WEBVTT - Phages: Bacteria’s Worst Nightmare 0:00:02.120 --> 0:00:03.920 There's a question. I've been waiting a long time to 0:00:03.960 --> 0:00:06.800 ask you phage or phage? 0:00:08.440 --> 0:00:11.600 I say phage. Some people say fage. 0:00:12.119 --> 0:00:15.600 Faj Come on, get the fuj out of here. What 0:00:15.720 --> 0:00:16.000 is it? 0:00:17.000 --> 0:00:19.919 I think phage and phage are so similar that we 0:00:20.280 --> 0:00:25.119 can work with that. It's Greek for killer or to 0:00:25.239 --> 0:00:25.799 sort of eat. 0:00:26.480 --> 0:00:29.240 But in English. Yeah, so you're saying, you say phage 0:00:30.000 --> 0:00:30.520 rhymes with. 0:00:30.560 --> 0:00:32.600 Age, I say phage. 0:00:33.080 --> 0:00:36.239 I'm talking with Tom Ireland. He is a science journalist 0:00:36.240 --> 0:00:39.080 who just wrote a book called The Good Virus, and 0:00:39.200 --> 0:00:43.640 it is all about phages. Phages are these amazing viruses 0:00:43.800 --> 0:00:45.800 that have sort of flown under the radar since they 0:00:45.800 --> 0:00:48.000 were discovered in the first part of the twentieth century. 0:00:48.720 --> 0:00:54.440 Phages also known as bacteria phages are viruses that kill bacteria, 0:00:55.120 --> 0:00:57.440 and that is a very useful trait if you need 0:00:57.480 --> 0:01:00.680 to kill bacteria that are making someone really sick. And 0:01:00.720 --> 0:01:03.360 in fact, Tom told me people are now turning to 0:01:03.400 --> 0:01:06.720 phages to try to treat infections that can't be cured 0:01:06.800 --> 0:01:07.840 with antibiotics. 0:01:08.440 --> 0:01:11.679 I think this year is the year that it all changes, 0:01:11.720 --> 0:01:16.319 because the crisis of drug resistance is so acute and 0:01:16.480 --> 0:01:19.480 so scary. Now that we have to take it seriously. 0:01:19.520 --> 0:01:23.520 So the World Economic Forum this year named phage therapy 0:01:23.560 --> 0:01:26.640 in their top ten Emerging technologies for twenty twenty three. 0:01:27.240 --> 0:01:30.360 You know, we're not just guessing and throwing viruses into 0:01:30.360 --> 0:01:33.960 people with bloodstream anymore. This is a kind of modern 0:01:34.520 --> 0:01:38.240 phage therapy two point zero, and there's some real momentum 0:01:38.240 --> 0:01:39.200 building behind the idea. 0:01:39.240 --> 0:01:43.680 Now, we spend a lot of time on this show 0:01:43.720 --> 0:01:47.720 talking about viruses that are bad for humans, Viruses that 0:01:47.840 --> 0:01:51.120 make us sick, viruses that have killed hundreds of millions 0:01:51.160 --> 0:01:55.240 of people. Today, for the season finale, we bring you 0:01:55.320 --> 0:01:59.600 a shocking twist show about viruses that are good for people, 0:02:00.080 --> 0:02:04.200 Viruses that help us fight disease. We'll hear the story 0:02:04.240 --> 0:02:07.040 of one of the first scientists to study phages. He 0:02:07.160 --> 0:02:10.239 was kind of a genius, but also he was kind 0:02:10.240 --> 0:02:13.799 of shady. And then we'll talk to a scientist who 0:02:13.800 --> 0:02:17.760 collects phages in lakes and sewage plants and then uses 0:02:17.800 --> 0:02:21.560 them to treat patients with life threatening infections that cannot 0:02:21.600 --> 0:02:26.280 be treated with antibiotics. I'm Jacob Goldstein. This is incubation 0:02:39.360 --> 0:02:42.919 in the world on planet Earth right now. How many 0:02:43.000 --> 0:02:45.840 phages not kinds of phages, but phages. 0:02:46.280 --> 0:02:49.440 So there's a number that goes around a lot. It's 0:02:49.440 --> 0:02:53.799 a very rough calculation, but it's ten with thirty one 0:02:53.880 --> 0:02:56.480 zeros after it. One way of thinking of that is 0:02:57.840 --> 0:03:01.920 a trillion phages for every grain of sand on the planet. 0:03:05.040 --> 0:03:06.639 So just just crazy numbers. 