Cole Hons: Greetings fellow Homo sapiens, and welcome to the third season of The Symbiotic Podcast. This is the last episode of our third season of the podcast, and I'm really excited about our guest today. We'll be introducing him in just a minute. I'm Cole Hons from the Huck Institutes of the Life Sciences, and we're going to have with us today Dr. Xiaojun “Lance” Lian, who is in the department of Biomedical Engineering, as well as the Department of Biology. He holds a dual position like so many Huck people do here at Penn State. And before I introduce him, and I'm very excited to do so, I just want to do a couple of housekeeping things for you. As you're watching, I encourage everybody to chat in and participate with us. There is a chat box either next to you or below, depending on how you're viewing this. It'll be next to you or below the screen. And you can be anonymous, or you can share your name, doesn't really matter. Make up your own name. We don't really care. But we do want you to participate, so please do participate in that chat.

You can put your questions in there for Dr. Lian. And later on in the show we will be taking those live, and he'll answer your questions, and you can also vote on other people's questions. So we'll start with the highest voted questions at the end. This is about a 45-minute show here. We're going to be showing some video that we've been shooting and producing about the amazing work that Dr. Lian's doing with stem cells. We'll be sharing some of that, and we'll be doing some other fun audience participation stuff that you can vote on in the chat. So please do take advantage of that chat and thank you for tuning in. So with that taken care of. Lance, hello?

Xiaojun (Lance) Lian: Hello. Hey Cole. Nice to be here. Nice to see you.

Cole: It's good to see you too. It's been a little while. We were trying to have you on. Boy, it's been a couple months and we ran into some problems here and there.

Lance: That's right.

Cole: Life can be like that. It can throw things at you between Covid, and hiring issues, and all sorts of things in our chaotic times. It took us a while, but we got here.

Lance: Finally, we make this happen.

Cole: Yeah, that's the important thing. And we're very excited to have you here. I was just mentioning the fact that you're in two different departments, which is such a Huck like thing because Huck is all about interdisciplinary collaboration. And we were just discussing before we started the show here that the work you're doing is a beautiful combination. It's a place that you can serve both biology and biomedical engineering. Can you tell us a little bit about that before we get into other things?

Lance: Sure. Yes. I was appointed by biomedical engineering and biology department. That's because my lab research is focused on stem cell engineering and stem cell biology. That's a very natural thing for me to be appointed by these two departments and I can contribute to both departments in different ways.

Cole: And you were saying even some new courses are emerging out of that reality, right?

Lance: That's right. Since I joined Penn State, I develop a cross listing course, which is called stem cell biology and therapy. So this course is open for both BME students and biology students. So during this course, I assign projects to students. So in this way, engineering students and biology students have the opportunity to work together for one project. So engineering students are more good at quantitative biology, such as use calculus and math to solve things. And biology knows better for biological mechanisms. So when I put them together, they can learn from each other. And this is more productive than just a group of engineering or students work together.

Cole: That's fabulous. I mean, that's what we're all about at Huck.

Lance: Right.

Cole: Kudos to you my friend. Thank you for doing that. It's exactly the kind of thing that we're championing and I think that the big complicated issues that we're grappling with, whether it's medical, or environmental, or even economic, you could go on and on with all the different challenges we're up against these days. But it really does take different kinds of people thinking different ways to take that on. So, thanks for your contributions there.

And then of course with your research, it's just fabulous. The amount of innovations, we'll get to those in a minute with what you're doing with stem cells. Just working with you on the video, I've learned so much, and I'm still learning, and there's no end. So that's why we have you on here in our risk taker game changer series as this great end to the season. It's a strong ending with you because there's so much to share that we'll be talking about.

But before we get into the science, I do this with every guest of this season. I want to know a little bit about you, Lance, and you chose the name Lance, right? Xiaojun is your name. You were born in China and took this nickname when you came here to states. So I want to know, Xiaojun, when you were growing up, when you were a kid, were you a risk-taker? Were you somebody who has changed things and what weren't just satisfied with the status quo?

Lance: Right, right. Yeah. So I was born in small town in China, in Jiangsu province. So when I grew up, I definitely liked to take risks. So for example, if I do hiking, I would like to go through these paths that no one else goes before. So the reason for that is because if you go these pathways, you will see unusual beautiful things that as compared to you use the pathways that everybody goes. And I like to see unexpected things. And especially for doing the research, I don't want to do something that everybody's doing. I want to go through these policies that no one does before. And I enjoy a lot about taking risks.

Cole: That's fantastic. I love that. I also love to go where there is no path. Try and find a path right there. I have a quote on a wall at home that says that do not go where the path may lead, set your own path, and make a trail for others to follow. I definitely relate. That's terrific. And Lance, why did you choose the name Lance? Was there any particular reason that you went with Lance?

Lance: Yeah. That's a good question. So in China when we grow up, we take English classes when we were in the middle school. And then usually the teachers will ask you to pick English name for yourself. And I started to think about it, and I was like, okay, I wanted to pick name. By that time, I just started to learn English and I wanted it to start with the letter L because my family name is L.

Cole: Okay.

Lance: I think it would be cool if I got two L, and then I just look at these English books, and I find when I see Lance, and I really like it. So that's why I just pick this one. Yeah.

Cole: It just appealed to you. And Lance Lian, it does sound good, it flows. Yeah, the two Ls.

Lance: That's right.

Cole: I love that. Terrific. Well, Lance Lian, let's talk about your research a little bit here. You've done so much with stem cells and you've taken some risks with stem cells. We'll be watching this in the video in a moment. And one of the things I learned working with you is about this Wnt pathway that we're going to be talking about a little more. And maybe you could share with us, one of the many innovations that hopefully we'll touch on, is that there are many different ways to differentiate stem cells, and there are many different pathways for the differentiation. But you had shared with me that many scientists working with stem cells try to work across maybe 10 different pathways and try to figure out all of them, and you chose one. I see that as a big risk that you took, you chose one single pathway, the Wnt pathway, and went deep deep on that, and it really yielded all sorts of incredible innovations and breakthroughs. Can you speak about what made you choose that one pathway?

Lance: Right. So stem cells, that the stem cell type that we are working on is called pluripotent stem cells. So naturally, if you have the embryo, if we have the stem cells, and in the modest uterus, these cells just naturally differentiate into all different type of cells in our body. So if you examine what signaling pathways, what signaling factors involved in these differentiation, you will find there are more than 20 different cell signaling pathways.

Cole: 20, oh, I was saying 10. There's more than 20.

Lance: Yes.

Cole: ... signaling pathways.

Lance: And if you check how many signaling factors involved, because each signaling pathway may have multiple signaling factors, you may end up with 100 factors. There's just so many things involved in this process. So when we do this in the Petri dish in the lab, if we try to a hundred percent recapitulation of what's going on in vivo, that is almost impossible because there are just so many factors involved in this process. And if you want to optimize concentration for each of them, you may end up with a combination of billions of combinations. You can never do billions of dishes for experiments. Right?

Cole: Right.

Lance: So what I do is, so my logic is, how about we find the most critical one, and if we systemically optimize this most critical one, can we yield similar results as compared to optimization of many of these factors?

Cole: I see.

Lance: To be honest, that's definitely a risk for me because it is quite possible that just optimize one signal pathway may not work at all. Because in nature you need so many different factors, and here you just try to optimize just a single one pathway and hope it's going to work. So I think I take the risk, and I did a lot of work. It took me about four years and it turns out it worked. So I'm very excited.

Cole: Yeah.

Lance: I think there's also a little bit lucky components here, but it indeed worked.

Cole: You did it. Yeah. A little bit of luck and a lot of hard work and sweat.

Lance: Yeah.

Cole: I mean, we talked about the hours that you had to run these experiments over those about four years. Did you just, three, four years?

Lance: Right. In total, it took me about four years.

Cole: About four years. And during the four years, because time is such an important element, right?

Lance: Right.

Cole: That people go in, three in the morning, checking on things, just watching 24/7 and just trying this, trying that.

Lance: Right.

Cole: And just doggedly going forward. And so when you say it worked, check me if I'm wrong here, Lance, if I'm misconstruing anything, but my understanding is that not only did you create a process for differentiation of stem cells into the other cells that you're trying to make, but you're doing it cheaper, you're doing it faster, and you're doing it with a lot greater efficiency, correct?

Lance: That's right. That's right. So the differentiation that we are talking about is called cardiac differentiation. So the goal here is we want to convert stem cells into cardiac myocytes. The reason for that is because cardiomyocytes are very critical for our heart function. And if a person have a heart attack, their cardiomyocytes died. And if we can generate these cells in the lab, we can potentially transplant these cells back into the heart failure patient. And indeed, this is happening. And during the time that I'm doing my PhD and the cardiac differentiation, efficiency is very low. So you do the differentiation, and it took you about three to four weeks, and your yield is about one to 2%. So the efficiency is very low. So my message greatly improved the efficiency. We can generate more than 90% of the efficiency, and we can achieve our goals in about 10 days.

Cole: 10 days.

Lance: So we both shorten the time and also we gradually improve the efficiency.

Cole: And then the cost associated that process too dramatically reduced, correct?

Lance: That's right. So the previous approaches use the serum and gross factors to do the differentiation, and these factors are expensive and not stable. So that's why you have to use these gross factors more quickly. You cannot store them for a long time. And instead, I did not use any serum, I did not use any growth factors. I used two small molecule compounds to do it. So these chemical compounds are more stable and much, much cheaper. So the cost of these chemical compounds is only 5% of the gross factor cost. So if they need a hundred dollars to do the differentiation, I only need $5 to do it.

Cole: That's fantastic that that's something that we do share in the video will be showing a sneak preview here in just a minute of a video about the cardiomyocyte work you're doing and also mentions pancreatic beta cells that are producing insulin. So before we run the clip, let's hear a little bit about that. And which came first, the cardiomyocytes or the pancreatic beta cells? And also I'm curious, is the same process you developed for cardiomyocytes, which are heart cells, is that's the same process then you're using to produce pancreatic beta cells, correct? And it has to do with the amount of activation and deactivation of the Wnt pathway, correct?

Lance: That's right. So cardiomyocytes differentiation happens first. So during my PhD, so I developed this robust protocol for generating cardiomyocytes. Essentially we can generate beating cardiomyocytes across the whole dish. And later, after I joined Penn State, I started to think about what type of projects that I should work on at Penn State because the cardiomyocytes efficiency is already great. So there's not much room for me to further improve it. And so I decided to look around, and see which other stereotypes are clinical relevant, and also very difficult to generate. So I like to take the risks, if no else can do this very efficiently, I want to do it. I want to make it better. So then I pick the pancreatic beta cells. The reason for pancreatic beta cells is they are very, very useful cells for treating type one diabetes. So these type one diabetes patients, their own pancreatic beta cells died because their beta cells under attack by their immune cells.

So basically their immune cells kill their beta cells. So they do not have beta cells. They cannot naturally control their blood glucose concentration. That's why they have the diabetes. So in this case, the stem cell therapy is very good for treating this disease, because if we can generate good amount of functional pancreatic beta cells, we can transplant these cells back into these type one diabetes patients, we can potentially cure the disease as compared to if you just do insulin injection, just treat the disease. So that's why in Penn State I decided to work on this. And it turns out very, very surprisingly that you can still use the Wnt pathway to regulate the stem cells to generate the pancreatic beta cell progenitors by adjusting the amount of activation. So if you activate the Wnt pathway with higher concentration of the chemicals, you generate cardiomyocytes. But if you activate a Wnt pathway at the intermediate level, you generate the pancreatic progenitors, so that's very surprising.

Cole: That's fantastic.

Lance: Yeah, nobody reported that before.

Cole: Now what about neurons? Because I know that neurons are a third very important cell that cannot be produced by the human body. We can produce skin cells and many different cells. We've talked about this, you and I, but heart cells and pancreatic beta cells and neurons are a third. Would you be able to produce neurons then with the same process?

Lance: Yeah, that's a great question. And based on the literature, my lab doesn't work on a lot of neuron differentiation. But based on the literature, it is very interesting that the Wnt pathway is also involved in neuro differentiation. But in this case, you must suppress the Wnt pathway in order to do the neuron differentiation. So in summary, you can regulate one signaling pathway and generate three different type of cells. If you suppress the Wnt pathway, you got neurons. If you intermediate activated the pathway, you got pancreatic progenitor. If you highly activated the pathway, you got cardiomyocytes.

Cole: Fantastic. Amazing. It's a good thing you went to look for a new path in the scientific woods there, Lance.

Lance: Yeah.

Cole: Really found some beautiful things in the process. Let's take a look at our video if we can. This would be a nice time. And I want encourage everybody to chat in with your questions. I'm trying to watch the chat over here so that we have some things to answer later on in the conversation. But right now, let's take a look at a sneak peek. This is three minutes of a video that when it's done will be probably about five minutes. Let's take a look now.

Narrator: The human heart is made of cardiomyocytes specialized pulsing muscle cells. Without them our hearts can't beat. Unfortunately, unlike many other cells in our bodies, cardiomyocytes don't naturally regenerate. That's one reason why heart disease is the number one cause of death in the United States. It's also the reason that stem cell therapy is considered the most promising treatment for repairing damaged heart tissue. As the raw material from which our bodies are made, stem cells have the incredible potential to form new cardiomyocytes or any other kind of cell. But these cells can only be therapeutically viable if we can control what kinds of cells they become, and successfully introduce them into a patient's body.

Lance: In total for human body, we have about 200 different type of cells, and now we can generate at least 50% of these cells, so around 100 different type of cells from stem cells. But many researchers are focusing on these cell types that cannot be regenerated naturally by our human body.

Narrator: Lance Lian is an associate professor of biomedical engineering at Penn State.

Lance: The hottest areas are three different type of cells. There are neurons, cardiomyocytes, and the pancreatic beta cells.

Narrator: At its outset, stem cell research was hugely controversial. When biologist James Thompson derived the first human stem cell line in 1998, he started with cells sampled from human embryos. In 2001, President George W. Bush banned funding of any new embryonic stem cell lines. But in 2006, Japanese researcher Shinya Yamanaka discovered that adult cells could be reprogrammed to become stem cells. An advance that won him a share of the 2012 Nobel Prize in medicine, and removed the need for embryos. With stem cells readily available to labs, researchers began to discover multiple methods to drive cell differentiation and obtain specific types of cells needed to advance new cell therapies.

Lance: Once you have iPS cell lines, one of the property of these iPS cells is they can proliferate almost indefinitely. So then you do not need to worry about the number of cells that you can have.

Narrator: Lian and his team have devised a novel way to produce new cardiomyocytes by manipulating the Wnt pathway, a sort of protein based communication network used by cells. By timing specific activations and inhibitions of this pathway. The Lian lab has advanced the effectiveness of stem cell differentiation from the highly random 1% yield produced by older methods to yield as high as 90%. They've also reduced the time it takes to produce cells from a month to around 10 days, and they've reduced the cost of the process by 99%.

Lance: We publish our paper, and now our methods become like a golden standard method in the field for all the other labs around the world if they want to make cardiomyocytes.

Narrator: In addition to cardiomyocytes, Lian's lab has used their differentiation technique to make pancreatic beta cells that produce insulin, a breakthrough that may lead to new therapies for type one diabetes.

Cole: Well, I hope you like what we did so far, Lance.

Lance: I really like it.

Cole: Oh good.

Lance: Yeah.

Cole: I'm glad. Yeah, we had a lot of fun coming out to your lab and shooting in the real stuff. There was no faking going on there. That was real science happening right in front of us, and just, it's beautiful to capture that. It seems like magic in a way, the stuff that's going on. So what we didn't get to in that video yet that we're going to get to is actually, it's funny, somebody just chatted in with a question. So I'm going to take this first question here, because it fits right in with another thing I wanted to touch on. David H says, Hello, senior biology major here at PSU. When the artificial pancreatic beta cells are administered to type one diabetics, will these patients’ immune systems attack these new cells? And that's what we were just about to talk about it. It'll be in the video later. We're talking about universal donor cells. Let's talk about that.

Lance: Sure. That's a great question. Thank you for the question. So, when we generate the pancreatic beta cells in the lab, and then we transplant back into the patient, the patient’s immune cells may still attack our transplanted cells. So the question here is, how do we protect our transplanted cells? So there are two ways that you can do it. The first way is use gene editing approach that we can generate the so called universal donor stem cell. So these universal donor stem cells, we locked out the genes associated with immune interaction with immune cells. So, the immune cells will not treat our transplanting cells as foreigners.

Cole: You locked them out. You locked out, you found those genes that would cause the immune system to react.

Lance: That's right.

Cole: You locked them out.

Lance: I locked them out with the CRISPR gene editing technology.

Cole: CRISPR.

Lance: Yes. So in this way, the immune cells such as T cells will not attack our transplant cells. So the stem cell derived the pancreatic beta cells can survive in vivo for many, many, many times, many, many years. That's one way to protect the transplanted cells. The second way to protect the transplanted cells, which is also going on in clinical trials nowadays, that is you use specific polymers to make the scaffold to encapsulate the beta cells. So these encapsulation devices have small, tiny holes on the surface, but these holes are small enough, they can only allow the insulin to come in and out, insulin, glucose, these small molecules to come in and out. They do not allow cells to come in and out. So the immune cells know there're foreigners are inside of the device, but they just cannot get in to attack them. So, in this way, you protect the transplant with the pancreatic beta cells.

Cole: Very interesting polymers. We're talking nanotechnology here. That reminds me of the whole convergence world of materials and life sciences.

Lance: Nowadays, many of these researchers, many of these problems that we are facing are extremely difficult to solve. So that's why we have to work with both biologists, biomedical engineers, and material scientists. We work together to solve these big problems.

Cole: Right on. And if we return back to the method you developed for the pancreatic beta cells to be donor cells, let's also touch on the fact that it's not just pancreatic cells we're talking about, we're talking about all of them, right?

Lance: That's right.

Cole: We're talking about the cardiomyocytes as well. So, if people watching this think about a heart transplant.

Lance: That's right.

Cole: And that's always a problem is you put the new heart in, but will the body reject that heart? And the same thing is happening on a cellular level with these differentiated stem cells. The cardiomyocytes into the, say, like a heart attack victim, like a patient who can't, like the body can't regenerate, just like it says in the video. They can't regenerate these cells. But if you put the cells in, that's another instance where the body could reject them. But this process you've developed with CRISPR and tricking it, it's almost like stealth cells.

Lance: Right.

Cole: That are not rejected. And you had shared with me that since you published that paper, and put the method out there, which is patented by the way, right?

Lance: Right.

Cole: Now, there are clinical trials going on right now in three countries with heart patients who are using these universal cardiomyocyte cells that derived using your methodology, correct?

Lance: So for the stem cell nature, you can use two different type of cells. One is called embryonic stem cell. So another one is called induced pluripotent stem cell, iPS cells. So for the cardiac therapy, if we use patient's own cell, so for example, we take a little bit of their skin biopsy and generate iPS cells and then generate a cardiac cell. If you transplant these cardiac cells back into the same patient, you may have much less concern about immune rejection. The reason for that is because the cells are coming from their own skin cells. So, in this case, you may not even need the universal donor stem cell.

Cole: Okay.

Lance: Yeah. In this case, in this specific case.

Cole: Got it.

Lance: But for pancreatic beta cell even you use patient's own cell to do iPS cell generation to do beta cell differentiation, and a transplant back, you may still have the problem.

Cole: Oh.

Lance: Because the patient, their immune cells just attack their own sale, so these are a little bit different. So for example, if we take the cardiomyocytes as an example, why cardiomyocytes, we may still need the universal donor stem cell? Why not do we just customize iPS cells for individual patients? The reason for that will be, the reason why the cost will be extremely high. That is every time I got the new patient, I have to generate a specific iPS cell line for that patient. And then I need to do differentiation. I cannot make the off the shelf product.

Cole: Got it.

Lance: The reason too, in some accurate situations, for example, heart failure, you didn't have time to do that. So the patient come to hospital and they may die in four to five hours. You cannot just say like, wait, I need to generate iPS cells, and that take about one month. The patient just didn't have time for you to do that. So then also for business and these pharmaceutical companies willing to do this, they don't want do personalized medicine because that cost, it's just too high, just no one can afford it. But if you can generate a universal donor stem cell, and then you can generate billions of cardiomyocytes, and then you freeze in the liquid nitrogen tanks, and it's like the off the shelf product. The patient come to the hospital, you immediately saw one valve of the cells and then you do the transplantation. That is more feasible business model to do this.

Cole: That's phenomenal. And I know that you do have some industry partners and when working with some iPS, do you want to talk about that? I know it's an important thing for Penn State, and one of the reasons we're doing this podcast is to tell some stories to others in the community who may want to do similar things. So, could you speak about what that experience has been like for you?

