them after the kids?
Speaker 1 (23:37):
Are the kids in the study? The kids? Who's who's
whose poop had the viruses in it?
Speaker 3 (23:42):
Exactly? So we shuffled all the names and then we
just distributed them over the two undred and fifty viral families.
So what are some of the names Christian Verde, Ucas Verde,
Josephinea Verde.
Speaker 1 (23:52):
Yeah, So you do this work, you identify all of
these previously undiscovered viruses that live in the guts of
these kids. Do you then start to try and understand
the health implications of different virmes et cetera.
Speaker 3 (24:08):
That was the entire purpose of this exercise, right, So
those bacterial phages which were also by far most of
all the families.
Speaker 1 (24:15):
The viruses that infect in bacteria.
Speaker 2 (24:17):
Okay, exactly.
Speaker 3 (24:18):
Those bacterial phage families can be divided into like two
broad categories. They are the virulent bacteriophages and the temperate bacteriophages. Right.
The virulent bacteriophages they just kill the bacteria, okay, whereas
the tempered bacteriophagies they integrate themselves as prophages on the
bacterial DNA.
Speaker 1 (24:37):
So first you look at the viruses that infect bacteria,
and then you divide those into two categories, and you say,
there's the viruses that just destroy the bacteria, and there's
the viruses that infect the bacteria but don't destroy it.
Speaker 3 (24:49):
Exactly.
Speaker 1 (24:50):
Does that tell you anything clinically?
Speaker 2 (24:52):
Yeah?
Speaker 3 (24:52):
So Christina who was the first author of that paper
that came out in Nature Medicine earlier this year, she
found that it was the temperate bacterial phages that were
predictive of later asthma. For some reason, the children that
end up developing asthma by age five, they had way
more temperate phages by pacteriophages in their gut at age one.
Speaker 1 (25:08):
Uh huh. And so the key data set is you're
looking at the virum of the kids at age one
and trying to understand is it predictive of asthma by
age five? And what answer do you and your colleagues
find to that question.
Speaker 3 (25:25):
What we find is that there are more temperate phages
in the kids who end up developing asthma later. Then
we look at the temperate phages specifically, and look, we
look at which families of temperate phages are predictive of disease.
And then what we find, which is kind of surprising
and funny, is that nineteen of the two hundred and
fifty families we had in total two hundred and thirty
of the more tempered nineteen of them. If you look
(25:46):
at the amounts of those nineteen families in the children,
you can actually distinguish between kids that end up developing
asthma as five year olds or not. And what's interesting
is that the kids that develop asthma as five year
olds have less of these nineteen families than the healthy ones.
Speaker 2 (26:01):
Aha.
Speaker 1 (26:01):
So, so is it right that these nineteen families of
viruses seem to maybe be protective against asthma? Like having
more of these of these particular viruses is correlated with
a lower risk of asthma exactly. That's very interesting. Now
I get nervous that even though it passes some set
of statistical tests, this is going to be a fluke finding.
(26:24):
You know, It's going to be due to random chance.
And so what I really want you to do is
go run this test on some other kids at age one,
make your prediction, and have it come true by age five.
Is that a reasonable thought?
Speaker 3 (26:37):
That is super reasonable, I have to say, Jacob. And
this is also something that Nature and Medicine asked us
to do, and we said, well, nobody else has virum
data for so many children. Unfortunately, such a cohord does
not exist. You know, COPSAC twenty ten is one of
the most deeply phenotype cohorts in the world, so we
were not able to replicate it in another cohort.
Speaker 1 (26:57):
Yeah. Yeah, So you have this finding that a certain
family of virus seems to be protective against asthma. Are
you able to understand anything about what causes a kid
to have or not have this apparently protective family of
viruses in their gut?
Speaker 3 (27:19):
Super good question. I don't know. I think it has
a lot to do with different environmental factors that end
up determining for random reasons, which viruses end up in
the guts of these children.
Speaker 1 (27:29):
I mean, when you say you don't know, does that
mean there's no way in your data set to investigate
the question?
Speaker 3 (27:34):
There definitely is, and this is what we're doing is
ongoing basically, right. So what we do see is that
there's a huge correlation in, for example, where the kids live,
whether they live in a rural environment or like a
city environment. Okay, the ones that really live in a
rural environment have a much more diverse, you know, ecosystem
in the gut. In terms of the bacteria. We haven't
looked at the viruses directly yet, but we have an
(27:54):
intuition that the same might apply for viruses as well. Also,
there's there are huge, you know, kind of links to
the diet, the kind of food that you eat, whether
it's very processed food or whether it's like whole foods.
