Cole Hons: Greetings fellow Homo sapiens, and welcome to The Symbiotic Podcast. We're here for our third season, which is all live in our studio out at College Heights in State College. And we're super excited today to introduce you to our guest of the hour, who is part of our game changers and risk takers season. But before I do, I just want to let you folks know that there is a chat just to the side of the video there. And please join in the chat if you wish you can be anonymous or you can share your name, and you'll be able to enter questions into the chat for our guest.

And at the end of our conversation we will look at those questions and whichever ones are voted to the top, we will ask live so you can hear answers to your questions. And if you just want to look at other people's questions and vote those up, you can do that as well. So, with that out of the way with no further ado will introduce our guest today, Dr. Laura Weyrich, who is an associate professor of anthropology here at Penn State and a member of our Microbiome Center at the Huck Institutes of Life Sciences. Hello, Laura.

Laura Weyrich: Hi, thanks so much for having me.

Cole: Thanks so much for being here. It's great to see you.

Laura: Yeah, likewise.

Cole: It's been really fun getting to know you a little bit as we've been working on a video about your work and reading about your work and learning about your history. Just so excited to have you here today. We have an anthropologist in the house today from College of Liberal Arts, which to me at the Huck, it's something I'm proud of, that we are broad in that way. That we're not, with the life sciences, we're really coming at it from many different angles, including anthropology. And I just love what anthropologists bring to the table. So, I'm super excited to hear a bit about your work and about you and to share that with our audience.

Laura: Awesome. I'm excited too. It's nice to be representing anthropology and life sciences. It's great.

Cole: Right on. So, Laura, before we kind of launch into our deeper conversation, I just want to ask you a little bit about yourself as you were growing up. I try to do this with all our guests. This season is called risk takers and game changers. And would you consider yourself either of those things, as you were kind of growing up as somebody who took a lot of risks or changed up the game in the world around you?

Laura: I think if I had to pick one, I'd probably be a game changer. I don't like doing things the way they've always been done. I always like taking new approaches. When I was a kid, I wanted to be a medical doctor and then watched my grandfather suffer from Alzheimer's and thought, gosh, I don't want to be a doctor. I want to be a scientist. I want to be somebody who creates new cures for treating these diseases and deals with prevention for them, rather than just treating symptoms and treating a disease after it's happened. So, I think I'm more of the, I don't know, going against the grain and swimming upstream mindset to try to change the way we think about the world and change the way we do things.

Cole: Very cool. Yeah. I can relate to that. Well, I think that's actually beautiful too, that someone in your family that you had that personal experience. I think many people who go into these fields of trying to create cures have stories like that. So, can you tell us a little bit about your journey of how that desire to change things and make a difference led you on a path that brought you into anthropology?

Laura: Yeah, absolutely. I grew up in a small town in Sturgis, South Dakota on a ranch. So, I'm not somebody who comes from a big city. And I was really always interested in the natural world and how it changed. And went, again, to college, to be a medical doctor and decided this is not for me. I really want to be a scientist and I really want to create new cures. And I was lucky enough to start working in a microbiology lab, which is why I'm rooted in the life sciences. And so I'm a trained microbiologist at the core. And so I've done a lot of research on microbes that live in soil, microbes that are used in fermentation.

And then eventually did a PhD here at Penn State in the biochemistry, microbiology, and molecular biology department. And there, I was really able to hone some skills on the microbiome, these beneficial communities that live in the body. And that was really my passion. I don't know, when I started doing research on that I never looked back. I really wanted to understand these diverse microbial communities and how they relate to disease and health. And how we might be able to use those and leverage those to really improve our health moving forward.

Cole: Very cool. So, something about those little microbiomes just really appealed to you. It spoke to you.

Laura: It makes a lot of sense to me. We think about bacteria being bad or being germs, and we need to kill them. There's all these things that kill 99.9% of all the microbes. But that's really the wrong attitude to have. A lot of these microbes are beneficial. And in fact less than 2% of the microbes, we know today are ones that we work with in the lab and that we might consider disease causing. Most of them are beneficial and underpins so many of these processes we take for granted in the world.

So, it made a lot of sense to me that there were these kind of invisible factors or invisible microbes around us in the world that are contributing to things that we can't see, but we understand. We know the nitrogen cycle happens, but what's actually driving that? Well, microbes are underpinning a lot of that. And we know we get cavities, but why do we get cavities? Well, it's microbes that underpin that, right? So, it makes a lot of sense to me to think about these microbes that we can't see, but we know are actively causing things that change in our life.

Cole: Right on. Very cool. I wanted to ask you how you ended up working on oral microbiomes in particular.