Lance: Sure, sure. So since I joined Penn State, my lab has filed through Penn State five to six patents. So they are covered different things. So for example, one patent is focusing on how to generate pancreatic beta cells from stem cells. Another one is related to how to generate these universal donor stem cells. Of course, we can combine these two patterns together to generate the so-called universal donor beta cells. But the universal donor stem cells has more broad applications than just beta cells. If you use universal donor stem cells to generate cardiac cells, to generate neurons, these cells after transplantation will also not be rejected by the patient’s immune cells. So that's why we are very interested in combining the universal donor stem cell and pancreatic beta cell protocol go together. And then we start a new company. And then I work with a business partner from New York and we try to recruit the funding to support our company. And then we try to push this forward for clinical trials using these universal donor beta cells for therapy.

Cole: Fantastic. Love it. Now I'm checking my notes because you've done some other things as well, even on top of that. When we talk about where stem cells come from, I want to make sure we touch on this too. In the little video that we showed, there's a quick and dirty little timeline there of embryonic stem cells were where the cells began. And it was very controversial, because people talk about the cells from embryos and the ethical dimensions of that, but then we were able to take these from adult humans. But you've taken it even further to the point where you don't even need blood or a biopsy, just from a urine sample, you're able to derive cells?

Lance: That's right. That's right. So I really want to talk about this topic because many times the audience may think all the stem cells are the same, but they are not. So we have the embryonic stem cells, they must derive from human embryos. So that's why they are ethically debatable. So that's why different people have different ideas on these cells. But the induced pluripotent stem cells do not need any embryos. We can use the adult person's skin cells, blood cells, but if you think about it, these processes are still painful. So you needed to draw some of the blood or you needed to donate some of the skin biopsy. So at Penn State, I decided to generate our own induced pluripotent stem cells or iPS cells for our lab. And we think about it, we were wandering, what about we just take the cells from the urine samples?

So we did that. We take some urines from one of our lab member, and then we applied the IRB through Penn State. Penn State agreed with our approach, and we spin down the urine, and then we collect the cells. So you got about 10 cells out of 100 ml of the urine samples. No a lot of cells, just 10 cells. But the good news is, these cells, once they attach to the Petri dish, they can proliferate. One cell become two to become four, become eight. And then after 10 days, we got about a couple thousand cells. And then starting from these sales, we use reprogramming technology developed by Dr. Shinya Yamanaka who won the Nobel Prize in 2012. And then we use similar technology and reprogrammed the urine cells to iPS cells. So, this process that's developed by us is a non-painful process at all because we just need to collect a little bit of urine samples.

Cole: Right.

Lance: That's it.

Cole: And the people who can collect a urine sample versus the training it takes to draw blood or get–

Lance: That's right.

Cole: So there's also the cost and the time and the effort. And so again, you're changing the game, I mean, in all these different dimensions of stem cell engineering and stem cell differentiation and even the sample collection, it's quite phenomenal. So what the heck are you working on next? What's on your agenda right now?

Lance: Yeah. Great question. So in my lab, we talk a lot about stem cells. Actually, in my lab we also work on gene editing.

Cole: Gene editing.

Lance: Yeah. Let me explain why gene editing and stem cell research are a very good match. So there are many, many patients that have diseases because they inherited the disease causing mutations from their parents.

Cole: Right.

Lance: Yes.

Cole: Hereditary.

Lance: So that's why we are very dedicated to develop gene editing technologies to correct these mutations in the patients. So recently, my lab published a newspaper in Cell Reports Methods. We showed that we can greatly improve the gene editing efficiency by using the so-called chemical and modified RNA. So this is a technology that used to generate the SARS Covid RNA vaccine. So we use this modified RNA technology to encode gene editing enzymes. And we find this method is much high efficiency as compared to traditionally people use DNA to encode these factors. So our efficiency can achieve about 85%, and the traditional efficiency is only 10 to 15%.

Cole: Did you say modified ions?

Lance: Modified RNA.

Cole: Modified RNA. RNA. I'm sorry. Yeah, I'm just making sure. Okay. RNA, that makes sense, because we've all heard about RNA with, as you said, the Covid vaccines.

Lance: RNA vaccine. That's right.

Cole: So now we're completely moving away from stem cells together, right?

Lance: No.

Cole: But you bring it back into the stem cell round.

Lance: No, not moving away from stem cells. Let me explain why this is still closely relates to stem cells.

Cole: Okay. Okay.

Lance: Because if you have a patient, that patient has a mutation, you can take that patient's urine cells and make iPS cells. So, the iPS cells will have the same mutation as the patient cell, because this is from the patient.

Cole: Got it.

Lance: So, it has a mutation.

Cole: Okay.

Lance: The question here is how do we correct the mutation? You cannot directly test your gene editing in the patient, but you can test with iPS cells derived from the patient.

Cole: Oh.

Lance: That's why it's a perfect match.

Cole: Wow. Yes. Okay.

Lance: So this is why we are working on in the lab. So we take the patient's urine cells, make the patient's iPS cell, and we deliver the gene editing into the iPS cell. And we want to see if we can correct the mutation. Yeah. I already receive many emails actually from different patients asking me to see if we can help them for this type of disease. Yeah.

Cole: Phenomenal. It's got to be a lot of fun working in your lab.

Lance: Yeah. We always work on different new projects and at take the risk steps. Yes.

Cole: Yeah. Never a dull moment. That's how it is around Huck and a lot of the Huck labs. Never a dull moment. Well boy, we're coming up pretty quick on time. I'm surprised at the number of questions I'm not seeing, and I don't know if that's because something's malfunctioning on my end with what I'm able to see on my screen, but I'm going to try one more time to check in. Oh boy. Okay. So there is a follow up question here. Okay. I just had to refresh. What are your goals for the clinical application of generated neurons? Are you looking to treat any conditions in specific at this – any specific conditions?

Lance: Right. Great question. So my lab actually didn't work a lot on the neurons, but talking about iPS cell derived neuron application, I think one of the biggest application would be related to stroke.

Cole: Stroke.

Lance: Yes, stroke. Let me make an energy in the heart, the heart of failure causes the cardiomyocytes to die. The stroke caused the neurons to die.

Cole: Yes.

Lance: So basically if you can generate iPS derived functional neurons, you can also transplant these neurons to replace the damaged neuron area. So, then you can have the new neurons grow in that area.

Cole: That's phenomenal. That could just be a whole new world medically speaking. Well, it's fantastic. I'm so glad, I'm checking to make sure that I... Did I miss anything? We talked about patents, we talked about clinical trials, we talked about what's next. Cheaper, faster, more efficient. Deriving, getting stem cells from urine samples, Wnt pathways, insulin producing pancreatic beta cells, neurons, you're all over. And now CRISPR as well. We're going deeper into CRISPR, and addressing some of those mutations as well. Phenomenal. So, there's only really one thing left to do on this episode, Lance, and that is to talk a little bit about our plushies over here.

Lance: Sure.

Cole: I can't let you go without talking about our plushies.

Lance: Yeah. We were looking at–

Cole: Yeah, we've done this all through our entire third season with our Risk Takers and Game Changers. It's just our way of having a little fun. And we're doing our own little research, Lance. I'm researching people like you, this phenomenal risk takers and game changers in science. And I'm trying to find out how you compare, if I give you, it's a social science experiment. If I show you these alternative plushies, we've got a unicorn over here, Dan's going to show our little video so that our audience can really get a good look at these. Let's take a look, Dan, if you can run that clip, we'll really show this off. There we go. It's 2022 people. And we can go deeper into plushy land than just the usual Nittany Lion that everybody's used to. Everybody loves the Nittany Lion, we love him. But if you're not a lion person, you could go with a Nittany unicorn, you could go with a Nittany little bear. I like to call that the infinite indoctrination bear.

And if you have little ones in your life that you want to get into the Penn State community, we also have the old gnome, the wizened gnome in the middle there for watch over your garden and keep the Penn State vibes going. We even have a llama, and see they all get along with our lion. You can see the lion right there. And by the way, I heard the lion's in a 12-step program now. So we're all very, very happy with the lion. He's making up with everybody in his life, doing all his good work and getting his life together. So I want to ask you, what's your favorite alternative plushy, Lance? Are you a unicorn man, a bear man, a gnome, or a llama?

Lance: Right. Great question. So my top one choice is for sure, go with Nittany Lion. Okay, because I'm a Penn Stater. So, the second choice I would go is this, the unicorn.

Cole: The unicorn. The unicorn would be your favorite alternative.

Lance: Yeah. The reason for that is because unicorns are associated with dreams.

Cole: Oh really?

Lance: Yeah. So in China we saw many description about unicorns with dreams. I just hope that I'm a person that want to dream big, want to do risky things. So that's why I like unicorns very much.

Cole: I love that. I like the unicorn too. That's phenomenal. So everybody out there watching before you sign off here, please, please vote. You can go in the chat right there. You can vote llama, gnome, bear, unicorn. And then what we're going to do is we're going to compile all the data. We're looking at which scientists liked which plushy, and then which the audience members of the different scientists, how did the audiences break out? And then we may start our own journal. We're thinking about starting a journal of social science journal just called Plushy. And this will be our first paper, and we'll see. I'm not sure if we're going to be able to apply that to anything practical, but maybe it doesn't matter. Maybe it's just something fun for us. But in all seriousness, Lance, thanks so much for coming down and sharing a little bit about what you're doing.

It's phenomenal. Thank you. One of the reasons that Penn State is great as people like you doing the work and inspiring the next generation and collaborating with colleagues across disciplines to really make a difference in the world. So thank you very much more power to you as you go forward. If people want to follow Lance's work, keep up with the Huck. You could subscribe to our newsletter, The Pulse, at our website, and you'll be getting updates about what Lance is doing and others at the Huck. I encourage you to do that. Also, if you subscribe to our YouTube channel, when we finish our video about Lance's work, that's our Life From All Angles video, the whole thing, you'll be able to watch that and share it with others. This episode will be on the YouTube channel [The Symbiotic Podcast video playlist] as well. So, if somebody missed this and you think they ought to see it, pay attention there.

You can share it with others there. We're also going to be releasing our video about Dr. Sally Mackenzie. We never finished off, there was an animation, we're just finishing up. So her video is also forthcoming. So stay tuned for that. And we're going to take a hiatus from The Symbiotic Podcast. We're taking a little break and we're going to come back with something totally different in the new year. So stay tuned for that. But again, Lance, thank you so much for coming down. It's always a pleasure.

Lance: Thank you, Cole. Nice to be here.

Cole: Take good care. And everybody out there, thanks again for watching and don't stop co-evolving.

---

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.

Cole Hons: Greetings fellow Homo sapiens, and welcome to the Symbiotic Podcast. I'm Cole Hons, your host from the Huck Institute of The Life Sciences. And it's really great to be back here in the studio after a month off. We had no podcast last month. I think we all needed to take a little break and now we're back. And we're very excited today, because we've got a super fantastic guest. Dr. Sally Mackenzie is with us today. Sally is a professor of biology and of plant science, the Huck chair of functional genomics and the director of the Penn State Plant Institute. Hi, Sally.

Sally Mackenzie: Hi.

Cole: Thanks for being with us today.

Sally: Very nice to be here.

Cole: So before we get into our conversation, Sally, which I'm super excited about, I just want to let everybody out there watching know that you can chat in live today on this live stream. You just go to the little chat box near the video screen, depending on your device, where that might be located underneath or to the side. And you can chat in, you can use your real name, you could use a pseudonym, whatever you want to do, but you can participate by putting in a question. There's a little button to ask a question for Dr. Mackenzie.

Cole: And at the end of our 45 minute conversation, towards the end, we will do a Q&A session live and we can also let you vote on questions if you don't want to ask your own, or if you like somebody else's question, please vote on it. And we are going to take the highest voted questions towards the end of our conversation and ask those to Dr. Mackenzie live and you get to hear the answers. So with that out of the way, hey Sally. We were talking earlier when you first came in and you were saying you're very busy this summer. Busier than you expected to be. Is that right?

Sally: Yeah, probably everyone is, right? We're sort of post pandemic. And now all of a sudden you've got this mountain ahead of you, of things that somehow slid for a while. So yeah, it's a busy time and it's really a busy time for science. It seems like I'm not the only one who's really busy now. So everybody's big piles are colliding with everyone else's and everything feel urgent.

Cole: Yeah.

Sally: Time dependent.

Cole: Yeah, we feel it too.

Sally: Yeah.

Cole: Yeah. With all the different folks at the Huck we deal with and on our own team. Yeah, we're trying to keep breathing and just keep going, but I'm so glad you found some time in your busy schedule to come out and talk to us. So I know you're familiar with the podcast, so you kind of know what you're in for a little bit. And as you know, I'm going to ask you about yourself a little bit before we get into the science, because one thing we're interested in in this season of the Symbiotic Podcast is, what is it with these people we call risk changers, excuse me, risk takers and game changers, right?

It seems that some folks in science are a little bit more conservative and are happy to just kind of stay in their lane and maybe some incremental things, or just kind of take their time and stay on a track that feels kind of safe and comfortable. And other folks really want to just do something dynamic. They're not satisfied with the status quo. They want to ask deep, challenging, tough questions that might shake people up. And so you made it into that category. That's why you're on the show. And do you think there's anything in your personality, maybe in your upbringing, in your past, that would, would categorize you as somebody who's like a risk taker or a game changer?

Sally: When I was growing up, I was not someone who stayed in one place for a long time. My father, because of his business, we had to move quite a lot. And when you do that, I think you don't really establish deep roots in any one place. You have friends, but your social life really is never a deep one. And so I think it makes you more willing to take whatever comes and make the most of it, without the fear of how others might think or feel about what you do. I think also, I'm interested in this idea that if you're somewhat bored by school.

When you're growing up, you're always sort of looking for something new, I was that way. I was an experimentalist. I didn't like to sit in a classroom and just listen. And so I was considered a little bit of the troublemaker in school because I was impatient and I would become bored and therefore start finding my own way of learning things. I don't know whether that trend is a trend you'd find with people that are willing to back the system a little bit. Either speak their mind or are willing to take things, opportunities that come their way and really pursue them.

But I do think that people who become passionate about things later often have something like that in their background, sort of an impatience. You'll see it in their school life as being, not particularly good students or maybe students that got themselves into trouble. Kids who got themselves kicked out of school a time or two. But ultimately, that turns into something that really translates into passion for the things they care about. I've never done that study, but I wouldn't be surprised if that's the case. And I was that way.

Cole: Got it, got it. Yeah, you're making me remember my high school. Once my principal said to my mom, "Your son just doesn't fit in here, Mrs. Hons."

Sally: Yeah.

Cole: So I can relate to that. So good to know. Yeah. But it's fun because a lot of times the kids who have that kind of trouble later on turn out to have some wild, original ideas. And like you say, find their passion. I'd love to see an educational system that could do a better job with kids who have that kind of quality earlier on to help them find their lane faster and not have to be disciplined like that. But I guess that's another conversation. We're here to talk about plant science today, but then again, at The Huck, we're all about all the disciplines coming together and how do they relate, right?

Sally: Right.

Cole: And that's why we educate our graduate students a little differently at the Huck as well. Give them more freedom to try out different disciplines and just sample this and that, and find their way and see how different things blend together. And we'll be talking about how you're blending together some disciplines in your work as well in just a little bit here. But Sally, if you don't mind, I think I'd like to play a little clip for everybody, a little teaser.

It's a sneak preview, folks of, a video we're working on about Sally's work. It's from our Life From All Angles series, which run about five minutes and explain the science of some of these game changing scientists. And this will be a little precursor to our conversation to give you a sense of what Sally's up to. So we've been working real hard on this. We're very excited about it. Dan, if that's ready, why don't we cue that up and play that for the audience, then we'll be back and talk about the research.

Narrator: Every summer, this string of pearls plant sits outside on a porch enjoying near ideal growing conditions. But as the days grow shorter and the temperature drops, this plant will only survive if brought indoors. Though we may not see it, there's a lot going on inside this plant that helps it adjust to its new winter home. And as it turns out, the more precisely we understand the mechanisms regulating a plant's response to changing environmental stimuli, the better we'll be able to help farmers maximize their yields and more successfully adapt in a climate stressed world, and the better we'll be able to understand human health as well.

Sally: Plants are really interesting creatures because they have to process their environmental information and make use of it in how they will adapt to their environment.

Narrator: Sally Mackenzie is a professor of biology and of plant science at Penn State, Huck Chair of Functional genomics, and director of the Penn State Plant Institute.

Sally: You know, a plant makes a decision every day, "Do I hunker down and deal with this stress, or do I spread out my leaves and grow as fast as I can to outcompete my neighbors?"

Narrator: Mackenzie works in the rapidly growing field of epigenetics and has pioneered an entirely new way of manipulating plants to improve their resilience and yield.

Sally: When most people think of epigenetics, they think about the way genes are expressed. But more recently it's become clear that there's another feature of epigenetics and that is it isn't just the way genes are expressed, but the way that expression is transmitted as a pattern to the next generation.

Narrator: To produce next generation plants pattern for desired traits, Mackenzie's team has devised an ingenious, but simple method. First, a plant like this canola is epigenetically reprogrammed to behave as if it's experiencing extreme environmental stress. That plant is then turned into a root stock by trimming off flowering branches. A cutting is taken from the wild variety of the same kind of plant. This cutting called a cion is then grafted onto the distressed root stock forming a hybrid. Mackenzie has discovered through careful field testing that the seeds produced by these hybridized plants are significantly more resilient and productive than wild type versions of the plant. And this holds true, not just for canola, but for every species of plant Mackenzie's team has tested to date.

Cole: Very cool stuff. We had so much fun going to the greenhouse and in your lab and checking that out. And I've been showing the footage to even people in my family. Everybody just thinks it's so cool. Just even the grafting process and to think where we go next with that video is the deeper explanation of what happens after the grafting of that epigenetically modified of the cion onto... Excuse me, the wild cion onto the epigenetically modified plant. And let's talk about what happens after that, Sally, when you do this work and why do you do that? Let's get into why, why that happens.

Sally: Yeah, so that system in my lab is the product of our efforts to exploit what we know about the way that plants use their epigenetic system to change. So when we think about a plant or a human, you think about the genetic information, and we know a lot about that. Now, we have complete genomes, but the genetic information is basically static. That means genetic information from the beginning of life to the end of life doesn't change. But epigenetics means that there are decorations, if you will, proteins and small RNAs and methylation events that will come in and modify that DNA, and it's open or closed features in order to change the way it expresses.

And so those features will change over the lifetime, and then into the next generation. And those features influence not the genes themselves, but how they're expressed once. Once you know what that system is and how it works, you can start exploiting it. So what you're seeing there is that we take a plant and we basically fool it epigenetically into thinking it's under stress. It grows differently, it's slower, it's hunkering down and it's expressing lots of defense related genes. We use that as a rootstock, and then we graph to it.

Sally: And that wild type or unmodified plant we put on the top as a cion basically is going to receive small RNAs, which are basically messages of stress coming from that lower part. Those messages of stress are received in the upper part of that plant to the progeny and actually modify the progeny. It turns out, something that couldn't have been predicted is that when you take that stress signal and put it in what we call a naive genome one, that's never seen that stress, you get an enhanced growth figure. You get a plant that wants to outcompete its neighbors, that gives you higher above ground biomass, higher yield, more resilience.

Higher above ground biomass, higher yield, more resilience. And that vigor is the outcome of those small RNAs basically encountering what we call a naive genome, a genome that hasn't seen that stress. So that's more or less the big discovery, but we can now, of course, capitalize on that. In agriculture we can capitalize because we can make crops more resilient than we can just with traditional breeding, which takes much longer. A graft takes you a matter of a few months and you're there. But we can also capitalize on that in a more fundamental way to understand what those signals are that allow a plant to change its whole growth dynamic within its generation and to its progeny. And as I said, those small RNAs we know are vital and we can use genetic tricks, mutations that cut off those small RNAs so we can show that that is really the ideology, the cause of that change. So, you can do beautiful biology to fundamentally understand something that really has utility in agriculture and really in human health as well.

Cole: Right, right. We had that conversation. And that's where this video, again, is going to go deeper into something a little bit more fundamental, because as we say later in the video, it's not just plants that change because of the conditions around them, but all life changes. And you had sent me an article recently about this being an issue in science writ large in evolutionary biology, this idea that how fast will change happen and are we really seeing the fuller picture? And maybe we need to add some subtlety in there to account for these epigenetic changes that can occur very rapidly and be passed on to progeny just very quickly. Could you speak to that a little? And this is going to give us the ability to read, as you've talked about the methylome. And I'd like to hear about your partnership with a colleague in computational biology and this methyl IT system you've developed. So maybe we could hear a little bit about that for the audience?