Whole foods are generally associated with way way higher diversity.
So if you want to increase your chances of having
the good viruses in your gut, then it's a good
idea to live you know, rurally or at least spend
(28:15):
some time in nature. It's a good idea to eat
whole foods instead of process foods, et cetera.
Speaker 1 (28:19):
Okay, so that's based on what we know about bacteria
and what you suspect is true also for viruses. Let
me ask you this, when you think about the future,
what do you hope we know about the virme in five, ten,
twenty years that we don't know now.
Speaker 3 (28:43):
I'm hoping in the future that we have a much
better overview in terms of what kinds of chronic diseases
are caused by deficits in which viruses, but also in bacteria,
so that we can prevent maybe ten twenty thirty years
from now, we can prove event a lot of time
diseases that cause a lot of problems today that those
(29:03):
can just be prevented by giving babies viruses or bacteria
or even adults.
Speaker 1 (29:13):
Thank you so much for your time. It was great
to talk with you.
Speaker 3 (29:16):
Good to talk to you too.
Speaker 1 (29:21):
Shiraz Shaw is a senior researcher at the Copenhagen University
Hospital ghenth HOFTA. Thanks to both of my guests today,
Shiraz Shah and Ken Steadman. Incubation is a co production
(29:44):
of Pushkin Industries and Ruby Studio at iHeartMedia. It's produced
by Kate Furby and Brittany Cronin. The show is edited
by Lacey Roberts. It's mastered by Sarah Buguer, fact checking
by Joseph friedman Or. Executive producers are Lacey Roberts and
Matt Romano. I'm Jacob Goldstein. Thanks very much for listening
to this season of Incubation. I hope we'll be back
(30:05):
next year with Season three.
Viruses are in the air we breathe, in the water
we drink. They're in the ground we walk on there,
on our skin, they're in our bellies. They have us surrounded,
and the wild thing is we've only identified a fraction
of them. In other words, not only are we surrounded
(00:25):
and permeated by viruses, we're surrounded and permeated by viral
dark matter, by viruses that we don't even know exist.
Speaker 2 (00:34):
We have lots of viruses in us and we have
no idea what they're doing, and potentially in that dark matter,
there are some answers to the questions on what are
they doing there.
Speaker 1 (00:48):
I'm Jacob Goldstein, and this is Incubation. Today, on our
final episode of season two, we're going out to the
scientific frontier to talk about all the viruses we don't
know about in the world and in our bodies. In
(01:12):
the second half of the show today, I'll be speaking
with a researcher who has recently discovered hundreds of families
of viruses that live inside the human gut, and he's
found a link that suggests some of those viruses could
actually help kids stay healthy. But first I'm going to
talk with Ken Steadman he's a professor of biology at
(01:33):
Portland State University. He studies viral dark matter, which basically
means he goes looking for viruses in wild places. To start,
I asked him, how do you look for a virus
that nobody knows exists?
Speaker 2 (01:46):
A couple of different ways. All viruses that we know of,
by definition, have to have a host that they infect.
What we do is we'll go and collect samples in
the craziest places we can find, usually volcanic hot springs,
and then we bring them back to lab and see
if they infect our favorite microbes that also happen to
grow in these hot springs.
Speaker 1 (02:07):
I've read a little bit about your work at last
in Volcanic National Park in northern California, So tell me
about what's going on there. Tell me about Boiling Springs Lake.
Speaker 2 (02:16):
So, Boiling Springs Lake I like to describe as the
biggest hot spring in the world that nobody has ever
heard of. It's a slight exaggeration. The low temperature in
the lake is about one hundred and thirty hundred and
forty degrees fahrenheit.
Speaker 1 (02:29):
And so what does that mean for finding weird viruses?
Speaker 2 (02:32):
Well, hang on just a second, that's the temperature. I
haven't told you about the pH yet, have I Wait
a minute.
Speaker 1 (02:37):
If you like the temperature, you're gonna love the pH exactly.
Speaker 2 (02:41):
So the pH is about two.
Speaker 1 (02:43):
pH of two means it's it's acidic. It's highly acidic.
