September 8, 2026 | You can’t forecast the next epidemic with precision, so why do we keep building preparedness plans that depend on guessing? Host Dennis Burton, Ph.D., sits down with Jim Crowe, Jr., M.D., professor and director of the Vaccine Center at Vanderbilt University, to map a more durable approach: AHEAD 100—Advanced Human Epidemic Antibody Defenses 100—an index-fund-style program to create and stockpile human monoclonal antibody drugs for the 100 infections most likely to spark major outbreaks. The goal is to take best-in-class neutralizing antibodies, move them beyond early clinical testing, and get them ready to deploy when the world needs them. They also honestly discuss scientific accountability, what the public is asking of researchers, and how to think about gain-of-function research without slogans.

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The Scripps Research Institute

Vanderbilt University Medical Center

GUEST BIO

James E. Crowe, Jr., M.D., Ann Scott Carell Chair, Professor, and Director, Vaccine Center, Vanderbilt University Medical Center
Dr. James Crowe is director of the Vanderbilt Vaccine Center and the Ann Scott Carell Professor of pediatrics, pathology, microbiology, and immunology at Vanderbilt University. He is the director of the Human Immunome Project, an ambitious effort to identify the sequence of all transcripts for human adaptive immune receptors. He is an elected member of the National Academy of Medicine and National Academy of Inventors. His research group uses a very broad array of techniques, including molecular and cellular biology, state-of-the-art imaging and flow cytometry, bioinformatics, and bioengineering approaches to attack scientific problems at the forefront of immunity research. The group has been recognized as the Best Academic Research Team for the 11th Annual Vaccine Industry Excellence Awards, World Vaccine Congress, and was the recipient of the 2019 Merck Future Insight Prize for Pandemic Preparedness, as well as large-scale research grants and contracts from NIH and DoD, including the DARPA Pandemic Prevention Program (P3).

MODERATOR BIO

Dennis Burton, Ph.D., Chairman and Professor, Immunology and Microbiology, The Scripps Research Institute
Dennis Burton is the chairman and professor in the department of immunology and microbial science at The Scripps Research Institute. He was awarded the James and Jessie Minor Chair in Immunology. He is the scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Consortium and Neutralizing Antibody Center, director of The Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) at Scripps, and a member of the Ragon Institute of MGH, MIT, and Harvard. He has received numerous awards including the Jenner Fellowship of the Lister Institute and a Fellowship in the American Academy of Microbiology. His research focuses on infectious disease, particularly the interplay of antibodies and highly mutable viruses (notably HIV). He is interested in the potential of broadly neutralizing antibodies to inform vaccine design.

He received his bachelor’s degree in chemistry from Oxford University and his doctorate from Lund University, Sweden in physical biochemistry.

TRANSCRIPT

Welcome To The Chain

Welcome to The Chain, the podcast exploring the lives, careers, research, and discoveries of protein engineers, scientists, and biotech professionals. We look at the impact their work is having on the field and where the industry is headed. Tune in to stay up to date on the newest advancements and to hear the stories that are impacting the world of biologics.

Jim Crowe’s Big-Science Vision

Welcome everyone. My name is Dennis Burton. I am a professor at the Scripps Research Institute in La Jolla, California. I've worked for many years on antibodies, particularly antibodies to pathogens and particularly HIV, and in more recent years of being involved with a large consortia trying to learn from bordering neutralizing antibodies to HIV how to make an HIV vaccine. And I've known today's speaker, Jim Crowe, for very many years. We've been colleagues and friends for, as said, many years, and hopefully today we're going to find out what what what Jim's doing, what his what his uh his aspirations are, and uh some of his opinions on the the field and where it's or the fields and where they are going. So first of all, I I think we'll do this in historical manner. So I'll try and uh get Jim to talk about his uh career from the beginning. But first of all, let's let's ask uh let me ask Jim to uh summarize what he's doing now, what his uh position is, what he's thinking that he would like to do, and then we'll um we'll go into his his story. So let me hand over to you, Jim, and and ask you to uh uh do that brief summary to start.

