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Speaker 1: There's a battle being fought every minute of every day.

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Speaker 1: It isn't a traditional war on the battlefield between armies

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Speaker 1: of soldiers. It's a battle within us, between our immune

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Speaker 1: system and invading microbes. And we're not alone fighting off pathogens.

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Speaker 1: We have hosts of microbial allies. Inside our bodies are

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Speaker 1: multitudes of microbes, some helping us digest, others starving out

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Speaker 1: potential invaders. But until recently, infections were too often deadly,

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Speaker 1: and there was not much we could do other than

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Speaker 1: try to avoid them. Treatment options were thin. But almost

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Speaker 1: one hundred years ago we discovered a powerful new ally.

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Speaker 1: Some fungi were the enemy of our enemy, able to

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Speaker 1: kill bacteria and halt infections, and so antibiotics became our friends.

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Speaker 1: But bacteria respond and evolve, developing protections against antibiotics and

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Speaker 1: overcoming them. It's possible again today to become infected by

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Speaker 1: a resistant strain and for doctors to have no real

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Speaker 1: treatment options. Is it time to recruit a new ally

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Speaker 1: in the microbial war? Today, we'll welcome a visiting dignitary

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Speaker 1: and expert working on the front lines to find microbes

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Speaker 1: capable of killing resistant bacteria with techniques that can be

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Speaker 1: tailored to produce the particular microbe needed to halt your

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Speaker 1: individual infection. Welcome to Daniel and Kelly's extraordinarily individual universe.

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Speaker 2: Hello, this is Kelly Windersmith.

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Speaker 3: I study parasites and space, and I think probably maybe

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Speaker 3: the second or third critter on our planet was probably

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Speaker 3: a parasite taking advantage of the first. Hi.

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Speaker 1: I'm Daniel. I'm a particle of physicists and professor at

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Speaker 1: UC Irvine, and I'm definitely the second most useful person

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Speaker 1: at the Whiteston Institute for Advanced Science.

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Speaker 3: And the good news is today we're getting the first

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Speaker 3: most useful person back on the show.

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Speaker 2: This is the third time.

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Speaker 3: Katrina has joined you and I and I enjoy it

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Speaker 3: every single time.

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Speaker 1: Yeah, listeners seem to really enjoy having her on. And

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Speaker 1: of course I love talking to Katrina and she knows

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Speaker 1: so much about so many fascinating topics, especially the topic

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Speaker 1: we're tackling today.

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Speaker 3: Yeah, and today we learn a really fascinating fact about

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Speaker 3: what kind of organism on our planet is the most common.

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Speaker 3: And I was I can maybe a little bit surprised,

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Speaker 3: but so Daniel, I'll give you a little quiz here.

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Speaker 1: You were hoping she was going to say parasites, wouldn't

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Speaker 1: you Well, I mean.

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Speaker 3: The answer is a kind of parasite really or pathogen,

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Speaker 3: depending on how you find these things.

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Speaker 2: So I felt very validated today during our conversation.

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Speaker 3: But Daniel, if you had to guess what order of animals,

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Speaker 3: and remember it's Kingdom Philum class order or of animals

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Speaker 3: has the most species in it?

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Speaker 1: This is totally fair because I do a pop quiz

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Speaker 1: on our listeners all the time, and so here I've

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Speaker 1: had no chance to prepare you turn. I'm gonna have

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Speaker 1: to go beetles? Is it beetles or ants?

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Speaker 3: You have perhaps heard that folks think beetles are the

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Speaker 3: most common organism out there, and there's you know, claims

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Speaker 3: that God loved beetles more than any other organism and

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Speaker 3: that's why there were so many beetles on the planet.

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Speaker 3: But it looks like actually the most common kind of

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Speaker 3: animal is not a beetle, but it's like wasps and hymenopterans, because.

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Speaker 2: Each of those beetles species.

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Speaker 3: Is infected by one or more wasp that lays its

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Speaker 3: eggs inside of those beetles. And so yes, you have

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Speaker 3: a lot of hosts, but you, as is so often

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Speaker 3: the case, and we'll hear more about today. Hosts usually

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Speaker 3: harbor a diverse community of things that are willing to

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Speaker 3: live inside of them and eat their insides up, and

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Speaker 3: there's often more of those than there are the hosts.

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Speaker 3: Good luck, sleeping friends, And.

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Speaker 1: Those parasites have their own bacterias, and those bacterias have

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Speaker 1: their own little critters that live inside them. And today

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Speaker 1: we're gonna be hearing about how that all works and

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Speaker 1: how it might chart a new course for treatment for

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Speaker 1: difficult infections in humans.

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Speaker 3: It reminds me of a poem that goes, great fleas

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Speaker 3: have little fleas upon their backs to bite them, and

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Speaker 3: little fleas have lesser fleas, and so add infinitum, and

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Speaker 3: the great fleas themselves, in turn have greater fleas to

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Speaker 3: go on, while these again have greater still, and greater

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Speaker 3: still and so on.

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Speaker 2: Anyway, so there's always levels of infection going on.

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Speaker 1: It's infection all the way down.

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Speaker 2: It's amazing, sure is.

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Speaker 1: And so on today's program we have my wonderful wife

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Speaker 1: and colleague at the Whites Institute who is coming back

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Speaker 1: to the podcast to tell us about how she personally

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Speaker 1: is developing treatments against resistant bacteria.

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Speaker 2: Best whites in.

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Speaker 4: Just kidding, just.

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Speaker 1: Kidding, totally undrescent agree with you on that one. So

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Speaker 1: then it's my pleasure to welcome to the podcast Katrina Whitson.

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Speaker 1: She's a full professor recently promoted from Associate professor, congratulations,

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Speaker 1: and Chancellor's Fellow at UC Irvine, where she studies microbial

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Speaker 1: communities and how they interact with their hosts. That's us,

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Speaker 1: we're the hosts. She also holds a dual appointment at

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Speaker 1: the Whitsun Institute for Advanced Science, where she's the director

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Speaker 1: for wet lab science not just stuff on the computer,

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Speaker 1: and has won awards for her innovative salad dressing recipes

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Speaker 1: and her energetic insertion of chia seeds into every possible recipe. Katrina,

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Speaker 1: welcome back to the podcast.

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Speaker 4: Thank you very much for the overly kind introduction.

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Speaker 1: Well, if this whole podcast and science thing doesn't work out,

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Speaker 1: I'm counting on you to launch a line of salad

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Speaker 1: dressings featuring chia seeds.

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Speaker 4: Okay, I could probably do that. I just hope this

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Speaker 4: time people would like to have a second helping that's all.

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Speaker 3: Is this an inside joke? Does Daniel not have second helpings?

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Speaker 3: Of salad or something.

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Speaker 1: No. No. Katrina was one time making salad and we didn't

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Speaker 1: have any vinegar, so she drained a jar of pickles

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Speaker 1: and used pickle juice in the salad dressing, and one

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Speaker 1: of our guests called it a one helping kind of salad.

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Speaker 4: Us only after they learned what I had put in there.

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Speaker 4: They were gobbling it up, just buying before I said anything.

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Speaker 3: Oh, I see, I see you. We should never tell

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Speaker 3: people what's in the food until the end of the meal. Yeah,

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Speaker 3: but I imagine you could make a salad dressing with all

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Speaker 3: kinds of like microbiome related claims.

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Speaker 2: I would probably buy it.

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Speaker 4: It's true.

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Speaker 1: But today we're not here to talk about how to

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Speaker 1: make your salad tastey. We're here to understand how to

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Speaker 1: stay healthy and what's going on inside all of us.

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Speaker 1: And so we want to get to the topic of

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Speaker 1: phage therapy. But let's set the stage and remind ourselves

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Speaker 1: what's going on with traditional antibiotics. So, like, give us

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Speaker 1: the very basics. When you take penicillin or you take amoxicillin,

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Speaker 1: what's going on? How do those work? How do those

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Speaker 1: help you combat pathogens?

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Speaker 4: Really big question because each antibiotic is a molecule that

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Speaker 4: has its own type of mechanism, and so we now

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Speaker 4: have dozens of different kinds of antibiotics. They each work

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Speaker 4: in different ways. Some of them are called bacteria static,

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Speaker 4: so they'll halt the growth of the bacteria, they won't

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Speaker 4: directly kill them, and others are called bacteria cytle because

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Speaker 4: they can actually kill the bacteria. But the point is

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Speaker 4: that whichever antibiotic you're taking, the goal is that it's

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Speaker 4: going to prevent the bacteria from continuing to grow and

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Speaker 4: cause infection, and between the antibiotic and your immune system,

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Speaker 4: hopefully you're going to end up clearing the infection within

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Speaker 4: a day or two. You know, all of us have

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Speaker 4: probably had the experience of taking an antibiotic and feeling

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Speaker 4: better relatively quickly, and that's because the antibiotic is getting

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Speaker 4: in there, stopping or killing the bacteria, and then your

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Speaker 4: immune system helps clear the infection. And so we've all

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Speaker 4: also heard stories about how before around the era of

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Speaker 4: what World War two and antibiotics became more widely available,

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Speaker 4: people would often succumb to very normal infections that people

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Speaker 4: survive all the time. Right now, so we've become accustomed

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Speaker 4: to being able to survive infections that took people down

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Speaker 4: before the era of antibiotics and around the time of

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Speaker 4: World War two.

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Speaker 2: I like that. I like that a lot for bacterio

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Speaker 2: static stuff.

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Speaker 3: Is the goal here just that you are trying to

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Speaker 3: make sure they don't grow any more to give your

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Speaker 3: immune system time to kill them, or are you making

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Speaker 3: it so they can't reproduce and the goal is that

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Speaker 3: they'll die of old age at some point.

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Speaker 4: I think either of those would be good outcomes. So yeah, okay,

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Speaker 4: But the point is just the population of bacteria is

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Speaker 4: halted in its tracks, and then your immune system has

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Speaker 4: a better chance to catch up.

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Speaker 2: Got it.

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Speaker 1: And last time you're on the pod, you were telling

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Speaker 1: us about all the beneficial microbes that live within us

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Speaker 1: and among us. When you take one of these things,

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Speaker 1: are they somehow targeted towards pathogens or the things that

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Speaker 1: are hurting you, or is it just like an nuclear

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Speaker 1: bomb and it's just killing all of your microbes.

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Speaker 4: That's also nuanced because it depends on the antibiotic. But

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Speaker 4: on average, antibiotics have broader spectrum, which means that they

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Speaker 4: take out lots of different types of bacteria, or at

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Speaker 4: least a subset of bacteria, and to be honest, I'm

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Speaker 4: not a deep expert on exactly what each antibiotic can cover,

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Speaker 4: but it's definitely the case that when you take antibiotics,

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Speaker 4: you're likely to kill bacteria that we're not causing any

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Speaker 4: trouble at all. So there's there's pros and cons to that.

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Speaker 4: On the pro side, you don't have to think too

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Speaker 4: hard about which antibiotic to take. That doctor can be like, well,

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Speaker 4: your infection is probably kind of one of these types

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Speaker 4: of things, and then this antibiotic will probably take care

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Speaker 4: of the problem. So it's good in that sense. And

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Speaker 4: to be honest, at the time when we started using

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Speaker 4: antibiotics in the mid twentieth century, we didn't really appreciate

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Speaker 4: our microbiomes. We thought it'd be great if we could

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Speaker 4: just all be sterile, so it was kind of viewed

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Speaker 4: as a positive, like, yeah, just get rid of all

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Speaker 4: that stuff that's only causing trouble. And now we actually

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Speaker 4: have more nuanced appreciation for the fact that we don't

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Speaker 4: want to be decimating our microbes all the time. So

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Speaker 4: now it's we kind of appreciate that you don't necessarily

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Speaker 4: want these broader spectrum antibiotics taking everything out, and some

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Speaker 4: are a little bit more targeted than others.

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Speaker 3: Totally okay if this question is too far afield and

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Speaker 3: you want to shoot it down, but could we give

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Speaker 3: an example of how one kind of antibiotic focuses in

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Speaker 3: on one kind of bacteria or a group of closely

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Speaker 3: related bacteria. I think that's pretty interesting. I guess I

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Speaker 3: had mostly thought that when you take an antibiotic, you're

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Speaker 3: probably wiping out just about everything. How do you get

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Speaker 3: certain kinds of bacteria targeted?

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Speaker 4: Some molecules are focused on certain subsets of bacteria. I mean,

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Speaker 4: for example, tobramycin is a recently developed antibiotic that people

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Speaker 4: as cystic fibrosis used to treat pseudomonous infections in their lungs,

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Speaker 4: and so that has relatively targeted action, but of course

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Speaker 4: it can still understanding is that it can still kill

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Speaker 4: other gram negative bacteria. There's a few big categories of bacteria,

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Speaker 4: and some antibiotics target broadly those categories. So if you

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Speaker 4: to have a gram negative targeting antibiotic, then your gram

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Speaker 4: positives will be protected. For example, and I know there's

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Speaker 4: certain antibiotics that are used when you're trying to target

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Speaker 4: the anaerobes, which have different metabolisms. So a mira penem,

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Speaker 4: for example, is something I hear doctors saying they're using

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Speaker 4: to include coverage of the anaerobes. And you know, for example,

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Speaker 4: they've even shown that if you take antibiotics that do

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Speaker 4: not target the anaerobes, that can protect you in the hospital,

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Speaker 4: because the anaerobes are the gut bugs that are producing

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Speaker 4: all those healthy molecules when they digest your fiber, So

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Speaker 4: sparing them by using antibiotics that do not target anaerobes

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Speaker 4: can be protective. And then I think we did talk

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Speaker 4: about this last time, but if you decimate all your

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Speaker 4: gut microbes with antibiotics, which happens pretty frequently in the hospital,

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Speaker 4: then you can be susceptible to other infections like the

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Speaker 4: clusterradia defecal that causes recurrent diarrhea.