Laura: Yeah. I did my PhD looking at infectious disease and looking at whooping cough specifically, and how the microbiome changes when you get disease and how you might use the microbiome to prevent disease. And I was doing a lot of mouse model research, and again, realized that we have a lot of problems that we're trying to use mice as analogs for humans. Mice are very different. And if we think about their bacteria, they're even more different. Mice are doing all sorts of weird and wild things, including eating their own feces. That humans just don't do. So, if we really want to understand how the microbiome changes and how it shifts, we really need to look in humans. But how do you do that, right? Do you have massive clinical trials or massive human studies? Or can you use ancient DNA? And can you go back into the past and look at these natural human experiments that have already occurred?

And so I looked for postdocs using humans as natural model systems to really understand how microbiomes change and was lucky enough to land a post at the University of Adelaide at the Australian Center for Ancient DNA. And the weird thing about ancient microbiomes is they pretty much only preserve really well in your mouth. They don't preserve well in your gut or on your skin. Obviously your soft tissue will decompose after you passed away. But these bacteria on your teeth are calcified in place in this really hard rock like matrix, which is kind of like cement. And so it'll survive along with bone in the archeological record. And so we have a means of going back in time and going around the world and looking at these microbes in our mouths and how they've changed through time.

Cole: That's fascinating. That's just so cool. That kind of cool science stuff that reaches through the public with you can picture NPR and little kids getting excited about digging up bones and scraping the teeth and what can you find on those teeth? Really cool stuff. So, when you started to dig deeper into the oral microbiomes and looking over time, what were some of the earliest findings that you had that kind of made you go, aha. This is really interesting. This is really something.

Laura: Yeah. Some of the earliest work that we did really showed that people who were hunter gatherers a long time ago had very different oral microbes than people who were practicing agriculture, 7,000 year ago in Europe, for example. And that those microbes were even very different from people who live during the industrial revolution compared to what we have today. So, these microbes have been changing along with us through time and all of these changes that they've been adapting to are inherited in us. We transfer these microbes from mother to child.

We pass them down just like we do our own genes. And so that for us was a really big aha moment. Like if we have this history encoded in our microbes, then we need to understand that history because it probably is really the origin to many of the disease issues that we have today. So, if we can understand that origin, if we can retrace that history, we might be able to undo it, or we might be able to fix it if we can understand the origin.

Cole: I remember in our conversation leading up to this, as I was learning more about your work, we had a little Zoom and you were giving me some background and there were some fascinating details that stick out to me. One was about this idea that you can look at modern people today. So, maybe some indigenous folks living kind of close to the land in a lifestyle that's closer to a hunter gatherer style perhaps, or one that through anthropology might be considered to represent a more ancient style of living. But that it's not necessarily a good model to look at today because so much has changed over time. Could you speak to that a little bit?

Laura: Yeah, absolutely. So, a lot of microbiome research today uses indigenous people as proxies for ancient human populations. And we think that's highly problematic. And I want you to just picture for a second, the ancestors that lived in Great Britain 500 years ago. They're still living in London, they're still living in cities. They're still working on things. They're still going to markets. That's very different from say, people living in the middle of central Australia today, living in the bush. Or people living in central Africa. The [inaudible] are a group of people that are used very frequently in microbiome research as sort of this indigenous group that's meant to be similar to pre-industrialized humans.

And we think that's a very different lifestyle than pre industrialized humans actually would've had. So, we really need to use ancient DNA and go back in the past of industrialized populations if we really want to understand how industrialized diseases, things like obesity and diabetes. How those have originated. Sure, we will gain information from working with indigenous communities and understanding their microbiomes. But that is likely a very different history than what we see in industrialized populations. We shouldn't conflate the two.

Cole: Right. Right. This brings up another topic we had spoken about in terms of ethics and protocols and practices. And I understand that one or two of the ways that you are changing the game, I would say as your strong advocacy for certain ethical principles involved with microbiome research and also with some protocols related to the standardization of decontamination that really could use some work. Could you tell us a bit about those?

Laura: Yeah. I had the fortunate luck doing a PhD of studying bioethics as well as the science. And so I like to really bring in the ethical, legal, social implications of our research into what we're doing. And so right now in the ancient DNA space, I'm really fortunate to work with a group of indigenous and non-indigenous scholars as part of the ancient DNA ethics project. And what we're really trying to do is bring in indigenous voices and let them lead the conversation in ancient DNA research. Often we think of ancient samples as samples or skeletons, but these are people, these are our ancestors. And so we need to let the folks who have relationships or arrangements with those ancient individuals guide the conversation and guide the research that we're doing today. So, we're really providing space and time to let those conversations happen and ensure that we're arguing and pushing for ancient DNA researchers to really make ancient DNA research community based rather than just basic foundational biology based.

