Harnessing Microbial Weapons for Future Medicine

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He also addresses the dangers of irrational beliefs and the risks of applying astrology to serious decisions Wide ranging and entertaining, What Science Says about Astrology is the first book in the new What Science says series. Available now wherever books are sold. WNYC Studios is supported by the New York Hall of Science, a hands on science center and leararning lab in Queens, focused on inspiring curiosity, problem solving, and encouraging creativity through science, engineering, and math More at nYsci. org In biological systems, microbe on microbe crimes are considered especially heinous In the science world, the dedicated detectives who investigate these vicious attacks are members of an elite squad known as microbiologists. These are their stories Today, we are turning our attention to the serial killers right under your nose and perhaps inside of it Microbes armms with weapons to eviscerate, assassinate, and detonate s What turns a microbe murdders? How do they choose their victims? and can we harness their weapons for good Today, we're talking with two biological detectives who've documented this microbe on microbe crime Dr. Glen Deusa, an expert on Bacterial Butchers AKA cell to cell interactions at Arizona State University, and Dr. Ben Larson, who just described a cannibalistic super microbe in the proceedings of the National Academy of Sciences and studies how cells behave at Renilier Polytechnic Institute Detectives, welcome to Science Friday. Thanks. I'm excited to be here. Hello, glad to be out Should I picture you both in Fedoras smoking cigarettes, looking at a bulletin board with red string? Like is that your day Yeah, probably a cigar. That's one of our labros. I think glued to the eye piece of a microscope is probably the right picture for me Glen, take me into this Ittyy bitty frightening world. I mean, do microbes have weapons Yeah, and they are weapons, but it's nots only one weapon. There's like a million different ways to kill, right? So So you can put them in two broad classes You can have a weapon like like a sword, you can keep on poking your neighbour You can have these sort of teinyini bombs you sort of Unload into the environment and then kill whoever is out there, right? So that's sort of the two broad classes can get even more complicated. you can weaponize something else, right. You can have these viruses that you can you sort of Cry along with you, benign And then suddenly decide you're deployed to attack a neighborhood And so yeah, there's there's there's a million different ways how badly I can kill out there How murderous is this community? Do all bacteria have weapons Yeah I mean, that's like a difficult question. So two levels, right? becausecause we do not know how many bacteria are in the first place, right? You know we pretty much, I think only describe about five percent of maybe most of all the bacterial life that is out there in nature. Okay. But of what we know, I think I think their are estimates depending on which environment you look at, right. So for instance, we've looked at the ocean and about ten percent of all ocean microbes do at least have one weapon. Most have many mle weapons in that they carry. But now if you look at the planted root, for instance I don't know what's happening there. That's like an entire sort of war zone. The plant root has like, I think, thirty percent of all microbes that carry at least one weapon. Wait, plant roots have thirty percent of microbes that carry at least one weapon. Yeah, exactly. So if you look at the microbiome of plantrooots, I mean, you can imagine the plantrooot is an extremely play so mic clos to stay, right? So you know the plant keeps on throwing out stuff or teiny beenie pockets of sugar, candies, etcer. that I think bacteria can go happily on. And if you are now in this amazing environment, you need to make sure you get it and your neighbor doesn't, right? So it makes sense to carry a lot of weapons out there Ben, they'reighting over territory. Are they fighting over other things I mean There can be fighting over territorory certainly, but a lot of the cells that I think about and study are fighting to get food. And so there can be know arms races where they're battling one another Or you there are all sorts of fascinating predatory strategies that exist in the protist world that I think about. So the microbial eukaryotes Give an example, give me some of those examples. Okay, so the first one that comes to mind is one of my favorites. So there is this type of cell. It's a type of dinoflagellate. you might know about these things. Some of them are bioluminescent or some of them can form these harmful blooms and become toxic. But there' a certain species where The cell actually has a structure, it's called an ocaloid, and it's basically an eye for the cell. So it's like a camera eye with a lens and a photos sensor I mean a dinoflagellant has an eye It has an eye. o, but not only does it have an eye, this cell also this type of cell has a weapon. So it's not entirely clear how they're using the eye, but people have hypothesized that it's actually using that eye to track down prey. So it's light sensing, looking for the things that it feeds on. And then it has a little harpoon gun. So it's a structure that people call it a nematocyist. That's also what people call the stinging cells of jellyfish, but in this case, it's actually a subcellular structure. So this pressurized haroon gun in the cell that it uses to stab prey and get on a little tether and drag in and engulf. So that's one of the craziest ones that I know of That sounds very advanced Absolutely. And I think that's one of the things that's most fascinating to me about all these prodce, these microbial eukaryotes is there's an incredible amount of complex cell structure and cell behavior associated you know, with things like predation and navigating environments Glenn does this reframe how we think about? microorganisms Yeah, I think so. I mean, as Ben mentioned right, like getting food, no one has thought about that until now, right? Everyone thinks o you have a weapon, you kill, you get territory happy. or you have a contested resource. You displace your weaker competitor, you get access to your port of gold and you're sitting there happily. The world is not a happy place, right? L so you will have these cycles of feast and famine, right? You might be on an amazing mutant patch, but suddenly there might be no nutrients out there. So where do how do you grow, right? You need to grow One idea