October 26, 2023 • 30 mins
Can bacteriophages help us in the fight against antibiotic-resistant infections? Author Tom Ireland joins the show to discuss the fascinating world of bacteriophages, also known as phages – viruses that attack bacteria.. Then, Ben Chan, a researcher with a fridge full of phages, tells the story of what it was like putting them to use in a high-stakes case.
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Speaker 1 (00:02):
There's a question. I've been waiting a long time to
ask you phage or phage?
Speaker 2 (00:08):
I say phage. Some people say fage.
Speaker 1 (00:12):
Faj Come on, get the fuj out of here. What
is it?
Speaker 2 (00:17):
I think phage and phage are so similar that we
can work with that. It's Greek for killer or to
sort of eat.
Speaker 1 (00:26):
But in English. Yeah, so you're saying, you say phage
rhymes with.
Speaker 2 (00:30):
Age, I say phage.
Speaker 1 (00:33):
I'm talking with Tom Ireland. He is a science journalist
who just wrote a book called The Good Virus, and
it is all about phages. Phages are these amazing viruses
that have sort of flown under the radar since they
were discovered in the first part of the twentieth century.
Phages also known as bacteria phages are viruses that kill bacteria,
(00:55):
and that is a very useful trait if you need
to kill bacteria that are making someone really sick. And
in fact, Tom told me people are now turning to
phages to try to treat infections that can't be cured
with antibiotics.
Speaker 2 (01:08):
I think this year is the year that it all changes,
because the crisis of drug resistance is so acute and
so scary. Now that we have to take it seriously.
So the World Economic Forum this year named phage therapy
in their top ten Emerging technologies for twenty twenty three.
You know, we're not just guessing and throwing viruses into
(01:30):
people with bloodstream anymore. This is a kind of modern
phage therapy two point zero, and there's some real momentum
building behind the idea.
Speaker 1 (01:39):
Now, we spend a lot of time on this show
talking about viruses that are bad for humans, Viruses that
make us sick, viruses that have killed hundreds of millions
of people. Today, for the season finale, we bring you
a shocking twist show about viruses that are good for people,
(02:00):
Viruses that help us fight disease. We'll hear the story
of one of the first scientists to study phages. He
was kind of a genius, but also he was kind
of shady. And then we'll talk to a scientist who
collects phages in lakes and sewage plants and then uses
them to treat patients with life threatening infections that cannot
(02:21):
be treated with antibiotics. I'm Jacob Goldstein. This is incubation
in the world on planet Earth right now. How many
(02:43):
phages not kinds of phages, but phages.
Speaker 2 (02:46):
So there's a number that goes around a lot. It's
a very rough calculation, but it's ten with thirty one
zeros after it. One way of thinking of that is
a trillion phages for every grain of sand on the planet.
So just just crazy numbers.
Speaker 1 (03:07):
I don't know what to do with that. You said
a trillion for every grain of sand. That's like a
come on kind of number, right, I mean, I guess
one way to think of it is like we actually
live on phage planet. Like we think we're the main
thing going on on the planet, but maybe we aren't.
Speaker 2 (03:21):
Yeah, life is evolved in a soup of viruses, and
most of those viruses are phages. And if a kind
of alien life form was to just pluck a random
bit of the Earth and look for life, they would
probably find phages and nothing else, you know, if they
just took a random bit of sea water.
Speaker 3 (03:40):
Huh.
Speaker 1 (03:40):
So we've been talking about phages at this sort of
macro level, big picture level at a more micro level,
like what's a phage look like? I know they're very small,
but if you look really closely, what to look like?
Speaker 2 (03:56):
So one of the reasons I'm so interested in phages.
Is that actually extraordinary looking things? And there was some
discussion in the phage community that the lunar landers were
actually based on a certain type of phage. I was
never able to confirm that, but they have a remarkably
(04:17):
similar structure, and they look almost like kind of tiny
robotic nano machines or spiders. They're weirdly angular. So they
have this twenty sided head which looks quite sinister, which
contains all of the DNA. Then they have this long
tail which actually acts like a kind of molecular syringe
(04:38):
which can inject the genes from the head into the bacteria.
And then they have these kind of spider like little
legs which they use to land on the surface of
the bacteria and bind to it. There's this head that
has the payload in whether that's astronauts or genes, and
then the landing legs. And then once once the phage
(05:01):
is landed and injects the DNA, and it essentially hijacks
the bacteria and turns it into a virus factory.
Speaker 3 (05:09):
Amazing.
Speaker 1 (05:10):
You know, viruses are generally thought of as bad, and
it is sort of delightful to encounter this large universe
of helpful viruses, like I'm very happy to be discovering
these good viruses.
Speaker 2 (05:24):
Yeah, and they vastly outnumber the ones that we fear
and hate. It's really interesting that the idea of using
them to kill bacteria and kill the bacteria that caused
disease is not new at all. You know, they were
being used in medicine decades before the first real antibiotic, penicillin.
They were being used in the twenties and the thirties,
(05:46):
and this idea of using them as allies as medicines
is becoming you know, it's being taken really seriously again. Yeah.
Speaker 3 (05:55):
Right.
Speaker 1 (05:56):
That goes back to the early part of the twentieth century.
And there is this key figure who you write a
lot about in your book. Really interesting story. So tell
me about him. Tell me about Felix Durell.
Speaker 2 (06:10):
So, Felix Durel's fascinating character, a real maverick. He's kind
of self taught, volatile, has none of the diplomacy that
was expected of kind of gentlemen scientists of the early
twentieth century. There's a dispute about whether he's French or
Canadian or Belgian because he kept changing his name. He
(06:30):
didn't really go to college to university. He spent his
teenage years traveling around Europe. He moved over to Canada,
declared himself a microbiologist. He was commissioned by the Canadian
government to make whiskey from maple syrup, which maybe the
most Canadian thing I've ever heard. And then he had
this period of kind of conducting completely wild, lawless science
(06:55):
as an infectious disease doctor in Mexico and Watemala, where
he was really given free reign to do what he wanted.
So a really unconventional background, very brash and terrible diplomacy,
you know. So he made lots of enemies. People were
very suspicious of him, and he was just, you know,
(07:15):
just the ultimate kind of outcast, I suppose in a
very important scientific field.
Speaker 1 (07:23):
How does Dourell make his discovery about features.
Speaker 2 (07:26):
In the nineteen tens, He essentially stumbles across this amazing
of observation, which is that he has plates of bacteria
that he's working on. It's called a lawn of bacteria.
It doesn't look like much, but it's kind of opaque
and milky, and that means all of your bacteria is
growing nicely on whatever medium. You've given it to grow on.
