 Bingo, we're back, two o'clock, rock, likable science, pushing the envelope in science without chief scientist Ethan Allen, think-text chief scientist, a great guy and the ordinary host, but we work together on these shows and we're calling this one the zoo and you. Why are we calling it the zoo and you? Well because we're a team, we're all a team and we're trying to get along in this universe by collaboration, you know, it's the original collaboration between us and the biome, that means all the bacteria and whatnot that we have living with us as symbiotic collaborators in this life. And there was a show on, was it yesterday, Terry Gross on NPR where she interviewed a guy named Ed Young who wrote a book called I Contain Multitudes and the multitudes are the reference to all these bacteria and he also has a blog called Not Exactly Rocket Science, he talked about that. What was really interesting and I do want to pursue it and you're the perfect guy to pursue it with Ethan is exactly what's going on at the edge of science here. We know the problem, we did not know it before but in recent years we have learned that we are a team with all these bacteria and our health is dependent on having a good relationship with all these bacteria and I guess the question I put to you is you know just exactly how dependent are we could we live without them and if we're going to live well I guess we need to live with them but how do we live with them well? Ethan Allen our chief scientist, take it away Ethan. Well they are part and parcel with us from the day we're born and they change over our lifespans. We have types of colonies of bacteria that populations alter and shift. There's a typical infant colonization and it gradually changes as we move into adulthood. Fairly stable, you can change your gut bacteria by changing your diet radically. That's usually fairly plastic that comes back. We don't actually apparently desperately need all of our bacteria. We could live without them. It would be a very different life. There's lots of animals that couldn't live without them. All the ungulates who go around eating grass, they can't digest the grass. It's their bacteria that can't digest the grass. Termites can't digest wood. It's their bacteria that digest wood. So lots and lots and lots of animals that would promptly drop dead. We probably wouldn't but the world would be so changed without our bacteria that we wouldn't recognize it basically. But how do we get them originally? I mean when we come out of our mother's womb, you are basically infected. It's an interesting point to bring up because when you, a typical vaginal delivery actually inoculates an infant with bacteria, the womb itself is actually sterile basically and has no bacteria in it. And you get your first dose basically coming out that way. And so if you were born via C-section, you actually have a rather different set of bacteria. Interesting. Yeah. No, this has actually been shown. They've actually done swabs from kids and they find out the kids' bacterial colonies are quite different from those two modes of delivery. Which way is better? Because we know that if you have, you know, a good collection of bacteria, you're going to live really well if you don't, you're not. They gradually meld back to where you can't tell in an adult necessarily which way they, whether they were born by C-section or not. So there's some plasticity in it. But probably it's not very reasonable to suspect that in these first hours, days, weeks, months, perhaps even years of life having a good start with the right bacteria that you picked up from your mom is probably a real advantage to that. Now there's two kinds. One is on your skin, right? Many, many, many, many. Well, I should say one, yeah, one. And the other is in your passages. Right. That doesn't mean in your flesh. That means in your passages where you breathe, where your blood flows, your intestine, all that. Those passages, you know, reminds me of the whole notion that we came from the sea. And way back when all of our surfaces, if you will, including the surfaces of these passageways were exposed to the sea, and we had all these symbiotic relationships. Now we have evolved into closed passages, I mean inside passageways, but that doesn't mean we don't have these symbiotic relations. And for the symbiotic bacteria live on the skin which is exposed and in the passageways which used to be exposed. Yeah, they live everywhere. I mean realistically, you say on the skin, realistically they live under the surface layers of the skin. There are some on the very surface, but there's lots more. There's about a million per square inch. A million per square inch under the lower levels of the skin. I mean they're everywhere. They're bacteria, they outnumber your own cells 10 to 1. You have probably 20, 25,000 genes, but the bacteria in you probably have 500 times that many genes. So assuming the symbiosis, then we are dependent on all of those genes. They do good things for us certainly. We can digest very simple sugars, short little