The good virus

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We're getting to that part of summer where there's nothing better to do than sit by a beach or by a pool with a good book. Or hide inside.
blasting the AC,

also with a good book.

So we thought, why not have another edition of our Unexplainable Book Club?

That's where one of us picks a book, we tell you exactly why we picked it, and then we call up the author and talk to them about it. This week, senior producer Bird Pinkerton has a book for us.

The book I chose is by a science writer named Tom Ireland, and it has a name that sounds almost like an oxymoron. It's called The Good Virus.

Essentially, there is this amazing group of viruses that exist solely to infect and kill bacteria. So they're called phages.

We call them bacteriophages, and that's just become shortened to phages. And phages have started to get some attention in the last few years.

Yeah, so there's a lot of interest, especially right now, about the use of phages as alternatives to antibiotics.

But it wasn't until I read Tom's book that I realized that phages aren't just going to help us fight pathogens in some newfangled future. They are helping us fight pathogens right now.

Because we already have a very intimate relationship with these viruses. Actually, we live with an unbelievable amount and an unbelievable diversity of different phages in us and on us all the time.

We are, it turns out, basically a whole bunch of phages in a trench coat. There's probably more phages in the human body than there are actual human cells.

And yet, we know very little about these microscopic roommates. Like, we only discovered one of the most abundant phages in our bodies about a decade ago.

And we still have a lot of questions about what role all these phages play in keeping pathogens at bay.

They're a really massive component of what's going on in our lives, which is just kind of crazy not to know about.

This is unexplainable, and today, on another edition of our book club, Tom Ireland tells us what we do and don't know about the phages inside of us and what that might mean for our health.

So let's start with the most basic of basics here. Most simply, What is a phage and how does it work?

So a phage is a virus that infects bacteria.

And personally, I think as viruses go, they're pretty cool and a bit more interesting than the viruses that infect humans because bacteria are a lot harder to infiltrate.

So these phages kind of look like mini spaceships. You know, they have these kind of angular,

weird, 20-sided heads. called a capsid.
They also have a tail and these little crazy legs that they use to kind of land on a bacteria and puncture its surface. And then they inject their genes in.
And

those genes hijack the bacteria to make it essentially a phage factory. So instead of using all of its metabolism to grow and replicate, the bacteria is just...
pumping out components of more phages.

And then those phages eventually burst out of the bacteria and they go on to infect other bacterial cells.

Where do we find these bacteria eating, bacteria fighting phages? Yeah, so they are absolutely everywhere and that's another reason I wanted to sort of try and celebrate them in this book.

They're out there in the environment, they're in rivers, they're in soil, they're in the seas, they're in some of the most inhospitable places on earth.

They are just everywhere that you'll find bacteria. You'll also find viruses or bacteria.
Sometimes there's more viruses than the bacteria themselves.

And you could scoop up some seawater from the middle of the ocean, and there would be literally millions of phages in what looks like completely pristine, clear seawater. Interesting.
So

they vastly outnumber the viruses that we fear and try to avoid.

How much have we studied phages in general? Are they sort of

a complete mystery we barely scratch the surface of? Do we understand them pretty well? Like, where do we stand?

So what's really interesting is that phages were first discovered in the 1910s, late 1910s. And they were immediately, there was lots of controversy around this discovery.

Some people just didn't believe that it was possible that there was a microbe smaller than a bacteria that could kill bacteria. It just seemed too far-fetched.

People immediately started using them in medicine. So people were very interested in phages that could cure disease, essentially.
That was sometimes successful, sometimes not.

It went in and out of fashion, but that was very much the focus. And so people started using phages as like a tool in genetics and in molecular biology.

And there was actually this treaty called the phage treaty, where a very powerful scientist who was at the head of this kind of field of science said everyone doing this, everyone using phages as like a tool for molecular biology has to use the same half a dozen phages so that we've all got the same kind of so that we can all compare data right we're all working on the same thing and we can all compare and contrast our data and that was amazing for molecular biology and it achieved huge breakthroughs but it's really like kept the number of phages that have been studied by scientists really really narrow and it's only recently that people have started to actually look at phages and try and categorize and classify all of them.

And so they've got a lot of work to do.

And what have researchers found as they've actually started to look at phages, as they've kind of branched out here? Is there a particularly interesting example?

So there's a guy called Forrest Rower

who was really interested in the viruses of corals.

And he would go and dive underwater and he was collecting viruses that

infect the bacteria that infect corals.

So one of the most obscure things you could probably do as a biologist,

you're looking at the viruses that infect the bacteria that infect corals.

But what he really started to notice was that corals are covered in this kind of protective mucus, and the mucus had actually evolved to attract phages into it. Wow.

So the corals were using this mucus

covered in phages as a kind of protective layer.

It was like an immune system because if your outer layer is covered in phages, then that's going to make it less likely that any bacteria can infect you.

Because as soon as the bacteria land on you, they get attacked by phages. So they're,

I just want to make sure I'm following. All these different corals have this like symbiotic relationship with phages where they say, we'll give you a home.

You

are like our little bodyguard, like our bouncers at the club or something, keeping stuff out. Acting like bodyguards.

It's like being covered in Velcro and there's bodyguards stuck all over the Velcro.

Really weird

analogy.

But they've made themselves an immune system in this way.

It works for the phages. They have a home that they know bacteria are going to come along and stick to, and they can use that to replicate in.

And the coral gets to have these little viruses living on it that are going to kill the bacteria that want to harm the coral.

So, Forrest and his colleagues started looking at other organisms that have this kind of mucus layer on them and finding phages in those mucus layers.