(07:49):
And he starts noticing on some of his plates there's
holes and there's literally nothing there. Ah, And he takes
a little touch from the middle of one of these holes,
and he just which is another plate of completely healthy, uniform,
milky bacteria. A hole starts growing on that too, And
then he can do this indefinitely. He can take a
(08:09):
touch from the hole and touch it on another healthy
plate of bacteria. The hole starts growing again. So he
knows this isn't just something that's a kind of antibacterial chemical.
This has the power of replication. This is growing at
the expense of the bacteria. So it's a double whammy
of scientific discovery because he's he's found something that seems
(08:34):
to be killing bacteria really quickly and really efficiently, all
at once. He has a suite of theories. He theorizes
that this is a virus that kills bacteria. He works
out that they are replicating inside the bacteria and then
bursting out. He also theorizes that phages are maybe part
of our immune system, and that when someone spontaneously recovers
(08:57):
from a disease, perhaps it's phages in our guts or
in our body that has helped us recover from that disease.
So as well as being completely groundbreaking, that latter idea
of them being part of our immune system was kind
of heretical at the time. You know, it was a
completely wild and wacky theory.
Speaker 1 (09:19):
This is a moment when there are no antibiotics in
the world, right, this is the moment when, no matter
how rich you are, if you get a little infection
on your foot, you might die from it. Right, truly,
like there is no way to reliably and safely kill bacteria.
So like this is a huge, huge thing.
Speaker 2 (09:40):
Yeah, when he presented these ideas to the world, the
establishment of these huge you know, microbiologists of the time
they just said, there's no way this is true. I
think one of them actually said, if this microbe exists,
I would have found it by now. People just couldn't
(10:00):
believe that he'd discovered this entirely new form of life
that had such a powerful potential use in medicine.
Speaker 1 (10:07):
So he has discovered this incredible thing, there's this obvious
potential for clinical applications, right, how does he try and
take this idea and actually use it as a treatment.
Speaker 2 (10:22):
Yes, So this is before clinical trials. Felix Drel walks
into a children's hospital in Paris and says, I have
a way of treating dysentery, this horrible inflammation of the
bowels which causes you to essentially have such severe diarrhea
that you die. And they decide to give a dose
(10:42):
of phases to two young kids from a particular family
who've come in with very severe dysentery, and you know,
they make a full recovery.
Speaker 1 (10:53):
I mean, one question is how often does that happen
in the absence of treatment?
Speaker 2 (10:57):
Right?
Speaker 1 (10:58):
Like the reason you really want a randomize trial is
to know is this the treatment, is it in this
case the phage, or is it just would have happened anyway.
Speaker 2 (11:07):
Exactly So Durrell he tries it on a few more
kids in this hospital. It's successful. He's essentially selling his
own cocktails of phages for various different bacterial diseases, and
he's in this really unusual situation where the establishment microbiologists
are still suggesting he's wrong, and they don't believe his theory,
(11:31):
and they're trying to disprove his theory. But he is
a great salesman of these phage based potions and he
starts traveling the world and selling them to ministries of
health and hospital directors, and they don't really care what
the kind of academics are saying. And within a decade,
phages are everywhere.
Speaker 1 (11:52):
Does it work? Like? I can't tell? Like he still
seems shady, Like it could be snake oil.
Speaker 2 (11:59):
I think Felix Drell, who had an understanding of phages
that was greater than anyone else on the planet. He
developed a way of actually understanding which strains of bacteria
were circulating in a given place at a given time,
and then creating a remedy based on phages that he
knew could kill those bacteria. As soon as pharmaceutical companies
(12:22):
got involved and started trying to make products that were
like mass market products, you know, it was completely hit
and miss. So there was this complete inconsistency. At the time.
People didn't understand phages well enough, and so phages got
this reputation as being inconsistent, which they really struggled to
shake off until antibiotics came along.
Speaker 1 (12:45):
So let's talk about that. So antibiotics come along in
the what nineteen thirties, nineteen forties, Ah, what does the
rise of antibiotics mean for phage therapy.
Speaker 2 (13:01):
Penicillin was discovered, it was you know, it really was
a miracle drug. You know, you could mass produce it.
Doctors knew that if a bacterial disease was one of
these forty different types of bacteria, if it was caused
by those bacteria, then penicillin was good for it. And
so really that phage therapy started to look logistically very
(13:22):
difficult to administer. You know, you've got to match the
phage to the bacteria, or you've got to create a
cocktail of different phages. It just all of a sudden
seemed like a kind of wild and old fashioned and
backwards way to treat bacterial infections. And in the West,
at least, the idea of using phages was like, rah,
forget it.
Speaker 1 (13:42):
So what's the end of the story of Felix Durell.
Speaker 2 (13:47):
Well, it's not a happy ending for him. Really. He
died without any kind of acknowledgment of his work. He
was actually nominated for the Nobel Prize about thirty times
but never won it. He was a genius in his
own way and really set the ball rolling for this
idea of using phages to treat bacterial infections.
Speaker 1 (14:10):
So let's talk about the present. Antibiotics are amazing, but
bacteria are constantly evolving to resist antibiotics. Ken phages help
us with intibiotic resistance.
Speaker 2 (14:24):
Yeah, they absolutely can. I mean, it's as I've said,
it's not straightforward. This is very different to having a
pharmaceutical chemical that we can use on millions of people.
There is lab work involved with each case, and you're
talking about treating people with a living, evolving thing, often
that's been found in a kind of river or a sewer.
(14:46):
So there's just huge numbers of like logistical and regulatory
challenges around this. But you know, they have been evolving
for billions of years to kill bacteria. They are amazingly
good at it, and there are countless examples now of
phage therapy being used to save the life of people
who have infections that are resistant to every known antibiotic
(15:08):
in the cabinet.
Speaker 1 (15:13):
Tom Ireland's book is called The Good Virus, The Amazing
Story and Forgotten Promise of the Phage. We'll be back
in just a minute to talk to a scientist who
is using phages to treat disease. Now. In the first
(15:34):
half of today's show, Tom Ireland talked about how phage
therapy is being used today to treat people who have
antibiotic resistant infections. In the second half of today's show,
I'm going to talk with one of the few researchers
in the country who is actually doing this work. His
name is Ben Chan. He's a research scientist in ecology
and evolutionary biology at Yale. How did you come to
(15:58):
be a phage guy? How to get into phages?
Speaker 4 (16:02):
Back in grad school I studied amphibian biology. I studied
parental care behavior of poison dart frogs.
Speaker 3 (16:10):
And you got to do this.
Speaker 4 (16:12):
Amazing field work in amazing places and loved it. And
there was this fungal disease that's driving amphibian decline.
Speaker 3 (16:19):
And what I really.
Speaker 4 (16:20):
Wanted to do is I wanted to engineer the skin
microbiome of these poisoned dart frogs by making the bacteria
produce anti fungals so that they'd be resistant to this disease.
And I was like, that's how I'm going to save,
you know, frogs, And I wanted to do so with
a phage. Actually, I was going to engineer these bacteria
with phage.