So not great for soaking is what you're not great for.
Speaker 2 (02:49):
We've seen people walking up there and they're a swimming
gear and we tell them not a real good idea.
Speaker 1 (02:55):
So you go to this hot, acidic lake and what
what do you do there?
Speaker 2 (02:58):
We just took about two hundred liters worth of water
from the lake and then purified all of the virus
sized particles in it, then determined what their genetic sequences were,
what we call them meta genome, but basically all the viruses,
what genes do they have in.
Speaker 1 (03:17):
So you're basically just what pouring this acid into a
machine and saying, tell me all the genes that are in.
Speaker 2 (03:25):
Here or or less. Yeah. So one of the things
about viruses which makes virus is incredibly unique is they
have what we like to call we call it a
very on it's the virus structure. So the lunar lander
module kind of thing.
Speaker 1 (03:40):
Right, your classic virus looks like a little lunar lander
like a pod, and then little legs coming out right.
Speaker 2 (03:46):
Absolutely, and it's relatively small.
Speaker 1 (03:48):
So what you do is sayge right, that's the classic phase.
That's the thing that lands on the bacterium and then
inserts its genetic material.
Speaker 2 (03:54):
Injects it exactly. But even if you think about no
Sarscobe two virus that causes COVID nineteen also is a
little bag which has genes on the inside of it.
So you break up in the bag and you throw
it into the machine and then it gives you back
hundreds of thousands of sequences in our case now millions
(04:14):
of sequences with the newest technology, so millions of genes,
hundreds of thousands of genes. But they're not genes, they're
gene fragments, they're little pieces. Now, at first you just
want to look at what those little pieces are relative
to known sequences.
Speaker 1 (04:31):
Uh huh.
Speaker 2 (04:32):
That the dark matter is going to be, you know,
those little pieces that don't match anything, and the light
matter is going to be stuff that does Ninety plus
percent of the sequences that we got back of our
hundreds of thousands of sequences didn't match anything.
Speaker 1 (04:45):
And what did you think when you saw that, Oh.
Speaker 2 (04:48):
It's like other environments, other people seemed very similar things.
So you do this with seawater, you do this with
things you find in soil. Ninety odd percent plus or
minus don't match anything.
Speaker 1 (05:01):
Does that mean that we don't know about ninety percent
of the viruses that are out in the world. Is
that broadly what that implies?
Speaker 2 (05:09):
That is exactly what it implies.
Speaker 1 (05:11):
And it's not just in a weirdo boiling acid lake.
How about just in the dirt. If I just went
into my yard and dug up some dirt and send
it to somebody who could put it in one of
your machines. What percentage of the viruses in my backyard
are known to science?
Speaker 2 (05:26):
Roughly?
Speaker 1 (05:29):
Wow, eighty percent are dark matter are unknown. I love that.
Speaker 2 (05:35):
It's keeps us employed.
Speaker 1 (05:38):
Yeah, so okay, so you get this result back it's
ninety percent is unknown. What like? And so what you
just have is like a genetic mess that you don't
know what to do with, because it's not like each
little fragment is like, oh, that's a new virus. It's
just these are weird fragments that we don't understand.
Speaker 2 (05:56):
Yeah, exactly weird fragments if we don't understand. But one
of the other things that we found is some of
the fragments that we could actually identify didn't look like
sequences that we should have found, Meaning not only are
they different than anythings that's been found before.
Speaker 1 (06:16):
They are like too weird, They're like, wait, that doesn't
make any sense.
Speaker 2 (06:20):
How could that even be? Exactly did you think you
had made a mistake of some sort so that the
machine was broken. We thought that we had absolutely screwed
up in this case. So we've got genetic material virus,
you've got RNA viruses, you got DNA viruses, right, So.
Speaker 1 (06:33):
Basically a virus is just like a bag with genetic
material in it. And there's some viruses have DNA and
some viruses have RNA. And even though these are like
two types of viruses, sort of historically evolutionarily, they're like
really different from each other.
Speaker 2 (06:48):
Right, DNA viruses and RNA viruses we always thought were
completely different relative to each other. And if you think
about the evolutionary relationship between between RNA viruses and DNA viruses,
there basically seems to be almost none.
Speaker 1 (07:07):
Like how big is the gap? Sort of whatever evolutionarily,
how different are DNA and RNA viruses?