tiny sugars, the little monosaccharides and little bit bigger disaccharides. But the big complex sugars, we can't digest. Very fortunately for us our bacteria can digest those. Just like the grass. And they break them down for us and allow us to eventually digest the simpler ones. So it's, I mean, they do a lot of good for us. If your bacteria get out of whack, they can start causing trouble. Your intestines get a little bit leaky. You start having fluids that shouldn't be sort of inside you. That is away from your intestines. You're talking about diarrhea? No, no, they get into your body and cause inflammation. It's thought they maybe underlie that kind of problem, a bacterial problem, a microbiome problem, may underlie autoimmune diseases, diabetes, all these kinds of conditions. Well, yeah, and we don't know yet, do we? Right, right. What you say makes. But in fact it could be, and hopefully in a few years we will know, whether a bad biome will give you all these other problems, including immune problems, which leads to everything else. Right. So how do we find out what our biome is? You know, I can take my DNA, I can swab my mouth and send it in, and they'll give me a complete report, and they know a lot. They know, you know, they know 100,000 years of my background in one swab. Right. But, you know, with the biome, we don't have that technology, or do we? Well, the problem is, again, one, the human genome has been pretty well studied. So they know what human genes are, and they can identify those pretty quickly and easily and tell you what yours are. But it's not just you've got one bacteria, or 10 kinds of bacteria, or a thousand kinds of bacteria. There are probably 100,000 kinds of bacteria in you, many of which have not been identified yet. And mine are different from yours? Yep. We have different sets. We may have some strains in common, but we have different amounts of those strains. We have different outliers. So yeah, there's so much more information. They can't go and sequence 100,000 different organisms. Well, my organism is going to be related to my DNA. What I mean is, if my 100,000 years of experience, and it's probably more than that on the planet, makes me this way the way I am, does that mean that I'm carrying bacteria that is different from the bacteria you have, because you have a different 100,000 years behind you? Now, that's an interesting question. I don't know how much our evolution shapes are the biomes that we carry versus our personal experience. Well, put it this way then. I'll change my question. If I take your bacteria, am I going to be more like you? It is interesting, actually, if they find people who have inflammatory bowel disease, that kind of stuff, Crohn's disease, and they essentially take, and this sounds sort of weird, but they do what's called fecal transplants, and they basically take some poop from somebody who's healthy and implant that into the intestines of the person with Crohn's disease. They get a lot better. You know, this is a family show. On the other hand, fecal transplants happen to be the center of this whole discussion, so get used to it, girls. No, I mean, it's true that when you get, if you take a lot of antibiotics, right, and knocks out a lot of your bacteria, and you have digestive problems, typically after that again, that can be set right by sort of recolonizing you with a proper balance, you know. And it turns out that micro and biome balance is very predictive of things. Infants who are malnourished in third world countries have a very different biome than infants who are well nourished in those same countries, and they're neighbors basically. Can you explain that? Well, probably, I mean, their whole diet has been different, and that's given a different environment within their whole system, and there are different things we'll colonize that. You know, if it's not been as rich in some substances, or it's been overloaded with other substances, different kinds of bacteria are going to go for that. What I'm getting here is that, okay, you come out of your mother's womb, you are immediately covered and infused with a certain biome, maybe from her, you know, the non-sterile part of her, and maybe from the air, who knows what, and there you are. You're outfitted with your biome. Okay, but then you go out and you start eating, and you may eat this kind of food of that. You may live in a place where the food is different than the other place. You may have contact with different people and touch them and breathe air that's different, so the result is your biome is going to be different. You are gathering new bacteria all the time, and some of them will colonize, some of them won't, but your mix, I mean, talk about fingerprints and the signature of an individual human being, your biome is going to be so complex we don't even know how complex. They can actually do that, no, they can take a fingerprint and sample the DNA, not from you, from the microbes they are, and link it to individuals now actually, and it is unique. But getting the infants