0:03:07.400 --> 0:03:09.120 I don't know what to do with that. You said 0:03:09.120 --> 0:03:11.200 a trillion for every grain of sand. That's like a 0:03:11.200 --> 0:03:13.080 come on kind of number, right, I mean, I guess 0:03:13.080 --> 0:03:15.720 one way to think of it is like we actually 0:03:15.800 --> 0:03:18.440 live on phage planet. Like we think we're the main 0:03:18.520 --> 0:03:20.560 thing going on on the planet, but maybe we aren't. 0:03:21.160 --> 0:03:24.400 Yeah, life is evolved in a soup of viruses, and 0:03:24.440 --> 0:03:27.839 most of those viruses are phages. And if a kind 0:03:27.840 --> 0:03:31.720 of alien life form was to just pluck a random 0:03:31.919 --> 0:03:35.840 bit of the Earth and look for life, they would 0:03:35.840 --> 0:03:38.000 probably find phages and nothing else, you know, if they 0:03:38.040 --> 0:03:39.840 just took a random bit of sea water. 0:03:40.040 --> 0:03:40.800 Huh. 0:03:40.880 --> 0:03:43.280 So we've been talking about phages at this sort of 0:03:43.680 --> 0:03:49.120 macro level, big picture level at a more micro level, 0:03:49.160 --> 0:03:52.400 like what's a phage look like? I know they're very small, 0:03:52.640 --> 0:03:55.600 but if you look really closely, what to look like? 0:03:56.520 --> 0:03:59.560 So one of the reasons I'm so interested in phages. 0:03:59.640 --> 0:04:04.520 Is that actually extraordinary looking things? And there was some 0:04:06.600 --> 0:04:10.760 discussion in the phage community that the lunar landers were 0:04:10.760 --> 0:04:13.760 actually based on a certain type of phage. I was 0:04:13.800 --> 0:04:17.200 never able to confirm that, but they have a remarkably 0:04:17.240 --> 0:04:19.960 similar structure, and they look almost like kind of tiny 0:04:20.279 --> 0:04:26.240 robotic nano machines or spiders. They're weirdly angular. So they 0:04:26.279 --> 0:04:30.800 have this twenty sided head which looks quite sinister, which 0:04:30.839 --> 0:04:33.680 contains all of the DNA. Then they have this long 0:04:34.240 --> 0:04:38.520 tail which actually acts like a kind of molecular syringe 0:04:38.560 --> 0:04:43.760 which can inject the genes from the head into the bacteria. 0:04:43.800 --> 0:04:46.559 And then they have these kind of spider like little 0:04:46.600 --> 0:04:49.560 legs which they use to land on the surface of 0:04:49.560 --> 0:04:52.960 the bacteria and bind to it. There's this head that 0:04:53.000 --> 0:04:56.400 has the payload in whether that's astronauts or genes, and 0:04:56.440 --> 0:05:01.040 then the landing legs. And then once once the phage 0:05:01.120 --> 0:05:06.240 is landed and injects the DNA, and it essentially hijacks 0:05:06.279 --> 0:05:08.600 the bacteria and turns it into a virus factory. 0:05:09.200 --> 0:05:09.719 Amazing. 0:05:10.279 --> 0:05:14.200 You know, viruses are generally thought of as bad, and 0:05:14.240 --> 0:05:18.960 it is sort of delightful to encounter this large universe 0:05:19.480 --> 0:05:22.320 of helpful viruses, like I'm very happy to be discovering 0:05:22.360 --> 0:05:23.320 these good viruses. 0:05:24.160 --> 0:05:27.599 Yeah, and they vastly outnumber the ones that we fear 0:05:27.880 --> 0:05:31.880 and hate. It's really interesting that the idea of using 0:05:31.920 --> 0:05:35.200 them to kill bacteria and kill the bacteria that caused 0:05:35.240 --> 0:05:38.720 disease is not new at all. You know, they were 0:05:38.760 --> 0:05:43.640 being used in medicine decades before the first real antibiotic, penicillin. 0:05:44.080 --> 0:05:46.400 They were being used in the twenties and the thirties, 0:05:46.839 --> 0:05:51.480 and this idea of using them as allies as medicines 0:05:51.560 --> 0:05:55.599 is becoming you know, it's being taken really seriously again. Yeah. 0:05:55.720 --> 0:05:56.080 Right. 0:05:56.360 --> 0:06:00.159 That goes back to the early part of the twentieth century. 0:06:00.640 --> 0:06:03.839 And there is this key figure who you write a 0:06:03.839 --> 0:06:07.320 lot about in your book. Really interesting story. So tell 0:06:07.360 --> 0:06:09.239 me about him. Tell me about Felix Durell. 