Speaker 2 (07:14):
So the difference between DNA and RNA viruses is probably
billions of years evolutionarily speaking.
Speaker 1 (07:23):
Okay, I was gonna say, like, it's like as big
as the difference between mammals and reptiles, but it's way
bigger than that.
Speaker 2 (07:31):
It's probably more like the difference between you know, bacteria
and people, bacterian people exactly, much more like that in
terms of evolutionary difference.
Speaker 1 (07:41):
Wow. Okay, So there are these profoundly different things.
Speaker 2 (07:45):
So we sequenced a bunch of DNA put into our machine,
you know, said hey, get some DNA sequences, and then
some of those proxially a couple of thousand sequences that
actually match. Something in those sequences were things that look
like RNA viruses in terms of their sequence.
Speaker 1 (08:03):
But it's DNA that you're But we sequenced DNA.
Speaker 2 (08:06):
Yeah, but we and when I say we, mostly a
graduate student working in our group, Jeff Deemer. He then
started to try and put some of these pieces together.
What he found was those pieces that looked like RNA
viruses were connected genetically to sequences that looked like DNA viruses.
Speaker 1 (08:29):
Okay, and connected like physically like that they were physically
almost like the one piece of a chain of genetic
material exactly.
Speaker 2 (08:38):
And then what we did is we went back to
the samples that we collected from Boiling Springs Lake, and
instead of pouring them into the machine to get the sequences,
we then made many many copies of whatever this piece was.
And this piece was to show that were actual connected
to each other. So there are these what we're now
calling cruci viruses that appear to have evolved by DNA
(09:02):
viruses and RNA viruses coming together.
Speaker 1 (09:04):
Okay, so we thought these were like totally different kinds
of viruses, but now you have discovered this new kind
of virus that's kind of like a cross between the
two of them. Right, what does that mean? Like, what
does it mean for how we think about RNA viruses
and DNA viruses.
Speaker 2 (09:20):
It means that there's communication between them, and there's this recombination.
So it's not billions of years of evolutionary difference, which
is what we thought. Now it looks as if they
can be exchanging genetic information with each other, which is
really kind of revolutionary in terms of thinking about virus
(09:41):
evolution and what it means is. We always thought DNA
viruses evolved like this and RNA viruses evolved like this,
But if they can exchange genes with each other, that
kind of throws a lot of what we think about
virus evolution kind of out the window. Turns out that
these viruses in and of them els are just so
(10:01):
different from any other virus anybody's ever seen before, in
terms of their shape, in terms of their genes, what
is in them?
Speaker 1 (10:11):
So you and your colleagues found this, this crucivirus in
the boiling acid Lake. I know that since then a
number of other of these cruciviruses have been found. So
just give me the landscape. Give me what we know
so far of like where are they, what are they doing, etc.
Speaker 2 (10:27):
We do not know what they're doing. Crucy virus has
been found in boiling Springs Lake, Antarctic lakes, in deep
sea sediments off the coast of Greenland, in Korean air samples,
isopods off the coast of Oregon, monkey feces, in dragonfly guts,
soil just outside the lab at Portland State University. Basically
(10:50):
anywhere that we have looked, we've found these crucy viruses.
Very low amounts of them, but seem to be very ubiquitous.
So where are the everywhere?
Speaker 1 (11:01):
Love it?
Speaker 2 (11:01):
What are they doing? We don't know.
Speaker 1 (11:03):
Are they in my body right now?
Speaker 2 (11:06):
Probably in your body right now.
Speaker 1 (11:09):
So these things are all around us, all over the world,
possibly in our guts, and nobody knows what they're doing.
Speaker 2 (11:17):
That is exactly correct. I love it me too.
Speaker 1 (11:23):
So what do we know about like what they're doing.
Speaker 2 (11:26):
We're trying to figure out what they infect. We think
they're infecting microbial EU carry out, So things like fungi
or protus, these paramesia things you know swimming around in lakes.
Speaker 1 (11:40):
Are there are those things? Also? Are there also organisms
like that in our bodies?
Speaker 2 (11:46):
There definitely are?
Speaker 1 (11:47):
Is that part of the microflora?
Speaker 2 (11:49):
Yeah, we have. We have a euchreytic microflora. Mostly these
are going to be fungi, some kinds of yeats, et cetera.