Speaker 1 (16:38):
Ben told me he couldn't get funding for his save
the Frog's idea. But he wanted to continue his work,
and in twenty thirteen he started working at a lab
at Yale where he finds and studies phages. And it
was there that Ben connected with the surgeon at Yale
New Haven Hospital. The surgeon told him about this one
really challenging case.
Speaker 4 (16:58):
So this guy had and aneurysm on his A order. Right,
the vessels weaken, and when that's a vessel in the body, like,
if that thing explodes, that's really bad news, right, especially
the A order, which is like the largest vessel. So
they you know, bring him into surgery. They cut out
that piece and replace it with a plastic piece. And
then it turns out that got infected somehow, So he's
(17:20):
got this artificial graft onto his heart and then there's
like pseudomonius bacteria growing on it.
Speaker 1 (17:29):
So to be clear, he has this infection in a
place you really don't want an infection. Yeah, it's a
bacterial infection, So great, give him antibiotics. They give him antibiotics.
Speaker 4 (17:38):
What happens, it sort of just suppresses it at best, right,
So it won't go away with antibiotics, but you can,
you know, prevent it more or less from killing you,
I guess, but it's like a slow battle that eventually
you're gonna lose, and so they're kind of out options.
Speaker 1 (17:54):
So this patient has is infected with this bacteria that
you can't wipe out with antibiotics. So how does that work?
How does the bacteria survive the antibiotics?
Speaker 4 (18:05):
Yeah, So there's a few ways that bacteria can survive
antibiotic exposure.
Speaker 1 (18:09):
Right.
Speaker 4 (18:10):
They can either have an enzyme that chops up the
antibiotic before it does its job, or they can decrease permeability.
And then there's this other way, which is called antibiotic eflux,
where it's the antibiotic gets into the cell and could
otherwise function and kill the bacteria. But there are these
special pumps that the bacteria have that recognize antibiotics and
other sort of toxins and then they pump it out
(18:32):
before it can do what it's meant to do.
Speaker 3 (18:34):
That's rad yeah, the way they're so smart, right, the yeah.
Speaker 1 (18:39):
And so that's what's going on in this case. Right,
The bacteria inside this guy has a pump. So you
give him antibiotics, it goes into the bacteria and the
bacteria pumps it back out.
Speaker 4 (18:49):
Yeah, and so our natural response would be like, okay,
let's just throw more antibiotics there, right, And when you
do that, it makes them make more pumps, right.
Speaker 3 (18:56):
So there it's a tough arms race.
Speaker 1 (18:59):
It's the kind of antibiotic versus pathogen arms.
Speaker 3 (19:04):
Race, yeah, exactly.
Speaker 4 (19:05):
And the more you get in, eventually you're going to
start seeing some side effects.
Speaker 2 (19:08):
Right.
Speaker 4 (19:09):
You can only put so much chemical in someone before
there's there's problems.
Speaker 1 (19:13):
Yeah, And what is your idea when you show up?
Speaker 4 (19:15):
So I just was like, well, why don't we try
to use you know, a bacteria phage, which is a
virus of bacteria to try and kill this infection because
it's independent of antibiotic resistance, right, And that's not like
my idea. Right, They've been doing this since they found
bacteria phages, or they've been trying it. But I was like,
you know, it's been years since we've actually done this
seriously in the United States. Maybe we should, Maybe this
would be a good case to try it. And so
(19:38):
the surgeon was like, perfect, let's try it.
Speaker 1 (19:41):
Okay, So the surgeon's on board. What do you do
from there?
Speaker 4 (19:45):
The first thing is we get the isolate, so the
clinical lab guy here in the hospital was like, Okay,
here's your plate of bacteria. So we take this bacteria
back to the lab and we need to make sure
that we have a phase that can kill the bacteria.
Speaker 3 (19:58):
Right, ok So we've got this like, you know, fridge
full of phage.
Speaker 1 (20:01):
And the fridge full of phages, like all different phages, Yeah,
more or less. How many different phages.
Speaker 3 (20:07):
Do you have.
Speaker 4 (20:11):
Within an order of magnitude one thousand, a thousand?
Speaker 1 (20:15):
So how do you come to have a fridge with
a thousand?
Speaker 3 (20:19):
Yeah?
Speaker 1 (20:19):
Different kinds of phage.
Speaker 4 (20:21):
Yeah, so you know, regular trips to the sewage treatment
plant or you know, we're collecting from rivers, our ocean,
water lakes. We have all different phages for all different
bacteria because they're really really host specific. So it's not
like I can take any Coli phage and try to
kill Staph aureus with it or something. We had sort
of built up this library of Pseudomonus phages and we
(20:43):
took his sample and we basically tested all these phages
on his bacteria I see which ones would kill it.
And so we had phages and we've had one that
was I think slightly biased, really cool and that the
receptor binding site. So what the phage use is to
grab onto the bacteria and recognize it was this eflux
(21:04):
pump that we were talking about.
Speaker 3 (21:06):
Huh.
Speaker 4 (21:06):
So you know it in a sea of pseudomonas, not
all of them have these eflux pumps, and so the
phage is like looking for just those guys.
Speaker 1 (21:16):
So specifically, this phage, this particular phase that you're optimistic about,
is actually targeting the thing that allows some of the
bacteria to resist the antibiotics exactly. So this phage is
sort of optimal to use in combination with antibiotics. Yeah, right,
because either the bacteria has a pump and is therefore
(21:39):
antibiotic resistant but targeted by the phage, or it doesn't
have a pump, in which case the antibiotics will kill
it exactly.
Speaker 3 (21:46):
Yep.
Speaker 1 (21:47):
It's a great theory, yeah theory.
Speaker 4 (21:49):
Yeah, yeah, but that's what we had to go with, right.
It was this this theory and that like the thinking
that the phage it could either it could kill all
the bacteria, right and that would be a great out
come for this guy, or it could kill a lot
of them and then they could evolve resistance, which would
not be ideal. But it'd be antibiotic ex sensitive, so
maybe a win. And we tested it in the lab
(22:10):
and everything looked great. So I brought this data to
the surgeon. I was like, look, it seems like it's
pretty good at what it does. And then he's like, well,
let's try it cuz you mean, what else we need
to do? So, you know, it gets the FDA on
the phone and like, okay, here's a few things you
need to do to make sure that you're not going
to like do harm. So we did those quality control
(22:31):
things and then then they're like, okay, cool'll do it.
So we had the FDA, the institution, everyone was on board,
and then all we had to do was the actual procedure.
Speaker 1 (22:41):
So once you get the approval, you've got a patient
out in the world. You've got this one kind of
phage yeap, how do you get it into the guy?