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Speaker 1: All right, So for hundreds of thousands of years, if

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Speaker 1: you've got an infection you scratched your leg or whatever,

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Speaker 1: you are at risk of dying. And then for fifty

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Speaker 1: golden years or so, we've had these powerful antibiotics to

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Speaker 1: protect ourselves and to make parents more relaxed when kids

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Speaker 1: are climbing on rusty playground equipment. But what's happening now,

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Speaker 1: Why are we hearing so much about antibiotic resistance? Why

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Speaker 1: are these things not working anymore?

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Speaker 4: Great question. Well, to be honest, every time we've started

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Speaker 4: using an antibiotic, within five or ten years we've found

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Speaker 4: bacteria that resist that antibiotic. So this is not a

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Speaker 4: new problem. This has been going on ever since we

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Speaker 4: first started using antibiotics. So during the whole second half

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Speaker 4: of the twentieth century, you know, we got penicillin, and

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Speaker 4: within a couple of years we had, you know, bugs

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Speaker 4: that could resist the antibiotic penicillin. But then we would

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Speaker 4: come up with new abiotics, and so during the second

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Speaker 4: half of the twentieth century, if you look at the

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Speaker 4: timeline of the discovery of antibiotics, you see all this

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Speaker 4: beautiful new stuff emerging from the pipeline of research every

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Speaker 4: few years. So there were always new options emerging. There's

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Speaker 4: a few reasons we don't really have that pipeline right now.

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Speaker 4: One of them is just the financial structure of the

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Speaker 4: way drugs are being paid for in our society. Because

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Speaker 4: antibiotics typically are acute treatments, and so it's not a

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Speaker 4: lucrative business for pharmaceutical companies to invest in the production

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Speaker 4: of new antibiotics, because, first of all, if we get

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Speaker 4: a new antibiotic, the doctors are going to conserve it

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Speaker 4: because they don't want new resistances to emerge. They're going

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Speaker 4: to be like, oh man, this is my lucky ticket.

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Speaker 4: I'm saving this for the moment I really really need it.

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Speaker 4: But that's going to be completely the opposite of the

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Speaker 4: profit structure you would need for a pharmaceutical company to

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Speaker 4: be willing to invest. So, to be honest, it's a

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Speaker 4: little bit of a financial reason, but we've had a

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Speaker 4: real slow down in the pipeline of the discovery of antibiotics.

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Speaker 4: There could be something to the fact that we found

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Speaker 4: the low hanging fruit, but the truth is, the world

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Speaker 4: of microbiology has so much diversity. It's hard to even

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Speaker 4: begin to explain how little of it we have discovered,

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Speaker 4: Like we haven't even started to look at ninety nine

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Speaker 4: percent of what's out there. So it's very impossible to

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Speaker 4: me to imagine that we don't have lots of options

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Speaker 4: out there if we were to put energy into it.

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Speaker 4: We just haven't really had the resources to put energy

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Speaker 4: into it lately. And so there's been really cool ideas

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Speaker 4: for alternative financial structures that could help. Like, for example,

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Speaker 4: there was a big meeting at the UN a couple

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Speaker 4: of years ago where they were talking about having a

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Speaker 4: subscription model where countries are pharmaceutical companies or even healthcare

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Speaker 4: companies could pay into a system where they could have

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Speaker 4: access to a certain drug with a solid rate and

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Speaker 4: then it didn't matter how much they actually used it,

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Speaker 4: So then there would be a financial structure independent of

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Speaker 4: the use of the drug. But I mean in comparison

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Speaker 4: to the Blockbuster's statins or ozembic, you know, antibiotics are

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Speaker 4: just never going to be as lucrative. So that's a

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Speaker 4: real problem. And then I guess another thing I absolutely

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Speaker 4: have to say is that about eighty percent of the

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Speaker 4: antibiotics used, at least in the United States are in

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Speaker 4: the context of agriculture. So while we do need to

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Speaker 4: reduce the human use of antibiotics, and I obviously support

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Speaker 4: antibiotics stewardship programs, the main way that we use antibiotics,

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Speaker 4: and probably where a lot of the resistances are arising,

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Speaker 4: is in agriculture. So that's where we could make a

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Speaker 4: lot of gains if we could reduce the use of

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Speaker 4: antibiotics and animals, which is a hard thing to do.

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Speaker 4: There's really cool models, like in Denmark they had to

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Speaker 4: disrupt the relationships between farmers and veterinarians in order to

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Speaker 4: stop the prescription of antibiotics, because if the farmer was

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Speaker 4: working with their old buddy veterinarian and asking for a prescription,

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Speaker 4: they would say. Yes. It was so hard to get

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Speaker 4: out of the social pressure of doing something you were

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Speaker 4: accustomed to.

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Speaker 1: But is this because like cows are getting scratches in

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Speaker 1: the need treatment or is it just like they're pumping

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Speaker 1: antibiotics in because it makes them grow faster.

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Speaker 4: Yes, exactly. Most of the antibiotics being used in animal agriculture.

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Speaker 4: It's because the antibiotics help the animals grow faster, which

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Speaker 4: in itself is actually a fascinating science question, like why

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Speaker 4: does it make them grow faster? Maybe it takes some

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Speaker 4: of the energy away from fighting infection and then you

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Speaker 4: can put that energy into beefing yourself up or literally.

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Speaker 1: Or poorking out a little bit.

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Speaker 3: Yeah, I was reading about tuberculosis the other day, and

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Speaker 3: you know, I think I said in a prior episode,

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Speaker 3: like oh, there's all these diseases we don't have to

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Speaker 3: worry about anymore, like tuberculosis. And then I started reading

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Speaker 3: about tuberculosis and it's a huge problem in India. And

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Speaker 3: there is recently a new antibiotic that for the same

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Speaker 3: reasons you mentioned, they've been holding back because they want to, like,

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Speaker 3: you know, make sure they can save it for the

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Speaker 3: special cases or whatever. But there's all these people who

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Speaker 3: need it now, but you know, they're worried about using

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Speaker 3: it and antibiotic resistance building up. So our audience seems

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Speaker 3: really interested in evolution and so we don't need to

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Speaker 3: get into it at like the molecular level. But could

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Speaker 3: you talk a little bit about like the microevolutionary process

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Speaker 3: that results in antibiotic resistance.

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Speaker 4: Yeah, definitely. In fact, I think it's kind of interesting

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Speaker 4: to think about. You know, just imagine a pile of bacteria, like,

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Speaker 4: are you thinking about the fact that there's a bunch

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Speaker 4: of diversity in there because each cell could be a mutant.

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Speaker 4: Microbes have very high mutation rates, so in any given population,

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Speaker 4: the standing diversity is quite high. Every time of cell copies,

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Speaker 4: there could be a mutation in there. So when we

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Speaker 4: talk about antibiotic resistance, cells emerging. Really, what that means

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Speaker 4: is that you put the selection pressure of the antibiotics

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Speaker 4: onto an existing community of bugs, and some of them

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Speaker 4: have intrinsic capacity to resist the antibiotic. So those cells

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Speaker 4: are the ones that survive when you give the antibiotics.

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Speaker 4: So I have a lecture slide that's in my brain

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Speaker 4: right now that you guys can't see. Where it's got

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Speaker 4: like all different colors of circles for the different cells,

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Speaker 4: and some of them are read for resistance, and that's

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Speaker 4: already like that at the beginning, before you even took

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Speaker 4: the antibiotic. Then when you take the antibiotics, some of

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Speaker 4: those cells survive. So that I think is a conceptual

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Speaker 4: difference between how most of my students think it happens

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Speaker 4: when I'm teaching about this. So, really, there's already resistance

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Speaker 4: in the population, and when you give antibiotics, some of

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Speaker 4: the mutations that are already there help the cells resist antibiotics.

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Speaker 4: Now how do they resist. Some of them have pumps

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Speaker 4: that can shoot the antibiotic out of the cell so

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Speaker 4: they can survive. Others have mutations in a part of

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Speaker 4: the cell that the antibiotic is trying to target. So

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Speaker 4: it's just like kaping, it doesn't do anything. In fact,

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Speaker 4: there's are really interesting diversity for the different types of

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Speaker 4: ways that cells can resist antibiotics. It's not only the

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Speaker 4: classics that you read about in textbooks, but overall, once

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Speaker 4: those trade become enriched in a community, they can start

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Speaker 4: to spread them to other cells nearby. You've probably heard

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Speaker 4: about like the spread of antibiotic resistance, and it's true

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Speaker 4: that bacterial cells are really good at sharing information. They

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Speaker 4: can put the information into little circular pieces of DNA

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Speaker 4: and shoot them around in the community, and then that

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Speaker 4: will help neighboring cells learn how to resist the antibiotics too.

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Speaker 4: So anyway, there's a number of different mechanisms for how

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Speaker 4: cells are able to resist antibiotics, and that's usually a

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Speaker 4: trait that already exists in the population and you're just

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Speaker 4: enriching for it at first.

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Speaker 2: That's really interesting.

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Speaker 3: So, like as someone who studies parasites, when we think

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Speaker 3: about resistance to drugs for parasites, you get, you know,

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Speaker 3: like the hookworm that randomly is able for whatever reason,

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Speaker 3: to resist the medication that you put in there, and

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Speaker 3: then they produce eggs that pass with the environment, and

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Speaker 3: then more people get infected by this resistant to medication hookworm.

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Speaker 3: But bacteria have the additional ability to be able to

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Speaker 3: share the traits for resistance between them, which speeds up

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Speaker 3: the rate of resistance moving through the population. Is it

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Speaker 3: would that be fair to say, yeah, ah, bacteria are tricky.

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Speaker 4: Definitely, Yeah, big time. They're very tricky. Yeah. And sometimes

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Speaker 4: the trait for resisting antibiotics comes at a cost, And

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Speaker 4: so if you take the pressure off and the antibiotics

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Speaker 4: aren't there anymore, they'll lose that trait. But it's interesting

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Speaker 4: sometimes the same pressures like antibiotics that help the traits

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Speaker 4: stay in place can come from other sources, like in

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Speaker 4: a wastewater treatment plant for example. There well, there might

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Speaker 4: actually be some antibiotics around, but there also might be

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Speaker 4: like heavy metals or pesticides or other kind of intense

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Speaker 4: molecules that sometimes the traits that the bacteria need to

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Speaker 4: survive antibiotics can also help them survive other situations. So

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Speaker 4: there's a lot of situations in our modern world that

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Speaker 4: push bacteria towards having these traits that help them resist

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Speaker 4: antibiotics direct.

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Speaker 1: I think there's a major misconception and that I think

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Speaker 1: you really helped untangle a little bit there, which is

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Speaker 1: that the traits are already there. It's not like the

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Speaker 1: community is seeing this attack and thinking, what can we

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Speaker 1: do to defend against this, let's brainstorm and come up

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Speaker 1: with something. It's just selecting for the folks that already

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Speaker 1: have or the bugs that already have these traits exactly.

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Speaker 4: Yeah, I watched that light bulb go off in my

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Speaker 4: classrooms my whole life, where I think a lot of

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Speaker 4: students imagine that you add the antibiotic and then all

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Speaker 4: of a sudden the bacteria start mutating in this crazy

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Speaker 4: new way and then they have this crazy new trait

403
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Speaker 4: or something. But it's interesting, like it's usually already there.

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Speaker 4: It just becomes enriched. And of course it can get

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Speaker 4: passed around too.

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Speaker 1: And what kind of infections typically cause trouble? Are there

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Speaker 1: some kinds that are more likely to have bacteria.

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Speaker 4: That are resistant, Yes, definitely. In fact, there's even an

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Speaker 4: acronym that the global health organizations are constantly talking about.

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Speaker 4: It's called the escape pathogens, which stands for enter caucus Staphylococcus,

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Speaker 4: club Ciela, Acinitobacter, Pseudomonas enterobacter. And sometimes we say escape

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Speaker 4: to add eqalie.

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Speaker 3: I mean, I would have guessed. I would have guessed

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Speaker 3: that's what that Acroym meant.

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Speaker 1: I totally have all those in the top of my head. Also,

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Speaker 1: let's just hope you don't put those into a salad dressing.

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Speaker 1: It sounded like a recipe.

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Speaker 4: Oh my gosh.

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Speaker 1: Yeah.

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Speaker 4: And there's other bugs that are not on that list

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Speaker 4: that do cause a lot of trouble that I work

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Speaker 4: on in my lab. For example, like a lot of

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Speaker 4: people with cancer and cystic fibrosis get lung infections from

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Speaker 4: a bug called Stina tripomonas, also berkel darrhea. Those are

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Speaker 4: gram negatives. We sometimes call them water levers. You find

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Speaker 4: them in tap water, Like, they can live in tap water,

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Speaker 4: isn't that amazing? And they can live in soil, so

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Speaker 4: they're You're often exposed to them in water or outside,

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Speaker 4: and if your immune system is compromised, they can cause

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Speaker 4: a lot of trouble.

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Speaker 1: Sorry, why is it amazing they can live in tap water?

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Speaker 1: I can live in tap water?

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Speaker 4: How long? Though? I mean you could. It's true. Water

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Speaker 4: will sustain a human for like a little while, but

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Speaker 4: at some point you're gonna need some calories and.

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Speaker 2: You're gonna get pruney.

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Speaker 1: Oh mean they can eat tap water like that's their

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Speaker 1: only source of calories. That's amazing.

439
00:23:07,440 --> 00:23:10,719
Speaker 4: I see, okay, exactly, Wow, that is amazing. Like, if

440
00:23:10,760 --> 00:23:12,520
Speaker 4: you pick up a bottle of water at the store,

441
00:23:13,080 --> 00:23:15,439
Speaker 4: it probably has some of those cells in there. And

442
00:23:15,480 --> 00:23:18,040
Speaker 4: I don't mean to make people not want to drink water,

443
00:23:18,119 --> 00:23:20,560
Speaker 4: because when I hear that there's microbs in something that

444
00:23:20,600 --> 00:23:23,520
Speaker 4: doesn't creep me out, I'm just like, oh cool, I'm

445
00:23:23,560 --> 00:23:27,680
Speaker 4: happily you know, living among them. So I'm not saying

446
00:23:27,680 --> 00:23:31,040
Speaker 4: you shouldn't drink water, but it's probably true that bottled

447
00:23:31,080 --> 00:23:35,800
Speaker 4: water has higher microbial load from those gram negatives compared

448
00:23:35,800 --> 00:23:36,880
Speaker 4: to like even tap water.

