The Bioinformatics CRO Podcast

Episode 40 with Nicholas Heaton

Nicholas Heaton, Assistant Professor of molecular genetics and microbiology at Duke University School of Medicine, talks about influenza, SARS-CoV-2, and potential future pandemics.

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

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Nick is Assistant Professor of molecular genetics and microbiology at Duke University School of Medicine. His lab usually studies influenza viruses; however, when the pandemic started, he shifted the focus to SARS-CoV-2.

Transcript of Episode 40: Nicholas Heaton

Grace: [00:00:00] Welcome to The Bioinformatics CRO podcast. My name is Grace Ratley. And today I’m joined by Nicholas Heaton, who is Assistant Professor of Molecular Genetics and Microbiology at Duke University. Welcome, Nick.

Nick: [00:00:11] Thanks, Grace. Great to be talking today.

Grace: [00:00:14] Yeah. So let’s start off with talking a little bit about what you study at Duke, and that is the influenza virus and other things occasionally. Can you tell us a little bit about that?

Nick: [00:00:26] Yeah, absolutely. So our lab, you know at the highest level is kind of broadly interested in understanding how these viruses make you sick. We basically modify the virus itself so that that virus will act as a tool that we can then use to ask whatever kind of scientific questions that we’re interested in.

Grace: [00:00:45] What kinds of things in particular do you study? Are you looking more at the genetics aspects of influenza viruses or at the structure or how they infect cells?

Nick: [00:00:55] Yeah. So a lot of the things that we’ve been working on, we kind of think about them as falling into the margins or like the gray space of what happens during a viral infection. So for the most part, when a cell is infected by a virus, scientists think of like a program being initiated. And the same thing essentially happens over and over and over. And what we found and others have appreciated as well, is that it’s more complex than that. The different cell types can respond different ways, and that happens at various frequencies. So that’s what we’ve been studying. The more rare outcomes of infections and trying to understand the nuances of how the virus can interact with its host can really then go on to dictate high level phenomena like disease severity or transmission or something like this.

Grace: [00:01:44] And could you tell our audience a little bit about influenza viruses? I mean, most people have heard of flu season and things like that, but what are some basic virology things that people may not have heard about?

Nick: [00:01:56] Yeah. So these viruses, they fall into a family they are called Orthomyxoviridae. And it’s a huge family of viruses. A lot of them are insect viruses, actually. But the ones that fall into the influenza virus family are influenza A, B, C and D. And when we talk about flu, like clinically people getting the flu or mostly talking about influenza A and influenza B. In a given flu year, it’ll be about two thirds influenza A and a third influenza B. Sometimes those ratios can flip. Influenza C’s can infect children sometimes, but they have animal reservoirs. And influenza D’s are rarely, if ever, detected in people. But these viruses, they have genetic material that’s encoded in RNA.

[00:02:31] So influenza viruses are called RNA viruses. And they’re envelope, which just means they take essentially part of the cell membrane with it when they leave. And that’s how they essentially incorporate it into an actual physical particle that can be sneezed on somebody or breathed in. And these are respiratory viruses like coronaviruses or other viruses.

Grace: [00:03:01] Awesome. So where do they originate? Influenza is a zoonotic virus, if I’m not mistaken. So what’s their normal reservoir?

Nick: [00:03:10] Yeah. So the answer is that it’s complicated. The family of influenza virus especially, so influenza A’s, which, you know are kind of the predominant flu strain. It’s really a bird virus. So there’s lots and lots of different subtypes of influenza that are all found in birds. Migratory waterfowl is where you find these things. And that’s probably almost certainly in the initial kind of introduction of those viruses into people or into mammals. But now we just have human strains of flu that just spread from person to person. It’s not like it goes from person to bird, back to person to bird. Now, we have human strains, and our human strains of flu are to a large extent still related to those bird viruses. But yeah, now they just circulate in people. And the subtypes I mean, the letters and numbers that you hear are like H1N1, that refers to the subtype of the virus. And so H1N1 and H3N2’s are what actively circulate in people right now.

Grace: [00:04:08] And for our listeners, the H’s and the N’s refer to the proteins that are found on the envelope of the virus, is that correct?

Nick: [00:04:15] Yes. On the very outside of the virus there’s two kind of dominant proteins:  H is the hemagglutinin protein and N the neuraminidase protein. And that’s where the H and the N come from. And basically there’s dozens of different types of hemagglutinin and different types of neuraminidase’s. So H1N1 that I referred to, that’s a subtype one hemagglutinin and subtype one neuraminidase. And again, these are just the proteins that are on the outside of virus that actually help the virus get into the cell. And because that’s what the immune response is mostly directed against, people have characterized them in these groups based on reactivity of antibodies, is essentially how the subtypes are defined.

Grace: [00:04:56] Yeah. So talking a little bit about how we prevent influenza infection every year, you know, we have our seasonal flu vaccine. But there’s a lot of, I don’t want to say controversy, but I feel like a lot of people are really reluctant to get those vaccines. And I feel like a lot of that has to do with people questioning the effectiveness of the vaccine. So can you tell us a little bit about what it means to produce a vaccine for influenza?

Nick: [00:05:23] Yeah. So we’ve been making vaccines against influenza viruses for a long time. So there’s different kinds of vaccines now. The majority of them are what we call split vaccines, which are viruses that are grown and then purified and then treated with a detergent so that they fall apart. So you just have all the pieces of the virus, but there’s no infectious particles there, and that’s what’s injected into your shoulder. Like I said, the vast majority of people get vaccines, get those. There are also some purified protein vaccines where just the virus is never involved. You just express different proteins from the virus that can be injected. There are some live attenuated vaccines, those are the ones that get squirted in your nose.

[00:06:03] And that’s essentially a version of flu that can’t replicate enough to make you sick, but enough that your immune system can react. And those are basically the three kind of flavors of FDA approved vaccines for flu. The flu vaccine, the efficacy is actually pretty good against matched strains. But therein lies the issue, right. So we know flu season is going to happen. We know when it’s going to happen, right. It’s in the late fall or early winter. And because it takes a long time to produce the vaccines and formulate them and get them distributed to hospitals and physicians and companies like Walgreens and things where people get their flu shot. We basically have to start making those vaccines early, like well before flu season starts.

[00:06:50] And so essentially what people at the World Health Organization do is look at the viruses that are circulating and they predict which ones are going to then circulate when the next flu season comes along. So part of the reason that the flu vaccines don’t always fully protect people is that sometimes a different virus that we weren’t predicting circulates. So you get vaccinated with something that’s kind of close to the virus that you’re going to be exposed to, but not close enough to give you 100 percent protection. The other thing that can happen is sometimes, even if we picked correctly the viruses that we want to turn into vaccines, they don’t grow particularly well under vaccine production conditions. And so in those cases, we essentially select for viruses that grow better. So it’s feasible to produce these vaccines.

[00:07:42] And the viruses that grow that are slightly mutated relative to the viruses that are circulating in people. Any time you are vaccinated with something that’s not exactly what you’re being exposed to, the vaccine doesn’t work as well. But I will say that the vaccines, even if they’re not super efficacious in preventing infection, they still do a really great job of keeping you out of the hospital. So, I think that flu vaccines get a bad rap because it’s true: sometimes you can get your flu vaccine and then you can still get sick with the flu. The chances of that happening are decreased dramatically, but it can still happen. But basically, it almost always keeps you out of the hospital which is important as well.

Grace: [00:08:24] Yeah. And then talking more about these prevention efforts. So what we’ve seen this past year is that there was a really large decrease in flu cases during the pandemic. Can you talk a little bit about what may have caused that?

Nick: [00:08:38] Yeah, absolutely. So there’s a ton of surveillance. We call it surveillance for flu. Places all over the world are testing people when they come in and they’re sick or even just testing people off the street. We test them and we look for viruses. So we have a pretty good understanding of when flu is infecting people, what kinds of flu are infecting people. Over the last year, the last flu season, there was very little flu and nobody knows for sure, but almost certainly the answer is that wearing masks and social distancing helps prevent the spread of respiratory viruses. And flu is a respiratory virus, which transmits in the same way as SARS-CoV-2. So when you take into account that people already have immune responses to flu, everybody is exposed to a virus either by vaccination or infection. Essentially when they’re born, within the first couple of years, they have antibodies against flu.

Even if they haven’t been exposed to the exact strain, their immune system has seen something that’s similar. So, when you take people’s exposure histories, combined with getting flu vaccines, along with social distancing and mask wearing, essentially flu can’t circulate the human population. SARS-CoV-2 has also been controlled efficiently with behavioral practices, right. But the lack of pre-existing immunity is what flu benefits from. And SARS-CoV-2 has benefitted from that at least until recently, now that we have vaccines against it.

Grace: [00:10:08] And so do you think that these measures will be implemented every year for seasonal flu, or do you hope that they will or do you think we’ll probably just go back to getting the flu, getting sick and all that?

Nick: [00:10:20] Yeah. I mean, it’s an interesting debate. You know, it’s kind of been an experiment, right. We’ve never made everybody in the country wear masks and stay away from other people before. And now we know if we do that, we can stop transmission of these and other viruses, right.  The question is where’s the line? Right. Like we could say nobody’s going to be around anybody and everybody’s going to wear a bubble and keep them away. And for sure, that would stop the spread of infectious disease. I think that we’ve done a reasonably good job of controlling flu with vaccination. And the other thing that we have for flu that is really limited for SARS-CoV-2 are antivirals. These are pharmaceutical drugs that you can get when you go to the doctor and you’re sick with flu.

[00:11:05] So if you’re vaccinated and you have an exposure history, you’re already reasonably safe from flu. But if you still got sick and went to the hospital, we could give you drugs that will stop the virus. So we have a lot of tools in our arsenal to combat flu, which we didn’t have when the SARS-CoV-2 pandemic started. So this is the big difference. And that was the concern. That was really the impetus for the public health measures. Like if you get this thing, you’re on your own, right. There’s no medical interventions which are proven to be efficacious to stop you from dying from this disease. But now the vaccines against SARS-CoV-2 are amazing. And there are antivirals which are approved and tons that are in development. So I imagine that in the not too distant future, we’ll have more ways to fight this virus, which I think will help, so that we don’t need to wear masks for forever. But essentially at the end of the day, everybody will make that decision for themselves. But it is interesting to know kind of the magnitude of how much can be accomplished if you implemented those measures.

Grace: [00:12:07] Yeah. I don’t mind mask wearing. I had really bad allergies when I was growing up. And one of the things that they said you could do was wear a mask to prevent pollen from getting in your nose and mouth. And I was like, oh, but if I did that, everyone would think I was weird, you know, like really sick and avoid me. So for my own personal reasons, I hope that mask wearing is a little more accepted, at least in allergy season.

Nick: [00:12:34] Yeah. And it’s worth pointing out. We’re obviously talking about kind of a US centric look at these practices. But in other parts of the world and other cultures mask wearing is much more normal. That could be an outcome of this, right. It could be normalized in the United States and more of a culturally accepted practice. It’ll be interesting to see. Again, it’s kind of a big sociology experiment, how are people’s behaviors and actions being changed by a biological phenomenon like this.