Speaker 4 (22:50):
Yeah, so it's like a little clear vial. It's a
clean phage only solution. And then we brought that from
the fridge over to the hospital. I just in like
a little foam cooler, and then we go to the
operating room where they had had this guy sedated and ready,
and then the surgeons there, he's like, Okay, we're gonna
(23:12):
do this. One of the nurses is like, okay, do
you guys need the like the crash cart.
Speaker 1 (23:16):
To be clear, that crash card is for if the
patient's heart stops beating, essentially if they die.
Speaker 4 (23:21):
Yeah, And so I'm like, all right, well, now it's
like definitely real, like it was real before, but now
it's like, dude, like, don't screw this up. Then they
start they're like, okay, so here's what we're gonna do.
We're gonna take this crazy long needle and we're just
gonna like jam it way down by the base of
the air or to The hope was they would take
this needle and get down into the area like and
(23:45):
puncture a little area where there was the bacteria. Right,
So they wanted to get into the spot, rinse it out,
and then shoot in the phage.
Speaker 3 (23:52):
And that was the dream.
Speaker 4 (23:53):
And they just couldn't puncture this area because there's all
this scar tissue, and so then they're like, well, we're
just gonna have to call it because we can't get
in there, and if we push too hard, you know,
like stab the guy in the heart.
Speaker 3 (24:05):
So we're stuck. And then this.
Speaker 4 (24:07):
Surgeon was like, okay, so here's what we can do.
This draining hole here that's draining out of him already.
What if we just pipe the phage up that hole
and then it'll track back to the infection site.
Speaker 3 (24:18):
We can try that.
Speaker 4 (24:20):
So he, you know, he calls the pharmacy, gets the
some antibiotic, mixes it with the phage in the operating
room in a syringe, and he just like just basically
pokes it in there and just like shoots it in.
Speaker 1 (24:30):
Shoots it into the hole on the guy's on the
patient's chest.
Speaker 4 (24:32):
Yeah, So then he covers it up with a bandage
and he's like, let's see what happens. Right, So they
close him up and then they discharge him the next
day and then like I'm like, okay, I wonder if
it worked. I'm sitting here like everything's fine. Like then
like it turns into like weeks and I'm like, dude,
(24:55):
and then uh, the surgeon just emails me like out
of the boy's like, oh, you'll never guess you turned
up in my off looks like a million bucks.
Speaker 3 (25:01):
Everything's fine.
Speaker 1 (25:02):
So it worked. So the Finch therapy works.
Speaker 3 (25:04):
Yeah, as far as we can tell.
Speaker 1 (25:06):
Like the infection that had been persisting for years by
that point, it just went away entirely.
Speaker 4 (25:12):
Yep, yeah, five years and then gone. So he stopped
antibiotics and then he was fine.
Speaker 1 (25:19):
So this this whole thing happened several years ago, right
like seven years ago now, and I'm curre's what's happened
since then? Like, have you still been treating other patients?
Do you hear from people who were interested in phage therapy?
Speaker 4 (25:32):
So that first case was twenty sixteen, and then we
treated another seventeen and then like eighteen nineteen, like you
just went crazy from there. Then things went like extra crazy, right,
So you get emails all the time from people from
their physicians, from their loved ones, from whoever who had
these horrible infections. I mean, you know, like how big
(25:52):
of a problem antibiotic resistance is, right, You read the
news and the headlines and stuff, but like I feel
like it really hits home when someone sends you in
email that's like, dude, here's my story. I've been on
these antibiotics constantly. I'm writing you from a hospital on
my phone right now. This fucking sucks, like like things
aren't working, and like when you get like after the
(26:12):
first you know, ten of those, You're like, this is
like a really serious issue, Like it really hits home
more when when someone sends you a note like that.
Speaker 1 (26:21):
So where where are we now? Is phage therapy like
a thing in US medicine? And I just don't hear
about it because there's a lot I don't hear about.
Speaker 4 (26:30):
It's slowly becoming a thing more with these clinical trials
going on and like compassionate cases being treated fairly regularly.
Speaker 1 (26:36):
And so in the US at this point, like rough
order of magnitude estimate how many people a year, say,
are treated with phage therapy?
Speaker 4 (26:45):
Ooh, within an order of magnitude you know, one hundred,
one hundred, Yeah, so very small yeah still yeah yeah.
Speaker 1 (26:53):
And you mentioned some clinical trials that are ongoing. I mean,
is it the kind of thing where if those clinic trials,
you know, demonstrate safety and efficacy, it'll become a much
bigger thing. It'll be thousands or tens of thousands of
people that you're being treated with phage therapy.
Speaker 4 (27:10):
Well, we'll find out. I guess we're sort of finding
out as we go. But you know, the safety problem
is it's not an issue I think that's that's got
a lot of support that they're safe. The efficacy we're
trying to figure out still, but you know, assuming all
goes well on these trials, unfortunately, it probably comes down
to people deciding economically how to make it work.
Speaker 3 (27:34):
Right.
Speaker 1 (27:35):
What are some of the limits of phage therapy.
Speaker 4 (27:38):
You know there are cases in which it hasn't seemed
to have done anything. The problem with those is that
they don't often get written up and published, so we
don't know what we're not doing correctly in a lot
of these cases, or why it may have failed. But
that's changing now a little bit.
Speaker 1 (27:55):
Like in this story you told of this one compassionate
use case, very bespoke, right, and if we want it
to get to tens of thousands of patients a year
or thousands of patients a year, even seems like you
would want it to be less bespoke, You would want
it to be more industrialized and standardized. Is it possible
(28:18):
to do that or is the nature of phage therapy
such that it has to remain you know, very kind
of artisanal one by one.
Speaker 4 (28:27):
I think it's somewhere in the middle. So it's not
just me like you know, custom brewing a batch for
every person that has an infection. So we're past that part.
But I think it's also not someone just comes in
and like, here's an injection of phage and you're done.
But standardization and distribution and all these things are details
we have to sort of establish. But it's it's definitely doable.
(28:50):
And the part that I really really love about phage
therapy is that it it more or less democratizes a
lot of infection management in that the cost is not crazy,
the technology is not crazy. I mean there's some meant
there's some costs, but like any country can do it.
Speaker 1 (29:10):
If things go well, what does phage therapy look like
five or so years from now?
Speaker 3 (29:15):
I would see it being more readily available.
Speaker 4 (29:18):
I would love to see, you know, people all over
the world having access and producing their own pages. I
mean to take a lot of work, but I think
we could do in five years.
Speaker 3 (29:29):
It was great to talk with you. Thank you for
your time. Great to talk to you.
Speaker 1 (29:34):
Thanks to my guest today, Tom Ireland and Ben Chan.
Incubation is a co production of Pushkin Industries and Ruby
Studio at iHeartMedia. It's produced by Gabriel Hunter chang Ariela
Markowitz and Amy Gaines McQuaid. Our editors are Julia Barton
and Karen Shakerjie Mastering by Anne Pope, fact checking by
(29:57):
Joseph Fridman. Our executive p you Sirs Are Katherine Girardeau
and Matt Romano. I'm Jacob Goldstein. Thanks for listening.