There's a lot of implications for descendant communities today and we need to let them be part of that scientific conversation. So, we've worked a lot in that space. We're also working on that space in modern microbiome research. So, we're thinking about how microbiome researchers should be working with indigenous people today. I would argue that people should have ownership over their own microbes, especially if they've been living a lifestyle that selects for and curates different types of microbes. We've put work into that. And so we want to ensure that indigenous communities we work with have benefits, have ownership, have rights to their microbiomes and the data that comes out of that. There's a lot of microbiome researchers using microbiomes from indigenous people as a tool to think about repopulating microbes that have been lost in industrialized countries. That's a really cool idea, but it also opens the door for a lot of exploitation of indigenous people to take their microbes and use them for benefits that don't necessarily benefit those communities themselves.

So, we want to make sure we're watching out and ensuring that research is beneficial for all and not just some. And last but not least, we think a lot about contamination and think about how our results could be driven by the microbes that are living on the benches and living on our skin. So, there's been a lot of microbiome studies that don't publish controls, which sounds bonkers for our scientist, right?

Cole: Yeah.

Laura: And this stems from the early human genome sequencing where it was so expensive to sequence a sample. So, you didn't have negative controls, you just paid for your one sample to sequence it, because that's all you could scrap together. And so we really have to change the game in that and really think about what is the contamination and what are these microbes that live in our water and live in our regions and live in our labs and live on our skin and in our lab coats, how do those get into our experiments.

And how do they alter the signals that we see. We really want to make sure that we're producing robust and rigorous microbiome research moving forward. This is an even trickier issue in ancient microbiome research, you can imagine that somebody's oral microbiome may also be mixed with soil microbes. So, it becomes really important, we can tease apart those signals and really get reliable ancient microbiomes.

Cole: Wow. Good for you. That's all fantastic stuff. As you're explaining that to us, it's reminding me of how new this particular branch of science is. And we discussed that too. And you had me looking up some research and I found the year 2005 is what I found a certain company finally, they went from, I think it was 96 data points along with the 96 strands and suddenly went up to 10 million. And everything came down to about a thousand bucks to what's the right terminology to-

Laura: To sequence the DNA.

Cole: To sequence. Thank you very much. Yeah. I work with all these scientists and sometimes I stumble over my words.

Laura: That's okay.

Cole: But just to think from 96 to 10 million sort of overnight and for the cost to just drop. What did it cost to sequence DNA prior to that, do you think?

Laura: Yeah, I mean, when I started in this field, it was impossible for us from a cost perspective to do the analysis that we're doing today. We were using very early methods and high throughput sequencing. So, we're using 454 for those of you who are familiar with that. And now today we can do the DNA sequencing and get 100 to a thousand times more DNA for sometimes the 10th of the cost, depending on what we're doing. So, it's made it so much easier to reconstruct these microbial communities. And in ancient DNA space, I mean, this was not even possible until really 2012 and 2013.

So, we published the first paper looking at ancient oral microbiomes, using high throughput sequencing in 2013. And even that was a nightmare because a lot of companies producing lab reagents, what they'll do is they'll irradiate their lab reagents to make them sterile, but that doesn't remove the DNA. It just fragments and it makes it really tiny, which is exactly what ancient DNA looks like. And so for us, reagents were way too dirty and we really had to get a good handle on contaminants and what was in these reagents before we could really suss out what was indeed in ancient oral microbiome. So, for us, this is even younger, like we're in the 10th year of this research really. So, it's good to think back about how far we've come, but also how far we have to go.

Cole: Yeah, absolutely. Well, I'm really glad that you're one of the forerunners in this field here that you're so ethically minded. Because so often you think about a business, let's say that grows really fast. And you think about going 96 to 10 million and just how much growth and things scale beyond belief and super fast. And people can forget all those little ethical concerns, especially if there's a profit to be made. And I think it is so important that both of those things you're working on, that the science is good and you're really thinking it through. And also that people are thinking about the ethical dimensions. But as you talk about how clean everything has to be, you're making me think of the video we've been working on about your work. We've got a little sneak peek preview today of the next life from all angles video that we're making here at the Huck Institutes of the Life Sciences, our comms team.