449
00:23:37,160 --> 00:23:40,080
Speaker 3: So when we say these infections cause trouble, do we

450
00:23:40,160 --> 00:23:42,399
Speaker 3: mean that they are bad for humans? Or do we

451
00:23:42,480 --> 00:23:45,240
Speaker 3: mean that they're more likely to be resistant to antibiotics?

452
00:23:45,520 --> 00:23:48,400
Speaker 4: Those are well, the list I just gave you are

453
00:23:48,600 --> 00:23:54,000
Speaker 4: of common infections that are frequently becoming resistant to antibiotics

454
00:23:54,080 --> 00:23:56,880
Speaker 4: in a way that's untreatable. So for each of them,

455
00:23:57,480 --> 00:24:01,920
Speaker 4: there's your annual statistics being compiled on a global level

456
00:24:01,960 --> 00:24:04,680
Speaker 4: to talk about how many infections are caused each year

457
00:24:04,720 --> 00:24:09,040
Speaker 4: and how many of them resist antibiotics. Sometimes meaning you

458
00:24:09,119 --> 00:24:11,480
Speaker 4: just have to switch antibiotics a few times, but eventually

459
00:24:11,480 --> 00:24:14,040
Speaker 4: you find one that works, and sometimes meaning that you

460
00:24:14,160 --> 00:24:17,240
Speaker 4: like literally never find an antibiotic that works. And so

461
00:24:17,359 --> 00:24:19,840
Speaker 4: there are a lot of people in the world right

462
00:24:19,880 --> 00:24:23,840
Speaker 4: now who have chronic infections that they cannot clear, like

463
00:24:23,920 --> 00:24:27,520
Speaker 4: from urinary tract infections are a really really big one.

464
00:24:28,119 --> 00:24:32,720
Speaker 4: Sometimes lung infections. Wound infections can last forever and just

465
00:24:32,800 --> 00:24:35,240
Speaker 4: be very very hard to treat. And they're hard to

466
00:24:35,280 --> 00:24:38,200
Speaker 4: get the medicine too as well, because there's poor circulation

467
00:24:38,320 --> 00:24:41,960
Speaker 4: in wounds. So I hear your question, and I guess

468
00:24:42,000 --> 00:24:45,520
Speaker 4: the answer is both. Those are bugs that through human

469
00:24:45,600 --> 00:24:49,159
Speaker 4: history have always caused a lot of infections. Many of

470
00:24:49,200 --> 00:24:52,879
Speaker 4: them are bugs that are normal parts of our microbiome

471
00:24:53,160 --> 00:24:58,440
Speaker 4: under good circumstances. But if your immune barriers break down,

472
00:24:58,600 --> 00:25:00,600
Speaker 4: which can even just mean a scrap on your skin,

473
00:25:00,760 --> 00:25:02,480
Speaker 4: like you could be a healthy person who just gets

474
00:25:02,480 --> 00:25:04,480
Speaker 4: a scratch, and then all of a sudden, staff that

475
00:25:04,680 --> 00:25:08,880
Speaker 4: was happily living in normal amounts on your skin can

476
00:25:08,920 --> 00:25:10,360
Speaker 4: then cause a terrible infection.

477
00:25:11,040 --> 00:25:13,479
Speaker 3: Well, I've discovered a new thing to fixate on tonight.

478
00:25:14,240 --> 00:25:16,800
Speaker 3: That's what's gonna keep me up. Let's take a break,

479
00:25:16,840 --> 00:25:20,159
Speaker 3: and when we get back, we'll talk about harnessing viruses

480
00:25:20,320 --> 00:25:23,520
Speaker 3: to try to kill bacteria now that antibiotics aren't really

481
00:25:23,520 --> 00:25:24,080
Speaker 3: doing the job.

482
00:25:46,240 --> 00:25:49,320
Speaker 1: Okay, we're back, and Kelly is covering herself with bubble

483
00:25:49,320 --> 00:25:53,320
Speaker 1: wrap to protect herself from the future of infections.

484
00:25:55,640 --> 00:25:58,159
Speaker 2: I can't imagine a chronic uti. That sounds awful.

485
00:25:58,400 --> 00:26:00,000
Speaker 4: It does sound awful, doesn't it.

486
00:26:00,080 --> 00:26:02,159
Speaker 1: Kachina has a salad dressing that'll fix that for you.

487
00:26:02,359 --> 00:26:05,679
Speaker 3: Oh my gosh, Oh that's great, that's great, or cranberry

488
00:26:05,680 --> 00:26:08,160
Speaker 3: pills or something. But anyway, all right, so we talked

489
00:26:08,200 --> 00:26:11,560
Speaker 3: about how antibiotics are not working anymore in a lot

490
00:26:11,600 --> 00:26:14,520
Speaker 3: of cases, and so you work on phage therapies.

491
00:26:14,960 --> 00:26:16,760
Speaker 2: So what is a phage.

492
00:26:17,200 --> 00:26:21,199
Speaker 4: Phages are viruses that kill bacteria. And so, just to

493
00:26:21,240 --> 00:26:25,120
Speaker 4: back up, for every cell that we have on the planet,

494
00:26:25,200 --> 00:26:28,359
Speaker 4: there's usually about ten kinds of viruses that can infect it.

495
00:26:28,520 --> 00:26:31,920
Speaker 4: So there's always viruses around that can infect every kind

496
00:26:31,960 --> 00:26:34,760
Speaker 4: of cell. Like that pepper or tomato on your plate,

497
00:26:35,280 --> 00:26:38,600
Speaker 4: there's tons of viruses that can infect that. So similarly,

498
00:26:38,680 --> 00:26:41,560
Speaker 4: for all of the bacteria that we've talked about, there's

499
00:26:41,640 --> 00:26:45,879
Speaker 4: usually about ten viruses or so that can infect that

500
00:26:46,000 --> 00:26:49,359
Speaker 4: cell type. So the idea of phage therapy is to

501
00:26:49,560 --> 00:26:53,960
Speaker 4: take the viruses that can infect bacteria and use them

502
00:26:54,240 --> 00:26:56,359
Speaker 4: as a medicine, kind of like the enemy of my

503
00:26:56,480 --> 00:26:57,359
Speaker 4: enemy is my friend.

504
00:26:57,880 --> 00:26:59,480
Speaker 2: Do the viruses have viruses?

505
00:26:59,640 --> 00:27:03,200
Speaker 4: Yeah, while there's actually yet maybe they do. Actually there's

506
00:27:03,320 --> 00:27:07,720
Speaker 4: kind of little hitchhiker DNA pieces that could be considered

507
00:27:07,800 --> 00:27:10,800
Speaker 4: viruses on viruses. So yeah, it never ends.

508
00:27:10,760 --> 00:27:13,760
Speaker 1: Okay, And should we think of these viruses the way

509
00:27:13,800 --> 00:27:16,560
Speaker 1: we think of our microbial community, like are they sometimes

510
00:27:16,560 --> 00:27:19,760
Speaker 1: helping the bacteria sometimes it's not so clear, sometimes hurting them?

511
00:27:20,000 --> 00:27:22,320
Speaker 1: Or are they're always invading and taking over? Is there

512
00:27:22,320 --> 00:27:25,360
Speaker 1: always a negative relationship between the viruses and the bacteria.

513
00:27:25,840 --> 00:27:28,639
Speaker 4: It's definitely not always negative. And I think one of

514
00:27:28,640 --> 00:27:30,960
Speaker 4: the big lessons of the last few years of our

515
00:27:31,000 --> 00:27:34,040
Speaker 4: field is that it's pretty hard to categorize them. There's

516
00:27:34,040 --> 00:27:38,560
Speaker 4: more of a gradient, so there's sometimes very direct killing

517
00:27:38,600 --> 00:27:41,240
Speaker 4: types of relationships, but there's also a lot of kind

518
00:27:41,240 --> 00:27:43,960
Speaker 4: of infect and hang out for a long time kind

519
00:27:44,000 --> 00:27:46,960
Speaker 4: of relationships. And the truth is there is no bacterial

520
00:27:47,000 --> 00:27:49,240
Speaker 4: community in the world that doesn't have viruses in it,

521
00:27:49,640 --> 00:27:52,120
Speaker 4: So we can't really talk about what it would mean

522
00:27:52,200 --> 00:27:55,040
Speaker 4: to be a bacterial community without viruses. They're just part

523
00:27:55,080 --> 00:27:55,800
Speaker 4: of the situation.

524
00:27:56,000 --> 00:27:58,680
Speaker 1: You know, viruses are here to stay, you're saying.

525
00:27:58,600 --> 00:28:00,320
Speaker 4: They're here to say, and they are a big part

526
00:28:00,359 --> 00:28:04,440
Speaker 4: of how bacteria work. I mean, anytime a bacterial community

527
00:28:04,520 --> 00:28:08,080
Speaker 4: experiences some kind of stress, they're going to be enriched

528
00:28:08,080 --> 00:28:10,760
Speaker 4: for the cells that can handle the stress, and viruses

529
00:28:10,800 --> 00:28:13,200
Speaker 4: are going to be transmitting the information to help them

530
00:28:13,200 --> 00:28:15,720
Speaker 4: do that. So a big part of how bacteria can

531
00:28:16,000 --> 00:28:19,480
Speaker 4: adapt to new situations is that the viruses help them

532
00:28:19,480 --> 00:28:21,000
Speaker 4: out by transmitting information.

533
00:28:21,480 --> 00:28:23,200
Speaker 1: I don't know how to feel about this. At first,

534
00:28:23,200 --> 00:28:25,920
Speaker 1: I was like, bacteria are pathogen, They're hurting us, they're

535
00:28:26,000 --> 00:28:28,240
Speaker 1: killing people, they're painful. UTI is now you're talking about

536
00:28:28,280 --> 00:28:32,159
Speaker 1: them experiencing stress, and I'm like sympathetic towards them, and

537
00:28:32,200 --> 00:28:34,800
Speaker 1: so like, what am I supposed to feel about bacteria, Patrina?

538
00:28:35,000 --> 00:28:38,040
Speaker 4: I mean, most bacteria are not pathogens, like by far,

539
00:28:38,400 --> 00:28:41,280
Speaker 4: Like I just named a couple bacteria that cause infections,

540
00:28:41,280 --> 00:28:45,360
Speaker 4: which actually are usually healthy, normal parts of our communities,

541
00:28:46,000 --> 00:28:48,959
Speaker 4: And then that doesn't even begin to talk about all

542
00:28:49,000 --> 00:28:51,840
Speaker 4: the microbes in the world. Very fewer pathogens. It's just

543
00:28:51,880 --> 00:28:55,200
Speaker 4: the ones on the news are pathogens. They should write

544
00:28:55,240 --> 00:28:58,320
Speaker 4: more positive stories about helpful microbes should.

545
00:28:59,120 --> 00:29:01,000
Speaker 3: I do see a lot of them, although they're not

546
00:29:01,120 --> 00:29:05,280
Speaker 3: very good scientifically, but always But okay, So if every

547
00:29:05,360 --> 00:29:09,880
Speaker 3: bacteria has ten viruses, does that mean that viruses are

548
00:29:09,960 --> 00:29:13,880
Speaker 3: the most like diverse and specios life on the planet

549
00:29:14,080 --> 00:29:17,320
Speaker 3: or is are the same viruses infecting lots of different

550
00:29:17,400 --> 00:29:18,400
Speaker 3: kinds of bacteria?

551
00:29:18,480 --> 00:29:21,760
Speaker 4: They are by far the most diverse. That is exactly

552
00:29:22,080 --> 00:29:24,600
Speaker 4: the thing to say. I mean, I've got all like,

553
00:29:24,800 --> 00:29:29,200
Speaker 4: there's so many cool analogies. There's more viruses than stars

554
00:29:29,240 --> 00:29:32,120
Speaker 4: in the galaxy or grains of sand on the planets.

555
00:29:32,400 --> 00:29:34,360
Speaker 4: I think it's ten to the thirty one. If you

556
00:29:34,440 --> 00:29:36,720
Speaker 4: line them up head to head, they go to the

557
00:29:36,840 --> 00:29:39,040
Speaker 4: edge of the galaxy back and forth a bunch of times.

558
00:29:39,080 --> 00:29:41,640
Speaker 4: You know, it's a crazy number of viruses. Yes, they

559
00:29:41,640 --> 00:29:46,080
Speaker 4: are super super diverse, and you asked a really important

560
00:29:46,160 --> 00:29:49,560
Speaker 4: question about how specific they are. Like, is a virus

561
00:29:49,560 --> 00:29:53,160
Speaker 4: that infects one of those bugs, the pseudomonis also able

562
00:29:53,200 --> 00:29:56,400
Speaker 4: to infect a different bug that staphylococcus or something like that.

563
00:29:56,600 --> 00:30:00,400
Speaker 4: Typically know, in fact, it's at a substrain level. A

564
00:30:00,440 --> 00:30:04,280
Speaker 4: phage that infects one pseudomonis. It's it's like a sub

565
00:30:04,360 --> 00:30:09,000
Speaker 4: type of pseudomonis, Like like any type of bacteria has

566
00:30:09,240 --> 00:30:12,080
Speaker 4: genus and species names. You know, King's play chests on

567
00:30:12,160 --> 00:30:15,200
Speaker 4: fine grain sand. The taxonomy going down to genus and species.

568
00:30:15,560 --> 00:30:17,480
Speaker 2: Oh, you learned a nice one.

569
00:30:18,240 --> 00:30:20,280
Speaker 4: Yeah, there's probably less of for a free ones going

570
00:30:20,280 --> 00:30:21,200
Speaker 4: around the schoolyard.