Grace: [00:13:02] Yeah, certainly. So kind of moving into a discussion more about the SARS-CoV-2 pandemic. I really loved your lab’s bio on Twitter, which for our listeners was “we study influenza viruses that cause disease except for when we get interested in something else…” And I can only assume that that’s something else is SARS-CoV-2, given that you’ve recently been publishing a little bit in that space.

Nick: [00:13:27] Yeah, absolutely. So, the SARS-CoV-2 pandemic happened and at least for us, we’re working on these viruses that are kind of similar. Maybe we would have some insight, some things to add to the field. But more than that, the university shut down. Everybody went home. And the exception to that was if you were working on coronavirus. And so that helped increase our motivation to take on this new challenge because it was that or it was sit on the couch. There’s amazing groups who’ve been working on coronaviruses for a long time, and they’ve really led the effort, and a lot of this work. The viruses are different than influenza viruses, obviously, but they still use the same cell. They still use the same host, right.

[00:14:14] And one of the things that we had been working on with influenza was trying to understand what do they need to take over? What do they need to co-opt from the cell they’re infecting in order to replicate? We had been studying those questions for flu and we thought maybe that’s an area that we could work on to try and understand what the coronavirus would need to take from the cell such that it could efficiently replicate. I think people appreciate this, but there really is a dramatic difference in the genetic potential of a virus and its host. Even a big RNA virus, like coronavirus is a pretty big RNA virus, encodes less than 50 proteins, maybe on the order of 30 or so. Influenza viruses encode anywhere between 12 and, I don’t know, 20 proteins or something like this.

[00:14:58] And human cells encode genes is probably about 20,000. And if you take into account splice variants and these types of things it can be hundreds of thousands of different kinds of proteins that all have different jobs. So when you think the virus is going to be able to replicate itself, it’s come up with 20. It’s going to gather some from the host. And that’s an area of interest. A lot of groups, including ours. What does the virus need? Because it opens up kind of a practical option for not just stopping virus proteins, not just inhibiting virus proteins, but if you can inhibit either the interaction between a virus and a host factor that it needs or inhibit the factor that the viruses use. These are new possibilities for kind of antiviral treatments.

Grace: [00:15:38] Yeah. I mean, there was a lot of movement when the coronavirus pandemic started from different fields into virology. So I imagine you had a bit of a head start on that moving in from one field of virology into another compared to someone who moved from engineering, I don’t know something like that.

Nick: [00:15:56] Yeah. It was interesting, you know, science is always better with diverse perspectives. And I think the field has benefited from somebody who thinks about a totally different question or usually thinks about different questions and now says based on how I think about things, what do I think is going on? It has moved the field forward rapidly. And, we know a lot more about these viruses than we did a year ago. I mean, that’s been the good side of the spirit of scientific collaboration and discovery that’s been all focused in this area.

Grace: [00:16:29] How do you think that the pandemic has changed the way that the general public thinks about virology?

Nick: [00:16:36] Yeah. I mean, that’s an interesting question. I think people think about viruses now. For some people the level of resolution is germs. And there are things that make you sick. There’s all kinds of things, right. There’s bacteria, there’s viruses, there’s protests and all kinds of things. The idea of a virus has certainly come to the forefront in people’s mind. I mean, which is cool, right. These are things that we think about all the time. But not everybody does. So it’s kind of cool to have more universal recognition of the types of questions and things that we’re interested in. I think there’s also been an interesting kind of realization and attention paid to the scientific process in general, which I think is really going to be a helpful thing to come out of the pandemic because it costs money, right.

[00:17:24] A lot of the biomedical research in the US is funded by taxpayers. I mean, the lion’s share for sure, is people’s taxes, right. And the question is, what are we studying and how is it helpful? What’s the return on this? Right. And, you know, I would say that the coronavirus pandemic has demonstrated what this return is. You know, it sometimes frustrates people that we don’t have all the answers right at the beginning. But when there’s a question, we can activate this biomedical research machine. We can understand things like how transmissible are these viruses? How long do they stay in the air? Can you transmit them by touching? These are all experiments that are done that answer those questions.

[00:18:03] And I mean, the most dramatic one is the development of these vaccines. I mean, the development of vaccines takes decades. And the fact that collaborative teams were able to come together, pharmaceutical companies and industry and academic institutions for testing and development of all these things, and have a vaccine essentially a year that is highly efficacious. I mean, this is what that money is going to. Discoveries that enable this type of stuff. This is the payoff for supporting that kind of endeavor.

Grace: [00:18:31] Do you think that sort of interest will continue beyond the pandemic or do you think people will as soon as it’s over, be like, oh, forget biology, let’s go back to normal life?

Nick: [00:18:43] Yeah. I mean, I think that’s a natural tendency that will occur to some extent. But, hopefully this will remain fresh enough in people’s minds that I mean, you see these things in congressional hearings, right. Where they’re discussing the budget on science. Why do we need to give this much money to research? At least for the short term and hopefully for longer we’ll be able to say this is why. God forbid, there’s another pandemic. But if there is, we need these people working on these kinds of questions and developing these things. We can’t be caught flat footed.

Grace: [00:19:11] And would you care to make any predictions about what you think the next pandemic might be? Do you think it’ll be pandemic flu or another coronavirus or Ebola? What do you think?

Nick: [00:19:22] Yeah, historically, at least from 1900 on, there’s been a series of pandemics and they’ve all been flu pandemics. There’s been coronavirus outbreaks and they’ve been epidemics. This is like SARS and MERS, the viruses that are very similar to SARS-CoV-2, but they were regionally contained. So just numbers wise, starting again with the 1918 Spanish influenza epidemic or pandemic. We’ve had a number of these flu. Most recently in 2009, the H1N1 swine flu pandemic. They’ve all been flu. So I think if you were betting, you would bet on it being a flu pandemic, the next one. But you know, who knows? And as the environment changes and people are living more places in more proximity to kind of reservoirs of animals. I mean, we’re just increasing the contact between people and things they weren’t exposed to before, including viruses.

[00:20:18] You know, I think one thing that will come out of it is the flu field has been engaged in the surveillance that I was talking about earlier in the development of interventions or countermeasures for pandemics. With the idea that another one is going to happen at some point, we need to be prepared. There is much, much less emphasis on coronaviruses because we hadn’t had a coronavirus pandemic at least since the molecular age. And we could really identify what these viruses were that were causing disease. But obviously, now it’s clear that they can. So I think the same type of effort and in terms of surveillance and predicting these things will be applied to coronavirus. And if it should happen again, I think that we will be much better prepared.

Grace: [00:20:56] Yeah. And I know there’s been some talk in the science community that the frequency of pandemics might be increasing. Can you speak a little bit on that and why you think that may be?

Nick: [00:21:08] Right. So it’s impossible to predict. But if you look at the things that affect transmission of disease, which is required for a pandemic, people move across the world at an unprecedented rate compared to what we used to do. That I can be anywhere in the world and can be anywhere else in the world within 36 or 48 hours is a bad thing in terms of transmitting pathogens around. So that’s a big part of it. The second thing is that we have more people, right. More people closer together. The cities are bigger and it’s much easier for pathogens to transmit when there’s just more people that are infectable around. So that’s a factor. And then, of course, this is what I was referring to before: a lot of viruses are transmitted by vectors, mosquitoes, for example, right. And as climate changes, animals and insects change their distribution as well. So populations come into contact with these viruses or the animals or the insects that carry viruses, which then facilitates these spillover events, which probably happened with SARS-CoV-2 at some point.

Grace: [00:22:13] Do you think there’s anything that we can do to reduce the rate of these pandemics happen?

Nick: [00:22:18] I mean, these are hard questions, right. Because people will have to live and work and travel where they travel and these types of things. Obviously dramatic things like that. I don’t think that’s likely to happen. I think that what’s much more likely in terms of being able to prevent pandemics or to contain them as epidemics and prevent them from becoming pandemics is just surveillance and countermeasures, right. If we know when these things start, we can detect them right away and quarantine people or if we can rapidly make countermeasures, right. If we could have made these vaccines within a month of detecting the virus, that would have presumably made a big impact on how far the virus was able to spread. So I think that’s probably where most of the effort is going to be focused. Understanding where these things are coming from. Understand quickly when they’re in the human population, and then being able to respond rapidly is probably the direction to go.

Grace: [00:23:15] So moving into more of a discussion about you as a person and as a scientist, I’d love to hear a little bit about how you came to virology and influenza and how you made it your way to Duke? Yeah. So start from whenever you first got interested in science at all.

Nick: [00:23:34] Yeah, it’s been a while. So I guess it started in high school. When I was in high school, I took all of the science classes that were offered and there was nothing else to take. And then I ended up going to the university. It was in my town, Utah State University, for credit to work in a research lab. And then when I went to college, when I was doing my undergraduate studies, I had this experience now like I was qualified or at least more qualified to work in a laboratory. And so I got a job working in a lab to pay the bills. I was in a great lab, they gave me some opportunities to develop some of my scientific skills. And then basically I became good at it. You know, I thought this is something that I like doing and something that I think I can do well.

[00:24:19] And from there, I went to graduate school based on that interest. My undergraduate degree is actually in bacteriology. And I went to graduate school to work on bacteria. And then in this kind of fortuitous event, the guy that I ended up doing my thesis work with, we were in the elevator. He was asking me how graduate school is going. We start graduate school. You do rotations where you essentially work in a few different labs and kind of figure out what’s a good fit for you. He asked how my rotations were going, and I said I didn’t know which lab I was going to rotate in next. He said, well, we just got this grant to work on a virus called dengue virus.

[00:24:52] I don’t know anything about dengue virus, but it sounded kind of exotic and cool. And so he said, come rotate if you want. And I ended up working on that virus. It’s one of those mosquito transmitted viruses that’s prevalent in the tropics. And then I was good at virus research. That’s what I was qualified to do. So I kind of kept doing it. I did my postdoc on influenza, then I’ve been working on flu and the respiratory viruses ever since.

Grace: [00:25:18] I always love hearing about the serendipity of people’s journey. I think that’s really awesome. What exactly was your thesis research on?

Nick: [00:25:28] Yeah. So we were working on dengue virus. And one of the questions that we were really interested in was the interactions between the virus and the hosts. And the reason that we were interested in that question in particular was the virus replicates in mosquitoes, right. It lives in mosquitoes. And that’s how you get it. A mosquito bites you. And so this virus has to exist in mosquito cells and in human cells. And those are really different environments, right. A mosquito is very different from human. And so, anyway, those were some of the questions that we were interested in. We ended up doing a series of experiments looking at the role of cholesterol and fatty acids, which make up membranes and how the virus essentially reprogrammed the host cell to make the membranes that it needs for its replication and its assembly.

[00:26:13] That’s what my thesis was on. We published a couple papers on that. Towards the end of it. So we had looked at the host side, and what we really wanted to then do was look at the virus side of things. But the genetic tools for dengue virus at that time were not particularly developed. It’s really hard to make a mutant virus. We were trying to make a virus that couldn’t reprogram the host cell to move these membranes around and see what would really happen. So anyway, this was something we were interested in but were unable to do at the time. And then I was thinking about what I wanted to work on next and this is one of the reasons that I picked flu, because flu had a really good genetic system and there were a lot of things you could do with the virus. And that’s kind of what I was interested in getting trained to learn how to do.

