Focus In Sound

FOCUS In Sound #37: Jennifer Brophy

ERNIE: Welcome to FOCUS In Sound, the podcast series from the FOCUS newsletter published by the Burroughs Wellcome Fund.  I’m your host, science writer Ernie Hood.

In this edition of FOCUS In Sound, we welcome a young investigator who is pioneering in the field of plant tissue engineering—a remarkable emerging technology that just might eventually save the human race. Jennifer Brophy received one of the Burroughs Wellcome Fund’s Career Awards at the Scientific Interface, or CASI, in 2019. She is an Assistant Professor of Bioengineering at Stanford University, and is a Noyce Family Faculty Fellow and a Chan Zuckerburg Biohub Investigator. 

Jenn received her BS in bioengineering from the University of California, Berkeley in 2009 and her PhD in biological engineering from MIT in 2016. She did her postdoc work at Stanford, where she started looking at plants. Today in her lab, she and her colleagues are developing technologies that enable the genetic engineering of plants and their associated microbes with the goal of enabling innovation in agriculture for a sustainable future. 

Jenn Brophy, welcome to FOCUS In Sound!

JENN: Thank you, I’m happy to be here! 

ERNIE: To get us started, Jenn, why don’t you give us a quick overview of your field, which is known as synthetic biology?

JENN: Certainly. Synthetic biology can mean a lot of different things to different people. In my lab, we think of it as advanced genetic engineering, which is essentially applying the principles of engineering to biology in order to reprogram living cells or organisms to do something new. In our lab, that means changing the shapes of plants as they grow, but for different people they engineer organisms to do different things. 

ERNIE: I see. Building on what you just told us, I’d like to find out more about one of your major areas of research, which is called synthetic gene circuits. I know that it was the subject of one of your most important publications to date, which came out in Science last year. Please explain…

JENN: In that work, using synthetic genetic circuits to control gene expression patterns in multi-cellular organisms. This work is really borne out of the observation that gene expression patterns are important for development. In the 1980s—I’m going to do a little historical bit—in the 1980s, scientists discovered a gene in Drosophila called antennapedia that controls the formation of legs, and stunningly, if you express that gene in cells on the head of a fly, you can actually get it to produce legs where it would usually have antenna. Now that’s shocking, but it’s also really highly conserved across organisms. Where you express genes in the body affects the way it develops. And so we were interested in trying to control where in an organism we’re expressing genes in order to change its development. But it raised this question of how do you control gene expression across the body of a multi-cellular organism? So what people usually do when they want to pick out specific cells within a body to express a gene in is they look for a promoter, a region of DNA in that organism’s genome that usually drives expression in only those cells. And that’s great, it works well, but there are a limited of characterized promoters, characterized tissue-specific promoters, that have this capacity to control gene expression so precisely. And so we looked at that, and we were like, well, we can use synthetic genetic circuits to take a limited number of tissue-specific promoters and combine their activities in new ways in order to generate new patterns of gene expression. So the circuits that we built perform Boolean logic operations. They can take two different tissue-specific promoters, for example, and then say, okay, we only want to express our gene of interest where those promoters are both on, in cells where those promoters are both on. And using this type of Boolean logic, we’re able to generate new patterns of gene expression, which we then use to control development, and we demonstrate in this paper that a combination if tissue-specific control and control over gene expression levels allow us to tune a single aspect of a plant’s root system. We can change how many root branches the plant makes, and that changes that we made don’t affect any other aspect of the plant. So it’s kind of allowing us to do a little bit of design of the structure of the organism. 

ERNIE: Jenn, it all sounds kind of mundane and esoteric until we get to the unbelievable implications of your work. Can you give us that incredibly exciting outlook?

JENN: Yeah, we’re excited about controlling development in plants, controlling the size and shape of plants, because of how important the structure and the shape of the plant is for survival in a challenging environment. So unlike animals, plants can’t run away when conditions get bad, right. If it’s hot, you or I can go find shade to stand in. But a plant just sits there in the sun and takes it. And the shape and angle of its leaves will affect its susceptibility to heat stress, its photosynthetic efficiency. The shape of its root system will affect its ability to acquire water when there is drought. And as climate change advances, these environmental stresses that a plant it expected to endure will increase. And what we want to do is have the capacity to introduce changes in the shapes and sizes of plants that should make them more resilient to environmental stress. But what we don’t want to do is change the aspects of the plants that we like, right? And so this control over gene expression, it’s important for being able to modify one part of a plant without modifying other parts. So we get the best of both worlds. 

ERNIE: That’s very cool. Of course people have been bioengineering plants for a very long time…what is it about this work that represents a major leap forward?

JENN: It’s the specificity. Most of the bioengineered plants we have, in fact all of the ones that are on the market today, they express a single gene in every tissue within the plant throughout the plant’s entire life. And so that works well for getting things like pest resistance, where if an insect bites the plant, you want it to be resistant and producing something that wards off the insect all the time. But for changes in structure, you cannot express a gene throughout the entire plant throughout its whole life. Imagine if you had done the same thing in that fly example, you’d have antenna growing out of every cell in the fly. That’s not a functional organism, so to me, the type of changes that we want to make to improve resilience, you need this precise expression control. 

ERNIE: I understand that you’re also working on genetically engineering soil bacteria in the plants’ ecospheres. Tell us about that aspect of your research…

JENN: Yeah, so the bacteria research actually predates plant research for me personally. I love microorganisms.  I think they are really fascinating, and the way that they can influence health of an ecosystem, health of a host, there is really fascinating. And when I was a graduate student I got interested in trying to make probiotics for plants, and trying to engineer them to support plant growth. But what I realized while I was doing it was that a lot of engineered soil bacteria especially don’t do that well, and when they are put out in the environment, because they are at a fitness disadvantage and the environmental conditions fluctuate so much, that they can easily get lost and not be able to help the plant much. So what we’re trying to do now is sort of engineer both sides, the plant and the microbes, so that the two of them kind of help each other along. The plant maybe provides some things that help the microbes survive, and the microbes then return the favor when conditions are less favorable for the plant. So most of that stuff in my lab is at a really early stage, so we don’t have a ton to share about it, I guess. But it’s an area that we’re interested in. I love kind of having all of these different organisms growing in the lab. 

ERNIE: So it really becomes a very symbiotic relationship, then, right?

JENN: Yeah, it’s difficult, I mean we certainly don’t ever grow plants in the field without microbes, right, they’re non-sterile environments, and the interactions between the two can influence how fit either one are. There are some super-famous examples of plant-microbe interactions, like the bacteria that form nodules on the roots of some legumes, like some bean plants, to help fix atmospheric nitrogen. So they fix nitrogen and then gives the plant this essential element for growth, and the plant in return gives the bacteria sugars that it needs to survive. Those are interactions that people would love to better understand and to introduce into more of our food crop varieties. But it’s just one way in which the two play together. They’re important in a bunch of ways. 

ERNIE: Jenn, I’d like to turn our conversation now to a dialogue that you and some of your colleagues addressed directly in your July 2023 publication in PLOS Biology, and that of course is the issue of genetically modified plants, which have become so controversial in recent years. In the PLOS publication, you make very compelling arguments for the place of synthetic biology and plant genetic modification to create climate-resilient plants and be vitally important and effective stalwarts in resisting the devastating impacts of climate change. Would you share some of your thoughts on that?

JENN: Yeah. Here I want to emphasize just how challenging it might be to make climate-resilient crops. We have seen a lot of differences across the globe in regulations on transgenic plants, some of which allow for no modifications to be made at all, and some of which are more amenable to small modifications to the plant’s genome being made by tools like CRISPR or TALENs, basically gene editing to be done. But we really think that we should be able to bring to bear all of our tools and creating climate-resilient plants to ensure that we do have agricultural and food stability into the future, and we think that having regulations that facilitate innovation in that space are going to be really important, right? You see already how the regulations shape what seed companies and researchers go after in terms of traits and modifications, but if we were to more fully embrace all of the different types of modifications that we could make, then I think we would have a better arsenal at our disposal for making sure these agricultural systems are really resilient. So in this piece we were really just trying to put forth an argument that changes in regulation, which are also tied in to how people feel about genetically modified plants, are going to be important for actually realizing or producing these resilient crop varieties, and that we would really like to see advancement in that space. 

ERNIE: It sounds like the debate may be really subject to change as the pressures grow.

JENN: Yes, I think that that is entirely possible. It just would be nice to not be in a completely reactionary position, where we are faced with threats that are so urgent that we’re reacting to them by changing regulations, and instead being a little bit more forward looking and thinking like, okay, we can see that these things are likely going to be a problem in the future, like let’s start facilitating the development of the technologies that will get us there now. 

ERNIE: Jenn, as we’ve certainly seen this year of 2023, climate change is no longer on the horizon, it’s happening now and likely to increase in the near future, with huge planetary impacts that we’ve already started seeing. I know you’re working hard to do your bit, but in your estimation are mitigating scientific advances happening fast enough? Are you optimistic at this point? 

JENN: I’m going to have to be optimistic about it just to get through the day-to-day. I have small children, I have to be optimistic about their future, too. But I think we could certainly see more scientific advancement happening. Where I am more disappointed is actually not in the scientific advances but in the politics around all of it. I think there are many things that we could be doing now with the technologies that we have that we are not doing, which would have an outsized impact on the climate. And relying on some magic science silver bullet to fix the environment to fortify us against climate change is kind of silly, and we should really be doing more than just relying on new technological achievements in order to address some of these issues. That’s not what everybody wants to hear, but I do think that those things go hand in hand. You can develop the new technology too, but if there’s not incentives in place for people to switch over to use it, then it won’t matter. 

ERNIE: So Jenn, where is your research headed from here?

JENN: It’s growing, it’s growing, no pun intended, in a bunch of exciting ways. We’re trying to move some of the circuit technologies that we have established in the model plant Arabidopsis into crop varieties. We’re trying to apply it to engineer other traits aside from just this root branching trait, which is what we showed in the Science paper that we talked about earlier. We’re starting up some of the microbe-plant interaction stuff, and we’re really excited about all of the different ways that we are hoping to be able to manipulate plants and modify their growth. It’s been fun over the last couple of years as my lab has started to grow to see there being new plant varieties growing, to watch the growth room spill out and stuff, and we’re really excited about just all of it.

ERNIE: Last but not least, Jenn, I always like to conclude these chats by asking what the support from the Burroughs Wellcome Fund has meant to you, both personally and professionally… 

JENN: The Burroughs Wellcome Fund support has been amazing. It came at a time in my career when we had ideas about using synthetic genetic circuits to make these types of very precise gene expression control elements, and yet very little proof that it was going to work, and Burroughs Wellcome Fund, unlike some other places, were really willing to take a risk on that, and I think it’s paid off really well. And it just helped me gain confidence that we were going to go in a direction that was impactful, that people cared about, and yeah, I couldn’t be more grateful for it. 

ERNIE: Jenn, it’s been a great conversation. I’ve certainly learned a lot, and wish you the best of luck in your ongoing research. Thanks for joining us on FOCUS In Sound.

JENN: Awesome! Thank you so much for having me, it’s been a pleasure to be here. 

ERNIE: We hope you’ve enjoyed the program, and will join us again next time. This is Ernie Hood. Thanks for listening!

FOCUS In Sound #36: Leenoy Meshulam 

Octopus during active sleep video:

Welcome to FOCUS In Sound, the podcast series from the FOCUS newsletter published by the Burroughs Wellcome Fund.  I’m your host, science writer Ernie Hood.

In this edition of FOCUS In Sound, we get to know a young researcher who in 2022 was the recipient of a Burroughs Wellcome Fund CASI award, the Career Awards at the Scientific Interface. Those awards recognize outstanding scientists who have made significant contributions at the interface of biology and quantitative sciences, bridging the gap between disciplines, and fostering innovation. It’s a five-year grant totaling $500,000.

Leenoy Meshulam is a theoretical physicist who is also interested in biological phenomena, especially nervous systems and the brain. She explores the interface between physics and neuroscience. She received her PhD from Princeton University, after completing her master’s degree in physics and biology at Tel Aviv University. She is now a Swartz postdoctoral fellow at the University of Washington in Seattle. 

Leenoy’s research endeavors have already taken her in some fascinating directions, which we will hear all about, including a remarkable recent publication about the sleeping habits of octopuses.

Leenoy Meshulam, welcome to FOCUS In Sound!

LEENOY: Hi Ernie. It’s very nice to be here.

ERNIE: Let’s start with your latest accomplishment as a co-author of a paper in the journal Nature called “Wake-like skin patterning and neural activity during octopus sleep.” Tell us about the overall findings…

LEENOY: So this paper concentrates on a main finding where we saw that the octopus, much like in other animals, actually has two stages of sleep. So we managed to prove that every about hour the octopus goes into a different kind of stage of sleep—an active sleep bout, where similarly to REM sleep for humans, for example, the type of brain waves and the neural activity changes, and this is accompanied by a lot of color and pattern changes on the skin of the octopus while the octopus is still asleep. And so the way the cycle looks is, we have about an hour of sleep that is not the active part, and then a few minutes bout kind of like REM, with lots of color changes on the skin, different kind of neural activity that accompanies it, and then back to the stage that is most of the sleep. Something to keep in mind is that this is the first time that neural activity was recorded in this way in the brain of an octopus. So this is a sleeping octopus we managed to put a Neuropixel in, which means that there is an electrode inside the brain of the octopus that’s, we’re able to filter brainwaves out of to see what the signals look like. Also to see spikes in the brain of the octopus. And we can really see the activity of the brain while this is happening. So it’s both the underlying activity of sleep and the behavioral aspect of the two stages of sleep, and very high-resolution filming of the pattern changes on the skin of the octopus. The skin of the octopus is normally a system that we’re looking at for things like the camouflage of the octopus, right. This is why it has the ability to change so much color to have these coordinated, beautiful patterns that look like the coral reef that it is trying to match behind it. It also has texture changes there. And we just didn’t know before that this happens during the sleep of the octopus. So there are just these bouts of color changes that happen during sleep. 

ERNIE: So you were really able to correlate the visual and the brain phenomena?