571
00:30:21,840 --> 00:30:23,480
Speaker 2: Yea, I won't repeat mine.

572
00:30:23,280 --> 00:30:27,640
Speaker 4: Go ahead, And so there's even substrains, So like Pseudomonius

573
00:30:27,640 --> 00:30:32,560
Speaker 4: originosa is a genus and species name, but there's subtypes

574
00:30:32,640 --> 00:30:37,000
Speaker 4: beyond that, and whether the phage infects is usually at

575
00:30:37,000 --> 00:30:39,880
Speaker 4: a sub type level like that, and it's kind of

576
00:30:39,880 --> 00:30:42,240
Speaker 4: interesting to think about it. I mean, the bacteria are

577
00:30:42,280 --> 00:30:46,920
Speaker 4: constantly making small mutations to resist the phages, so the

578
00:30:47,040 --> 00:30:50,680
Speaker 4: trait of resisting a phage turns on a dime. It's

579
00:30:50,760 --> 00:30:54,240
Speaker 4: just one mutation can probably do the trick, so it's

580
00:30:54,240 --> 00:30:58,080
Speaker 4: not like a big complicated trait like using oxygen and

581
00:30:58,120 --> 00:30:59,959
Speaker 4: then you would need like a whole bunch of different

582
00:31:00,440 --> 00:31:02,880
Speaker 4: and it's like very conserved, and if you looked back

583
00:31:02,880 --> 00:31:07,160
Speaker 4: in the history of bacteria, you'd see big movement towards like, oh,

584
00:31:07,240 --> 00:31:10,040
Speaker 4: now they can use oxygen or something like that. Phage

585
00:31:10,040 --> 00:31:12,600
Speaker 4: infection is like a tiny little thing. It's very easy

586
00:31:12,640 --> 00:31:14,680
Speaker 4: to change it. It's at the tippy tippy branches of

587
00:31:14,720 --> 00:31:15,800
Speaker 4: the toxinomic trees.

588
00:31:16,160 --> 00:31:18,520
Speaker 1: And so if there are all these viruses out there

589
00:31:18,600 --> 00:31:22,360
Speaker 1: that are infecting bacteria, and they're very specific to the bacteria,

590
00:31:22,400 --> 00:31:25,160
Speaker 1: but a very small change in the bacteria could mean

591
00:31:25,200 --> 00:31:27,840
Speaker 1: that they can't be infected by the viruses. Is there

592
00:31:27,920 --> 00:31:30,600
Speaker 1: some vast ocean of viruses out there that can't infect

593
00:31:30,680 --> 00:31:33,920
Speaker 1: any bacteria yet and some mutation of the bacteria makes

594
00:31:33,960 --> 00:31:38,000
Speaker 1: them therefore susceptible or do viruses only exist and propagate

595
00:31:38,040 --> 00:31:39,360
Speaker 1: if they can use bacteria.

596
00:31:39,760 --> 00:31:43,200
Speaker 4: Well, I think there is an ocean of viruses out

597
00:31:43,240 --> 00:31:45,520
Speaker 4: there that never get to infect a cell. So they

598
00:31:45,520 --> 00:31:49,560
Speaker 4: have kind of an unrequited dream of finding a host

599
00:31:49,600 --> 00:31:53,840
Speaker 4: and they just never do. However, the dark virus, the

600
00:31:53,880 --> 00:31:54,640
Speaker 4: lonely ones.

601
00:31:55,080 --> 00:31:58,600
Speaker 1: But now you're making a sympathetic to viruses, Katrina, You

602
00:31:58,640 --> 00:31:59,480
Speaker 1: are too empathetic.

603
00:32:00,680 --> 00:32:03,959
Speaker 4: But so, yes, there's going to be viruses out there

604
00:32:03,960 --> 00:32:07,040
Speaker 4: that never get to infect a sell. But the strategy

605
00:32:07,080 --> 00:32:11,040
Speaker 4: of a virus is to make a bajillion copies with

606
00:32:11,160 --> 00:32:14,440
Speaker 4: lots of variation and hope that you know several of

607
00:32:14,480 --> 00:32:18,760
Speaker 4: them have the capacity to go and find a host

608
00:32:18,800 --> 00:32:21,880
Speaker 4: in a changing world. You know. It's like and rather

609
00:32:21,920 --> 00:32:24,800
Speaker 4: than training one kid with lots of skills and hoping

610
00:32:24,800 --> 00:32:26,720
Speaker 4: they'll find a job in a changing world, it's like,

611
00:32:26,760 --> 00:32:30,280
Speaker 4: you got to raise billions of viruses and a few

612
00:32:30,320 --> 00:32:33,840
Speaker 4: of them will continue to be able to infect. And

613
00:32:33,880 --> 00:32:35,640
Speaker 4: I mean it's been going on for a long time,

614
00:32:35,720 --> 00:32:37,880
Speaker 4: and in a way it's quite stable. Like if I

615
00:32:37,960 --> 00:32:42,640
Speaker 4: took samples from anybody listening to this podcast right now,

616
00:32:42,720 --> 00:32:46,719
Speaker 4: and then in five more years took another sample, most

617
00:32:46,760 --> 00:32:50,360
Speaker 4: of the gut viruses would still be there. They might

618
00:32:50,400 --> 00:32:53,560
Speaker 4: have evolved, even one to three percent of their genome

619
00:32:53,600 --> 00:32:56,560
Speaker 4: could have changed in a new direction, but I would

620
00:32:56,600 --> 00:32:59,520
Speaker 4: be able to recognize them as themselves. So it's not

621
00:32:59,600 --> 00:33:02,800
Speaker 4: like it's this raucous thing that's turning over and becoming

622
00:33:02,800 --> 00:33:06,440
Speaker 4: a totally different thing all the time. There's some stability there,

623
00:33:06,600 --> 00:33:09,000
Speaker 4: especially within the individual. Just each of our guts is

624
00:33:09,040 --> 00:33:12,760
Speaker 4: like a little chemostat with tons of virus and bacterial

625
00:33:12,880 --> 00:33:16,760
Speaker 4: evolution happening all the time, and it drifts around a bit,

626
00:33:16,880 --> 00:33:19,200
Speaker 4: but it's it's quite stable in some ways.

627
00:33:19,400 --> 00:33:22,720
Speaker 1: So we are the interlopers, the weird ones in a viral.

628
00:33:22,440 --> 00:33:24,840
Speaker 4: World, Right, That's certainly one way of looking at it.

629
00:33:24,880 --> 00:33:27,840
Speaker 4: I mean, I think we have some advantages. I think

630
00:33:28,320 --> 00:33:34,440
Speaker 4: consciousness does have a does distinguish us from viruses.

631
00:33:34,600 --> 00:33:37,000
Speaker 2: There's days when I'd rather not have consciousness.

632
00:33:37,040 --> 00:33:40,800
Speaker 3: But anyway, Okay, so we've got viruses and some of

633
00:33:40,840 --> 00:33:44,600
Speaker 3: them are bad for bacteria. How do we harness that

634
00:33:44,760 --> 00:33:46,320
Speaker 3: to fight bacteria?

635
00:33:46,400 --> 00:33:50,640
Speaker 4: So basically, the way that phage therapy has worked since

636
00:33:50,680 --> 00:33:53,479
Speaker 4: even before we had antibiotics, So we've been doing this.

637
00:33:53,760 --> 00:33:57,760
Speaker 4: Phages were discovered in nineteen fifteen or nineteen seventeen, depending

638
00:33:57,800 --> 00:34:01,320
Speaker 4: how you look at it. And what we do is

639
00:34:01,440 --> 00:34:05,200
Speaker 4: if you have a bacteria causing an infection, you use

640
00:34:05,280 --> 00:34:08,600
Speaker 4: that as a hook and you go hunt for phages

641
00:34:08,800 --> 00:34:11,640
Speaker 4: in a sample that has a lot of microbial activity

642
00:34:11,680 --> 00:34:15,040
Speaker 4: to it. Wastewater is a popular place to hunt, but

643
00:34:15,880 --> 00:34:19,240
Speaker 4: freshwater ponds, puddles in front of your building.

644
00:34:19,840 --> 00:34:22,200
Speaker 1: Wastewater is such a euphemism. I mean, you're talking about

645
00:34:22,200 --> 00:34:26,000
Speaker 1: poop to pills, right, We're like finding medicine in sewage.

646
00:34:26,320 --> 00:34:31,200
Speaker 4: Sewage is such a concentrated way to grab the microbes

647
00:34:31,239 --> 00:34:34,239
Speaker 4: of humanity that it's a very tempting place to look. Yes,

648
00:34:34,640 --> 00:34:37,160
Speaker 4: because it's going to represent, it's going to represent a

649
00:34:37,200 --> 00:34:39,120
Speaker 4: lot of people. Like when we were doing our wastewater

650
00:34:39,160 --> 00:34:43,000
Speaker 4: sequencing project during the pandemic, we were getting eight samples

651
00:34:43,000 --> 00:34:46,480
Speaker 4: per week from southern California wastewater treatment plants that represented

652
00:34:46,520 --> 00:34:49,960
Speaker 4: sixteen million people. Wow, from just eight samples.

653
00:34:50,480 --> 00:34:52,080
Speaker 2: You are the queen of silver linings.

654
00:34:53,440 --> 00:34:55,720
Speaker 1: Sewage is so tempting, said nobody.

655
00:34:55,760 --> 00:34:56,040
Speaker 5: Ever.

656
00:34:56,239 --> 00:35:00,520
Speaker 1: Anyway, maybe we're not going to put you charge of

657
00:35:00,560 --> 00:35:05,040
Speaker 1: marketing and flavors for the new cell addressing company. So

658
00:35:05,040 --> 00:35:07,280
Speaker 1: you're saying you have a bacteria you're looking to target.

659
00:35:07,640 --> 00:35:11,319
Speaker 1: Then you go out and you search extent of communities

660
00:35:11,360 --> 00:35:14,359
Speaker 1: of viruses and you're trying to find one that will

661
00:35:14,440 --> 00:35:16,680
Speaker 1: kill this particular bacteria exactly.

662
00:35:16,719 --> 00:35:21,120
Speaker 4: So you take the infecting cells, you mix them with

663
00:35:21,160 --> 00:35:26,359
Speaker 4: some wastewater, and then we use a technique. I mean,

664
00:35:26,400 --> 00:35:28,919
Speaker 4: I need slides. Man, This is hard on a podcast, but.

665
00:35:29,120 --> 00:35:31,040
Speaker 2: I don't want to show you guys pictures it is.

666
00:35:31,000 --> 00:35:35,120
Speaker 4: But you know, you make a plate of the bacteria

667
00:35:35,480 --> 00:35:39,080
Speaker 4: mixed with the material that you hope has phages in it.

668
00:35:39,120 --> 00:35:41,719
Speaker 4: And an important thing to say is that we filter it.

669
00:35:41,800 --> 00:35:43,400
Speaker 4: We try to get the cells out of there. So

670
00:35:43,440 --> 00:35:46,680
Speaker 4: it's just viruses left behind, because otherwise you might imagine

671
00:35:46,760 --> 00:35:49,399
Speaker 4: everything from the whole wastewater treatment plant growing on your plate.

672
00:35:49,480 --> 00:35:52,879
Speaker 4: But actually you filter and hopefully there's viruses in there

673
00:35:52,920 --> 00:35:55,839
Speaker 4: that infect your cell. But it's a mystery every time.

674
00:35:55,960 --> 00:35:58,640
Speaker 4: Sometimes we spend six months hunting for a phage for

675
00:35:58,719 --> 00:36:01,840
Speaker 4: one strain, even though I've got like really good people

676
00:36:01,880 --> 00:36:04,400
Speaker 4: with lots of experience, and I've got tons of great wastewater.

677
00:36:04,440 --> 00:36:04,920
Speaker 4: I'll tell you that.

678
00:36:06,560 --> 00:36:08,160
Speaker 1: So it's sort of like you have a lock and

679
00:36:08,200 --> 00:36:10,040
Speaker 1: you're putting it in a bag of keys and shaking

680
00:36:10,080 --> 00:36:11,960
Speaker 1: it around and hoping and one of them goes in.

681
00:36:12,320 --> 00:36:15,680
Speaker 4: Yeah, And then then you get more experience with knowing

682
00:36:15,760 --> 00:36:18,920
Speaker 4: what kinds of wastewater treatment plants are enriched for the

683
00:36:18,920 --> 00:36:21,920
Speaker 4: bugs you care about. Like for Ourstina tri Promona's project,

684
00:36:22,000 --> 00:36:25,560
Speaker 4: the wastewater in Escondido is like amazingly good. So if

685
00:36:25,560 --> 00:36:28,279
Speaker 4: I get astino infection, I'm like telling the students, please

686
00:36:28,320 --> 00:36:29,719
Speaker 4: get the Escondido wastewater.

687
00:36:30,080 --> 00:36:32,200
Speaker 1: What are they eating in Escondido or.

688
00:36:32,120 --> 00:36:34,920
Speaker 4: Is it because of like an agricultural influence or I

689
00:36:34,920 --> 00:36:36,600
Speaker 4: don't know. I would love to know the answer to that,

690
00:36:36,719 --> 00:36:38,600
Speaker 4: but I can tell you it's been true for years

691
00:36:38,600 --> 00:36:41,640
Speaker 4: and lots of other labs failed to find Stina Tripromona's phages.

692
00:36:42,120 --> 00:36:44,640
Speaker 4: But when we use Escondido wastewater. We've even sent our

693
00:36:44,760 --> 00:36:48,040
Speaker 4: Escondido wastewater to collaborating labs and they've also succeeded.

694
00:36:49,360 --> 00:36:50,360
Speaker 1: It's liquid gold.

