Intro (Nina Jablonski): Evolution involves more than the survival of the fittest. It's also about the survival of the most cooperative and mutually beneficial relationships are critical to the survival of every species. Welcome to The Symbiotic Podcast, where we will explore the collaborative side of life and work to consciously evolve science itself.

Cole Hons: Greetings, fellow Homo sapiens and welcome to The Symbiotic Podcast. I'm Cole Hons from the Huck Institutes of the Life Sciences at Penn State, and I'm here today with my colleagues from the Huck. I've got Beth McGraw to my left professor and Huck scholar in entomology, who directs Penn State's Center for Infectious Disease Dynamics. Her research focuses on dengue virus transmission by mosquitoes. McGraw is currently investigating evidence that mosquito and virus genotypes, affect patterns of human disease. She is also interested in the use of a bacterium called Wolbachia for bio control.

Matt Ferrari across from me is an Associate Professor of Biology at Penn State. He uses the mathematical and statistical tools of computational biology, to understand patterns of disease incidence, and the effects of heterogeneity across time and space. Ferrari currently collaborates with Doctors Without Borders to track incidents of measles in Sub Saharan Africa. Nita Bharti is Lloyd Huck early career professor and assistant professor of biology at Penn State. She investigates the interactions between behavior and biology to inform public health intervention strategies.

Using satellite data, Bharti has pioneered new methods to track seasonal movements of the human population, with profound implications for improving vaccination campaigns. Welcome to the podcast, everybody.

Matt Ferrari: Thanks.

Beth McGraw: Thanks for having us.

Cole: Thanks for coming on short notice, I dragged you all in here very quickly because the whole world is heating up around the latest coronavirus outbreak and I know it's been a busy week for so many of folks talking to the media and we're all trying to keep up with what's happening, before we get into our conversation, I was just looking on my phone at my New York Times app. The coronavirus beyond China has spread to 23 additional countries right now, over 20,000 infections in China, which is about 5000 more than the SARS outbreak. We're under 100 infections outside of China, including 11 in the United States.

It's been the first death in Hong Kong today. Hong Kong medical workers protesting going on strike too close borders down. Lots of auto plans shutting down. It's pretty hot stuff in the media. I just thought, I don't know what the situation will be when this actually goes live at the end of the month. We'll see where things are at that point, but I expect we'll still be in the middle of it a month from now, but I would like to have a conversation with all of you because you folks work on this stuff every day all the time.

Even though as I shared your bios, you each have different things you focus on, you all do work together at the Center for Infectious Disease Dynamics at Penn State, which is well known globally for bringing together many disciplines and looking at infectious disease and movements across populations in unique ways. So I really want to do a deeper dive with you on what you can contribute to the conversation that maybe people aren't getting in the mainstream media. So Beth if I could start with you, how would you describe CIDD and what's special of the Center for Infectious Disease Dynamics, that makes it a little different in the way that we look at these things?

Beth: Yeah, so CIDD's pretty special and then it brings together a large number of experts in infectious disease, puts them together in this really rich collaborative environment, and by working together from across a range of disciplinary boundaries, so we've got people doing really basic molecular work, really reductionist work, people working on modeling, people working in the field, by working together it really elevates everyone's ability to have an impact on public health. Additionally, people are reaching outward across more traditional science boundaries into the social sciences to partner with people who might help as we move into more complex social environments or applications in the field.

Cole: [inaudible 00:04:20] Nita, Matt, would you like to talk a little bit more? You've been at CIDD a good long time now, right?

Matt: I have been at CIDD a good long time. I think one of the things that's really special about the group that we have here is in contrast I think, to the way a lot of conventional infectious disease biologists studied at traditional academic institutions would it tends to be discipline or host focused. So infectious disease biology tended to be isolated within either a medical department for humans, a public health department, maybe a veterinary biology department, or a plant pathology department, or entomology right? So they're really tied around the specific thing that's getting sick.

So the focus is on, "What are these pathogens doing to their host and the sickness or the disease associated with it?" Right? But I think what we've done here at the Center for Infectious Disease Dynamics is to turn that story around and say, "Well, what's common about the parasitic lifestyle writ large, and what is special about viruses and bacteria and fungi and these things that tend to use other organisms as their both environment and their resources?" What that allows us to do is to look for commonalities across the biology of plant pathogens and human pathogens and animal pathogens and actually learn from each other, because of the common processes that are happening across all those systems.

I think what that's been really enlightening for me, as a biologist to see that, in fact I can oftentimes just by expanding the scope of people that I'm talking to, can learn all these extra concepts and tools, right? Because something that worked in plants that maybe human folks hadn't ever thought about ... human biologist hadn't really thought about, translates over really well and can all of a sudden expand the way that we see the world around us.

Cole: Right on that's precisely what we're trying to explore with our podcasts as well. Is just everybody teaching one another. Nita, do you have anything to add to that?

Nita Bharti: In support of what Matt said and what Beth said, I think it really is true that CIDD is run and operates as a place where we focus on the underlying aspects of infectious disease, and I think that allows each of us to be more efficient because we're working across fields without intentionally doing so, because we're staying within our infectious disease discipline in some way, but that would be cross college and cross departmental, in other situations. So in that way, it makes us really efficient. It also makes us well versed in things.

I think, for me ... I'm probably the newest person, I don't know, for me, one thing that I really appreciate about CIDD is that our seminar series is built that way. So we're able to learn from external visitors, visitors who are ... I guess all visitors who're external. We're able to learn from visiting speakers about how they're looking at infectious diseases or infectious processes in a multitude of different systems. That may be the work that's not represented at CIDD but because of the way we've structured our seminar series and what we prioritize, we're able to learn from those things.

Cole: Fantastic. So we're getting a really rich, and almost a 360 degree view of infectious diseases right here, regular pulse week in week out. I go to some of those coffees and pick up from my non scientist perspective. It's a lot. It's a lot happening. So I want to ask you, as people who work in this field day in, day out, year in year out, working on your research projects and learning from one another in this rich environment, how prepared do you think we are as this emergent global culture, this international, emerging global world that's more and more connected with technology, et cetera?

How are we doing in terms of being prepared for something like the coronavirus that's on us right now.

Matt: It's a really interesting challenge. I think we can maybe answer that question by comparison to large scale outbreaks that have happened in the past.