people haven't thought about and I think Ben kind of put that off nicely is every other cell is a pocket of food except's this amazingly encased in a way that no one else can get it, right? How calcul peers are food. They're like peers or a snack. Exactly. So this gives me a great opportunity to jump in and talk about this cannibal that we mentioned here. So yes, tell us about the super giant cannibal protist. Okay, I'll tell you about the super giant cannibal. So one of the cells that I study in the lab right now are that the lab studies is this single celled organism, a ciliate that can form these super giant cannibal cells. And they seem to do this under conditions where small prey items become scarce. So what happens is they're in this growing population The small bacteria that most of the cells are feeding on start to become scarce and then This small subset of the population makes this choice T to grow dramatically in size, rescale the cell structure, and adopt these different behaviors and become cannibalistic. So instead of filter feeding on bacteria, they raptorially pounce on their con specifics and devour them and eat them. And so there may be some competition for resource involved. We don't really know exactly what's driving the transition. This is giving Marvel Universe vibes. Like this feels like the hulk to me, you know, where you just, I mean, how much bigger are they getting Yeah. so, you know, the seell is about Cannibals are three times as long as the normal filter feeding cells. And cell volume, we haven't carefully characterized this, but you know up to ten times the volume of the normal cells. So they get a lot bigger. I mean, it's very, very clear under the microscope if you look at these. Give us a little just so we can picture it. What does it look like Yeah, you can absolutely see this under the microscope. So What you see is mostly these normal sized cells and then these much, much larger cells next to them that they're densely packed with with protein, you know the body parts of the cells they've eaten and they run around like crazy. I think they will probably eat any big thing they can find to fit in their mouth. so they almost never stop moving except after they've caught a prey item, then they'll stand still for a little while and ingest it. Digest. They're very clear under the scope. Yeah. Well, why are some lucky ones getting to blow up and eat their specifics, as you say Sure they're they're sisters and cousins We don't know. So this is something that we are actively trying to figure out. It is It genuinely is a mystery because as far as we can tell, it seems to be this random subset of the population that's making this choice. And we really don't know what they're specifically using to make that decision, what sort of underlying cell machinery makes that transition happen Nevertheless, you know it's maintained at this relatively low level. So maybe it's risky decision. We don't really know. There's more that we don't know than that we do know at this point, I think. But that's interesting because it's only some of them. Right? So yes. does that mean that Some of them have different geneans, like is it encoded on the DNA level, how does that work? that clones, some of them blow up and others don't Yeahes, so it seems unlikely that there's a genetic basis. likeike you said, it's in this clonal population. So It's genuinely a mystery. I mean, it could have to do with RNA levels, with protein levels, with other, you know, physiological levels in the cell. And it may be very hard to find that, you know, what flips that switch. But one little piece of information that we do have is that, okay, so it's An extremely small subset, there's maybe, you know, On up to five percent of the population that we ever see in this cannibalistic form, it may be that more cells are sporadically trying to become theseese giants. so the first sign that the cannibals are going to show up is that Basically the mouth of the cell gets much bigger So before the cell body scales up, there's a bigger mouth that can maybe accommodate these large prey items And I think that these cells that are sort of an intermediate phase, they're very bad at hunting And so it ensures that you know there's this population density that's high enough that even a bad hunter can catch a prey item. And so it may be a very rare event that these big mouthed but small cell bodies cells can capture a prey item and that's required to sort of flip the full transition to the super giant state And so that might be partly limiting the number. And so it may be that there's some regular probability of the cells trying to become cannibals, and only a few really make it Are there places like where bacteria get along? Like is my armpit actually like a beautiful bastion of peace? Yeah, So if you ask microbar ecologists, I think you'll create like you know they'll always fight with each other because there's a school of thought that says, o everyone likes everyone. I do not think so. I think there's these arms races everywhere, right So essentially I think another sort of arena, as you said, is inside us, right. So there's a lot of competition that's happening in my gut right now, right? Because I just had breakfast. So maybe my microbiome is happy it's getting food. But if I had extremely fiber heavy breakfast, so no simple sugars, no corn syrup, et cetera Bacteria have to make an effort to digest that, right? That thoseose are these huge blocks of carbohydrates. not like that's not easy for bacteria to degrade, right Inside me, there's a lot of bacteria that cannot do this There some bacteria that can do this, right? So the ones that can't do that. So you know we call them scavengers or exploiters essentially have to depend on someone else, the degraders to do this. And if you don't want to do this, an easier way is well, I use my weapon, I wait for the degraders to do this and thenll come and kill you and then eat you, right? So yeah, that'' digesting my food for me I'll eat you Exactly. But I mean, the degraders might seem to be you know things are stacked against them, but no, they have an important card in this, right? They are the ones that can break down the food. they can control what goes out So essentially that happens in my gut. So I think it happ it's happening everywhere. We see these systems in wastewater treatment plants, for instance. We see that in agricultural context in the ocean It's funny, we found a lot of signatures of warfare or microbial warfare about six thousand feet on the ocean flow, right? So and it might makes more sense there, right? becausecause