LEENOY: Exactly. So this is the underlying neural activity to this active sleep bout that makes it so interesting, because we can actually look at what is happening in the brain and show that this is really sleep. You can really see when you’re looking, if you look at the plotting in the paper, you can see the immediate, sharp transition into active sleep that is change in the neural activity, and if you’re looking at the brightness of the color of the body of the octopus, you can immediately see a drop, because it starts having color instead of being transparent. So the transition is immediate and is completely synchronized. 

ERNIE: Just so everyone is aware, we will post a link to video of the sleeping octopus along with this podcast. It’s well worth seeing! Leenoy, I understand that these findings point to the idea of convergent evolution. Would you elaborate?

LEENOY: There are multiple elements of the system of the octopus that are similar to what we see in other animals. And because the cephalopods, which is the family the octopus is part of, so that’s cuttlefish, octopus, and squid—these are the cephalopods—the convergence in the evolutionary tree from us, for example, we’re talking 600 million years ago. That is around the time that on earth we moved from single cellular organisms to multi-cellular ones. It’s a very, very long time ago. And yet, there are a lot of parallels. So for example, the visual system, the eye. The octopus has a camera-like eye, much like ours. It has some things that are different, and some things that are very much the same, the basic structure of camera-like. And with the sleep, we didn’t know if this is a system that is similar to ours or not. We didn’t know that they have two stages. Humans definitely have two-stage sleep that is very well researched. We know that there is offline learning that without which we can’t actually make progress in learning. It is incredibly important to have rest periods, like any person who tried to play an instrument or tried to juggle or tried to learn anything, motor or not, knows, right, without rest, without sleep, both of these things, there are no leaps in the learning. You can only get so far. And so that two-stage sleep is something that is incredibly important, and we know from human performance and from other animals. The fact that the octopus has two-stage sleep as well definitely points to thinking about this as, oh, we have two types of stages of neural activity, two types of the behavior during the sleep, and maybe this is also a system that is a parallel to our system, and the mechanism behind it might be the same. And because we are able to penetrate the system and measure the system in a very different way than what we do in humans, for example, the fact that we can actually see the output of the motor system on the skin, basically record the entire output, because we can film the entire octopus (definitely can’t record the entire brain of a sleeping human, right?) suggests that if there are parallels we might be able to get to them by researching this animal, where we have a different kind of access to a system that might be functioning in a similar way. 

ERNIE: So what was your role in the project?

LEENOY: Right, so maybe the most important thing to say is that I’m only the theorist on this project. The main thing that was happening here is that the incredibly talented and incredibly hard-working group of Sam Reiter in Okinawa, the Okinawa Institute of Technology, that’s a university that is in Japan, the Okinawa island, has amazing facilities of marine biology and marine neuroscience to be able to research things like this. This group concentrates on cephalopods, and fortunately for me, they have agreed to collaborate with me. So there are multiple people who are driving this project, who did all of the filming, all the looking inside the brain, all the imaging, all the recordings of the surgeries, and have lifted this incredible, incredible project with Sam, the PI of this group, who designed this all and looked into everything, and that’s just an amazing, amazing feat that they achieved. The collaboration with a theorist like me comes in with looking at both the short-term and the long-term goals of this project, designing the ideas to begin with, such that we have experiments and computational work and theory work, because you need all of these elements in order to create understanding of the system. Recording is not enough, computational models is not enough, you need to think through all the elements of the scientific endeavor. It is a very interdisciplinary science. We have physics inside it, and coding inside it, computer science and biology inside, and molecular things and imaging things, and that’s a lot of types of skills that had to come together in order to create this paper. So I am the part that is more methodical, that is more looking at computational things and thinking how to design those things to begin with, because we have a lot of thinking through the long-term goals of this project, and what is the kind of resolution we would like to measure something in. And it’s the collaboration, the multiple viewpoints, I think, that is the important part that is underlying this research. 

ERNIE: Leenoy, how did this collaboration with the Okinawa Institute of Science and Technology come to be?

LEENOY: Maybe something to mention is that I am coming from a background of physics. I am a physicist who’s interested in biological systems, and specifically in the nervous system and in the brain more than anything.  Like we said, the system of the octopus is a very special one, where you are able to actually record all of these pigment cells on the body, we call them chromatophores. These are specific pigment cells that change for the camouflage and also during sleep. There are about a 100,000 of them on even those small octopuses, that cover them. And you can measure their color and their size for a long time very well in very high resolution. That means that this is a system that for a person like me who is in interested in systems where we have a lot of small elements that are pretty similar to each other and interact to create a global pattern, something that is emerging for a global pattern, needs to be coordinated from a lot of small interacting elements, it’s the ideal system. My Ph.D. was on recordings in the hippocampus of mice, where you could even 2000 neurons that are simultaneously recorded, and you could definitely look at the kind of physics I’m talking about, which is looking at all 2000 and looking at the collective behavior of them, looking at the global patterns, looking at what emerges from a lot of interacting things together that individual ones could not carry on their own. And after this I thought, well, really what we would like is to be able to look at an entire system like this, and to be able to measure to the highest resolution each one of the small elements. And the octopus system, the cuttlefish system, this camouflage is something where we know the function really well and we can measure the underlying elements really well, and look at the entire system. Sam Reiter, who is the senior author and experimentalist on the paper that we’re talking about, had a beautiful science paper on the camouflage of cuttlefish. And after they published it, I read it, and I looked at it and thought, this is just the perfect system for doing the kind of theoretical work and the kind of computational analysis that I’ve been most interested in. And I contacted Sam, who said that he is starting a lab in Okinawa and he would love to collaborate, and I am grateful to this day. A very important element of our ability to collaborate was the fact that OIST, the university, has a Theory Visiting Fellows program that was incredibly helpful in me being able to visit and spend months in Japan in order to design this project with them, to help in whatever way I can, to my work with them, and to think through our future goals together. And so this program basically allows for residency of theorists, having big white boards and big blackboards around, to be able to come and discuss and interact with the institute, which has been incredibly insightful and really helpful to be close to the lab and to the data and to the octopuses and to the researchers who are doing this incredible work. 

ERNIE: Will the work on octopus sleep continue? And will you continue to be involved?

LEENOY: Absolutely. First of all, as long as Sam and his group allow me to be involved, I’d love to keep being involved. I’m feeling very fortunate that they do. In a very immediate way, we have the very next steps coming up, which is that there is more computationally heavy parts and theoretically heavy parts that are a different paper that we are going to eventually wrap up, that have to do with different kinds of calculations than the main finding that we’re seeing here. And then after this, we would love to be able to record from the octopus when it is also awake, not just when it is asleep. And I’m sure you can imagine that this comes with incredible technical challenges, but also this group is so good that I think they’re about to figure it out, so a lot of motion, right, being able to put an electrode, as a rigid thing, in a super-flexible animal that has no bones, that makes for a lot of noise artifacts. However, if you’re able to stabilize the system and to prevent some of the movements or have something that is more flexible in the recordings, then maybe you can have more neural recordings and you can do more and look at the awake octopus and the camouflage, and see how this affects what’s happening during sleep. Do they have any types of learning or effects from what has been their experience during their wake time to what they seem to be replaying on their skin during sleep time. I’m very much looking forward to that. 

ERNIE: We will certainly keep our eyes open for that (so to speak). I know that much of your previous work, Leenoy, has been on the theoretical side, so I have to ask, was this an especially fun project for you?

LEENOY: It’s a great question. It is an especially fun project, but I feel sometimes like all the projects seem to be especially fun in their own way. Octopuses are an especially fun system, maybe that’s the best way to say it. In a biological way, there are a lot of things about them [that] are very special, and not that many people work on them. So the kind of neural activity that you look at and the kind of challenges that you have to face and think about are very different. It is also incredibly fun when one has a very nice mathematical problem to solve, or when you’re looking at mice who play video games and you’re looking at their memory, right, which is an element from things that I did before. Or trying to make decision making, which is part of the projects that I’m having now. So I think every model system has its own kinds of fun. Octopuses are particularly fun in the sense that nobody knows anything about them, so you get to have just the best conversations. And maybe a really fun thing that happens specifically with octopuses is that the first basic questions of an audience when you give a talk or somebody engages on this topic are always incredibly interesting, because people would like to know how smart are they? What does their nervous system look like? Do they spike? Do the neurons, are they active in the same way that ours are? Is their consciousness the same? What can we expect from them? How do we think about the nervous system? Is it concentrated? Is it distributed? And so the questions are incredibly fun. Finding out these things that in other systems we have already figured out and in this system we are yet to find out is incredibly fun. Finding out what are the right questions to ask mathematically is particularly fun in this system and the thing we are finding most illuminating. And interacting all over these kind of new landscapes is very wonderful. This new advantage of technology that has progressed, that Sam’s group now have, like this high-resolution, the neuropixels and recordings in the brain, that’s all just new technology that is now allowing us to start looking into the system in the kind of rigor that we can do in other systems, and ask critical questions. And this is incredibly exciting. 

ERNIE: So Leenoy, let’s explore your research on the interface between physics and neuroscience. What is the relationship between the two, and how is it shedding new light on the principles of brain function? 

LEENOY: Thank you for asking this. I think the basic principle of the subfield of physics that I’m coming from, from statistical mechanics, and of brain function, are in a way very similar. So let’s think together about how a magnet works, for example. This is something we have the physics of very well figured out. A magnet is made of a lot of spins. Every spin can have a direction, can be up or down. But magnetism as a property is not a property of one spin. Only if you put all of them together, then you get a collective property, something that emerges in the system. A magnet, all of it together has magnetism, not one tiny element. This idea of a collective property is language and math that you can see immediately how it’s very attractive for the brain, because one neuron doesn’t have a function, cannot carry out, throw the ball, cannot underlie decision-making. It does not have any consciousness. But many neurons together have something magical happening. They are together able to coordinate complex patterns of activity that underlie all of the behavior we have, everything. And so, the idea that we can take this kind of physics, this kind of math, and think how to create this for the nervous system, I find very attractive. And this is also why I am working in this kind of interface, why I think eventually the entire field of physics of biology, and physics of life, that taking these kinds of concepts not as an application but as we are trying to create physics and trying to create concepts and trying to understand the principles of a whole new kind of system, of a biological system that is active and is changing and is dynamic and is a lot more complex than a magnet and has many functions, is going to give us some avenue to understand and to gain insight into both the mathematical principles that are underlying it, but also the function, because we definitely need new kinds of insights, right, we need new physics and new math and biology, because the brain is incredibly complex. We are still trying to figure out even very basic questions. I remember sometimes when I give outreach talks in schools to children, I start talking about the brain, and the very first smart girl who raises her hand asks, “How does memory work?” And the first thing that happens is I need to say, “Well, we’re not quite sure yet!” And it is amazing, because when you ask a very basic question in physics, it seems like we have figured out some of the kind of childlike questions, or at least many of them. And in neuroscience, we’re still yet to figure out even the childlike questions, and there is something very exciting about this. And I’m hoping that the interdisciplinary approach is going to help us out in actually being able to figure this out. 

ERNIE: It seems like the neural networking in the human brain is similar to what’s going on with artificial intelligence. Is that accurate?

LEENOY: The field of AI and artificial intelligence has made incredible strides in the past decade, the past two decades, I would say. Principles that were there since the eighties in the last ten years with a lot of computational power have just [made] incredible strides. There are a few things to keep in mind that are still different between the research of AI versus the research of the brain. So these things can definitely benefit each other, and have been benefiting each other a lot. In AI, the kind of basic units in the networks that we’re talking about, the very structure of the artificial neurons look very different than what is happening in the brain. There may be a few basic things that are very different. One is that the kind of connection in between the different layers, between the neurons, is one-directional a lot of the time, while in the brain we have a lot of what we call recurrent space, a lot of feedback that is happening. So it’s a different kind of processing. Another thing that is different is that we as humans, with our neural networks that are not artificial, are able to learn things from looking at them once and being able to extract patterns. The thing that remains a challenge for artificial networks, and that we know that for the brain is a very basic property, that we’ve yet to figure out how an artificial network can really do this well, to learn many things and to learn them fast. And maybe the last thing is that the artificial networks are something that you build and they come in with no evolutionary constraints that have designed them. You can build a lot of flexibility, a lot of degrees of freedom into them. The brain is under evolutionary constraints. There are rules of what you can and cannot do. And yet, it functions magnificently. And so, how do you create a system that can actually by design that is under evolutionary constraints in development get to be what the brain looks like? It is under compactness constraint, it is under the type of learning, the capacity constraint, it has its own kind of biological substrates that need to process, that need to be able to support all this. We are still a little far from being able to just take the research in AI and know that this is what is happening in the brain. That being said, a lot of things that we thought we would never be able to replicate that the brain can do, we can now do in AI, in a different way than what the brain does, but still in a way that is very impressive and is definitely very insightful as to how other systems can maybe implement these kinds of things with other kinds of constraints. 

ERNIE: Leenoy, I’m going to hit you now with a question you asked as the title of your presentation at the Okinawa Institute: “Can We Hope for Simplicity When Describing the Brain?” So, can we?

LEENOY: That remains a really good question. I think when I titled my talk this way, I was hoping that the audience was also going to engage with this. And maybe try to be also a little optimistic. Because part of the challenge of biological systems that are that complex, like the brain, is that it really seems like there is a lot of devil in the details. A lot of exceptions, a lot of things that are very hard to find a rule for, a lot of details that remain incredibly important, and maybe we don’t have underlying principles. The worry is the person who tries to simplify then generalize, which are maybe the two big objectives of a theorist, definitely of a person who comes from a field like physics, where we have for very complex systems, the ability to write at least much of what’s happening in the system in simplified equations that actually give us a lot of the behavior of the system. The worry is that we won’t be able to do it, that it’s too complex or there is too much detail that is important that we’re not sure what to strip down and still retain the essence of the system. That is the biggest, biggest challenge of what researchers like me do. I am optimistic, because with the kind of modeling and the kind of research that we have been pursuing, you can definitely see that there are trends that you can write down simple equations and principles of and get a lot out of, and capture the essence of the system. And so specifically if we look at how to systematically simplify a system with inspiration that comes from statistical physics, concepts like normalization group, we can systematically simplify and still retain the essence of the system. So that makes me very optimistic. It doesn’t mean that we’ve managed to do this in every possible function of the brain, and it doesn’t mean that did it in every possible brain region, but we have hints, which mean that we might be able to get one day to underlying principles that when you ask a question, one can communicate within under two minutes of, how does that work? Instead of really, really complicated drawings. 