Cole: Okay.

Matt: Right? Two important things have changed, right? So characteristics about the world itself have changed that we can't possibly be prepared for, right? A lot of people are making comparisons to SARS in this outbreak and when you look at the integration of China into the global economy, at the time of SARS versus now, their economy has doubled or tripled in global relevance and the intricacies of the Chinese supply chain interacting with global economic forces, has increased dramatically. So there are things that are changed that we can't possibly be prepared for, because this is the first time that we're seeing them.

So there are aspects of that I think that we always need to be aware of whenever these new things happen, they're always going to be learning some new things that we can't again ... These are the first time that we're seeing them. But, some of the things that have happened since those ... The lessons that have been learned since those previous outbreaks, are the global connectedness through things like airline travel, and the potential for things to spread rapidly around the world, and that actually has important practical consequences in terms of the way that we say prioritize surveillance.

How we look and keep an eye on sick travelers or ... and how we might identify high risk areas, high risk places, high risk flights, where we can then identify people say or do fever checks and actually be much more prepared for containment, right? These things are going to spread without a doubt. So, all we can is do the best we can to contain the magnitude of that spread. I think some of the other things that we've done is, through the course of the experience in previous outbreaks, we've really done a lot to identify knowledge and training gaps throughout the world, and try and expand the global academic community and create partnerships with academic institutions and ministries of health and other organizations to broaden the scope of international collaboration and understanding.

That's what I think is really facilitating rapid sharing of information, rapid sharing of data. Those kinds of relationships, I think or what science is built on and the trust that science is built on, we've been able to develop that really rapidly over the last couple of years. I think that's really critical to our ability to understand what's going on in this outbreak and really enlist a global scientific workforce, to help us understand what's going on.

Cole: Thanks for that.

Nita: I would add that, of course, global travel and connectedness has increased vastly since SARS or since whatever previous outbreak you want to pick it's, right? It's basically always increasing. But at this point, we're in February. We're into month two and a half ish of this outbreak, 99% of the transmission is in China, 97% of the cases are in the province where the virus spilled over. So this really still is very high risk, mostly within that area. So that speaks a lot to the strengthening of local health systems, given the amount of large scale travel we have.

A lot of the focus on the international spread of the virus is helpful for preparedness for countries that are highly connected to China, or areas that are highly connected to the city in the province of the spillover. But for the most part, I think that that balance of there's been this huge increase in travel, but we're still seeing a really localized effect for the highest risk, speaks to strong healthcare systems. The other thing that I would add about what's new now, is obviously the increase in the speed and the volume of transfer of information. We're all looking at things like Twitter, and how rapidly information can get out.

The WHO and Dr. Ted Rose are tweeting about these things. That's one way that information is spreading. That's pretty different from a lot of earlier outbreaks. Certainly, if we think back to SARS, the way that information spread was different. Obviously, with all of these things, there's a tradeoff. So the speed of misinformation spreading is just as fast, right?

Cole: Right.

Nita: When you speed up the sharing of information, you're necessarily removing some of the gate keeping or filtering and so, we're still looking for a balance for that. How do we share information and ensure something about the quality of it, while we're trying to do something to squelch the misinformation and maybe help people react properly rather than overreacting or panicking? And that's a place where I think we still have work to do.

Cole: Thank you.

Beth: I think technologically, we've made a lot of advances as well. So after the SARS epidemic, a lot of people started working on SARS. We got people who're starting to do work on coronaviruses at a higher rate than they were before. There's been a SARS vaccine that's been made. So I just heard that they're going to try to roll that out and see if that had any protective ability for this coronavirus, and also some new antivirals that are going to be tested from some Chinese companies. So I think it's motivated people to work in this broader space. So these past epidemics of related viruses have put us probably on a better footing to deal with this one in terms of potential treatments and vaccines.

Cole: So I hear universally from all of you that things are getting better. We have some work to do in terms of disinformation, but the global community is becoming more connected, we're becoming more unified, we're taking these things on a more serious way. So all of those are very positive developments.

Beth: I would say for some other diseases we're backsliding or we're not making the progress that we should around vaccines. So-

Cole: Oh, we want to mention a couple of those?

Beth: ... Matt can probably speak to that very closely, but also there are a number of pathogens that we've been working toward developing vaccines for decades, and we haven't been able to do it. So I think we have more work to do, not just on coronavirus, but other pathogens. Do you want to speak to the vaccine issues probably?

Matt: Sure. So, two classic examples of areas where we as a global community have either either stagnated or backslide would be measles and polio. So polio we've gotten very close to near global elimination, the number of wild polio cases and children around the world has several times been below 50 cases per year in the last decade. But getting all the way to zero is very costly both internal of time and resource. Time, money and resources issue, and keeping up the vigilance has been really, really hard. Particularly these diseases, both measles and polio, tend to be diseases of both poverty and health access in areas with weak access to health care and preventative services, as well as areas of political and military conflict.

These preventative services tend to fall by the wayside during those instances, and we tend to see then losses in our global gains to eliminate those diseases. So again, we've seen increases in polio cases over the last number of years. We've just recently had reports of polio vaccinators being killed buying insurgents. We have the world's largest measles outbreak in DR Congo right now with over 300000 cases and more than 6000 children that have died in the last year. These are all pathogens for which we have a standard vaccines [crosstalk 00:17:12] standard vaccines that have been around in some cases for 50 years.

Cole: What are the headlines? These children are not getting on planes.

Matt: Right.

Beth: Yeah.

Cole: They're not flying around the world, right?

Matt: So-

Beth: And these are low cost vaccines.

Matt: Right.

Cole: Yeah. So vaccination is fantastic, it's without a doubt the most bang for your buck in public health. Super cost effective, but also it's an inherently slow process of developing vaccines. When we see a ramp up and discussion about novel vaccines whenever a new thing comes up during the West African Ebola outbreak, there was a lot of talk about rapidly developing new vaccines. There's a lot of discussion now for the coronavirus. Can we rapidly develop a vaccine for this and in a sense, the easy part relatively speaking is developing the vaccine, is getting a vaccine candidate. The hard part then is proving that it's effective.