Great. Well, it's good to be with you, Dennis. And uh as you said, we've known each other for decades. It's fun to talk life and also antibody science. I trained as a pediatrician in infected diseases at Chapel Hill, and then I went, you know, I was seeking to make a broader impact than only seeing patients, but to try to do something larger that would prevent disease all over the world. I got inspired to do that by mentors I had at Chapel Hill, and I ended up in the laboratory of Bob Chanock at the NIH and have had a 30 or so year career in in vaccines and antibodies. What I'm doing now, I'm trying to do some big science initiatives, the the most central of which we've called AHEAD 100, which is to make human monoclonal antibody best in class drugs that can prevent or treat in the most likely infections that are going to cause epidemics, the most likely 100. So we're trying to make 100 drugs and get them on the other side of phase one and stockpile them to be ready for epidemics. So that's taking a lot of time and energy. I'm also interested in marrying that to rapid and efficient and cheap manufacturing, because if antibodies were cheaper, they would be used more frequently. And so we're we're trying to pull manufacturing all the way up into antibody discovery. So that's a another initiative. And uh even have fantasies of doing what's called on-demand manufacturing, where you'd have something like a almost like a 3D printer at your pharmacy, or why not in your house, where you you order from a site the the recipe and it downloads to your printer and you print out an antibody and you can use it in your house or your clinic or wherever you are. So these are more tractable problems all the way to more fantasy things. And uh and then I, you know, I get distracted sometimes. I'm I've got a whole new program going in ancient DNA and studying mummies and trying to define the immune system response to ancient infections by studying ancient tissues. And this came out of studies we did on 1918 flu, and then I was thinking, how can we go back farther? So now we're studying tissues that are thousands of years old. So that's kind of an overview of the things we're doing, and they're they're mostly immune-related and antibody-related, and it's it's it's a lot, but we're enjoying it.

NIH Years And The Antibody Pivot

Thanks, Jim. That's great. So we first met, as I say, I think about 35 years ago in the lab of uh Bob Chanock. Can you tell us, well, first of all, how how a little bit more about how you got there and then your experiences at the um at the NIH and particularly in uh in Bob's lab?

Well, I was a pediatric resident at Chapel Hill, and I started thinking about public health, and I even contemplated uh an entire career working as a physician in Sub-Saharan Africa, and I had mentors there who sort of probe my interest in that, and really I was interested in bettering the health of the most vulnerable people in the world, which included children in Sub-Saharan Africa. And when you look at what kills millions of children in Sub-Saharan Africa, it's either prematurity or infection, and within infections, diarrhea or pneumonia. So I I was encouraged to sort of sort through that, and I decided, okay, I'm gonna work on pneumonia of children. That's gonna be my lead target. And my mentors connected me to Bob Chanock, who'd been very involved in the early identification around the time of my birth in the early 60s of viral pathogens because self-culture had come out and he had trained with Albert Sabin. And this was a real connection for me because my mentors had shown me the stories of the eradication of polio, in which my mentors had taken care of children on iron lungs at Chapel Hill, but now those devices don't even exist, except in museums. And that was very inspirational to go from a ubiquitous experience that was very debilitating and just make that go away. And of course, Sabin was very involved in that. So I ended up with Sabin's main protege, Bob Chanock, and sort of pursuing that dream. But you know, polio had already been dealt with. So the next frontier was really respiratory viruses. And so I went and worked on RSV, which is the most common cause of hospitalization of children all over the world and hundreds of thousands of deaths a year, and worked on vaccines. But at that time, and I'm obviously a large proponent of vaccines, I've spent a lot of part of my life researching them, but uh you and others were developing really innovative techniques to make human monoclonal antibodies. And this captured my attention. So I I basically shifted my career there, my attentions from uh vaccines that induce antibodies to making the antibodies themselves. And there was a it was a fantastic experience at NIH in the intramural program because there were so many leaders who had historical impact on so many fields. And we had lunch together. I learned so much just in the lunchroom, much less in the lab. And of course, Chanock was very inspiring of having known Saban, but also all the leaders of that generation in the ways they thought. And I guess one other thing that really impacted me there was Chanock was very focused on the idea of functional antibodies or neutralizing antibodies in particular, being the most common correlate and mechanism of protection induced by infection or vaccines. And that's been sort of a North Star for me to uh probe that idea. It's not always true, but it's generally true, especially for RNA viruses. So using neutralization as a benchmark to pursue antibodies as drugs has turned out to be a really important tool. And I think that that really came from Sabin and then Chanock, understanding and studying first the viruses that cause the diseases and then the immune correlates. That was the foundation on which we're still building.