Grace: [00:26:54] So when you aren’t busy being a scientist, what do you do? What do you do for fun? Who’s Nick the nonscientist?

Nick: [00:27:03] Well as you know the process of science takes a lot of time. My wife works in the lab with me, so it’s kind of a family business. And we have two young sons. So between the two of us working and then taking care of the kids, that’s essentially the full schedule of events for us.

Grace: [00:27:20] That’s the life. That’s awesome. What’s it like to work with your spouse?

Nick: [00:27:24] Yeah. As you can imagine there’s pros and cons. There’s way more pros. I think in our particular case, we met in graduate school. And so we’ve always kind of interacted doing science and talking about science and troubleshooting experiments. And so it’s just kind of been a natural evolution. And now it’s really great because, you know, she gets it right. Like when there’s an experiment that has to be done or a time point that’s really late or something spills into the weekend or something like that, it doesn’t take explanation. It’s just as things go and she knows the details, she gets it and we figure out how to make it work. That’s been a huge benefit.

Grace: [00:27:59] It’s better than someone who has no experience in science, because it really does take a lot of work and odd hours and that’s pretty cool. And you always have a carpool, buddy.

Nick: [00:28:09] Yeah, that’s right. Reduce our carbon footprint.

Grace: [00:28:13] Yeah. So as we wrap up the episode. What sorts of advice would you give to people who might be entering the field of virology today?

Nick: [00:28:24] I guess I would have two pieces of advice. The first is that you really need to become good. And what I mean by that is there are metrics in science, right. If you publish papers or you get fellowships or you get grants or these kinds of things. And I think a lot of people focus on hitting tangible metrics so you can put a line on your resume. I got this or I published this or whatever. And I think sometimes there’s less of an emphasis on really becoming an expert in the process of doing science. How do you set up the best experiment so you can make the clearest conclusion from it? And so that’s what I would tell people to start with. All the rest of that stuff comes if you’re doing good, thorough, reproducible science.

[00:29:09] You get all the rest of that, but at the beginning, that’s really what the focus should be on. And it’s satisfying. You know, sometimes from a CV building point of view because there’s nothing you can see, right. You’re thinking about questions better and more precisely. That’s really important. The other thing I would say is that there’s lots of reasons why people go into different fields or pick different topics to study. And I think that science is an endeavor where it’s really important to be excited about the specific thing that you’re working on. And it means different things for different people, even within the context of like working on one virus. There’s all kinds of different directions that you can approach it from. And figuring out what excites you, which little nuance of the questions are you most excited about?

[00:29:55] That’s no small part of being able to be successful and invest what’s required and when an experiment doesn’t work, something like that. I think it’s that that gets you out of bed the next morning. You know, you really care about it and you’re really working on the right question, helps you get through the lows, which always happen.

Grace: [00:30:11] Two excellent pieces of advice. And I hope our listeners can take those away with them after this episode. Thank you so much for joining me, Nick. It was really awesome talking to you and hearing your perspective about viruses and the pandemics and advice for life.

Nick: [00:30:27] Thank you. It’s been a pleasure.

The Bioinformatics CRO Podcast

Episode 39 with Becca Chodroff Foran

Becca Chodroff Foran, Head of R&D at Wisdom Panel, describes the recent advances in pet genomics and how we can use genetic data from dogs to guide research on human health.

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

You can listen onSpotify, Apple Podcasts, Google Podcasts, Amazon, and Pandora.

Becca is Head of R&D at Wisdom Panel, which offers genetic testing for dogs and cats to identify breed, health risks, and traits. She is also using this data to guide research in both veterinary medicine and human health. 

Transcript of Episode 39: Becca Chodroff Foran

Grant: Welcome to the Bioinformatics CRO podcast. I’m Grant Belgard. And joining me today is Becca Chodroff Foran.

Becca: Hi, Grant. Thank you so much for having me today.

Grant: Thank you for coming on. So Becca is the head of R&D at Wisdom Panel, a pet tech company focused on pet genetics. Really looking forward to hearing about Wisdom Panel.

Becca: Yeah. I’m thrilled to tell you more. It’s been a pleasure working at Wisdom Panel, and we’ve been through quite a journey.

Grant: So you’ve been at the company two years, right?

Becca: That’s right. I’m coming up on my second anniversary. And just to tell you a little bit more about Wisdom Panel, like you said, we’re a pet tech company. We’re focused primarily on strengthening the bond between pets and their parents through genetics.

Becca: And what that actually means is that we offer an array of products that give pet parents insights into their pets and that’s cats or dogs, breed backgrounds, health risks, and different types of phenotypic traits. In the background, because I’m on the research side, we’re also endeavoring on the largest ever dog DNA study.

Becca: We’ve tested over two and a half million dogs to date over 15 years. And we’re just starting to scratch the surface in analyzing those DNA sequences with phenotypic information that we’ve collected along the way.

Becca: And we’re starting to uncover some really exciting associations. Our help, actually, is that we can use that information to both strengthen precision care offered to cats and dogs. And my personal hope is that we can start translating some of those insights to human medicine as well.

Grant: Like Elaine Ostrander, right?

Becca: Exactly. So we were in the same lab, and I’m sure that you shared this similar experience of walking by her lab every single day and her rows of accolades. One image that specifically is burned into my mind is a framed picture of, I think it’s a Nature cover where there’s a really, really big dog and a really, really tiny dog.

Becca: And that study uncovered one of the first major associations of size in dogs. The gene was IGF-1. And what Elaine Ostrander found is that mutation in that one gene was responsible for a significant amount of the size variation in dogs.

Becca: It also laid a lot of the groundwork for why dogs are such an important model in genetic research, taking size as an example. In humans, there are probably hundreds of single nucleotide polymorphisms that are responsible for the differences in size.

Becca: In dogs, it’s likely a few dozen that can explain 90 percent or more of the variability in size. Interestingly and quite usefully, the same logic applies to a variety of diseases in dogs, which is why I’m so excited to have the opportunity to do the research that I’m doing today.

Grant: How much work do you do in linking that back to what we see in human genetics or mouse genetics efforts? Do you see any similarities in genetic architecture?

Becca: Yeah. So I’ll start with the genetic architecture. And by and large, the genetic organization across humans and dogs is remarkably similar. We share 86 percent of our genomes with dogs.

Becca: The genes are in the same order. We have 23 sets of chromosomes, dogs have 39. But that essentially just means that the genetic order is extended across more chromosomes in the same order.

Becca: Going to phenotypes, there’s also a remarkable amount of similarity, some of that’s attributed to physiology. A lot of it’s also environment because dogs, more than any other species, shares our environment as far as lifestyle, the food that they eat, the houses that they live in, in my case, the beds that they sleep in.

Becca: So in that way, we can study a lot of the same diseases that impact both humans and dogs. There have been some discoveries in autoimmune disorders, cancer, neurological disorders, and dogs that have helped us elucidate the underlying mechanisms and human diseases and vice versa. So it’s more of an interplay, as opposed to taking one and then shifting over to the other.

Grant: How about dog evolutionary genetics? So if you look at recent selection events in humans and so on, you see prolonged tolerance for lactose and things like this, are there similar selective events in dogs with them sharing human diets and so on and so forth?

Becca: There are, and I’ll start first by giving a bigger picture of dog evolutionary biology because it’s unique. They’ve been subject to both natural selection and a host of artificial selection events. At this point, they’re one of the most diverse species on the planet, ranging in size from two pounds to over 200. They have different behaviors. They have vastly different phenotypes. And a lot of that diversity has just emerged over the past 150 years. That’s also the case when you look at nutrition. So you’ll find that different breeds require different types of nutrients.

Becca: And we’re just starting to understand, in molecular detail, what those requirements are. There are certain disorders, for example, hyperuricosuria in which certain minerals are not processed quite as well. And the list goes on. Dogs have allergies just like we do. They have preferences for different types of food. And we believe that a lot of that is associated with genetics.

Grant: What phenotypes are you looking at? Are you looking at behavioral phenotypes above and beyond just breed level differences? How do you gather that data objectively right? Because if you ask pet owners, I’m sure you could get very different answers from different owners of essentially the same dog.

Becca: You’re exactly right, which is one of the reasons why there have been an array of standardized surveys developed over time that ask questions in a sneaky way. So as opposed to asking, is your dog excitable? We can ask a series of questions about whether your dog barks when there’s a visitor, whether they jump up and down when you shake a treat bag, and so on and so forth.

Becca: As far as your initial question, we’re looking at a full range of phenotypes. We have the privilege of being partnered with Banfield Veterinary Hospitals, which has vet clinics across the country. And they’ve offered our genetic task to hundreds of thousands of puppies. We can take those genetic results and associate them with their medical records.

Becca: We’re just now starting to link the genetic data with the clinical data and try to find associations between various disorders. We started the study back in 2019, and we enrolled puppies. These puppies are now at most two years old. So most of them are just starting their lives. There haven’t been that many disorders, but we anticipate that over time will get more and more data so that we can understand the ideology of a variety of diseases. And we’re primarily focused on several of the same diseases that afflict humans, ranging from cancer, epilepsy, diabetes, neurological disorders, and osteoarthritis. And the list goes on and on.

Grant: So that sounds like an incredible data set. What are the long-term plans for that?

Becca: There are multiple. So the first is, actually, the medical data gives us a small window into the dog’s day to day life. We’re also in the process of launching a community science platform in which we’re going to start surveying pet parents about their dog’s daily lives, their health, their behavior. And then we’ll combine those massive data sets together and hopefully build out some risk prediction models.

Becca: One of the goals on the horizon is to start building out risk models for more common disorders so that pet parents can make more informed decisions early on in life.

Becca: If the dog has a really high risk of a particular cancer, they might choose to engage in additional screenings. If the dog has a risk of osteoarthritis, there might be some recommendations as far as curving the dog’s weight. So there are a variety of opportunities we have short term.

Becca: In the long term, we’re hoping that these insights can be coopted by veterinary clinics to make care more precise, more personalized, or pup-sonalized, whatever you want to call it.

Becca: And we hope that our insights will help veterinarians make more informed decisions about what types of treatments are given to dogs or what types of wellness protocols are offered to dogs. And finally, as I alluded to earlier, we’re hopeful that some of these insights will be translated to human medicine, and that on both the human side and the veterinary side, some of these insights could lead to additional discoveries in therapeutics.

Grant: So we have a career-changed service dog. It’s a nice euphemism for a flunky from Service Dog School. And obviously, it is quite expensive to have a dog sent out of a Service Dog School a year and a half or two years in. Do you think there are still variants to be found and so on that could be used as part of the screening process for service dog training? For example, where they can say this dog would be better as a pet versus we’re going to spend tens of thousands of dollars training this dog to be a working dog?

Becca: Absolutely. We’ve been in contact with a variety of service dog organizations to help build out screening paradigms so that they can identify dogs that are more likely to go through their training programs, which can be thousands of dollars and a lot of resource for each one.