695
00:36:50,560 --> 00:36:53,319
Speaker 4: Yeah. So then once you if you're lucky, and you'll

696
00:36:53,320 --> 00:36:55,120
Speaker 4: come in in the morning and you'll see a white

697
00:36:55,200 --> 00:36:58,640
Speaker 4: bacterial lawn, and then you'll see these clearance zones on

698
00:36:58,680 --> 00:37:02,200
Speaker 4: the plate. Those represent the phages. So if you get

699
00:37:02,200 --> 00:37:05,279
Speaker 4: one of those, then you have a manufacturing project on

700
00:37:05,320 --> 00:37:07,919
Speaker 4: your hands. Then you have to get the phage into

701
00:37:07,960 --> 00:37:10,360
Speaker 4: big enough amounts and clean enough amounts.

702
00:37:10,480 --> 00:37:12,399
Speaker 1: Right back up and explain what you were talking about.

703
00:37:12,400 --> 00:37:14,680
Speaker 1: There a white bacterial.

704
00:37:14,239 --> 00:37:19,040
Speaker 4: Lawn, so you'll have a plate of bacteria that look white.

705
00:37:19,080 --> 00:37:21,120
Speaker 4: So you'll have like a flat white background.

706
00:37:21,400 --> 00:37:22,759
Speaker 1: Why do they look white.

707
00:37:22,520 --> 00:37:25,080
Speaker 4: Well, some bacteria are a little bit yellow, or most

708
00:37:25,120 --> 00:37:28,400
Speaker 4: bacteria are white or yellow. Sometimes they turn a little blue.

709
00:37:28,440 --> 00:37:32,000
Speaker 4: But the point is you have a clear growth of

710
00:37:32,120 --> 00:37:35,799
Speaker 4: cells on your plate. And then you can see with

711
00:37:35,880 --> 00:37:38,600
Speaker 4: your naked eye that there are clearance zones from the

712
00:37:38,680 --> 00:37:42,560
Speaker 4: viruses and so that represents if one virus infects one

713
00:37:42,600 --> 00:37:45,480
Speaker 4: of the cells on that plate, it will keep replicating

714
00:37:45,880 --> 00:37:49,239
Speaker 4: and chewing up and eating and breaking the cells, so

715
00:37:49,320 --> 00:37:51,799
Speaker 4: you'll get a clearance zone that's visible to the naked eye.

716
00:37:51,800 --> 00:37:53,759
Speaker 4: I mean, obviously one virus is not visible to the

717
00:37:53,840 --> 00:37:55,960
Speaker 4: naked eye. But what is visible to the naked eye

718
00:37:56,000 --> 00:37:58,879
Speaker 4: is it's called a plaque, and it's a bunch of

719
00:37:59,480 --> 00:38:03,120
Speaker 4: cell death caused by the virus in one little zone

720
00:38:03,120 --> 00:38:04,920
Speaker 4: of the plate. And you can see that.

721
00:38:05,320 --> 00:38:07,680
Speaker 1: And how do you know which virus has done it?

722
00:38:07,880 --> 00:38:10,320
Speaker 4: You don't. You just know it looks like a virus.

723
00:38:10,360 --> 00:38:12,319
Speaker 4: And if you've done it for a long time, you

724
00:38:12,360 --> 00:38:15,160
Speaker 4: start to get familiar with the way the shape and

725
00:38:15,200 --> 00:38:18,520
Speaker 4: the size of the of the plaque the clearance zone.

726
00:38:19,320 --> 00:38:22,480
Speaker 4: You can usually distinguish it from an air bubble or

727
00:38:22,480 --> 00:38:25,479
Speaker 4: something like that, but not always. So it's definitely still

728
00:38:25,520 --> 00:38:29,439
Speaker 4: an identification project once you get the plaque. But that's

729
00:38:29,520 --> 00:38:32,600
Speaker 4: kind of step one. So really, in my lab, if

730
00:38:32,600 --> 00:38:35,600
Speaker 4: someone sends us every week or two, we get a

731
00:38:35,640 --> 00:38:38,319
Speaker 4: new isolate into our lab where a doctor has a

732
00:38:38,320 --> 00:38:41,279
Speaker 4: patient who has antibiotic resistant infection and they want to

733
00:38:41,320 --> 00:38:44,319
Speaker 4: know do we have a phage. So the first thing

734
00:38:44,360 --> 00:38:46,919
Speaker 4: we do is we reach into our freezer, which where

735
00:38:46,920 --> 00:38:49,879
Speaker 4: we already have about two hundred phages, and then we'll

736
00:38:49,880 --> 00:38:52,480
Speaker 4: see if one of the ones that infected a similar

737
00:38:52,520 --> 00:38:56,080
Speaker 4: strain can infect this new one. That's the easiest answer,

738
00:38:56,080 --> 00:38:58,200
Speaker 4: because then we'll have already sequenced it, we'll know what

739
00:38:58,280 --> 00:39:02,160
Speaker 4: it is. It's a big head start, but it's not uncommon.

740
00:39:02,200 --> 00:39:04,440
Speaker 4: I'd say easily half the time that none of the

741
00:39:04,440 --> 00:39:07,680
Speaker 4: phages we have can infect. So then we do a

742
00:39:07,719 --> 00:39:09,239
Speaker 4: new hunt in wastewater.

743
00:39:09,440 --> 00:39:12,120
Speaker 1: And you have like your own personal lab library, like

744
00:39:12,120 --> 00:39:14,280
Speaker 1: the ones you're talking about in your freezer. There's another

745
00:39:14,320 --> 00:39:16,719
Speaker 1: lab somewhere else to have a different set. Yeah, another

746
00:39:16,800 --> 00:39:19,080
Speaker 1: lab has a different set. This is like Katrina's personal

747
00:39:19,120 --> 00:39:19,920
Speaker 1: phage arsenal.

748
00:39:20,080 --> 00:39:23,000
Speaker 4: That's right, Yeah, And it's the way that you protect

749
00:39:23,040 --> 00:39:26,479
Speaker 4: the information is really complicated, and we're all everyone's always

750
00:39:26,560 --> 00:39:29,120
Speaker 4: changing their mind about that. My general attitude has been

751
00:39:29,160 --> 00:39:31,759
Speaker 4: to be very open and if somebody at another university

752
00:39:31,800 --> 00:39:34,120
Speaker 4: needs one of our phages, I just send it to them.

753
00:39:34,400 --> 00:39:37,319
Speaker 4: But we could be shooting ourselves as a community all

754
00:39:37,360 --> 00:39:40,480
Speaker 4: in the foot because we're removing the capacity to make

755
00:39:40,600 --> 00:39:43,320
Speaker 4: money off of them, so then nobody would ever invest

756
00:39:43,320 --> 00:39:45,640
Speaker 4: in what we need is for like real investment to

757
00:39:45,840 --> 00:39:48,080
Speaker 4: get this thing off the ground, you know, all right.

758
00:39:48,000 --> 00:39:50,640
Speaker 1: So back on the process. Here, you have the isolate.

759
00:39:50,840 --> 00:39:52,960
Speaker 1: You scan through all your phages by just like mixing

760
00:39:52,960 --> 00:39:55,640
Speaker 1: them together and seeing if one of them kills your bacteria.

761
00:39:55,680 --> 00:39:57,719
Speaker 1: Maybe you have to go out to Escondido or somewhere

762
00:39:57,760 --> 00:40:00,399
Speaker 1: else to find more phages. But now you have one

763
00:40:00,440 --> 00:40:02,880
Speaker 1: that you think kills the bacteria, what do you do next?

764
00:40:03,440 --> 00:40:08,560
Speaker 4: Then we purify. We have to like continue propagating and purifying.

765
00:40:09,080 --> 00:40:11,960
Speaker 4: Most phage preps are contaminated in some way. It's actually

766
00:40:12,080 --> 00:40:14,160
Speaker 4: very hard to get a prep that has just a

767
00:40:14,200 --> 00:40:16,239
Speaker 4: single phage in it because they come out of these

768
00:40:16,280 --> 00:40:20,560
Speaker 4: communities with a lot of different members. So step one

769
00:40:20,680 --> 00:40:25,040
Speaker 4: is propagating, where you pick the plaque and you reinfect bacteria,

770
00:40:25,840 --> 00:40:29,160
Speaker 4: and it's like a twenty four hour project each time.

771
00:40:29,760 --> 00:40:32,760
Speaker 4: And you do that easily, like three or four times,

772
00:40:33,120 --> 00:40:35,680
Speaker 4: and some phages will kind of peter out at that

773
00:40:35,719 --> 00:40:38,120
Speaker 4: point and reveal themselves to be hard to work with.

774
00:40:38,239 --> 00:40:41,640
Speaker 4: And so if you have multiple different types emerging on

775
00:40:41,680 --> 00:40:44,080
Speaker 4: your plate, you just abandon the ones that are difficult

776
00:40:44,080 --> 00:40:46,160
Speaker 4: to deal with, because what you want are easy to

777
00:40:46,200 --> 00:40:46,560
Speaker 4: deal with.

778
00:40:46,600 --> 00:40:49,760
Speaker 1: Phages difficult to deal with. Like they send grumpy emails

779
00:40:49,840 --> 00:40:51,120
Speaker 1: late at night or what's going on.

780
00:40:51,360 --> 00:40:54,319
Speaker 4: Like they one day they make a beautiful plaque, and

781
00:40:54,360 --> 00:40:57,000
Speaker 4: then the next day, even though you did everything exactly

782
00:40:57,040 --> 00:40:58,759
Speaker 4: the same way, as far as you know, it just

783
00:40:58,800 --> 00:41:01,239
Speaker 4: doesn't do anything. And you're like going back to the

784
00:41:01,280 --> 00:41:03,319
Speaker 4: plate from two days ago and hoping you can get

785
00:41:03,360 --> 00:41:05,480
Speaker 4: it to cooperate again. That kind of thing.

786
00:41:06,040 --> 00:41:09,520
Speaker 3: It's biology, So it depends, yes, And by a beautiful plaque,

787
00:41:09,520 --> 00:41:11,319
Speaker 3: you mean like one day it beats the heck out

788
00:41:11,320 --> 00:41:13,080
Speaker 3: of the bacteria, and the next day it doesn't seem

789
00:41:13,080 --> 00:41:13,759
Speaker 3: to kill them at all.

790
00:41:14,160 --> 00:41:17,440
Speaker 4: Yeah, Like maybe you'll get a nice, big, visible plaque,

791
00:41:17,480 --> 00:41:20,120
Speaker 4: which means it's easy to pick so you can get

792
00:41:20,120 --> 00:41:22,839
Speaker 4: material to work with for the next day. And then

793
00:41:22,880 --> 00:41:25,160
Speaker 4: the next day your plate has nothing on it, so

794
00:41:25,280 --> 00:41:26,440
Speaker 4: you're like, where did it even go?

795
00:41:26,600 --> 00:41:29,000
Speaker 3: So each time you're picking the viruses that killed the

796
00:41:29,040 --> 00:41:31,759
Speaker 3: bacteria and putting them onto a new plate exactly and

797
00:41:31,880 --> 00:41:33,880
Speaker 3: hoping to get a pure culture eventually.

798
00:41:33,480 --> 00:41:36,320
Speaker 4: Exactly, and then then you find out all these finicky

799
00:41:36,360 --> 00:41:39,720
Speaker 4: things about how to deal with them. Some viruses prefer

800
00:41:39,800 --> 00:41:42,640
Speaker 4: to grow in liquid, others prefer to grow on a

801
00:41:42,680 --> 00:41:46,120
Speaker 4: solid plate. Others do really well, when the cells are

802
00:41:46,160 --> 00:41:49,520
Speaker 4: multiplying quickly, others do better when the cells are like

803
00:41:50,200 --> 00:41:54,000
Speaker 4: kind of overnight growths that got tired out, and we

804
00:41:54,040 --> 00:41:56,279
Speaker 4: call them stationary phase. You know, they're like not as

805
00:41:56,360 --> 00:42:00,520
Speaker 4: actively growing anymore. And viruses have all different mechanism as

806
00:42:00,520 --> 00:42:04,800
Speaker 4: of entry and preferences for metabolism. So all of those things,

807
00:42:04,920 --> 00:42:07,080
Speaker 4: you don't know them about your new virus yet you're

808
00:42:07,160 --> 00:42:10,200
Speaker 4: just like trying to propagate it. So then we'll do

809
00:42:10,239 --> 00:42:13,799
Speaker 4: all kinds of things where we'll do temperature gradients and

810
00:42:14,560 --> 00:42:18,760
Speaker 4: different types of media growth, and we'll try like triangulating

811
00:42:18,760 --> 00:42:22,080
Speaker 4: all the conditions to learn what this particular virus likes

812
00:42:22,120 --> 00:42:24,439
Speaker 4: the best, so then we can do a better job

813
00:42:24,440 --> 00:42:26,600
Speaker 4: of propagating it in successful conditions.

814
00:42:26,840 --> 00:42:28,800
Speaker 3: All Right, So we've learned how to make a virus happy,

815
00:42:28,800 --> 00:42:31,720
Speaker 3: and when we get back, we'll talk about actually giving

816
00:42:31,719 --> 00:42:32,840
Speaker 3: those viruses to people.

817
00:42:52,719 --> 00:42:55,919
Speaker 1: Okay, we're back, and we're hearing about how Katrina's lab

818
00:42:56,080 --> 00:42:59,200
Speaker 1: might save somebody who's out there with a really difficult

819
00:42:59,200 --> 00:43:02,160
Speaker 1: infection whose doctor emails her and asks her if she's

820
00:43:02,200 --> 00:43:04,839
Speaker 1: got something cooking up in the freezer that can kill

821
00:43:04,880 --> 00:43:07,480
Speaker 1: their bacteria. So we've heard about how you find a

822
00:43:07,520 --> 00:43:11,799
Speaker 1: fade that can help infect your bacteria, you purify, you isolated.

823
00:43:11,960 --> 00:43:14,920
Speaker 1: How do you actually go all the way to putting

824
00:43:14,960 --> 00:43:16,839
Speaker 1: it back into human and treating them.