Then developing the production systems and the supply chains, and the public health infrastructure to get it out to enough people for it to be functional and effective at the large scale. And especially given the safety concerns surrounding these things, those processes themselves will take five to 10 years. So it's absolutely an important thing, and it is certainly something that we should be talking about, and the energy associated with every new outbreak I think re intensifies the discussion about development of novel vaccines, but what needs to go along with that is not just the consideration of the technological improvement, "Can I make the thing to put in the needle?"

But it's, can we create safe and effective protocols and workflows for testing and evaluation of those vaccines in a scientifically rigorous and operationally effective manner to get them to populations in need as fast as possible? Again, in these settings, the global health impact of a vaccine for the new coronavirus, is unlikely to be felt in respect to this particular outbreak right? If this coronavirus goes global and is persistent, then the value of that vaccine will become much, much greater. But right now we're dealing with conventional public health interventions of sanitation and isolation and monitoring and contact tracing.

All these really classic boots on the ground kinds of activities. Those are the things that are really what's necessary to stem the growth of an emerging outbreak.

Beth: Let's say going along with that though, that our diagnostics have improved. So it's become cheaper and easier and faster to identify in particular, where you've got people who are transferring virus around, but who aren't showing any symptoms. So it's become easier to try and figure out who are the hidden transmitters in populations?

Cole: Yeah, absolutely. I think every runs to vaccines is being the exciting new technological thing, but diagnostics, just being able to identify the bug, which is banal as a thing, is far and away more important and more useful on the ground right away.

Matt: Right.

Nita: So I think that's been huge in this outbreak. So here we are with a respiratory infection during flu season. There's a lot of filling in the gaps, diagnostics goes a long way with understanding what's going on. So I would say that, for this outbreak being huge, but on top of what Matt said, where we have this basic public health and these basic health care responses that are going to make the most difference right now, it is on top of that infrastructure that you administer a vaccine. So you need to have that trust between the public and the healthcare system, and between the people providing that health care.

You need to build vaccine acceptance through that. So just because you have a vaccine, does not mean that it's going to work. It's only going to work in the people who get it.

Cole: Right.

Nita: So we certainly have examples about measles vaccine refusal, but we also have gaps in trust for places where an Ebola vaccine would carry some mileage. It's not necessarily getting into the people who need it the most because there are gaps in trust. That has to be built up over the long term of doing things the right way.

Cole: That's social science, right? Those are social factors. So how much do sociol-

Nita: [crosstalk 00:21:57] epidemiology, right?

Cole: Yeah. Right, Well, true. But yeah, changing people's trust, people's belief, that's a matter for social scientists, how much do social scientists work with you folks it CIDD and collaborate this?

Beth: I think, particularly for people who are working in the field and love working at that endpoint of really trying to alter public health translational activities. Those are the people who tend to be doing more in terms of the social sciences. So we've got people doing vector control in the field. We've got Matt here who's talking about deploying measles, and the best way to do that. I'm sure you guys are involving social sciences-

Matt: Deploying measles vaccine.

Beth: Sorry, did I say measles? Measles vaccine – we don't want to be known for that. Nita, maybe your stuff as well with respect to interacting with animals in the field. So I think there are a lot of points of interaction, particularly as you get to those end points. Maybe less so for the people who are starting right back at the beginning of the bench. I think more the concerns for people who are working at the very reductionist end is, sure I could create this intervention, but will it be accepted by the public? And so should I even be doing it? Because, will it ever be something that would be taken up? And so I think the social science questions at one end of the spectrum are maybe a bit different from the ones where they're actually out working at the level of translation.

Nita: Yeah, so I actually do a lot of work with humans in the field. I have a pretty solid background in anthropology.

Cole: Oh, helpful. Right, okay.

Nita: Had a master’s degree there. So I'm a little bit versed in social science and it doesn't really feel that difficult or interdisciplinary to work cross that bridge. It really seems like it's just part of ... It's just part of [crosstalk 00:23:48] epidemiology.

Cole: Okay.

Nita: It really shouldn't be another thing.

Cole: Got it. Yeah, but I do think that there is some real potential to close the loop and learn from the experiences that we've had over the years. As Beth said, I think there is ... For those of us that didn't come up through an ethological training or a traditional social science training. Many of us think about fine scale biological problems, just tinkering and learning about this cool mechanism. I really want to figure this thing out. I'm going to tell myself that it's going to save the world one day, and I motivate myself from day to day, right? Then you may do that, and then get to the end of your career and find out that the thing that you were working on was never going to be acceptable, if you put it out in the marketplace, right?

Matt: Yeah.

Cole: If you were thinking about that as a product developer, that would never happen, you would do some market-

Matt: [crosstalk 00:24:49].

Cole: ... focus groups up front to decide is it worth going down this path? I think there's a real potential as Beth alluded to, to try and close that loop in the development of applied biology and applied research. I think there's absolutely a home here for basic fundamental science and tinkering and all of that cool stuff. So I don't mean to distract from that in any way, but I think the really exciting thing is to try to bring some of that problem focused discovery to the front end of these discussions. I think that's very much how we entered into this discussion here, right?

What can we learn from the experience of previous outbreaks, that can help guide the research that we're doing in real time during this outbreak? We can learn from all the things that failed during SARS or H1N1 or these previous things ... All of the research endeavors and the loose threads. We can learn that maybe in real time, let's not focus on those and let's really target towards the kinds of engagements, the interactions, the kinds of questions, kinds of analyses that are going to be helpful in the moment.

Then five years from now when the coronavirus has died down, then somebody wants to go back and really dig into some nitty gritty fundamental questions about how coronaviruses do what they do, then that's really the time where you have the scientific luxury of engaging in things that perhaps have a lower probability of coming to fruition. But I think we can really learn from past experience and the downstream failures of scale up and implementation of some of these things to help direct the questions that we're asking now. I think that's where that continuous cycling discussion between people at all stages in the scientific discovery to implementation process becomes really, really important.

Thank you for the whole conversation. I'm Cole Hons, this is The Symbiotic Podcast. This wraps up part one, we're going to take a little break. We'll be back in part two to talk about the spillover from animals to humans, and a little bit about new emerging technology and how we can use that to address these kinds of outbreaks. Stick around. Thanks a lot.

