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!