Sally: Sure. So, as we initially conceived of evolution, as Darwin initially conceived of evolution, we really thought about evolution in the DNA context, your genetic information. And it does change over time, longer time by mutation, recombination, chromosome breakage, et cetera. Those kinds of changes do take place, we've document it. And we understand that evolution fairly well and its subsequent selection for the very best combinations that will go on. And that evolution is intact. But what we never really factored in to that was the epigenetic component. Meaning that change was over the long period of time. And epigenetics allows the system to accelerate evolution. And the way that happens is now you take that genetic information, mostly static, and now you add epigenetic changes or changeability to it. And suddenly you have the ability over the lifespan of an individual to come across and introduce changes, maybe by environment and stress, disease, et cetera. Those changes could then be inherited to the next generation and have some stability for X number of generations, that becomes this accelerated view of change we never factored into our original models.

It doesn't in any way invalidate our understanding of fundamental evolution. It just helps us to enhance, enrich our understanding of the long time span. And that second element of epigenetics we don't understand fully. And what I mean by that is, for us to really understand genetics, we had to decode it. You have to systematize this process. So we decoded it by understanding that DNA sequence could be interpreted as basically words of three we called codons. And those words of three could be mixed in various combinations to give rise to new proteins or products. And so the more we could decode that, the more we could predict it, the more we could manipulate it. Thus, here we are today with molecular biology.

Epigenetics will be the same, but the code is different. Because now what you have is, instead of looking at nucleotides, some of those nucleotides can be changed. You can add methyl groups, for example. And by changing these decorations on DNA, if you will, you can change the overall local landscape, and that will impact gene expression. So just as we understood how genes could be decoded, we could now take that methylation pattern and decode that into, what does that tell us? So now an organism sees a stress, a change in development, what have you, a change in epigenetic state. We can read that methylome, decode that information, and it tells us two fundamental things. It'll tell us what genes are responding and what networks does that involve. So suddenly you're now looking at when I create that stimulus, who's responding, what networks respond, and that tells you how an organism is perceiving its environment.

But the second is, you also have the ability to now understand on a global scale just the, let's say the energetic properties, the entropy properties in that system. In other words, is that system a healthy system, or is it a system that's dysfunctional? It's in a new state that's not a good state, that maybe is a less ordered state. There you get into early disease diagnostics, places I never knew my lab would go. But in fact, you can see this very easily in the methylome profile. So, as we think about our genetic characterization and understanding our predisposition to genetic disorders based on our gene sequence, I believe we could now use DNA methylation profiling. Imagine having that taken in your life at age two, again at age 10, again at age 16 and 30 and 45. And you'd be able to actually look at the changes and the impact of your lifestyle, your environment, your development on those profiles. And you'd have a much better understanding and predictive ability about your own health and wellbeing as a system.

We never really envisioned we could use the system in that way. So that's why we're putting so much time into this decoding, if you will, the understanding. The more we turn this into the language that we want it to be, the more we'll understand in agricultural context how crops can respond to their changing environment and how human health responds to its changing environment over time.

Cole: I've heard you say again and again that this is like a new language that you're decoding. You're decoding this new language similarly to when we map the human genome that this could be just as impactful. And we had a conversation earlier about, when it became available to the public to do 23andMe and everybody's going and getting their DNA tested, but it's not giving you the utility that you'd have from this methylome profile, which is, what can change in your lifetime? Because our genetics are going to stay static for our entire lives. But what we're talking about with epigenetics is how they are expressed, which in practical terms in somebody's life for their health, their wellbeing is maybe more impactful. Once what your genes are your whole life that's your norm, but all those different changes you go through are epigenetic changes fundamentally, right?

Sally: Right, right.

Cole: Yeah, it's phenomenal. And you have, you've put together, how many patents do you have now worked out from the research that you've done in this area?

Sally: So then, yeah, then you get into, how do you protect this information in a way that can be of most utility to whomever would use it? So some of the patents we've sought have been sort of agriculturally leaning. And that means we've sort of developed IP around this idea that you could introduce epigenetic variation that could be of agricultural value. And the reason we seek protection for that is so that we can in fact control the way that it's used, because we want to be able to deploy that in the ways that we think would be most efficacious and let's say advantageous to the broadest group that might benefit. And they were really just patenting the technologies as they're applied to crops, the grafting methodologies, the understanding of how to create epigenetic change.

On the other path is this idea of decoding, it's the methyl IT platform, it's various decoding efforts that we do to understand, as I was saying, entropy, energy features of the methylome, as well as identifying gene networks that are responsive. There you get into identifying genes that are good targets for drug design, or understanding pathways that would be good targets for drug or treatment design, as well as just understanding predictive capabilities. Are we likely on the decline here in this particular system? Is this individual actually headed for health problems and why are those arising? That capability we also think needs to be protected so that it can be deployed.

And there we envision perhaps creating a platform where there is the opportunity to let's say, instruct others on how to use that platform. Those that are in diagnostics, those that really want that predictive capability. That will never be a 23andMe kind of, "Here, you can get it in the mail." Because the real key there is the interpretation. That won't be left in the hands of just anyone. That clearly is going to be a much more robust dataset and an informative dataset that's going to need expertise to mediate that. And that's kind of what we're trying to learn now.

Cole: Got it.

Sally: What can we read? What can we understand, and what can we predict?

Cole: Yeah, with that in mind, I mentioned earlier, you've got a colleague in computational science. If you could speak about him a little bit and what he brought to the table, because I was fascinated when you explained, you have all this data and a lot of folks have had this data. But the thing that's different with what you're doing is you teamed up with a computational biologist who can see the math and interpret that data differently and find these signals, these specific areas in the data that are significant and that can give you the kind of power you're talking about for diagnostics, et cetera?

Sally: Right, so I'm the plant geneticist in the team and Dr. Robersy Sanchez is the computational biologist/statistician/applied mathematician in the deal. And so, Robersy obviously sees the world through a very different lens. So, his thinking is it runs along the realm of information theory that in fact everything that has thermodynamic properties adheres to certain principles and methylation wouldn't be any different. And so we can use what we understand of response and thermodynamic principles and bioenergetics and entropy relationships to derive meaningful information. So you treat it like a communication system, and you apply mathematical principles to that. And what you derive is the capability to look at changes in state. And then to be even more refined and ask if you're just using signal detection to siphon out only those methylation changes that are happening in response to whatever the perturbation is you're creating.

So you now introduce an environmental change. Who's changing in direct response to that perturbation? Those are the treatment associated changes that we now weave into gene networks to say, who is responding and how are they responding. And integrating all that information suddenly gives you this power, this ability to say, "When I introduce this change, that, that, and that network all come to the fore and become quite active. Now, how they're responding takes additional information, but just that power of being able to siphon through all that information, because this is a highly complex or stochastic system. So, being able to decipher out just those pieces you need from the myriad of noise in the system is vital. And that's what you need an applied mathematician to do is to teach you those tricks, so.

Cole: We love it. I mean, that's what the Huck's all about, right? It's like getting people with different disciplines seeing the same thing in a completely different way. And then being able to share that and translate it across, which is generally the challenge, because usually the first early conversations with folks like this tend to be, "What are you talking about? No, you're totally wrong. We can't be right." And then eventually they, "Oh no, no. Okay, oh now I see what you're saying." Yeah, and it's amazing what can come forward to evolve the entire process.

Come forward to evolve the entire process. So very cool. Very cool. I feel like there's one more thing I wanted to touch on and then I see the questions are really popping up here. So I want to take some of these questions from our viewers here, but I just thought this was such a cool idea and image that stuck with me, Sally, since you talked to me about it. The idea that a woman could be in the future in a hospital giving birth, and you said that you'd be able to take like from placental cells and if you had the right technology and people trained and knowing how to read the methylome, you could just tell from a placental cell so much about that infant that we are not able to see right now.

Could you just speak about some of the things that people might be able to see? I mean, this would be down the road. We're not there yet-

Sally: Yeah.

Cole: But that's the potential of what we're looking at.

Sally: Yeah. And so, one of the challenges for my lab is, of course, we don't do biomedical research. So we are sort of limited in testing our system to those available data sets that are robust enough that we can extract from them information we want. And one of them we started with was an autism related data set where they had basically taken placental tissue from births where that child had then later been diagnosed with autism and then those that where you had a normal child that was presenting as normal later in development.

And the real challenge with autism, of course, is that any mother having a child won't necessarily know for at least three, maybe seven, maybe even 10 years that child really is dealing with something different going on in their system neurologically. And so, and yet we know that if you could have intervened from day one, we could have really changed a lot of those outcomes when it comes to autism because so much remains undeveloped when a child is born. And so imagine from that infant on, you would really have a way to sort of reprogram a lot of those neurological behaviors had we had that information.

So we took this autism data set that had already been published with relatively little information coming from the original publication, but then applied our methods of analysis and suddenly you see all these networks emerging. Really interesting and very exciting things. In fact, certain genes in some networks had already, we found out, been patented by companies thinking about autism, so we knew we were on the right track in finding these. But we could see so much more in these datasets that it really did convince us had we had this dataset at the time that those placental tissues had come forward and not years later, would we have had the capability, or whoever would've had them, of notifying that physician you need to be talking to that mother.

There's a really high probability, you're going to see autism presented in this child. And the changes that a mother might have imposed in that situation, having that information would've been huge. So, that system's in place. It's just now presenting it to the right people who could now start to implement it. But yeah, we have published that work trying to get interest by the community. But I would say cancer's the same. I would say that we're able to really see, for instance, in pediatric leukemias, we were able to see all of the really vital networks quite early-

Cole: Wow.

Sally: So I think you can be predictive there as well.

Cole: Wow. That's phenomenal.

Sally: Yeah.

Cole: Who knew you'd start with plants and end up with this kind of capability like at your fingertips. It's amazing. I'm going to look at some of these questions that we have here. If I look at poplar, what do I see? Looks like Mark is at the top of voted up here. Mark, 11 minutes ago, asked "Could we create epigenetic seeds to help native plants like Chestnut trees defend themselves against invasive pests?" Wow. What do you think?

Sally: Yeah. So, that's really an exciting area. Because remember that with a lot of trees, what they have, not all, but most in common is not only can they be grafted, but they can also be vegetatively propagated. And so we're starting with a really simple system in poplar. And we're not very far along there because I'm still learning the language of trees, if you will, just how to grow them and how to vegetatively propagate them. But there are a lot of tree species where this would be feasible. We've also been working on things like, for instance, strawberry.

Strawberry also a species where you can vegetatively propagate it easily, and that's how they do this commercially. So we're also interested in can we introduce these features? And there, the trick is that you don't want to go through seed. You want to be able to vegetatively propagate and then have those changes occur without what we call gametogenesis, the producing of seed or going through reproduction. So we're using strawberry as that model, but that would be equally vital to trees because you don't want to wait until that tree is flowering, is putting out seed.

You're talking lifetimes to do that. So what we really need is that ability to create the graft, transmit the change, and then vegetatively propagate from the meristem regions of that cion so that we can now emulate those effects we've created in a whole forest of newly improved trees. And that is really my goal. That's part of what moved to me to Penn State-

Cole: Wow.

Sally: Was that we are sort of the keepers of the Mid-Atlantic forest region and we've got a lot of problems that would really be addressed by this. So-

Cole: That's right.

Sally: Yeah. I think you could.

Cole: Pennsylvania was not named Pennsylvania for nothing. That's right. I'm a big tree person myself.

Sally: Yeah.

Cole: Very cool. All right. Let's check another question. Michelle has asked "How is this pathway to cell signaling in humans" oh, this is live people. I make mistakes. Sorry, Michelle. Let's try that again. "How similar is this pathway to cell signaling in humans and bacteria?"

Sally: So in terms of the epigenomic language of methylation and methylation re-patterning over chromatin, excuse me, how you get there is a little different in those different organisms, the machinery used, but the outcomes are really quite similar. So we use the methyl IT platform and our various methods of analyzing data pretty much the same way in human datasets as we do in plant data sets. Now we don't look at microbial right now, but I'm assuming that there would be similarities at least down to yeast, whether you can go to bacteria. That's all together a different system.

But the idea of the outcomes and the decoding, amenability to decoding of the outcomes, that works fine. So we can work in a pediatric leukemia system and work in an epigenetic reprogramming of crops and have that be going on in parallel in the lab. No problem. There are features that are different, but they don't impact the outcome. Yeah.

Cole: Right on. Thank you. And I've got, let's see, one, two more, two more questions. We've got Tony Flores, nine minutes ago. "What are some medical conditions that could be seen in the methylome?" I heard you speak about autism. I heard you speak about cancer. And perhaps that question was submitted before we got to that. Are there some other ones you could name?

Sally: Yeah. Yeah. So for me personally, when I read the literature, I'm always looking for evidence that somewhere in that abstract or in that initial description of the disorder, they refer to it as complex. This is really particularly applicable to what we call complex traits in plants and animals. Often we'll call those quantitative traits, but complex traits. That's just code for saying there's a strong environmental influence on the expression of that trait. So, there's a genetic component and then there's this what we call G by E genetics or genotype by environment interaction that happens.

So, anything that has turned out to be a complex trait, and there are just whole myriads of them in humans. I mean, most of our traits are complex. We are defined by our environments, what we eat and where we've grown up and whether we're exposed to pollution and so many features of our environment define how we grow, how well we grow and the same with plants. So anything that is a trait that is defined by a huge environmental feature, like yield in crops would be really amenable to epigenetic analysis because that is a trait that is changing over time within a generation, and then of course transgenerationally.

So, it's really amenable to decoding in this way and you get the most value from decoding in this way.

Cole: You're making me think about some of the social justice environmental stuff in terms of where pollution is and who lives next to the pollution.

Sally: Right.

Cole: If you think about water, Detroit, just horrible stories and you probably could check out and learn more about kids and people living close to that stuff, that could gather more powerful data about it faster. I mean, that comes to mind for me. But yeah, that's really something.

Sally: Well, not only that, but even thinking, I mean, going back to the autism idea, we don't really know the ideology of autism. We don't know where it comes from. How much of that actually could be a consequence of the way parents lived or the environment that they had basically experienced before they've had that child? We've never asked that question, but we could. And with a lot of traits like that, to what extent can we link things that would be heritable that we've never known to be heritable? There are studies now about the way that populations lived during war time and living long periods of time with inadequate nutrition and the fact that they may have in fact had transgenerational effects subsequent to that.

You could use the decoding system to basically trace that. What were the gene networks that were really vital to that process and how were those inherited? And we don't really have that power in the systems that we use currently. There isn't methylome data in the literature, but it does not have that power. Yeah.

Cole: Ladies and gentlemen, I meant to say Flint, Michigan. I think I said Detroit. So please, people, and if Beth McGraw is watching, I particularly apologize to her. She's from that area. Yeah. You're just blowing my mind. Let's look at one more question. I think we've got one more here. And there's Michelle, there's Mark, there's Abby. Oh, "You've figured out methods to manipulate epigenetics in plants. Can it be done with animals?"

Sally: So, I'm less well-informed about the capabilities of manipulating animals. We analyze data after it's generated in animals. So, we are great at predictive, but in terms of actually introducing change there, I'm ignorant when it comes to animals. Because with plants, of course, as I said, we can graft. We can introduce genes transgenically fairly easily. And that's really how we do this. We basically go in and target a particular gene our lab discovered, and we downregulate that gene, and that's what creates the signals that create the nuclear response for epigenetic reprogramming.

Whether there's a parallel system in animals, I'm not aware of that. The closest you're going to come is work that you can see in C. elegans, worms-

Cole: Yeah.

Sally: Where they can create, or they can at least induce transgenerational changes and understand the small RNAs that go into to that transgenerational effect. But, in animals, in general, the ability to go in and create that epigenetic change is something I'm just ignorant of. It doesn't mean it can't be done-

Cole: But there again, maybe that knowledge could be translated to somebody working with animals.

Sally: Sure.

Cole: People and all that good stuff. Because we know we're not going to hack somebody's arm off and stick it on another body and see like the wild type version of Fred.

Sally: Yeah.

Cole: And the epigenetically modified Fred. So we have a better Fred baby, Fred Jr. Anyway, just teasing. So, wow, we're at 12:38. We've got just a little more time. This has been an amazing conversation. I would be remiss if I didn't mention Epicrop while we still have you here before we talk about our little friends like we like to do on The Symbiotic Podcast, but-

Well, friends, like we like to do on The Symbiotic Podcast, but could you tell us so that our viewers can hear a little bit about Epicrop in case they wanted to check that out or learn more about that?

Sally: Sure. So when we started on this journey, my thinking was once we recognized there could be implications for agriculture and/or biomedicine, we need to figure out what to do with this. And I was totally naive to commercialization and how to establish relationships with companies. And one way that faculty in general can do this is just to make a relationship with a company, come up with a licensing agreement. Maybe they help support the research. And you're basically sort of funneling information to them that they can then capitalize on.

And I was not really in favor of that model because I wanted this to be more far-reaching. I didn't want this to simply be used by one company simply because I didn't think one company would necessarily know how to use it. I think it really needs to be out more generally. So instead we started our own startup company, which is called Epicrop Technologies Inc. And it starts out strictly agriculture. And it's a company that basically takes our platform and takes our information on how to manipulate crops to introduce epigenetic change and move that into the commercial sphere. So my lab works with a plant species that's just a model. It's Arabidopsis thaliana. It's a little weed in your backyard. It's a weed in my backyard I find really aggravating at home. I pull them up and at work I take extra care of them.

Cole: You don't bring them into the lab.

Sally: But when you then take this into the agricultural sphere, this system will create 30% increases in yield in tomato. It'll create 30% increases in yield in sorghum, which is a major crop of Africa.

Cole: Phenomenal.

Sally: It will work in soybean. It will work in canola. Those are the major crops. We have it now working in strawberry and so on. Now we're starting poplar. So it gives us this opportunity to branch out. And there isn't a crop that won't go through this process. We just need to figure out the way that we want to utilize it. So the company's job is then to do that, to take what we know, turn it into a crop modification, and then try to be a conduit to companies that really could capitalize. So obviously strawberry might go somewhere completely different than soybean would.

And that's what Epicrop is, is just sort of that conduit to get it into the hands of people who could really exploit it and understand it and elaborate it beyond what we can do. And then at the same time, there's this platform of being able to predict how crops are behaving. There, you're getting into understanding crop phenotypes and their gene networks. That's very vital information for a lot of companies that they don't currently have. So that's a different part of Epicrop's goal is to help provide that information so that people can understand their own systems, not just ours, in new ways. So Epicrop is kind of that resource allocation process, if you will, because my lab just can't manage that. So we hand all this off and then the company is expected now to make those connections with who can use this information in the best way possible.

So Epicrop is right now stationed in Lincoln, Nebraska, because it's central for the agricultural community. Now that I'm on the East Coast, I doubt it will stay there forever. It'll probably find a closer home at some point. But it's a good, very little, just a startup now, but that's what we foresee it in its future is to have these relationships with the larger companies that can be really useful to facilitating improvements in agriculture that you really can't make with traditional breeding. Yield resilience. These are not easily bred traits. Complex traits, as I said.

Cole: Complex traits. And as we mentioned in our video, there are implications here as the climate stressed world continues to face more and more stress. This could be really important. It's such exciting work. And in this world of so much bad news and so much that is heartbreaking and hard to deal with, it's wonderful to see this work going on that gives us some hope that human ingenuity and creativity are still alive and there's still a lot of wonderful stuff people can do to make the world better and to deal with the challenges that we have. So thank you for the work that you're doing. I'm going to be watching. I hope others will watch as well. If people want to follow along with your work, is there a particular place they would go, like to your lab website? I know we're going to put it at the end of the video when we publish that, but is there a place that you send people most commonly to follow along?

Sally: Well, right now, this is fairly rapidly merging. And very new information. So usually we have different connections with different people. There's the ag community, which won't read any of the mathematics, and there's the mathematics community that has no interest in how plants grow. And so we're kind of spread all over. But yeah, we're going to try to redesign my lab's website to be a little bit more of a conduit for that beyond our publications.

Cole: Okay. So people can Google Dr. Sally Mackenzie, Penn State, and follow along and reach out and get in touch. I know we're trying to connect you with a Huck graduate who is a lead life scientist with NASA working in the international space station with the garden there. She recently did a presentation to some of our Huck graduate students in plant biology. And I know you've mentioned that your method could be very useful for growing plants in space. So there's just so many cool things that can come out of this work. So very exciting. So wonderful to have you on.