Commercial: Hey, Symbiotic Podcast listeners. My name is Jenna Spinelli, and I'm part of the team that produces Democracy Works, a podcast from the McCourtney Institute for Democracy at Penn State and WPSU, that examines what it means to live in a democracy. Each week, we present intelligent and thought provoking conversations about topics ranging from immigration to impeachment, and conspiracy theories to climate change. You can find Democracy Works at democracyworkspodcast.com, or by searching Democracy Works in any podcast app. Thank you to Cole and the Symbiotic team for letting us put this ad in their show. We hope you'll check out Democracy Works.

Cole: Welcome back to The Symbiotic Podcasts, I'm Cole Hons for the Huck Institutes of Life Sciences at Penn State and we are talking about global outbreaks and what we know about them and what we can do about them. In part two of the conversation, we're going to be looking at spillover from other species. And interspecies interaction of the vast majority of human viruses actually originate through human interactions with either animals, I think it's a two thirds are called zoonotic infections. Then if you add in mosquitoes and other insects, which are considered vectors, is the terminology for that, the number increases even more.

I know at CIDD where you all work, we do a lot of work looking at mosquitoes and looking at animals and looking at those interactions and certainly with this coronavirus outbreak yet again, we're looking at the human animal interface. So what can you tell our listeners and viewers that they might not know about these interfaces between humans and other species, what do we know here?

Beth: I think they're happening all the time. We might call them different things in one context or another. But if we think about all the mosquito transmitted viruses, they were all originally probably animal based diseases, so zoonotic origin. Some of them we see like recent spillover events. So we think about dengue has been in human population for a while, being transmitted by viruses, but then we think about things in our lifetime. So we've seen Zika emerge onto the scene and that's connecting together humans to non-human primates, via vectors. So mosquito was biting monkeys and picked up this Zika virus infection.

This is a mosquito that's flexible on the type of thing it bites. So some mosquitoes only bite humans, but the ones that are less picky, are the ones that are involved with these events that can start out as a spillover but becomes something that then cycles in the human population, like we saw with Zika. West Nile is another example of that. So we've got viruses that are commonly in birds, and then occasionally coming through Culex mosquitoes which bite both humans and birds and spreading it into human populations.

Cole: There are molecular factors as well as environmental factors. We're trying to put the big picture together, correct?

Beth: Sure.

Cole: Yeah.

Beth: [crosstalk 00:30:16] just the molecular factors are just the beginning. I think from the way many of us think that's the easy part. Then the tricky part is the environmental factors. So when we start zooming out and looking at global patterns of disease and understanding how all of these multiple organisms are coming together and interacting, and how under different circumstances, they may have one outcome versus another, how environment may dictate whether we have an outbreak or a spillover event or not. When I think about the next 10 years of vector biology, it's about that interaction with the environment.

Cole: Sort of an ecological perspective-

Beth: Exactly.

Cole: And then you can have better interventions based on different regions and the weather in those regions-

Beth: Especially with changing climate. So a number these mosquito species are just having massively expanding distributions. So both in response to climate, but also in response to changes in human society. So as we become more and more urbanized, the mosquitoes that specialize and living in and around houses are doing better and better. That's just increasing our possibility for disease transmission. So when we think about the environment, we can think about it as human associated environments, as well as things like weather and humidity and other factors that impact the success or fitness of these mosquito factors.

Cole: I understand in your research, there's a certain bacterium you're looking at that can be maybe a biological, it's taking it to another level.

Beth: So the biotic interaction and so when we think about whether a mosquito is a good transmitter of a virus, we have an additional partner to play in that system. So it's not just the virus genome, and the mosquito genome, but it's this bacterial agent that's been put inside mosquitoes intentionally, because it limits the ability of viruses to replicate. Then you have these three interacting genomes at least, if not others, and the insects microbiome that might be playing a role in determining whether a mosquito is going to transmit a virus or not.

Cole: It's so incredibly complex.

Beth: Yeah.

Cole: To churn up with these-

Beth: Lovely.

Cole: So fascinating from a scientific perspective, but doing something about it gets, how do you figure out what to do?

Matt: Yeah. I think well really important ... Well, for me, I think a really interesting aspect about this whole thing is that, so we often put a lot of focus on these individual spillover events that cause a large amount of morbidity and mortality in human beings, the classics being HIV, dengue, SARS, periodic influenza, things like this. But in a sense, these are actually really, really rare events, given the ubiquity of viruses and bacteria across the world and in all organisms, right? We're just bags of these things, right? There's billions and billions of these things in this all the time. So these kinds of spillover events are, in fact happening constantly rapidly on a day to day basis.

It's only a handful of them that actually give rise to these larger scale outbreaks. So really one of the fundamental questions that biology is grappling with is, which are the ones that for which that is going to happen? Is it something inherent about the biology of those particular viruses, that's what made that happen? Is it something about the social or cultural or ecological [inaudible 00:33:32] in which it found itself that gave rise to that? Or is it just some bizarre roulette wheel random chance, that just happened to ... The stars aligned in this thing happened to go that way?

I think trying to disentangle those things is really the critical thing because that is going to help guide how we would target interventions. Should we be going after pharmaceutical interventions that target the bug itself or should we be going after cultural or social and interventions such as sanitation or social distancing or changes in food preparation and those kinds of things? Which are the things that are actually going to have bang for the buck and what that root causes is, is fundamental to being able to figure out what the right intervention should be.

Nita: Following up on that yeah, these things are happening all the time. We're not doing ourselves any favors. So Beth mentioned climate change, that's our fault. We have a lot of human encroachment on wildlife habitat or destruction outright. So there's a lot more cross species interactions as we destroy habitat, that's our fault. So we got to solve these problems, or we got to stop creating them. So we're looking at pharmaceutical solutions. We're looking at social solutions, but we have to look back at the ecological and environmental solutions. So how do we back out of this problem that we created?

Cole: Yeah. Big questions, big important questions to look at. So we could just explore a little bit I know for example, Nita, you're working with bats, you've got a big research agenda, just going around bats, if I got that right. So you also mentioned earlier Matt, that we're putting together all the pieces from different places. So whether it's mosquitoes or bats or plants, you're looking for bigger patterns that you can see. So what are some of the bigger patterns that have been discovered throughout CIDD, across the different species or, are there some that you can point to? I heard you answer part of that to say, "We have to stop causing the problems in terms of the ecological piece of it." I totally get that.

That makes a lot of sense to me. But are there also just more fundamental scientific, biological factors and patterns that we see that are more universal across zoonotic spillover?