again, it's intriguing, and Ed Young mentioned just in his book that mother's milk, it turns out, has all these, a bunch of it, it's actually these very complex sugars that we cannot digest, and these sugars are there apparently for one reason to one reason only, it's to feed the infant's microbiome. And so of course, again, if you turn on and give an infant cow's milk, you know, that doesn't have that same mix of things in it. So mother's milk would be better. Oh, absolutely. Because it's dedicated. Yeah, yeah, it's fine-tuned to adjust that right mix. Well, we get a benefit out of it. Oh yeah, it's not just for the bacteria. Well, but the bacteria then make us thrive, basically, as infants. So yeah, so I mean, it's a symbiosis, as you say, a mutualism, as it were, you know. Okay, but we've been raised, you and me and everybody around has been raised to think the bacteria are germs, bacteria are not good, you don't want to have bacteria, you have, you know, penicillin and many other drugs that dedicate it to killing bacteria. Right, that's not so. Very few bacteria are all and all bad. Now, as Ed points out in his book, it's all a matter of time and place. And even nice, good, healthy bacteria in one place can be very harmful if it gets into another place or another time, basically. So a good gut bacteria for you probably isn't going to be so good if it's sitting in your brain, you know. Yeah. This is getting scary. So much so that I need to take a short break just to sort of integrate and digest, if you will. Exactly. Everything that Ethan has been saying is Ethan Allen, our chief scientist, the host of Likeable Science. We're talking about the zoo in you and why not. For a very healthy summer, watch Viva Hawaii. We're giving you the best tips and with our best health coach here. So, Viva health coach. Viva la comida saludable. Aloha. My name is Josh Green. I serve a senator from the Big Island on the Kona side and I'm also an emergency room physician. My program here on Think Tech is called Healthcare in Hawaii. I'll have guests that should be interesting to you twice a month. We'll talk about issues that range from mental health care to drug addiction to our health care system and any challenges that we face here in Hawaii. We hope you'll join us. Again, thanks for supporting Think Tech. Hello. I'm Marianne Sasaki. Welcome to Think Tech Hawaii, where some of the most interesting conversations in Honolulu go on. I have a show on Wednesdays from one to two called Life in the Law, where we discuss legal issues, politics, governmental topics, and a whole host of issues. I hope you'll join me. Oh, my God. That's just fabulous to have this conversation with you, Ethan. I really enjoy it. So, let's talk about the deeper level, the deeper meaning, the cells of your body, and the relationship of bacteria and virus, whether virus works in the same way, because with bacteria is complex, virus would be much more complex. Well, viruses are actually a lot simpler in some sense. Oh, good. Right. I mean, bacteria are cells, somewhat like our own cells, so they have a membrane around them that got nuclear material. They have a whole cytoplasm of stuff that's within the cell. A virus is just some reproductive material in a shell, and that's all it really is. And it's, they're very tricky. They're not even really alive for much of their existence. You'd rather have a bacteria than a virus, right? You can kill a bacteria. Viruses tend to be a little tougher. But the viruses need the bacteria or our cells to live. But our cells themselves are actually, it turns out, fusions of bacteria and other cells. Probably, actually, our very cells themselves are probably originally a fusion of a bacteria and a so-called archaea, an archaeon, which is another whole group of organisms look like bacteria, but are at least as old, if not older, and run differently. Trying to tell me that we are the evolution of the bacteria that we are actually made of, I mean, not our hosts. I mean, our synergistic bacteria, but we are really bacteria. So when somebody calls you a bacteria, there's some truth to that. Well, I mean, really, for something like 99% of the time that life has existed on Earth, the only things that existed were essentially bacteriotype creatures. Multicellular creatures are sort of a quick flash in the pan in the history of life on Earth. Haven't proven their staying power at all. Oh, that's exciting, but also disturbing. Yeah, I mean, the world was really built by and run by those things for a long, long time. But so, yeah, the energy sources for all our cells are these little so-called organelles called mitochondria, and all of our cells have these mitochondria, and then they crank out the energy molecules for us and all. They have their own genes. They reproduce independently of the cells. They divide by themselves within your cells. They were probably, at some point, another organism that got incorporated at some point, same with the chloroplasts in plant cells. Those were probably separate. So the miracle is that