825
00:43:17,239 --> 00:43:19,880
Speaker 4: Well, that's a really big question, but it's actually an

826
00:43:19,920 --> 00:43:25,000
Speaker 4: old question. So since around nineteen twenty, especially in the

827
00:43:25,080 --> 00:43:28,640
Speaker 4: former Soviet republics, phages have been used as medicine since

828
00:43:28,680 --> 00:43:31,160
Speaker 4: before we even had antibiotics, and they were actually used

829
00:43:31,160 --> 00:43:34,480
Speaker 4: in the Western world, you know, before the era of

830
00:43:34,480 --> 00:43:38,160
Speaker 4: World War Two as well, Like for example, when Elizabeth

831
00:43:38,200 --> 00:43:40,759
Speaker 4: Taylor was filming Cleopatra, I think she was in the UK,

832
00:43:40,880 --> 00:43:43,600
Speaker 4: she got a terrible staff infection and they used phages

833
00:43:43,680 --> 00:43:45,799
Speaker 4: to help clear her infection. Wow, there's a lot of

834
00:43:45,800 --> 00:43:49,000
Speaker 4: stories like that from around that time. And so at

835
00:43:49,000 --> 00:43:53,200
Speaker 4: the Eliava Institute in Tiblis, Georgia, which is probably the

836
00:43:53,239 --> 00:43:57,360
Speaker 4: most famous of these centers, they've been using phage therapy

837
00:43:58,000 --> 00:44:01,640
Speaker 4: to treat infections for more than a century and so

838
00:44:01,680 --> 00:44:03,840
Speaker 4: they it's the process like I just told you about.

839
00:44:04,000 --> 00:44:05,920
Speaker 4: They have a much bigger bank of phages than I do,

840
00:44:05,960 --> 00:44:08,600
Speaker 4: I'm sure, but they will find a phage. If one

841
00:44:08,600 --> 00:44:11,000
Speaker 4: of their standard ones doesn't work, they'll go find a

842
00:44:11,040 --> 00:44:14,680
Speaker 4: new one and they prep it and give it to you.

843
00:44:15,239 --> 00:44:19,040
Speaker 4: But in the United States, there is no approved way

844
00:44:19,120 --> 00:44:23,680
Speaker 4: to use phages. It's not sold. There's no FDA approved

845
00:44:23,760 --> 00:44:26,920
Speaker 4: medication that your doctor can prescribe. So all of it

846
00:44:27,000 --> 00:44:32,400
Speaker 4: is happening through labs like mine and through applications to

847
00:44:32,440 --> 00:44:36,239
Speaker 4: the Federal Drug Administration asking for an exemption, either as

848
00:44:36,239 --> 00:44:40,719
Speaker 4: an emergency authorization or as a compassionate use exemption. So

849
00:44:40,800 --> 00:44:44,360
Speaker 4: it has to be a situation where somebody's in really

850
00:44:44,400 --> 00:44:47,640
Speaker 4: dire straits and taking on the risk of an experimental

851
00:44:47,640 --> 00:44:51,160
Speaker 4: treatment makes sense. So in my lab, for many years,

852
00:44:51,600 --> 00:44:53,840
Speaker 4: I've been growing up these phages out of wastewater, and

853
00:44:53,880 --> 00:44:56,840
Speaker 4: people were sometimes sending me their patient's isolates and asking

854
00:44:56,840 --> 00:44:59,240
Speaker 4: if we had a phage, and we almost always succeeded.

855
00:44:59,280 --> 00:45:02,640
Speaker 4: That was not the bare, but usually the person would

856
00:45:02,680 --> 00:45:06,160
Speaker 4: either get better or pass away before we could get

857
00:45:06,200 --> 00:45:08,319
Speaker 4: the phage prepped in order to help them. And that

858
00:45:08,400 --> 00:45:11,560
Speaker 4: went on for years, and every time I would have

859
00:45:11,600 --> 00:45:14,279
Speaker 4: a student who was such a good spirit and would

860
00:45:14,280 --> 00:45:17,120
Speaker 4: spend the whole weekend working really hard to get the phages,

861
00:45:17,160 --> 00:45:19,000
Speaker 4: and we'd be so proud of the fact that we

862
00:45:19,080 --> 00:45:21,560
Speaker 4: had one, but then it wouldn't actually help anyone because

863
00:45:22,000 --> 00:45:24,840
Speaker 4: the whole process is too slow to help someone in

864
00:45:24,920 --> 00:45:28,200
Speaker 4: really dire straits. So about a year ago I went

865
00:45:28,239 --> 00:45:31,520
Speaker 4: to the Infectious Disease Department Grand Rounds at UC Irvine

866
00:45:31,600 --> 00:45:34,560
Speaker 4: where I work, and I talked to all the doctors

867
00:45:34,600 --> 00:45:36,239
Speaker 4: about it, and I got a lot of help from

868
00:45:36,360 --> 00:45:39,160
Speaker 4: Jessica Satcher of the Phage Directory. This was her idea,

869
00:45:39,160 --> 00:45:42,760
Speaker 4: I think, actually, and we talked about how we should

870
00:45:42,760 --> 00:45:46,479
Speaker 4: aim for people who are not quite so acutely ill,

871
00:45:46,680 --> 00:45:49,439
Speaker 4: people who have a more chronic infection, where their life

872
00:45:49,480 --> 00:45:51,759
Speaker 4: would change and be improved if we could help them,

873
00:45:52,160 --> 00:45:54,080
Speaker 4: but where if it took us like six months or

874
00:45:54,080 --> 00:45:55,879
Speaker 4: a year to get all the approvals and to prep

875
00:45:55,920 --> 00:45:59,320
Speaker 4: the phage, that would be okay. So that was April

876
00:45:59,360 --> 00:46:02,400
Speaker 4: twenty twenty five. So since then I've had ten cases.

877
00:46:02,920 --> 00:46:05,960
Speaker 4: We found phages in every single one, but only once

878
00:46:06,040 --> 00:46:09,000
Speaker 4: have we gotten all the way to the FDA approval

879
00:46:09,040 --> 00:46:11,640
Speaker 4: and actually give the page to a person step. And

880
00:46:11,719 --> 00:46:14,960
Speaker 4: it's all thanks to a student named Ritwick Kumar. You know,

881
00:46:15,040 --> 00:46:18,040
Speaker 4: he's really the reason this all happened. So he personally

882
00:46:18,520 --> 00:46:21,400
Speaker 4: found well with a team of other students and a

883
00:46:21,440 --> 00:46:24,440
Speaker 4: medical resident who joined our lab as a volunteer. Actually

884
00:46:24,520 --> 00:46:27,120
Speaker 4: Ritwick hunted for a staff phage for the patient I'm

885
00:46:27,160 --> 00:46:30,520
Speaker 4: talking about for about six months and never found one.

886
00:46:30,800 --> 00:46:33,960
Speaker 4: Then the first week our new medical resident Alexandra showed up,

887
00:46:34,040 --> 00:46:37,400
Speaker 4: she found a phage. So there must have been something

888
00:46:37,440 --> 00:46:41,440
Speaker 4: different about her technique or the patch of wastewater we

889
00:46:41,560 --> 00:46:44,880
Speaker 4: used that week or something. Anyway, we got a wonderful

890
00:46:45,000 --> 00:46:48,800
Speaker 4: staff phage. We named her Lude Miller, and Alexandra I

891
00:46:48,840 --> 00:46:54,160
Speaker 4: named her Lude Miller and so since last summer we

892
00:46:54,280 --> 00:46:57,840
Speaker 4: have been prepping this phage Ludmilla to help a patient

893
00:46:57,880 --> 00:47:01,720
Speaker 4: at the CI Medical Center who as a chronic sinusitis

894
00:47:01,800 --> 00:47:05,560
Speaker 4: with MRSA meth cylline resistant Staphylococcus aureus in their nose.

895
00:47:06,560 --> 00:47:09,080
Speaker 4: And the doctor felt that it was a good case

896
00:47:09,160 --> 00:47:14,120
Speaker 4: because the patient is getting frequent fevers and so their

897
00:47:14,200 --> 00:47:17,640
Speaker 4: quality of life is very affected. But they're stable enough

898
00:47:17,680 --> 00:47:19,719
Speaker 4: that if we took six months or a year, it

899
00:47:19,760 --> 00:47:21,759
Speaker 4: would be okay. And that is how long it took.

900
00:47:21,920 --> 00:47:25,160
Speaker 4: So I actually sent Ritwick to my friend darray Vantyne's

901
00:47:25,200 --> 00:47:27,480
Speaker 4: lab at pitt to learn how they prep the phages

902
00:47:27,560 --> 00:47:29,080
Speaker 4: because we were a little new at it and I

903
00:47:29,080 --> 00:47:31,360
Speaker 4: wanted to make sure that we were getting good advice

904
00:47:31,400 --> 00:47:35,080
Speaker 4: and he could like watch somebody else doing all the steps.

905
00:47:35,880 --> 00:47:40,040
Speaker 4: And then we also chose a gram positive bacteria, Staphylococcus,

906
00:47:40,120 --> 00:47:43,319
Speaker 4: because it doesn't carry endotoxins, which are really hard to

907
00:47:43,360 --> 00:47:46,480
Speaker 4: purify out of bacterial preps. So it kind of made

908
00:47:46,520 --> 00:47:49,680
Speaker 4: the process simpler by starting with a gram positive anyway,

909
00:47:49,719 --> 00:47:53,360
Speaker 4: so Ritwick made a big batch of these phages.

910
00:47:53,680 --> 00:47:56,000
Speaker 1: He stewed up some lud Milli soup, he.

911
00:47:56,000 --> 00:47:58,520
Speaker 4: Stewed up some lud Milli soup, and then he filtered

912
00:47:58,560 --> 00:48:01,120
Speaker 4: out all the stuff that could cause trouble. And I mean,

913
00:48:01,960 --> 00:48:04,439
Speaker 4: I probably should not go into so many details about

914
00:48:04,440 --> 00:48:07,400
Speaker 4: the protocol, but ask questions if you're interested. And so

915
00:48:07,520 --> 00:48:10,000
Speaker 4: we prepped up the phage in a safe way, and

916
00:48:10,040 --> 00:48:12,920
Speaker 4: then we actually even sent it out to a third

917
00:48:12,960 --> 00:48:17,000
Speaker 4: party lab to test for storility and endotoxin. And because

918
00:48:17,000 --> 00:48:18,480
Speaker 4: I didn't want it to be just like yeah, I mean,

919
00:48:18,560 --> 00:48:21,040
Speaker 4: my students think this is really clean. I wanted it

920
00:48:21,080 --> 00:48:23,480
Speaker 4: to be like official, you know, yeah, and that's actually

921
00:48:23,480 --> 00:48:26,680
Speaker 4: required by the FDA as well. And so once we

922
00:48:26,760 --> 00:48:29,560
Speaker 4: had all that stuff done, we made this fifty page

923
00:48:29,760 --> 00:48:32,920
Speaker 4: document and sent it to the FDA asking for authorization

924
00:48:33,080 --> 00:48:36,640
Speaker 4: to use the phage. Actually it was very interesting. Initially

925
00:48:36,680 --> 00:48:39,720
Speaker 4: we wanted to use the phage in an IV form,

926
00:48:40,440 --> 00:48:43,120
Speaker 4: and the FDA came back and suggested instead that we

927
00:48:43,200 --> 00:48:46,120
Speaker 4: do a sinus rinse, which I think was a really

928
00:48:46,160 --> 00:48:51,440
Speaker 4: smart move because there's less chance for immune reaction. I

929
00:48:51,480 --> 00:48:54,520
Speaker 4: don't have high expectations of problems with this, by the way,

930
00:48:54,680 --> 00:48:58,279
Speaker 4: I mean beyond the Eliava Institute's century of experience. Now

931
00:48:58,320 --> 00:49:00,920
Speaker 4: in the United States, there's been several hundred cases in

932
00:49:00,920 --> 00:49:03,279
Speaker 4: the last couple of years, and I'm not aware of

933
00:49:03,280 --> 00:49:04,400
Speaker 4: any adverse events.

934
00:49:04,640 --> 00:49:06,480
Speaker 3: And by that you mean nobody's had like a weird

935
00:49:06,520 --> 00:49:09,920
Speaker 3: immune response to getting viruses put in them, Like, yeah,

936
00:49:09,920 --> 00:49:12,360
Speaker 3: everybody's fine. Maybe it doesn't kill the bacteria, but it

937
00:49:12,400 --> 00:49:13,000
Speaker 3: doesn't hurt.

938
00:49:12,880 --> 00:49:16,560
Speaker 4: The people exactly. The person doesn't have a negative reaction

939
00:49:16,880 --> 00:49:20,200
Speaker 4: to the treatment so far. I mean, it's still experimental,

940
00:49:20,400 --> 00:49:25,520
Speaker 4: but so far there haven't been people having negative reactions. Great.

941
00:49:25,760 --> 00:49:28,560
Speaker 1: What an amazing bespoke process though, like a lab with

942
00:49:28,600 --> 00:49:31,719
Speaker 1: a student focused on one patient for months and months

943
00:49:31,760 --> 00:49:34,360
Speaker 1: and months. What a huge process and all this application

944
00:49:34,680 --> 00:49:36,480
Speaker 1: All right, so tell us what happens.

945
00:49:36,560 --> 00:49:40,120
Speaker 4: Yeah, did Ludmilla helpful? Well, I don't know yet. Yesterday.

946
00:49:40,160 --> 00:49:44,640
Speaker 4: It's been three weeks, so it's a six week treatment process,

947
00:49:45,560 --> 00:49:49,720
Speaker 4: so it's daily sinus forrinstance for six weeks. Good news,

948
00:49:49,840 --> 00:49:53,799
Speaker 4: nothing bad has happened, But really we won't know. I mean,

949
00:49:53,800 --> 00:49:56,080
Speaker 4: I think it's possible that they're feeling a little bit better,

950
00:49:56,280 --> 00:49:58,759
Speaker 4: but they're also getting antibiotics at the same time. So

951
00:49:58,880 --> 00:50:01,920
Speaker 4: the moment of truth will about three to four weeks

952
00:50:02,160 --> 00:50:06,799
Speaker 4: after the six weeks treatment because usually after the antibiotics

953
00:50:06,800 --> 00:50:09,680
Speaker 4: are stopped, the fevers come back. So we're gonna wait

954
00:50:09,800 --> 00:50:13,200
Speaker 4: to see if the fevers do not come back at

955
00:50:13,200 --> 00:50:14,280
Speaker 4: the end of the six weeks.