0:06:10.240 --> 0:06:14.920 So, Felix Durel's fascinating character, a real maverick. He's kind 0:06:14.920 --> 0:06:19.440 of self taught, volatile, has none of the diplomacy that 0:06:19.560 --> 0:06:22.960 was expected of kind of gentlemen scientists of the early 0:06:23.000 --> 0:06:26.440 twentieth century. There's a dispute about whether he's French or 0:06:26.440 --> 0:06:30.520 Canadian or Belgian because he kept changing his name. He 0:06:30.560 --> 0:06:34.120 didn't really go to college to university. He spent his 0:06:34.279 --> 0:06:37.919 teenage years traveling around Europe. He moved over to Canada, 0:06:38.240 --> 0:06:42.719 declared himself a microbiologist. He was commissioned by the Canadian 0:06:42.720 --> 0:06:46.880 government to make whiskey from maple syrup, which maybe the 0:06:46.920 --> 0:06:50.480 most Canadian thing I've ever heard. And then he had 0:06:50.520 --> 0:06:54.839 this period of kind of conducting completely wild, lawless science 0:06:55.320 --> 0:07:00.880 as an infectious disease doctor in Mexico and Watemala, where 0:07:00.920 --> 0:07:03.480 he was really given free reign to do what he wanted. 0:07:03.680 --> 0:07:09.800 So a really unconventional background, very brash and terrible diplomacy, 0:07:09.960 --> 0:07:12.720 you know. So he made lots of enemies. People were 0:07:12.800 --> 0:07:15.480 very suspicious of him, and he was just, you know, 0:07:15.680 --> 0:07:19.920 just the ultimate kind of outcast, I suppose in a 0:07:20.960 --> 0:07:22.840 very important scientific field. 0:07:23.200 --> 0:07:26.520 How does Dourell make his discovery about features. 0:07:26.840 --> 0:07:31.760 In the nineteen tens, He essentially stumbles across this amazing 0:07:31.800 --> 0:07:35.840 of observation, which is that he has plates of bacteria 0:07:36.000 --> 0:07:39.280 that he's working on. It's called a lawn of bacteria. 0:07:39.720 --> 0:07:42.040 It doesn't look like much, but it's kind of opaque 0:07:42.080 --> 0:07:44.560 and milky, and that means all of your bacteria is 0:07:44.600 --> 0:07:48.720 growing nicely on whatever medium. You've given it to grow on. 0:07:49.080 --> 0:07:52.840 And he starts noticing on some of his plates there's 0:07:52.920 --> 0:07:56.280 holes and there's literally nothing there. Ah, And he takes 0:07:56.360 --> 0:07:58.960 a little touch from the middle of one of these holes, 0:07:59.360 --> 0:08:02.880 and he just which is another plate of completely healthy, uniform, 0:08:02.960 --> 0:08:07.120 milky bacteria. A hole starts growing on that too, And 0:08:07.160 --> 0:08:09.680 then he can do this indefinitely. He can take a 0:08:09.760 --> 0:08:13.560 touch from the hole and touch it on another healthy 0:08:13.560 --> 0:08:17.320 plate of bacteria. The hole starts growing again. So he 0:08:17.440 --> 0:08:21.600 knows this isn't just something that's a kind of antibacterial chemical. 0:08:22.080 --> 0:08:26.200 This has the power of replication. This is growing at 0:08:26.360 --> 0:08:29.640 the expense of the bacteria. So it's a double whammy 0:08:29.760 --> 0:08:34.480 of scientific discovery because he's he's found something that seems 0:08:34.480 --> 0:08:38.480 to be killing bacteria really quickly and really efficiently, all 0:08:38.520 --> 0:08:41.800 at once. He has a suite of theories. He theorizes 0:08:41.880 --> 0:08:45.400 that this is a virus that kills bacteria. He works 0:08:45.440 --> 0:08:47.880 out that they are replicating inside the bacteria and then 0:08:48.480 --> 0:08:53.600 bursting out. He also theorizes that phages are maybe part 0:08:53.640 --> 0:08:57.160 of our immune system, and that when someone spontaneously recovers 0:08:57.160 --> 0:09:01.240 from a disease, perhaps it's phages in our guts or 0:09:01.320 --> 0:09:04.720 in our body that has helped us recover from that disease. 