Becca: So if they’re able to more effectively identify, as you say, the flunkies versus those that will be successful. It’s a lot of time and money spent. So I’m aware of the a few programs that are in action right now, and we’re hoping to kick off many others.

Grant: Can you comment on the linkage disequilibrium (LD) structure in dogs? In my understanding, which could be wrong, the LD blocks are sometimes a bit larger and so on. How does that impact fine mapping? With a database of millions of dogs, how are you getting around these issues?

Becca: Yeah. So I think it depends. The general answer is the LD blocks are much larger. When people give that answer, they’re typically talking about purebred dogs, AKC registered dogs that have been selectively bred for multiple generations.

Becca: When you’re thinking about the entire dog population of the world, close to a billion, I believe about 750 million of those dogs are what’s called village dogs or street dogs or some combination where humans don’t actually control their breeding. In those cases, the LD blocks look much more like humans.

Becca: So pedigree dogs, those pure bred dogs, are much more frequently used in studies right now. And in those cases, it is generally more straightforward to fine map to the causal mutation. So those dogs, their LD structure, as well as the really great record keeping that breeders have at their disposal have made studies into the genetics of a variety of diseases very fruitful.

Grant: I guess maybe you could do a dog decode genetics or something, right? Where you have the pedigrees going back a bunch of generations, and you can genotype the living dogs.

Becca: Yes, exactly. We have a team based in Helsinki. We’ve talked about doing something quite similar. We’ve also been very lucky to work with dedicated breeders across the world who keep those pedigrees. And we’ve had efforts on going to map a variety of genetic traits and diseases through generations and generations.

Grant: And you also have cat products, right? Can you comment on what are the major differences between working with dogs and cats?

Becca: Everything. And I’m not a cat owner, but I’ve had cats in the past, and I think cat owners will appreciate that as well. At present, the products are quite similar. So we offer an ancestry report that shows that cat’s breed background, health risks, and traits. What we’ve found in working with cats is that their population structure is much more similar to humans. There’s much more admixture. There’s a lot of free breeding across populations.

Becca: And as some of our veterinarians like to say, that’s primarily because cats were doing a pretty good job at the job that humans gave them, which was to be pest control. It’s only in the past 100-150 years that cat fanciers have come in and have started to control cat breeding. And in those cases, you start to see the LD structure that’s more similar to what you see in pedigree dogs.

Grant: So what’s new?

Becca: A lot actually. We are super excited to announce that we’ve recently launched a brand-new breed detection system. And we’re happy to say that we’re now the most accurate breed detection system available anywhere on the market.

Becca: And this was a huge effort on our side. So we pretty much started from scratch two years ago. That’s where I came into Wisdom. And I also brought in a few lead population genetics from and 23andMe. And one of our primary goals was to bring our pet parent community the best and most up to date science available.

Becca: So where we started was with a database that’s now over two and a half million dogs that represent breeds across the world. We’ve collected samples from over 50 countries at this point and over 15 years of documentation on the profiles of those breeds.

Becca: And we wanted to bring the insights that we’ve gleaned from all of that dog DNA to our customers. So in order to do that, we reasoned that we wanted to create a local ancestry classifier, which basically means that we could pinpoint ancestral breeds to very specific locations in a dog’s DNA.

Becca: The other thing we knew is that we wanted to leverage as much as possible of that massive two and a half million dog DNA database. And one of the challenges that population geneticists have faced since starting ancestry detection is a problem of computational power and efficiency.

Becca: So we started with that problem first to figure out if we could increase the speed of the ancestry calculation and decrease the computational power needed. One of my scientists named Daniel Garrigan, had this idea that he could take what’s called the Burrows–Wheeler transform, it’s an extremely efficient computational construct, basically, that rearranges character strings into runs of similar characters.

Becca: It’s used all over the place. So the primary uses for data compression, and it’s the basis of the bZIP compress. It’s also the B and the W in BWA, which a lot of people on this call, or excuse me, on this podcast probably recognize.

Becca: So he used that perspective. And he also recognized that back in 2014, Richard Durbin, who is a scientist at Sanger, published a paper on using the positional Burrows-Wheeler transform, which is a much more computationally efficient method versus something like a hidden Markov model.

Becca: So we could rapidly go through DNA sequence very quickly. It’s primarily being implemented in phasing right now. And finally, he thought he could apply the positional Burrows-Wheeler transform to the Li and Stephens chromosome painting model.

Becca: The chromosome painting model is, if you can imagine a map of chromosomes and colors distinguishing the most likely ancestral population in specific chromosome regions. So he proposed to apply the Burrows-Wheeler method to approximate the Li and Stephens chromosome painting.

Becca: And what he was able to accomplish is a much, much more efficient way to index thousands and thousands of reference samples and assign them to their closest match with a test DNA sample.

Becca: So what we’ve established is a new way of processing lots of data very quickly. And what that’s allowed us to do is to create the largest dog reference panel available and the most accurate way to predict a dog’s breed backgrounds.

Becca: We’re really excited, as I mentioned, and this product is now available through in addition to cat DNA testing there. They happen to be on sale now.

Becca: So it’s a really great opportunity to experience the new science that we’re bringing to our customers. One of the other really exciting opportunities that we’re going to open up in the next few months is a community science effort.

Becca: So I mentioned that we use a lot of the data that we’re collecting from our customers in key studies to help elucidate some of the genetic architecture underlying K-9 diseases.

Becca: In order to expedite that research and discover more in a shorter period of time, we’re going to start asking our community of pet parents about their dogs, and we’ll ask questions about their dogs behavior, their dogs health, their dogs longevity, and a number of other questions, similar to what human genetics companies have done.

Becca: And our hope over time is to start researching some of the information that our community has given us and then bring that back to the product itself so that we can start telling our pet parents about some of the health insights we can glean from looking at their dogs genetics.

Grant: Very cool. What do you think is to come? If you look way out, say, 10 years, how do you think genetics will impact pet owners, will impact veterinarians and veterinary care, will impact pets and service dogs?

Becca: Ten years from now, I believe that every single human, every single dog, every single cat, will have their whole genome sequenced. And we’ll be able to use that information in all aspects of our life from what type of diet we need, what type of exercise is going to enhance our longevity, what type of medications, what wellness regimes are ideal for our underlying genetics.

Becca: So much of what you’ve heard on the human side is also going to be true of the dog and cat side. We’ve seen over the past two decades or so that dogs and cats have evolved from a possession to an actual member of the family.

Becca: And what also happened during that period of time is that people and pet parents are expecting the same level of medical care for their pets as themselves. So now there’s a tremendous focus in bringing precision veterinary medicine up to the same level as human medicine.

Becca: So we’ve seen the market pay much more attention to this. Pharmaceutical companies focus much more on veterinary pharmaceutical pipelines that resemble human pipelines. And my belief is that that’s going to continue over time, so that the same types of genetic technologies that humans are going to start using on a day to day basis will also be applied to their free family members.

Grant: Do you think there could be a pet to patient pipeline, treat aging and dogs, and then take those learnings over to people?

Becca: Well, that is exactly what Daniel Promislow and Kate Creevy are hoping. They recently launched the Dog Aging Study. I think it was about a year and a half ago, and it’s been very successful. It’s NIH funded.

Becca: And their general position is that, as I said before, dogs in a lot of ways are sentinels for the human life and that they can be examined on a much more condensed time scale. So human life average is 70 years, dog average life, 10-12 years.

Becca: They can collect a lot of information about dog longevity over that period of 10-12 years and then hopefully translate those insights into applications for both humans and dogs.

Becca: To date, there has been a lot of interesting observations. One that we’ve known for years is that small dogs tend to live longer than large dogs. Why is that? We have some hypotheses. It’ll be nice to test them further. Are there exceptions to those hypotheses? Are there certain genetic signaling pathways that are underlying longevity or shorter life? And then can we reverse some of those pathways and actually extend lives and dogs? And then finally, the big question is, can we also identify similar pathways in humans and thus extent human life as well?

Grant: I wonder if you bootstrap your way into right into it. You get a revenue stream going in dogs and then use that to fund on the human work. Earlier, while you’re talking, I was hearing K-9 in the background. Can you tell us about your dog or dogs?

Becca: So, Peanut. Yes, I actually brought up Peanut during my job interview. I think it’s the only time that I’ve ever brought up my dog during a job interview.

Becca: Peanut is six years old and is a pretty funky looking dog. So we never really knew what she was. I tested her, I think my first couple of weeks on the job. When we bought her, she was supposed to be half Shi Tzu, half Bichon. For those that are familiar with what those dogs look like, each of them have what are called furnishing.

Becca: So they have furry eyebrows and a furry mustache. And Peanut has a naked face. So she looks more like a long haired chihuahua. That’s always what I thought she was.

Becca: And then I did the genetic testing and low and behold, she actually is a Shi Tzu and a Bichon, but she carries this unusual trait for both of those breeds and that she has a naked face, she doesn’t have furnishing. And for a while, when we had the old breed detection system, we didn’t have resolution into breeds on particular chromosomes. It was a different approach to hone in on the breed background.

Becca: This new approach is based on local ancestry, which means that we can map breed specific positions in the chromosome. So I got the Peanut’s full genetic map. And really interesting, on chromosome 13, on the top tip, she had two different colors, and those colors also mapped to the furnishing gene.

Becca: So it turns out that on that little tip of chromosome, her breed is actually Japanese Chin. So somewhere along the line, there was a Japanese Chin, or there was an unusual line that introduce this unusual phenotype.

Becca: So I have to say it was pretty fun to learn about her background and understand more of her behaviors and the reason why she sheds. And it really did help me connect more with our little Peanut. So that was a lot of fun.

Grant: That’s pretty cool. Is Wisdom planning to or do you maybe already have narratives like you get with direct consumer human genetics companies, where you have big explainers for things, and you can take someone through a little bit of a journey for the ancestry of their dog?

Becca: Yeah. So we actually were, I believe, the first company that introduced genetic family trees. So a representation of what a dog’s family tree could have been based on their DNA.

Becca: So I mentioned that we use local ancestry now, and we can use that information to basically determine what breeds came from mom, what breeds came from dad. And then we can go further from there, much in the same way that you can walk humans through their ancestors, migration through Russia, Europe, Africa, what have you, you can do something similar with dogs.

Becca: So you can trace back a little bit of Rottweiler all the way back in the grandparents, a golden retriever that was one of the grandparents, and so on.

Becca: We’re also in the process of looking into mitochondrial DNA and chromosome, and with those additional measures, we can track specific migratory patterns from the maternal line and the paternal line.

Grant: Super interesting. So what are you most excited about in the pet genetic space?

Becca: I’d say that pet genetics is a decade or so behind human genetics, and some people might look at that as a negative. I’m taking it as a positive, because what that means is that we can apply the learning from the past decade of them half from human genetics to pet genetics and hopefully leap frog with that information, even past human genetics to the next stage.

Becca: What that next stage is, is hopefully injecting some of the insights that we’re getting from the genetics into clinical practice. I’m optimistic that the change in veterinary medicine will be faster than the change in human medicine, and that’s for a few reasons.