Matt: Well, if since you asked about what is CIDDs contribution to that, right? If I could just highlight something that I think has been really fundamental about threads that go through CIDD is that, variability matters enormously.

Cole: Variability.

Matt: Variability. So a lot of people think about ... when they think about characterizing risk, they think, "Well, what's the temperature there, and what's the humidity there and which animals are there? And is there a forest cover?" Whatever. They think about the average characteristic of a place.

Cole: Okay.

Matt: But one of the things that folks within CIDD have really focused on is not just describing the average risk in a place, but the variation, the fluctuation and risk. From the variation from time to time or from place to place. So Matt Thomas, a colleague of ours, has done some really fundamental work on this looking at how day to day temperature fluctuations, affect the success of mosquitoes in transmitting malaria. And actually looking at future climate change scenarios. So we think about when we talk about climate change, we think about the average temperature rising. But what Matt Thomas has shown is that it's actually more important, how the highs and lows are going to change, because the high temperatures astronomically magnify the risk, and the low temperatures have a slower dampening of the risk.

So actually, the peaks and valleys become really enormous, right? And that becomes really important. Actually, that view of things is really a fundamentally different way of looking at the world. It's not just what does the world look like now? It's how is it changing from day to day.

Cole: Right. Infectious disease dynamic such as in the name of the [crosstalk 00:37:50].

Matt: In some of my work, we focused really heavily on not just what the average vaccination coverage is in a population, but how variable that is. And actually that can really dramatically alter the risk and in fact mask some of the risk, if really what you've got is not just that 80% of people are vaccinated, but who are the 20% that aren't. Are those people that are aggregated in place because of low access to care, or some other disenfranchisement, or access to health services? If those are clustered versus broadly distributed through the population, those can have dramatically different outcomes.

Nita's work has really highlighted some of this in terms of not just where people are, but how people are moving around.

Cole: Right, how they're moving. Yeah, I wanted to segue when you mentioned that about the dynamics that I know Nita you've been doing a lot with satellite imagery that is really innovative. Could you speak to that a little bit the movement of people?

Nita: Yeah, a lot of our default assumptions about human populations when we're doing simple math, is to assume that they're somewhat static, and what we're finding increasingly is that, not only that there's a lot of movement within and between human populations, but that that movement disproportionately is important for public health, whether it's prevention or care, or simply just understanding what's going on in a population. So that movement has been overlooked largely because it's hard to measure. So one of the things that we've been able to put into place is a way to measure that.

There are a lot of ways to measure that, if you know you're putting population really well or if you know who you're measuring. But if you're trying to do that, at a relatively large scale, you're bound to end up with biases. So one of the things we're trying to do is stop missing the populations that may be most need to be counted in some of these efforts, whether that's low access to care, low access to other resources. So I think the thing that you're referring to one of the things that we've done is to use anthropogenic illumination. So lights from human settlements and to serially quantify those.

So we're able to estimate how much populations or settlements are changing from season to season and how that impacts when and where you might want to scale up your public health, or your healthcare capacity or your vaccination efforts, or your preparedness for an outbreak. We know for things that are easily transmitted like measles, that makes a big difference, probably also a factor for things like flu. But that additional component of time and understanding what your population is doing, and how that denominator is changing over time, really helps you put into perspective what's happening with diseases and what's happening with contacts.

Cole: Right.

Beth: Can I just add something?

Cole: Yes, please.

Beth: I like that Matt said variation. Because I was thinking about variation, but I was thinking about it in a different way. So I was thinking about a number of our faculty study evolution. So they study in cases like antimicrobial resistance. So how does variation in terms of genetics in the pathogen population predict long term efficacy of antimicrobials? Or how does evolution in viruses or mosquitoes impact long term efficacy of our body control? How does variation in these different lock and key fits of vectors and humans and pathogens? There are interactions in the immune system? How does that dictate the cycling of diseases at the huge population level and global patterns of emergence and spread of different pathogen types?

So I think we think about variation on many different levels. But it's common across CIDD.

Matt: Yeah. I think the dynamics in the name right? Center for Infectious Disease Dynamics, I think that's the really key thing. It's that in a sense, it's what keeps us employed is that, any science that we learn now, is going to give us a snapshot of what we understand about the world. But the world is changing. The world is changing on its own, but the world is also changing in response to things that we're doing. Populations are growing, we're learning more, we're developing new drugs that then the implementation of those new drugs is now going to change what the health landscape looks like.

So, we'll have consequences to our failures, the kinds of destructive forces that Nita was mentioning, but we'll also have consequences to our successes, because of the introduction of new drugs, the introduction of new vaccines, and so the world around us is constantly changing under our feet. To the extent that we can understand how those processes react and change, we can start to anticipate what the scientific needs are going to be and what the public health needs are going to be down the road.

Cole: Right on.

Beth: Yeah. As we as the center do better and as infectious disease control improves, we hope to be looking at diseases of old age being bigger problems, right? Because more people are going to make it to old age.

Cole: Right. So, as we talk about all this data and all these moving dynamic factors, whether environmental or whether genomic or evolutionary on all these different scales, how important are technological breakthroughs to the mapping and integrating of all this information? We talked about computational biology a little bit and data streams.

Beth: Can I go back to something-

Cole: Oh, sure yes. Yeah, no go ahead. Yeah, okay. Yeah.

Beth: Happening all the time, and relating to this, and that we only see the big ones that become problematic. I think one of the things that we fail to understand is, what are all the viruses in our body at any one time? What's there and then we just see these little blips that rise up above background. So with an ability to do virome scanning and people's bodies, we'll get more of that baseline knowledge about what's out there. What does the state of play look like when something emerged? What is the soup that it emerged out of? So I think we'll have much better context for all the real biology that's driving what makes something emerge as a pathogen or not.

I think we're acting quite blindly right now. Because we don't understand the context that they come out of. So the fact that it's becoming easier and easier to take a sample from somebody, and go and screen what's in there, what bacteria, what viruses, we no longer just have to do that for sick people, we can afford to do that for your average person. So I think that's a really exciting direction for the next 10 years, is a much better context, because we can finally afford to do it quickly and cheaply on lots of people.

Cole: Virome scan? You said.

Beth: Yeah, so you can get a pattern across signal of all the viruses that someone is currently having in their body.