Before we end, and I know I'm going a little long because it's hard to stop talking to Sally, but I do want to do what we do on every episode of The Symbiotic Podcast livestream season, which is to just let folks out there know that when it comes to diversity, we really embrace it at the Huck Institutes, so much so that we decided that we could celebrate the diversity of Penn State people by exploring alternative plushies for Penn Staters.

And so Dan's probably going to pull up a video here in a second and show you. We are no longer limited, ladies and gentlemen, to just the lion. We love the lion, the lion's terrific. We all love to see him at the football games doing gymnastics, et cetera. But if you're not a lion person by nature, you could go other ways now. You could go with a Penn State pink unicorn, for example, or perhaps you could go with a Penn State gnome. Or if you have a little baby child in your life who needs something to play with, a little beanie bear, a little Penn State beanie bear, just to get them indoctrinated the Penn State way before they even get to preschool. That's available to you.

There's even at this stage a llama. That's Lisa Llama, the only one of these plushies that comes with a name. And I'm not hawking these for any local businesses or anything. But if you search around, if you see a plushie here that you really like, and you're a Penn Stater who might be a little different, maybe you check that out. So, like I say, there are gnomes. There are unicorns. There are llamas. There are bears. Penn State's big. There's enough room at Penn State for all of these lovely animals to coexist.

So right now with our audience, Dan's got a screen up and we're just going to ask you, you can vote right there in the chat. You can vote on your favorite plushie. And I really encourage you to do so because we're doing our own research, Sally. We're researching, I don't know if it's a psychological profile, if it's social psychology, I don't know where we're going to publish this research. But the idea is we're going to find out from all the different scientists on the show which audiences liked which plushies, and then we're going to share that data with you at the end of the season. So my last question for you before we wrap up, Sally, is do you have a favorite plushie? What would your favorite be?

Sally: It's the llama, for sure.

Cole: It's the llama. Lisa Llama. Is it the eyes? It's the eyelash? She just has that look. What's about the llama?

Sally: It's the different.

Cole: It's the most different.

Sally: Yeah.

Cole: It's the most different for you.

Sally: It's the difference that I'm attracted to.

Cole: All right. Well, Sally Mackenzie, Dr. Sally Mackenzie is a llama person, ladies and gentlemen. Well, thank you so much again for coming out. I want to let our audience know that we'll be back in one month with Lance Lian, who's doing phenomenal things with stem cells, just mind blowing. He's created pancreatic cells that actually produce insulin from stem cells, which is not an easy thing to do. So he's another one of these risk taker game changer people. So come back. It'll be one month from today, the last Thursday in July. I hope you'll make it back. And if there's other people you think should see this, we are going to have this out in about a week, so others can watch. And then we will also be releasing the full five minute or so video about Sally's work. So watch for that as well. So without any further ado, thanks so much, Sally, again. Thanks everybody for watching. 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.

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.

---

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.

Cole Hons: Greetings fellow homo sapiens, and welcome to The Symbiotic Podcast. We're here in our third season, streaming live from our studio at College Heights in State College, Pennsylvania. Thanks so much for tuning in. It's my pleasure today to introduce you to our guest, Dr. Steven Schiff. Welcome, Steven. Dr. Schiff is a pediatric neurosurgeon and Brush Chair Professor of Engineering here at Penn State. Great to see you, Steve.

Dr. Steven Schiff: Good to see you too, Cole.

Cole: So, are you over your jet lag from coming back from Africa this latest time?

Steven: Mostly. Still getting up at four in the morning, each morning. Which does get me to start my day early, but it also ends pretty early.

Cole: How often are you running back and forth to Africa these days?

Steven: Well, before the pandemic, it was every three to four months. During the pandemic I made it back once. And then this was the first more normal visit where we could get people together on this last trip.

Cole: Right on. And you have a long history in your life with Africa. Is that right? Can you speak about that a little bit as we jump in here? Oh, before we do, this is live, this is live stuff. I should let the audience know. I'm so excited to talk to you. For all of you watching out there if you want to participate, please join the chat. You can put your name in there. You can stay anonymous if you wish. You can see the little chat box next to the live stream, and you can put your questions in there. You can also vote up other people's questions. And at the end of our conversation today, we'll ask the top voted questions to Dr. Schiff, and you can hear his answers. Sorry about that Steve. It's live, no net. Here we go. So, again, let's talk about Africa a little bit.

Steven: Well, I first visited Africa as a boy with my family. And I was just fascinated. And it was so different from anything that I'd ever encountered here in United States. And I had harbored this childhood dream that if I could ever go back and be able to do something useful and helpful to people on that continent that I wanted to do so. And so later in my career, I found that opportunity.

Cole: That's terrific. And how old were you the first time you went to Africa?

Steven: I was 11.

Cole: 11 years old.

Steven: Yeah.

Cole: Oh, wow. That's an interesting age. And was it for a good, long chunk of time?

Steven: I was in Africa for about six weeks then. But those memories as a child just stuck with me forever.

Cole: Yeah. Cool. I went to Bumpus Mills, Tennessee as a six and seven year. And that formed me as well, but maybe in different ways. But we won't go there. We're here to talk about you.

Steven: I have family in Tennessee. I understand.

Cole: Bumpus Mills, Tennessee in particular.

Steven: Yeah.

Cole: Yeah. So, anyway, it's been so great getting to know you a little bit in this last month, as you've worked with the team here at the Huck Institute, and we got to learn more about your work and make the video that we're going to be showing, debuting in a few minutes here for our audience. It's just fantastic stuff. And to lead into that, I just want to remind all our viewers, this third season we're doing of the podcast is about risk takers and game changers. And the reason we wanted you on the podcast is we feel you fit that mold of a scientist who's taking risks and really changing the game. And so I've been asking all of our guests, were you always a risk taker? Do you consider yourself a big risk taker? Were you as a kid?

Steven: I don't think so, except in one domain. When I was a kid, I was pretty good at ski racing. And you got pretty good at ski racing because tended to take more risk along with some skill than other people might have been willing to take. I say that now, it sounds like I was insane as a kid, but you don't think that you can be hurt out there. And I was actually a finalist in New York as a high school kid, but too much of a nerd to make much further than that and eventually stopped it because it seemed too risky. Too many other people were getting hurt.

Cole: Yeah. Yeah. You can definitely hurt yourself. Yeah. My son went skiing for the first time recently and came back in one piece. No broken bones. We were very happy about that. And ski racing is by yourself though, right? You never see people skiing next to each other.

Steven: Oh, they do some of that these days. But in the classical forms of Alpine racing, it's just you by yourself.

Cole: Yeah. Should just try to get down there as fast as you can. Just a wild man. So, you're a wild man on the slopes.

Steven: Well, not anymore. Although, training as a physician, especially with things such as infectious disease, you learn how to control the risks of exposure and keep yourself calm and faced with people with contagious and dangerous diseases. And it becomes something that you absorb professionally. And so that has helped, but I'm a much more cautious person now than I was as a teenager.

Cole: Got it, got it. Well, that's interesting. And I would say, one thing we're fascinated in learning more about is what causes people in the scientific realm to take a risk. And I know that you are the recipient of two major NIH grants that are considered high risk, high reward grants. And here at the Huck Institutes, we've got a little seed fund that's called HITS, the Huck Innovative and Transformational Seed Fund. And it's supposed to be stuff that's too risky for the NIH to even look at. But the NIH does have a program for things that they consider risky. And you're one of the few people that's hit it two times, not just once, which is pretty phenomenal, like very, very rare that somebody would be given that kind of money two times. So, what's your magic sauce? What do you think is going on there?

Steven: The first time back in Africa as an adult, I visited an old and very dear friend of mine who had moved to Africa and built a hospital. And I was amazed at the struggles and the types of disease that he was treating. And perhaps searching for good problems. I mean, if you are at a university and your faculty, and you're doing research, you can work on things that are of no interest to anyone and including yourself. Or you could find things that are just the best use of your precious time on earth. And I asked him, he's Ben Warf, he's now a professor at Harvard. Very well known for his surgical work. And I said, "What's the most important problem you can't solve?" And he thought about for a moment. And he said, "Maybe I could help figure out what makes thousands and thousands of these infants sick."

Steven: And they had never been able to recover what organism gave these babies brain infections. And then in the survivors, they often needed brain surgery for the fluid that built up. And I thought, okay, how hard can that be? 15 years later, you and I are now talking and we're beginning to crack this problem open in a useful way. But faced with something that could be solved, but no one had. And from someone like myself who did not have a background you would've expected to have been an expert on baby infected with organisms that got into their brain. It was a struggle.

Steven: So, this isn't like an airplane pilot, where if that plane crashes, everyone and the pilot dies. This is risky in the sense that we needed a lot of resources to crack this problem. We had burned through a number of different seed grants, which got us started, got us looking at some of these samples. But we needed a major investment. And there was no expectation that this would succeed, but the NIH and very thankfully the NIH director decided that this was worth the risk. That we would fail, because if we could succeed, it was a huge impact and potentially one that had global impact around the planet.

Cole: So, you feel it was that potential impact that moved the needle for you, so to speak.

Steven: Definitely. And the same story for the second one of these grants that we received, we had been the only people really in that space, working on these problems. Part of that is a cultural and political issue around the world. We testified to Congress about 10 years ago on the fact that these newborn infant infections were unstudied, uncharacterized and were killing about a million babies a year around the planet. And much more than many of the other diseases that we put enormous resources into such as malaria.

Cole: We put some of that footage in our video, which we're very proud that we were able to try and condense. That was the hard part was condensing into five minutes, all these different pieces of what you've been doing for 15 years, right? At this stage. And we're going to cue that up in a minute. So, folks can see some of what you just shared is in the video, but it'll be nice to just have that out to the world to get that story out there, which I think is really important. There's so much good work going on that people don't know about. And I think that making more people aware of what the problems are and how big the problems are can only help to muster more support in the public and hopefully with lawmakers and institutions like the NIH, et cetera.

Cole: So, why don't we go ahead and cue that up and I'll just remind everybody, if you have any questions as you listen to Dr. Schiff, and there's anything you'll want to know as you watch the video, as we go through the Q&A here with myself and Steve. You can ask your questions too. You can just pop those in the chat and we'll get to those a little later. So, at this point, Dan, if you're ready, we could cue up that video and we'll take a little look at our latest life from all angles, featuring the work of Dr. Steven Schiff.

Narrator: If you've ever watched a medical drama, you might recognize these, their MRI scans of human brains. The scan on the left shows the brain of a healthy infant from Uganda. But in the scan on the right, there's this circle, it's an absces. A fluid filled swelling. All of these scan show them too. These abscesses are linked to a condition called hydrocephalus. It affects more than 400,000 newborn children around the world each year, and could lead to cognitive issues, brain damage, and death. What causes these cases of hydrocephalus in the African nation of Uganda is at the center of a medical mystery that tells us a lot about how global health works and can be improved.

Steven: Hydrocephalus is a condition where you don't clear the fluid that is made in your brain every day and helps nourish it and suspend it adequately. And in a young baby, the fluid builds up in the head because the bones of the skull are not yet fused. The head gets large.

Narrator: Steven Schiff is a pediatric neurosurgeon and Brush Professor of Engineering at Penn State. He's leading a global effort to better understand and treat childhood diseases in general and hydrocephalus in particular.

Steven: So, we think that upwards of a million infants a year die in the first month of life, around the planet from an infection.

Narrator: In 2007 Schiff spent a week in Uganda to help address technical problems with diagnosing epilepsy. He examined the equipment and made some professional connections, but what really caught his attention was the number of babies he encountered with enlarged heads.

Steven: At the end of that week, I asked my colleague, well, what's the most important problem that he needed help solving? And he said, "Well, why don't I try to figure out what makes these infants sick?" I thought, how hard could that be? And here, 15 years later, we're finally getting answers to that.

Narrator: The doctors in this hospital had treated over a thousand cases like this without ever knowing the cause of the condition. To gain some clues Schiff turned to genomics.

Steven: There's a piece of a gene that all bacteria have that we have large databases for. So, if we sequence pieces of that, we often can determine pretty close what the species is.

Narrator: Working with an international team of colleagues for over a decade Schiff discovered that almost all the hydrocephalus in Uganda was caused by one organism, a specific variant of the bacterium Paenibacillus Thiaminolyticus.

Steven: It was never known to cause serious illness. If we offer it to mice, the strain that we knew well, doesn't hurt them. The strain from the African infant kills them usually in a day or so.

Narrator: It took more than 4 million and over a decade to identify and characterize a sea single pathogen in Uganda. Until similar work is performed in every low and middle income country Schiff points to the promise of highly integrative prediction techniques to help reduce the burden of infection on infants globally.

Steven: And although in the future, I think we're going to be able to have new technologies that enable us to do a much better job of determining what makes an individual sick from a given bacteria or a virus. Today a workaround is what we call predictive, personalized public health.

Narrator: The key, says Schiff, is to cross reference relevant data streams, including location of infections, prevalence of specific bacteria in specific places and environmental factors like rainfall, temperature, and humidity. By combining satellite data with on the ground surveillance over time, this novel approach could empower doctors to far more accurately diagnose patients at the point of care. As he testified to the house foreign affairs and committee in 2011, Schiff sees this work as a moral imperative.

Steven: As a physician and scientist, and as a father, I'm struck by how much we don't know about newborn infections in developing countries. I am concerned that one reason is that the newborn infants who die there have no political voice.

Narrator: Schiff is quick to point out that none of the work he's doing would be possible without scores of people willing to cooperate in pursuit of a higher purpose. Something bigger than anyone's individual career.

Steven: We put 50 people on some of these scientific papers. You can get buried in the large numbers of names that are credited with authoring these discoveries. But people really surprise you and faced with a project worth doing. I've been just so proud that the teams we've put together are just as dedicated today as they were when we first asked, "Would you be interested in ... It's funny, you tell people, we got a lot of, we have thousands and thousands of infants dying in some of these sides. Would you want to help us? And I usually don't get to finish the sentence before most folks who I would approach will go, "I'm in. What do you need?" And that's part of the reason I think we're doing a good job.

Narrator: To keep up with the latest developments in Dr. Steven Schiff's work along with other scientists at Penn State's Huck Institutes of the Life Sciences visit huck.psu.edu/subscribe.

Cole: Great story, Steven. Yeah. We're so proud to be able to work with you and help more people see what you're up to and all the people you're working with. You just sent me a new photo today that we're going to put in that video. When we put it out as a separate piece, the big team, that was taken last week, right? All those folks that have come together. And I love when you shared that people just step forward because they want to make a difference. They're inspired by something bigger than themselves. That's been a theme for all of our guests here is this idea that it's not just science for science sake, although that can be inspiring as well. But science that makes a difference in the lives of other human beings. It's really powerful stuff. And thank you for doing that.

Steven: I used to think that it was a personal decision on my part to focus on children's medicine. Because originally I had trained as an adult surgeon. But dealing with infant disease is just universal around the world. It doesn't matter what the politics are in a government or between different political factions. It's one of the great unifiers of humanity. And I just think I'm very lucky to be able to wake up each morning and work on problems like that. And with so many people who are so dedicated to working with us.

Cole: Yeah. That's a good attitude to have. Yeah. I think that meaningful work inspires us to keep going.

Steven: Well, it's also important I think, Cole, in a university. So, we train a lot of students at the graduate level either to work in industry or government or the majority to go into academics. And I tell them, there's no difference so far as I'm concerned between the three different domains, we're supposed to introduce them to. Research, education and service. And if we pick the right domains to work on it all blends into one. And I tell my grad students, don't waste your precious life on anything and you don't really believe you should be working on.

Cole: Yeah. That's great advice. That's great advice. Well, as you mentioned, the next generation of scientists, you're reminding me that there's a component to your work that includes bringing knowledge, but not just technology, a knowledge, but also starting program in the countries where you're working. Could you speak about that a little bit?

Steven: So, we try very hard, even when they're not designed, the grants are not designed to build capacity, to build capacity. A lot of the science in developing portions of the world as for better or worse, and for lack of a better phrase, but called colonial. We come in from Europe or from the United States with clever ideas. We do research projects, we leave. And the goal in all of our work is that when we're done that the people in the countries facing the problems that they face that are currently insurmountable will have the skill and the capacity and the training to take up the work themselves and to deal with future problems.

Cole: What does that look like on the ground?

Steven: Well, we put teams together to not just do the work, but to be research units. So, we have a very good research unit at one of the hospitals in Uganda that we piece together from three different NIH grants. Both grants here at Penn State and also grants at Boston Children's Hospital. And I probably have helped half a dozen students at the graduate level now get their masters or PhDs mostly in Africa. But we do work closely now with a graduate student from Vietnam. Another site that NIH has encouraged us to branch off to.

Cole: Yeah, let's talk about that a little bit because you've been in Uganda largely there for a good long time, proving things out. And the bacteria that was mentioned in our video, which I want to revisit in a minute. But that's been the core and you've learned a lot. But now you can take that model and go to other places. So, where is it taking you?

Steven: So, pediatric neurosurgery has about a 150 of certified practitioners in the United States. It's a pretty small club. And we basically know each other. So, within that group, we also know closely those who were deeply embedded in working in low and middle income countries. And so in the same way I was introduced to some of the pediatric neurosurgery problems and diseases in Uganda. I had colleagues, oh, several colleagues from the University of Alabama who'd been very intercalated into training and education of neurosurgeons in Vietnam. And the first day, I walked into an operating room in Hanoi I saw exactly the same type of case that we'd been trying to understand in Uganda.

Cole: Oh wow.

Steven: And what I proposed to NIH is that we don't know if it's the same organisms, but if we're going to make sure the strategies we're using in Africa are universal, then an Asian site, such as that was ideal. And they agreed.

Cole: That's terrific. So, that's scaling up now?

Steven: We actually, during COVID, it was very difficult. It was very difficult to get in and out of almost any country for periods of time. But with good teams in place, we continued and finished our recruitment of patients and our sampling of infants from Vietnam. A few months ago, we got about 500 frozen specimens sent to us here at Penn State and were feverishly working on analyzing them to begin to answer some of the questions you probably would like to ask me.

Cole: Yeah. Well, you sort of mapped out your methodology as my understanding in Uganda. And I want to hear about the difficulties that you encountered bringing those samples into the lab. Because we talked about that in our interview. There wasn't enough time to get it into a five minute video, but I'd love to hear you recount that story a little bit of the specific challenges that you encountered when trying to find the cause that bacteria, that was the cause of hydrocephalus in Uganda.

Steven: Originally we tried using very inexpensive methods. The are forensic methods. The police use these here where you'd take some blood and you'd put a few drops on a filter paper card and then you dried it out and put it in a FedEx envelope and mailed it. There are some molecules that survive that fairly well. But the quality of specimen that we needed to accomplish what we ended up accomplishing needed to either be flash frozen at such cold temperatures that everything would be preserved or they would be placed in preservative and still kept cold, but there was special preservatives for molecules now, DNA and RNA, that are the molecules that either code for our lives or for the bacteria and parasites that we find in the babies, as well as the next molecule that the DNA is translated into, which helps code for the proteins.

Cole: Got it.

Steven: That give us life. So, those two methods required a cryogenic infrastructure be set up. Originally, especially in regions where the electricity supply isn't great. We did this with liquid nitrogen and giant thermos called dewars. And often there was no known supply of liquid nitrogen available in the country, but some of our colleagues were extremely good at making sure they could find liquid nitrogen when we needed it. And it's those human touches that ensured that we could be successful. And as you mentioned, or in the video, this whole procedure setting up in infrastructure, currying thousands of tubes overseas with the shippers that we use are liquid nitrogen based. They can go in cargo on airplanes, but they only last about six days before they thought. And I think all of them ended up coming in about five days and 12 hours into the trip. So, it was pretty nerve wracking.

Cole: Yeah, high stress situation.

Steven: But we got everything here and then we've spent literally years carefully preparing, sequencing, analyzing. The analysis is very difficult. So, I was giving a talk at NIH once a and I said, "At this point, this is the current technology. And you could give me large grants to go into every impoverished country on earth and try to do the same work. But what we've done doesn't scale. It doesn't broadly disseminate, not with current technology." So, the other approach, which we're very vigorously working on is taking this kind of surveillance and producing models to forecast. If you know where a baby comes from and when the infant got a bad illness in the first few weeks of life, we appear to be able to do a reasonable job of predicting what the likely organisms are and therefore what the doctors at the hospitals and clinics should choose that week for their first line antibiotic treatments.

Cole: Right, right there at the point of care, to sure it's the correct medication or condition.