There's a question. I've been waiting a long time to
ask you phage or phage?
Speaker 2 (00:08):
I say phage. Some people say fage.
Speaker 1 (00:12):
Faj Come on, get the fuj out of here. What
is it?
Speaker 2 (00:17):
I think phage and phage are so similar that we
can work with that. It's Greek for killer or to
sort of eat.
Speaker 1 (00:26):
But in English. Yeah, so you're saying, you say phage
rhymes with.
Speaker 2 (00:30):
Age, I say phage.
Speaker 1 (00:33):
I'm talking with Tom Ireland. He is a science journalist
who just wrote a book called The Good Virus, and
it is all about phages. Phages are these amazing viruses
that have sort of flown under the radar since they
were discovered in the first part of the twentieth century.
Phages also known as bacteria phages are viruses that kill bacteria,
(00:55):
and that is a very useful trait if you need
to kill bacteria that are making someone really sick. And
in fact, Tom told me people are now turning to
phages to try to treat infections that can't be cured
with antibiotics.
Speaker 2 (01:08):
I think this year is the year that it all changes,
because the crisis of drug resistance is so acute and
so scary. Now that we have to take it seriously.
So the World Economic Forum this year named phage therapy
in their top ten Emerging technologies for twenty twenty three.
You know, we're not just guessing and throwing viruses into
(01:30):
people with bloodstream anymore. This is a kind of modern
phage therapy two point zero, and there's some real momentum
building behind the idea.
Speaker 1 (01:39):
Now, we spend a lot of time on this show
talking about viruses that are bad for humans, Viruses that
make us sick, viruses that have killed hundreds of millions
of people. Today, for the season finale, we bring you
a shocking twist show about viruses that are good for people,
(02:00):
Viruses that help us fight disease. We'll hear the story
of one of the first scientists to study phages. He
was kind of a genius, but also he was kind
of shady. And then we'll talk to a scientist who
collects phages in lakes and sewage plants and then uses
them to treat patients with life threatening infections that cannot
(02:21):
be treated with antibiotics. I'm Jacob Goldstein. This is incubation
in the world on planet Earth right now. How many
(02:43):
phages not kinds of phages, but phages.
Speaker 2 (02:46):
So there's a number that goes around a lot. It's
a very rough calculation, but it's ten with thirty one
zeros after it. One way of thinking of that is
a trillion phages for every grain of sand on the planet.
So just just crazy numbers.
Speaker 1 (03:07):
I don't know what to do with that. You said
a trillion for every grain of sand. That's like a
come on kind of number, right, I mean, I guess
one way to think of it is like we actually
live on phage planet. Like we think we're the main
thing going on on the planet, but maybe we aren't.
Speaker 2 (03:21):
Yeah, life is evolved in a soup of viruses, and
most of those viruses are phages. And if a kind
of alien life form was to just pluck a random
bit of the Earth and look for life, they would
probably find phages and nothing else, you know, if they
just took a random bit of sea water.
Speaker 3 (03:40):
Huh.
Speaker 1 (03:40):
So we've been talking about phages at this sort of
macro level, big picture level at a more micro level,
like what's a phage look like? I know they're very small,
but if you look really closely, what to look like?
Speaker 2 (03:56):
So one of the reasons I'm so interested in phages.
Is that actually extraordinary looking things? And there was some
discussion in the phage community that the lunar landers were
actually based on a certain type of phage. I was
never able to confirm that, but they have a remarkably
(04:17):
similar structure, and they look almost like kind of tiny
robotic nano machines or spiders. They're weirdly angular. So they
have this twenty sided head which looks quite sinister, which
contains all of the DNA. Then they have this long
tail which actually acts like a kind of molecular syringe
(04:38):
which can inject the genes from the head into the bacteria.
And then they have these kind of spider like little
legs which they use to land on the surface of
the bacteria and bind to it. There's this head that
has the payload in whether that's astronauts or genes, and
then the landing legs. And then once once the phage
(05:01):
is landed and injects the DNA, and it essentially hijacks
the bacteria and turns it into a virus factory.
Speaker 3 (05:09):
Amazing.
Speaker 1 (05:10):
You know, viruses are generally thought of as bad, and
it is sort of delightful to encounter this large universe
of helpful viruses, like I'm very happy to be discovering
these good viruses.
Speaker 2 (05:24):
Yeah, and they vastly outnumber the ones that we fear
and hate. It's really interesting that the idea of using
them to kill bacteria and kill the bacteria that caused
disease is not new at all. You know, they were
being used in medicine decades before the first real antibiotic, penicillin.
They were being used in the twenties and the thirties,
(05:46):
and this idea of using them as allies as medicines
is becoming you know, it's being taken really seriously again. Yeah.
Speaker 3 (05:55):
Right.
Speaker 1 (05:56):
That goes back to the early part of the twentieth century.
And there is this key figure who you write a
lot about in your book. Really interesting story. So tell
me about him. Tell me about Felix Durell.
Speaker 2 (06:10):
So, Felix Durel's fascinating character, a real maverick. He's kind
of self taught, volatile, has none of the diplomacy that
was expected of kind of gentlemen scientists of the early
twentieth century. There's a dispute about whether he's French or
Canadian or Belgian because he kept changing his name. He
(06:30):
didn't really go to college to university. He spent his
teenage years traveling around Europe. He moved over to Canada,
declared himself a microbiologist. He was commissioned by the Canadian
government to make whiskey from maple syrup, which maybe the
most Canadian thing I've ever heard. And then he had
this period of kind of conducting completely wild, lawless science
(06:55):
as an infectious disease doctor in Mexico and Watemala, where
he was really given free reign to do what he wanted.
So a really unconventional background, very brash and terrible diplomacy,
you know. So he made lots of enemies. People were
very suspicious of him, and he was just, you know,
(07:15):
just the ultimate kind of outcast, I suppose in a
very important scientific field.
Speaker 1 (07:23):
How does Dourell make his discovery about features.
Speaker 2 (07:26):
In the nineteen tens, He essentially stumbles across this amazing
of observation, which is that he has plates of bacteria
that he's working on. It's called a lawn of bacteria.
It doesn't look like much, but it's kind of opaque
and milky, and that means all of your bacteria is
growing nicely on whatever medium. You've given it to grow on.
(07:49):
And he starts noticing on some of his plates there's
holes and there's literally nothing there. Ah, And he takes
a little touch from the middle of one of these holes,
and he just which is another plate of completely healthy, uniform,
milky bacteria. A hole starts growing on that too, And
then he can do this indefinitely. He can take a
(08:09):
touch from the hole and touch it on another healthy
plate of bacteria. The hole starts growing again. So he
knows this isn't just something that's a kind of antibacterial chemical.