the bacteriotype cells got together and became us. At some point, there were some pretty amazing fusions that went on. Wow, wow. Okay, so how can I tell the difference between a bacteria that I like and a bacteria that I don't like? I mean, can I look at the microscope and identify the goodies and the baddies? Not necessarily. Again, there are bacteria that are fine in modest doses for you. You can have them. They live quietly. Then for various reasons, they go berserk at times. And we don't always know why, why their population suddenly explodes, and you're having a few staff bacteria on your skin. That's nothing particularly harmful, but a bad staff infection can be lethal. So, Ed Young puts it, you know, it's all about the right time and the right place for bacteria. You want to keep them happy where they belong, basically. He talked about, in the program, he talked about C. diff. What is C. diff? So that's a bacterium that is very good at colonizing us, particularly our intestinal systems, if we've had them sort of fleshed out with multiple doses of antibiotics a few times. And C. diff then gets established. Everyone else keeps a lot of other bacterial populations at bay, doesn't let them establish themselves, and keeps you with very nasty diarrhea and can kill you eventually. C. diff is not a good one. No. In general, C. diff is one of that tiny minority who basically, I don't think you'd really want them at all at all at all. And he and Terry Rose talked about how you take a, what do you call it, a fecal transplant, and that would correct the problem with C. diff. 97% of the time. Right. If you do that, yeah, you'll get a much, you can hopefully then, you know, re-establish your environment in there for a healthy community that will then, your healthy bacteria will keep the C. diff away. They'll basically won't let the C. diff in. We'll kill them off as soon as they show up. But the comparison was that if you went to a vitamin store and you bought what do you call it, biotic drugs, bioded drugs. The prebiotics. The probiotics. Probiotic drugs. That would not be as effective. That does not achieve 97%, more like 25%, which means that you do better with the fecal transplant. Yeah, yeah. The probiotics are apparently pretty limited classes. They're small numbers of acury. You're sort of, they're a little drop in the bucket kind of thing. And they're ephemeral. Yeah, right. They don't stick with you. They typically don't get well-established. So, yeah. The fecal transplant is weird as they sound, turn out to be an increasingly popular and increasingly, why they recognize treatment for being, that's pretty effective against a lot of things actually. So why don't you just make a little pill, a capsule? Okay. If the necessary biota, is that the right word? That you take and keep everything in balance and get healthy when you're not so healthy and just hit the ideal that way with a little pill about that big. Well, it's real tough. There's a fair amount of sort of numbers and mass that you've got to deal with there. What's healthy still isn't really well understood. The things besides the bacteria and the fungi and the protus and the viruses. Oh, I forgot about the fungi. Yeah, it's going to be a very complex pill to make up and to pack enough of the right things in together tight enough to keep them all viable in a dry pill form. What he is saying though is that one day we will have a pill like this. Probably. Probably. We'll know more. Oh, yeah. Because it's like my sense of it is that we, science did not really deal with this issue only a few years ago. We started really dealing with it and now that we're dealing with it, we realize that we're at the very beginning of the science. We have a long way to go, but we know what we have to do. Yeah, we've just sort of, you know, cracked a window on it and can now look out and say, ah, here's a huge frontier that we have to deal with. And it's happening sort of everywhere. If you look, the oceanographers have discovered the ocean is just filled with viruses. Viruses by the gazillions. Viruses no one had any idea about just a few years ago. And strains of virus that we have never seen before. Yeah, and most of them don't do anything bad to us. They may perform vital functions for all we know for the sea life. The paint from the oceans. Yeah, so this stuff, and as you say, the technology now, we've gotten gene sequencing up and running to sort of a model T stage where we're suddenly cranking, we're able to crank these things out pretty good. And so we can actually look at this now in some sensible fashion. But there's sort of a huge universe still out there to explore, basically. Well, as in so many other things, it seems to me the solution here is because what we have, it's a universe and it's millions and billions of things and different kinds of strains and different kinds of material that we have to not only identify, but we have to distinguish and we have to sort it out and find out how it relates to each other. I mean, it's really hard to complicate