But there are many other of the And again this
is something which has been not very well studied, so
you kind of put in environmental viruses have not been
well studied. These microbial EU carry outs have not been
(12:11):
very well studied. So you put those two together, extremely
poorly studied.
Speaker 1 (12:16):
Very dark. It's very dark matter.
Speaker 2 (12:20):
Very dark matter, but at the same time really exciting
because there's so much to discover.
Speaker 1 (12:25):
Like why does microbial dark matter matter?
Speaker 2 (12:29):
Besides being cool, I think it's an area where we
can make discoveries. There's so much we don't know. We
have lots of viruses in US and we have no
idea what they're doing, and potentially in that dark matter
there are some answers to the questions on what are
(12:50):
they doing there? So I think that that's a very
important thing to think about.
Speaker 1 (12:55):
Not just how are they making us sick, but how
are they keeping us healthy? How might they get out
of balance at times and contribute in indirect ways to sickness?
Certainly seems plausible. We know that happens with the bacteria
in our gut.
Speaker 2 (13:08):
Yeah, I think that that's a very reasonable thing to
think about. And then just in a larger ecological sense,
you know, understanding the ecology. There's still so much that
we don't know. I think understanding that virus' role in
not just us, but also in life on our planet.
I think understanding that dark matter will really help us
(13:31):
understand what's going on with all of these different pirates.
Speaker 1 (13:44):
I appreciate your time. It was a fun conversation.
Speaker 2 (13:46):
Yeah, it was fun conversation for me too. I learned things,
So thank you for that good.
Speaker 1 (13:54):
Ken Stedman is a biology professor and extreme virologist at
Portland State University. His work and his team's work are
expanding our idea of what a virus can be in
a minute, discovering hundreds of kinds of new viruses that
(14:14):
live in the human gut. I'm going to go out
on a limb and say the most underrated viruses are phages.
(14:36):
Phages are the viruses that infect bacteria. They're the most
abundant biological entity on Earth and their killers.
Speaker 3 (14:45):
Every other bacterium on Earth gets killed by a virus
every day.
Speaker 1 (14:50):
Actually, that's wild to think about.
Speaker 3 (14:53):
It really sucks for them.
Speaker 1 (14:55):
Shiraz ali Sha studies the phages that live inside people.
Your researcher on a project called COPSAC, the Copenhagen Prospective
Studies for Asthma in Childhood. The project is following hundreds
of kids from birth into childhood to try to understand
the causes of asthma. Shiraz focuses on the human virum,
(15:17):
the universe of viruses that live in the human gut
and he told me that studying the viroom from birth
is really important.
Speaker 3 (15:24):
In the first year of life, the baby has an
immune system that has not yet matured, so it does
not know how to distinguish friend from foe. What happens
in the first year of life is that the immune
system is still trying to get to know what is
it supposed to attack and what is it not supposed
to attack. And it seems that there's more and more
evidence showing that if you are not exposed to a
diverse array of good bacteria in the body and on
(15:48):
the body within the first year of life, then the
immune system is not properly trained, and then you're way
more prone to chronic inflammatory or immune diseases in the future,
like asthma like asthma, like allergy like asthma, even stuff
like depression and anxiety, inflammation linked heart disease, most definitely cancer,
most definitely diabetes, most definitely yes.
Speaker 1 (16:09):
So okay, so now you're getting into some of what
you study, right, tell me about your work on this.
Speaker 3 (16:14):
So this is a place called COPSAC Copenhagen Perspective Studies
for Asthma in Childhood.
Speaker 1 (16:19):
It's a place where they're trying to understand how asthma
works in kids.
Speaker 3 (16:23):
Exactly, Okay, and so and so. The way that they
do this is basically, they have a bunch of kids
that were born in twenty ten and they've been following
them since the moms got pregnant and today they're like
fifteen years old.
Speaker 2 (16:34):
Right.
Speaker 3 (16:34):
What they're doing is they're recording as much data on
these children as possible as humanly possible, like where do
they go to date hair, how many siblings do they have,
but also blood tests, you know, which chemicals do they
have in their bodies in their pee, what bacteria do
they have in their poop, in their lungs, et cetera,
et cetera. So we have like jigabtes upon jigabat also
their own genes, their own genomes we also have.
Speaker 1 (16:54):
And so, just to be clear, it's the idea of
doing all this and starting before the child is even born.
Is the question they're trying to answer, why do some
people get asthma and others don't?