So, I'm going to ask Dan to cue that up. We're going to watch just the first couple minutes. The full video is going to be about five, but it's taking us a while. We had to get some footage from France because we didn't have the time or money to decontaminate our stuff. We had to get some footage from France, from a crew that came in and they're going to include your lab in. I love this, the title of this documentary they're working on, neolithic cuisine from a French company, I'll call them Grand Angle, although they probably pronounce it differently over there. So, it's just lovely to see that footage, even though we couldn't get into that particular lab. So, Dan, why don't you cue that up please? We'll let our audience take a quick peek at what it looks like inside the Ancient DNA lab at Penn State.

Narrator: What can we learn from a box of teeth? Well, if we know where the teeth came from, and if we have access to advanced scientific instruments in a decontaminated meticulously clean lab, we can learn quite a lot.

Laura: When we study teeth in my lab, we're studying more than just the teeth. We're studying the microbiomes on those teeth, if we can figure out who they belong to.

Narrator: Laura Weyrich is an associate professor of anthropology at Penn State and a member of the Huck Institute's Microbiome Center.

Laura: Microbiome is a community of bacteria, archaea, viruses, produce and parasites, all these microscopic organisms that live in a particular environment. And one of those environments is the human body. And so you have a microbiome that lives on and in you. In fact, more than 50% of your cells in your body are actually microbial. So, it turns out you're more microbial than you are human.

Narrator: With the development of NextGen sequencing technology, whole new areas of research opened up for scientists, including the human microbiome among other exciting aspects of discovery. This rapidly emerging field holds potential to help us treat and prevent diseases and live healthier lives.

Laura: We study the microbiome in the mouth because we think it's really important, not only for oral health things like cavities and periodontal disease, but it's also really important for systemic health. So, things like Alzheimer's and colon cancer and arthritis have also been linked to the types of microorganisms that live in our mouth. So, if we're going to understand how we improve human health, we need to think not just about microbes that live in our gut, but also about microbes that live on the surface of our teeth and on our tongue. In fact, microbes that live on the surface of our teeth are in direct communication with our immune system and with our bloodstream. So, it's really important to understand what those microbes are and what they're doing.

Cole: I hope y'all enjoyed that little sneak peek into our video. Stay tuned. We'll be finishing that up in the next week or two. And putting that out on YouTube, along with the other videos in that series, I hope you check them all out. We're really trying to feature these scientists here at Penn State that are doing wild, exciting things, changing the game in science, helping us to understand more about our world. And a lot of these scientists are doing things with really amazing implications. Let's talk about the world in the microbiome a little bit.

Or let's talk about what people would typically think of when they think microbiome. I think a lot of folks might think of an aisle in the supermarket where there are certain supplements or something that they need to take for a healthy gut, you hear that all the time right now, right? The healthy gut thing. But as I've been talking to you and some of your colleagues about that, it's a different story than maybe with the marketing and advertising folks in that industry are talking about. What do you think of all that stuff, about what's a healthy microbiome?

Laura: Yeah, that's a great question. I mean, everybody has a slightly different microbiome. There's no such thing as one type of microbiome. So, healthy is a spectrum. And yeah, I think most people think about these pills they can swallow or yogurt. That's the other thing, right? Some sort of probiotic in order to fix their guts. And in fact that's probably a drop in the bucket as far as things that we can do to really improve our health. The research says it's more about plant diversity and the types of plants you're eating and also about grass fed type meats and really going back to all natural diets. And it's also just not about doing that a couple days a week. You have to do that all the time.

Folks who eat junk food two days a week and eat healthy five days a week, still have the same gut microbiome as people who eat junk food seven days a week. So, it's a bit of a misnomer, I would say in the field, that's really linked to marketing and to the way the microbiome has become embedded in our culture. I know a lot of people, when I talk to them about the microbiome too on their teeth, everybody's like, okay, great. So, I don't have to brush my teeth anymore. I should let these microbes grow. And so I think a lot of people are thinking now about, okay, well, what are these bacteria on my teeth? And do I need to brush and do I need to floss? And do I need to use mouthwash?

And in most industrialized countries, we have awful oral microbes. We've really kind of selected for a diseased state in our mouth. We shouldn't expect to have cavities and periodontal disease. That shouldn't be the norm. And in fact, dentistry is kind of just trying to keep those microbes tamped down enough to keep you healthy. And we want try to change that game and change that logic, and really say, let's put in some healthy microbes. And those healthy microbes are not going to come from yogurt. They're not going to come from a pill. They're going to come from people who have naturally really healthy mouths. And so we're going to be developing transplantations and probiotics that come from taking microbes and people with really healthy mouths and transplanting them, or moving them into people who have more problems with carries and periodontal disease. So, people probably don't think about swapping plaque when they think about treating microbiomes, right?