956
00:50:14,360 --> 00:50:16,800
Speaker 1: All right, Well, we're recording this episode in mid August,

957
00:50:17,160 --> 00:50:19,800
Speaker 1: but we're gonna post it later, so just before posts,

958
00:50:19,840 --> 00:50:22,719
Speaker 1: we'll get an update from Katrina on how this is going.

959
00:50:22,800 --> 00:50:25,400
Speaker 1: So listen at the end of the episode for a

960
00:50:25,440 --> 00:50:27,160
Speaker 1: more recent update from Katrina.

961
00:50:27,200 --> 00:50:29,399
Speaker 4: Oh what a good idea. I'm excited, but there's I mean,

962
00:50:29,440 --> 00:50:32,080
Speaker 4: there are actually a lot of interesting cases to follow.

963
00:50:32,239 --> 00:50:35,400
Speaker 4: In fact, I was at the Evergreen Phage meeting in Knoxville, Tennessee,

964
00:50:35,520 --> 00:50:38,640
Speaker 4: last week, and I met a man who has been

965
00:50:38,640 --> 00:50:40,279
Speaker 4: coming to the meeting a couple of times who had

966
00:50:40,320 --> 00:50:43,680
Speaker 4: a really terribly coli infection, and he actually traveled to

967
00:50:43,719 --> 00:50:46,319
Speaker 4: the Eliava Institute and too Blisi, Georgia, where they do

968
00:50:46,400 --> 00:50:50,839
Speaker 4: these phage treatments. They cooked up a specific phage just

969
00:50:50,920 --> 00:50:53,640
Speaker 4: for his infection because none of the ones in their

970
00:50:53,680 --> 00:50:59,000
Speaker 4: bank were effective, and the doctors there had him do

971
00:50:59,280 --> 00:51:02,840
Speaker 4: three twenty day courses of three times a day phage

972
00:51:02,840 --> 00:51:07,080
Speaker 4: treatment and it wasn't until the second twenty day course

973
00:51:07,280 --> 00:51:10,279
Speaker 4: that he started to feel better and then his bacterial

974
00:51:10,320 --> 00:51:13,960
Speaker 4: load and his blood dropped. So it's not necessarily that

975
00:51:14,000 --> 00:51:17,120
Speaker 4: you would see a big effect in the first couple weeks,

976
00:51:17,160 --> 00:51:19,640
Speaker 4: like in his case, at least it took several times,

977
00:51:19,960 --> 00:51:21,520
Speaker 4: and he wrote a book about it. He's been on

978
00:51:21,520 --> 00:51:23,960
Speaker 4: a lot of podcasts. It's a really really cool story.

979
00:51:24,160 --> 00:51:26,480
Speaker 4: So I's so cool that it worked for him. And

980
00:51:26,680 --> 00:51:28,520
Speaker 4: if you look at the summary of some of those

981
00:51:28,640 --> 00:51:30,560
Speaker 4: hundreds of cases that have been going on lately, it

982
00:51:30,560 --> 00:51:34,040
Speaker 4: looks like seventy five to eighty percent of people have

983
00:51:34,719 --> 00:51:37,400
Speaker 4: a positive responses and like their infection is helped.

984
00:51:37,560 --> 00:51:39,080
Speaker 2: Wow, but it's still.

985
00:51:39,000 --> 00:51:41,239
Speaker 4: Very early days. I mean, as you say, Daniel, it's

986
00:51:41,280 --> 00:51:44,799
Speaker 4: like kind of crazy to imagine that there's an individual

987
00:51:44,920 --> 00:51:48,600
Speaker 4: lab customizing a treatment to each person. But on the

988
00:51:48,640 --> 00:51:50,880
Speaker 4: other hand, the skills it takes are not that crazy,

989
00:51:50,920 --> 00:51:53,880
Speaker 4: Like I don't understand why we wouldn't have phage therapy

990
00:51:53,960 --> 00:51:56,319
Speaker 4: clinics to be able to do this for people, Like

991
00:51:56,360 --> 00:51:59,440
Speaker 4: the resources are not that intense. Then, know how is

992
00:52:00,120 --> 00:52:02,040
Speaker 4: you know something that a good student can learn how

993
00:52:02,080 --> 00:52:02,279
Speaker 4: to do.

994
00:52:02,719 --> 00:52:04,680
Speaker 3: I mean, we've known about this for one hundred years.

995
00:52:04,680 --> 00:52:08,560
Speaker 3: There's an institute in Georgia. Why isn't it more common? Like,

996
00:52:08,640 --> 00:52:11,520
Speaker 3: why doesn't the US allow this to happen all the time?

997
00:52:11,960 --> 00:52:15,080
Speaker 4: I think it's a medical history question. I think we

998
00:52:15,239 --> 00:52:18,719
Speaker 4: just went down a road using antibiotics and they were

999
00:52:18,920 --> 00:52:23,000
Speaker 4: approved into the medical system that we have, and it's

1000
00:52:23,040 --> 00:52:27,080
Speaker 4: a very different system. For antibiotics. There's a few dozen molecules,

1001
00:52:27,520 --> 00:52:30,520
Speaker 4: so it's possible to approve each of one of them

1002
00:52:30,760 --> 00:52:32,880
Speaker 4: in a trial that these days would cost one hundred

1003
00:52:32,920 --> 00:52:34,960
Speaker 4: million dollars to get a drug through a Phase three

1004
00:52:35,000 --> 00:52:39,400
Speaker 4: clinical trial. You can't really do that for every single phage. Obviously,

1005
00:52:40,320 --> 00:52:44,600
Speaker 4: it's possible that the FDA will approve the preparation methods

1006
00:52:45,040 --> 00:52:47,240
Speaker 4: that we use and then that would work for multiple

1007
00:52:47,280 --> 00:52:50,280
Speaker 4: different kinds of phages. But using the model of clinical

1008
00:52:50,280 --> 00:52:53,319
Speaker 4: trials that we currently have for approving drugs won't work

1009
00:52:53,320 --> 00:52:56,000
Speaker 4: for phages because you need different ones for each infection.

1010
00:52:57,000 --> 00:53:00,319
Speaker 4: So that's the real reason that it's not happening as

1011
00:53:00,360 --> 00:53:02,359
Speaker 4: much right now. I would say, how do you.

1012
00:53:02,320 --> 00:53:04,839
Speaker 1: See it scaling up? Like is there a future in

1013
00:53:04,880 --> 00:53:08,600
Speaker 1: which people have individualized medicine where I don't need Katrina

1014
00:53:08,719 --> 00:53:11,120
Speaker 1: and her lab like working on me individually, it's like

1015
00:53:11,280 --> 00:53:14,960
Speaker 1: roboticized or automated, or how do we make this more

1016
00:53:15,000 --> 00:53:15,600
Speaker 1: wide threaten?

1017
00:53:15,920 --> 00:53:19,440
Speaker 4: It could be that we can develop, evolve or engineer

1018
00:53:19,520 --> 00:53:22,719
Speaker 4: phages that have broader host range so that we would

1019
00:53:22,719 --> 00:53:25,799
Speaker 4: only need a relatively small number of phages to cover

1020
00:53:25,920 --> 00:53:30,279
Speaker 4: most common infections. So that is certainly one possibility. That's

1021
00:53:30,280 --> 00:53:32,960
Speaker 4: a science question. I don't know if that's possible or not,

1022
00:53:33,040 --> 00:53:35,480
Speaker 4: but like in my own lab, we often do experiments

1023
00:53:35,520 --> 00:53:38,480
Speaker 4: where we evolve our phages to try to have broader

1024
00:53:38,520 --> 00:53:41,759
Speaker 4: host strange to be able to infect more different subtypes

1025
00:53:41,800 --> 00:53:46,000
Speaker 4: of the same bacteria. You could also use molecules to

1026
00:53:46,040 --> 00:53:49,839
Speaker 4: try to assist the infection, and that might make one

1027
00:53:49,880 --> 00:53:52,440
Speaker 4: phage work in more context. Those are like two main

1028
00:53:52,480 --> 00:53:55,759
Speaker 4: research areas in my lab. Actually, so that's possible, that's

1029
00:53:55,800 --> 00:53:59,200
Speaker 4: still a science question. But then even just using exactly

1030
00:53:59,239 --> 00:54:02,319
Speaker 4: the model of the l Yava Institute, I really love

1031
00:54:02,360 --> 00:54:04,239
Speaker 4: that idea. I just don't know how it would work

1032
00:54:04,280 --> 00:54:07,439
Speaker 4: in our current healthcare system. Maybe it has to be

1033
00:54:07,760 --> 00:54:10,479
Speaker 4: more like the way that supplements are sold, where they're

1034
00:54:10,560 --> 00:54:15,000
Speaker 4: generally regarded as safe, and so people could use phages

1035
00:54:15,239 --> 00:54:19,680
Speaker 4: as a kind of augment, like an addition to their antibiotics.

1036
00:54:19,880 --> 00:54:23,480
Speaker 1: Uh oh, are we walking towards the podcast supplement industry

1037
00:54:23,520 --> 00:54:27,920
Speaker 1: that so many people get sucked into. We are not

1038
00:54:28,000 --> 00:54:29,160
Speaker 1: building supplements here.

1039
00:54:29,320 --> 00:54:32,200
Speaker 4: I was thinking more like a I think like a

1040
00:54:32,239 --> 00:54:35,680
Speaker 4: wellness spot, Like apparently the onlyav Institute is an integrative

1041
00:54:35,680 --> 00:54:37,640
Speaker 4: health center where you get a massage every day and

1042
00:54:37,640 --> 00:54:40,000
Speaker 4: you meet with a team of doctors and psychiatrists and

1043
00:54:40,040 --> 00:54:43,840
Speaker 4: everybody helps you get better. And so heck, yeah exactly.

1044
00:54:43,880 --> 00:54:46,680
Speaker 4: So like, hey, we're in sunny Sokal, maybe we should

1045
00:54:47,000 --> 00:54:50,719
Speaker 4: make a clinic some of us. Yeah, that's right.

1046
00:54:51,160 --> 00:54:53,160
Speaker 2: Can we talk a little bit more about the trade off?

1047
00:54:53,239 --> 00:54:55,160
Speaker 3: So you were talking about how your lab is trying

1048
00:54:55,200 --> 00:54:57,879
Speaker 3: to evolve the phages to be able to attack more

1049
00:54:57,960 --> 00:54:58,840
Speaker 3: kinds of bacteria.

1050
00:54:59,400 --> 00:55:00,000
Speaker 2: So two thoughts.

1051
00:55:00,080 --> 00:55:02,120
Speaker 3: One thought is that we talked earlier about how each

1052
00:55:02,160 --> 00:55:06,400
Speaker 3: phage is usually specialized on one species or even strain

1053
00:55:06,560 --> 00:55:08,920
Speaker 3: of bacteria. So I imagine it's very hard to evolve

1054
00:55:08,960 --> 00:55:11,080
Speaker 3: it to be more of a generalist. And then two,

1055
00:55:11,719 --> 00:55:13,719
Speaker 3: you know, one of the benefits of this technique to

1056
00:55:13,719 --> 00:55:16,279
Speaker 3: me seems to be that you don't wipe out the

1057
00:55:16,280 --> 00:55:19,440
Speaker 3: rest of your bacteria. You can like maintain your microbiome

1058
00:55:19,760 --> 00:55:22,279
Speaker 3: and just target the bad guy. Yeah, so, like, what

1059
00:55:22,400 --> 00:55:25,120
Speaker 3: are the trade offs with with trying to make a

1060
00:55:25,160 --> 00:55:26,200
Speaker 3: more general phage.

1061
00:55:26,800 --> 00:55:29,919
Speaker 4: Well, a more general phage would likely still be way

1062
00:55:30,000 --> 00:55:33,360
Speaker 4: more precise than an antibiotic. So if you were to

1063
00:55:33,440 --> 00:55:38,400
Speaker 4: take a phage that can kill most of your Enercoccus

1064
00:55:38,400 --> 00:55:41,719
Speaker 4: fecalus or pick one of those escape pathogens, that would

1065
00:55:41,760 --> 00:55:44,799
Speaker 4: still leave tons of other bacteria alone in a way

1066
00:55:44,840 --> 00:55:48,200
Speaker 4: that antibiotics really never do. So I think it would

1067
00:55:48,239 --> 00:55:52,279
Speaker 4: still be way more specific even with a more generalist phagel.

1068
00:55:52,520 --> 00:55:54,960
Speaker 4: So then the question is just whether we can evolve

1069
00:55:55,000 --> 00:55:59,839
Speaker 4: those generalist phages. For some industrial applications. There has all

1070
00:56:00,000 --> 00:56:02,880
Speaker 4: already been signs of success for that, like, in fact,

1071
00:56:02,960 --> 00:56:08,880
Speaker 4: the deli meat industry and the food spoilage industry have

1072
00:56:08,960 --> 00:56:11,399
Speaker 4: been using phages for a long time and I think

1073
00:56:11,440 --> 00:56:13,480
Speaker 4: that there's a lot of industrial know how that I

1074
00:56:13,520 --> 00:56:16,640
Speaker 4: am not privy to that suggests that this has been possible.