ERNIE: Leenoy, what has the CASI award meant to your career at this point and your ability to pursue your scientific interests?

LEENOY: The CASI award has been incredibly helpful to me. In a very honest way, I just want to say I’m so grateful, because as a postdoc, you are really trying to find your own way and your own ideas in order to, if you want to keep on going with an academic career, which I do, in order to know what your group, what your research group one day is going to pursue. What kind of ideas, where is your strength, where your curiosity lies most, after your Ph.D., after your main stage of training. And as one does this, I found that I got interested, for example, in the octopus system, because I thought, wow, this idea of trying to look at lots of coordinated elements that give something global, and look at the emergence, and use these kind of concepts, is incredibly attractive to me and I would like to dive deeper into this. And for this,, the ability to just look around and say, what is the best system for it, and be able to just go for it, because you know you have the back of a fellowship that will fund you to pursue your ideas. You will even tell them your crazy ideas, and instead of telling you, “Wow, that sounds like it’s never going to work,” they will fund you. I remember my interview, where they were like, “Okay, let’s try to do this.” It’s so refreshing and so, unlike some other interactions for scientific endeavors which sometimes maybe encourage you for more incrementalism, the CASI and the Burroughs Wellcome as a foundation, the entire vibe seemed to be, “Take all the courage you want, we are behind you.” Pursue any system you want, pursue multiple model systems in parallel to get inside the comparison between model organisms, which is what I would like to do. The nervous system is incredibly complex. “We’re with you on this, try to take all the physics you can, all the neuro you can, go wherever you need, go to Japan, we will support you.” It still feels like being part of a family that is so incredibly supportive of brave endeavors and of curiosities that might completely fail, but might succeed, and it gives such a calm to understanding that this family is going to be with you, and is encouraging you all the way through, and it is just a wonderful experience. 

ERNIE: Leenoy, you are doing tremendously important and fascinating work, and best of luck for continued success. Thanks for joining us on FOCUS In Sound.

LEENOY: Thank you so much, Ernie, it was really nice to be here. 

ERNIE: We hope you’ve enjoyed the program, and will join us again next time. This is Ernie Hood. Thanks for listening!

FOCUS In Sound #35: Michael Ferdig

Welcome to FOCUS In Sound, the podcast series from the FOCUS newsletter published by the Burroughs Wellcome Fund.  I’m your host, science writer Ernie Hood.

In this edition of FOCUS In Sound, we welcome a biomedical scientist who in 2022 was the Burroughs Wellcome Fund’s first Resident Faculty Scholar. Michael Ferdig is a Professor of Biological Sciences at the University of Notre Dame, where he has been on the faculty since 2001. He specializes in the genetics and genomics of drug resistance and virulence in the malaria parasite. Malaria is a parasitic infection transmitted by the Anopheles mosquito. Malaria drug resistance is an ongoing topic of major importance in global public health, where the disease is still a significant worldwide contributor to mortality, with nearly a half-million deaths annually.

Mike received his BS and MS degrees from the University of Nebraska-Lincoln, his PhD from the University of Wisconsin-Madison, where he also served a postdoctoral fellowship. He also did a postdoc at the National Institute of Allergy and Infectious Diseases from 1997 to 2001.

Michael Ferdig, welcome to FOCUS In Sound!

MIKE: Oh it’s a pleasure to be here, nice to meet you, Ernie.

ERNIE: Mike, there is so much for us to talk about, but I’d like to start with what brought you to the Burroughs Wellcome Fund to be its first Resident Faculty Scholar…

MIKE: Well, I love the question, because it makes me smile. I was sitting up there in South Bend, Indiana with the fall season approaching, and going into another teaching semester, and putting in another load of grants, trying to get them renewed. And I was in this mental place of, you know, getting to this place in my career where I’ve had plenty of success and things are going well, and I just felt like I was turning the crank and perpetuating myself, and looking around and realizing, in my business, in the business of academic research science, it tends to be what we do. We get to a career place where we almost are content to settle into this safe bubble of self-perpetuation. And I had almost a little bit of a panic about, oh no, is this it? And it happened to be at the same time I was noticing that—I was familiar with the Burroughs Wellcome Fund, just like we are out there as scientists—had just announced this Resident Faculty Scholar. And I thought, this is what I need to do. I need to step away. I had been 20 years at Notre Dame with no request for leave or what they call sabbatical sometimes, and I thought, I need a place where I’m not just going to go make more versions of me, I’m going to go try to find the next version of me, and sort of move into this later phase of my career, and hopefully do things a little more useful and interesting. So it was just kind of magic how it all fell together, I reached out. I had known Victoria McGovern at the Fund for years. She had long been an advocate for infectious disease research, and she said, “Oh yeah, by the way, we do have this fellowship, why don’t you look into it and see if it might fit?” So I applied, and a summertime later, there I was.

ERNIE: I know Mike it’s been quite a formative experience for you. Can you tell us a little bit more about some of your activities during the scholarship? Did you have a specific project that you worked on during the sabbatical?

MIKE: I did. As imagined in the first place, I do need to strengthen my program, basically I wanted to expand and extend my lab science. We’ve always been what they call bench scientists, experimentalists in the lab. But I work on malaria, which is an organism that infects people around the world and has caused devastating disease for millennia, and I really feel the need to move my work towards the field. So that kind of relevance and extending. But I’d also really noticed, I do a lot of teaching, a lot of moving toward more administrative roles, and I just noticed that this problem of needing to bust out of our bubble, out of our cocoon, was really pervasive across all the things I was working on. So I set up some aims. Aim One of my project was just very literally to take what we do in the lab and move it into a more field and clinical relevant place. Which is a pretty big, it’s a very different way of doing our workaday. And I knew down here in the Triangle, there are some really good researchers who do more clinical work in the malaria world, so I thought, a-ha, this would be a great chance to pull some of those people together, bring in some outside experts, the people I admire and respect, and sort of bring everybody together, and it just has been amazing how things fell into place. And then I had a little more aspirational goals, and one was getting more out of my immediate research focus into where is the field going, what is malaria, [what does] the future of malaria research look like? And these are more community oriented, open science, data sharing, resource sharing, beginning to anticipate how climate and the ecology of the disease. Mosquitoes transmit malaria, and they are super sensitive to whatever is happening in the environment. And to bring in that piece, so that was kind of the second part. And then finally, I’ve become fairly dismayed at how science through the last five to ten years is kind of getting a, its name isn’t as gold as it used to be, right? There’s a lot of science skepticism and a lot of missed opportunity for science to be a really positive and exciting voice. I think we’ve lost our way a little bit. We kind of have done this to ourselves, and I want to understand those factors. How can we do a better job? All the way that science in general at communicating ourselves and being effective.

Those were my three aims, and to different degrees, I was very successful on the first part, and some of the later ones I feel are still work in progress, but things I’ve become basically more excited about.

ERNIE: So what was it about the Burroughs Wellcome Fund atmosphere that you found to be inspiring? Did the location and the experience exceed your expectations?

MIKE: Literally when I was sitting there writing this proposal, it was, I have to get out of town and find the next version of me, and it really wasn’t, the Burroughs Wellcome Fund is, they’re smart enough to have these kinds of programs and appreciate there are people like me out there, even when I don’t realize it. But I had no idea what I was getting into, in terms of how wonderful the synergy or the magic that can happen when you literally for me moving south, moving and experiencing Durham is a great town for me, but the physical setting, the building of the Burroughs Wellcome Fund is, it’s peaceful and inspiring. It’s the lighting and the layout. So you go to work every day and this physical space just makes you feel like, hey, I can do some good things here! And then add to that the people. Brent is there to let you in the front door, and he’s proud of the building and knows all the nooks and crannies, and then you’ve got everybody lending their support. “Hey, are you getting what you need here? Are you comfortable here?” And then more on the inspirational level. I had a couple of colleagues there. You throw ideas around in the hallway, and you start to learn, I start to learn things and start to realize there’s just a really good flow of energy and information. And you know, then maybe the philosophy. Like I said, I knew about the Burroughs Wellcome Fund long ago. When I was a graduate student my advisor back in the day had gotten a grant from the Burroughs Wellcome Fund. And I knew that they were always kind of out of the box a little, pushing the envelope, finding that edge of science that’s not standard, the regular NIH-funded things, but pushing the boundaries. So I knew about generally the philosophy, but I think there’s been a freshening, even. So that’s always been true. Burroughs Wellcome is viewed in an honored role around across the science community. But then when I got there and started to hear some of Lou’s ideas as he’s taken over fairly recently and there’s a good energy post-COVID of a lot of bodies and bustle around the place. But they just really stand for I think the forward-looking. They appreciate certainly the power of ideas, where ideas tend to get hung up in the system of traditional funding and traditional models at academic institutions, and I think are just really finding ways to support up and coming careers, and yeah, that got me really excited to hear just a lot of the priorities and initiatives that really have been happening under Lou’s leadership. And so, right, to just walk into that in an unsuspecting way and have that filling my sail every day was really spectacular.

ERNIE: So Mike, how has the fellowship affected your thinking about science in general and your role in it?

MIKE: What I do has really been strengthened, like the workaday things related to my lab and malaria and how we want to make a big difference in the world. But it was just the freeing, the ability to be sitting there and not have the rat-a-tat-tat of the regular workday all around me, and all of the obligations you have as a regular faculty at Notre Dame. And then just sort of confidence that starts to develop. So you get a chance to be with your ideas, to share them with others and start to pull together people and have this sounding board situation, and you really start to think, “Hey, I’ve got some good ideas here that people are interested in, and maybe we can start implement some fresh ideas that would really help me do my job better.” But I think of it as, I’m a token, privileged, aging, white professor in the Midwest at an elite institution where you get the spotlight shined on you and say, “Oh great professor,” and you come to that realization that you could do a lot better. And that’s really what I feel. The fellowship is spilling into me being a better role model, not just for students and mentees but for other faculty. For me to be able to go to my dean and my chair and say, “Hey, we need to rethink some of the things we’re doing around here.” So to walk in with a fresh perspective and the confidence that you have after a fellowship like that. I’m really hoping it’s a lasting change. So I’m enjoying it a lot.

ERNIE: That’s great to hear. So how will you follow up on what you’ve accomplished and what you’ve learned in your term as Burroughs Wellcome Fund Resident Faculty Scholar?

MIKE: Most tangibly, so I’m the head of a called a P01 that’s a large NIH grant. It’s a program project grant that involves multiple institutions. And we were nearing the end of its, it had been funded for five years and I think we had plenty of successes to point to, so we decided to try to renew that. And so in these few months since I’ve been down in the Raleigh-Durham area, I came home and I put together a brand new, not just the same old way we were doing it. And a key part of this is, what I work on is drug-resistant malaria, and it’s beginning to spread through, certainly it’s now in East Africa, and [there are] indications that we’re starting to see the tip of the iceberg of a really horrible new level of drug resistance that’s going to undo what has been a couple of decades of progress against the disease. And so I just situated this new proposal to be focused entirely on what’s happening in Africa, and saying, “OK, fancy lab researchers, make your work relevant to what’s happening right now.” And so that has involved partnerships, so I’ve sort of learned through my UNC colleagues that I met while I was down here, and my Duke colleagues, what it’s really like to work in the field, the work in these clinical settings, how you start to build relationships and not just be that Western, Northern scientist that’s going to swoop in and save the day, but to be a true partner who’s there to work alongside people in the clinics and understand the immediate problems and needs. So literally, I would not have had any of this in my renewal proposal had it not been for the fellowship. And so, that’s a big part of it. It’s the connecting, the partnerships, the relationships that I think that really I learned about how to do while as part of my work down there.

But the other is on the communication side. So I feel like I have a lot of unfinished business, things that I started to explore and really Lou and the folks there have invited me to continue to show up and interact and share my ideas. So I call it Aim 4. My original proposal had three aims, and now all of the things that I learned while I was down there, I kind of want to do more, do an Aim 4. It’s kind of like, how do we as scientists get out of our own way? One is we use our success as a hiding place. We don’t really need to share and tell our stories as scientists, we don’t need to make science a human endeavor to the general public, because we’re just that smart and that important. I feel like we do this to ourselves, and that that plays very badly ultimately, that it doesn’t resonate with people, and that is how is science really making a difference? What is exciting about the problems that we feel confident we can solve? We need to be able to describe and explain what’s exciting about it. And there’s no doubt, and human nature is to sort of cheer and get on board and be enthused, but you have to share it in the right kind of way. And I feel like that Aim 4 is really where we haven’t done a good job. We’ve learned to be more like salespeople, convinced that what we’re doing is important, only talk about the good stuff, don’t make it an endeavor, a process, and a sport almost. You can have wins and losses when you’re trying to do science. And so you I have a colleague up at Notre Dame who works on scientific humility. It’s a philosophy basically, a humanity professor. And really what that means is just accurately assess yourself and your abilities. Don’t oversell what you’re not, but also celebrate what you are the best at, right? And so it’s just this kind of a pervasive honesty that I think we need in the way we communicate our work. And this trickles up if department chairs and deans appreciate that. I think we can do a better job with our mechanisms for training and promoting and those kind of things. But also it trickles down. I remember as a brand new PhD postdoc looking for a first faculty job, you’re full of big ideas and you’re sort of brave because you have to be, you’re on the survival mentality, and you’re going to make it. And that sort of goes away. I think we almost teach that out of young scientists, or we beat it out of them because they have to jump through certain hoops or follow certain rules of the road. And I feel like with fairly subtle and modest, we’re not talking dramatic things, we’re just talking about slight shifts in how we go about communicating and talking about and rewarding and incentivizing science at the very local level. And so I really do think some of these things I’m very excited to dig a little deeper, make sure I know what I’m saying, and then do things.