0:09:09.320 --> 0:09:12.880 So as well as being completely groundbreaking, that latter idea 0:09:12.920 --> 0:09:14.720 of them being part of our immune system was kind 0:09:14.760 --> 0:09:16.840 of heretical at the time. You know, it was a 0:09:16.880 --> 0:09:18.439 completely wild and wacky theory. 0:09:19.120 --> 0:09:23.120 This is a moment when there are no antibiotics in 0:09:23.160 --> 0:09:25.560 the world, right, this is the moment when, no matter 0:09:25.600 --> 0:09:28.200 how rich you are, if you get a little infection 0:09:28.880 --> 0:09:32.720 on your foot, you might die from it. Right, truly, 0:09:32.840 --> 0:09:36.800 like there is no way to reliably and safely kill bacteria. 0:09:36.880 --> 0:09:39.720 So like this is a huge, huge thing. 0:09:40.400 --> 0:09:44.520 Yeah, when he presented these ideas to the world, the 0:09:44.720 --> 0:09:48.880 establishment of these huge you know, microbiologists of the time 0:09:49.080 --> 0:09:52.440 they just said, there's no way this is true. I 0:09:52.480 --> 0:09:57.640 think one of them actually said, if this microbe exists, 0:09:57.920 --> 0:10:00.680 I would have found it by now. People just couldn't 0:10:00.679 --> 0:10:03.880 believe that he'd discovered this entirely new form of life 0:10:04.200 --> 0:10:06.800 that had such a powerful potential use in medicine. 0:10:07.200 --> 0:10:11.319 So he has discovered this incredible thing, there's this obvious 0:10:11.640 --> 0:10:16.960 potential for clinical applications, right, how does he try and 0:10:17.000 --> 0:10:20.840 take this idea and actually use it as a treatment. 0:10:22.120 --> 0:10:26.120 Yes, So this is before clinical trials. Felix Drel walks 0:10:26.160 --> 0:10:30.040 into a children's hospital in Paris and says, I have 0:10:30.120 --> 0:10:33.600 a way of treating dysentery, this horrible inflammation of the 0:10:33.640 --> 0:10:38.080 bowels which causes you to essentially have such severe diarrhea 0:10:38.080 --> 0:10:42.160 that you die. And they decide to give a dose 0:10:42.200 --> 0:10:46.640 of phases to two young kids from a particular family 0:10:46.880 --> 0:10:52.360 who've come in with very severe dysentery, and you know, 0:10:52.480 --> 0:10:53.640 they make a full recovery. 0:10:53.760 --> 0:10:56.320 I mean, one question is how often does that happen 0:10:56.400 --> 0:10:57.559 in the absence of treatment? 0:10:57.720 --> 0:10:57.920 Right? 0:10:58.000 --> 0:11:00.640 Like the reason you really want a randomize trial is 0:11:00.679 --> 0:11:03.440 to know is this the treatment, is it in this 0:11:03.520 --> 0:11:06.359 case the phage, or is it just would have happened anyway. 0:11:07.000 --> 0:11:10.520 Exactly So Durrell he tries it on a few more 0:11:10.600 --> 0:11:15.200 kids in this hospital. It's successful. He's essentially selling his 0:11:15.280 --> 0:11:19.920 own cocktails of phages for various different bacterial diseases, and 0:11:19.960 --> 0:11:25.600 he's in this really unusual situation where the establishment microbiologists 0:11:26.120 --> 0:11:31.960 are still suggesting he's wrong, and they don't believe his theory, 0:11:31.960 --> 0:11:34.960 and they're trying to disprove his theory. But he is 0:11:35.200 --> 0:11:39.160 a great salesman of these phage based potions and he 0:11:39.480 --> 0:11:43.440 starts traveling the world and selling them to ministries of 0:11:43.480 --> 0:11:46.559 health and hospital directors, and they don't really care what 0:11:47.240 --> 0:11:50.400 the kind of academics are saying. And within a decade, 0:11:50.679 --> 0:11:51.960 phages are everywhere. 