This has the power of replication. This is growing at
the expense of the bacteria. So it's a double whammy
of scientific discovery because he's he's found something that seems
(08:34):
to be killing bacteria really quickly and really efficiently, all
at once. He has a suite of theories. He theorizes
that this is a virus that kills bacteria. He works
out that they are replicating inside the bacteria and then
bursting out. He also theorizes that phages are maybe part
of our immune system, and that when someone spontaneously recovers
(08:57):
from a disease, perhaps it's phages in our guts or
in our body that has helped us recover from that disease.
So as well as being completely groundbreaking, that latter idea
of them being part of our immune system was kind
of heretical at the time. You know, it was a
completely wild and wacky theory.
Speaker 1 (09:19):
This is a moment when there are no antibiotics in
the world, right, this is the moment when, no matter
how rich you are, if you get a little infection
on your foot, you might die from it. Right, truly,
like there is no way to reliably and safely kill bacteria.
So like this is a huge, huge thing.
Speaker 2 (09:40):
Yeah, when he presented these ideas to the world, the
establishment of these huge you know, microbiologists of the time
they just said, there's no way this is true. I
think one of them actually said, if this microbe exists,
I would have found it by now. People just couldn't
(10:00):
believe that he'd discovered this entirely new form of life
that had such a powerful potential use in medicine.
Speaker 1 (10:07):
So he has discovered this incredible thing, there's this obvious
potential for clinical applications, right, how does he try and
take this idea and actually use it as a treatment.
Speaker 2 (10:22):
Yes, So this is before clinical trials. Felix Drel walks
into a children's hospital in Paris and says, I have
a way of treating dysentery, this horrible inflammation of the
bowels which causes you to essentially have such severe diarrhea
that you die. And they decide to give a dose
(10:42):
of phases to two young kids from a particular family
who've come in with very severe dysentery, and you know,
they make a full recovery.
Speaker 1 (10:53):
I mean, one question is how often does that happen
in the absence of treatment?
Speaker 2 (10:57):
Right?
Speaker 1 (10:58):
Like the reason you really want a randomize trial is
to know is this the treatment, is it in this
case the phage, or is it just would have happened anyway.
Speaker 2 (11:07):
Exactly So Durrell he tries it on a few more
kids in this hospital. It's successful. He's essentially selling his
own cocktails of phages for various different bacterial diseases, and
he's in this really unusual situation where the establishment microbiologists
are still suggesting he's wrong, and they don't believe his theory,
(11:31):
and they're trying to disprove his theory. But he is
a great salesman of these phage based potions and he
starts traveling the world and selling them to ministries of
health and hospital directors, and they don't really care what
the kind of academics are saying. And within a decade,
phages are everywhere.
Speaker 1 (11:52):
Does it work? Like? I can't tell? Like he still
seems shady, Like it could be snake oil.
Speaker 2 (11:59):
I think Felix Drell, who had an understanding of phages
that was greater than anyone else on the planet. He
developed a way of actually understanding which strains of bacteria
were circulating in a given place at a given time,
and then creating a remedy based on phages that he
knew could kill those bacteria. As soon as pharmaceutical companies
(12:22):
got involved and started trying to make products that were
like mass market products, you know, it was completely hit
and miss. So there was this complete inconsistency. At the time.
People didn't understand phages well enough, and so phages got
this reputation as being inconsistent, which they really struggled to
shake off until antibiotics came along.
Speaker 1 (12:45):
So let's talk about that. So antibiotics come along in
the what nineteen thirties, nineteen forties, Ah, what does the
rise of antibiotics mean for phage therapy.
Speaker 2 (13:01):
Penicillin was discovered, it was you know, it really was
a miracle drug. You know, you could mass produce it.
Doctors knew that if a bacterial disease was one of
these forty different types of bacteria, if it was caused
by those bacteria, then penicillin was good for it. And
so really that phage therapy started to look logistically very
(13:22):
difficult to administer. You know, you've got to match the
phage to the bacteria, or you've got to create a
cocktail of different phages. It just all of a sudden
seemed like a kind of wild and old fashioned and
backwards way to treat bacterial infections. And in the West,
at least, the idea of using phages was like, rah,
forget it.
Speaker 1 (13:42):
So what's the end of the story of Felix Durell.
Speaker 2 (13:47):
Well, it's not a happy ending for him. Really. He
died without any kind of acknowledgment of his work. He
was actually nominated for the Nobel Prize about thirty times
but never won it. He was a genius in his
own way and really set the ball rolling for this
idea of using phages to treat bacterial infections.
Speaker 1 (14:10):
So let's talk about the present. Antibiotics are amazing, but
bacteria are constantly evolving to resist antibiotics. Ken phages help
us with intibiotic resistance.
Speaker 2 (14:24):
Yeah, they absolutely can. I mean, it's as I've said,
it's not straightforward. This is very different to having a
pharmaceutical chemical that we can use on millions of people.
There is lab work involved with each case, and you're
talking about treating people with a living, evolving thing, often
that's been found in a kind of river or a sewer.
(14:46):
So there's just huge numbers of like logistical and regulatory
challenges around this. But you know, they have been evolving
for billions of years to kill bacteria. They are amazingly
good at it, and there are countless examples now of
phage therapy being used to save the life of people
who have infections that are resistant to every known antibiotic
(15:08):
in the cabinet.
Speaker 1 (15:13):
Tom Ireland's book is called The Good Virus, The Amazing
Story and Forgotten Promise of the Phage. We'll be back
in just a minute to talk to a scientist who
is using phages to treat disease. Now. In the first
(15:34):
half of today's show, Tom Ireland talked about how phage
therapy is being used today to treat people who have
antibiotic resistant infections. In the second half of today's show,
I'm going to talk with one of the few researchers
in the country who is actually doing this work. His
name is Ben Chan. He's a research scientist in ecology
and evolutionary biology at Yale. How did you come to
(15:58):
be a phage guy? How to get into phages?
Speaker 4 (16:02):
Back in grad school I studied amphibian biology. I studied
parental care behavior of poison dart frogs.
Speaker 3 (16:10):
And you got to do this.
Speaker 4 (16:12):
Amazing field work in amazing places and loved it. And
there was this fungal disease that's driving amphibian decline.
Speaker 3 (16:19):
And what I really.
Speaker 4 (16:20):
Wanted to do is I wanted to engineer the skin
microbiome of these poisoned dart frogs by making the bacteria
produce anti fungals so that they'd be resistant to this disease.
And I was like, that's how I'm going to save,
you know, frogs, And I wanted to do so with
a phage. Actually, I was going to engineer these bacteria
with phage.