Steven: Exactly. Today, all over the world, infants who come in with a very severe life-threatening infection in the first few weeks of life are all recommended the standard treatment of two old inexpensive antibiotics. And it works for some of them. But the death rate and the damage rate under that type of treatment is far too high to be acceptable. And we can do a much better job.

Cole: Right. And that is what we called in the video. It's predictive personalized public health. It's all that data just layered on top of each other to, comes down to like, where's this baby from? And then you start to collect what are the different causes of the infections and the different parts of the world based on rainfall and all these environmental factors, correct?

Steven: The basis to all of that, Cole, is surveying just like we surveyed patients with the different COVID 19 variants. For babies with bacterial and parasitic and viral infection, you can make a map. And if that map were static in time, it would be easier. But many infectious diseases fluctuate with the environmental conditions. In east Africa in the highlands, you get two rainy seasons a year to worry about. And we're picking up these rainfall links. Many bacteria come from soil, for instance. Many come through insect vectors. All of that conditions and soil, breeding of insects, all of that is dependent on environmental factors. And all of it can be put into the same framework we use to predict the weather.

Cole: Got it. Yeah. Good use of technology.

Steven: Well at Penn State, we also have the great benefit of really high class meteorology and geography and statistics. And these are problems nobody solves on their own. I'm here, if anything, the spokesman for a fantastic group of people who work together as one. These are problems, which demand that people from many different disciplines are brought together. So, I would like to think, and I think it's true that our meteorology, that we're doing to understand African weather patterns, is just as good as the infectious disease genomics that we use to identify what the organisms are.

Cole: Absolutely. You're preaching to the choir here, because at Huck that's our core belief. That's really what I think the Huck exists to do in the life sciences framework is to bring the disciplines together and make a bigger map or Troy Ott, who helps run our graduate programs, where our graduate students go to all these different disciplines too. We had this mapping conversation recently. He said, "No, at the Huck, it's more like we're making the maps." He's like, "We're out there following the rivers and like chopping down some ... You know what I mean? And I would consider you one of those path makers. So, you're going to go in a new place and new maps will be built to follow what you're doing. And to your point, it's not going to be one person doing it.

Cole: It's going to be a whole lot of different folks making a map that just didn't exist before. The data's never been brought together. The teams have not been brought together. That's what's so exciting for us working at the Huck is seeing folks like you and telling these stories. I know it's about 12:30 right now and we've got about 15 more minutes together. I think I'm going to join into a chat here and see if we've got any need questions that people have put in. Oh, here we go. We definitely have some questions. Oh, ask ... So, right now, reduce the number ... Now that you have ... Oh, great question. Great question. I had this one in my mind too. So, Kenny asks, "Now that you know what bacteria is causing these infections, what interventions or precautions, if any, can be taken to reduce the number of them?"

Steven: Oh, great question. That was several hours of morning discussion with colleagues, both here in the US, UK and Africa. There are broadly speaking, you divide this into two domains. When an infant hits the clinic door and is sick. How can you better treat them for an organism that we have no experience treating in the past? There's one known case recently published of this organism. And that was a postmortem examination of an infant who had died. And so what we literally spent last weekend doing in [inaudible 00:33:42], Uganda, gathering all of our physicians and investigators together is what evidence do we have that we can bring to the table to make a guess at best practices? That is which antibiotics and for how long. And since we've never looked at this before, randomizing that first guess against our second guess, as long as the, we have no reason to think one is more effective than the other, is begin to see which two paths might give better outcomes. Then pick the best path and then try variations of that.

Steven: Again, seeking to both cure these infections before they cause major damage or kill the infant. And of course, we'd also like to prevent this very high load of infants that survive, but then need brain surgery in order to clear the fluid that builds up. What you'd really like to do though, is prevent the infection. So, part of this conversation is how broadly do we have to sample soil, water supply, animal products? Is it in the mothers? We've done maternal trial. Sampling mothers at the time of birth. Failed to find any evidence that this one bacteria is maternally transmitted, but that doesn't mean it's not going on either in certain cases.

Steven: Because in many other illnesses where infants get infection around the time of birth, most of these babies get sick in the first week. And so we do have to worry about their home environment and whether any of this is transmitted, because the mom carries the bacteria or other pathogens with them. And so all of this over the next several years will require new funding streams, which we'll raise and then gathering the teams and effort together to do those steps.

Cole: Thank you. I'm going to hit you with another question. This comes from anonymous. "If you solved all the infant infection problems, what other kind of research would you be interested in doing?" Boy that ... All the ...

Steven: All the infections. Well, I've worked on controlling seizures and spreading depression, which is one of the triggers for migraines and cerebral palsy spasticity in children for many years. And if I did solve all of the infections, what I really do know something about won't be solved, and I would put a lot of time into that.

Cole: Got it. Thank you. Here's an interesting one. Also, anonymous. It says, "What subject area has been the hardest to pick up after shifting from surgery to this research?"

Steven: I think the hardest part is all of the changes in our understanding of the genome. I wake up, I think every morning, wishing I knew more. But so do my colleagues who do that for a living. It's such a fast breaking avalanche of knowledge about how we are encoded and what we do with those codes.

Cole: Do you think that AI has a role to play there in managing that avalanche of data? Do you think that-

Steven: It's the universal question, Cole? I mean all of us who are a little old, we all got taught to model things like Newton modeled throwing a ball. You come up with first principles and you study it for years and you understand gravity and you write down simple equations. AI has proven again and again that it can do things with understanding physics and biology and public health in ways that even if we don't understand completely what the computer's doing, look, I want results. And we heavily use artificial intelligence and machine learning in almost every domain that I work on now.

Cole: Yeah. That's a critical one in terms of the disciplines coming together, just coding. And I mean, God, the digital world we're living in. Going back to our digits and our hands, right. That's always every once in a while that hits me because we're using our little fingers and being digital.

Steven: I'll date myself. When I was in college, they had the first teletype, a computer at Dartmouth where you could enter lines of simple code and it would spit back answers. It was a programming language called Basic. And I used to crawl up to the one room in the department that had one of these. And it was just amazing that you could do such a thing. Now our students not only come with complicated machine learning network architectures that I honestly have no idea other than magic, how they pull that one off. And the next morning they come in with a web app and go, oh yeah, I took that thing and if you want to post it on the website, anyone in the world can now upload their data and it'll spit out the answers. And I go, oh sure. Why not?

Cole: Yeah. Why not? Go ahead. Pop that out. Yeah. Well those moments can give you hope. Because we hear a lot in the mainstream and in the media about like the evil stuff that can happen with social media and misinformation and people getting depressed and upset and jealous of one another, body image ... There's a lot in the media about the dangers of tech, but there's also amazing stuff going on, on the flip side. And I do feel that the global community of scientists when they do get together on something, it's incredible, the potential of what we might be capable of.

Steven: These are tools, Cole. You can use tools for good things and bad things.

Cole: Yeah, absolutely. Well, let's see. Oh, I've got one other question. And then we're going to have to start to wrap up. I have a fun way that we wrap this thing up. But I'm going to ask one more question. This is from Sam. It says, "Now that you've identified the bacteria, where do you think it is coming from in the environment?" This will be our last audience question.

Steven: Sam, I'll give you my best guess, but a warning every guest that I've made about what I expect to define working in Africa have all been wrong. But my guess is that this is a soil organism. It lives next to on the tree of life, similar organisms or soil organisms. It infects the babies when the rains come in, not during the dry seasons. That's my guess today.

Cole: And so you'll be proving that out or disproving that out in the next phase of the work.

Steven: Ask me in a year.

Cole: In a year. Okay. We'll come back in a year. Okay. Speaking of coming back later, this is how we like to go out this season. You may have noticed we have some friends here, we're not alone and maybe we can cut wide and Dan can show who we have with us today. We mention this on every episode. This is just so that we don't get too serious about all the perils of life on earth. I consider this, I've been meditating on it lately. I feel like it's one way that we can contribute to the diversity of Penn State in a different kind of way than people are used to thinking of. And that is the diversity of plushies that you can get in the world today that are Penn State. Each one of these plushies has a Penn State logo on it.

Cole: And Dan's going to queue up in a second, a little video that we made about the plushies. And I see this as the evolution of Penn State. You no longer are limited just to the Nittany Lion plushie. If you were to go, and these are all available at stores right here in State College, PA. You can get a llama plushie. You can get a gnome plushie, Penn State plushie. You can get the little baby bear plushie, which I like to call the infant indoctrination bear. Because it's growing the next generation of Penn Staters to grow up with some allegiance to old blue and white. And you can even get yourself a beautiful pink horned, unicorn plushie. And so we like to end every episode by letting our guests vote for whatever their favorite plushie is.

Cole: So, if you go into the chat, there's a little button where you can vote and it asks you which alternative plushie is your favorite. Do you like the Lama? Do you like the gnome? Do you like the bear? Or do you like the unicorn? And everybody loves the nitany lion. So, we don't have the nitany lion as a choice because that's a given. We all love the nitany lion. But this is our own research project, Steve is that we're going to collect the data on every episode of the podcast. And we're going to see how the audiences stack up. For instance, Nita Bharti was on last week. I think that the Lama was the number one plushie choice of that audience. For David Hughes, I believe it was the gnome if I'm not mistaken. And we're going to see what your audience thinks. And I'm going to ask you directly, do you have a favorite alternative plushie? If you wanted to take one of these home to your office or off to Africa on your next trip, which plushie would you go for?

Steven: I'd have to pick the gnome for two reasons.

Cole: Okay.

Steven: It's kind of a homely looking creature and he always wears a hat in the sun.

Cole: Oh, he wears ... I've seen the pictures of you in the hat. You've got the African travel hat.

Steven: I swear I burn in about five minutes in the equatorial sunshine. So, yeah.

Cole: Oh boy.

Steven: I keep extra hats in case I lose one.

Cole: You got a backup hat. That's good. So, you're a gnome man. Duly noted. I believe David Hughes was a unicorn man. And Nita I think went with the Lama. she liked the unicorn as well. And so as we go out, we'll be sharing those with you folks out there watching, we'll see how this all turned out. And at the end of the season, we'll be back in touch with you with a report that you can share with colleagues and let them know how you stack up plushie wise. I'm sure that's going to be really important to you in your future career.

Steven: Well, thanks very much, Cole. I look forward to that.

Cole: Well, in all seriousness, thank you so much, Steven. It's been a real pleasure talking to you, getting to learn a little bit more about your work. It's absolutely fabulous. You're one of those people that makes me proud of Penn State, proud to be here. And let's keep in touch. We'll be following along. And if you saw the video, if you want to follow along with Steven Schiff's research at the Huck, we do like to share news as things go on so you can subscribe. If you go to huck.psu.edu/subscribe, you can get our pulse eNews letter about not just Dr. Schiff, but all the amazing scientists at the Huck, excuse me. The Huck Institutes here at Penn State University. I'm running out of time. But I want everybody to know if come back in a month on Thursday, April 28th, we'll have Dr. Laura Weyrich on the podcast talking about ancient microbiomes and ancient DNA. And some fascinating stuff. So, again, thanks a lot, Steve. Take good care. Everybody out there, thank you for watching The Symbiotic Podcast and don't stop co-evolving.

Steven: Thanks, Cole.

---

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.

Cole Hons: Greetings fellow homo sapiens, and welcome to The Symbiotic Podcast live in the studio for our third season. This is our second live stream. It's all completely live. We're out here without a net on the high rope talking to some of our favorite scientists at Penn State who are taking risks and changing the game. I'm going to introduce our guests today in just a moment, but before I do, I just want to let you know that if you want to participate today, you can just join the chat. Just put your name in or stay anonymous if you wish. Right there next to this streaming window, you can see a place to pop your name in. Hit accept and you'll be able to put in your questions. There's a little button that will come up allowing you to ask questions. Also to vote for other people's questions. And at the end of our 45 minutes here, we'll be asking those questions live to our guest, Dr. Nita Bharti, who's with us today, our buddy, Hey, Nita.

Nita Bharti: Hey, Cole. Thanks for inviting me.

Cole: Thank you for coming out here. And I know you're so, so busy. We managed to pull you out of this. We're putting the phones aside. We're talking in real life in the same spot with our masks on safely. I wore my pink mask just for you.

Nita: I love it. I was going to say, I love the pink mask.

Cole: Thank you. Well, I know you like our unicorn and he's got a pink horn, so I thought I'd try and pink it up a little bit for you. So thank you so much for coming out. It's great to see you again. This is your second time on The Symbiotic Podcast.

Nita: Yeah, it is. I think our first time was sort of like the first week that the news was breaking about COVID.

Cole: That's exactly right. I think it was February 2nd if I'm not mistaken.

Nita: We weren't calling it COVID yet.

Cole: No, no. It wasn't even called a pandemic. It was called an outbreak. The first death had just happened in Hong Kong. There were no deaths in the US and already people were starting to freak out. Some healthcare workers, I remember, in Hong Kong. I kind of went back and looked at that a little. We talked about a lot of things, though, that have played out. I mean, we talked about vaccine hesitancy right out of the gate. We talked about some ugly, racist, horrible, xenophobic things and a lot of those things have played out two years later. It's like being in a different world. I'm hoping we're getting to the tail end of this thing. What do you think about that?

Nita: So I would say a couple things. The-

Cole: And I'll ask you to just turn that mic towards you just... There. Perfect. Thank you. It should stay. That's great.

Nita: All right. So I'll say that a couple of things that we had talked about during that early podcast were really just recognizing patterns that happen over and over again with disease outbreaks and spillover events, and then eventually pandemics. So that pattern recognition, it's kind of sad that we see these same behavioral emergences with really every time they could be avoided. Like the vaccine hesitancy, which has been around as long as vaccines have been around. And the racism and the xenophobia, which happens every time we see geographical spread of an infectious agent.

Nita: Coming back to your other question, I don't really think that this is over. We're seeing new news about variants and other emerging variants, and I think this will continue to be something that we have to worry about.

Cole: Try and fix this for you. Sorry. Keith was sitting in here. There. I think we [crosstalk 00:03:41].

Nita: Oh, that's perfect. Yeah. I don't think this is over by a long shot. I don't think that it's going to be over as long as we keep pretending that it's over. I think a lot of the backing off and the behavioral interventions that we keep doing, so talking about lifting mass restrictions and reducing distancing guidelines and things, I think those are all pretty good ways to make sure we're not going to be done with this.

Cole: I mean, we're here really to talk more about your research in general and some of the ways that you've been pushing the envelope and trying new things. But I just had to bring that up considering the last time we talked. And I know that there's such a range of how people react and have reacted and continue to react. And there's so much just exhaustion around the pandemic that so many people just feel. I hear people say like, "I'm done with this," because we all feel like we want to just be done. But before we get into to your research in particular, I'd like to touch on this word "endemic" because that's a word that we hear a lot. That this virus is going to become an endemic part, just kind of floating around almost like the seasonal flu eventually. Could you speak to that for just a minute? Your thoughts on that?

Nita: So I think a lot of epidemiologists feel like the word "endemic" is sort of going the way of the phrase "herd immunity", where it was just misunderstood and used incorrectly for a long time. So the word endemic doesn't mean that it's not a problem anymore. The word endemic really means that there's a pretty consistent level of either incidents or prevalence of a pathogen in an area over a certain amount of time and you can define what that time is. So if we talk about flu, your example of seasonal flu, we see increases and decreases seasonally. But for the most part over the course of a year, year to year, we see a pretty predictable number of cases. And then there's the years where we don't and we can talk about that in a minute. But for the most part we say that that's endemic because yeah, we see these seasonal fluctuations, but we also kind of know what the annual level of cases is going to be for influenza.

Nita: That's basically all it means. It doesn't mean that it's not a problem. We could say, okay, we're at a place where we've decided that COVID is endemic. And that means that we are okay with the level of morbidity and mortality that we're seeing on a really predictable and regular basis. We're okay with saying that's how many cases and deaths we're going to have caused by COVID every month or every year or whatever, in the US or in the world, whatever we decide. And so we could make that decision. We could. I think it would be a huge misstep because we are experiencing a very high level of excess deaths and cases still, but that's really what it means. It doesn't mean it's not a problem. It means it's something that we have to worry about a lot.

Cole: Yeah. Something it makes me think about is deaths in cars. Like so many traffic accidents a year and you just sort of... It's not that we become numb to it, but as you say, there's a level of acceptance of this is just how things are and we go on and we go back to that phrase we've heard so much over the last two years, when does it go "back to normal?"

Nita: I mean, I think there's something really interesting there about that analogy, right Cole? So we have so many things in place to reduce traffic deaths and to minimize the number of accidents. Seat belts, airbags are getting better all the time. Crumple zones on cars are improving. We have constant improvement about that because we sort of feel like traffic deaths are avoidable and should not happen. And then I would also say with the flu we have a huge amount of infrastructure in place to sound alarms when we get beyond a certain level of either early cases or mortality in alarming age ranges. There are ways that we manage those things so that they're either constantly trying to be reduced or that we really have pretty strict thresholds about what's acceptable and what's not. And so to say that we're going to get to a place where COVID is endemic with what we're seeing now, we could make that decision, but it would be pretty callous.

Cole: Well, we could spend this entire time just focusing in on COVID and we're going to speak a little bit about some of the things that we did early in the pandemic when we were answering questions from the public. You and Beth and our team was helping. We'll touch on that in a little bit, but I don't want to go too deep. We'll get lost in it-

Nita: We will.

Cole: ... and we'll be out of time before you know it. So I do want to do make sure I'm staying on point with this season. This third season of the podcast we're really focusing on risk takers and game changers, and you've made our list because we see you as somebody who is changing up the game in epidemiology in a way. And with conversations that you and I have had, I don't see you as a person who's necessarily breaking rules or throwing the baby out with the bath water or like a total revolutionary.

Cole: But we've talked about this. You're adding a new dimension, and I see you as more pushing the boundaries of the way epidemiology is done in some fresh new ways. So before we talk about the science, I want to ask about you. I asked David Hughes, our first guest for this season last week, and he shared about his teenage years and getting kicked out of high school. And he's doing pretty good for somebody who got kicked out of high school. But what about you, Nita? Were you a boundary pusher growing up as a girl? And what's your background and how would you describe yourself personality-wise?

Nita: I don't think I was really a boundary pusher. I didn't love school. I didn't get kicked out of school, but I didn't love school. I think that my, sometimes I call it a superpower and sometimes I just say that it's my unique perspective. I grew up in an immigrant family, so my parents immigrated to the US in the '70s and me and my brother were born here. And so when you're born and you're raised in an immigrant family, you're always noticing what's different. What's different about your family and the other kids at school. What's different about the way you do things, even little things. And when you're little, you're usually trying to make those assessments constantly so you can assimilate and fit in. And then when you age out of that you sort of realize there's huge benefits to seeing things in different ways. And there's really, really massive improvements to be made if you don't assume that everything is, always has been, and should be the way that everyone's doing it.

Cole: Yeah. So not just taking everything as the only way, this is the way, and it's the only way because right there in your house, you're experiencing a different perspective every day. That's really interesting. I also have noticed, and this is from following you on Twitter because sometimes we'll go back and forth and promote each other and we're always trying to promote your career because it's just fabulous to watch and be a part of that, but I would call you a critic. That's one thing I would say. You are a very critical person, I've noticed. And it seems that you're not satisfied with the status quo, I've noticed. You know what I mean? Do you think that impacts the way you approach science, too, having a critical mind? Which is of course essential. It's essential to have the critical faculties in full play to approach science.

Nita: I think I might need maybe a little more clarity on what you're referring to. I do have a very critical scientific mind obviously, but that's not what you're talking about.

Cole: Well, just like if there's a software that's terrible, you know what I mean? And maybe that's just your Twitter. Maybe Twitter's where you go to vent and get that out.

Nita: No, I do think that, yeah, I mean there are inefficiencies built into the ways that we do things. I think everyone has those inefficiencies, but yeah. I mean, what's Twitter for? That's where we air our grievances. I don't know.

Cole: For many, I believe it is. But do you think that ties into the immigrant side of things? Seeing things from another perspective helps you to have more of a critical eye of what's not maybe working in the mainstream or what's accepted as normal and right and just fine in the mainstream?

Nita: So I don't know if that's necessarily related to being from an immigrant family. I do think that probably has something to do with being a woman of color and a little bit of an outsider in science or feeling like a little bit of an outsider in science. Of course I belong here, but there's not a lot of people who look like me in this field and in this profession. So, I think that makes me more aware of things that aren't working.

Cole: Right on. Thanks for sharing that. Do you have any ideas of what we might be able to do to improve that? I know that's a huge topic. Again, we could spend an entire podcast on that easily. And I don't know. It's a lot to ask you just off the cuff, but do you have any ideas of things you think that the community could do better? Academia?