Becca: The primary one is that the regulation is different, and in veterinary medicine it can be faster. Key example here is drug development. Instead of going through animal models and then eventually graduating to clinical trials, you can test the drug in the subject animal at the beginning. That does have an elevated level of risk, but it also means that drug development can go a lot faster.

Becca: At the same time, there are different types of regulation as far as devices and clinical decision support tools, where we have some more opportunity to work directly with practitioners to observe how these tools are impacting clinical decisions going forward.

Becca: So I’m hopeful that in 10 years, genetics is going to be one of the key elements in the tool box for veterinarians and vet techs and will be leveraged just as much as the standard blood panel that’s used today.

Grant: Vet schools better get ready, yeah?

Becca: That is certainly something that’s top of mind for a lot of vet schools now. There are just a handful of vet schools that have geneticists on the team, and I think that we’ve spoken to several that are interested in incorporating more genetics education into their fundamental program, similar to medical schools.

Grant: Very cool. So let’s talk about you. Where did you grow up? What were you interested in as a kid?

Becca: So I grew up in Delaware. I was born in Philly, and then I moved out to Delaware shortly after. And I was a pretty quiet nerdy kid. I don’t think I really realized that I had an affinity for school until seventh or eighth grade. And then I started to bring home good report cards. And I got attention from my parents, and I realized, oh, this is fun. So I kept on going that direction.

Becca: In high school, I’ll say that I was a legitimate nerd. I remember I was in this AP biology class. And we started talking about evolution. And I brought in a book that I had just been casually reading at home about the origin of humans. I mean, what 14-year-old reads about that stuff?

Becca: So surprisingly, I didn’t have a date to prom, but I think that that interest eventually evolved. I did in college, developed social skills, or maybe I just found a whole bunch of other nerds to hang out with who appreciated my nerdiness.

Grant: Now you go to the right college, you’re no longer weird?

Becca: Exactly. So I went to college, I went to UPenn, and I majored in anthropology. And I had no idea what I wanted to do. I tried out everything. I thought about being a doctor. I thought about being a lawyer. I thought about just not doing anything, being a consultant, which I think is what people do when they can’t decide what they want to do. So the whole thing.

Becca: Anthropology was always had a strength through my entire career trajectory because I was truly interested in human evolutionary biology, the origin of consciousness, migration through various continents, and that seed continued to go through grad school.

Becca: I did eventually decide to go to grad school. And I think part of that was thanks to some amazing mentors that I had as an undergraduate who encouraged me to stay curious and interested, and just enjoy graduate school and then figure out what would happen.

Becca: So I ended up in the NIH Oxford program like you as well, Grant:. And I did a PhD with Eric Green at the NIH in the Genome Institute and Zoltan Molnar at Oxford.

Grant: Shoutout to Zoltan, you’re probably listening to this. You need to come on the podcast.

Becca: So I’ll say hi to Zoltan, too, and I hope that you come on right after me and correct everything that I’m saying, or hopefully not correct everything that I’m saying. And I have to say that at the beginning, the connection between Eric and Zoltan was almost incidental.

Becca: So Eric is one of the pioneers genome technology in sequencing and had built a lab around comparative genome sequencing. Zoltan focused on neuroanatomy and development, which seemed like two completely different areas.

Becca: The way that they were the same is that they were both using a variety of organism across reptiles, birds, mammals, fish. There may have been some amoeba work in Eric’s lab, but the whole gamete.

Becca: What I thought is that, hey, maybe we can apply these really high tech genomic sequencing technologies to neuro and anatomical fundamental and figure out whether we can identify some key pathways that are conserved across very distantly related species.

Becca: In the end, we settled on an investigation of a variety of noncoding, excuse me, long noncoding RNA genes, and I can still rattle off their sequence of letters and numbers that don’t make sense to anyone else.

Becca: So I should credit Chris Ponting for first identifying these long noncoding RNAs and claiming their functionality, and Jasmina Ponjavic for doing some of the initial computational analysis to expose the exquisite conservation of these genes, which was really striking. They looked just like protein coding genes with a few exceptions.

Becca: So we just couldn’t figure out what they were doing. The other thing that was really interesting is that they were very precisely expressed in specific areas of the human brain, the mouse brain, the chicken brain, and that expression pattern was conserved as well.

Becca: I wish that I had a huge message at the end of this, and we discovered them, and we were intensely important for some biological pathway, unfortunately, and it’s often the case in graduate research, we couldn’t. We still believe that they are likely involved in regulatory processes. I actually haven’t looked at them for a while, so I don’t know if there have been further studies on them.

Becca: I actually made a knockout mouse for one who didn’t have a phenotype, which was is quite disappointing, but I think it certainly gave me a lot of tools that I’ve used through my professional life.

Becca: And what I tell my team over and over is how important failure is. It sucks in the moment, but it makes you stronger and it makes you more creative, and it makes you more intuitive. And it forces you to think in different ways and think about how you can not fail the next time or just fail better or faster so you can move on to the next thing. And I think that that skill in and of itself has been so critical to my success in startups.

Becca: And now at Wisdom Panel in product development, in particular, I think one of the mantras is to fail fast so that you can move on. And that’s certainly something that I think PhDs do very well.

Grant: So how did you get into biotech?

Becca: For a number of years, I had a curiosity in biotech, and I think that that started mostly during my time at the Genome Institute because it was so connected with biotech and academia. So it was nice to see the interface between them and the differences.

Becca: I moved to New York after grad school. I just followed my husband there. I was finishing up my PhD. I had just submitted my thesis and I was waiting to defend.

Becca: So moved over with him and thought it’s New York, I’ll find a job. I thought that I wanted to be a professor, so I was looking for a postdoc in the area. And I did find a quite short-lived postdoc at Cornell. It was at a great lab, but I realized very quickly that it wasn’t for me.

Becca: And this was 2010, 2011, funding was not great at that time. So I worked there for a few months. And I have to say Cornell had a really great professional development program, in addition to working directly with postdocs on an academic trajectory.

Becca: So they hosted a number of career development events and I attended all of them. One in particular stood out to me. So I went there. I listened to the presentation. It was given by an alum named Piraye Yurttas Beim on a new company that was called Celmatix.

Becca: At the time, it was five or six people, and she was talking about stepping across the line from academia to startup world and how she did it. And I was so inspired by her presentation that I actually just walked up to her right after and I said, I love what you’re doing, how can I start?

Becca: And two weeks later, I was at her office in the meat packing district in New York, and the rest of history. One of the lessons that I last thinking about it now that I’ve told several of my team afterwards is how important networking is. And it’s something that I hated so much. I hated getting that advice, but it’s really the best advice.

Becca: And through my career, I think that’s really how I’ve navigated. I’ve figured out where I want to go. It’s just by talking to people and making connections and maintaining them.

Grant: What do you think people do wrong when it comes to networking?

Becca: Not networking. I don’t think there’s too much you can do wrong. I think the worst thing that will happen is that you’ll walk up to someone and they’ll walk away from you. So you don’t really have that much to lose.

Becca: So I’d say just go in with an open mind and introduce yourself and talk about what you’re interested in. In general, most people are relieved that you’re making the first step in introducing yourself.

Grant: And now that you’re on the other side, what’s changed about your perception? What misconceptions did you have as a grad student and postdoc that you can now dispel?

Becca: I’ll start as a college student because I was so focused on success, and I had a really narrow definition of success. So I define success as getting good grades and being in the good graces of your professor.

Becca: I hit this realization in grad school that that doesn’t really matter anymore. It doesn’t matter if you got an A or a B or a C or a D. What matters is that you’re doing work that you think is important and engaging.

Becca: It took me a really long time to process that and actually make it part of my view on the world that success is great or financial success or the other way that people see you, but that’s not actually going to significantly impact your state of being. It really comes down to how happy you are, how motivated by work you are, that you have a good work life balance and so on. So it’s something that I’m still working on, but I think that it’s so key. And I wish that I had known that earlier.

Grant: Yeah, I think that’s a process a lot of top students go through as they get through their 20s and sometimes into their 30s.

Becca: Yeah, it’s funny. Actually, I had this professor and he had these two young sons who called his PhD students gradual students instead of graduate students. And that really stuck with me because I really did feel like I had this extended out of lessons through my PhD.

Becca: You don’t have quite as much responsibility, I’d say, as if you just jump into the corporate world. There are a lot more people looking out for you, which is really nice. I had great relationships with my mentors, and I think I’ve really lucked out because they were watching out for me and making sure that I was making productive decisions. But at the same time, I didn’t feel that push or that weight of responsibility until I finish grad school.

Grant: Right. What advice would you have for yourself five years ago?

Becca: Let’s see, five years ago, I had just had my daughter. So I had a six month old at home and I had taken some time off of work. And I was really confused about the next step, actually, because of all of the emotions when responsibility is running through my mind and probably running through most professional women after they have their first kid.

Becca: So I have to be honest, I desperately wanted to stay home. When she was three, four months old, I thought about just taking a couple of years off of work.

Becca: I ultimately chose to go back to work to start out part time and then ultimately to go back full time. And I’m so happy that I did. I can say it’s a personal decision. And I have many friends that have chosen other paths that worked out best for them.

Becca: But I think that what I’d probably tell myself five years ago is that looking now at my colleagues, and there are different trajectories, you eventually get to the place where you want to be.

Becca: It might take a couple of years longer if you choose to spend more time at home, but you’ll be grateful for the time that you spent at home, or you can choose to go back to work earlier.

Becca: Something that helped me later on is a call that I had with one of my mentors, Mark Adams. And it was actually when I was considering switching careers, moving from human fertility, where I have been for a number of years at Celmatix to pet genetics, which was pretty drastically different.

Becca: I was worried that if I took a step away from human genetics that I wouldn’t be able to go back. And what he told me really stuck with me. He just said, maintain your storyline. Just make logical steps that continue to build on your experience. If this is going to give you the opportunity to grow as a person, to get more experience in population genetics, to explore something that’s more consumer focused, go for it, and then obviously you can bring it back to other areas. So I could also pass that along to my younger self.

Grant: And how have you found the transition from individual contributor to manager?

Becca: In a lot of ways, it’s like going from a single person to a married person to a person with a family. So it’s actually nice that my wife followed my career that way, and I was able to apply some of my mom’s skills to play professional life and backwards.

Becca: So I think what that means is that you start thinking about people besides yourself, you need to. And I think if you’re a good manager, you need to pick your team’s interest ahead of your own in order to succeed. Otherwise, your team’s not going to be functional.

Becca: So what I try to do every day now is think about how this is going to impact this person, this person, and this person before actually making a decision. I’m also much more intentional with my messaging and my explanations.

Becca: I think that being a manager has helped me grow quite a bit as a person. And as I mentioned, I think it’s made me a better mom in some ways. As an individual contributor, I think that there was a bit more freedom to try and fail. But I’ll say that that might also have been because of the environments where I happen to have very supportive managers that offered me constructive criticism or support at key points that I needed it.

Grant: And do you have any final words of wisdom for our audience?