ERNIE: Mike, those sound like terrific ideas. I would like to spend a little bit of time on the science now…As you mentioned earlier, you specialize in working on overcoming drug resistance in the malaria parasite, which has long been a quite vexing problem and challenging. As we speak here in mid-2023, where do we stand in terms of conquering anti-malarial drug resistance?

MIKE: You’re right, I’m the one that’s saying, let’s tell our story better. Conquering, of course, we’re coming to learn is we’re going to have to use a different word. Something that’s been around as long as the malaria parasite and even now we’re hearing of actually naturally transmitted malaria in the U.S. this year for the first time in 20 years. You know, it’s a beautiful beast. It evolves and it does amazing biological things, and it’s very hard to just stop in its tracks. But, as science does, incrementally, we get better all the time. Fewer and fewer people are dying of malaria. We’re quicker to see emergent new forms of drug-resistant malaria. We are not as far behind the curve to come up with solutions as we see emergent. And so it’s really just sort of shifting the needle, and I think part of it is changing that mentality that we’re just going to conquer this thing. And much more kind of honor it as a beautiful beast that it is, and yet we can get ahead of it. We’re going to use its wiles against itself as we understand how it evolves drug resistance. As we understand how we can intervene with the spread of new forms of resistance. And a lot of that is just seeing it as happens, as opposed to retrospectively working out why we failed to control it. So you just want to slowly shift until you’re keeping the pace with, and maybe eventually anticipating how these new versions are going to spread at the end, getting out ahead of it.

ERNIE: Tell us about your latest collaborative publication in Nature Microbiology, which implicates a second gene in resistance to the malaria drug chloroquine. I understand that is a real breakthrough that flies in the face of existing conventional wisdom…

MIKE: A little bit about what I was just saying. We used to just chase, and we would chase after…so chloroquine really did put us on the brink of eradicating malaria. I think that’s when we first realized that it’s going to be a hard battle to win, but as far back as the 1960s there was even boasts that we would eventually eradicate malaria. And that was because chloroquine was an incredible drug that killed the parasite on the spot, that had low toxicity, it’s cheap, it’s stable, it’s easy to administer. You could literally imagine just dropping this out of airplanes the whole world over and, end of malaria, right? Until resistance emerged and spread quickly, to where for a while no chloroquine was used anywhere in the world and it was like completely no longer useful. And in that process, this was back in my days as a postdoc at NIH with Tom Wellems, there was amazing work to find a gene that was completely predictive of, and thus diagnostic for chloroquine resistance. Mind you this was after the chloroquine no longer worked. But we began to understand the basically underlying genetic mechanism of resistance. So on top of that, we’ve come to, and this is true of humans, now that they have sequenced the human genome, the idea would be, well, we’re going to sequence the genome and find all the genes that cause disease and then we’re going to cure the disease, right? Well the great lesson out of that was, oh my, it’s more complicated than that. There is not a one gene to one disease or one trait relationship. There are many, many genes sometimes, and the way they interact is really important. And so, yes, the paper you’re referring to, I just love how it’s come full circle. When I first started there was really just this one gene called pfcrt, chloroquine-resistant transporter, thought to be the cause of chloroquine resistance. And now we’ve found another gene that is basically a partner, and it’s a hidden partner that lurks in the background. It doesn’t, it’s not as easy to find for lots of technical reasons. But it turns out it was crucial in the original evolution of chloroquine resistance. That one gene can’t do it by itself, partly because when you make a new mutation in that gene, it doesn’t do its natural job very well. So it’s bad for the parasite. The parasite is unfit. But you need these secondary genes to fine tune, and make what would be like superbugs. So parasites are like bacteria or pathogen that is both drug resistant but also still a really good, virulent, growing, thriving organism. And so this second gene we found, it’s called amino acid transporter one (pfaat1), works in partnership with that what used to be the only gene we thought caused chloroquine resistance. So why does this matter? It teaches us how to think about and go look for new, emerging resistances. So this failure to artemisinin is what’s happening in Africa.  And there’s still very little we understand about this, all the partner genes that work to do that. And so this gives us a new viewfinder, a looking glass for how we go discover as it’s happening these new mechanisms. And so I’m super encouraged that this new paper will be a steppingstone to quickly getting ahead of this new form of resistance we’re seeing in Africa.

ERNIE: So Mike, where is your research headed from here?

MIKE: Well I do feel weirdly, I think, thanks to the Burroughs Wellcome Fund and my fellowship down there, that I’m at a kind of a fresh start. I really feel like a lot of our ideas can be re-energized with new things we know, new tools, these partnerships of working directly with the clinical sites in Africa. And so, yeah, I’m almost frantically re-tooling. I’m getting new bodies in the group who are very interested in the sort of immediacy of this problem and wanting to get involved. And so I think on the science front, I definitely want to implement some of these new things I’ve learned from these new partnerships. On the communication side, I want to continue to affiliate with Burroughs Wellcome, I want to, I guess something I am good at, so we have to not oversell ourselves but also accurately help assess. And I’m a good connector, bringing together faculty down here in the Triangle with the Burroughs Wellcome was something that I think went really well. I want to do that again, only on some of these topics more oriented to the science. The ways that we shoot ourselves in the foot and we need to do a better job of communicating what we do, and build into our administrative systems the smarter process of training and promoting young scientists. So I do want to convene a meeting or two, maybe down here at the Burroughs Wellcome Fund, in the coming year.

ERNIE: Generally speaking, Mike, do you think we will ever eradicate malaria, or at least significantly reduce its global public health impact?

MIKE: I think I have to say absolutely, partly because there’s already been, and you know this is a massive, concerted effort from multiple funding and worldwide there’s been amazing progress against malaria. And it has the irony of the dipping down sort of puts us, it relaxes us a little, and it also lowers overall awareness, even human immunity to the disease, and then tend to see these sort of frightening returns. And so I think learning to manage that cycle, and that’s a matter of acknowledging the things we pat ourselves on the back for what we’re accomplishing but recognize where we are falling short, and be ready for that. And so I think we’re going to get better and better at knowing that the next frightening situation is just around the corner, and being well situated for that, certainly with better understanding of what drug resistance looks like as it’s emerging, better understanding of factors that promote spread of these new, dangerous forms, and better communication. So if we are well-partnered with sites where these are happening in the immediate, day-to-day basis, then we’re going to be much better situated to act. So I think the answer is, I would be very hesitant to say we’re going to eradicate malaria, but I would definitely say we will continue to decrease the number of cases and the number of deaths and move much more quickly when hot spots emerge.

ERNIE: Mike, before we wrap things up, is there anything else that we haven’t touched on regarding your work or the science of malaria or your experience at Burroughs Wellcome Fund that you want to be sure that we include?

MIKE: I really want Burroughs Wellcome folks to know how meaningful this has been for me personally, but then to get a guy like me at this point in his career, it can actually have some real spin-off value. So it was inspiring, and I think if they appreciate that, then I think they’ll also maybe keep kind of going for some of these. I would like to think this has been a pretty good success, certainly for me personally and career-wise it’s been a massive success. But in terms of the kind of communication and ideas flying around, I think that’s also been a success. And so I just laud their recognition that this is a good niche for them to keep the ideas flying around, and I hope they’ll keep doing that.

ERNIE: It’s been a terrific conversation, Mike. Congratulations on your time as Resident Faculty Scholar at Burroughs Wellcome Fund, and best of luck in your important work on anti-malarial drug resistance. Thanks for joining us on FOCUS In Sound.

MIKE: It was a great pleasure, and thanks for having me.

ERNIE: We hope you’ve enjoyed the program, and will join us again next time. This is Ernie Hood. Thanks for listening!

FOCUS In Sound #34: Lisa Hara Levin

Welcome to FOCUS In Sound, the podcast series from the FOCUS newsletter published by the Burroughs Wellcome Fund.  I’m your host, science writer Ernie Hood.

In this edition of FOCUS In Sound, we meet a veterinarian who has become one of the leading voices in the movement to reduce, refine, or replace the use of animals in research and product development testing, also known as the 3Rs. As we will hear, she recently teamed up with Burroughs Wellcome Fund president Dr. Lou Muglia to publish a highly influential paper called Alternative Thinking about Animals in Research.

Lisa Hara Levin is a graduate of Cornell University, received her veterinary degree from the Cummings School of Veterinary Medicine at Tufts University, and completed her postdoctoral research training at the Johns Hopkins University School of Medicine. Her professional career has been spent in the animal protection and research environments, notably occupying positions as the Medical Director for New York City’s Animal Care Centers, and now as the Alternatives Director for Coridea, LLC, a premier biotechnology incubator based in New York.

Lisa Hara Levin, welcome to FOCUS In Sound!

LISA: Thanks, Ernie, I’m happy to be speaking with you.

ERNIE: Lisa, to get us started, tell us how you got interested in the cause of promoting alternatives to animal use in testing…

LISA: Oh that was a long time ago. I was a veterinary student working summers in a research lab at Johns Hopkins, and I was very fortunate to be mentored by a laboratory animal veterinarian having a great interest in animal welfare, so I started making my baby steps in the 3Rs, that’s the refinement, the reduction, the replacement of animals in research, and that’s a style that I carried with me through into my fellowship at Hopkins and later professional roles, where I was in the animal shelter setting, or I was doing research consultancy, and it’s served me very well. But your question did ask specifically about testing, and I want to make it clear that mentally, I place testing, research, and drug development all in the same what I call philosophical basket, so while maybe I started my career in research my field of vision has enlarged to include the other two areas.

ERNIE: Tell us how you and Dr. Muglia connected, and how did the paper come about?

LISA: I wanted to launch a project from a university, and I met him during that funding search. He thought the work I proposed was out of the box, and very happily for me, Burroughs Wellcome funded it. It did launch, set off from a different location, but the content remained the same. It was to have two roundtables with what I call the A-plus team from different groups having interest in the development, the regulatory approval, and the implementation of new approach methods. We also call them non-animal methods, or by the acronym NAMs in research, safety testing, and drug development. In terms of the paper, I’d been thinking a while about writing an article examining the NAMs and animal research question, and after the second roundtable was finished, I was scratching my head and said, you know, these conversations should have some place in the piece. So I spoke with Dr. Muglia, and he agreed to be my co-author.

ERNIE: Tell us a little bit more about the two roundtables that you mentioned…

LISA: I wanted to have the roundtables because to me there has been this needless argument between folks on one side who are endorsing animal use, and folks on another side, and it really is that polarizing at times—folks on the other side, who are in favor of NAMS. And in my view, I think this is entirely due to misunderstandings about each of their roles, in the past, the present, and what the predicted future may be for them in advancing science. So I invited members from the eight stakeholder groups that in my view are most closely associated with these areas, the development, again, the regulatory acceptance and the implementation of NAMs, and I wanted to seat them in one place and have some very relevant conversation. So they came, and who I mean by “they” are academics and industry who are working with NAMs, government regulators, government funders, venture capital, philanthropy, venture or otherwise, animal research advocacy, and animal protection. I won’t give you the names of those attending because that’s a confidentiality issue, but I can tell you and will tell you—there was a lot of magic that happened at these roundtables, and it was a beautiful thing to hear and to watch. I was really entirely my privilege to be part of those conversations. Everybody was so smart, so honest, so collegial.

ERNIE: What were your objectives for the roundtables?

LISA: If I look at several years back, and probably more than that, cause I’m an old lady, let’s say decades back, of observations about how stakeholders have problem-solved, they take these very siloed approaches. That’s not helpful, and my work recommends putting ideas and concerns out into the ether so that everyone has a chance to study that, and the roundtables let us do that. It was a nice beginning. We all went agreeably into a deep dive to explore the major pain points that each group had about NAMs, and we also started developing action items that we’ll use to create a very well-reasoned and evidence-based path towards integrating NAMs, whether as partial or full replacements. I want to comment about how brilliant these people were who came. One of, I’d really like to mention his name and he knows who he is if he’s listening to this, and everybody else does, but it was such genius, he said such a smart thing, and he said it more than once to remind us: “Let’s focus on best science, not on the question of using animals or using NAMs.” So it was a great kick start for roundtable purposes, and actually does reflect my efforts, which are focused on harnessing these intellectual giants to collaborations that are beneficial to them and to science and to healthcare and certainly animal welfare. And believe it or not, the environment, because animal husbandry and animal use does have a fair amount of pollution so to speak attached to it, and in fairness, in fairness, there’s a good amount of plastic waste associated with NAMs as well. But the folks I’m speaking with about that are working on it, and I think that’s going to come to a good end. So to get us going, I set four objectives for the roundtables. First was that we would identify support structures, optimal support structures for the development of NAMs, and what were the roadblocks that could prevent that? Second, how do figure out how to push forward these support structures and remove the obstacles? Third, we needed to estimate a realistic timeline, and wow, “timeline” surfaced as a very dirty word, but to estimate a timeline, a realistic one, for the regulatory approval and the implementation of NAMs, either as partial or full replacements. And last, we needed to think about developing a metric system to evaluate progress on what I call an approximated continuum, and I say approximated because it does not necessarily follow that the more knowledge you acquire will let you move forward. Sometimes, and I have embarrassingly experienced this in my life, I learn something more, and oh, well, I guess I was mistaken about that something, and now I need to backtrack. And I think other folks do this as well in their work, and need to rethink that something a bit before moving forward again.

ERNIE: One thing we haven’t mentioned, Lisa, is when did these meetings take place?

LISA: We had the first roundtable in the middle of March, 2022, and the second one was the beginning of June, 2022, and I am really grateful that everybody found time. These are folks with extraordinarily busy schedules, and to give their time and attention, there has to be a new descriptor for that, they were terrific.

ERNIE: Well Lisa, what would you say were the main takeaways from the roundtables?

LISA: Well, you need more time than the podcast to review all of them, but I will showcase the highlights for you. Both roundtables were historic meetings for seating all of the relevant stakeholders in one place, and also, for the level of engaged and respectful conversation. And that, in my opinion, was the first and most important outcome from these meetings, was that diplomacy works. Rather than these silly siloed efforts that I spoke about before toward problem solving, you really have a good way forward now. This benefits the stakeholders, it benefits science, it benefits healthcare outcomes, it benefits animals, and it benefits the environment. If I had to give you another takeaway, it’s that there is an interest, and I think a commitment from the stakeholder groups, to responsibly, and I underscore that responsibly, get to a place of best science with all that’s going to bring to us.