Nita: I mean, I think that one of the things that's been holding back improving diversity in academia is again, kind of doing things the way that we've been doing. And for a long time science and really most professions throughout the US were we're white men. And so there's networks that exist that are in place to sort of promote that, promote those connections. And I think we will rely on those networks a little more than we should, because we're not recognizing the value of other networks that integrate a lot more diversity, or that are centered on different cultures or different races. So, I think those things are difficult.

Nita: I also think, without being a total pessimist, I think we're stuck on a little bit of a hamster wheel. So I say this a lot. Common's phrase, "Why do I need ID to get ID? If I had ID, I wouldn't need ID." I think we're sort of in this loop where you need diversity to get diversity. It's hard to attract diversity with a panel of all white men because it's not easy to see yourself at that institution. So I think there's a little bit of that happening. Schools have had success with cluster hires, so hiring a bunch of or a number of new tenure line faculty that maybe don't fit the current demographics. And I think that that can be successful if it's managed correctly and supported financially.

Cole: Financial support always comes into play.

Nita: I mean, it comes back to that all the time, right?

Cole: Yes. Absolutely. Well, I know our time with you is limited and I do really want to show this video because we've been working really hard, and I hope you're going to like it because you haven't even really seen it yet.

Nita: I'm dying to see it.

Cole: So I'm going to ask Dan to cue up the video and then we'll have a discussion specifically about your research. So if you're ready, Dan, we're going to cue that up for the people. This is a sneak peek. It'll be lightly edited a little bit more before it's released. This is from our new Life From All Angles video series.

Narrator: This traffic camera sits atop of pole at the intersection of Atherton Street and College Avenue in State College, Pennsylvania. It records grainy, low-quality video used to monitor traffic flow. 700 kilometers above that camera, a 600 million satellite moves at over seven and a half kilometers per second. It captures high resolution images used by governments, private companies, and scientists. For one team at Penn State, both the humble traffic camera and the cutting-edge satellite represent an opportunity. Each can play a role in more effectively responding to future outbreaks of disease.

Nita: So when we're thinking about disease ecology, we're really concerned with three interlinked factors. The host, the pathogen, and the environment. And they all control what's going to happen with interactions and movement and disease transmission.

Narrator: Nita Bharti is an assistant professor of biology, and a member of Penn State's Center for Infectious Disease Dynamics.

Nita: And what we find is that the interactions between the human and the environment can often drive the interactions between the human and the pathogen. And if we miss that, then we miss a really important part of the system.

Narrator: In some of her earliest work, Bharti used satellite imagery to track seasonal population shifts in the African country of Niger. Driven by the Sahel's seasonal wet/dry cycles, many of the nation's laborers are semi-transient. The population of cities like Niamey, the national capital, swell when people move there to find work in the dry season. When the rains return, workers leave to cultivate their crops. Similarly, the number of people coming down with measles, a highly infectious disease, spikes on the same cycle. Cases flowed during times when people crowd into urban areas and drop back down when people return to the countryside.

Nita: So highly mobile populations or migrant populations are more vulnerable to vaccine preventable diseases than largely sedentary populations. Some of that is due to the fact that a lot of our disease response strategies are built around assumptions of sedentary populations.

Narrator: To better track seasonal population movement, Bharti and her team used nighttime satellite imagery to demonstrate predicted density fluctuations. This enabled more accurate, targeted interventions with the measles vaccine. Bharti's research group has also used satellite imagery to examine disease ecology. Using thermal satellite and on the ground monitoring, Bharti's team and collaborators in New South Wales showed that the Eastern Australia mega fires of 2019 and 2020 burned more than a third of the habitat used by gray headed flying foxes.

Nita: So we're working on Hendra virus, and Hendra virus is a virus that spills over from fruit bats called flying foxes to horses, and then to a number of other species, including humans. Fruit beds that are infected with Hendra virus seem to be fine. It's just the spillovers that are a problem. Those spillovers seem to be a factor related to loss of habitat, and encroachment of a human system on the wildlife system.

Narrator: And as for those traffic cameras, Bharti's lab used data from them along with anonymized mobile phone location data to track compliance with lockdown measures from March to August 2020. The team found that as restrictions were eased, increased traffic was a clear predictor of increases in COVID cases. Non-intrusive surveillance methods such as these could help public officials predict and allocate limited medical supplies during future outbreaks.

Cole: That was really fun to work on. Neato. We're so excited to be able to share these stories of all this cool stuff going on at Penn State. And blow us away. You're all over the planet. You're in Africa, you're in Australia. You're right here in Centre County. It's local. It's global. And when we talked about doing this thing, the video in this live stream, we were trying to figure out what ties all this together. And for us, the thing we noticed is this use of digital data streams in a new way. And I know it's not just you, it's your team as well. And we're The Symbiotic Podcast. We always talk about that team and the different disciplines coming together. So could you tell us a little bit about how you came to use the satellite data that was considered junk data, for example, or the traffic cameras in Centre County and working with your team on that? Could you tell us a bit about that?

Nita: Yeah. So we could go way back. The exploration of satellite data to better understand human infectious diseases, that started maybe almost 15 years ago. So I started that work when I was a grad student and it was the first time that anybody had done anything like that. And luckily, I didn't quite know that because I might have been deterred if I had thought that it wasn't a normal thing to do. But I also, luckily, was in a position where I had a lot of freedom to fail. So I had a very supportive advisor and he was kind of just very trusting with me to go off on these weird tangents and directions. And so that's how that work started.

Nita: And then it just grew. We basically were trying to understand why the dynamics of something we understand as well as measles looked so different in places where it continued to persist. And we've talked about this before, but basically it goes back to the assumptions that we were making about populations didn't match up with those populations where measles was still persisting. And so all of the dynamics that we had expected to see for measles and other infectious diseases just didn't hold true. So, this kind of goes back to backing up and really reexamining your assumptions.

Cole: Yeah. Take a look from another perspective like you spoke about earlier.

Nita: Yeah. So that's kind of where that came from. The traffic camera data is a fantastic story. So Brian Lambert is a programmer in my lab and I didn't even know about these traffic cameras. We were doing this work in Centre County. We were talking about how to get sort of eyes on movement and eyes on how people would be moving around. And we had looked at some satellite imagery, but it wasn't really ideal for what we were trying to do. And Brian said that he knows that there's these traffic cameras and that PENNDOT maintains them. And they just stream live video from-

Cole: Almost all the time. Some of them are always, so 24/7.

Nita: I mean, it's 24/7, yeah. And so they're streaming live video of roads and highways and intersections and just scattered throughout the county, and that they're publicly available. So you could go look at them right now and anybody could. And so he basically developed a way to grab a still image every 20 seconds from each of these cameras and use slightly modified off-the-shelf object recognition packages in Python to count the cars and the pedestrians in each image every 20 seconds.

Cole: Wild, yeah.

Nita: And so it turns out that the reason that he knew about these traffic cameras is because when he needs to leave the house on football Saturdays, he likes to be able to see if he's going to be able to get to the grocery store easily.

Cole: Yeah. Living in this town, I understand that's really important.

Nita: So seven days a year this is super handy.

Cole: Yeah, that's right.

Nita: Which is, I got to say, probably the best life hack I've ever heard.

Cole: That's great.

Nita: And so he brought this idea to the table and we loved it and he really kind of took it from an idea to a product. He's really the brains behind that operation.

Cole: That's fantastic. I love that story. Well, let's also talk about the cell phones, because I don't know if our viewers all caught that in the video, but you also use, let's see if I can say this right, anonymized, right? Anonymous cell phone data, which freaks out a lot of people, the idea that we're being tracked everywhere. If you've seen the Snowden movie or you look at Facebook and all the data that's bought and sold about all of us, a lot of people get very concerned. They have a lot of issues with this idea of our data versus privacy. And I know that you've gone pretty deep into that subject. Could you tell us a little bit about that? How do you do that responsibly?

Nita: So I think the first thing is that yes, your data that you generate and that you should own, you don't own. It is out there. It can be bought and sold and it often is. Phone companies are held to, I mean, reasonably high standards about what they're allowed to share, but what they have and what they can use is theirs. What they share, like with people who are doing research like us, is some small fraction of the total number of phones or visit counts or mobility traces, whatever it would be. Some fraction of the network that they share that is completely anonymized and with which you can't track or trace a single phone. You can see population level movements or population level behaviors and activities and changes, but you really don't see anything that's identifiable and that's critical. We don't actually want to know what everybody's doing. And if we need to know that level of detail to understand infectious diseases, then we're no longer looking at patterns.

Cole: Yes. So with that in mind, you explained a bit in the video of the big three of epidemiology, about people and the environment and the pathogens and how they all interact. What do these digital data streams give us that we didn't have before?

Nita: That's a great question. Why do we need these? How have we been fine for so long without them? In a way they give us a lot more information on the host, in this case, humans. They give us a lot more information because it's at larger scales. It's a slightly different type of information than you might get from a conversation or an interview, but it's from a lot more people. So there's that aspect of it. And then you're also able to see what these sort of larger scale interactions, what the environment look like. And in this case, the environment can really be anything.

Nita: One of the really nice examples from Centre County is that we can easily see when home football games are happening in the cell phone data. So I don't know whether you went to the game or not. I don't know what individual people did, but I can see that a lot of people... A huge increase in visits to Beaver Stadium happened on seven Saturdays. Well, eight, because we also see the Blue-White game. Eight Saturdays a year. So we're able to see how people are interacting with the events around them, with their environment, and a little bit with each other.

Cole: And how do you take that kind of data and put it back into your epidemiological forecast?

Nita: Yeah. What is it? Why do we care people are at Beaver Stadium? What does that tell us? So really what we're able to do, what's really useful about a lot of these sort of passive surveillance kind of strategies, including satellites and phones and traffic cameras, is that we can look at relative amounts of movement. And that really gives us a proxy for contacts and interactions. And the reason that's important is because contacts and interactions are what drives transmissions, so me transmitting an infectious pathogen to you. But transmission events are not observable. We cannot see those. What we can see are proxies for contacts or interactions or movements. So if you're out and you're moving and you're interacting with one person, then another person, and then another person, that's a string of interactions or contacts. So that's a baseline for where we can set some knowledge about risk of transmission.

Cole: That's it, that word risk. And you and I have talked about this before as we were talking about risk-taking scientists and good risk versus bad risk and how much risk is acceptable. That seems to be at the crux of so many arguments and discussions and battles, even throughout this pandemic of what's acceptable. Is this riskier than that? And what's the right intervention? And it sure gets dicey when you add layers of sort of politics and ideologies and belief systems into the matrix. I mean, that seems to me to be the hardest piece of all. We can look at who's moving around, but what those individuals are doing, the choices they're making, what they believe, what they choose to do, where their value system is, how much risk they're willing to take personally for themselves, how much they care about the risk to others, that's really tough to manage, right?

Nita: So in a lot of ways, I would say managing that is one thing, but understanding that is really kind of where we have to start.

Cole: How would you start to try to understand? I mean, I'm not asking you to solve it for the world, but what the heck? We have all this information and we still, like you said earlier, just that hamster wheel. How do we get off the hamster wheel?

Nita: I mean, I think there's a lot of things that have been done that have been helpful. A lot of things that remain to be done that could be helpful. But really the biggest one is understanding where people are coming from. So we have, we all do, I do this, too. We have a sort of knee-jerk reaction to people who are doing things that we think are too risky or that we think are unsafe or uninformed. And oftentimes when we drill into it they are operating on different information. And whether it's accurate or not is a different story, but they don't feel uninformed. And so understanding where people are coming from and what they're afraid of. So sometimes people are just afraid of things that we are not afraid of and so that makes us feel that they're acting irresponsibly or in an uninformed way.

Nita: And it's really just that we haven't addressed their fears or maybe they have a very different risk level, a risk threshold. A lot of people who are really very, very afraid of this pandemic and kind of unable to function, they have a very different risk threshold. And that may be because they're more vulnerable. So a lot of times when we're talking about what's okay to do, what society should move towards, what restrictions to lift, we're kind of thinking about maybe the healthiest people in society. We're not necessarily thinking about the most vulnerable. And really our obligation is to protect those first and foremost, and we just sort of keep missing that.

Cole: Well, I know you have a great passion for informing the public because you worked with us, with our team here at Huck to put out... We did 63 Ask CIDD videos, CIDD being the Center for Infectious Disease Dynamics, of which you are a member, along with your colleague, Beth McGraw and our team here. We were answering questions from the public that they would submit. Made 63 of those videos. And while I have you here and we're doing this livestream, we need to share this with you audience out there. Of all those 63 videos that we made to answer questions, to try and give the best information we were able to offer to the public, of all those 63 videos, the top two... It's always very interesting to me that the top two most shared and viewed videos on our YouTube page.

Cole: It was kind of surprising because I would've thought they would've been flip flopped. The top two videos were, can you get COVID? Can it be transmitted sexually, through sexual activity? And how does alcohol kill the virus? And I don't know if it's the Penn State community or what it says about it, because a lot of these folks were at Penn State, but it turns out the number one video was the alcohol video, not the transmitted during sex video, which had about twice as many views for some reason. But I bring it up because, you know where I'm going with this, at about 3:00 one night, somebody decided to randomly email the Huck website, which I'm the primary. It'll hit me and my team first. And we got an email from the Netherlands from a DJ by the name of Jerry Guild-Brandson who goes by the name of Techneck.

Cole: And I'm going to ask Dan. I asked him to put this in here because these are one of the moments that life can be pretty grim, particularly in the middle of a pandemic with people dying all around you. And you do all this work and sometimes it's very frustrating because sometimes it doesn't even seem to be catching. But Jerry Guild-Brandson, Techneck, from the Netherlands was so inspired by your video about how alcohol can kill the virus that he decided to do something a little special. Dan, can you play this? We'll play this for the people.

[upbeat, techno music begins]

Nita: In addition to soap and water, alcohol is a recommended cleaning agent to destroy the coronavirus, by destroying the lipid or fatty bilayer that holds it together.

Kill the virus.

Kill the virus.

Kill the virus.

Kill the virus.

Kill the virus.

Kill the virus.

Destroy. Destroy. Destroy. Destroy the coronavirus.

You shouldn't try to use alcohol ... You shouldn't try to use alcohol ... You shouldn't try to use alcohol ...

You shouldn't try to use alcohol that is meant for human consumption to kill the virus.

You shouldn't try to use alcohol that is meant for human consumption to kill the virus.

Kill the virus.

And 60 to 80% alcohol cleaners are also highly effective.

[music ends]

Cole: So needless to say, people, we were not ever expecting some DJ from the Netherlands to pick up one of our Ask CIDD videos and take it into the clubs. But Techneck just appeared and it just shows you the power of passion and you just never know in this crazy, mixed up, globalized world where your content might end up. So all you scientists out there, if you want to get into the clubs, Nita's pioneering the way for you. Anything's possible.

Cole: So it really was remarkable to make all those videos, in all seriousness. It was nice for me to be involved because people would come up on the street and just say, "Oh, thank you for doing those videos." People had questions. They still have questions. I sense that as we've got the vaccines now and we're boosted and people feel safer than they did at the time that we were just cranking those out every day, but as you said earlier, I don't think we're out of the woods yet.

Cole: Wait. What's going on over there guys? I'm sorry. Somebody's-

Off-camera Producer: Can we help you?

Cole: Hello?

Batty: How's it going?

Cole: It's going all right. Who are you?

Batty: I have a battygram.

Cole: A battygram?

Batty: Yeah. The bats have been loving you and loving your work. They're sending all their bat-love your way.

Nita: Thank you, Battygram.

Batty: You're welcome.

Cole: Thanks, Batty.

Nita: Wow. Should I actually open this right now?

Cole: Why don't you just open it up. Yeah. What is that?

Nita: It's all very unexpected, people. But I'm going to need to know where you got that bat costume.

Cole: Well we couldn't help loving on the bats when you sent us the pictures for the video of all those bats in Australia. What did they send you there?

Nita: "Dear Nita, we just wanted to thank you for all the hard work you've been to on behalf of people, bats, and the entire natural world. You're the best, like flying grey-headed foxes of Eastern Australia." And there's a little drawing. I don't know if we can get that.

Cole: Wow. That's really special.

Nita: It's really cute. This is adorable.

Cole: Well, obviously you have friends in the bat world.

Nita: Friends everywhere, man. This is adorable.

Cole: That's terrific.

Nita: And there's a diagram here too. I don't know if you guys can see that. Fantastic.

Cole: You got friends in the Netherlands. You got friends in the bat world in Australia. That's going to be a pretty nice segue, actually. We talked about Penn State's ongoing diversity challenges. Like every other university we're trying to meet those challenges. But I'm taking hope when I see some of the new plushie mascots that are available at Penn State. And I don't know if you noticed with David Hughes. We're going to be doing a little research of our own, Nita. For every audience that we see from every one of our guests, we're going to ask which of the alternative plushies people like, because you don't just have to go with the Penn State Nittany Lion anymore. Dan, do you want to show people the nice little feature that we have put together for our plushies? If you'll let me know when that's running. Like I say, you don't have to stick with just the Nittany Lion, who, by the way, to the alcohol point, sometimes I think the regular Nittany Lion plushie maybe needs to be in a 12-step program. Possibly. Possibly.

Nita: Does he drink a lot?

Cole: I don't know. It wouldn't surprise me, but I would support him in getting the support. But maybe he's getting support.

Nita: He does a lot of pushups. I know that. So he's got a gym membership probably.

Cole: Yeah. Not the guy who's in the costume. I just mean this plushie in particular, that particular mascot.

Nita: I think does a lot of pushups.

Cole: Yeah, he definitely does. But it's nice that he is in a larger, broader community now. So we're going to ask people to vote. You can vote for your favorite alternative plushie. We've got a pink unicorn.

Nita: So wait, so when you say that-

Cole: Yeah. Go ahead. Yes.

Nita: When you say you can vote for your favorite alternative plushie, are you telling them that they can't vote for the lion?

Cole: No. No. The lion is not involved. No.

Nita: So they can only vote for anybody but the lion.

Cole: Anybody but the lion. But I mean-

Nita: I just want to understand the rules.

Cole: It's just to see if people are given an alternative to the usual, where are people on this? Do people like the unicorn? Do people like the little bear, the little baby bear? That's like the little baby indoctrination bear to get your infant to be a Penn Stater right out the gate.

Nita: Is that a beanie?

Cole: It is a beanie. He's got a beanie butt. And then there's the gnome, kind of the wizened old gnome. That's been very popular. And we also have a llama. There's also a Penn State llama, which surprised me. It surprised me that Penn State could kind of open up like this to new ideas. So what we're doing is we're asking everybody out there, you can vote right now, the unicorn, the gnome, the llama, or the bear. And then based on where those votes go, we'll be able to see at the end of the year for each one of our scientists which audience tracks with which plushie. And we'll let you know how that all pans out at the end of the season. Do you have a favorite?

Nita: So I know that I have previously said that I like the unicorn. But I've been sitting here and there's these really adorable llamas behind you. So I feel like I'm a little primed for the llama right now. I don't know if that's subliminal messaging on your part, but I'm kind of leaning towards the llama today.

Cole: I like the llama too. That's the only one with the name. I believe it's Lisa Llama is the name of that.

Nita: That's good to know.

Cole: All the others, we may have to name them in future episodes. So it's 12:45 and I just realized that we didn't get to, oh my goodness, the questions. Can we hang for just the top question that's voted? Because I did promise the audience. Like I say, it's live so anything can happen.

Nita: Sure. Yeah.

Cole: We haven't crashed and burned yet.

Nita: I could storm out if I don't like the question. We don't even know.

Cole: You could just storm right out. That's right.

Nita: I'm taking this llama and I'm leaving.

Cole: So this top question from Jamie wants to know, how do we deal with public health messaging fatigue and people getting used to being at risk and starting to ignore it? Do you have any thoughts on that?

Nita: Yeah. This is, I think, a really important question. It's a question that we clearly don't have an answer to because we are struggling with it. But I think one of the things that has been a real problem throughout this pandemic is not just the volume of information, but the volume of either low-quality or false information. And so people are getting bombarded with a lot of information and not really knowing what to trust. Yeah, I mean, I think having credible sources of information that you really rely on is an important thing during a pandemic. But then people are free to make choices about what they think is credible. So I think we have a lot of confounding problems there.

Nita: The issue of fatigue. I mean, I feel you there. The issue of pandemic fatigue and information fatigue, and we've been living in a state of really high alert for two years now because of this. And so there's a point at which you do have to stop. And whether that means that, this goes back to something that you said earlier, whether that means that you sort of settle into a new normal that is a different level of risk than you would've been pre-pandemic, like different behaviors, can be one way to sort of tone down the hyper attentiveness. But really kind of trying to be on high alert all day, every day for two years is not sustainable.