Becca: I think I found the most success in just pursuing my interests and satisfying my curiosity. And in general, even if things felt uncertain, they usually work themselves out.

Becca: And what that’s given me is the opportunity to have a really interesting career and work with really interesting people. So I hope that I can pass that insight along to my team and my mentees and my kids.

Grant: I think that’s pretty core. You’ll always be the best at being yourself and at doing what you like to do. And so where you find that intersection with what the world needs and so on, it’s a good place to be.

Becca: For sure.

Grant: Well, thank you so much for joining us.

Becca: Thanks so much, Grant. It was great catching up.

The Bioinformatics CRO Podcast

Episode 38 with Stacy Horner

Stacy Horner, associate professor of molecular genetic and microbiology at Duke University Medical School, compares hepatitis C and dengue virus to SARS-CoV-2 and suggests policy changes to make academia more inclusive.

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

You can listen onSpotify, Apple Podcasts, Google Podcasts, Amazon, and Pandora.

Stacy is an Associate Professor in the Departments of Molecular Genetics and Microbiology and Medicine, and also the Co-Director of the Duke Center for RNA Biology. Her lab studies the molecular mechanisms that regulate flavivirus-host interactions.

Transcript of Episode 38: Stacy Horner

Grace: [00:00:00] Welcome to The Bioinformatics CRO podcast. My name is Grace Ratley, and today I’m joined by Dr. Stacy Horner. Stacy is co-director for the Duke University School of Medicine, Center for RNA Biology, as well as associate professor. Welcome, Stacy.

Stacy: [00:00:15] Thank you for having me, Grace.

Grace [00:00:16] I’m excited to have you on the podcast. So can you tell us a little bit about your research on flaviviruses?

Stacy: [00:00:22] Yeah. So my lab studies virus-host interactions. And so what that means is that we’re really interested in how viruses infect cells, how cells sense these viral infections, and then how the cells in our body fight back to viruses and then how viruses try to get around that immune response. And so, as you mentioned, we do this in the context of viruses in the flaviviridae family. So that includes viruses like hepatitis C virus, dengue virus, Zika virus, West Nile virus, all viruses that many of you may have heard of before.

[00:00:53] And I mentioned that these are positive strand RNA viruses. So they’re very similar in some respects to SARS coronavirus too, which is the virus that’s causing the current COVID-19 outbreak, which also has a positive-sense RNA genome. And so fundamentally, what we’re learning and how we study how these flaviviridae viruses interact with the cells in our body, our principles that can actually go beyond just these viruses, because many RNA viruses are viruses that generally interact with cells in the same way.

Grace: [00:01:23] Can you tell us a little bit about hepatitis C in particular? So hepatitis C does have an effective treatment. So why is it important for us to continue studying this virus?

Stacy: [00:01:35] Yeah. So hepatitis C virus, as you know, we have great direct acting antivirals to this virus that can actually cure the virus. So unlike HIV, which when you’re infected, it goes into kind of like a latent state and heads out of your body, we can eliminate HCV from people. So that’s very exciting. And in fact, the scientists who discovered aspects of hepatitis C virus infection and how to cure it, actually just won the Nobel prize last year. And so the reason why it’s important to study this virus, even though it’s already cured, are two big reasons.

[00:02:09] The first is that there’s actually no vaccine, so we can’t prevent infection. And one of the largest sources of new HCV infections every year is through IV drug users. And in fact, at least a year or two ago, the number of new infections per day was equivalent to the number of people being cured from the virus. And so the only way to actually eliminate the virus is to prevent infection. And we really need a vaccine for that. And so while my lab isn’t studying the immune responses that would lead to a functional vaccine, there are many labs that are doing this. And I think having a vaccine to prevent infection by HIV is something that we really need.

[00:02:46] So that’s one reason why people in general should still study it. But from my lab, we like to study this virus because it interacts with our host cells in a lot of interesting ways. And by understanding how this virus interacts with our host cells or causes infection, we could actually learn general principles about how viruses can cause disease. And so we can use this virus as a model virus to learn how these things happen and then compare and contrast to other viruses to see if it’s similar or different.

Grace: [00:03:15] And you mentioned that some of the RNA biology is similar in both flaviviruses as well as SARS-CoV2. Can you talk a little bit about that and what you’ve found so far?

Stacy: [00:03:28] Yeah. So the most important thing that’s similar is that their genomes are what we call a positive sense polarity. And so that means when the virus infects a cell, the viral capsid un-coats, the viral RNA gets into the cell and immediately that RNA is translated to make the viral proteins for both viruses, the flaviviridae and for coronaviruses in general. The first thing that needs to happen is that the viral RNA dependent RNA polymerase gets made and this viral protein can then replicate the viral RNA to make more copies. Actually, in the viral RNA dependent RNA polymerase is a big drug target for hepatitis C virus at some of our drugs that are in the clinic are used to that.

[00:04:10] And you could imagine that for coronaviruses it would be a similar type of idea. One major difference between the two viruses and this is why actually there isn’t a drug that targets the coronavirus, RNA dependent RNA polymerases is that the coronavirus because its genome is very large. So it’s RNA genome is 30 kilobases long, whereas viruses in the flaviviridae family are around 10 kilobases long. So it’s three times bigger. And so because of that, when the viral polymerase copies the genome, it makes many errors, right. And the longer genome, the more areas that you can make. And so coronaviruses actually encode a proofreading enzyme that can fix mistakes.

[00:04:52] Many times in virology, we want to target the polymerase, but actually in coronaviruses it could maybe fix mistakes that happen because they also include what we call exonuclease that can help to repair the genome. So I think the exonuclease might be a good molecule to target in coronaviruses. And in fact, a new paper came out, I think today sharing the crystal structure of that protein of the virus. So that’s very exciting for people who study coronaviruses.

Grace: [00:05:20] So how do you think the pandemic has changed the way that people think about the field of virology as a whole?

Stacy: [00:05:29] Right. So I think it depends on who you ask, as we all know. So in my family, I’m very popular right now because a lot of my family has a lot of questions like probably many of us do about: how the virus works, how do you get it, what’s safe, what’s not. And the fun part of being a virologist is that I actually read the scientific papers. And so I know the data in the papers and what seems right and what’s not. And one of the interesting things in the last year is that the media has been covering the virus a lot and sometimes they aren’t able to quite capture the nuance of science, right.

[00:06:08] And so sometimes I look at a paper and I come to a conclusion and then I read a news article, and they come through a different conclusion. So that’s something that’s been pretty interesting. And for my family, as we’re trying to all make decisions to keep us safe, I’ve actually relayed some of like, well, I know that’s what the article said, but this is kind of what I think based on the data in this paper. And so if we go to a broad level now, a lot of people are, what we call armchair virologists, which is kind of exciting to have new people from other fields interested in how viruses work.

[00:06:40] We’ve made a lot of progress in only about a year, which is really remarkable, right. We didn’t even know the virus existed and now we have a vaccine that’s in like at least half the people over 18 in the United States, right. So I think that’s very exciting. One of the hard things, one of the challenges has been that many people think they know everything about virology and they come in from a different field. And there’s actually a pretty well established coronavirus literature. And so I know some of my colleagues who are coronavirologists have been a little bit irritated if people don’t know the literature.

[00:07:13] So that’s something like the scientific sphere. But if we go to a global sphere, a lot of people say, well, I am really good at predicting these things. I’m really good at epidemiology. I am really smart generally. And so I want to tell you how you can cure this virus. I think we can all appreciate everyone’s efforts to come together on this. Sometimes we wish that people would spend a little bit more time preparing and actually going to the experts who really do know what’s happening, the advantage of people from outside as we get more creative solutions, the disadvantage is they have to get up to speed. And as someone who’s been studying viruses for 20 years, that’s a lot of speed to catch up to, right.

Grace: [00:07:51] Yes, certainly. We had a person on the podcast recently who was using CRISPR-based technologies for COVID diagnostics, which was a really exciting new development. They’ve been using it to try and diagnose other conditions. And when the pandemic started, they quickly jumped in and helped out there. Can you think of some of the more exciting technological advances that have come as a result of people entering the field of virology from other fields?

Stacy: [00:08:20] Yeah. So I think, one, that is pretty exciting, and I don’t actually know the people who did the work, but I’m sure you can find the publication for the listeners, is novel methods to detect coronavirus infection. So currently you have to do like a PCR test, which takes a while and is expensive. You could do an antigen test which is much cheaper. But I read a report of a study that can take the air that people are breathing and then do mass spec on the air–I think it’s mass spectrometry–to identify the exact molecular weights of the things that are in that air and they could actually detect the virus.

[00:08:58] This is super cheap. You could put it in like train stations. I thought that was really cool. So that’s like some of the really cool technology that you would have expected. And I think a lot of this comes from, you know, maybe people in the engineering world. And then, you know the other big thing for my field that I think is very exciting is the fact that the COVID vaccine is the first mRNA based vaccine that has gone into people and been approved for this kind of global use as emergency authorized, right. So while a lot of the technology for mRNA vaccines has been around for a really long time, it wasn’t until right now that we had to make a vaccine really fast, what are we going to do?

[00:09:39] They kind of had done all the research over the years to be ready right for this moment. And the fact that it works so well and so quickly is very exciting, because that means that then we can use this technology for future pandemics, for a lot of other diseases or viral infections. I would say from my point of view, the fact that you could go from not knowing a virus to get an FDA approved vaccine in people in a year… I actually did not think it was possible, and it actually was, which is really exciting.

Grace: [00:10:07] Yeah, it is. It’s so exciting. So one of the things that I’ve always wondered about is why did it take us like a pandemic to get these things to market? Like what do you think is the difference?

Stacy: [00:10:18] Yeah. So it was really an accelerated timeline, a lot of resources put into it in an urgent need. So if you talk to people who work for companies and do clinical trials, clinical trials are very expensive. And you start with your phase one, which is a small safety trial, then you start the phase two, which is like a little more safety, a little more efficacy. And then you go to phase three and these will often be spread apart by several years as they review the data and think about as a company, what strategy do you want to go after. Can we raise the funds for the Phase three trial, which is very expensive?

[00:10:52] And so in this particular case, they just did all those back to back to back. They didn’t do a lot of the optimization that goes through, like, what is the right dosing? There was a little bit of that, but not as much as is normally done. And I just had to say, let’s go for it. And so because the vaccines had the support from the federal government, they could actually take the risk to go through all the trials, right. Because they’re very expensive. If you fail, you just kind of lose all that money. But because the government partnered or was willing to buy the doses, that really took that risk out of the picture for those companies.

[00:11:27] So I think that was the big thing. And also that the other big thing that I would say like from a virology point of view is that the pandemic was still ongoing. And so you could actually do the clinical trials. You might remember a few years ago in 2016, there was Zika virus pandemic. And in fact there were Zika virus vaccine candidates, even a mRNA vaccine candidate. But the Zika pandemic pretty much died out. And so you had a vaccine, but you had no way to test its efficacy. And so in this particular case, we are still testing a lot of efficacy. And so you need enough study participants to do the trial. You have to recruit them.