Cole: Yeah. Very interesting. You were telling me earlier again, as we were working on that video, et cetera, that colonialism perhaps played a pretty big role here, as you look through ancient history towards modern history. And I found it very fascinating that we know now through your work, that Neanderthals had extremely healthy teeth and that's going to be in the video too. We didn't have time to get all the Neanderthals stuff in there, but it's coming. So, could you speak to that a little bit? And what happened? Why do we have all these problems in the modern world that the Neanderthals did not seem to have?

Laura: Yeah. I always tell people, I wish I had teeth as good as a Neanderthal. Most of them have brilliantly strong teeth. No cavities and carries. They can [inaudible] have them. There's a group in Neanderthals, for example, that ate a lot of acorns and have a lot of problems with cavities. But for the most part, they have really great oral health. And you can liken this to maybe your domesticated dog compared to a Wolf. A Wolf has in general, pretty good oral health. Whereas your dog, you might have to take it to the vet to have his teeth cleaned and they might have periodontal disease. The same thing is going on in humans today, right? So, very ancient hunter gatherers and Neanderthals as a proxy for that had really great oral health, but they're forging most of their food.

They're living a very connected lifestyle to the environment around them. And in Europe and in places where people start practicing agriculture, we see this big shift in the microbiome, in our research anyway. And we think that continues to change when we get to industrialization. And we think a lot of that is associated with sugar. In fact. And so sugar starts becoming much more accessible in Europe. In the 1600, 1700, people are eating lots of sugar. It tastes great. We're putting it in our drinks. And so we really think that sugar probably negatively impacted Europeans microbiomes anyway. To the point where today, if you're reading a dentistry textbook, you're taught about one type of microbiome and that's this diseased European microbiome. Now, if we look at indigenous people all over the world, they have different microbiomes. There's some microbes that are shared across everyone, but a lot of microbes are different and they're completely tied to people's communities and environments and lifestyles.

So, the colonial era, when Europeans were then spreading all over the world and spreading disease, they were also spreading other microbes too, we think. And so we're really trying to understand what was the microbial diversity in people prior to the colonial era and how was that maybe associated with health or disease in those populations. And then how did it shift when Europeans started arriving in all these different places. And not only arriving with their microbes, but also arriving with diets and with sugar and things like that, that will continue to select for, and enhance this sort of European diseased microbiome that then spreads around the world today. That's our working hypothesis. And we really think we have an opportunity here to provide information and provide feedback for communities that are going through this industrialization and going through colonialization today. We can learn from these mistakes and not necessarily do them again.

Cole: Right on. Before we start looking into some questions from our audience here, there is one fun little fact. I thought of it as a fun fact, you talked about in Australia, some tribal, indigenous, Australian, Aboriginal people had a very curious microbiome, which really seemed to epitomize for me, it really stood out as human beings, adapting to the environment and their oral microbiomes, just being incredibly differentiated and adaptive to where they were living in balance. And I think you know the one I'm talking about.

Laura: Yeah, absolutely. It's one of my favorite findings as well from our research. So, we worked with Lisa Jamieson at the Australian Population Center for Oral Health at the University of Adelaide. And we worked with Aboriginal Australian communities as well as Torres Strait Islander communities and then far north. And really what we were trying to do was describe the oral microbiome in Aboriginal Australians. So, many of these communities have only been exposed to this industrial lifestyle for the last 70 to a 100 years. So, it's relatively recent. And so some of these indigenous microbes that may have been lost in other cultures may still be present in Aboriginal Australians. And in fact, that's exactly what we see. So, we were looking at the microbes that live in adult Aboriginal Australian mouths from the central desert. And we found upwards of 50 different species that had not yet been described in other populations.

And one of those fascinatingly enough is endomicrobium. And so endomicrobium is typically found in the guts of termites. And it's the microbe that helps you digest cellulose and digest wood. And get energy out of that. And so working with communities and talking with people, if you are in the central desert, a great source of protein are termites. There's awesome, huge termite mountains in central desert. And so a lot of folks in historical practice and even today, right, will eat termite as a source of that sort of dietary protein. And so some of these termite bugs doing phylogenetic analysis, some of these termite bugs have gotten introduced into the Aboriginal Australian oral microbiome based on their diet. And based on their environmental exposures. And we can still see these antimicrobial microorganisms even today in Aboriginal Australian communities.

And we think they're probably playing roles in disease that we don't yet understand. And so that's where a lot of our research with those groups is now focused, trying to understand these unique microbes and what roles they might be playing in disease. We know that some chronic noncommunicable diseases are up to five times higher in Aboriginal Australians compared to Australians of European descent. There's a pretty big health gap there. And so we need to figure out what these indigenous unique microbes are doing in the context of industrialization.