Cole: How much of that is going on right now?

Beth: It's just starting.

Matt: Let me just comment actually, because again, this is one of the things that emerges from having a really broad interdisciplinary group. So some of that stuff is really just starting in practical application in human populations, right? But Marilyn Roossinck just retired from CIDD this year, the foundation of her whole career was studying what she would always call the 99% of viruses that don't cause disease. Now, she did that in plants. She worked in plant pathology departments and she's also studied the viruses that cause disease in plants. But really started with a foundational description of all the possible viruses that were out there.

Beth: Natural historian

Matt: Exactly. To give herself-

Beth: [crosstalk 00:45:38] yeah.

Matt: Yeah, to give herself the context for understanding what was special about the ones that caused disease. In fact, the fantastic things that she showed was that, the really special viruses were the ones that in fact, created benefits for plants. In fact, there are beneficial symbiosis between viruses and plants that perhaps, in her case, conveyed drought resistance or thermal tolerance, and they've actually looked at and use some of that to help engineer now plants that can be infected with those things that are now able to be grown as crops and in otherwise marginal soils.

So, this is one of those cases where you actually have the transfer of a concept, from the plant world into the human world, that's now being merged with the rapid availability of technology that these kinds of diagnostics can be done at huge scale, to be able to be relevant on a individual to individual health level.

Cole: Fantastic. We can test plants as well as animals?

Beth: Sure.

Matt: Yes.

Beth: Plants have already been tested.

Matt: Yeah.

Cole: You're testing them [crosstalk 00:46:49].

Matt: Yeah.

Cole: So if there are viruses that can help a plant, there must be viruses that can help human beings as well, right?

Beth: Surely.

Matt: Absolutely can.

Beth: Just harder to do the experiments on the humans to test that.

Matt: Yeah.

Beth: These are big data questions. You'd have to be able to look at the prevalence of those across human populations, score them in association with some trait or phenotype. So that's where big data comes in.

Cole: Big data back to computing, which is my original question. This does touch on it. I'm really glad you went where you did, because that was enlightening. So if we bring it back to computers and big data and technology, what does that look like? We're talking terabytes of data collecting. Anybody got any wonky, little tidbits numbers we can throw around to get a sense of how fast this is expanding? And I'm really interested in what the data streams are. How globalized is it? Where do you guys get your information? Where do you share your information to ... I picture this global mind growing, our internet is the place with all digital natives with every generation everybody's walking around with your extra brain in your hand.

But how does that translate into our knowledge about infectious disease dynamics?

Nita: Yeah, I would say there's an abundance of data. Some subset of that is information, some set of that is translated to be interpretable or usable information. There's a lot of access to data. There's a lot of open access data. There's a lot of data that are out there that are available to anybody. But again, what do you do with it? Right? So where do information streams come from? How do we get knowledge? That's a slightly different thing.

Matt: Yeah, I think some of Nita's work is actually a really great example of this. So some of these stuff that she's done with satellite imagery, right? There are satellites circling the globe all the time taking pictures nonstop.

Beth: You can just download those pictures.

Matt: Right.

Beth: You can just ...

Matt: So those are data that are being accumulated at a just a horrific rate, right? Not all of them are information and not all of them are relevant. Some of the pictures ... Again, some of the work that Nita has done has been to try and create workloads that can rapidly assess the information content, information value of those things and get them quickly out of hard drives on satellites and into the hands of policymakers.

Nita: That's actually a good example. So the imagery that we used to quantify human populations was originally just junk data. It was data that was a byproduct of an actual surveillance effort. Those images of elimination, were junk. So we turned junk data into useful information.

Cole: Cool.

Matt: Right. In fact, probably many things that we deal with, the data leads the information gathering and I think where the real science is and the real importance of understanding fundamental biology and then public health application is in going from that massive quantity of stuff that's out there, and filtering that down to the points that are actually relevant and important. Because while everybody does get excited about terabytes and zettabytes and all these kinds of things, those are big, exciting numbers that get people jazzed, and they look really cool in movies, right? But the truth of the matter is ...

Cole: Yeah, sure. Yeah.

Matt: ... the truth of the matter is that it takes a human being at some point to take all of that stuff, condense it, and then pass that along to the next person in the chain that's going to do something. So the physician at the endpoint who's treating a child, they benefit from all of the information that's gathered everywhere down the chain, but they're not holding all of that in their hand. So the important thing is for the rest of the community to help in trying to parse that information down and present it in actionable format to the next person along the chain.

Cole: Who decides that becomes an important question. Who decides? And what are the parameters of decision making, is the World Health Organization the go to place? My brain goes when I think about global health implications and interventions, and we're talking about international politics and relationships between different countries and borders and state actors. That gets pretty interesting. In part three, I want to unpack the social dimensions of all that, but, so much of this data is universally accessible. Yes, I hear what you're saying about somebody has to interpret it.

So who does interpret it? I guess, you folks, the media is coming to you asking you to chime in or go into the World Health Organization. It's these established big global players that are making the biggest decisions, is that correct? And then-

Beth: I'll give you a good example this week. So I had a reporter ask me whether people can get viruses from packages from China, and she'd gone and dug up some paper from a literature in a journal that's maybe not very high quality, but they had grown virus in flasks and sprayed it onto surfaces and then looked at transmission, and said, "Look, you can get it off the surface." She was saying, "This is counter to what the CDC is saying and what everyone's saying." So it was like, there's some information and it's readily available, but it's being used in the wrong context. So because in a natural environment, you're not growing virus in cells and dumping it on a surface, someone might sneeze.

So maybe there's way less virus being put on the surface, and then the surfaces are going to matter, and then how long they're in their environment and how the virus is going to interact with environmental variables, and a whole range of other things that are not captured in this artificial environment in the laboratory. So it can be a little bit difficult for someone to interpret the value of that and whether you could apply it to a real life scenario without someone helping out, without a scientist saying like, "Oh, and I'm not sure they did the study appropriately." So, it's a worry when things are just taken at face value without having some interpretation, I think.

Cole: Thank you. Well, I'm Cole Hons, this is The Symbiotic Podcast. We're going to take one more break and be back for part three to really unpack some of these social dimensions about what is good data, how can we get it and how can we do a better job of making sure more people get real useful information and not a bunch of junk. Stick around. Thanks a lot.