0:11:52.120 --> 0:11:56.880 Does it work? Like? I can't tell? Like he still 0:11:56.920 --> 0:11:59.520 seems shady, Like it could be snake oil. 0:11:59.840 --> 0:12:03.400 I think Felix Drell, who had an understanding of phages 0:12:03.559 --> 0:12:06.240 that was greater than anyone else on the planet. He 0:12:06.400 --> 0:12:11.520 developed a way of actually understanding which strains of bacteria 0:12:11.559 --> 0:12:14.520 were circulating in a given place at a given time, 0:12:14.880 --> 0:12:18.520 and then creating a remedy based on phages that he 0:12:18.600 --> 0:12:22.320 knew could kill those bacteria. As soon as pharmaceutical companies 0:12:22.360 --> 0:12:25.120 got involved and started trying to make products that were 0:12:25.160 --> 0:12:29.280 like mass market products, you know, it was completely hit 0:12:29.320 --> 0:12:33.360 and miss. So there was this complete inconsistency. At the time. 0:12:33.440 --> 0:12:38.400 People didn't understand phages well enough, and so phages got 0:12:38.440 --> 0:12:41.599 this reputation as being inconsistent, which they really struggled to 0:12:42.120 --> 0:12:44.880 shake off until antibiotics came along. 0:12:45.120 --> 0:12:50.520 So let's talk about that. So antibiotics come along in 0:12:50.760 --> 0:12:56.360 the what nineteen thirties, nineteen forties, Ah, what does the 0:12:56.440 --> 0:12:59.680 rise of antibiotics mean for phage therapy. 0:13:01.200 --> 0:13:04.640 Penicillin was discovered, it was you know, it really was 0:13:04.720 --> 0:13:07.040 a miracle drug. You know, you could mass produce it. 0:13:07.559 --> 0:13:10.880 Doctors knew that if a bacterial disease was one of 0:13:10.920 --> 0:13:14.920 these forty different types of bacteria, if it was caused 0:13:14.920 --> 0:13:18.280 by those bacteria, then penicillin was good for it. And 0:13:18.360 --> 0:13:22.560 so really that phage therapy started to look logistically very 0:13:22.600 --> 0:13:25.680 difficult to administer. You know, you've got to match the 0:13:25.720 --> 0:13:28.080 phage to the bacteria, or you've got to create a 0:13:28.120 --> 0:13:31.000 cocktail of different phages. It just all of a sudden 0:13:31.120 --> 0:13:34.320 seemed like a kind of wild and old fashioned and 0:13:34.360 --> 0:13:37.880 backwards way to treat bacterial infections. And in the West, 0:13:37.920 --> 0:13:40.679 at least, the idea of using phages was like, rah, 0:13:41.360 --> 0:13:41.839 forget it. 0:13:42.559 --> 0:13:46.199 So what's the end of the story of Felix Durell. 0:13:47.480 --> 0:13:49.640 Well, it's not a happy ending for him. Really. He 0:13:50.080 --> 0:13:53.520 died without any kind of acknowledgment of his work. He 0:13:53.559 --> 0:13:57.840 was actually nominated for the Nobel Prize about thirty times 0:13:58.200 --> 0:14:01.120 but never won it. He was a genius in his 0:14:01.160 --> 0:14:04.280 own way and really set the ball rolling for this 0:14:04.400 --> 0:14:08.959 idea of using phages to treat bacterial infections. 0:14:10.320 --> 0:14:15.440 So let's talk about the present. Antibiotics are amazing, but 0:14:16.240 --> 0:14:22.000 bacteria are constantly evolving to resist antibiotics. Ken phages help 0:14:22.080 --> 0:14:23.480 us with intibiotic resistance. 0:14:24.600 --> 0:14:27.000 Yeah, they absolutely can. I mean, it's as I've said, 0:14:27.040 --> 0:14:31.120 it's not straightforward. This is very different to having a 0:14:31.120 --> 0:14:35.200 pharmaceutical chemical that we can use on millions of people. 0:14:35.240 --> 0:14:39.080 There is lab work involved with each case, and you're 0:14:39.120 --> 0:14:43.680 talking about treating people with a living, evolving thing, often 0:14:43.720 --> 0:14:45.920 that's been found in a kind of river or a sewer. 0:14:46.440 --> 0:14:49.840 So there's just huge numbers of like logistical and regulatory 0:14:49.960 --> 0:14:53.040 challenges around this. But you know, they have been evolving 0:14:53.080 --> 0:14:56.560 for billions of years to kill bacteria. They are amazingly 0:14:56.560 --> 0:15:00.800 good at it, and there are countless examples now of 0:15:00.840 --> 0:15:04.440 phage therapy being used to save the life of people 0:15:04.520 --> 0:15:08.680 who have infections that are resistant to every known antibiotic 0:15:08.920 --> 0:15:09.720 in the cabinet. 