[00:12:04] And in this case, we had so many people that you could recruit for a study. It was actually able to get your end points, you know which is how effective is it in a controlled study with a matched-control group. So I think that was very exciting. And some of the reasons we were able to accelerate are support from the government, financial backing, the urgent need, and having a huge study population.

Grace: [00:12:25] So do you think there will be long lasting changes in the way that the government interacts with and funds virology research or medical research in general?

Stacy: [00:12:35] We would hope so. Others might know that as a professor at a medical school, one of the things we have to do is raise grant money, right. Grants fund our research. So the school doesn’t give us the money for that. They support us, but we have to get the money from the government. My dad always says this should make getting grants easier for you. You wish it would be the case. I think the NIH has always had a commitment to funding virology, but there are other diseases that are really important, too. And so it’s really kind of the budget isn’t large enough for the research that we really need.

[00:13:09] And so I’ve heard from people in Congress and many senators are supportive of biomedical research and increasing funds, but there’s just not enough money to go around. I think that one of the biggest lessons we learned this year is funding basic science is important. So the technology that led to the mRNA vaccines came from basic science and a key discovery that was made in 2004-2005. And we didn’t realize how important that was? I don’t want to predict, but I imagine they’ll get a Nobel Prize for it. Actually, that would be my prediction.

[00:13:45] So basic science is important. All science is important. And fundamentally, we need to just increase our funding for all science. That’s my take on it. Hopefully a lot of people have realized the importance of funding basic science from this pandemic. So the other thing that I want to say about funding science is I think that this pandemic has really also shared with us the lack of a public health infrastructure in the United States. We used to have a strong public health infrastructure. But in this case, when a new virus came out, we should have known what to do. We should have had a plan and there really wasn’t.

[00:14:21] And that’s because things like epidemiology, your local county small town public health departments have been underfunded a lot and that’s over the last 10-15 years. And so I think you need to keep those things funded because every day you might not need them, but when you need them, you really need them. People like to listen to people in their communities rather than the federal government. And so funding these kind of pandemic preparedness at the local level I also think is really important.

Grace: [00:14:49] Yeah. So I was a public health major in college. And one of the things I was super surprised to find was that if there was some sort of like Ebola outbreak in a particular place, the people in charge would be the local public health officials. Like it wouldn’t be the federal government coming in. It’s not like the FBI takes over a criminal case or something. It’s those local governments leading that response. So, yeah, I would have to definitely agree with you that investing in those infrastructures is very important. So if you were to put yourself in the shoes of the people who are deciding where funding goes, if you had maybe a million dollars to give, what sorts of research efforts would you be most excited to invest in?

Stacy: [00:15:30] So, first of all, I would say that a million dollars is enough to fund three people for five years. So we actually need to go like one hundred million dollars. But I think one of the biggest problems actually in our biomedical scientific enterprise is the lack of diversity in science. And so this means black and brown or people of color really need to be better funded. We know that there is data that the grant peer review process is actually quite biased in a number of different ways. And we also know that diverse teams are more successful.

[00:16:06] And so not only from an ethical point of view, but from actually how are we going to solve problems as a country, as a world? How do we fight the next pandemic? We need people from every walk of life to see scientists that look like them, to want to become scientists and to bring their creativity, their energy and their communities to the table. And so if I had a lot of money, I would use all of the existing research that has been done by a lot of my colleagues around the country into this space and change policy to fund black and brown scientists.

Grace: [00:16:39] What sorts of policies would you change? Would it be maybe replacing the people who are deciding where the money goes or would it be educating them or what kinds of changes are needed to drive that increase in diversity?

Stacy: [00:16:54] You know, this is not my area of expertise, so I’m not going to presume to know the right answers. But I think there has to be a real commitment from the NIH to not just talk about changing these problems, but to do bold solutions. And so they have advisory committees with the right people on them who can help them make these decisions. I think the peer reviewers of the grants are people like me who are trained in such a way to value certain things in the grant review process that will disadvantage certain groups.

[00:17:24] We all know this. So it needs to be led by people on the review panel saying, like, hey, those words that you use, they’re actually not okay. That’s not what we’re looking for, we are looking for good science. And that’s kind of risky. You could also just commit to funding more people of color. Everyone will say like, oh, well, we want the science to be a certain quality. Trust me, the quality is good. It’s not a problem of that. It’s about the structures in place are biased in judging what is good science or not good science. And so I think that’s a problem.

[00:17:58] At an institutional level, we need to hire more people of color. But not only do we need to hire them, we need to make them feel supportive, give them mentoring, treat them as colleagues, not as people who can make our quota of having more people in the pictures. And so access to mentoring, not overburdening them with service and thinking about our promotion criteria. So someone like me, I just got tenure. So I’m now an associate professor, but I went through that process. That whole process is biased and favors certain things that will be disadvantaged by other people who do not fit into the mold of what a scientist or what publishing should look like. Many of us know what’s wrong. It’s pretty bold move that to change that system. And I think that’s what really needs to happen.

Grace: [00:18:48] Do you think that sort of change would take a long time or do you think it would need to be something like kind of like what we saw in the last year with the Black Lives Matter movement, where it’s just like intense social support moving towards a single goal?

Stacy: [00:19:01] Yeah. So I think some things are easy and some things are harder. You’re not going to change everyone’s mind. That’s not why you do it right. I think those kinds of things could be harder. But there are easy things you could do. For example, when people are coming up for tenure, have them talk about their commitment to diversity, equity and inclusion. Make white people do some of that work, too. That’s like something that actually costs zero money. It takes time, but I think that we should be giving that time. So, yes, mentoring programs, that don’t actually cost that much money.

[00:19:32] Fundamentally, I think we should just hire more black people or brown people as assistant professors, but then also support them. And so that means every institution needs to take a hard look at how they have supported people like this. What do they do to help them get tenure? Because processes like promotion or even if you’re a PhD student, graduation, those are all biased and they’re geared towards a white male demographic, which is kind of historically how it was. But that doesn’t mean that it’s right and that doesn’t mean that we should be still be doing that.

Grace: [00:20:05] So kind of changing gears a little bit. I’d like to get into what inspired you to become a scientist. And when you were growing up, were you always really interested in science?

Stacy: [00:20:16] So when I was a child, I was always interested in how things work. I remember my mom had a book, How Things Work. I just was like that’s cool. I want to learn a little bit more about that. I always hated science class in school because it just seemed really boring and like memorization, so I actually never wanted to be a scientist per se from a young age, but I was curious about how things worked. I have a very defining moment, which is when I don’t know what year it came out, but it has to do with the movie Jurassic Park.

[00:20:48] I think I was probably a junior in high school somewhere around that time. I remember riding the car with my dad and my dad liked to listen to NPR. And NPR was playing a show about the movie Jurassic Park. So I hadn’t read the book yet, but I was listening to this podcast, not podcasts, this radio show about Jurassic Park. And they were talking about the whole premise of Jurassic Park is that these people, we can recreate dinosaurs from fossilized mosquitoes. You could extract the DNA–because some mosquito bit the dinosaur–pull out the dinosaur DNA and then do some kind of magic, basically to make a dinosaur.

[00:21:32] Well, when I heard about the science behind that, there must have been some scientists talking about it, I just thought that was the coolest thing that I’d ever heard. You could go from the DNA to making a whole animal or an organism. So I went back to my high school teacher and I asked him about DNA. I guess I missed that day in biology class because I was like I want to study DNA. What is that field called? And he said biochemistry, chapter twenty four. I opened the book and it had a picture of DNA. And I was like, okay I’m going to be a biochemistry major. It really was as simple as that.

[00:22:05] And probably as naive as that, to be honest. From then on that’s what I wanted to do. I pretty much didn’t know what that meant. I didn’t know what being a scientist would be like. One of my grandpa’s was a chemistry professor at a small school in Minnesota. So in theory, I should have understood what that meant. But I thought maybe I’ll do pre-med biochemistry. When I got into college, I realized I didn’t want to do pre-med because I was really interested in the small little things like nucleic acids. And so I didn’t want to study bone or the body. I wanted to get right into those details. I’m like, how do they work? Like, how do molecules find each other? That sounds really cool.

[00:22:45] So that was why I wanted to be a scientist. The reason why I wanted to be a virologist is not as clear to me. Although I do know that my first or second year in college, I’m from Minnesota. I went to a small liberal arts college there, called this Gustavus Adolphus College. And every year at Gustavus, they hold something called the Nobel Conference. Gustavus is a Swedish Lutheran college. I’m not Swedish, but that’s the school I went to. And so they have an affiliation with the Nobel Foundation in Sweden that helps them organize a really large conference for a very small liberal arts college in middle-of-nowhere, Minnesota.

[00:23:22] And this particular conference was on viruses. So they brought in all these world leading virologists to the conference to talk about virology. And I’m assuming that that’s what really piqued my interest. Because after that point, I knew I wanted to be a virologist. And before that, I don’t have any memory of that. So why did I want to be a virologist? It was cool to me that viruses can go on to cells, change cell biology. And not only help you learn about the viruses, but also help you learn about the cells that they infect. So a lot of key discoveries in biology had been made by using viruses as tools to study this biology. I thought that was really cool and that’s why I wanted to do it.

Grace: [00:24:02] Yeah, I totally get that. Viruses are just little machines and are very interesting. So when you were pursuing virology, were there any moments where you were like, this isn’t at all what I expected? Or what were your expectations versus reality when it came to being a scientist?

Stacy: [00:24:21] So I did my Ph.D. at Yale. And when I was a graduate student at Yale, I, like many graduate students, struggled at some level. Mostly because I felt like I wasn’t good enough to be a scientist or to be a professor. From a young age I actually always wanted to be a teacher, and so being a professor to me seemed like the career path that I would want to choose. And I remember going to seminars or going to research and progress talks about other graduate students and thinking, wow, their science is so much cooler than mine. They are so much smarter than I am.

[00:24:59] And then you hear all about how like it’s really hard to get a grant. It’s really hard to be a professor. And I thought, well, you know, I’m not smarter than these five people I know. So I’ll never be a professor. I’ll never get the grant. And so that was really disheartening. You could do all this work and then try to get a job as a professor, you would never get one. And that seemed like a little too risky for me. It made sense to finish the PhD, and for all students out there, I would say if you can stick it out, it makes sense to stick it out.

[00:25:29] There are obviously cases where that doesn’t make sense. And so I’m not going to speak to all situations, but having a PhD opens a lot of doors. And when I thought about what I really wanted to do, I thought that being a virus hunter sounds cool. I want to travel the world and do that. And so I was already working on my application to try to get into the Johns Hopkins public health program for people with a PhD And then maybe work for the CDC or the WHO as a virus hunter. So I was putting that application together. Now I’m really glad I didn’t did that because it actually is like a lot less glamorous than you see it in the movies.

[00:26:04] I was talking to some of my committee members and then to my graduate advisor who really convinced me that I had what it takes to be a scientist and to be a professor, which is something I hadn’t seen in myself. I just thought I was so different than all the people I had seen in a science professors. I was so different than my classmates who were like, “I want to be a PI.” I don’t want to do that. I don’t look like you. I don’t do the same things you do. It didn’t seem like it was something that I could do or that I could be part of that community.