Commercial: Huck Institutes of the life Sciences at Penn State offers six inter college graduate degree programs, in bioinformatics and genomics, ecology, integrative and biomedical physiology, molecular cellular and integrative bio sciences, neuroscience and plant biology. We also offer an accelerated Professional Science master's program in biotechnology. At the Huck, we immerse students in a groundbreaking environment built on interdisciplinary collaboration among some of the world's most innovative research scientists, and our students receive unparalleled access to bleeding edge technology in world class core facilities. If you're looking for a deeper, more holistic grad school experience, you owe it to yourself to look at the Huck. Visit us online today at huck.psu.edu.

Cole: Welcome back to The Symbiotic Podcast. I'm Cole Hons from the Huck Institutes of the Life Sciences at Penn State.

In this last part of our conversation, we're going to dive into some topics that are a little bit uncomfortable for us to talk about as human beings, or not the best parts of being human beings on planet earth and some of our big challenges that we're facing globally. I don't want to go too deep because we could spend a long time but sometimes things like we're experiencing right now with coronavirus can lead to xenophobia, can lead to racist overtones and people othering one another and getting all bent out of shape with borders and blame, et cetera. I know that some of the media inquiries that you folks have been fielding this week border up against some of that, can we just break that out just a little bit and address that?

Beth: Yeah, I think that's been a common response. I think a lot of this reaction to the other is fear based, and especially when you overlay a pathogen on top of that, I think it gets people a bit crazy. So what I've been trying to focus on whenever I get those questions is to stick to the facts, but also just really highlight how the opposite of the other, the opposite of this global cooperation with driven by governments and the World Health Organization and the sharing of information and working together is exactly what is going to protect the global health community when these things happen.

So trying to spin the story on its head back at people about working together, and this could be in our backyard. This could be us next time. In this case it's in neither part of the world but we're all globally connected and we all care about each other and working together is the only thing that's actually going to shut this down. Yeah.

Nita: Yeah. I would say this, this is pretty common every time there's an outbreak. It quickly turns to xenophobia and racism. We saw similar responses during the 2014 Ebola outbreak, similar inquiries from the press. There's a lot of that sentiment out there and it is part of our job to dispel that and stick to the facts and really make everyone realize that this risk is everywhere all the time.

Matt: Yeah, I think in a very real way the risks inherent in any spillover event, novel virus, all these things, these are universal across the planet. Humans interact with wildlife, everywhere around the world. Humans interact with livestock everywhere around the world. There's nothing special about any one place or another for those things. again, keeping in mind that these things that we see are individual rare events that have amplified. I think failing to recognize that, clouds some of the universality of the underlying biology, the underlying processes, and the risk that are inherent everywhere around the world.

So there really is very little otherness in all of this, right? There are a lot of these things that are really consistent that we could point to in Pennsylvania's backyard. We have novel zoonotic spillovers in Pennsylvania all the time, the increases in risk of Lyme disease and risk of other tick borne viruses that we're seeing slowly encroaching into our local backyard here in Pennsylvania. That's because human beings are out in the woods, what's one of the primary risk factors for Lyme disease in Pennsylvania? It's whether or not you hunt, right? It's whether you interact with wildlife.

So again, these are really these are just really commonplace things that we see in all cultures and all societies around the world. And I think, failing to recognize that actually closes our mind to being able to understand the underlying mechanism and to find appropriate solutions to mitigating these things.

Nita: We know that house cats are having negative health effects on their human roommates. We know dogs eat poop, and lick their humans. We know these things are pretty gross, but we overlook that for some reason.

Beth: Yeah. Blind eye. Yeah.

Cole: Well, thanks for that. I really appreciate your perspective. That's the perspective that I would like to see more in the public debate, so it's nice to be able to insert that into the dialog. Let's also look at some other social dimensions. Let's talk about economics. Let's talk about wealth disparity. Earlier you were talking about measles outbreak in African countries for example. Nita you were talking about access to health care, and some things that don't end up in the headlines perhaps, which is another dimension is where the media eye is placed based on who's actually getting sick and who's dying. So how much of a factor is that in terms of infectious disease dynamics, the social economic, socio economic dimension?

Nita: I reckon that's the biggest factor.

Beth: It's huge. I think if we think about all the neglected tropical diseases, I know we call them neglected, because they're largely ignored by the developing world, because they don't affect us. But they're primarily seated in the tropics, and they're often present in countries that can least afford to manage them in terms of not having the strong enough health and infrastructure and ability to try and protect their people from these diseases. So I think it's actually the biggest determinant and disease patterns globally.

Matt: Yeah, there's two stages in every disease process. There's the exposure of the human to the pathogen. Then there's the course of disease of that pathogen, in that human being. So we can talk about variation in that risk of exposure in the first place, then we can talk about variation and what's the outcome in that individual. I spent a lot of my time worrying about measles virus and the global distribution of measles virus and what we've seen, there was a measles outbreak in the United States last year, 1300 people were infected. There were no deaths associated.

Cole: No deaths.

Matt: But in areas with very low access to health services, where it's likely that a child may experience the full course of measles disease in the community without ever being able to be seen by a physician, the likelihood of that child dying due to that infection goes up astronomically. You might have a 10 or 15% mortality rate. That's really, really significant and in fact, far greater than what we're talking about with coronavirus.

Cole: Right. We shouldn't be seeing that in 2020.

Matt: Yeah. So accessibility of health services, both that the global distribution and at the local scale, who has access to care, which individuals can take time off of work to take their kids to school? What are the costs to take their kids to the doctor? What are the costs inherent in those things? I think a lot of folks around here aren't thinking very actively about how different the rest of the world experiences these infections.

Beth: Just household income level some studies have looked at how much vector control costs, and if you think about what people are spending their money on, it's housing and food, and there often isn't enough money left over every month to consistently use insecticides in your house, or when you're living in an environment where there's constant rain, and trying to keep down breeding sites around your property is a nonstop job. If you've got other things demanding your attention, work, family feeding your family, basic living, that stuff tends to fall by the wayside. So even when we think about interventions, they're going to work in these contexts.

They have to be amenable to these situations, where people have much higher list of other needs, I think compared to what we're dealing with here.