And then they thought, hey, we've got mucus layers like in our intestines and on the surface of our lungs.

So they started looking, and exactly the same thing happens in our intestines and in our lungs.

Any part of the body that's exposed to the environment is going to be full of bacteria and full of phages.

It seems that our bodies have evolved a certain type of mucus with proteins in it that actually bind to the phages that are going to protect us.

So we have this kind of layer of protection, of immunity, sort of stuck into those important surfaces where the inside of our body meets the outside of our body. And

again, this was only just discovered. So we're only just learning about this kind of completely new way that we protect ourselves from bacteria.

So, what have we discovered about these phages so far? Like, what have we figured out about how they're acting in our bodies? And what do we still need to figure out? That

is after the break.

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Viruses, and there are many different kinds of them, can be scattered with each unexplainable.

Welcome back. This is the Unexplainable Book Club, and we are talking about Tom Ireland's book, The Good Virus, which explores phages, these viruses that infect bacteria.

Phages are all over the planet, but also, as Tom told us, they are all over us. And they're helping us eliminate bacterial pathogens in ways that we don't fully understand yet.

In his book, Tom talks about how these phages might keep us healthy.

One researcher referred to them as another immune system, and researchers are studying how these phages work in concert with the rest of our microbiome.

People talk about the microbiome as the different populations of bacteria in the body, but it's really any microbe. So we should be considering phages as part of our microbiome.

I've heard it also called the phagiome or the virome.

So, yeah,

it's definitely a part of our microbiome, but it's a massively mysterious and understudied part.

What do we know about it, I guess? Like barely anything.

That piece of work, moving from corals to, you know, human mucus layers was really the starting point.

And really, not many groups of researchers are working on this.

People have just started to see that some phages actually make it through the barriers of the gut, through the mucus layer, and are present in areas of the body that we thought were completely sterile.

So, the blood, the spleen, even the brain have got phages in them.

And so, people are now starting to ask: have they been allowed through into these sterile areas of the body to act as kind of like antibacterial agents that circulate in our body, in our blood, and in our brain, just in case some bacteria manage to squeeze through into those sterile areas?

They'll immediately be pounced on by these select few bodyguards that have been let in through the barriers of the body.

So it's completely in its infancy, this area of science, but obviously it sounds super important to the future of our health.

Do these phages interact with

my regular immune system?

So what we do know about the way phages interact with the human immune system is that because we have co-evolved with phages all around us, our immune system doesn't really see see them as a threat.

So if a human virus entered the bloodstream, the immune system would kick off and take any number of steps to try and neutralize that invader.

But generally, what we know is that phages tend to float around in our bodies undisturbed.

And are there particular diseases that we think

we might be able to treat in some way if we followed this path of research further? Yeah, so cystic fibrosis is particularly relevant because it is a disease of the body's mucus.

It's an excess of mucus in the lungs and it often causes bacteria to colonize the mucus in a way that is kind of not responsive to antibiotics.

There's often different types of bacteria colonizing the lungs of cystic fibrosis patients all at once.

So yeah, it's absolutely essential that we understand what phage's role is in that mucus layer and how we can sort of add to it or modulate it in a way that can help protect patients from the bacteria trying to colonize their lungs.

Why do you think

recently phages have come back to the fore or people have restarted this exploration? Yeah, I guess for many, many years, the focus for virologists, i.e.

people who study viruses, was on the viruses that are killing and maiming people, like millions of people every year. And that's understandable understandable why that would take the focus.

Whereas people studying the viruses of bacteria, maybe, you know, they're not going to,

they're not getting the sexy grant money, right?

It's going to be seen as obscure.

I think what's changing now is that as we look desperately for ways to fight bacterial infections, as I mentioned earlier, antibiotics are not as effective as they used to be.

That is causing a real interest in understanding how to use phages. And the reason phages haven't been effective as medicines in the past is we didn't understand enough about them.

And so people are having to work backwards to sort of fundamentally understanding what phages are and how they work. It's normally the other way around.

You would understand something really well before you start using and thinking of developing medicines. It's kind of the other way around with phages.

People are desperate to use them as medicines now, but actually people have to take a massive step back and go like, well let's just start from the beginning like how did phages and bacteria evolve inside and on other life forms like we need to understand that three-way interaction um we even just need to understand how many there are how many there are what they're doing you know if we all have the same kind of phages or if we all have different ones

we just have to go back to the beginning and really like understand these relationships in like a molecular detail because it's just an unknown at the moment. There's just so many unknowns.

It's called the dark matter of biology because there's just so many different types of virus, so many of them, and yet we know so little about any of them.

Tom Ireland's book is called The Good Virus. And if you want to learn more about phages and about the people trying to use them as a tool to fight off bacterial infections, I really recommend it.

I also recommend sticking around because next week we'll be sharing a favorite episode of ours about how Cold War politics held phage research back for decades.

This episode was produced by me, Bird Pinkerton, and edited by Meredith Hodnott with help from Jorge Just. Meredith runs the show, Noam is our host and does the music.

Christian Ayala did the mixing and the sound design. Melissa Hirsch did our fact-checking.
Manding Wen is the fact that Nuthatches spend so much of their time upside down.

And we are always, always grateful to Brian Resnick for co-founding the show.

If you have questions about this episode or thoughts, please send them to us. We are at unexplainable at vox.com.

You can support the show and all of Vox's journalism by joining our membership program today. That's at vox.com slash members to sign up.

Or you can always support the show by leaving us a nice rating or a review. Reviews mean a lot.

Unexplainable is part of the Vox Media Podcast Network, and we'll be back next week.

Support for this show comes from SC Johnson. We've all been there.
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