Cole: Yeah. I guess we're still figuring it out as we go in the broadest sense.

Nita: And I think that there's definitely a place for us to sort of... Instead of saying, we started here and we're going to go here for the pandemic and then we're going to go back, I think that there's a way to sort of go from where we are to somewhere that's better for everybody, or better for a lot more people, at least.

Cole: Right on. Could I throw one last one at you?

Nita: Yeah.

Cole: We'll just do one more. If we could put that up, Dan. Are there diseases that could end up like COVID-19 that epidemiologists are worried about right now? Are there any ones that are high up on the alert list for folks like yourself?

Nita: Yeah. So the official answer to this question is that yeah, in 2018, the WHO released a list of Blueprint priority diseases, and it was a list of 10 disease. I think it was 10, and this list is online. It's not classified or anything. You can go look it up. They update it from time to time when they think it needs it. But it's a list that basically represents diseases that they think present a significant risk to the public, or to people or to wildlife. And that they think propose a significant risk of disease that are understudied both for research and for public health. And so they're basically diseases that the WHO says we should probably be focusing on a little bit to improve of our understanding of what the risks really are and how we would manage them if these were to become epidemic problems.

Nita: On that list are a couple of corona viruses that we've seen before. And then some of the diseases that we've talked about that I work on. Hendra virus is one of the diseases on that list. But then additionally, there is this. The last disease on the list is Disease X and Disease X represents a disease that we don't know about but that could emerge that we are unprepared for. And so, yes, there are diseases that we think are diseases we should be paying attention to, but we also have the knowledge that there are going to be diseases that are not on our radar that we need to be prepared to manage.

Cole: And that's just what the more general approach of managing whatever could hit? Is that the idea there with Disease X?

Nita: Yeah.I mean, I think that really sort of highlights the importance of baseline, basic access to healthcare and disease surveillance everywhere. Not just for the 90% of the world it's the most accessible, but really for everybody everywhere.

Cole: Right. With everybody.

Nita: So these issues of health equity really come into play when we talk about these kinds of issues.

Cole: Yeah, for sure. And I should have mentioned earlier, that's a huge passion of yours, is equity. And with our first podcast two years ago, that's where we came down to the money. If money and access to healthcare were evenly distributed throughout the planet, we'd be doing a lot better collectively. Along with not encroaching onto wild spaces, which is something that never quite makes it into the public dialogue about this. We'll talk about was it from a lab? But we won't talk about how much should we be encroaching into these wild spaces. Well, at least the bats know that you're on their side and that there are folks who care and are doing things. So I-

Nita: So I should highlight really quickly, Kelsee Baranowski in my lab is doing a lot of that bat work and a lot of the environmental data analysis. So probably the bats should thank her quite excessively. And then of course, that's part of a much larger project that we've talked about with collaborators all around the world. And that's part of why it's able to make some progress and understand these larger issues.

Cole: Right on. We'll get some battygrams out there. And this time we'll know where they are and hand it off the poor bat so she actually has her battygram to hand to you. So we're learning as we go. But Nita, thank you so much for taking the time and coming out. It's always a pleasure talking with you. Just keep doing. If people want to follow your work, what's the best way to follow you and what you're up to next and where you're going?

Nita: So you can check out our website. We keep our publication list is up to date. And that is humidlab.com. Human infectious disease, so humid, ID. Humidlab.com. And then I'm on Twitter. Some of the people in my lab are on Twitter as well. I'm @Nitanother. So it's N-I-T-A-N-O-T-H-E-R. I'm not used to promoting my Twitter feed, because I feel like it's not a place where I communicate with people, but I do complain about things there as you heard about from Cole.

Cole: We can hear your critique of what sucks this week. No, that's good, though.

Nita: And then of course I also do post about our research papers and our talks at our lab's accomplishments and things. And then of course I boost my colleagues because they're amazing.

Cole: Yeah, absolutely. It's a team effort for sure.

Nita: Well, thanks for having me here, Cole. This is so fun with the plushies.

Cole: My pleasure. It's my pleasure.

Nita: I mean, this is a great setup you've got.

Cole: We're trying to have a good time. We're trying to keep things as positive as we can [inaudible 00:49:28].

Nita: Yeah, you guys are killing it.

Cole: Right on, right on. Well, thanks again. Really appreciate it, Nita. Take care and everybody out there, thanks for joining us. We'll be back in a month with Steve Schiff to talk with him about what he is up to in pushing his own boundaries. And until then just be good. Have the best time you can, and don't stop co-evolving. Thanks a lot. Cheers.

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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.

Cole Hons: Greetings fellow Homo sapiens, and welcome to the third season of The Symbiotic Podcast. I'm your host Cole Hons from The Huck institutes of the Life Sciences, and it gives me great pleasure today to introduce you to our first guest of our livestream season, season three. We're back after a year off, a year's hiatus working on a lot of COVID things. Now, we're back live once a month kicking off our new season where we'll be talking to individual scientists, which is a big change for us. In the past, we've always talked to groups of scientists collaborating.

This year, we're breaking our own rules, which makes a lot of sense because this third season is about "Risk Takers and Game Changers" – people who aren't afraid to take risks and try to do things a little differently. Our first guest for this season is Dr. David Hughes, the Huck Chair of Global Food Security. Hello, David.

David Hughes: Hi. How are you doing, Cole?

Cole: I'm doing well. How are you today?

David: Grand.

Cole: So you rode your bike up here in zero degree weather, didn't you?

David: Yeah, I did. Yeah.

Cole: I just want to point that out. I'll just introduce you to the world that way because hats off to you, sir! That's probably how you've made it through these few years of the pandemic still trim and fit like you are.

David: Yeah. Well, it's a good way to do things. It keeps me warmer and the planet less warm.

Cole: Yeah. Well done. Yeah. I put on about a pandemic 25, I think. Are you still working out? I used to see you at the YMCA lifting weights. You're lifting at home now?

David: I still do. Yeah.

Cole: You still go to the Y?

David: No. I still do it at home.

Cole: Do it at home. Pandemic times.

David: Yeah, exactly. Stay away from the Y.

Cole: Yeah. Well, well done, sir. Appreciate that a lot. So how do you like our new set, David?

David: I think it's fantastic. I've liked this podcast a lot. I think what you're doing here is really nice and constantly trying to change it up and perhaps also having a nicer space. We've gone in and occupied your old space.

Cole: You did. Well, we used to battle about that day back in the day.

David: We did.

Cole: A friendly competition for space.

David: I think this truce benefits us all.

Cole: Absolutely. Well, if there's anybody I would not worry about handing space over to you, it would be you my friend, because I think what you're doing over there is fabulous. We shot some video in there recently. We'll be watching that video in a little bit. Let me just let the audience know that we're 100% live here, so anything could happen. If there's any glitches or things, we apologize in advance. Hopefully, we'll get it all out there smoothly. There's no editing involved. This is happening right here, right now, live. No net.

I do want to point out that there is a chat. It's going to be to the right of the video stream. You can just accept the terms there. You can chat in. You can use your real name or be anonymous. Anything you want to do. We're also going to have a live Q&A once you're in there. If you have a question for Dr. Hughes that you would like to ask, you can put that question in at any time, and you can also vote up other people's questions. Towards the end of our 45-minute conversation, we're going to look at those questions, and we're going to see which ones are the most popular. Dr. Hughes will answer those live right here for you, which will be interesting to see what kind of questions we have.

David: Great. Excellent.

Cole: With that said, David, this is all about risk taking and game changing. Game changing, you hear that a lot out there in the public sphere. People throw that term around a lot, but what we're interested in at the Huck is what does it really mean to change the game? On the risk taking side, what's an acceptable level of risk? What is a healthy kind of risk? What are the dangers of not taking risks? And then conversely, what are the dangers of taking irresponsible, dangerous risks? In science, these are huge, huge topics. Just looking at you, first thing I wonder is, were you a risk taker as a kid when you grew up? Can you talk about your background a little bit? You consider yourself a risk taker?

David: Yes. I'm the fifth of six children. Grew up in Dublin in the 1980s, a poor household. Nobody in my family ever went past high school at 11 years old. I got kicked out of high school at the age of 15 for constantly fighting with the teachers and the system. Ever since then, that's the perspective I'm coming at things from. We often talk in PlantVillage of who's not in the room, and the people in my community in Dublin in the 1980s were certainly not in the room. These were individuals who were excluded from the benefits the society brings, meaning jobs and education and so on.

I've always railed against that. If we think of Dublin in the eighties or Africa today, there's just a large group of people who know how to game the system, know how to do better in the system, and they purposely or without purpose exclude others. That's the perspective I'm coming at things at. I'm best described as an angry Irishman. I'm angry at the system, the historic system, the current system, and the future system. I think we need to be more inclusive, not in a very easy-going woke language, which tends to try to bring people in, but in a purposeful language which has a bias to action. If you really mean what you say, bring people into the room.

Cole: Yeah. You're reminding me of grandmother Agnes Baker Pilgrim. I used to be involved with the The International Council of Thirteen Indigenous Grandmothers, and grandma Aggie used to say, "You can't just talk to talk. You got to walk the walk." She talked about being a voice for the voiceless. I absolutely hear what you're saying. I think it's very valid and I think that's the kind of thing we need more of. I think about you at 15 getting kicked out of high school. What were you fighting with people about in high school?

David: Ireland's a very religious country. We tend to be educated by priests and what are called brothers or the Christian brothers. I fought with them over religion. I'm an atheist and so I questioned some of their doctrines and issues. That should be good. You would imagine a school would be a place for questioning, as we would imagine university would be, but consistently we see that's not the case. So they kicked me out.

Cole: Wow. Wow. They kicked you out of there.

David: I was very annoying.

Cole: Yeah. I can believe it. You do have a reputation and I'm sure you're self-aware enough to know.

David: Absolutely.

Cole: How long have you been at Penn State, actually? I don't think I ever asked you that.

David: I came in 2011, so I came to the United States in 2008. I had a fellowship at Harvard, and I just wanted to see the U.S. and intended to go back. Fell in love with the country, myself, my wife, she's Italian, Alba, fell in love with the country in a few weeks. We had two kids in Boston. It was great. I'm Irish, she's Italian. We hit a quarter of the population, but of course subsequently fell out of love with the country and back in love on various stages. It is an extraordinary country to be in.

Once I was in Boston, I came down to Pennsylvania to visit Penn State. Really had not understood the land grant system or been exposed to it. We're just blown away by its potential. It is an extraordinary system. Andrew Read brought me down to give a talk with the idea of looking into joining the faculty here, which I did. It was excellent. It's a phenomenal place with extraordinary history and potential, and CIDD and Huck are just wonderful. I came to Penn State with my ants, my rainforest work on the ecology of ants being manipulated by parasites, and I in my job talk I showed a picture of Old Main and the beautiful mural on the wall and said, "I want to do something that's useful." And here we are.

Cole: Terrific. Yeah. I remember Alba worked at the Huck for a little while.

David: She did.

Cole: It is kind of a fun, odd couple. She's so Italian and you're so Irish, and in Boston I'm sure you're surrounded by some Irish. I don't know how much you get that in Central PA here. It's a little more dramatic, I guess.

David: Not, not many. Yeah, for sure.

Cole: We're very international now. I came here in 1987 for school and never managed to leave. I'm one of those guys, like a lifer at Penn State. I've seen it get more and more international as each year go goes by.

David: Yeah.

Cole: Certainly, your team is incredibly international in the work that you're doing. Was this the place that you really were able to tap into an international community? Can you talk a little bit about that journey?

David: Yeah. I came here and I came up with this idea of PlantVillage, which is now what I work on. I no longer work on the ants system. The Huck have supported that through their innovative system, the transformative science approach HITS, which is great. They really made a big bet on me, and I've slowly grown it upwards. We have benefited from the diverse students here. Right early on in 2013, 2014, we'd have students from Ethiopia or Bangladesh translating content for us. We've had over 230 undergraduate students in our lab since we've come here.

Cole: Wow.

David: And then of course, the staff members and the postdocs are coming from a wide range of countries, but PlantVillage is not Penn State. PlantVillage is a global movement. There's over 120 people who are just what are called Dream Team Members in eight countries. In addition, there's lots of staff members to help us with developing the engineering solutions, and they're spread across four or five countries at this stage. So really it takes a village, as we say, and that village should be diverse. We often say that if you had a village and everybody was a blacksmith, it wouldn't be a good village.

Cole: That's right.

David: So we need lots of diversity.

Cole: Absolutely. That's what this podcast is supposed to be about, is people with different skills coming together for a common purpose and helping one another to achieve something bigger. Maybe I'll back up a second and we'll talk about PlantVillage. We did it in the marketing and I think most of the people watching know that you're the founder of PlantVillage, hopefully. We just came in conversationally. Maybe we could back up a little bit and I could ask you about what were the origins of PlantVillage? When did that idea first hit you? Was it a response to the HITS call? That was the Huck Innovative and Transformational Seed grant in 2012, I believe. Was it the call that got you thinking, or were you already looking and envisioning something like that?

David: It was in the rainforest of West Africa in Ghana in 2010 when I was traveling around the world with my colleague, Harry Evans, who's an expert on fungi affecting plant diseases. As a side thing, he looks at fungi affecting ants, so we had traveled over 110 days on three continents going at the rainforest and coming out of rainforest. Every time you come out of a rainforest in South America, Africa, Asia, you walk into a farm decimated by diseases, but we actually know what the answers to those diseases are. The birth of plant pathology was 1846 with the Irish potato famine, the birth of extension, which is the cornerstone of Penn State, was 1846, also in Dublin. It's really, really bad that the knowledge that we should use and could use to help people control problems is not accessible.

It's not accessible by design. We decide who's in the room, who's not in the room. We're at Penn State and we spend three million dollars a year in our library, seventh best library in the country, but that's not accessible if you go five miles off campus, for example, and it's certainly not accessible in Ghana. In Ghana, I was looking at a publication on cocoa diseases, which I was looking at, at the time. It might cost you $45 to buy a paper, a journal article from the 1980s that was paid for by the taxpayer in the 1980s. That is just absolutely immoral in my mind.

If I look at the land grant universities, as I had, as I said I didn't know much about them, and I look at technology and Moore's law and computing, I put those two things together and saying, "We can have a land grant and a phone." Phones are going to get better and better and better. My colleague, Harry Evans, a global expert, we could put Harry in a phone. This is the vision. Not just Harry, but thousands of scientists like him. That's what we're doing. We knew we could benefit from scalability and computing, better and better AI and so on and so forth. We began that journey in 2012.

Cole: Wow. Harry was an entomologist?

David: He's a plant pathologist working for the British government for 35, 40 years. Just a walking encyclopedia of knowledge. Unfortunately, we're not making people like him anymore because we don't value that. Despite our land grant heritage, what we do value are people bringing in NIH R01 grants with large amounts of overhead publishing in Nature of Science and so on and gaming the system for some arbitrary set of metrics that we've judged to be important for the tenure and promotion package. We have a different approach, which is to solve the problems, in the case of Penn State, for the Commonwealth. If you buy into what we say in Old Main, for the mission to solve the problems for the world, you want to be a global land grant. If that's true, first principles, then live a up to that mission and actually work for the problems which we can solve today.

Cole: Right. To be that one community that is impacting many, as we say, around the world.

David: Yeah.

Cole: Well, I salute you for having that vision. I'm also curious as we look at the history of PlantVillage, did you have sort of a technical guru? Because it's so technical. I'm going to say something different about the mic than I did before. I think if I get you a little closer on the mic, we'll be able to hear you a little.

David: Yeah. Sure.

Cole: There. That's terrific. Sorry. It's our first go here. Did you have a technical guru on the AI side, or did you just see it? Did you just look at your phone and see, "I know this could be in a phone?" Was there somebody guiding you there?

David: Yeah. Well, initially I worked with Marcel Salathé who was also a faculty member here. Marcel and a chap called Mohanty, who was with him, we worked on a very old system called Café, which is a bit of a clunky system. And then we reached out to Google. If I'm good at anything, I'm good at mooching, meaning I find people, so I found Vint Cerf. I found him through the Huck actually, through Nina Jablonski here. Vint Cerf is such a grandfather of the internet. He invented some really critical parts of the internet structure. He put me in contact with people at Google, Kevin McCloskey was one, and we began to start working on some of these datasets we had. We worked with domain experts in Africa at IITA, James Legg, and we put those together. And then, the real opening was Pete McCloskey, Kevin McCloskey's brother. He was an undergraduate at PIT and came to Penn State and hasn't left, thankfully. He's really combining the approach and driving forward our AI. He's the critical person in this conversation.

Cole: Cool. Thank you. I was just curious. I do want to make sure we stick to our theme which is that risk taking, because I'll have a little fun with you here. You're not unlike me, I think your reputation sometimes precedes you and you can be maybe a thorn in the side of folks who want to do things in a very traditional manner and stay in their lane. The marketing world that I'm in, it makes me think of the Apple commercial. Did you ever hear of the Apple commercial in 1984?

David: Yeah.

Cole: Where there's all the brain-dead drone, zombie people, and the woman comes in with a big hammer and smashes it. When they went in front of their board to do that for the Super Bowl and no one had seen it, and people were just losing it. They were ready to walk out the door tearing their hair out and having a real meltdown, but Steve Jobs was right. That was exactly the right message to give to the world. I think that that battle still goes on. Do you feel like we're starting to win a little more in terms of loosening things up and being creative and dynamic and breaking away from that stale, static mind thinking? How hard is it as an academic to do that? How risky is it? How risky has it been for you?

David: It's extraordinarily risky because if you're pre-tenure and you come in to do one thing, and then you start another thing, then you have a high chance of failure, and the system doesn't reward this. The system rewards the addition of small incremental steps in order to get the next grant, in order to get the next paper, and then to sign off on your dossier. Certainly, as I did at the University, annoy a lot of people, that's not helpful. That doesn't help.

I'm rather stupid and tough skinned, and so I just kind of plow ahead, but nonetheless, I think the University should do a better job of enabling risks because all the people that you see or content that you mention or companies like Apple which are successful, all of those successes are a long history of failures. Success only comes from a long history of failures, and we are now scaring young faculty coming in not to take risks for fear of getting this big ax fall upon them, which is deny tenure.

Cole: I see. Deny tenure. Yeah. Well, we could shift gears a little bit and maybe we could check out one of these videos. Just to let anybody who doesn't know and didn't see the marketing, it's been a very great year for you, David. It's funny because you had said, "Yes, Cole. I'll do this podcast with you. I'll be your first victim for the first podcast." We didn't know at that time that you were going to be named in Fast Company's Most Creative People in Business, which is really interesting for an academic to be a creative person in business when you're solving problems related to global hunger.

Also, the Newsweek named you in their inaugural list of America's Greatest Disruptors, which is no surprise because we all know you're a disruptor. Also, USAID would look at your proposal and award you and your team with up to $39 million to a USAID innovation, the Feed the Future Innovation Lab on current and emerging threats. That's all fabulous. I just wanted to let the audience know if they didn't know that. You know, I didn't go the traditional route, "This was David Hughes and here's his bio and here's all the great things that he's done."

I do want to show this video. We were so excited about what you did during the African locust plague of 2020. It was such an amazing story. My team came to me and were like, "Cole, we want to do a video about this. We want to do a really detailed video to try to tell this story," because we felt more people needed to hear that. You worked with us and we're going to bring that up in just a second so that the folks watching can see it. It's about five minutes long. This is the first time we're showing it to anybody a other than yourself and a small group of folks that signed off. I'm going to get ready now. Dan, or is that all queued up? We're ready to go. We're going to let everybody check this out.

Narrator: This is a grasshopper and these are locusts. When conditions are just so, certain grasshoppers become locusts and that can be really bad for farmers because this is what 15 million locusts can do.

David: When there's abundant rain in the desert, there's abundant vegetation and this leads with increase in the population. All these grasshoppers bump into each other and they go through a dramatic change in their behavior and physiology to become swarming locusts.

Narrator: This is Penn State entomologist, David Hughes, Huck Chair of Global Food Security and founder of the PlantVillage project.

David: The mission of Plant Village is not only to help farmers cope with the stresses of climate change, but actually thrive. We do that through the combination of world-class data in a cloud system, AI working on phones, and a community of youth across Africa called the Dream Team.