ERNIE: It sounds like it was a wonderful set of meetings and I’m sure it moved the field forward. Tell us more about the paper that you and Dr. Muglia recently published in the National Academy of Medicine Perspectives…

LISA: It’s a good time to be talking about questions, animal research, NAMs, there’s certainly been a lot of dialogue about animal research, because it’s existed since at least the fourth century BCE. On the other hand, NAMs are infants, and it’s important to know where they fit in now and how they might fit in in the future. So our article poses a question in the context of history and the future. The piece also calls for an entity that would focus full-time analysis on the policy issues and let’s say catalytic investments in NAMS.

ERNIE: Lisa, please fill our listeners in on some of the technical aspects of the conversation.      You’ve already talked about NAMs, but what are MPSs, HOOCs, PDTs, and PBTs?

LISA: We’re going to get to some of my favorite NAMs. Alright. MPS is the abbreviation for microphysiological systems. There are some really bright people who create these functional microenvironments to study normal and abnormal physiology. And my favorite NAMs are two that you just mentioned—the human-on-a-chip and the patient digital and biomimetic twins. The first one, the human-on-a-chip, is called an organismoid, rather than organoid, as a lot of people may already recognize the term, an organismoid by a friend and colleague Dr. Marx. And he’s correct, because this isn’t the single organ-on-a-chip or two or three, this is upwards of ten body organ systems. It’s simply amazing, and it really does recreate, I should say aims to recreate, human homeostasis. Wonderful stuff. The developer of the patient digital and biomimetic twins, Dr. Lans Taylor, is also doing great things, because these are both systems generated from electronic data and from individual patient MPS linked to the patient with the idea or interpretation and hopefully prediction of outcomes, healthcare outcomes in a certain disease, and once that one gets figured out, then gee, that can get templated for a whole lot of things. Just super developments. I think you can already tell I’m in their cheering sections. I don’t’ want to let artificial intelligence or AI go. That’s important. Talking about more friends and colleagues, Drs. Isaac Bentwich and Szczepan Baran are leading in this field, and that’s more geared to pharma contributions, but we all know the importance of drug discovery, so that’s a big thing.

ERNIE: So how far along are these technologies?

LISA: I think they are farther along than their detractors would say, and not as far along as the developers might want, and that I believe is going to come down to a funding issue, because one of the takeaways from the roundtables was that funding, whether it’s government or from VCs, is much more heavily invested in animal studies than it is in NAMs. That changes the face of things.

ERNIE: How would you envision that these NAMs will contribute to advancing the 3Rs?

LISA: Well, replacements are the pinnacle of the 3Rs, and those are NAMs, and it doesn’t get better than that. I think all of us, every one of the stakeholders, can appreciate a reliable NAM, and I’ve said that more than once.

ERNIE: How will these technologies support the rapid development of precision medicine?

LISA: Well, there again, that concept of funding comes up. It’s going to depend, in my opinion, on how well NAMs development is funded, and if it’s funded well, then the resources that are used are channeling towards NAMs are going to let them proceed forward more rapidly.

ERNIE: What about regulatory acceptance? I know that that’s a very important consideration…

LISA: The regulators I’ve spoken with are open to simply things that work, whether that’s an animal test or a NAM. They want something that’s reliable. I personally know a regulator who is pretty pro-active and is very welcoming to folks who want to discuss their alternatives. And I think that’s probably most of them. She’s just a little bit more forward. I like that. Rah rah!

ERNIE: Also, Lisa, I wanted to ask you about, are your thoughts about the FDA Modernization Act 2.0, which was signed into law by the president in December 2022, and specifies that the FDA will no longer require animal test data for new drugs to be approved…although it will still allow animal testing should pharma wish to employ it?

LISA: Well I think it’s very balanced. It addresses the sensitivities of those for animal use, those for NAMs, and those who can see the utility of both. And most people I think do see the utility of both. Now that the FDA Modernization Act is law, it is a great opening for drug companies particularly to submit their new drugs for approval using NAMs, and also eliminating the testing for biosimilars. That’s a big deal. From my experience as a veterinarian, I know that my colleagues and I will just sigh a heavy sigh, “We’re testing another vaccine that’s the same thing, and why do we need to do this?” But I’m not a regulator, and they are in tough positions. I do not envy them. They never have a good day. They’re blamed for something and not often applauded for doing things. It’s a tough job. But I think this is another tool for allowing best science in, and that’s important.

ERNIE: What do you see as the current major obstacles to widespread adoption of non-animal methods?

LISA: I’m going to sound like a broken record. Numbers one through ten are funding. That’s really it. It is the rate-limiting feature of this. I am not judging the prudence of investing in NAMs or in investing in animal studies. All I can say, or present, is just the logic arguments. Not enough money goes in, not enough it going to come out, and I think it’s very worthwhile investing in these.

ERNIE: Do you think that’s a roadblock that will eventually be overcome?

LISA: Yes, I think it is, because there are some large companies out there doing wonderful work with single and multiple organs-on-a-chip, and again, with artificial intelligence, they need to be given their chance. Funding will do that. It’s really an equation: funding plus really smart people benefits healthcare outcomes and the other factors that I discussed.

ERNIE: Lisa, do you think we will ever completely replace the use of animals in research and product development?

LISA: Ever is a long time. It’s going to take a while to reproduce very complex biological systems to the level where they’ll be accepted by investigators, but I think that will happen well before “ever.” I have been criticized by some as having a very Pollyana-ish view about it, but I have faith in really smart people, the integrity of regulators, and this working out. So I think with increased funder interest, which I also faith in, I think it’s going to work out.

ERNIE: By the same token, would you foresee a total ban at some point?

LISA: No, I don’t see that unless all the stakeholders, and I expand that beyond the eight stakeholder groups I spoke about and we can talk about patient advocacy groups and clinicians, decide to vote in favor of a ban. I think the more likely scenario is that NAMs will develop as better and best science, and will replace the use of animals, again using that dirty word “timeline.” I don’t know when that’s going to be, and there were stakeholders at the roundtable who had different ideas about the time it would take to get there. But, you know, there are social interests involved in this, and that doesn’t rule out the strength of voters’ voices.

ERNIE: Well Lisa, before I let you go, I wanted to be sure to hear about your venture called CARAT—the Center for Animal Research and Alternative Technologies. Where does that project stand at this point?

LISA: That’s the most important thing I can’t speak about with you in great detail, but I’ll tell you what I can. CARAT is designed to function as a full-time policy institute for NAMs issues, and should have its own areas of curated studies to accelerate the regulatory acceptance and implementation of NAMs. I did want to make the reveal after the second roundtable but there were confidentiality issues and I couldn’t do it at that time. And now that CARAT has way outgrown its original dimension and involves other people, more people, I’m even more limited in what I can say. But I don’t know if this is a teaser, and I kind of hope it is—let’s just wait and see what grows in the spring, OK, we will revisit it then. There is no full-time think tank for these issues, and that’s the proposed function for CARAT, and as I say, I hope that’s a nice big tree that grows in the spring.

ERNIE: We will certainly look forward to it. Lisa, it’s been a fascinating conversation, and best of luck in your efforts to eliminate the scourge of animal use in research and product development, and thank you so much for joining us on FOCUS In Sound.

LISA: Thanks Ernie, it was a pleasure.

We hope you’ve enjoyed the program, and will join us again next time. This is Ernie Hood. Thanks for listening!

FOCUS In Sound #33: Tammy Collins, Innovation in Regulatory Science Awards (IRSA) Program

Welcome to FOCUS In Sound, the podcast series from the FOCUS newsletter published by the Burroughs Wellcome Fund.  I’m your host, science writer Ernie Hood.

In this edition of FOCUS In Sound, we meet one of the newest members of the Burroughs Wellcome Fund family, Program Officer Dr. Tammy Collins, who joined the Fund in October 2022. Tammy leads the Fund’s efforts in interdisciplinary science, including the Career Awards at the Scientific Interface and the Innovation in Regulatory Science Awards, which we will focus on for this edition of Focus in Sound.

Tammy spent the past decade at the National Institute of Environmental Health Sciences as its director of the NIEHS Office of Fellows’ Career Development. She received her B.S. in Chemistry from Appalachian State University and her Ph.D. in Biochemistry from Duke University. After a brief postdoc at Duke, she joined NIEHS in 2009, where she developed her passion for working in the scientific career development field.

Tammy Collins, welcome to the Fund, and to FOCUS In Sound …

TAMMY: Thanks, I’m glad to be here.

ERNIE: After so many years in government service mentoring fellows in their career development, what led you to shift your own career development path to the philanthropic sector by joining the Fund?

TAMMY: Well, I’m glad that you asked that. So actually, part of my previous role included mentoring fellows on how to apply for grants, including the K99-R00. So I was really excited when I learned about this opportunity at Burroughs Wellcome Fund, where I was still going to get the chance to mentor individuals through the grant process. Specifically, postdocs, with one of the other programs that I oversee, and then faculty. So I’ll be able to learn new skills in mentoring faculty with the Innovations in Regulatory Science program. And in terms of moving from government service to the philanthropic sector, I still see that I am working in the service sector and still providing a service, just in a different avenue. And I’m really excited about being able to have a broad impact in science as it relates to a wide variety of areas, both with the Career Awards at the Scientific Interface as well as the Innovations in Regulatory Science. So I’m excited about those aspects of my work at Burroughs Wellcome Fund.

ERNIE: So you didn’t even have to relocate, did you?

TAMMY: I didn’t, and actually NIEHS is less than four miles down the road from Burroughs Wellcome Fund, on the same road. So I’m still here in Research Triangle Park.

ERNIE: Well Tammy, to get us started on our discussion about regulatory science, would you give us a definition of the field, and tell us why the Fund invests in the sector?

TAMMY: Yeah. That’s a question I have gotten a lot of times. People asking, “What is regulatory science?” So regulatory science has actually been defined as the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. And Burroughs Wellcome Fund recognizes that regulatory science is a very important field, and it’s often an underserved area of research in the biomedical enterprise. And oftentimes what’s seen is that in translating or moving scientific discoveries into actual interventions that are going to help patients or therapeutic interventions, the regulatory science aspect is often what results in a bottleneck. And so what we want to do is actually help to close the innovation gap in creating new evaluative tools for new emerging technologies, and to do that in a wide variety of areas. We call out some of them in the RFP, but some of the things we’re looking at are specifically in gene therapy, artificial intelligence and machine learning, digital health, model-informed product development, and new technologies that might help to reduce animal testing. So these are just calling out a few areas, but really the field is wide open in terms of any individual that’s going to be helping to advance the field of regulatory science.

ERNIE: Let’s look at the Innovation in Regulatory Science Awards, or IRSA.  The awards program is going into its tenth year in 2023. Would you give us a brief overview of the IRSA program?

TAMMY: The IRSA program, or the Innovation in Regulatory Science Awards, it supports faculty over a period of five years, and the total award amount is for $500,000. And one of the key things is that we want to support researchers who are developing innovative solutions to solve regulatory questions. And another thing that’s key is we want these solutions to actually be implementable. So when individuals are applying for the IRSA program, we would like for them to address how they expect their solutions are going to expedite the regulatory decision-making process.

ERNIE: What types of researchers has it attracted in its existence?

TAMMY: IRSA has attracted a wide variety of researchers from many different fields and backgrounds. When I was looking back on this, I see we’ve supported toxicologists, biostatisticians, public health scientists, even organic polymer chemists and engineers. And we really anticipate that interdisciplinary work that’s being conducted at the interface of even fields such as physics, computer science, and engineering are going to go a long way towards helping to develop those new tools and approaches that are going to be aiding regulatory decisions. And we’re actually now in the process of systematically evaluating the fields of study of all of our past awardees over the past ten years, which is how long the program has been in existence, and we aim to include this in a publication as part of the overall program evaluation.

ERNIE: So what kind of impact do you think the IRSA program has had on the regulatory science field?

TAMMY: That’s a great question, and that is actually precisely one of the questions I had when I came here to Burroughs Wellcome Fund, and I’m actually working now with a team to set out on a project that I just alluded to before where we’re evaluating IRSA ten years later. And one of the things we want to look at are what actual new tools and methods were created with IRSA support. We’re curious about what are some of the FDA-focused areas of regulatory science that individuals have been addressing. We would like to see also if they were addressing an aspect of clinical trial development — what phase of the clinical trials process? And can we actually point to specific cases where regulatory decisions are expedited, and if so, by how much? So these are the types of questions that we want to be answering in this in-depth analysis that we’re going to be conducting over the coming year. We also have a lot of questions about to what extent the Burroughs Wellcome Fund IRSA program has helped to foster interdisciplinary collaborations and helped build a network of scientists, because that was one of the goals at the outset. Another goal at the outset was to move the needle on scientists choosing regulatory science as an actual career path. So these are some of the types of things that we are going to be looking at when we evaluate its impact.

ERNIE: So why would it be advantageous for a scientist to apply for this award?

TAMMY: Well beyond the most obvious reason for obtaining $500,000 over five years, really at Burroughs Wellcome Fund we seek to foster a network of our awardees, and not just IRSA awardees, but a network of awardees across all of the different programs. Each year we have a new awardee networking meeting, and we think that’s really important for helping to build connections and leading to additional collaborations and research that we have seen come out of that over the years. Also, Burroughs Wellcome Fund funding is flexible, as the funding is coming from the philanthropic sector. So I think those are some of the additional advantages of applying and receiving an IRSA award.

ERNIE: So Tammy, what should an interested researcher do to start the application process, and how can potential applicants find out about all of the details?

TAMMY: So I would suggest to review bwfund.org, our website, and look at the program on Regulatory Science, and we give lots of details. You can find our request for proposals there, as well as all of the deadline information. We have a section on Frequently Asked Questions, and I highly encourage individuals to reach out to myself as well, at [email protected] if you have questions about what your project is and whether it fits in line with the scope of the IRSA program. So really, that’s what we’re here for, so feel free to reach out anytime with any questions.