[00:26:38] Until my graduate advisor really stepped up and said, “Stacy, you have what it takes.” And also one of my committee members and so I’ll name them here. So Daniel DiMaio at Yale was my PhD advisor, and he was the one who really believed in me, as well as one of my committee members, Peter Lengyel, who’s now passed away. And so the two of them said, try postdocs, see if you like it, do one year. And if you don’t like it, I’ll write you a letter wherever you want. But we think you have what it takes. Actually after that it was very clear to me that I wanted to go and do a postdoc and then keep going on in science on the academic track.

[00:27:14] Because actually I think science is cool. I’m curious. I like thinking about big problems. I still didn’t know if I was creative enough to be like a cool, innovative scientist. But one thing that I say to all students is that by about year four of my postdoc after my PhD, I realized that I was creative. I had a lot of good ideas and so, you know, college student, first year graduate student, first year postdoc: you don’t have to know if you have what it takes. You just need to be curious and want to try. You don’t have all the information, I think, to make the decision to pull yourself out of the running.

[00:27:48] Now, if you don’t want to do that, that’s cool. But if you think you might want to do that, then try to find a mentor who can really talk to you about what the whole process was like for them. Because a lot of people have a story somewhat similar to mine, especially with women. We often have very different stories, unlike the kind of classic path. Everyone who thinks that they might want to do it owes it to themselves to try to find a mentor who can help encourage them along the way.

Grace: [00:28:13] So what do you think are the best qualities of a mentor? How can mentors better support their students to instil confidence in them or maybe a realistic view of themselves?

Stacy: [00:28:25] So I think if you’re a trainee, you should not think about only having one mentor but having multiple mentors. And these mentors will help you in all aspects of your career. And ideally you want to feel comfortable enough talking to them and being honest with them because they can only help you if they know what’s going on inside that brain of yours. And so you might have mentors that help you. For example, for me, that could be a mentor who looks like me. So that can be helpful. It can be helpful to have mentor who’s in your research area that you’re interested in.

[00:28:59] It can also be important to have a mentor that has a career like you have. So those are all things that one can look for in what we might call a mentoring team. Now things that mentors can do to help trainees as well–I actually just took six hours of mentor training and we learned a lot of thing. But I would say the biggest problem between a mentor and a mentee is ineffective communication. And so as a mentor understanding, that communicating with your mentee is important, the words that you use matter, and that our job as a mentor is not to get them to be you, but to help them assess their skills and figure out what they want to do based on their skills. And so I think those are effective mentors.

[00:29:43] And for mentees I mean, be open, be able to communicate and also tell your mentor what you need. As a mentor I really want my mentees or people that I interact with, even in class, to succeed. But I can’t read your mind. So it’s an important thing for the mentees to tell their mentor how they’re feeling. And for mentors to learn skills, to bring out the things that they need to help them be effective mentors.

Grace: [00:30:08] So you’ve been at a few different universities. So you’ve been at a small liberal arts college. You went to Yale for graduate school and then you moved to Duke. So what are some of the biggest differences that you’ve seen in the different cultures between those universities and some of the things that you like about being a Duke?

Stacy: [00:30:25] I think Duke and Yale are very similar in a lot of respects, to be quite honest. I did a postdoc at University of Washington in Seattle and that was very different as a public school. So that’s bigger, less personalized. And then a big difference between Duke and Yale is that Yale is a much older institution than Duke is. So fundamentally, there are some differences related to that. But I like being at Duke. And one of the reasons I also liked being at Yale is that they’re a little bit smaller. And so this is also related to kind of my undergrad, which was small liberal arts college.

[00:31:00] It’s so much easier, I think as a faculty and probably as a student to find different types of communities and interface beyond just your department into like the whole community. So I could go to like an English lecture just because I thought that was interesting. So I really like this kind of smaller aspect. What I also really like about Duke is how collaborative and interdisciplinary it is. It is quite common for me to be talking to someone in the biochemistry department, the chemistry department, or immunology.

[00:31:35] And I think this is really exciting. When I first came to Duke eight years ago or something like that, there were actually a lot of new assistant professors that were hired at that time. And so as a newer professor, I had all these friends. I didn’t know that I would be friends with other professors, but I certainly am. And so that’s fun because we all go through the same career challenges. But then, like, inevitably we get to talking about science or some new technique. Then you can build like, real collaborations and do cool discoveries together.

[00:32:08] So I think at a place like Duke it’s pretty easy. The pandemic has changed a lot of that. So for the new assistant professors who started in the last year or so, this is going to be one of the big challenges, helping them find that community in the next couple of years as they kind of do what I already did.

Grace: [00:32:24] Do you think a lot of the remote aspects of doing work, like maybe working from home a couple of times a week will be maintained?

Stacy: [00:32:30] I mean, I think some of them well. For example, certain kinds of meetings are really easy to have remotely. Everyone’s really comfortable with that. Having these Zoom meetings with colleagues all across the country a few years ago, I mean people did it, but it wasn’t super popular. Now, I think it would be pretty easy to move school-wide things to Zoom fairly easily like a training of some kind. But I do think that the real personal connection or the things that happen when you’re getting coffee, the people you run into, who you just casually talk with, those things will still be important in the future.

[00:33:09] I think one other thing that the pandemic has really taught us is the importance of having structures to promote or support people who have children. You actually can’t work from home if you also have children at home for school. It’s just not possible. And so I think those kinds of challenges and how we support folks with children, you know, pre-tenure with their grants at the university level. I think universities really need to support these things because they have caused huge differences in people’s productivity. Some people’s productivity went way up, some people’s way down. I hope that all universities are taking a hard look at their finances and giving support to those folks who need it.

Grace: [00:33:50] So as we wrap up, I always like to ask the people who come on the podcast if they have advice for people who might be trying to walk in your career path. I know you’ve given a little bit here, but could you maybe say a few words to students, which there may be plenty now who have become interested in virology. What advice would you give to them as they go forward?

Stacy: [00:34:13] So I think from the beginning, I will tell you that there’s no one right way to be a scientist or to be a virologist. You don’t have to do it like I did it. You don’t have to do it like the person next to you. If you’re curious, just keep trying to go one step farther. Along the way, I think it’s really important to find people who will support you and who will be mentors for you. This was really hard for me when I was coming to this system. Certainly I had them, but I don’t think I used them as much as I do now. And I wish I had them my whole career because I think that would have been helpful.

[00:34:47] I would say, just be curious. Go do what is interesting to you. You don’t have to try to predict what will be trendy or popular or important. If you like the science, you’ll find a way to make it important one day or you’ll leave, and so you want to do something that is cool to you and that can motivate you, because I think we all want to be happy in our jobs. And if you don’t love what you do, then you should get another job.

Grace: [00:35:14] Well, thank you so much for your time. Thank you for sharing your thoughts on virology and on scientific culture, if you will. Yeah. Thank you for coming on the podcast.

Stacy: [00:35:23] Thanks for having me, Grace.

The Bioinformatics CRO Podcast

Episode 37 with Jason Arnold

Jason Arnold, Technical Director of the Microbiome Core Facility at UNC Chapel Hill, describes methods of improving the scientific rigor of microbiota research and his experiences as a snake breeder.

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

You can listen onSpotify, Apple Podcasts, Google Podcasts, Amazon, and Pandora.

Jason is Technical Director of the Microbiome Core at UNC Chapel Hill. Aside from consulting on a variety of projects in the core facility, his research aims to determine how the intestinal microbiota influences aging.

Transcript of Episode 37: Jason Arnold

Coming soon…

The Bioinformatics CRO Podcast

Episode 36 with Bettina Hein

Bettina Hein, CEO and founder of juli, is a serial tech entrepreneur, using artificial intelligence to help people manage symptoms of chronic illness.

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

You can listen onSpotify, Apple Podcasts, Google Podcasts, Amazon, and Pandora.

Bettina is founder and CEO of juli, an AI based symptom tracker for people with chronic illness. A serial tech entrepreneur, she is a Young Global Leader at the World Economic Forum and was Massachusetts’ Immigrant Entrepreneur of the Year in 2018. 

Transcript of Episode 36: Bettina Hein

Coming soon…

The Bioinformatics CRO Podcast

Episode 35 with Bharath Ramsundar

Bharath Ramsundar, founder and CEO of Deep Forest Sciences, described many applications of artificial intelligence in biotech, society, and the military.

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

You can listen onSpotify, Apple Podcasts, Google Podcasts, Amazon, and Pandora.

Bharath is the founder and CEO of Deep Forest Sciences, which builds AI for deep technology applications, and is the lead developer of the DeepChem open source project. He has founded multiple companies and authored 2 books.

Transcript of Episode 35: Bharath Ramsundar

Coming soon…

The Bioinformatics CRO Podcast

Episode 34 with Saroja Voruganti

Saroja Voruganti, Associate Professor at UNC Chapel Hill, shares her passion for nutrition as she discusses the fields of nutrigenetics and nutrigenomics.

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

You can listen onSpotify, Apple Podcasts, Google Podcasts, Amazon, and Pandora.

Saroja is Associate Professor of Nutrition at the University of North Carolina, Chapel Hill, where her lab studies the interplay between nutritional and genetic factors influencing disease risk in ethnically diverse populations.

Transcript of Episode 34: Saroja Voruganti

Coming soon…

The Bioinformatics CRO Podcast

Episode 33 with Jon Chee

Jon Chee, co-founder and CEO of Excedr, shares his experience founding a life sciences equipment leasing company before the latest biotech boom.

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

You can listen onSpotify, Apple Podcasts, Google Podcasts, Amazon, and Pandora.

Jon is co-founder and CEO of Excedr. For the last decade he has been helping life science researchers reduce R&D costs through equipment leasing. Excedr’s founding was inspired by Jon’s experience working in a wet lab at UC Berkeley, where he observed high equipment costs impeding research efforts.

Transcript of Episode 33: Jon Chee

Coming soon…

The Bioinformatics CRO Podcast

Episode 32 with Ian Carroll

Ian Carroll, assistant professor of nutrition at the University of North Carolina, Chapel Hill, describes the relationship between the intestinal microbiota and eating disorders.

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

You can listen onSpotify, Apple Podcasts, Google Podcasts, Amazon, and Pandora.

Ian is assistant professor of nutrition at the University of North Carolina, Chapel Hill. His lab studies the mechanisms through which the intestinal microbiota influences gastrointestinal physiology, behavior, and weight regulation in eating disorders, especially anorexia nervosa.

Transcript of Episode 32: Ian Carroll

Coming soon…

The Bioinformatics CRO Podcast

Episode 31 with Mark Kotter

Mark Kotter, co-founder and CEO of Bit Bio, discusses the uses of reprogrammed human cells in research and drug development.

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

You can listen onSpotify, Apple Podcasts, Google Podcasts, Amazon, and Pandora.

Mark is co-founder and CEO of Bit Bio and neurosurgeon at the University of Cambridge. His team has developed a benchmark technology for the efficient and consistent production of human cells from stem cells for use in research, drug development, and cell therapy.

Transcript of Episode 31: Mark Kotter

Coming soon…