Speaker 1 (16:38):
Ben told me he couldn't get funding for his save
the Frog's idea. But he wanted to continue his work,
and in twenty thirteen he started working at a lab
at Yale where he finds and studies phages. And it
was there that Ben connected with the surgeon at Yale
New Haven Hospital. The surgeon told him about this one
really challenging case.
Speaker 4 (16:58):
So this guy had and aneurysm on his A order. Right,
the vessels weaken, and when that's a vessel in the body, like,
if that thing explodes, that's really bad news, right, especially
the A order, which is like the largest vessel. So
they you know, bring him into surgery. They cut out
that piece and replace it with a plastic piece. And
then it turns out that got infected somehow, So he's
(17:20):
got this artificial graft onto his heart and then there's
like pseudomonius bacteria growing on it.
Speaker 1 (17:29):
So to be clear, he has this infection in a
place you really don't want an infection. Yeah, it's a
bacterial infection, So great, give him antibiotics. They give him antibiotics.
Speaker 4 (17:38):
What happens, it sort of just suppresses it at best, right,
So it won't go away with antibiotics, but you can,
you know, prevent it more or less from killing you,
I guess, but it's like a slow battle that eventually
you're gonna lose, and so they're kind of out options.
Speaker 1 (17:54):
So this patient has is infected with this bacteria that
you can't wipe out with antibiotics. So how does that work?
How does the bacteria survive the antibiotics?
Speaker 4 (18:05):
Yeah, So there's a few ways that bacteria can survive
antibiotic exposure.
Speaker 1 (18:09):
Right.
Speaker 4 (18:10):
They can either have an enzyme that chops up the
antibiotic before it does its job, or they can decrease permeability.
And then there's this other way, which is called antibiotic eflux,
where it's the antibiotic gets into the cell and could
otherwise function and kill the bacteria. But there are these
special pumps that the bacteria have that recognize antibiotics and
other sort of toxins and then they pump it out
(18:32):
before it can do what it's meant to do.
Speaker 3 (18:34):
That's rad yeah, the way they're so smart, right, the yeah.
Speaker 1 (18:39):
And so that's what's going on in this case. Right,
The bacteria inside this guy has a pump. So you
give him antibiotics, it goes into the bacteria and the
bacteria pumps it back out.
Speaker 4 (18:49):
Yeah, and so our natural response would be like, okay,
let's just throw more antibiotics there, right, And when you
do that, it makes them make more pumps, right.
Speaker 3 (18:56):
So there it's a tough arms race.
Speaker 1 (18:59):
It's the kind of antibiotic versus pathogen arms.
Speaker 3 (19:04):
Race, yeah, exactly.
Speaker 4 (19:05):
And the more you get in, eventually you're going to
start seeing some side effects.
Speaker 2 (19:08):
Right.
Speaker 4 (19:09):
You can only put so much chemical in someone before
there's there's problems.
Speaker 1 (19:13):
Yeah, And what is your idea when you show up?
Speaker 4 (19:15):
So I just was like, well, why don't we try
to use you know, a bacteria phage, which is a
virus of bacteria to try and kill this infection because
it's independent of antibiotic resistance, right, And that's not like
my idea. Right, They've been doing this since they found
bacteria phages, or they've been trying it. But I was like,
you know, it's been years since we've actually done this
seriously in the United States. Maybe we should, Maybe this
would be a good case to try it. And so
(19:38):
the surgeon was like, perfect, let's try it.
Speaker 1 (19:41):
Okay, So the surgeon's on board. What do you do
from there?
Speaker 4 (19:45):
The first thing is we get the isolate, so the
clinical lab guy here in the hospital was like, Okay,
here's your plate of bacteria. So we take this bacteria
back to the lab and we need to make sure
that we have a phase that can kill the bacteria.
Speaker 3 (19:58):
Right, ok So we've got this like, you know, fridge
full of phage.
Speaker 1 (20:01):
And the fridge full of phages, like all different phages, Yeah,
more or less. How many different phages.
Speaker 3 (20:07):
Do you have.
Speaker 4 (20:11):
Within an order of magnitude one thousand, a thousand?
Speaker 1 (20:15):
So how do you come to have a fridge with
a thousand?
Speaker 3 (20:19):
Yeah?
Speaker 1 (20:19):
Different kinds of phage.
Speaker 4 (20:21):
Yeah, so you know, regular trips to the sewage treatment
plant or you know, we're collecting from rivers, our ocean,
water lakes. We have all different phages for all different
bacteria because they're really really host specific. So it's not
like I can take any Coli phage and try to
kill Staph aureus with it or something. We had sort
of built up this library of Pseudomonus phages and we
(20:43):
took his sample and we basically tested all these phages
on his bacteria I see which ones would kill it.
And so we had phages and we've had one that
was I think slightly biased, really cool and that the
receptor binding site. So what the phage use is to
grab onto the bacteria and recognize it was this eflux
(21:04):
pump that we were talking about.
Speaker 3 (21:06):
Huh.
Speaker 4 (21:06):
So you know it in a sea of pseudomonas, not
all of them have these eflux pumps, and so the
phage is like looking for just those guys.
Speaker 1 (21:16):
So specifically, this phage, this particular phase that you're optimistic about,
is actually targeting the thing that allows some of the
bacteria to resist the antibiotics exactly. So this phage is
sort of optimal to use in combination with antibiotics. Yeah, right,
because either the bacteria has a pump and is therefore
(21:39):
antibiotic resistant but targeted by the phage, or it doesn't
have a pump, in which case the antibiotics will kill
it exactly.
Speaker 3 (21:46):
Yep.
Speaker 1 (21:47):
It's a great theory, yeah theory.
Speaker 4 (21:49):
Yeah, yeah, but that's what we had to go with, right.
It was this this theory and that like the thinking
that the phage it could either it could kill all
the bacteria, right and that would be a great out
come for this guy, or it could kill a lot
of them and then they could evolve resistance, which would
not be ideal. But it'd be antibiotic ex sensitive, so
maybe a win. And we tested it in the lab
(22:10):
and everything looked great. So I brought this data to
the surgeon. I was like, look, it seems like it's
pretty good at what it does. And then he's like, well,
let's try it cuz you mean, what else we need
to do? So, you know, it gets the FDA on
the phone and like, okay, here's a few things you
need to do to make sure that you're not going
to like do harm. So we did those quality control
(22:31):
things and then then they're like, okay, cool'll do it.
So we had the FDA, the institution, everyone was on board,
and then all we had to do was the actual procedure.
Speaker 1 (22:41):
So once you get the approval, you've got a patient
out in the world. You've got this one kind of
phage yeap, how do you get it into the guy?
Speaker 4 (22:50):
Yeah, so it's like a little clear vial. It's a
clean phage only solution. And then we brought that from
the fridge over to the hospital. I just in like
a little foam cooler, and then we go to the
operating room where they had had this guy sedated and ready,
and then the surgeons there, he's like, Okay, we're gonna
(23:12):
do this. One of the nurses is like, okay, do
you guys need the like the crash cart.