So, Jim, the very or one of the first times that we met at the NIH, you were in a naval uniform. Do you want to can you tell us a little bit about that?

Well, I was in the what's called the Commission Corps, United States Public Health Service. So this is a a non-military branch of uniform service where you can choose in certain positions when you serve at uh FDA or CDC or NIH to, if you're invited, to join the Commission Corps or not. And I chose to do that. I I was at part of the corps. And from a practical standpoint, I was in the lab like any other postdoc, but there were connections to the United States government that were a little bit deeper. And when I left, I stayed in the inactive corps and made myself available. So in certain war situations, I'd be contacted, hey, are you available to backfill if physicians at the Navy hospital ship to the Middle East? And you know, the potential was for me to go back to Bethesda and work in the hospital just sort of backfill. That never actually happened, but I I felt grateful to the United States government for training me and making the resources available. And I I've always been, you know, essentially loyal to the country as a citizen. I want to be a good citizen. So it was sort of part of that notion. And, you know, I had a history of as of being a Boy Scout and all that sort of thing. So it sort of fit with my experience of good good citizenship. And it, you know, it it was a good

Accountability And Safer Virus Research

experience.

So a lot's been happening at the NIH in the last uh 18 months to two years. You know, many people that we jointly know have have moved on, for example. How how do you feel about that? What's what's your kind of view of what's happening at the NIH in recent times?

Well, it's uh it's a really interesting time in the history of infectious disease research. And I think what's really happening is the public and legislators and leaders of our country are asking for accountability of the research community. The research community is given enormous resources and opportunity and also responsibility to develop things that are beneficial for the nation. And I think we're just in a period of questions about uh accountability. What are we doing in terms of safety? Are we uh what is our our role and decision making about policy as scientists versus public health people and so on? And it's it's been rocky and there's been a lot of glitches in the discussion. But I, you know, I welcome the the overall public engagement with science, even if a lot of public seems skeptical, at least they're engaged. So we're talking about the role of science and scientific research and safety and resources. So I think long term it's it's actually gonna make our system more robust. In the short term, there I think there's just been a lot of change and and change is hard, uncertainty. And I think as a researcher, uh policy changes are are sometimes hard to understand, what what is intended? And I I think as scientists, we're trying to do the right thing to create beneficial medical countermeasures for people and for the country and to do it safely. So I don't I don't think scientists are are negligent, but I do think we have to learn how to articulate that we are accountable to the public and to the government, and I think we'll work through that.

Okay, let me let me just take one more kind of controversial issue, which I'd like to hear your opinion on, and that's gain of function. How do you how do you feel about that? I mean, I appreciate that there are many definitions of gain of function, but have you followed that, the discussions over the years there? And what do you think what do you think about gain of function research in well, particularly in pathogens, viruses?