ERNIE: That’s great to hear, thank you. Well Tammy, I know we want to point out at this point that interested folks should also be sure to watch the video we’ve posted accompanying this podcast, where you engage with three current IRSA awardees to get an in-depth look at their experiences with the program…

TAMMY: Yeah, I know, I’m really excited about the opportunity that we had to engage with some of our past IRSA awardees, and learn more about *** [what] the work that they’ve done and where it has taken them and how this has advanced their career, so please make sure to check that out, because it was a great conversation.

ERNIE: Well Tammy, this has been a great conversation too! Thank you so much for joining us on FOCUS In Sound.

TAMMY: Thanks for having me. It was really great speaking with you today.

ERNIE: We hope you’ve enjoyed the program, and will join us again next time. This is Ernie Hood. Thanks for listening!

FOCUS In Sound #32: Alfred Mays, Dr. Dudley Flood, Dr. Deanna Townsend-Smith

Welcome to FOCUS In Sound, the podcast series from the FOCUS newsletter published by the Burroughs Wellcome Fund.  I’m your host, science writer Ernie Hood.

In this edition of FOCUS In Sound, we meet a civil rights and education pioneer, Dr. Dudley Flood, and learn about the center named in his honor that is working to advance educational opportunities in North Carolina. To get us started, we will first hear from Burroughs Wellcome Fund Chief Diversity Officer and Strategist, Alfred Mays. Alfred also serves as a Senior Program Officer for the Fund and oversees a variety of significant programs addressing education and diversity. He is going to provide us with some background information about the Dudley Flood Center for Educational Equity and Opportunity, which is within the Public School Forum of North Carolina. Alfred, take it away…

ALFRED: Thanks, Ernie.

I am actually a board member of the Public School Forum. In 2015, the Forum kicked off its sixteenth biennial study group, a yearlong process that involved the work of three committees focused on topics related to expanding educational opportunity in North Carolina: racial equity, low-performing schools, and trauma and resiliency in learning. I had the honor of serving as a co-chair of the racial equity committee.

In 2016, Study Group XVI, as it was known, released its final report called “Expanding Educational Opportunity in North Carolina.” It was the product of the collective efforts of more than 175 committee members, and included a detailed Action Plan and Recommendations. The report set the course for the Public School Forum and its partners to continue addressing educational opportunity in North Carolina in the years ahead. One of the important developments was the establishment of the annual Color of Education event, which every year brings together the many stakeholders to address the ongoing issues.

Now fast forward to 2019. At the Color of Education event, we announced a catalytic grant of $150,000 from the Burroughs Wellcome Fund to stand up the Dudley Flood Center for Educational Equity and Opportunity. The Conway Family Foundation joined Burroughs Wellcome Fund in making a $30,000 gift to support establishment of the center.

Dr. Flood was brought on stage for the announcement that we were naming the new center in his honor. It was designed to be a surprise for him, and he was truly delighted.

Since then, the Flood Center has become fully staffed, including Senior Director Dr. Deanna Townsend-Smith, from whom we will hear shortly. They are working on a variety of programs, including the Color of Education event, which is coming up for 2022 on Saturday, October 22nd. The theme for this year is “A Walk Through History: How the Past Informs the Present.” The hybrid event will feature keynote speaker Jelani Cobb. To further the Center’s work over the next year, it’s a pleasure to share with you that the Burroughs Wellcome Fund has just made an additional $300,000 grant award to the Center.  The Conway Family Foundation has and continues to support fellowships and Color of Education within the Flood Center.  Additionally, the Flood Center has received key additional support from Amgen, Kellogg, MDC, Anonymous Trust, Goodnight Foundation, along with additional funding specifically for Color of Education from Corning, Lenovo, the North Carolina Department of Natural Resources, and EPIC.

That is where we stand today, and now let’s enjoy hearing from Dr. Flood and Dr. Townsend-Smith. To introduce Dr. Flood, I’m going to pass the microphone back to Ernie…

ERNIE: Thanks, Alfred, for that terrific summary of how we got to where we find ourselves today. That history will provide a great context for our conversations with Dr. Flood and Dr. Townsend-Smith.

Dr. Dudley Flood was born in 1932 in Winton, North Carolina, a tiny town in Hertford County in the northeastern part of the state. He received his bachelor’s degree from North Carolina Central University in 1954, his master’s degree from East Carolina University in 1970, and his doctorate from Duke University in 1980.

He has had a long and distinguished career as a teacher and school principal – a lifelong educator. He worked for many years at the North Carolina Department of Public Instruction.

In the late 1960s and early 1970s, he and his Department of Public Instruction colleague, the late Dr. Gene Causby, traveled the state to unite communities that were divided, sometimes bitterly, over integrating public schools. They are largely credited today with pioneering the process of integration in North Carolina public schools.

In 2020, Dr. Flood’s achievements were recognized as he was awarded the Friday Medal from the College of Education at North Carolina State University. In 2021, he received the prestigious North Carolina Award, the state’s highest civilian honor, and most recently, the NC Justice Center Lifetime Champions of Justice Award.

Dr. Flood, thank you so much for joining us on Focus in Sound…

FLOOD: It’s my pleasure.

ERNIE: I mentioned that you are a lifelong educator – teaching runs in your family, doesn’t it?

FLOOD: It does. I’m from a family of nine, six of whom were teachers, including myself. Of course, being the eighth child in that family, and having observed the others, I didn’t know there was an alternative. I just thought that was why you were put on earth, was to teach. Once having gotten into the field, I got hooked on it, and I teach now because I can’t help it. I really can’t help it. I have no choice but to teach. If I were to have my life start all over again, I would make the same decision. I do believe teaching is the best way in which I could render service. So I made that choice, and I have no regret about it.

ERNIE: That’s wonderful, thank you. You were brought up well before the height of the civil rights era…what was your schooling like in your early days?

FLOOD: My high school days were in the little town of Winton, population 698, give or take. It was a tri-racial town. And my background is that I was born into what is a tri-racial family, although at that time it was not particularly highlighted. My father was the son of a Native American woman. His father, whom he never knew, was a White man, and my mother was a Black woman. So I didn’t have anybody to hate, so I didn’t get into the cadre of, we’ve got to hate this race or that race or the other race. And that was never a discussion in my household. And I was born right on the edge of the Depression, coming out of it, but I don’t think we had come out of it at all. And the one thing I remember the most about having been brought up in that time was, strangely enough, I never heard any reference made in our house about our [status], I never heard we didn’t have this or we didn’t have that, I could only observe that some people appeared to have things I didn’t. But I always thought I had some things they didn’t, as well, and so I never got in the discussion of, poor me. It was always the discussion that you are born to serve. You have to render service. And any conversation that I brought up that would lean toward needing more, I would be told very quickly, you need to take what you have and dispense it among those people that don’t have it. And so obviously the avenue through which to do that was teaching. Not necessarily being a teacher with the job to do so, but whatever you were able to share that you might have had more of than anybody else. And that included experience. I became hooked on reading. As I sit in the subway, I read the stuff up overhead at the top, I just can’t, I have no choice but to read. So I was aware of a few things that were not in my general experience. So in the high school which I attended, which was a very old high school, preceding the state having taken it over, but its ethos was that of learning. We were an average athletic team, we were an average anything other than learning. So in that setting, I never thought beyond making a contribution. And I didn’t have any way that I thought I could make a contribution except through sharing with people whatever had been my exposure, experience, knowledge, accumulation of knowledge through reading…And I liked to be around old folk, I would always sit around the older people and listen to them wax philosophical. Because they had some genuine, not all were particularly literate necessarily, but they had some genuine perspective on life that I found to be very functional, very useful. In that little town, as I mentioned, our ethos was, you were white or you were colored. These other dimensions hadn’t even entered the discussion in an informative way. I always wondered, because the intermingling of the youth. I lived right on the riverbank, and everybody who wanted to swim, we had no pool, so they came by my house because the only passage to the riverbank was by my house. And I’d take them to the river without asking, what is your race, what is your creed, or any of that. But it’s my river, this is my river. That was the ethos. You knew whose river that was. My brother was like, and I mean that superficially, because I understood, they knew it wasn’t my river, but they also knew that it was tantamount to coming in my yard, as it were, to play. And so this notion of separation of races never dawned on me, except in school and church. Those were the only two places I ever saw that manifest itself. And it was puzzling. I didn’t understand then and I don’t understand now why the body which we thought would be most segregated, which was church, was the most segregated institution I was aware of. It still is, by the way. And we were adamant churchgoers. Not necessarily by our own proclivity, but our mother was a devout churchgoer, and after a while I got used to it and began to like it. So much so that I’m still a Sunday school teacher right now. But then in growing up outside of school, which wasn’t much, because school was most of it, in my little town there was an area called the Camp. Men who worked on the river, they had these little camps that they resided in. And when I was 8, 9, 10, I would go down there and they would have me read to them, the gentlemen that were not literate. They would send me to get comic books. And I would go and get comic books and I would read to them. They liked those that were humorous. They didn’t care so much for the action ones.  Although they liked Batman, Superman, Captain Marvel, but generally speaking they liked Dagwood and Archie and people who were funny. And when I would read one that was humorous, they’d make me read it again, you know, so we could all laugh together. So I developed an appreciation for humor, and that it tended to work. So growing out of that, and having a family that appreciated a fair amount of levity, I found that humor was better than anger. It really was better than anger. And so to this day, I still practice that. And it may be annoying to some folk, but most would rather have that than have bitterness. And so those were the things that I think had the greatest impact on how developed to become the kind of teacher that I hope I was, and like to think I still am.

ERNIE: It sounds like those were some wonderful years, Dr. Flood. If you would, paint a picture for us of the years when you and Dr. Causby traveled the state working on meeting the challenges around integrating schools…it was far from easy, wasn’t it?

FLOOD: It was challenging. I don’t know if I would determine that it was not easy, because we didn’t know enough about what we were getting into to have any fear of it. Gene’s mentality was very similar to mine, in that Gene didn’t manifest hatred for anybody. He was able to respect any- and everybody, not agree with, necessarily, but respect. I don’t need to agree with you to respect you. I respect your opinion and I really respect your circumstances that might have led to that opinion. That commonality made it very easy for Gene and me to work together with others. But very quickly we developed one or two strategies that we thought would get us into places that tended might have been disinvited. Number one, we were nobody’s enemy, we declared that right out. I don’t come here as your enemy. In most cases we had been invited to be there, may not by the people whom we were working with, but we were invited. So we didn’t trod our way in here, and made it clear that if you don’t find what we’re here to do useful for you, the minute you let us know that, we will discontinue this and move on, because there was always somewhere else who wanted us to be. We didn’t say that, but we had that attitude. If you find this isn’t something you need, you don’t have to chase me off, just let me know you don’t think you need this. So it happened many times that Gene and I enjoyed what we did, even to the point of talking about what challenge we might expect upon going this place or that place or the other place. And then we always had – almost always had some person on the inside who could give some sense of the culture in which we were going. We realized that was one narrative. We realized that we may not have a full scope of the culture. But at least it was a door opener. And generally we really identified with that person or those persons. Very often it would be a superintendent or a principal, sometimes a community member. But it would ensure that we didn’t break in here where somebody wanted us to come, and here is what we’re here to do. And then we always determined for them what we’re not here to do, and that is, whatever we do here has to have three dimensions. One, it has to be legal. We’re not here to help you break the law, or break the law ourselves. Second, whatever we do has to be educationally sound. We will not endorse or recommend something that we can’t demonstrate through knowledge or research that it will be educationally sound, because we’re here about children. The only person that has a right to be at school is children. Everybody else is here by privilege. The law doesn’t grant me a job. It grants children the right to education. So anything we ever did is education. And thirdly, whatever we do, it has to be mutually consensual. That is to say, we don’t all have to like and agree on it, but consensus to us meant that everybody had had an opportunity to have his or her perspective injected, and then we draw some conclusions and whatever we resolve here is consensus. So we might have to stay a little longer to get to that consensus point. We’re not going to take a vote, we’re not going to say all who raise your hand, we’re going to determine that we are in consensus, that what we have determined is good for your children here is what we will do. And so we really didn’t have time to be bitter, we didn’t think about ourselves to be honest with you. It was fairly challenging in some instances because you were starting with polarization. You were starting with people at different ends of the perspective about how they felt and thought. And then we understood as well, people don’t remember so much what you say, but they do remember how you make them feel. And we were able to cause people to feel differently about what they were doing, saying, thinking. You need language to do that. But I’m not sure that every single word that comes out of my mouth is golden. But I am sure for a fact that the way you perceive that I see you as a human being is golden. I’m certain of that. And so we were both fairly skilled but we didn’t need a skill, because of our nature to see the good in people, to see the positivity in people. And therefore, we never talked about what you’re doing wrong, we talked about how there might be some improvement to, which is very different from telling you how dumb you are. We never used that kind of terminology. It was always, have you given any thought to maybe this would work if? That sort of thing. And so it wasn’t because it was less, because it was natural for us. I think for somebody who didn’t have that natural tendency, it would have been an untenable job. But I couldn’t tell you what my hours were, I would be done on a Sunday and somebody calls and says, “We need you in Asheville at 8 o’clock tomorrow morning.” I’m having dinner at 5 o’clock in Raleigh! At that time, it was five hours best you could drive it. We didn’t I-40 at that time. So you couldn’t give a lot of thought to yourself. We were both very fortunate to have wives that understood what we did and understood why we were doing it, and they knew that it would never replace them, but it would replace everything else, because everything else would come second than what we were doing. So that commitment showed, people knew, we’re not here because this is a job, we’re here because we’re committed to what we’re doing. So I think that atmosphere makes it less than difficult. But we really had fun, and it was a challenge.

ERNIE: Dr. Flood, from your perspective, what is the state of public education in North Carolina today? I’m sure you’ve seen substantial progress over the years, but do you think there remains a great deal of work to be done?