Nita: Yeah, I think a lot of these preventative actions are long term risk avoidance, right? Whereas if you have immediate risks that you're dealing with, otherwise things like hunger, or just running out of money, those things will always take precedence. So it really is a really basic determinant of what you're able to act on, your basic economic level really determines how far down into the future you can look and act on risk avoidance.

Matt: Yeah, prophylaxis is really a luxury. It's only after you have the capacity to handle all of the immediate and acute issues that you're dealing with, getting through the day, getting to work, feeding your family. And it's only after that then you can have the luxury of spending additional funds on prophylaxis to improve your life.

Cole: Prophylaxis meaning?

Matt: Prophylaxis meaning-

Beth: Preventing future infection.

Matt: Prevention [crosstalk 01:03:40].

Cole: Okay.

Matt: Vaccines, mosquito nets, vector control, additional hygiene-

Beth: Filters for water.

Matt: ... filters water, these kinds of things.

Cole: So all your crazy infectious disease scientists are saying this isn't about being around wild animals in a meat market, it's about poverty? Is that what you're telling in the big picture?

Nita: I think it's connected. So I think that in some cases, access to food varies and that access to food will determine where you go for resources.

Cole: Yeah. So even there, we're talking about poverty too.

Nita: How you get your nutrition.

Matt: Right. Indeed, yeah. So, your body's ability to fight off infection is fundamentally tied to nutrition. So are you at subsistence? Do you have enough resources to be well fed? Or are you just getting by? These things again, are all part of the [inaudible 01:04:40] of this story.

Nita: When you mention wildlife and bush meat and things, there'll be recommendations issued from time to time, don't touch wildlife, don't eat bush meat. Those aren't necessarily realistic recommendations for people who rely on nutrition and protein from bush meat as a very important source of nutrition. So there's a little bit of what's your reality, and what can you really afford to avoid? Are you going to avoid hunger? Are you going to avoid maybe getting sick?

Cole: I have to ask in central PA here, would you consider deer to be bush meat? Is that our bush meat? People say bush meat you get this almost this racist over to bush meat.

Nita: Absolutely.

Cole: [crosstalk 01:05:20] bush meat.

Beth: And bear?

Cole: Guess what? My uncle just gave me some venison steaks. There's like it's thinking it's something different.

Matt: Yeah [crosstalk 01:05:27].

Nita: It's the same.

Matt: It's the same thing [crosstalk 01:05:27] yeah.

Cole: Wow, so what I'm hearing you say is, if we can stop messing up the environment and encroaching on wildlife, if we can curb climate change, and if we can help all people to have a higher quality of life with access to health care and enough money to take care of their families properly, a lot of these problems would go away.

Nita: I think those reflect a little bit of the UN's development goals.

Matt: Yeah.

Cole: Right.

Matt: Yeah. I think a lot of those problems are going to go away.

Nita: I don't think we're inventing the wheel here. I do think that those are well recognized solutions for better global health.

Cole: Yeah. But how invested are we? This is what I see in a broader sense when I look at the socio political environment of the world, and we're getting more and more tribal, we're getting more ... and in some sense people would say, our country, the United States, more and more divided, more tribalism, people leaving the EU et cetera. Right. Every man for himself, there's that dynamic. But at the same time, you're adding another piece of the story that there are intelligent, compassionate human beings all over the planet, who see the big picture and want to help one another out and are collaborating, and are coordinating their efforts to do good for everybody, globally.

So I guess, from what I see, I'm proud to know that you're all working on that cooperative side, and let's all hope we can continue to strengthen that in the face of these other factors.

Nita: I think that's been one of the big messages with this outbreak is that there has been a lot of data sharing. There's been a lot of cross institute collaboration. It's not perfect. But it is better than it's been before.

Cole: Well, good. So, I usually ask people on this podcast if you had any advice for people who want to break out of their boundaries and go cross disciplinary but I don't feel like it belongs in this conversation. It's too much of a canned question to ask you. But I'm going to ask you a different question. I'd like to hear an answer from each of the three of you, if you don't mind. If there was one thing you could do to change the global climate, whether it has to do with the information flow or whether it has to do with the money flow or whether it has to do with scientific cooperation.

If there was one thing you could do that you think it could help humanity writ large, to better cope with these global outbreaks, what would it be? If you get a magic wand do anything? If you had to pick something I know I'm putting you in the hot seat.

Beth: I can pick one. Yeah, I'm going back to the money again. I think if we could raise people's standards of living at the level of individual households, we could have impact across many diseases in one go. So you could reduce vector borne diseases, you could reduce diarrheal diseases, you could reduce diseases that are the result of poor nutrition. I think if you can have that impact on people's lives, and just to raise the standard of health across the board, we would need less of these other solutions. So it's not very exciting, it's not a vaccine is not an amazing new drug, but it's just getting people's standard of living up, so that these things become less of an issue.

Nita: I would agree with that. I would say equity in standard of living basic economic equity and access to healthcare equity, but on top of that, equity and access to education, and I think that doesn't just mean education, as far as Biology and infectious diseases and sanitation, but education about globally, similarities and interconnectedness instead of the sentiment that you mentioned, where there's this othering, and there's a tendency to cluster towards what's the same? Well, we're all the same. If we could increase education on that, and how connected and linked everything and everyone really is, I think that could make a difference with some of the really ineffective actions that people try to promote during these types of outbreaks.

Matt: Yeah, so without a doubt raising the quality of life of the lowest tier absolutely, I think is the best bang for your buck, and will have the biggest impact across the world and then yeah, if I can just add something on top of that, just so I can try and have my own answer to this right again, is increasing the interaction and understanding of everybody of what the other guy does? Right? That's just it. Is increasing that collective understanding of our own humanity. Like I said, so that's a very ethereal thing. That's because these guys gave the great practical answers already.

Cole: Sure, yeah. While I hear a common theme, take care of one another and learn about one another and educate everybody about the commonalities of who we really truly are. We'll get there right, we're going to evolve. We're not done evolving. Let's hope. We'll keep on evolving. All right, well, I just want to thank the three of you again for coming down at short notice to have this conversation. I think it was a wonderful conversation. I wish you all luck putting up with the media storm and staying focused on your good work. Let's look forward to continuing to evolve things through science and dialogue and communication and thanks again for being on the podcast [crosstalk 01:11:04].

Nita: Thanks Cole.

Matt: Thanks.

Beth: Thanks, guys [inaudible 01:11:06].