1075
00:56:16,800 --> 00:56:20,040
Speaker 4: So I don't know, but I think that there are

1076
00:56:20,080 --> 00:56:24,080
Speaker 4: a handful of staphylococcus and lysteria and phages that are

1077
00:56:24,239 --> 00:56:27,320
Speaker 4: used in the food industry that actually do have pretty

1078
00:56:27,320 --> 00:56:30,000
Speaker 4: broad host range, So it could be that we could

1079
00:56:30,120 --> 00:56:32,760
Speaker 4: use the same methods to make that happen for human

1080
00:56:32,800 --> 00:56:36,720
Speaker 4: medicine too, But there's still it's just a totally different

1081
00:56:36,800 --> 00:56:40,279
Speaker 4: regulatory framework than what we're used to for pharmaceuticals. So

1082
00:56:40,640 --> 00:56:44,839
Speaker 4: it's an interesting thing. I'm so curious if in ten

1083
00:56:44,920 --> 00:56:46,799
Speaker 4: years we're going to have this all figured out and

1084
00:56:46,880 --> 00:56:49,440
Speaker 4: it's going to be widespread, or if it's still going

1085
00:56:49,520 --> 00:56:51,480
Speaker 4: to be this kind of backwater. It's hard to know.

1086
00:56:51,560 --> 00:56:54,160
Speaker 4: It feels like there's a sea change right now that

1087
00:56:54,239 --> 00:56:57,239
Speaker 4: there are now hundreds of clinicians that are very interested.

1088
00:56:57,920 --> 00:56:59,680
Speaker 4: But on average, if you go to your doctor and

1089
00:56:59,719 --> 00:57:02,120
Speaker 4: ask a phage therapy, they're probably not going to have

1090
00:57:02,160 --> 00:57:03,720
Speaker 4: heard of it, you know, or not know much.

1091
00:57:04,120 --> 00:57:06,920
Speaker 1: And in that scenario, could phage therapy be a victim

1092
00:57:06,960 --> 00:57:09,040
Speaker 1: of its own success? I mean, if you have these phages,

1093
00:57:09,080 --> 00:57:11,680
Speaker 1: you start using them on bacteria, Are you then just

1094
00:57:11,760 --> 00:57:14,880
Speaker 1: going to end up with bacteria that are resistant to

1095
00:57:15,000 --> 00:57:18,000
Speaker 1: your phages? Couldn't it suffer the same fate as antibiotics.

1096
00:57:18,560 --> 00:57:23,680
Speaker 4: Yes, bacteria will evolve resistance to the phages, and that's

1097
00:57:23,960 --> 00:57:27,480
Speaker 4: exactly the same problem we have with antibiotics. You're right,

1098
00:57:28,280 --> 00:57:31,240
Speaker 4: I guess I look at it like the bacteria and

1099
00:57:31,320 --> 00:57:34,640
Speaker 4: phages have been in these arms races through the ages,

1100
00:57:35,360 --> 00:57:38,520
Speaker 4: and what you're trying to do in an infection is

1101
00:57:38,720 --> 00:57:42,240
Speaker 4: to give the immune system a leg up. And so

1102
00:57:42,680 --> 00:57:44,920
Speaker 4: in an acute sense, what you need is like a

1103
00:57:44,960 --> 00:57:47,480
Speaker 4: one two punch, and you could use antibiotics in phagies

1104
00:57:47,520 --> 00:57:49,960
Speaker 4: at the same time, and you get in there and

1105
00:57:50,000 --> 00:57:52,200
Speaker 4: you tap the infection down a bit, and you just

1106
00:57:52,240 --> 00:57:55,200
Speaker 4: give the immune system a moment of breathing rooms so

1107
00:57:55,280 --> 00:57:59,360
Speaker 4: that there's more chance for the human to survive the battle.

1108
00:57:59,520 --> 00:58:02,919
Speaker 4: You know. So, yeah, it's true that there could still

1109
00:58:02,960 --> 00:58:07,720
Speaker 4: be resistances arising to phages. But when people use that argument,

1110
00:58:07,840 --> 00:58:11,040
Speaker 4: I'm always like, hey, well antibiotics. You know, bacteria resist

1111
00:58:11,040 --> 00:58:14,200
Speaker 4: antibiotics too, and that didn't stop us from making good

1112
00:58:14,280 --> 00:58:17,959
Speaker 4: use of them and figuring out treatment plans that set

1113
00:58:18,000 --> 00:58:20,320
Speaker 4: things up so the human can succeed, So I think

1114
00:58:20,320 --> 00:58:22,400
Speaker 4: we just need to learn how to do that, which

1115
00:58:22,440 --> 00:58:24,919
Speaker 4: is very early days. As you can imagine, we've only

1116
00:58:25,000 --> 00:58:28,800
Speaker 4: used phages, like, you know, a couple hundred times probably

1117
00:58:28,840 --> 00:58:31,640
Speaker 4: in the United States in the last decades. So it's

1118
00:58:31,640 --> 00:58:34,200
Speaker 4: not like if people ask you questions like, oh, should

1119
00:58:34,200 --> 00:58:36,400
Speaker 4: we use this dose or that dose or this treatment

1120
00:58:36,440 --> 00:58:38,480
Speaker 4: time or that treatment time. I mean, we do not

1121
00:58:38,600 --> 00:58:40,080
Speaker 4: know the answer to things like that yet.

1122
00:58:40,880 --> 00:58:44,200
Speaker 3: There's a final question we have to ask, which is

1123
00:58:45,080 --> 00:58:49,520
Speaker 3: are there bacteria in space with phages? And are aliens

1124
00:58:49,600 --> 00:58:54,000
Speaker 3: using phage therapy? How would you phrase the alien question

1125
00:58:54,080 --> 00:58:55,400
Speaker 3: this time around, Daniel.

1126
00:58:55,360 --> 00:58:58,240
Speaker 1: No, I've trained you well, Kelly, that was perfect. Yeah, yeah,

1127
00:58:58,400 --> 00:58:59,720
Speaker 1: do aliens have viruses?

1128
00:58:59,760 --> 00:59:00,240
Speaker 4: Could you know?

1129
00:59:00,480 --> 00:59:02,560
Speaker 2: Well, am I in the whites and Institute? Now?

1130
00:59:02,760 --> 00:59:07,800
Speaker 1: Yes, yes, we'll send you some salad dressing. Yes.

1131
00:59:09,400 --> 00:59:13,640
Speaker 4: Well, we definitely have brought Earth's microbes out to space,

1132
00:59:14,240 --> 00:59:17,520
Speaker 4: although there is a whole division of NASA aiming towards

1133
00:59:17,640 --> 00:59:20,160
Speaker 4: preventing that from happening, so we work hard not to.

1134
00:59:20,480 --> 00:59:23,560
Speaker 4: But microbes are everywhere, so of course we've brought some

1135
00:59:23,720 --> 00:59:26,040
Speaker 4: out to space, so there's definitely going to be some

1136
00:59:26,120 --> 00:59:28,040
Speaker 4: phages out there. Would be my guess. I mean, they're

1137
00:59:28,040 --> 00:59:30,760
Speaker 4: probably not going to survive long. So would they make

1138
00:59:30,800 --> 00:59:33,320
Speaker 4: it to where aliens are, I would say.

1139
00:59:33,080 --> 00:59:36,080
Speaker 1: No, member would aliens have their own native viruses? Do

1140
00:59:36,120 --> 00:59:39,120
Speaker 1: you think viruses are a common feature of life everywhere

1141
00:59:39,160 --> 00:59:39,880
Speaker 1: in the universe?

1142
00:59:40,080 --> 00:59:42,880
Speaker 4: Yes, I definitely do. I mean I think most life

1143
00:59:42,960 --> 00:59:47,840
Speaker 4: will start from little self replicating things like are in

1144
00:59:47,920 --> 00:59:50,640
Speaker 4: a world. I mean, that's the only model in my head.

1145
00:59:50,680 --> 00:59:52,320
Speaker 4: So of course I need to meet an alien who

1146
00:59:52,320 --> 00:59:54,720
Speaker 4: has a different model in their head to contradict it.

1147
00:59:54,760 --> 00:59:57,880
Speaker 4: But I could imagine a totally different type of life

1148
00:59:57,880 --> 01:00:01,960
Speaker 4: emerging with the same order of events, where you start

1149
01:00:02,080 --> 01:00:06,640
Speaker 4: more from little self replicating things that essentially are viruses,

1150
01:00:07,040 --> 01:00:09,960
Speaker 4: and in general, yeah, it's hard for me to imagine

1151
01:00:10,000 --> 01:00:13,920
Speaker 4: an ecology that doesn't have infection and viruses going on.

1152
01:00:14,240 --> 01:00:17,040
Speaker 1: So then, actually, my last question, Katrina is where do

1153
01:00:17,120 --> 01:00:21,080
Speaker 1: your sympathies lie? I mean, you are growing up these phages,

1154
01:00:21,120 --> 01:00:23,200
Speaker 1: you're attacking the bacteria, but you're also talking about the

1155
01:00:23,200 --> 01:00:25,720
Speaker 1: bacteria getting stressed out. Are you in the camp of

1156
01:00:25,760 --> 01:00:28,919
Speaker 1: the humans or the bacteria or the viruses? Really, where

1157
01:00:29,000 --> 01:00:30,200
Speaker 1: should we put your allegiance?

1158
01:00:30,480 --> 01:00:32,479
Speaker 4: I mean, I do not think you need to have

1159
01:00:32,760 --> 01:00:36,880
Speaker 4: separate allegiances. This is like a big team dodging the question.

1160
01:00:37,160 --> 01:00:39,760
Speaker 2: No he's not. That's a perfectly valid answer.

1161
01:00:39,840 --> 01:00:43,680
Speaker 4: Okay, But here's what I'm saying. I think that the

1162
01:00:43,720 --> 01:00:48,880
Speaker 4: bacteria are invited when they are behaving themselves. I mean,

1163
01:00:48,960 --> 01:00:54,920
Speaker 4: I am not inviting crazy, infecting, drug resistant bacteria. Those

1164
01:00:54,920 --> 01:00:56,360
Speaker 4: guys have gone too far, you know.

1165
01:00:58,160 --> 01:01:01,000
Speaker 1: So there are some limits to Katrina's empathy. Even that's amazing.

1166
01:01:01,040 --> 01:01:04,040
Speaker 4: But like an average bacteria is not a pathogen. But yeah,

1167
01:01:04,040 --> 01:01:07,200
Speaker 4: the pathogens, they're like nihilists, you know, they're not invited.

1168
01:01:07,480 --> 01:01:07,880
Speaker 2: Amen.

1169
01:01:08,640 --> 01:01:10,960
Speaker 3: All right, Well, it has been a fascinating day here

1170
01:01:11,000 --> 01:01:12,880
Speaker 3: at Daniel and Kelly's Viral Universe.

1171
01:01:12,960 --> 01:01:15,080
Speaker 2: I always love having you on the show, Katrina.

1172
01:01:15,200 --> 01:01:18,000
Speaker 4: Thank you well, thank you for having me, and thank

1173
01:01:18,040 --> 01:01:20,840
Speaker 4: you guys for listening to phage therapy. And if your

1174
01:01:20,880 --> 01:01:25,160
Speaker 4: listeners have any suggestions about how our community should get

1175
01:01:25,160 --> 01:01:28,200
Speaker 4: phage therapy off the ground, we're really listening.

1176
01:01:30,880 --> 01:01:33,520
Speaker 1: All right. So it's August twenty fifth, and we're checking

1177
01:01:33,560 --> 01:01:36,200
Speaker 1: in for an update on that patient. Katrina, what is

1178
01:01:36,240 --> 01:01:38,640
Speaker 1: the status of the patient that your lab developed a

1179
01:01:38,680 --> 01:01:39,160
Speaker 1: page four?

1180
01:01:39,440 --> 01:01:42,800
Speaker 5: Well, it's week four out of six now, so the

1181
01:01:42,920 --> 01:01:45,800
Speaker 5: fifth week of treatment out of six will begin on Thursday,

1182
01:01:46,000 --> 01:01:49,040
Speaker 5: so we don't have any knowledge yet of whether it worked.

1183
01:01:49,160 --> 01:01:51,160
Speaker 5: We actually have to wait for a month after the

1184
01:01:51,280 --> 01:01:54,280
Speaker 5: end of the therapy to see whether the fevers return

1185
01:01:54,400 --> 01:01:56,520
Speaker 5: or not. And that's how we'll know whether the staff

1186
01:01:56,600 --> 01:02:00,880
Speaker 5: causing sinusitis in the nose has been damp and hopefully

1187
01:02:01,520 --> 01:02:03,040
Speaker 5: taken out by this page.

1188
01:02:03,120 --> 01:02:04,440
Speaker 1: All right, well, because we're going to have to have

1189
01:02:04,480 --> 01:02:06,760
Speaker 1: you back on the podcast for a follow up episode

1190
01:02:06,840 --> 01:02:08,080
Speaker 1: to see how this stuff works.

1191
01:02:08,240 --> 01:02:12,040
Speaker 4: I would love that great idea.

1192
01:02:16,320 --> 01:02:19,880
Speaker 3: Daniel and Kelly's Extraordinary Universe is produced by iHeartRadio.

1193
01:02:20,080 --> 01:02:21,600
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1194
01:02:21,720 --> 01:02:24,680
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1195
01:02:24,880 --> 01:02:27,520
Speaker 1: have about this Extraordinary Universe.

1196
01:02:27,600 --> 01:02:30,560
Speaker 3: We want to know your thoughts on recent shows, suggestions

1197
01:02:30,560 --> 01:02:31,560
Speaker 3: for future shows.

1198
01:02:31,680 --> 01:02:34,000
Speaker 2: If you contact us, we will get back to you.

1199
01:02:34,280 --> 01:02:37,800
Speaker 1: We really mean it. We answer every message. Email us

1200
01:02:37,840 --> 01:02:40,960
Speaker 1: at Questions at Danielandkelly.

1201
01:02:40,120 --> 01:02:42,200
Speaker 3: Dot org, or you can find us on social media.

1202
01:02:42,280 --> 01:02:46,080
Speaker 3: We have accounts on x, Instagram, Blue Sky and on

1203
01:02:46,160 --> 01:02:47,080
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1204
01:02:47,120 --> 01:02:50,080
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1205
01:02:50,320 --> 01:02:51,840
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