FLOOD: I think there has been progress, and I think there has been retrogression in certain arenas. We’ve recapitulated about race relations, there is no question about that. I don’t even want to be glib about it. Race relations are not where they were in 1970, 75. One of those reasons is we don’t have anybody whose full-time job it is to tend to that, and that’s not to self-aggrandize, but when we quit nobody took up the management, no official. There were people running around in pockets doing this or that or the other, but didn’t have the weight of the government behind them. We had the weight of the government. We represented the State of North Carolina, and no matter how good you are representing something other than that, you do not carry the clout that the state carries. So when we were speaking for the state, even though many times the state may not know what we were saying, it had much more of an impact than we were ever going to have again. And until we get back to where the state sees the importance in that, which now it hasn’t demonstrated to me that it does. Now otherwise that polarization was an accumulated polarization growing out of what they had experienced heretofore. We didn’t all experience the same thing they had heretofore. We weren’t starting at, we were starting at ground level, but not beneath that. Now, we have a different kind of society in which polarization is political. I never knew any instance in which we asked somebody what is your political persuasion. We didn’t even guess it, because we didn’t care. That isn’t what we’re here for. We’re here for your children. And if we needed to bring it back to the point, children would always do that. I’ve never met anybody who didn’t think children ought to have something. Maybe not all agree what that was and how they ought to get it, but something. So we would always stay away from that. Right now, there are instances in which I feel that we feel prohibited to say what we know to be the right thing, the best thing. We’re prohibited from doing the thing we know that would be better. We don’t go and do something worse, but that means that we’re idle. We’ve failed to do those things that we know would work well. I think there is less appreciation for the historical perspective of the progress we’ve made and have known there to be heretofore. So much so that except in an interview like this, I rarely talk about my past. I rarely talk about it. Because nobody, not many people want to know anything about what was. And certainly they don’t want to get beyond my past, they don’t want to go all the way back to the 16s and 17s, and that’s a difficulty, because that is what our culture stands on. Our culture stands on what was and how we matriculated from that to what we are. I always like that old saying that today was tomorrow yesterday. And I act on that. Today was tomorrow yesterday. If I didn’t know there was a tomorrow, how would I think there was going to be progress in front of us? So I can demonstrate that there will be a tomorrow, because today is that tomorrow that we were talking about. So when we can focus and get people to look out front of them, not so much through the back window but through the windshield, about what is a possibility, and it is built on what has happened, we’re better off. But when we begin to limit what we can have in discussion, when we begin to politicize discussions that ought to be educational in their nature. Nothing political about, I taught Karl Marx, I taught Mein Kampf when I taught history. That didn’t make me a Nazi. I taught Karl Marx, that didn’t make me a communist. It was teaching. And it didn’t make any of my students communists, either. And if I were teaching today, yes sir, I would teach enslaved people had this and all the rest, they’d just have to put me out. Because I don’t think you can be enlightened to the progress we have made, I don’t think you’re being inspired as a Black person without realizing things over which we have come, and that tells me that it’s possible; the great motivator is possibility. And if I don’t know it’s possible, how can I be motivated to do it? So if anybody knows how you get off that riverbank on which I grew and wind up in the state superintendent’s office, nobody knows that. They think that’s a myth. They think, OK, you lucked out, or somebody favored you. Or you kissed up to somebody. So unless we are able to teach our history in genuine fashion, then we are never going to be able to get what we need to get out of our youth, because the inspiration factor is missing. So I think we’re doing many things much better. We have more opportunities, we have more material things with which to work. We have this meeting, which we didn’t have when we grew up. But the personhood still needs the work. That person just still needs the work. And I say still needs because I’ll just tell you, I believe it’s doable. I wouldn’t be at it if I didn’t believe it was doable. I should have been retired 40 years ago, but I believe every day I’ve lived I’ve done some good, some for a lot of people, some for one or two people. But that’s what we have to believe. If we are going to be a good society, we have to keep on believing in the possibility. And we all have to be willing to put in his or her two cents in whatever we can. So I think education is at a point where we have to make some really serious decisions about what we want America to look like. Because education is going to look like what we want America to look like. And right now I’m not sure that’s clear.

ERNIE: So what about the state of racial equity in our schools today? Where do you think we stand at this point?

FLOOD: I think we’re at the point where we ought to be making more effort than we might have made in a time when it would have been more timely to have done so. But we can’t go back and undo any of that. Had the continuity been there, we wouldn’t be having this discussion. If we had that continuity and we capitalized on what we knew already in the mid-70s and continued that, we wouldn’t be having this discussion. But we had a lapse, and then we had a recapitulation. And now what we’re doing is taking out of the recapitulation factor. So, the degree to which we’re getting enough people who are comfortable even discussing these issues, and who have the knowledge and the skills to discuss them, and who have the language to do so. Language is an incredibly important thing in having these kinds of discussions. Not everybody has that language, and who have the temperament to do so. That’s another ingredient. And it’s hard to transport that temperament from somebody else, unless you have a lot of time around them. If you’re around them enough, it rubs off. But you can’t go in 30 minutes. Many of the invitations I get are 30 minutes. You’re wasting my time if you’re asking me to come somewhere and take 50 people or 60 people and modify them in 30 minutes. You’re just paying me too high a compliment, I can’t do that! Now I can make them think about a couple of things, but that won’t work. There has to be an opportunity to be more than what people are willing to put into these things. Now the excuses they give me is they don’t have time, they’ve got to get this done, they’ve got to get the other done, and I understand that. But the end result is what you’re getting is, you didn’t have an effective opportunity for your people to modify their paradigm about how they address diversity. And we might have opened their thinking so that they may be then better off, but they’re not where they need to be at. So I hope we can develop enough patience again. There was a time when everybody knew we had a problem. Everybody knew that. You might not have liked it, but everybody knew it. Most people don’t know that now. Most people look at how they’re doing. I’m doing well, so what is the problem? And I don’t want us to have to have another instance in which everybody knows there is a problem, necessarily, but I’m fearful that that is what it will take for us to say, we need to modify our direction here. And we need to understand we’re in the people business. And if you’re trying to put something into an empty mind, an empty body, an empty soul, you’re swimming upstream. If you can revive the mind, revive the soul, revive the spirit, teaching is a piece of cake. I’ve never found it hard to teach, never. When you came to my classroom the first day, everybody got an A. I had kids that had never had an A in their life. Everybody got A. today your grade is A. Now, you want to know how to keep that? We’ll have a discussion tomorrow about how you can keep that A. I’ve already got them motivated. “Mom, I got an A!” She’d be, “What?! Son, you never had more than a C!” And if you had categorized somebody as a C student, that becomes a self-fulfilling prophecy. You’ve already determined what his or her progress will be if they buy that. Now if they know enough to say, “I hear what you’re saying, but give me that book over there, not the math, but give me that science book.” They know enough to say that. And that’s why the work that you’re doing is so significant. It’s that we’re trying to get people to not start believing when somebody told you you can’t do it. Not to start with that. But even that takes an effort. The most important thing about it is focus, attention. Anybody whose attention I can get, I teach. Everybody doesn’t know how you get attention. You can’t demand attention, you earn attention. You earn that. And there are various ways that we can teach people how to get attention. You don’t have that avenue of ways to do it any more, so I’m hoping that the Dudley Flood Center will have that avenue, and that we will be involved in doing that kind of thing, open to that kind of thought, that kind of discussion, and we take every opportunity we can to wedge our thought into whatever discussion we’re having. I don’t care if I’m standing on a streetcorner. You stop and have a conversation to wedge some of that into the conversation. We have not had what we now have before, in the last 30 years, and that is a symbol that said this is something we ought to be doing. You’ve got to have a symbol that says that. It says that somebody thought that this was worthy of spending time and money. We’re doing it. That’s one of the greatest things that has happened in my adult life, that somebody has endorsed that this is worth doing. Somebody outside of me. It isn’t about me at all, it’s about Burroughs Wellcome and others have said, this is worth doing, and somebody is going to listen. Because it has been said by people who are thought to be capable of making good decisions. So that’s where I think we are now, and I’m happy about it. I’m happy. Not finished, but just happy. I’m going to be happy yet. But I’m happy about where we are, because we have an opportunity, and I haven’t had that opportunity for the last 30 years, so I’m partially happy.

ERNIE: You may have already just addressed the next question, but I’m going to go ahead and ask it anyway, to see if we can get a different perspective. How do you feel about the center named in your honor, the Dudley Flood Center for Educational Equity and Opportunity? Do you think it is fulfilling its mission to serve as a hub for the various stakeholders to implement the recommendations of Study Group XVI?

FLOOD: I think the Center is in its infancy, so it’s prejudging to say what it is going to be. Insofar as where it is right now, its mission has been clear in that regard, its effort has been clear in that regard, its staffing has been clear in that regard, its thrust has been clear in that regard, and it has gained respect so quickly. Now one would have thought it would take several years just to get respect for its existence, because keep in mind, we’re moving in a direction that has been moved in for a few years in an efficient way. And we spend some part of almost every day, some of us, in thinking about how we can strengthen those elements that we have in our mission statement. But I’m delighted at the progress we’ve made at this point. We have an amazing advisory board, we have amazing support from the Public School Forum per se, we have astonishing support from funders. Those are things that one could not anticipate going on here. You just have to say, if this would have happened, this is where we’d be. Who ever thought it would? And when it happened, there were still some people who said, this is going to last six months. We went through a little while, it’s what, two, three years old? We got everything else in the report except this. And I don’t want to blow Alfred’s head up, but had it not been for him stepping in when he did, this would never have happened. And I know he had to be at the right place, at the right time, at the right support around him. But now it belongs to everybody. Alfred doesn’t claim this, it’s everybody. And I don’t claim it, Deanna doesn’t claim it, it’s everybody’s. The key has to be that this is your center, it’s here for you. You tell us what you need from it. We know some things that we’ll provide you with, but you tell us what you need from it. And we haven’t said no to anybody yet. And that is what I view. I view it as being a catalyst to compelling us somewhere. But I also view it as being the reservoir of things that many of us know and haven’t had anywhere to store. And nobody has asked us in a profound way that historically continued it to use it. So, of my goodness, where the Center is now is so far beyond anything I’ve seen heretofore in education in this state, and I’ve been in education now since 1954, and I haven’t seen the like, even when we were at DPI, our job was this, but we worked for the state of North Carolina. We knew that we had one core vision, we knew how far we couldn’t go. The Center doesn’t have those limitations. I couldn’t have had this interview with you when I worked for the state of North Carolina. It would have belonged to it, they would have told me what I could say and when. That’s not pejorative, that’s a fact, that’s the way institutions work. I respected that. They gave me a great opportunity. Gene and I had very little surveillance over what we did and didn’t do, but we know constraints that were imposed by virtue of you having to work within the confines of what public education does and stands for. The Center is wide open. I’m working right now with churches. If I had worked with churches when I was at DPI, that would have been a conflict of interest. By the way, they are white churches, I should mention that. Although I would work with a black church if they asked me, so far none have. Maybe one day they will, but right now I’m working with various churches in the name of the Center. I wouldn’t have known I would do this had it not been for the Center, because I don’t advertise. Churches don’t pay, I don’t advertise things that don’t pay. In fact, it costs you to work with churches. If they give you a couple of dollars, you put that in collection. But we do that because it’s a way to get what we need to have done done. We can’t have just educators talking about this thing. Most of the problem here is having an educator come to you from somewhere else, and if the faith-based community is not involved, we’re not going to be successful. So every opportunity I get to gather the faith-based community’s attention to what we’re about, how we’re about it, and for them to need us and know that we need them, I just gravitate to such an opportunity. So I still think we’re onto something here, I really do. I think we’re onto something. It may not show, but I’m happy about that. I blown away by the opportunity that it presents for us to do what I’ve always known that we need to.

Alfred, your name has been invoked, so please jump in here…do you have any questions for Dr. Flood?

ALFRED: I do, thank you Ernie… Dr. Flood, your entire life has been devoted to addressing “systemic wrongs”, in summary, how do you see a future with true “systemic rights” that include equity, access, and opportunity?

FLOOD: I believe that we can develop a pathway to that. I may not live to see it concluded, but we can develop a pathway to that. I believe we already know way more than we need to know to do that. I think the question is whether we determine that that is what we are committed to doing, and I believe I’m surrounded now by people who are so determined. And being surrounded by that is motivation for those of us who think we know a little about that to scratch more deeply into ourselves and say, let’s make that pathway clear, let’s make it inviting, let’s make it not endangered and not dangerous, and I’m on the team that says we can do this. We can get it done. And I feel really, really optimistic about that. I think it’ll take us a while, but I’ll probably be around. I’m only 90 years old. And I’ve enjoyed the first half of my life, but I’m planning to use the other half in the same manner as I used the first half. We’re going to keep plowing until that pathway is so attractive that more people will say it’s safe to get on this, I can speak about this, I can acknowledge my goodness, I can acknowledge my respect for all human beings, I can acknowledge the dignity that is the driver that make America the democracy that it is. If we can just get that far in the next few years with a large number of people that maybe begin to spread that, we’re going to have very, very good results of our efforts.

ERNIE: Thank you, Alfred, and thank you, Dr. Flood…Now let’s bring in the Senior Director of the Flood Center, Dr. Deanna Townsend-Smith. Thanks for joining our discussion…

TOWNSEND-SMITH: Thanks so much for having us today, Ernie, it’s great to be here with you.

ERNIE: We wanted to mine your thoughts about the Flood Center. It’s been up and running for a while now, you’re fully staffed and operational. How do you think it’s going so far?

TOWNSEND-SMITH: I think that’s a great question. And to your point, yes, we are fully staffed right now, and as we continue to expand our programs to be that consistent resource to our diverse stakeholder group, we will need additional staff. So as I reflect on our programming and what those programs are doing to eradicate inequities in education, we are meeting a significant portion of our core strategic priorities and making progress to meet our mission. So I’m pleased with our progress, and we always aim to push to do more, because ultimately at the end of the day, it’s about having the greatest impact to improve educational outcomes for students. So that’s the reason we continue to do this work each and every day.

ERNIE: So what would you cite as the Center’s most important accomplishments thus far?