it. But also, I believe that in the laboratory, when you start isolating all this stuff and really sorting it out, the one thing that's critical is computer programming. It's keeping a database, a big database, a huge database. What do you think? This solution or this advance, if you will, medically is going to be dependent on the marriage of the biome and computer science. Yeah, certainly it's going to require big data. I mean, all we know now is pretty crude correlations. We know certain immune diseases and immune failures are associated with certain kinds of characteristics of microbiomes. But whether those are the ones causing the other, we don't know whether they both have some other causative thing that both just effects. That's not at all well understood and it's going to be a very data intensive laborious process to start tweaking factors one by one by one by one and seeing what is the causative agent or agents there. Sometimes you wouldn't know unless you had, you look at the cocktail, all the factors working and then you find out if you have a certain combination of factors, you get this result. But except that the number of possibilities are just enormous, huge. And we have to know this. Right, yeah. And now, of course, the new thing is this whole idea of synthetic biology, right? What is that? So scientists are now able to start building new genomes themselves. They can create genomes that never existed before. And they have taken shells of individual cells and stuck whole new genomes into them and had these created, these new organisms that are completely artificial. These organisms never existed. The boys from Brazil. Yeah. I don't mean the Olympics. So if we find out, if we, if I use our science, you know, we don't get distracted because it's really important for the future of humanity, I think. If we use our science and we figure out the relationship of what did you call it, tailor-made DNA, and then we bring in the whole study of tailor-made biomes too, then we can make people really healthy. Not only determine their characteristics, but determine their health characteristics, the way their bodies work in terms of immunity, in terms of strength, in terms of, you know, what weight they have, how well they process food, how well they live in general, how long they live. And it sounds to me like a lot of the answers here are not necessarily in modifying DNA. It's modifying the genome, which is less, you know, disruptive somehow to these species. It's not necessarily modifying our own DNA. It's in learning more about our microbiomes and modifying their DNA. Their DNA, yes. There you have it. And it wouldn't be a surprise to me that the science, instead of focusing on human DNA, starts focusing on biome DNA instead. Right, right. And as you say, it has, it's known that it can have profound effects. I mean, they can take mice that tend towards obesity and essentially clean them all out and infuse them with the microbiome of mice that tend towards being lean. And these mice will then lose weight and become lean mice. And become healthier in the process. As long as they've got a decent diet to work with. These are exciting times, you know, and you say to yourself, there's really no downside to this kind of science. This is all good. Tell me about the downside. I mean, like any technology, you know, it's subject to abuse. And I was on, you know, somebody can figure out how to start designing some super bacterium that's going to be very, very nasty to people. Unleash it, you know, in some sense it's a much easier game than blowing up a big bomb somewhere, you know. That's true. And if you've figured out well in advance and figured out how to make yourself immune to it and your friends immune to it. Then you have the advantage. Yes, you have a huge advantage. So yeah, or developing some kind of process where you kill all the bacteria or modify the bacteria in a bad way, even at distance. And now, you know, I'm a goner because I can't live without my bacteria. Yeah, that's a pretty, that's a pretty tall order. Bacteria are so diverse. So they live in so many different places. It's hard to envision that. I'll find some new ones. But this whole thing of the dual use technology now, you know, technology can be used for good and used for ill. It's a very, it's coming to the fore more and more in science now. And it's a thing that scientists have to grapple with. You know, if you begin working in this area, how do you, what do you do and how do you do to ensure that your work gets sort of used for good and not for ill? You know, as you begin to put stuff out and share it with a broader public. Moral questions. Yeah, yeah, yeah, they're whole issues. A whole new area of science really in our lifetimes and a whole new issue of moral questions and risks for that matter. Thank you, Ethan. It's been wonderful. It always is to talk with you about these things so stimulating like Mr. Science when I was a kid. Thank you for being my Mr. Science. Well, thank you, Jay. Always a pleasure to be here. Really enjoy it.