Speaker 3 (17:06):
Exactly Because even though asthma is such a common childhood
kind of disease, it's very poorly understrue. And this is
not only the case for asthma. It's also the case
for all the other chronic diseases basically that kill adults,
like cancer, heart disease, diabetes, you know, chronic respiratory disease,
multiple scrosis, you know, all of these. And so maybe
by collecting all of this data on the children, we
(17:28):
can start predicting based on the data, who's going to
get which disease, and based on that, maybe we can
figure out, Okay, if we do this, this and this,
maybe we can avoid that and that and that chronic disease.
Every time the kids visit us, and they do so
once a year, we take as money samples as we
possibly can.
Speaker 1 (17:44):
Right, So you have this whole poop library going over
the kid's whole lifetime that you can sort of examine
over time. Yes, and how many kids are in this cohort?
Speaker 3 (17:52):
So we have two horts and what I'm going to
talk about today. The data is from the corps AC
twenty ten cohorts. So they were born in twenty ten.
They're like fourteen years old now, right, And the twenty
ten cohort is seven hundred kids.
Speaker 1 (18:02):
So the cohort you're following is seven hundred kids who
were born in twenty ten. You're coming into this as
a person who has been studying viruses that attack bacteria
for purposes here, and so when you get there.
Speaker 2 (18:17):
What do you do?
Speaker 3 (18:18):
I get there and then my boss he basically explains
me some of the studies that they've been doing on
the bacteria in the gut so far. And one of
the major studies that they did just like one year
before I came was that they found that in one
year old, when you're basically still a baby, the bacteria
that you have in your gut when you're a baby
end up determining whether or not you get asthma as
(18:39):
a five year old. And I was like, what, I mean,
how is that even possible? And so what the general
picture is that if you have only a few different
bacteria in your gut when you're one year old, then
you have much higher risk of getting asthma as a
five year old, right, But if you have like loads
and loads of different bacteria in your gut when you're
one year old, then you're much more protected from asthma
(19:01):
as a five year old. And so basically that that
got me thinking, Wow, that means that most bacteria are
actually good for us. I mean, there are few bacteria,
maybe one hundred species in total that can cause infection,
But the total number of bacteria in nature is like
one hundred million species at least, So those other one
hundred million are not causing. It's just one out of a
million bacterium.
Speaker 1 (19:18):
That is bad and the other one in a million
gives him a bad name, and so go on.
Speaker 3 (19:24):
So I was thinking, Okay, if that's the case for bacteria,
then what about viruses. What if it's the same for viruses.
What if the only viruses that we know about are
the ones that cause disease and there are loads of
other viruses that are actually good for us. That's what
I was thinking back then. But the funny thing is
that this other guy called Dennis Nielsen, who is a
professor at copenha University because he's an expert at figuring
(19:47):
out which viruses are in a sample, he basically said, Okay,
you guys found this thing with bacteria, why don't we
look at the viruses in the gut and maybe we
can find something similar or even cooler. And so when
I started copsack, this data set is already in the
pro being generated. Dennis has taken seven hundred fecal samples
extracted viral particles, and then he has basically put them
through a sequencer and we're getting in sequences from each.
Speaker 1 (20:09):
Child's sequences, meaning genetic sequences that allows you to determine
what viruses. Yeah, exactly, So you get there in twenty seventeen,
and another researcher is already just starting to look for
what viruses are in the fecal samples of these kids
in the study. How do you get involved to what
(20:32):
do you do?
Speaker 2 (20:32):
What happens back then?
Speaker 3 (20:33):
What people used to do when they got gut VIRAM
data is that they would then take all the DNA
sequences that came out of that and they would then
blast it. Is what it is called against a public
database of viruses, viruses that scientists have already discovered and
know about, so that you can figure out which viruses
are in those samples. The problem is that most of
the viruses in the human gut at that time were
unknown to science by I love it. So by doing
(20:56):
that exercise, you're only going to get like a list
of contents of maybe ten virus, whereas the actual diversity
in each sample is going to be like maybe ten
thousand or maybe a thousand or something.
Speaker 1 (21:05):
Right, But the problem is you don't know what you're
looking for, right, You just have this random strings of
genetic material, and if you're trying to find newly discovered viruses, well,
how do you even do that? In fact, how do
you do it?