Cole: Yeah. The negative, the flip side, I mean, it's fascinating about termite populations and human populations sharing a microbiome. But where are we today? I've heard you say that's a statistic that actually could be applied across many different populations on the earth, correct? Not just in Australia.

Laura: Yeah, absolutely. We refer to this as the indigenous health gap and is present globally. Where indigenous populations who have gone through industrialization and gone through exposure to these European life ways. That they typically have an increase in these chronic diseases. And several programs in Australia, for example, like addressing the gaps there are able to improve social determinants of health, but they're not able to actually improve the disease numbers. And it maybe because we're not actually treating and not actually thinking about the root causes of these disease, some of these microbes that are in the body that we didn't even know were in the body. And so it could be that if they're living traditional lifestyles and traditional diets, these aren't disease causing microbes. But when you're eating a European industrialized diet, it actually is quite problematic. So, we've got to balance all of that history and all of that dietary difference and think about that in the context of health in the microbiome.

Cole: Yeah. That personalized health topic, that's getting more and more important as we continue to learn and grow. Getting the time. Oh, I'm getting a time check from one of my colleagues here. And I think it's time to see if we can get some question and answer going with our audience. Are you up for it?

Laura: Absolutely. Let's go.

Cole: Okay. Let's see here. Oh, Andrew F. Reed. I know Andrew. I was just talking to old Andrew Reed the other day. Let's see, "Laura mentioned oral microbiome has been linked to arthritis. Wondering what mechanism might cause that if causal?" Wow. That's very specific. Thank you, Andrew.

Laura: No, it's a great question. And we've been writing papers on this, both in the context of the indigenous health gap, as well as in the context of other systemic diseases. So, in arthritis, there's been some studies where people have done biopsies of arthritic joints and they actually find oral microbes inside of those arthritic joints. And so every time you brush your teeth microbes can enter into your bloodstream. When you floss and your teeth bleed, those oral microbes have a direct way to sort of get into your bloodstream and oral microbes elsewhere in the body can wreak havoc.

Cole: Really?

Laura: So, some of it is direct and some of it is indirect. So, oral microbes like Fusobacterium nucleatum that can get into the gut can be linked to things like colon cancer and can actually cause polyps in your colon. And we think that's kind of some of the similar mechanism in arthritis. These oral microbes are binding some of your joint tissue and actually causing problems. We know there's also other microbes that bind your heart tissue and actually bind plaques in your heart.

So, and now there's even oral viruses that are being thought of in Alzheimer's disease. But these oral microbes also can play with your immune system and influence how much inflammation you have in your body. We talk about guts and leaky guts with people who have inflammation in their guts. But the same thing's also going on in your mouth. And there was a paper just recently put out hypothesizing about the leaky gum hypothesis, right?

Cole: Oh yeah.

Laura: So, these oral microbes can cut in your systemic system, but also influence your systemic levels of inflammation in your body.

Cole: Everything's interconnected.

Laura: Yeah, exactly.

Cole: Deeply. Okay. Oh, now Andrew said, "Should I stop flossing?"

Laura: Yeah. There was a really awesome study a couple years ago saying flossing didn't have any benefits.

Cole: Oh no.

Laura: So, the jury is still out.

Cole: Oh no. Don't tell me that. It took me so long until I was felt mature. I felt like I was finally an adult when I was flossing every day. I was so proud of myself.

Laura: Oh.

Cole: Tell my mom, oh boy. Oh geez. I'm not listening to it. I'm wait for definitive research on that. Let's see. We've got Keith asks, "If you could look at the oral microbiome from any group of hominids from any time and place when and where would that be?" Ooh, that's interesting one.

Laura: Good, good question. I think we are going to be limited by the amount of time we can go back to reconstruct a whole oral microbial community. I think we're going to be limited to 200,000 years be my best guess. And so I have to keep my expectations probably within that window. And I would love to go back and start to look at some of these even earlier hominids, things like Denisovans. Right now we don't have an oral microbiome from Denisovans yet, even though we know that they're inter breeding with both humans, as well as Neanderthals. And so do we have Denisovan oral microbes in our mouths, we don't know if we do. We know we have some Neanderthal ones, which is really cool, but what does that look like from other ancient hominid species? That's a question I hope we'll be able to answer in the next decade or so.

Cole: Denisevids?

Laura: Denisovans.

Cole: Denisovans. Showing my ignorance now.