the nutrients there are extremely extremely difficult to get Oxygen is a problem. So yeah, so it's everywhere except it might be at different levels and different places Ben, where did you find the super cannibal So this was During fieldwor in the Caribbean on this island called Curasa, It's about thirty miles north of Venezuela. And so I had done some extensive sampling around the island looking for interesting sites. But one place I had not sampled was the lab itself And so these super giants actually came from a filter system on these water tanks that pump in water from the sea and fill up these tables that people keep animals in. and there's this disgusting filter and scraped that and lo and behold, I found some cannibals on that filter sandich. That seems right. So That's why they came. A dirty filter seems like exactly where I would find Villous beast, you know? Yeah, exactly. And for any, you know amateur microbe hunters out there, I would highly recommend fish tank filters as a great place to find interesting cells and perhaps violent cells as well. We have to take a quick break, but coming up, can we harness these microbial murder weapons for good Stick around WWNYC Studios is supported by Conn Edison. 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WNYC Studios is supported by Columbia University Press, publisher of What Science Says Aout Astrology by Carlos Orsi You may have heard the recent interview on Code Switch with Carlo Sorsi b why astrology appeals to so many people despite having no backing by scientific evidence What makes astrology so appealing and persuasive Is there any harm to believing in astrology anyway Carlos Orsi explores the importance of astrology to the history of science and the reasons it's been categorized as a pseudoscience Both empathy and skepticism Orcy illuminates the psychological and emotional mechanisms that cause people to find astrological predictions convincing He also addresses the dangers of irrational beliefs and the risks of applying astrology to serious decisions Wide ranging and entertaining, What Science Says About Astrology is the first book in the new What Science says series, available now wherever books are sold. WNYC Studios is supported by Poster House, a boutique museum in the heart of Chelsea, now presenting A Black, Posters from Black American Stage and sccreen, an exhibition centered on prominent theatrical performances and films from Jim Crow America These historical advertisements illustrate a hidden era of black cultural development when performers started to reclaim harmful narratives and demands for all bllack casts signaled a trend toward more diverse mainstream audiences On view until september sixth, learearn more at posterhouse. org slash stududios. WNYC Studios is supported by the New York Hall of Science, a hands on science center and learning lab in Queens Welcoming New Yorkers to explore, play, watch the World Cup, and more Tickets at nysci. org Glen, we've been talking about these micro murder weapons, microbial warfare Can we harness them Yeah, I mean, definitely we can, right? So One of these systems that I keep on saying is the spear gun, right? What the spear gun does is delivers toxins into another cell. We can we you know, essentially these are assassins What if you train an assassin or what if you train a hitman to find a rememove things you don't like, right? For instance, historically we've used antibiotics to get rid of undesirable bugs from our systems, except antibiotics are indiscriminate. They might just kill everyone. They might kill the good ones, right. we know that these killing bacteria are extremely specific in who they like to target or what kind of bugs they like to target, at least in many cases, what if we can learn more of this system And then engineer living antibiotics, right essentially, you can load any scaling systems and then create assassin cell that you introduce in your microbiome and say okay, go and find the undesirable one and displays it off right? So I think that's an important area of inquiry in at least my field I mean, are there specific disease candidates that you think this would work for Yeah. typh typhoid, for instance, or cholera, right? So the bugs we study are essentially the caitive agent of cholera. And one of the ways cholera can survive in our bodies or even salmoneella can breach our bodies. Saloneela is the causitive agent of typhoid can breach our bodies is one of these scaling systems, right? So If you study the systems in more detail or essentially what shields might work against this system, then essentially you can create a sort of a barrier for salmonella to not enter my epithetel cells in my intestine or cholera to not infect my gastric layer, right. So So yeah, if you could target those bacteria, I think that would be one. Wounds for instance, right. Staphorus creates these an pus like wounds in the burn patients We don't have a way to cure, but we have antibiotics, but staff always essentially becomes resistant to any antibiotic out there So if you can create living killers and you can introduce them againgain A long shot, but it is possible. I mean, Glen, you study a lot of bacterial species in the ocean That feels like a very different ecosystem from the body is there anything transferable there The ocean as a giant human gut Esentially Yeah, the reason we study the ocean is I mean yeah, we want to know more about the ocean, but I think the ocean is a simpler place to study, but you can have principles that are translatable, right? So for instance I eat a lot of food, the microbiome digest it and that's broken down and given to the cells in my body in the ocean algae produce a lot of food. bacteria now take all this food, break it down, give it to all organisms. So essentially the same processes happen in two different places, right? I think we can learn a lot of things that are immediately trans transferable, right? How do bacteria break these things down? How do bacteria kill and get nutrients out For instance stuff we do like, you know, killing to get nutriantents out that That happens in my gut, that happens in the ocean. You know, hearing you all talk about this. I think it challenges our assumptions of sort of the decision making that microorganisms are capable of. and maybe that's not even the right term, but how do you think about this Well, okay, so I think a lot about cell decision making in a few different ways. So you know, one thing I will add that may even further challenge basic assumptions about how cells work is that there are some siliates that have a well documented capacity to learn