0:15:13.040 --> 0:15:16.400 Tom Ireland's book is called The Good Virus, The Amazing 0:15:16.440 --> 0:15:19.600 Story and Forgotten Promise of the Phage. We'll be back 0:15:19.600 --> 0:15:21.640 in just a minute to talk to a scientist who 0:15:21.760 --> 0:15:34.960 is using phages to treat disease. Now. In the first 0:15:34.960 --> 0:15:37.600 half of today's show, Tom Ireland talked about how phage 0:15:37.600 --> 0:15:40.760 therapy is being used today to treat people who have 0:15:40.960 --> 0:15:44.840 antibiotic resistant infections. In the second half of today's show, 0:15:45.120 --> 0:15:47.440 I'm going to talk with one of the few researchers 0:15:47.440 --> 0:15:50.800 in the country who is actually doing this work. His 0:15:50.920 --> 0:15:54.560 name is Ben Chan. He's a research scientist in ecology 0:15:54.600 --> 0:15:58.560 and evolutionary biology at Yale. How did you come to 0:15:58.600 --> 0:16:01.760 be a phage guy? How to get into phages? 0:16:02.840 --> 0:16:06.720 Back in grad school I studied amphibian biology. I studied 0:16:06.720 --> 0:16:09.240 parental care behavior of poison dart frogs. 0:16:10.720 --> 0:16:12.000 And you got to do this. 0:16:12.000 --> 0:16:15.680 Amazing field work in amazing places and loved it. And 0:16:15.720 --> 0:16:19.560 there was this fungal disease that's driving amphibian decline. 0:16:19.800 --> 0:16:20.840 And what I really. 0:16:20.560 --> 0:16:22.680 Wanted to do is I wanted to engineer the skin 0:16:22.800 --> 0:16:27.080 microbiome of these poisoned dart frogs by making the bacteria 0:16:27.200 --> 0:16:30.160 produce anti fungals so that they'd be resistant to this disease. 0:16:30.200 --> 0:16:31.480 And I was like, that's how I'm going to save, 0:16:31.800 --> 0:16:35.160 you know, frogs, And I wanted to do so with 0:16:35.320 --> 0:16:37.360 a phage. Actually, I was going to engineer these bacteria 0:16:37.400 --> 0:16:38.000 with phage. 0:16:38.360 --> 0:16:40.800 Ben told me he couldn't get funding for his save 0:16:40.880 --> 0:16:44.040 the Frog's idea. But he wanted to continue his work, 0:16:44.440 --> 0:16:47.880 and in twenty thirteen he started working at a lab 0:16:47.920 --> 0:16:50.760 at Yale where he finds and studies phages. And it 0:16:50.840 --> 0:16:53.840 was there that Ben connected with the surgeon at Yale 0:16:53.920 --> 0:16:56.840 New Haven Hospital. The surgeon told him about this one 0:16:57.080 --> 0:16:58.280 really challenging case. 0:16:58.920 --> 0:17:02.040 So this guy had and aneurysm on his A order. Right, 0:17:02.160 --> 0:17:05.720 the vessels weaken, and when that's a vessel in the body, like, 0:17:05.760 --> 0:17:08.280 if that thing explodes, that's really bad news, right, especially 0:17:08.320 --> 0:17:10.959 the A order, which is like the largest vessel. So 0:17:11.040 --> 0:17:13.320 they you know, bring him into surgery. They cut out 0:17:13.320 --> 0:17:17.199 that piece and replace it with a plastic piece. And 0:17:17.240 --> 0:17:20.080 then it turns out that got infected somehow, So he's 0:17:20.080 --> 0:17:22.720 got this artificial graft onto his heart and then there's 0:17:22.760 --> 0:17:25.480 like pseudomonius bacteria growing on it. 0:17:29.400 --> 0:17:31.320 So to be clear, he has this infection in a 0:17:31.359 --> 0:17:33.720 place you really don't want an infection. Yeah, it's a 0:17:33.760 --> 0:17:38.400 bacterial infection, So great, give him antibiotics. They give him antibiotics. 0:17:38.440 --> 0:17:43.080 What happens, it sort of just suppresses it at best, right, 0:17:43.280 --> 0:17:45.000 So it won't go away with antibiotics, but you can, 0:17:45.080 --> 0:17:47.840 you know, prevent it more or less from killing you, 0:17:47.960 --> 0:17:49.800 I guess, but it's like a slow battle that eventually 0:17:49.800 --> 0:17:53.880 you're gonna lose, and so they're kind of out options. 