Laura: We don't have a full skeleton for them. They've only been identified using DNA and primarily the pinky bone from a young female, but now there's been teeth and some other things that have been found that are actually matched to this other ancient hominid species. So, they're roaming the world with us, tens of thousands of years ago and in breeding with us and they're different from Neanderthals. They don't look like that, but we don't really know what they truly fully look like, which is also really interesting.

Cole: Wow. That's cool stuff. Could they be hobbits? Could they be elves and dwarves? No. Sorry. I didn't say that. I wonder.

Laura: There are ancient "hobbits" and there's lots of people trying to get ancient DNA from them right now, including ancient oral microbiome DNA. So, it could be that homo fluoresces, which are what are locally called hobbits could actually be Denisovans. We don't know, or it could be Homo erectis or something else. So, the jury's still out.

Cole: Fascinating. Very cool. Let's see. Here's an anonymous question. We got two votes too, "Because it's so new. Is there any issue in standardization across different labs?"

Laura: Yeah. This is a huge issue right now in the field. It's a brand-new area of research and there's different teams that want to focus on different areas of the oral microbiome. And so we've been working to try to standardize our protocols, but also standardize and make publicly available and transparent our pipelines so that other people can use them. Small tweaks and microbiome pipelines can make a big difference on what comes out on the other end.

So, it really matters that we make these pipelines open access, that we make them available to people. And it's going to take the team really coming together. Ancient DNA historically is a very competitive field because there's only so many ancient people in the world. And so it's going to require us again, changing the game and ancient DNA to really come together, collaborate and be incredibly transparent about what we're doing moving forward to get everybody on the same page.

Cole: And that's international.

Laura: International. Yeah.

Cole: If you had to guess if there's the big conference and everybody shows up, who's got game in the game, about how many people would you say that would be? Would you be able to estimate like ...

Laura: Yeah. I mean the ancient oral microbiome field has grown tremendously obviously in the last 10 years, but it's probably only about 50 people in the world, maybe a hundred people. We just did a survey during COVID about people who are working on ancient calculus in different ways, shapes and forms. And we ended up finding a little under a hundred people that work in this field. So, yeah, it's going to require all of us getting together and agreeing on the same information collection and the same analysis pipelines. And we've got a couple papers coming up that will address just that.

Cole: Well, that makes me kind of hopeful though. If it's a small group like that. If you're throwing out a good enough party everybody can get along and have a good time.

Laura: I agree.

Cole: And work together. Let's hope so. Let's see. I'll do one other question here. I think we still have time for, we got about nine minutes left here. And Sam asks, "What types of outreach projects have you been working on to share your research?"

Laura: Ooh, good question. We've been working on all sorts of stuff. We're trying to integrate digital technologies into what we're doing. And so one of the projects we're working on right now is actually to do a 3D scan of the ancient DNA lab so that anybody who would want in the world could sign in online or use a virtual reality headset and actually walk through the ancient DNA facility as if you were putting on one of those biohazard suits and extracting DNA from an ancient tooth, you'd be able to fall along with us and actually watch and do that with your own hands. So, we're pretty excited about that. But obviously one of my big passions too, is just reaching out to school age kids.

I have two young children myself, and we really want to beat this dogma back about bacteria being bad and germs being bad. There's certain context where there's bad and there's certain times you need to wash your hands. But in general microbes are really, really good. And we need to stop using as much antimicrobial things as we do in the world. And so we're really focused on early childhood education and creating, teaching plans and lesson plans so that people can start to incorporate microbiology at a much younger age with students and with kids. Microbes really look very fuzzy and very different depending on what they are.

Cole: Oh, wow. Can you show that to the camera? What have you got there, Laura?

Laura: So, I noticed in previous podcasts that there weren't any microbial plushies or stuffies. And so I brought you Porphyromonas gingivalis, which is an oral microbe that we work on. And this is sort of a blown-up version of what it looks like, but they're all kind of really curious creatures. They all look very different. And if you can talk to a kindergartner about this, they can relate to this. So, that's where we're at. We're really trying to get this out to younger classrooms. So, I'll leave this sit here and hopefully he can find a home.

Cole: Maybe he can find his way in with the other plushies. That's fantastic. Thank you for bringing that in that's beautiful. Well, I love that you're reaching out to the next generation, and it makes me think of what you shared in that video that we just watched that clip that more than 50% of us is sort of microbial cells, not human cells. So, absolutely one would hope that most of that stuff is good stuff. And that we start to realize we are communities of all these different, small living beings. It's pretty freaky to think about. It's a whole other way of thinking about yourself as a community.

Laura: Yeah. And you have to take care of that community. Like you can't hurt it and harm it. And you've got to maintain it. You've got to be kind to it and good to it. So, change the mindset.