Narrator: The story of the 2020 East African locust swarms is a study in the real world impact of climate change. In 2018, an unusually active cyclone season in the Indian Ocean created storms that drenched the Arabian desert. The number of desert locusts exploded, by some estimates increasing to more than 8,000 times the size of their normal population. Over the next year, seasonal winds pushed these insects South and West across the Gulf of Aden where a wet autumn and a December cyclone, this time in Somalia, kicked off a crisis. Nations across the horn of Africa now faced the largest locust threat in 70 years, with swarms as dense as 15 million insects per square mile able to consume as much food in one day as an entire town. And the timing couldn't have been worse. It was early 2020 and the entire world was just beginning to notice the emerging coronavirus outbreak in Wuhan, China.

David: This was a crisis within a crisis. Actually, I was at the UN on the 29th of January talking to the Secretary of Agriculture at the time. They were really stuck because they weren't able to do surveying across Kenya because everything was shut down and closing. It was really important that we could get those necessary surveys for the necessary control. Because we had worked in building apps for them, they asked, "Could we do this?" Essentially, what we did was we built the airplane as we were learning how to fly.

Narrator: PlantVillage had already proven its viability to the UN by bringing agricultural knowledge and best practices to massive numbers of small-scale farmers across Africa. Nuru, an AI powered assistant distributed on inexpensive smartphones, was designed by the PlantVillage team to diagnose common crop diseases and pests like cassava mosaic disease and fall armyworm. It only took the PlantVillage team a month to build and deploy a new and effective tracking app, eLocust3m. Before the end of March, their new tech was on the ground in the hands of volunteers and available to anyone with a smartphone. Team members trained locals in hard hit areas to track and report locust sightings. Over the next year, almost a quarter of a million records flooded in. Vulcan, a Seattle-based geographic data company integrated the PlantVillage reports with a custom version of its own software to direct aerial spraying efforts in partnership with the UN and governments.

It worked. The westward movement of the locust was halted. The countries in the Sahel, a semi-arid region South of the Sahara, were spared thanks to the spraying. The UN's Food and Agriculture Organization estimated that in all these efforts saved more than a billion and a half dollars of agricultural products, the livelihood of 34 million farmers, and the food supply for tens of millions more. The PlantVillage story was covered by the New York Times in April 2021. A few months later, Hughes was hailed as one of the Most Creative People in Business by the magazine Fast Company, and at year's end, Newsweek had added him to their inaugural list of America's Greatest Disruptors. The PlantVillage team was also recognized by USAID, which awarded Hughes a major grant to scale up efforts across the globe.

David: We're lucky to be running a USAID innovation lab on current and emerging threats, and there are 21 Feed the Future countries. So naturally, our objective is to scale up PlantVillage to those 21 countries from Central America to Asia, which of course is over a billion people, and they're predominantly relying on agriculture. The goal is to get there, help over a billion people cope with the stressors of pests, weeds, and diseases, but at the same time, do that in a climate change world.

Narrator: For more information about the PlantVillage project and to find out how you can get involved, visit plantvillage.psu.edu.

Group: Thank you, PlantVillage!

Cole: We had so much fun making that video, honestly. I want to thank you for doing the work because… I'll be real. I haven't always felt great at Penn State. When the Sandusky thing was going on, good Lord. It really just destroyed me. Talk about a low point and a permanent stain on our reputation. The people who don't know Penn State sometimes they'll be like, "Oh." They'll make some crude joke about that as if that's all Penn State is about. We really have a lot to overcome there. When I see somebody like you, David, doing work like that, then I know that there's so much more to us and there's a whole other beautiful, wonderful side of what we really are about and what most of the people here are about. It's that land grant mission, and it's about being of service, and it's about taking that research prowess and putting it to good use.

David: I do need you to point out that it's not me, of course. I'm just one part of it. It's a village. It requires a communication team. The video you made is excellent, and getting that out is critically important. People who are not here but are critically important are people like Frank Doyle, who was the person who made that airplane while it was flying, but then our UN partners, our country partners, our Dream Team, Melodine Jeptoo, was mentioned that New York Times piece we talked about. Yeah. There's a huge number of people involved in this. I'm just the mouthpiece.

Cole: Well, thanks for getting them all together, corralling that energy. Speaking of that, now I'm going to go back to when I was a Penn State student because I'm an alum as well. I had a professor back in the day, her name was Dorothy Blair. I think it was 1987. She was the first person in Pennsylvania, she and her husband, created a community-supported agriculture farm, the first, the first in PA. So she's very innovator, forward-thinking person. She was teaching in the science technology and society program, which no longer exists sadly, but it was the earliest spot at Penn State when really people started thinking about sustainability and a lot of these issues that are so important now.

Dorothy taught me in a global food class. It was a class about global hunger. I took that because I really wanted to learn more about it. She taught us that a lot of times, the rich White Western world will go into another country thinking they have all the answers, and it's almost like a paternal, very negative thing, and it can go really wrong. Maybe they create more problems than they solve, but I don't get the sense that you're about that and you're doing that. I'd like to hear you talk about that a little. How do you avoid that cliché kind of approach?

David: The problems Africa has are problems of colonialism, and now increasingly neocolonialism. It's an incredibly rich continent with resources, natural resources and human resources and mineral resources, but they've been stripped away. People have been stripped away, cobalt is stripped away, and this has happened through the umbrella of colonialization by the Brits and the French and the Belgians, et cetera, but then increasingly now neocolonialism by the large corporations. So of course, I'm approaching this as a person who comes from a colonized nation. Ireland was colonized by the Brits in the same way Kenya was. Our potato famine was compounded by British efforts in order to use an infectious disease as a really good way to reduce the population size. This is the framework that we come at this from.

What we do at PlantVillage is work so incredibly closely with local communities. We're about 130 people in PlantVillage. Most of them, I'd say about 85% of them, are African. They come from eight different countries and predominantly youth. I'd say about 75, 80% are under the age of 30, and a lot of women, about 60% women. We also work intentionally with women farmers, about 83% farmers. I think it's really brought home to me last week when Annalyse Kehs, who's our director of operations and really runs all of this excellent work through the Dream Team as they're called, she said, "Is there a law against what we're doing? It's not what we do, but is there a law against it?" Because it seems so obvious to us that if you're going to work in Northern Kenya, you'd work with Turkana, Samburu, ane Rendile tribes. That just seems so obvious."

If you're going to work with making change, you'd employ 37 young people for the price of one FAO consultant, which is about $650 a day, gets you 37 young Kenyans, and you would just give them technology and bring them up to the level of the expert from Europe. That just seems really obvious. I was really struck by what she said. The model that we have is insourcing. We always talk about outsourcing being bad, but that's what we've been doing for Africa and development for the last 40 years. We're outsourcing. Only Europeans or Americans can solve the problem when they fly in an airplane and stay in an air conditioned hotel room.

Our model is the young people are already there. Let's insource. Let's just give them the technology and raise them up with technology. One phenomenal example besides the locust crisis is that we've just set up a Dream Team in Ethiopia, and for the listeners who know this, it's currently undergoing a quite severe civil war which has resulted in many aid agencies leaving, staff of the Irish embassy were kicked out, but we're able to set up a Dream Team in that country despite that stress because guess who hasn't been kicked out of Ethiopia – the 76 million Ethiopians. We want to work with local communities. Again, I loved what Annalyse says. "Is there law against it?" And apparently there's not, and there's great success to be had by going that path.

Cole: Right on. Thank you for taking us a little deeper into what you do and how it all works. I know I got to meet one young man from Ghana who was on your team, Edward Amoah. Again, we had an amazing time making a video about what he's doing because he and his team managed to win a student XPRIZE this year. Now, we haven't been able to really release that to Penn State, but I talked to corporate today, and I got permission to share a little of his story because we're still working through the contract, and we could have a whole other podcast about money and the strings that are attached to money and how that works. Go read the book Dark Money by Jane Mayer. Go read the book Dark Money by Jane Mayer everybody, because sometimes something is called philanthropy and it's not.

Not to say that that's the case with the XPRIZE, but it's always complicated. Big money is also really complicated almost all the time. What is less complicated and more exciting and inspirational is what Edward has been doing with the PlantVillage team. We're going to show a two-minute video just to celebrate his winning or his team, the whole collective, as you say. It's a lot of people working together and the vision. Can you talk a little bit about the vision of what they're doing to cue this up of what we're going to show?

David: In Africa, we have a huge problem of climate change and it's very unjust because Africa has contributed about 2% to global warming, but they're overwhelmingly paying the costs. One of the approaches we can take is agroforestry where you plant trees on the borders of the farms, and then you turn those trees through a technique called pyrolysis where you burn the wood at high temperatures and low oxygen and forms biochar. If you put that biochar into the ground, it's very, very useful in combating drought and helping the soil and regenerative agriculture.

We want to take this approach of growing lots of trees, storing biochar. It just so happens that that part which is called climate change adaptation is also as a side effect climate change mitigation. Our vision is to have 200 million farmers raise themselves out of poverty in Africa in a single generation pulling down one billion tons of carbon per year. Even though they didn't create the problem, Africa will help us solve the problem and also end this never ending cycle of philanthropy and charity and donations, and allow them to be profitable.

Cole: Yeah. I love the vision. It's amazing. Dan, he's giving me the thumbs up that we're ready for our audience to take a look. Check this out, people.

Edward Amoah: My name is Edward Amoah and I am doing ecology here at Penn State. I got involved in PlantVillage as an undergrad researcher in 2019. We've been working with small farmers in Africa, from Kenya to Burkina Faso. We have developed a technology that we are using to track and monitor pests in farms. We want to be able to adapt that same technology to help monitor and track tree growth with our farmers.

David: The XPRIZE pitch is remarkably simple. Philanthropy is not going to solve the problems that hundreds of millions of people facing the climate crisis. We believe at PlantVillage that the markets will be able to help, particularly the carbon markets. We're developing this system whereby we can plant and track trees at scale, not only to enable climate change adaptation at the farm level but provide an alternative source of revenue for these farmers.

Edward: So, we can help farmers in Africa be able to move out of poverty while also pulling down carbon at scale. Quite honestly, this is a win-win for the global community. I am an African. I grew up in Ghana. I grew up humble financially. I have seen some of these challenges that I hope to be able to address with the work that I'm doing with PlantVillage and with Penn State.

David: We need young people to be solving the climate crisis. Edward is one of many on our team, the Dream Team we have, the larger group at PlantVillage who are solving these problems every day.

Edward: I'm really excited about this XPRIZE award because we get to show the world what we are doing and the way forward to being able to address climate change and food security together. This issue is not an issue for only ecologists, but it's an issue for everyone. It's an issue that we all have to come together and address. I am grateful that PlantVillage at Penn State and Penn State as a whole provides that environment to help us be able to achieve that goal.

Cole: David, I get goosebumps every time I watch it. Again, thank you because I could show that to my kids and say, "Hey, this is the kind of stuff we're working on." I'm almost choking up. What you're doing there with folks like Edward, it's so inspiring, it's so meaningful.

David: The issue is not that I'm doing it. I hate to harp on this as if I'm trying to say something immodestly, but it's not. It's fundamentally the case that when you let different people into the room, amazing things happen. This story of Edward is one repeated daily across PlantVillage and our huge team. Just bring different people into the room who are not there, and then enable them through education and technology, and then the results are just extraordinary.

Cole: Absolutely. Yeah. It's fabulous. Well, we're not going to have too much ... Officially, maybe five, eight more minutes with you. We started a few minutes late, so I'm going to look at these questions while we still can. Let's see. Recent, popular. What's the most popular question? This was my first time going at this. This one had three likes: How did you switch from working on zombie ants to taking on global hunger? People want to know.

David: With great difficulty. It was extraordinarily hard to switch. Especially, I remember quite clearly the day I stopped, which was with Colleen, my last postdoc working on extremely interesting stuff. I think we were on Zoom, it was COVID, and I was very upset. I cried with her, and I had to stop. In that transition, it was very difficult. This is my life's work.

Cole: Yeah. For people who don't know, David made quite a name for himself working with zombie ant fungus. We made an art exhibit about it and, and I helped Daryl Branford make a thing for kids. It's amazingly cool, sci-fi, fun, and it got a lot of media attention. You were known as zombie ant guy. It was your Twitter handle, Zombie Ant Guy.

David: I grew up in a very chaotic place, and Sunday evenings watching David Attenborough take me through rainforest around the world was such a precious time for me. I had the great fortune after I got back into the educational system to get to places where I could spend my life describing species of fungi with João Araújo, one of our former students and now at the New York Botanical Gardens. It was wonderful. I wanted to do that. I still want to do that, but unfortunately the world has problems. I know I can take the great force of Penn State and I can apply that with the great force of technology to solve those problems. I know I can do that. I am a tenured professor at a university. I can't be fired. It's wonderful. I have freedom.

Cole: Say it as it is. Yeah.

David: No. It's true.

Cole: If I could just be a tenured marketing director, David.

David: Well, just recognize the privilege that you have and with the technology surrounding you to make videos to change the world and then involve other people.

Cole: Yeah.

David: How did I transition? It was a hard transition, but I did it.

Cole: Yeah. Well, kudos to you. If we could clone you, then you could still go chase the fungi.

David: Well, João is doing a great job.

Cole: He's doing that. Yeah. You get to do it through him a little bit. That's great. Vicariously. Here's another one. Number two question: Hello, Dr. Hughes. What is the most rewarding part of your work?

David: It's the cloning.

Cole: The cloning.

David: In 2019, we got money from Eric Schmidt and Wendy Schmidt, which really helped us do all that locust work. It was transformative. That's why gifts are important. I know you're going to talk about gifts later on. And then as part of that, I got Annalyse Kehs, who was just one of our undergraduates and she became the director of operations and just phenomenal. Very specifically phenomenal for organizing the large team through what's called our objectives and key results.

What's wonderful is now Annalyse is being cloned as Winnie Onyango in Kenya. Now Annalyse is not needed. We had this rule that what are the three things you're needed for today that other people can't do, because if you're not working on those, you should be, and you shouldn't be in a room somebody else can do it. So empowering other people to do it. James Mugo, another team member who just launched a Dream Team in Uganda, John Mayieka doing agroforestry, Melodine Jeptoo working in Northern Kenya, so on and so forth. I could just go through a list of names, and they're just cloning. It's just absolutely amazing. I talked to Annalyse about this the other day how you might have an idea and then the idea comes back to you after they do it. Just phenomenal. It's just wonderful.

Cole: I want to see your playbook, David. I need to clone myself because I'm running myself ragged. Well, you do too, but yeah, the cloning. Yeah. I've been thinking about that myself. How do I get others to maybe be able to do some of these things? That's brilliant. We only have about five minutes left officially. I'll ask one more question, and then I do want to make sure that we cover the donation side and you could talk about Eric Schmidt you mentioned a second ago and someone at Google is-

David: We have a matching fund.

Cole: That's that matching fund. Yeah. I'll ask one more question, then we'll put something up on the screen for folks. Let's see. There's two that have tied. You can, answer either one: How do you decide what countries to work in or what do you look for in students or researchers you partner with?

David: For the second question, we look for a biased action. It's fine to talk about these things all day long, but that's why we're in the current problem. So we want people who have a biased action and we're very good at finding that.

Cole: A biased action. Meaning?

David: Meaning they want to get working on a problem. If they're domain experts, if they're students, whatever the issue in front of them, what are they actually doing on a daily basis to change that? If we give them a task, will they do it and come back. They're just act rather than talking about it. That's very much related to the first question, which is which countries. We tend to gravitate towards opportunity we have. Currently, for example, we're really scaling up in Uganda and that's because of we're working with the world bank there and John Ilukor, a collaborator with us. It's just phenomenal. So active, so engaging, so much bias towards action. That's obviously where we're going to go more than a country where we don't have that strong partnership. That's how we would go with those two questions.

Cole: Yeah. So you follow where the energy is, where others have the passion and the energy. That makes a lot of sense because there's only so many minutes and hours in a day.

David: Yeah.

Cole: So you want to use them wisely. Thank you for not taking any texts from the UN or the USAID while we're on this because usually, I know they're always at you constantly, speaking of time. So as we just kind of wrap it up, I do want to make sure we put up on the screen, Dan, if you could put that URL up on the screen for people. It's plantvillage.psu.edu/donate. If anybody watching this wants to go there, there's actually a matching program going on. Explain for people, if you're getting up to 39 million from USAID, why do you need more money? Where does that money go? Let's really let people know what that's like.

David: Yeah. The USAID money is for research and development. We still need a lot of money for putting into action on the ground, operationalizing things on the ground. Things we know work, we could operationalize them. They might be boreholes or tree planting or providing farmers with phones or SMS for knowledge about what to do when to do it. Through Jeff Dean and Heidi Hopper, the Hopper-Dean foundation, Jeff is a lead AI researcher at Google and he's been working with us for a long ... Very, very great supporter of what we're doing.

They put up to 2.5 million matching funds, which is just so, so amazing. We want to match that and lead to a situation where we're doing climate change adaptation practically on the ground. We have a goal. We currently reach about four to eight million people a week. We have a goal to get to 50 million a week in the next two years. We need a lot of infrastructure for that. We need more team members and that's what gifts do. Gifts are just extraordinary because they allow us to operate flexibly.

Cole: We really do thank the Hopper-Dean Foundation. It's phenomenal. They've been there with you on the ground. The male side of that, Jeff, he had an experience going to Africa. He had a personal transformational experience himself. Is that right?

David: I don't know about transformational, but he lived there when he was a kid. I think he was about 11 years old. I think he lived in Somalian Uganda. Obviously, that flavors his thinking, but I also think it's their daughters. As a family, this is their gift giving, and their daughters are in their twenties and obviously are focused on climate change as many of our listeners are. It's the biggest issue we have.

Cole: Yes.

David: So we must solve it for the farmers and help them because they didn't create the problem, so why should they pay the bill? At the same time, we should solve it for the world. So we're trying to do those things. I think the Hopper-Dean Foundation have just been amazing partners as have Schmidt Futures and other donors like the Gates Foundation, Skoll Foundation, and so on.

Cole: Yeah. So many have all chipped in. I think it's your vision. I think it's that inspiring vision that you're walking your walk and you're talking your talk as well, but walking your walk is, as you say, that biased action. Bias is how you put it?

David: Yeah.

Cole: It means a lot.

David: Just do something.

Cole: Just do something real. Just be real and take things on for real. Well, kudos to you. If anybody goes to that link, if you have money and you're able to do that and feel inspired to do that, you can. You can go to that link and it'll be matched for the next two years that'll be running.

David: Yeah.

Cole: A matching fund up to an additional two million dollars they gave.

David: That's correct. That's correct.

Cole: For those of you watching who are in that category and are inspired by what you're hearing here and seeing, might want to consider checking that out. Also, I want to, before we leave, I'm just about at the end of our time, we'll let you know that next episode in one month, these are going to be every month, we will have Dr. Nita Bharti on the podcast. Nita is a great friend of ours. We worked on the Ask CIDD stuff. She's done a lot of public good, public service answering questions about COVID from the local community just because.

David: And a fabulous scientist. Excellent work.

Cole: And a fabulous scientist.

David: Her work in Africa on fire.

Cole: Taking risks and doing things that are a little different, taking junk data and making it into actionable data that makes a difference, a real difference in the real world.

David: Yeah.

Cole: Look forward to that. Bookmark it, folks. It'll be at this same page, it'll be on the 24th of February. It's always the last Thursday of the month. We're going to run these all the way through until October, and then we're going to fall down and go to Thanksgiving and have a break and regenerate. Next episode, come back because we may do a little something special with our ... If you've seen these over here, if you can cut wide, Dan, we have our little plushies here. We're going to do a little poll.

I just wanted to point this out. Dan's shot a little clip earlier. I love to say that Penn State's evolving. If you want to, Dan, you could even roll that clip on our way out here. Let's just do it. This is live. We're going to go along just for fun. You let me know when that's rolling. Okay. It's rolling. Today, the beautiful thing is you're not just stuck with the Nittany Lion. If you don't feel it, if you don't feel Nittany Lion-ish, you could get a llama. You could get a gnome, you could get a little baby bear, you can get a unicorn. I asked David earlier, and he's with me. His favorite is the unicorn. If you're still here and you want to vote for your favorite alternative plushy, the llama, the gnome, the bear, or the unicorn, this is your chance.

Just go in the chat and we're going to collect the data all year, and then we're going to see if the different audiences for the different scientists like the different plushies. And then, maybe we'll get back to you at the end of the year, David, and we'll see how many people are with you with the unicorn and who's with some of these others. We got a lot of gnome lovers, too. Anyway, all that silliness aside, thank you so much, David. It's just been brilliant talking to you. I don't even have to tell you good luck and do your thing because you're always doing it! You're like the Energizer bunny, just going. So just keep on going. We're all going to be watching and thanks again for taking time out of your busy schedule to talk with us today.

David: Thank you. Thanks to the team for inviting me. It was a pleasure.

Cole: Cheers.

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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.