Speaker 3 (21:19):
So what we first do is we assemble all the
sequences like a piece of a puzzle and get extended
so that you get larger and larger fragments of DNA
that must have come from the same virus.
Speaker 1 (21:28):
You have this weird set of little chains and you
need to put together like, ah, here is a virus
and here is a different virus.
Speaker 3 (21:36):
Yeah, exactly, And so that's then what happens. Now we
got a bunch of DNA sequences from each child, so
that then what I do is I annotate all the
protein coding genes on these strands of DNA, so that
I know which proteins are encoded on each DNA fragment,
and by looking at those proteins, what they encode, what
kind of functions those protein code, I can start making
(21:57):
qualified guesses in terms of Okay, this one a virus
and this one must not.
Speaker 1 (22:01):
Are you like actually looking at sequences and like look
at like at like one looks at jigsaw puzzle pieces
on a table.
Speaker 3 (22:08):
Yeah, I guess you could say. I mean, I can
look at the protein coding genes that are encoded on
each cluster, and I manually look through ten thousand clusters
of sequences, and out of those ten thousand, around three
hundred of them were the ones that I could confidently
say were viruses and they correspond to viral families.
Speaker 1 (22:23):
So when you're saying you're manually looking through ten thousand,
is that like years of work?
Speaker 3 (22:29):
Yeah, it took five years, actually four years.
Speaker 1 (22:31):
Yeah, And so you do this work, you spend four
or five years going through this data. How many viruses
do you find that live commonly in the human gut, in.
Speaker 3 (22:47):
The children who we looked at? And that's all we
can really say anything about. There are ten thousand species
of viruses distributed in around two hundred and fifty viral families.
Speaker 1 (22:57):
So so you discover all these new viruses, does that
mean you get to name them?
Speaker 3 (23:05):
Super good question? So this is and this is this
was actually a huge issue for us. So now we're
finding two hundred and fifty new viral families. How are
we gonna present this in a paper?
Speaker 1 (23:16):
Right? It can't just be like a b C. You're
gonna write out a letter Earth exactly.
Speaker 3 (23:20):
And so a lot of different suggestions were on the table.
Pokemon was one of them.
Speaker 1 (23:24):
Did you have a Pikachu in mind? That's the first question?
Speaker 3 (23:27):
Who gets to me exactly like Pikachu veradee? You know,
Charmander Verde, et cetera, et cetera. And then a colleague
of mine, Jonathan, who's the third author of this paper,
he suggested, why not just name them after the kids?
Speaker 1 (23:37):
Are the kids in the study? The kids? Who's who's
whose poop had the viruses in it?
Speaker 3 (23:42):
Exactly? So we shuffled all the names and then we
just distributed them over the two undred and fifty viral families.
So what are some of the names Christian Verde, Ucas Verde,
Josephinea Verde.
Speaker 1 (23:52):
Yeah, So you do this work, you identify all of
these previously undiscovered viruses that live in the guts of
these kids. Do you then start to try and understand
the health implications of different virmes et cetera.
Speaker 3 (24:08):
That was the entire purpose of this exercise, right, So
those bacterial phages which were also by far most of
all the families.
Speaker 1 (24:15):
The viruses that infect in bacteria.
Speaker 2 (24:17):
Okay, exactly.
Speaker 3 (24:18):
Those bacterial phage families can be divided into like two
broad categories. They are the virulent bacteriophages and the temperate bacteriophages. Right.
The virulent bacteriophages they just kill the bacteria, okay, whereas
the tempered bacteriophagies they integrate themselves as prophages on the
bacterial DNA.
Speaker 1 (24:37):
So first you look at the viruses that infect bacteria,
and then you divide those into two categories, and you say,
there's the viruses that just destroy the bacteria, and there's
the viruses that infect the bacteria but don't destroy it.
Speaker 3 (24:49):
Exactly.
Speaker 1 (24:50):
Does that tell you anything clinically?
Speaker 2 (24:52):
Yeah?
Speaker 3 (24:52):
So Christina who was the first author of that paper
that came out in Nature Medicine earlier this year, she
found that it was the temperate bacterial phages that were
predictive of later asthma. For some reason, the children that
end up developing asthma by age five, they had way
more temperate phages by pacteriophages in their gut at age one.
Speaker 1 (25:08):
Uh huh. And so the key data set is you're
looking at the virum of the kids at age one
and trying to understand is it predictive of asthma by
age five? And what answer do you and your colleagues
find to that question.