TOWNSEND-SMITH: That question always causes me to reflect a little bit, Ernie. I think the Center has accomplished much in our short tenure. Two areas of great accomplishment are directly related to our capacity-building and convening of stakeholders through a number of programs, but most importantly through our largest event, which is Color of Education, which brings together hundreds of key stakeholders focused on achieving racial equity and dismantling systemic racism in education across the state. Another area of accomplishment would be in the area of partnership. Each and every day, because of the model that we have in Dr. Flood, we are growing more skilled at developing our sustained and meaningful collaborative partnerships with organizations, philanthropy, and schools to maximize academic impacts across our state. Most recently, we released a Framework for Change, because earlier you heard from Dr. Flood that language is important. So this Framework for Change helps to solidify common practices to address those recommendations that were in the Study Group 16 report. Because common understanding, language, and practices help to guide everyone on what need to be done, and get us to the goal of achieving educational equity. Dr. Flood often says, and I’m a firm believer, that we don’t need another report, we need to act on what we know, and our framework is a start for us. It’s our commitment to act and to ground others on how we move forward to meet the needs of each and every child.

ERNIE: You mentioned moving forward, and I’m sure a significant part of your position with the Center is looking forward…what is your vision for the future of the Center?

TOWNSEND-SMITH: My vision for the Center is that this center becomes the consistent resource it was visioned to be. So we must continue to expand our programming and to support our stakeholder groups to eradicate systemic issues. The Center should and will be the constant resource to support others in this work, now and in the future. That’s my vision for the Center.

ERNIE: And finally, Dr. Townsend-Smith, what has the support from the Burroughs Wellcome Fund meant to the Center?

TOWNSEND-SMITH: It’s humbling, number one. But the support from Burroughs Wellcome Fund has meant that we can exist in a time when others have not wanted to take a stand to address equity. Their support has been and continues to be integral to our existence. Because of Burroughs Wellcome Fund, others are now willing to come to the table to support our work, and you see more organizations feeling empowered to lead in this equity space. One of the core competencies of our Framework for Change is modeling. Because of Burroughs Wellcome Fund, we are able to model how to achieve educational equity by allowing others to see what they can aspire to be.

ERNIE: Dr. Flood and Dr. Townsend-Smith, thank you so much for joining us on FOCUS in Sound.

FLOOD: Thank you, Ernie, it’s been a pleasure. Thank you very much.

TOWNSEND-SMITH: Yes, thank you so much for having us today.

ERNIE: I want to thank Dr. Townsend-Smith, Dr. Flood, and Alfred Mays for participating in this Focus in Sound podcast. This is Ernie Hood. Thanks for listening!

FOCUS In Sound #31: Florence Bourgeois 

Welcome to FOCUS In Sound, the podcast series from the FOCUS newsletter published by the Burroughs Wellcome Fund.  I’m your host, science writer Ernie Hood.

In this edition of FOCUS In Sound, we meet a Burroughs Wellcome Fund grantee who is researching issues related to the inclusion of children and adolescents in clinical trials. She has also recently published an important international study of pediatric COVID-19 patients.

Dr. Florence Bourgeois is an Associate Professor of Pediatrics at Harvard Medical School and a faculty member in the Division of Emergency Medicine and the Computational Health Informatics Program, or CHIP, at Boston Children’s Hospital. She is a graduate of Yale University and Washington University School of Medicine in St. Louis. She was an NRSA research fellow and earned her Master in Public Health degree from the Harvard School of Public Health.

In 2017, Florence received an Innovation in Regulatory Science grant from the Burroughs Wellcome Fund titled “Pediatric regulatory policy: advancing timely and rigorous evaluation of medicines for children.” The award was for up to $500,000 over five years. She has published several studies in the regulatory policy area, and this year she and her colleagues put out their work using electronic health records to track and analyze international trends in hospitalizations for children and youth with COVID-19.

Florence Bourgeois, welcome to Focus in Sound…

Thank you, thank you for having me. I’m delighted to be able to speak with you today.

Would you sketch the broad outlines of the pediatric COVID-19 study for us?

Absolutely. This study was a product of a large consortium that came together fairly rapidly at the beginning of the pandemic, so last March and April, leveraging existing infrastructure to be able to aggregate electronic health records across institutions. And not just institutions within the U.S., but internationally. And this presented a terrific platform to be able to look at pediatric patients in particular, since COVID-19 fortunately has had much lower morbidity and mortality in children. But this also means that the patient population that is accessible to us for study is much smaller. So we were able to take an international perspective to characterize the clinical presentation of COVID-19 across hospitals in a number of countries, and also demonstrate this type of large-scale, informatics approach to aggregating data in a rapid fashion, which is particularly important during the evolution of a pandemic like COVID-19.

What conclusions did you reach?

So we were able to find certain clinical features that were specific to patients with COVID-19, in terms of complications, as well as certain laboratory abnormalities, and we were also able to find that the data quality that we were able to produce using this approach was quite robust. So we are continuing additional studies now leveraging the same resource to dig into other aspects of COVID-19 specifically for kids.

How did the study advance our understanding of epidemiological and clinical features associated with COVID-19 in children and youth?

One of the findings was that there were abnormalities in coagulation in children. So that is a specific feature that has also been corroborated in other studies. So that would be one specific result. And another one is the complications we saw around cardiac rhythms, disturbances in cardiac rhythms, and also around seizure activity, as an example. So identifying those specific clinical features is another data point to guide further research.

During the pandemic, many of the skeptics have been spreading the misinformation that COVID did not affect young people and children. Although rates and severity of infections have been lower, they are far from immune, aren’t they?

That’s right. And in addition, not only can kids certainly be infected with SARS-CoV-2, so COVID-19, but they also have very specific and unique phenotypes. So for example, multi-system inflammatory syndrome is a phenotype or a disease presentation that we’ve uncovered that is very specific to children and not seen in adults. So understanding those disease presentations and being able to study them is certainly important. And beyond that, we’re concerned not just about kids being infected with COVID-19, but also their role in transmission and as vectors in the population and in the communities. So that’s another important factor to keep in mind, even if fewer kids are actually affected.

So Florence, what are the wider implications of your findings?

From this specific study, I think that one major takeaway is not even the actual clinical results, but really the methods themselves; this informatics approach to creating a network across institutions, across health care systems, and countries even, in order to characterize COVID-19. This could be extended beyond just our research question that we were addressing around COVID-19 to other conditions and diseases. So it really represents a platform of sorts on which we can build future investigations.

Have you been able to use these methods to address vaccination rates?

That’s a great question. That is not something we’ve tackled, and we’re still understanding exactly how we might be able to incorporate vaccination rates, but certainly it’s critical that we understand the importance of vaccination in kids, since there has been quite a delay in terms of vaccinating kids versus adults. So it’s only since March 10 that the FDA approved vaccination for kids down to 12 years of age, so there is a large portion of our children in the U.S. right now who are obviously unvaccinated.

You also assessed laboratory results as part of the EHR work, as you mentioned. What kinds of trends did you see in that data?

The biggest one was around coagulopathies. Those are the laboratory measures we use to measure something like blood clots. And we found abnormalities in those in particular. And again, this has been seen in other reports as well. So it’s a nice confirmation of other studies and provides a basis for future investigation to understand the pathophysiology behind those abnormalities.

Will the methodologies your group used in this study serve as a model for future research efforts?

Part of the underlying informatics infrastructure was already in place, which is what allowed the team to very rapidly repurpose it towards COVID-19. In April already, they had tens of thousands of hospital records already on patients across a network of institutions, which is quite remarkable. So the innovation wasn’t so much maybe in the basic features of the infrastructure, but certainly in the rapid repurposing and then further development specific to COVID-19.

Did the hospitalization rates for children and youth in the 6 countries mirror population-level infection rates?

That is a terrific question, and actually one of the findings that we highlight in our paper is that indeed, with this network we were able to mirror some of the national or population-level disease rates. So what this indicates for us is that using these computational methods we can do some level of surveillance that can in fact complement other types of surveillance that are done, for example through the CDC or other government agencies. So this can be another approach or another tool to monitor population-level infection rates.

What about clinical treatments? Were the approaches used in the pediatric population similar to those in the adults?

They were not, which wasn’t actually a surprise to me. Beginning in the first weeks and months of the pandemic, there was a lot of exploratory use of a number of therapeutics that we saw in adults. And parallel to that, there were a number of therapeutics such as remdesivir that were entering clinical trials and being developed for use in adults. For kids, all of the repurposing of existing drugs and exploratory use would be very much off-label. And so as clinicians we tend to be more hesitant to use drugs in ways that have not been established in terms of safety or efficacy already in adults. So it wasn’t surprising to me that there wasn’t widespread use of a number of those types of exploratory therapeutic approaches. What I think was more remarkable, though, is that there were very few children who for example received remdesivir, which is a drug that was quite promising, or there was a lot of hope that this would be an effective treatment early on. And the reason that kids were not receiving remdesivir was primarily due to the fact that they were not eligible for enrollment in clinical trials. So, many adults had access to remdesivir through clinical trials, but for children, they needed special types of permission in order to be eligible to receive remdesivir.

Florence, that brings us to your long-term work in regulatory issues regarding pediatric populations. I know that was the topic for which you received the Burroughs Wellcome Fund Innovation in Regulatory Science Award in 2017. How has that funding impacted your research?

The Burroughs Wellcome Fund award was really instrumental in allowing me to establish this discipline, or pediatric regulatory science specifically. And it’s allowed me to really dive into this and create a community in empiric research studies around this topic. At Boston Children’s Hospital, I established the Pediatric Therapeutics and Regulatory Science Initiative as a focal point to create a community and to spur research around this specific topic, and then I subsequently also took on a role as co-director of the Harvard/MIT Center for Regulatory Science, where I also work on a focused group of pediatric studies, again around regulatory science.

So are you seeing any movement toward more inclusion of children and young people in clinical trials by pharma?

Absolutely, and I think in large part this is due to two legislations that were passed now almost 20 years ago, the Pediatric Research and Equity Act, which was passed in 2003, and the Best Pharmaceuticals for Children Act, which passed in 2002. Both of these legislations were specifically designed to increase the amount of pediatric research for drugs and biologics. While there have been some limitations to their implementation and to the degree of research and certainly labeling of products that we’ve seen, they have changed the entire approach taken in term of how pharma thinks of and plans and times their pediatric studies. So I think that there has been substantial change related to those legislations, but I would say there is still a lot of room for improvement.

What has made the industry and FDA so reluctant up to this point?

Historically, the attitude really has been that we should be protecting children from research, as opposed to using research to support their care and to benefit them. So I think it’s taken a long time to reverse that attitude and to design approaches that are safe and are maximizing the benefits of any research for children. Of course we don’t want to start any product development in pediatric populations. Typically, we want some safety and maybe even some efficacy data from adult populations, but the exact timing of when the benefit/risk balance points towards inclusion of children, that’s where there’s still some room to move, and where there is still some debate.

What is the current regulatory situation?

We’re still largely dependent on these two legislations that I mentioned, and they haven’t evolved too much. So unfortunately one of them has a lot of carve-outs or exceptions and delays, which limits its impact a little bit. And the other one, the BPCA, the Best Pharmaceuticals for Children Act, is limited because it’s only an incentive mechanism, so pharmaceutical companies can choose whether or not to respond to a request. So I would say that we have two good legislations in place, but what we really need is ongoing, data-driven approaches or assessments for how they can be strengthened. So where there are still gaps, where there are loopholes, if you want to use that term, so that we can better incentivize and also mandate certain types of pediatric studies.

And that’s where you and your colleagues come in, right?

That’s right, exactly. So what we’ve tried to do is take all the data that’s been generated since the implementation of these policies and perform comprehensive analyses of the progress to date to we can try to pinpoint the specific shortcomings and areas where additional efforts are needed.

Florence, thanks for taking the time to speak to us.  We wish you the best for continued success.

Thank you so much for having me today, Ernie, it was a pleasure speaking with you.

We hope you’ve enjoyed this edition of the FOCUS In Sound podcast.  Until next time, this is Ernie Hood.  Thanks for listening!

This edition of FOCUS In Sound is a family affair, as we connect with two members of the Burroughs Wellcome Fund, gentlemen who are primary practitioners of the Fund’s profound commitment to supporting science education. I will mercilessly pick their brains to gather their thoughts about the Fund’s activities and the larger importance of science education in our society.

Alfred Mays is a senior program officer at the Fund, and serves as the Director and Chief Strategist for Diversity and STEM Education. He began his tenure at the Fund in 2015, and is responsible for strategic program development and diversity in science. He directs a portfolio of competitive and strategic grants and serves on a number of nonprofit educational and civic boards. And Dr. Samuel Houston, Jr., is President and Chief Executive Officer of the North Carolina Science, Mathematics, and Technology Education Center, better known as the SMT Center. He has held that position since 2003. The Center is housed at the Burroughs Wellcome Fund facility in Research Triangle Park, North Carolina, and is largely supported by the Fund. It is dedicated to the advancement of science, mathematics, and technology in the schools of North Carolina and around the nation. Sam has had a long and distinguished career in science education.

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In this edition of FOCUS In Sound, we meet Dr. Laura Ensign who is making important strides in nanomedicine for drug delivery, in a variety of therapeutic areas. 

Her wide-ranging interests and research pursuits focuses on the characterization of biological barriers in health and disease in order to design more effective formulations for prophylactic and therapeutic drug delivery.

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In this edition of FOCUS In Sound, we are honored to welcome to our microphones the winner of the 2012 Nobel Prize in Chemistry, Dr. Robert Lefkowitz of Duke University.

Dr. Lefkowitz is James B. Duke Distinguished Professor of Medicine, Professor of Biochemistry, Professor of Pathology, Professor of Chemistry, and Member of the Duke Cancer Institute. He has been at Duke since 1973.

He and his team pioneered understanding of receptors, particularly G-protein coupled receptors, or GPCRs.

He has been a member of the board of the Burroughs Wellcome Fund since 2019. Most recently, he just published his memoir, titled “A Funny Thing Happened on the Way to Stockholm: The Adrenaline-Fueled Adventures of an Accidental Scientist.”

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