Speaker 1 (23:16):
To be clear, that crash card is for if the
patient's heart stops beating, essentially if they die.
Speaker 4 (23:21):
Yeah, And so I'm like, all right, well, now it's
like definitely real, like it was real before, but now
it's like, dude, like, don't screw this up. Then they
start they're like, okay, so here's what we're gonna do.
We're gonna take this crazy long needle and we're just
gonna like jam it way down by the base of
the air or to The hope was they would take
this needle and get down into the area like and
(23:45):
puncture a little area where there was the bacteria. Right,
So they wanted to get into the spot, rinse it out,
and then shoot in the phage.
Speaker 3 (23:52):
And that was the dream.
Speaker 4 (23:53):
And they just couldn't puncture this area because there's all
this scar tissue, and so then they're like, well, we're
just gonna have to call it because we can't get
in there, and if we push too hard, you know,
like stab the guy in the heart.
Speaker 3 (24:05):
So we're stuck. And then this.
Speaker 4 (24:07):
Surgeon was like, okay, so here's what we can do.
This draining hole here that's draining out of him already.
What if we just pipe the phage up that hole
and then it'll track back to the infection site.
Speaker 3 (24:18):
We can try that.
Speaker 4 (24:20):
So he, you know, he calls the pharmacy, gets the
some antibiotic, mixes it with the phage in the operating
room in a syringe, and he just like just basically
pokes it in there and just like shoots it in.
Speaker 1 (24:30):
Shoots it into the hole on the guy's on the
patient's chest.
Speaker 4 (24:32):
Yeah, So then he covers it up with a bandage
and he's like, let's see what happens. Right, So they
close him up and then they discharge him the next
day and then like I'm like, okay, I wonder if
it worked. I'm sitting here like everything's fine. Like then
like it turns into like weeks and I'm like, dude,
(24:55):
and then uh, the surgeon just emails me like out
of the boy's like, oh, you'll never guess you turned
up in my off looks like a million bucks.
Speaker 3 (25:01):
Everything's fine.
Speaker 1 (25:02):
So it worked. So the Finch therapy works.
Speaker 3 (25:04):
Yeah, as far as we can tell.
Speaker 1 (25:06):
Like the infection that had been persisting for years by
that point, it just went away entirely.
Speaker 4 (25:12):
Yep, yeah, five years and then gone. So he stopped
antibiotics and then he was fine.
Speaker 1 (25:19):
So this this whole thing happened several years ago, right
like seven years ago now, and I'm curre's what's happened
since then? Like, have you still been treating other patients?
Do you hear from people who were interested in phage therapy?
Speaker 4 (25:32):
So that first case was twenty sixteen, and then we
treated another seventeen and then like eighteen nineteen, like you
just went crazy from there. Then things went like extra crazy, right,
So you get emails all the time from people from
their physicians, from their loved ones, from whoever who had
these horrible infections. I mean, you know, like how big
(25:52):
of a problem antibiotic resistance is, right, You read the
news and the headlines and stuff, but like I feel
like it really hits home when someone sends you in
email that's like, dude, here's my story. I've been on
these antibiotics constantly. I'm writing you from a hospital on
my phone right now. This fucking sucks, like like things
aren't working, and like when you get like after the
(26:12):
first you know, ten of those, You're like, this is
like a really serious issue, Like it really hits home
more when when someone sends you a note like that.
Speaker 1 (26:21):
So where where are we now? Is phage therapy like
a thing in US medicine? And I just don't hear
about it because there's a lot I don't hear about.
Speaker 4 (26:30):
It's slowly becoming a thing more with these clinical trials
going on and like compassionate cases being treated fairly regularly.
Speaker 1 (26:36):
And so in the US at this point, like rough
order of magnitude estimate how many people a year, say,
are treated with phage therapy?
Speaker 4 (26:45):
Ooh, within an order of magnitude you know, one hundred,
one hundred, Yeah, so very small yeah still yeah yeah.
Speaker 1 (26:53):
And you mentioned some clinical trials that are ongoing. I mean,
is it the kind of thing where if those clinic trials,
you know, demonstrate safety and efficacy, it'll become a much
bigger thing. It'll be thousands or tens of thousands of
people that you're being treated with phage therapy.
Speaker 4 (27:10):
Well, we'll find out. I guess we're sort of finding
out as we go. But you know, the safety problem
is it's not an issue I think that's that's got
a lot of support that they're safe. The efficacy we're
trying to figure out still, but you know, assuming all
goes well on these trials, unfortunately, it probably comes down
to people deciding economically how to make it work.
Speaker 3 (27:34):
Right.
Speaker 1 (27:35):
What are some of the limits of phage therapy.
Speaker 4 (27:38):
You know there are cases in which it hasn't seemed
to have done anything. The problem with those is that
they don't often get written up and published, so we
don't know what we're not doing correctly in a lot
of these cases, or why it may have failed. But
that's changing now a little bit.
Speaker 1 (27:55):
Like in this story you told of this one compassionate
use case, very bespoke, right, and if we want it
to get to tens of thousands of patients a year
or thousands of patients a year, even seems like you
would want it to be less bespoke, You would want
it to be more industrialized and standardized. Is it possible
(28:18):
to do that or is the nature of phage therapy
such that it has to remain you know, very kind
of artisanal one by one.
Speaker 4 (28:27):
I think it's somewhere in the middle. So it's not
just me like you know, custom brewing a batch for
every person that has an infection. So we're past that part.
But I think it's also not someone just comes in
and like, here's an injection of phage and you're done.
But standardization and distribution and all these things are details
we have to sort of establish. But it's it's definitely doable.
(28:50):
And the part that I really really love about phage
therapy is that it it more or less democratizes a
lot of infection management in that the cost is not crazy,
the technology is not crazy. I mean there's some meant
there's some costs, but like any country can do it.
Speaker 1 (29:10):
If things go well, what does phage therapy look like
five or so years from now?
Speaker 3 (29:15):
I would see it being more readily available.
Speaker 4 (29:18):
I would love to see, you know, people all over
the world having access and producing their own pages. I
mean to take a lot of work, but I think
we could do in five years.
Speaker 3 (29:29):
It was great to talk with you. Thank you for
your time. Great to talk to you.
Speaker 1 (29:34):
Thanks to my guest today, Tom Ireland and Ben Chan.
Incubation is a co production of Pushkin Industries and Ruby
Studio at iHeartMedia. It's produced by Gabriel Hunter chang Ariela
Markowitz and Amy Gaines McQuaid. Our editors are Julia Barton
and Karen Shakerjie Mastering by Anne Pope, fact checking by
(29:57):
Joseph Fridman. Our executive p you Sirs Are Katherine Girardeau
and Matt Romano. I'm Jacob Goldstein. Thanks for listening.
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