Speaker 3 (25:25):
What we find is that there are more temperate phages
in the kids who end up developing asthma later. Then
we look at the temperate phages specifically, and look, we
look at which families of temperate phages are predictive of disease.
And then what we find, which is kind of surprising
and funny, is that nineteen of the two hundred and
fifty families we had in total two hundred and thirty
of the more tempered nineteen of them. If you look
(25:46):
at the amounts of those nineteen families in the children,
you can actually distinguish between kids that end up developing
asthma as five year olds or not. And what's interesting
is that the kids that develop asthma as five year
olds have less of these nineteen families than the healthy ones.
Speaker 2 (26:01):
Aha.
Speaker 1 (26:01):
So, so is it right that these nineteen families of
viruses seem to maybe be protective against asthma? Like having
more of these of these particular viruses is correlated with
a lower risk of asthma exactly. That's very interesting. Now
I get nervous that even though it passes some set
of statistical tests, this is going to be a fluke finding.
(26:24):
You know, It's going to be due to random chance.
And so what I really want you to do is
go run this test on some other kids at age one,
make your prediction, and have it come true by age five.
Is that a reasonable thought?
Speaker 3 (26:37):
That is super reasonable, I have to say, Jacob. And
this is also something that Nature and Medicine asked us
to do, and we said, well, nobody else has virum
data for so many children. Unfortunately, such a cohord does
not exist. You know, COPSAC twenty ten is one of
the most deeply phenotype cohorts in the world, so we
were not able to replicate it in another cohort.
Speaker 1 (26:57):
Yeah. Yeah, So you have this finding that a certain
family of virus seems to be protective against asthma. Are
you able to understand anything about what causes a kid
to have or not have this apparently protective family of
viruses in their gut?
Speaker 3 (27:19):
Super good question. I don't know. I think it has
a lot to do with different environmental factors that end
up determining for random reasons, which viruses end up in
the guts of these children.
Speaker 1 (27:29):
I mean, when you say you don't know, does that
mean there's no way in your data set to investigate
the question?
Speaker 3 (27:34):
There definitely is, and this is what we're doing is
ongoing basically, right. So what we do see is that
there's a huge correlation in, for example, where the kids live,
whether they live in a rural environment or like a
city environment. Okay, the ones that really live in a
rural environment have a much more diverse, you know, ecosystem
in the gut. In terms of the bacteria. We haven't
looked at the viruses directly yet, but we have an
(27:54):
intuition that the same might apply for viruses as well. Also,
there's there are huge, you know, kind of links to
the diet, the kind of food that you eat, whether
it's very processed food or whether it's like whole foods.
Whole foods are generally associated with way way higher diversity.
So if you want to increase your chances of having
the good viruses in your gut, then it's a good
idea to live you know, rurally or at least spend
(28:15):
some time in nature. It's a good idea to eat
whole foods instead of process foods, et cetera.
Speaker 1 (28:19):
Okay, so that's based on what we know about bacteria
and what you suspect is true also for viruses. Let
me ask you this, when you think about the future,
what do you hope we know about the virme in five, ten,
twenty years that we don't know now.
Speaker 3 (28:43):
I'm hoping in the future that we have a much
better overview in terms of what kinds of chronic diseases
are caused by deficits in which viruses, but also in bacteria,
so that we can prevent maybe ten twenty thirty years
from now, we can prove event a lot of time
diseases that cause a lot of problems today that those
(29:03):
can just be prevented by giving babies viruses or bacteria
or even adults.
Speaker 1 (29:13):
Thank you so much for your time. It was great
to talk with you.
Speaker 3 (29:16):
Good to talk to you too.
Speaker 1 (29:21):
Shiraz Shaw is a senior researcher at the Copenhagen University
Hospital ghenth HOFTA. Thanks to both of my guests today,
Shiraz Shah and Ken Steadman. Incubation is a co production
(29:44):
of Pushkin Industries and Ruby Studio at iHeartMedia. It's produced
by Kate Furby and Brittany Cronin. The show is edited
by Lacey Roberts. It's mastered by Sarah Buguer, fact checking
by Joseph friedman Or. Executive producers are Lacey Roberts and
Matt Romano. I'm Jacob Goldstein. Thanks very much for listening
to this season of Incubation. I hope we'll be back
(30:05):
next year with Season three.
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