0:17:54.160 --> 0:17:58.840 So this patient has is infected with this bacteria that 0:17:58.880 --> 0:18:01.960 you can't wipe out with antibiotics. So how does that work? 0:18:02.000 --> 0:18:05.200 How does the bacteria survive the antibiotics? 0:18:05.240 --> 0:18:08.400 Yeah, So there's a few ways that bacteria can survive 0:18:08.840 --> 0:18:09.840 antibiotic exposure. 0:18:09.920 --> 0:18:10.040 Right. 0:18:10.040 --> 0:18:12.159 They can either have an enzyme that chops up the 0:18:12.440 --> 0:18:16.160 antibiotic before it does its job, or they can decrease permeability. 0:18:16.560 --> 0:18:20.040 And then there's this other way, which is called antibiotic eflux, 0:18:20.080 --> 0:18:23.160 where it's the antibiotic gets into the cell and could 0:18:23.200 --> 0:18:25.960 otherwise function and kill the bacteria. But there are these 0:18:26.000 --> 0:18:29.919 special pumps that the bacteria have that recognize antibiotics and 0:18:29.960 --> 0:18:32.280 other sort of toxins and then they pump it out 0:18:32.320 --> 0:18:34.320 before it can do what it's meant to do. 0:18:34.640 --> 0:18:39.120 That's rad yeah, the way they're so smart, right, the yeah. 0:18:39.400 --> 0:18:41.840 And so that's what's going on in this case. Right, 0:18:41.880 --> 0:18:44.639 The bacteria inside this guy has a pump. So you 0:18:44.640 --> 0:18:47.600 give him antibiotics, it goes into the bacteria and the 0:18:47.640 --> 0:18:49.360 bacteria pumps it back out. 0:18:49.240 --> 0:18:51.840 Yeah, and so our natural response would be like, okay, 0:18:51.920 --> 0:18:54.280 let's just throw more antibiotics there, right, And when you 0:18:54.320 --> 0:18:56.679 do that, it makes them make more pumps, right. 0:18:56.760 --> 0:18:59.480 So there it's a tough arms race. 0:18:59.520 --> 0:19:04.320 It's the kind of antibiotic versus pathogen arms. 0:19:04.200 --> 0:19:05.080 Race, yeah, exactly. 0:19:05.600 --> 0:19:07.399 And the more you get in, eventually you're going to 0:19:07.440 --> 0:19:08.800 start seeing some side effects. 0:19:08.880 --> 0:19:09.000 Right. 0:19:09.040 --> 0:19:12.320 You can only put so much chemical in someone before 0:19:12.320 --> 0:19:13.360 there's there's problems. 0:19:13.480 --> 0:19:15.600 Yeah, And what is your idea when you show up? 0:19:15.640 --> 0:19:17.720 So I just was like, well, why don't we try 0:19:17.760 --> 0:19:19.639 to use you know, a bacteria phage, which is a 0:19:19.680 --> 0:19:21.880 virus of bacteria to try and kill this infection because 0:19:21.880 --> 0:19:24.560 it's independent of antibiotic resistance, right, And that's not like 0:19:25.200 --> 0:19:27.680 my idea. Right, They've been doing this since they found 0:19:27.720 --> 0:19:30.080 bacteria phages, or they've been trying it. But I was like, 0:19:30.119 --> 0:19:32.480 you know, it's been years since we've actually done this 0:19:33.000 --> 0:19:35.359 seriously in the United States. Maybe we should, Maybe this 0:19:35.400 --> 0:19:38.360 would be a good case to try it. And so 0:19:38.520 --> 0:19:41.080 the surgeon was like, perfect, let's try it. 0:19:41.680 --> 0:19:44.679 Okay, So the surgeon's on board. What do you do 0:19:44.720 --> 0:19:45.080 from there? 0:19:45.680 --> 0:19:48.560 The first thing is we get the isolate, so the 0:19:48.600 --> 0:19:51.760 clinical lab guy here in the hospital was like, Okay, 0:19:51.800 --> 0:19:54.480 here's your plate of bacteria. So we take this bacteria 0:19:54.480 --> 0:19:56.360 back to the lab and we need to make sure 0:19:56.400 --> 0:19:58.600 that we have a phase that can kill the bacteria. 0:19:58.720 --> 0:20:00.760 Right, ok So we've got this like, you know, fridge 0:20:00.800 --> 0:20:01.920 full of phage. 0:20:01.840 --> 0:20:05.080 And the fridge full of phages, like all different phages, Yeah, 0:20:05.280 --> 0:20:07.879 more or less. How many different phages. 