Cole: All right. That's the kind of game changing I like to see in the world. So, yeah. Cheers. Well done.

Laura: Cheers. Thanks, Cole.

Cole: So, it wouldn't be an episode of The Symbiotic Podcast in the season if we didn't give a little time to our plushies over here, people. And since you were just talking about kids and you brought your own plushie along, which I love so much, Dan, why don't we let the people know we've got a little video about our plushies. This is the part of the podcast towards the end here, where we make everybody aware that here at Penn State, we are evolving. We're growing. We're recognizing the diversity of ourselves, not just in our microbiomes, but among one another. And the fact that we can all be in a community together. So, Dan, if you could roll that video about our plushies, I just want everyone to know that you are no longer limited as you once were to only the Penn State Nittany Lion plushie.

If you want to expand things out, there are other plushies available to you at this stage. There's a pink unicorn plushie. There is a little beanie baby bear plushie. Like I like to call that the infant indoctrination plushie, get them indoctrinated in the Penn State way early. At the other end of the spectrum we've got the more ancient venerable gnome plushie and all these do have Penn State logos. They've all been approved and branded. We've even got a Lama plushie available today. And there's probably other ones out there that I'm not even aware of. So, maybe that's a goal we need to set, Laura is to create like a microbial Penn State plushie. Maybe I need to talk to the branding people.

Laura: I would love that.

Cole: At Penn State and see. But for today, I'm going to ask the audience out there today to vote. And you can go down in the chat box there, you can actually vote on whatever your favorite alternative plushie is. We actually don't show the Nittany Lion because everybody loves the Nittany Lion just as he is. But we're just curious, we're running our own research project, Laura. We're asking each audience of each scientist to vote on their favorite plushies.

And then at the end of the season, we're going to look at that data and see what kind of information we can draw about your personalities, about the people who follow you. I don't know what we'll do with it. I don't know, but it's knowledge. We're increasing knowledge here. This is basic research basically. But I have to ask you, do you have a favorite of the alternatives that you ... Now you're not allowed to say your own? Well, I guess you could say your own, but then you're really going to throw our whole research project off kilter. So, if you had to pick one of these four that we have here, who would you go with?

Laura: I would definitely pick the llama.

Cole: Oh, you're a llama? You're a llama lady.

Laura: Yeah. We're working on a llama. We're working a lot in South America.

Cole: Oh, Yama. Yeah. Well that's Lisa Llama. That's the only plushie that came with the name.

Laura: Oh awesome.

Cole: It's the only one. All these other ones are just like gnome, unicorn, bear and Lisa Llama.

Laura: I love it even more.

Cole: Lisa Llama. Okay. So, as we wrap up today, when our last couple of minutes here and we'll share that poll as we're leaving our talk. And we'll see in your audience, if people agree with you or if they have a different favorite, we'll find out here in a little bit, we'll share that with you later. But I do want to thank you so much for coming down. Thanks for all this great work you're doing. Also, I'll make an announcement that you are going to be among our inaugural group of Huck Leadership Fellows. I now am officially allowed to announce that. So, congratulations to you.

Laura: Thank you.

Cole: I think we'll be working a little more closely together in the next year. You'll be sitting in with our Huck Exec. We're so excited that you're willing to step up like that and you'll be doing some DEI work with us. I understand you got some things, you're a busy lady. You got a lot going on. So, thank you for that as well. And thanks for taking time out of your busy day to come down here and talk to us.

Laura: Yeah. Thanks so much for having me. I'm so fortunate and so lucky to work with such a brilliant team of students and scientists. And it's been a great to be here today and share our work with you. Thanks.

Cole: Thanks a lot, Laura. And for the audience, come back. We won't be back until June. We're going to take May off. We got a lot of different things we're changing over in May. We're going to take a little break, but we'll be back on – it's June… let's see… 24th, I believe. No! June 23rd is a Thursday at noon with Sally Mackenzie, director of the Penn State Plant Institute. Put it on your calendar. We'll see again in June, have a fantastic May and don't stop co-evolving.

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Narrator: The Symbiotic Podcast is a production of the Huck Institutes of the Life Sciences at Penn State University.

Our video and livestream producer is Dan Lesher. Our sound engineer is Brennan Dincher. Our web developer is Jodie LeMaster, and our marketing manager is Keith Hickey. Cole Hons hosts and directs the show, and original illustrations and animations are provided by Sam Muller and Bethany Seib.

If you enjoy our podcast, we hope you’ll subscribe and share it with others. We’d also love to know what you think about our content, so if you want to get in touch, please email symbiotic@psu.edu.