0:20:07.680 --> 0:20:08.359 Do you have. 0:20:11.680 --> 0:20:15.400 Within an order of magnitude one thousand, a thousand? 0:20:15.440 --> 0:20:18.399 So how do you come to have a fridge with 0:20:18.680 --> 0:20:19.199 a thousand? 0:20:19.440 --> 0:20:19.640 Yeah? 0:20:19.800 --> 0:20:21.399 Different kinds of phage. 0:20:21.760 --> 0:20:26.040 Yeah, so you know, regular trips to the sewage treatment 0:20:26.280 --> 0:20:29.240 plant or you know, we're collecting from rivers, our ocean, 0:20:29.280 --> 0:20:32.520 water lakes. We have all different phages for all different 0:20:32.520 --> 0:20:36.320 bacteria because they're really really host specific. So it's not 0:20:36.359 --> 0:20:38.240 like I can take any Coli phage and try to 0:20:38.320 --> 0:20:40.760 kill Staph aureus with it or something. We had sort 0:20:40.760 --> 0:20:43.560 of built up this library of Pseudomonus phages and we 0:20:43.600 --> 0:20:46.600 took his sample and we basically tested all these phages 0:20:46.640 --> 0:20:49.639 on his bacteria I see which ones would kill it. 0:20:49.920 --> 0:20:53.480 And so we had phages and we've had one that 0:20:53.680 --> 0:20:57.560 was I think slightly biased, really cool and that the 0:20:57.640 --> 0:21:00.240 receptor binding site. So what the phage use is to 0:21:00.320 --> 0:21:04.440 grab onto the bacteria and recognize it was this eflux 0:21:04.440 --> 0:21:05.800 pump that we were talking about. 0:21:06.320 --> 0:21:06.639 Huh. 0:21:06.960 --> 0:21:09.919 So you know it in a sea of pseudomonas, not 0:21:10.000 --> 0:21:13.560 all of them have these eflux pumps, and so the 0:21:13.600 --> 0:21:15.960 phage is like looking for just those guys. 0:21:16.640 --> 0:21:21.119 So specifically, this phage, this particular phase that you're optimistic about, 0:21:21.400 --> 0:21:25.439 is actually targeting the thing that allows some of the 0:21:25.480 --> 0:21:30.040 bacteria to resist the antibiotics exactly. So this phage is 0:21:30.080 --> 0:21:34.880 sort of optimal to use in combination with antibiotics. Yeah, right, 0:21:34.920 --> 0:21:39.479 because either the bacteria has a pump and is therefore 0:21:39.480 --> 0:21:43.679 antibiotic resistant but targeted by the phage, or it doesn't 0:21:43.680 --> 0:21:46.160 have a pump, in which case the antibiotics will kill 0:21:46.160 --> 0:21:46.760 it exactly. 0:21:46.880 --> 0:21:47.120 Yep. 0:21:47.440 --> 0:21:49.399 It's a great theory, yeah theory. 0:21:49.960 --> 0:21:51.919 Yeah, yeah, but that's what we had to go with, right. 0:21:51.960 --> 0:21:53.960 It was this this theory and that like the thinking 0:21:54.000 --> 0:21:57.679 that the phage it could either it could kill all 0:21:57.680 --> 0:21:59.960 the bacteria, right and that would be a great out 0:22:00.080 --> 0:22:03.040 come for this guy, or it could kill a lot 0:22:03.080 --> 0:22:04.920 of them and then they could evolve resistance, which would 0:22:04.920 --> 0:22:07.439 not be ideal. But it'd be antibiotic ex sensitive, so 0:22:08.240 --> 0:22:10.440 maybe a win. And we tested it in the lab 0:22:10.480 --> 0:22:13.119 and everything looked great. So I brought this data to 0:22:13.200 --> 0:22:15.040 the surgeon. I was like, look, it seems like it's 0:22:15.080 --> 0:22:18.040 pretty good at what it does. And then he's like, well, 0:22:18.119 --> 0:22:20.399 let's try it cuz you mean, what else we need 0:22:20.480 --> 0:22:22.960 to do? So, you know, it gets the FDA on 0:22:23.000 --> 0:22:25.399 the phone and like, okay, here's a few things you 0:22:25.440 --> 0:22:26.760 need to do to make sure that you're not going 0:22:26.800 --> 0:22:31.840 to like do harm. So we did those quality control 0:22:31.920 --> 0:22:34.800 things and then then they're like, okay, cool'll do it. 0:22:34.960 --> 0:22:37.800 So we had the FDA, the institution, everyone was on board, 0:22:38.240 --> 0:22:41.160 and then all we had to do was the actual procedure. 0:22:41.520 --> 0:22:44.360