Yeah, absolutely. I think it's a really important discussion. And we do a lot of research in which we make antibodies that are have antiviral function. And in my case, historically, the FDA has required us to understand how do these antibodies work, where do they bind on the virus, and how would the virus evade the activity if it did so naturally? In order to do that, you would often select an escape mutant virus in vitro, and you can almost always do that for an RNA virus, not always, but very, very commonly you can do that. And in my opinion, this is still really important because escape happens naturally in the field. That's what you know, we've seen that broadly for SARS-CoV-2. Everyone's an expert on variants now. So variants occur in nature and understanding where the virus is going to go and how the viruses will naturally evade immunity, I think is important to do. But I think what we don't want to do is create viruses that are not likely to exist and engineer them with molecules in ways they they wouldn't ever happen naturally, just to see what would happen. I think that raises the risk of making something that would never exist and sort of what's the purpose of that. And then the public's asking, what if that leaked out of a lab and caused a worldwide problem? And I think that's concerning. I think there are some things we just shouldn't do and we don't we don't really need to know. But studying natural variants that have already occurred or are occurring or likely to occur, I do think it's a benefit. I think we need to articulate to the public and to the government and regulators the risk-benefit profile there. What is the risk? And I think the way forward generally in this area is going to be using biosafety level one or two reagents that are not the authentic virus, but doing this with proteins or or biosafety level two viruses in which we put the protein from a you know biosafety level three or four agent into that. And that's what we're doing now, generally. We're not using the authentic virus, so there's no risk that we'll generate an authentic virus that's worse or escape. We'll just we'll have the information, but not the actual virus. And I think that that's probably a way forward that everyone can settle on.

Good, yeah. So let's move on

Nashville Roots And Vanderbilt Calling

then. Vanderbilt, you are you are um a native of Nashville, I think. Were you do you like country music?

Well, I was born at Vanderbilt in Nashville, actually. My my family is from Nashville. So the the general culture and regional preferences and food and all, you know, it's familiar to me, and that's all good. I personally I love African music, and I'm mostly listening to African music. So, not you know, I'm not enmeshed in country music. Although, if you live in Nashville, you hear it all the time because every person who's waiting tables is also a songwriter and and maybe very talented. So you're just surrounded by music talent here and people who are in the business. And even, you know, we received some significant philanthropy from Dolly Parton during the the COVID outbreak that jumpstarted our research program. And I got to have dinner with Dolly, and I mean, there's just some amazing business philanthropic people in the music industry, and it's a big part of living in Nashville. So, yeah, I I like the the community, although I'm just generally listening to African music.

So, yeah, so when you move, yeah. So tell us the move from NIH to to uh Vanderbilt.

Yeah, when I was in NIH, I was a straight research postdoc in a lab and I was not seeing patients. And I had been there for five years, and I had to make a decision at some point. I was going to lose my clinical skills. And I was trying to decide am I going to be a laboratory scientist just straight up, and that's my full-time occupation, or am I going to be a physician scientist where I'm sometimes practicing and sometimes in the lab? And there is benefit, in my opinion, for having certain individuals who do both so they can be sort of an edge walker and translate science to the medical community and then define the medical need and bring it back to the research world. So I decided after five years, yes, I wanted to pursue a physician scientist career. So that really wasn't fully possible in the intramural program at NIH. So I made the difficult decision to leave that very robust environment and got a job at Vanderbilt as a physician scientist. And I finished my infectious disease training. And then I worked as a pediatric infectious disease specialist in the clinic for about 15 years, seeing patients with, you know, maternal infant HIV diads and TB and stem cell transplants with infections, just the wide variety of things that can happen in infectious disease world. But 80% of the time I was doing research, so I was sort of going back and forth. And at some point, about 15 years in, I just couldn't juggle all the balls because my research career was taking off. And I over time just sort of downsized the amount of clinical activity I was doing. And at this point, I have not seen patients for care for about 10 years. I still have my license and DEA and all that sort of thing. I still do all the doctor stuff because I do clinical research by obtaining blood or leukophoresis samples from patients who've had infection. So I'm still on staff, but I'm not seeing patients for care at this point.

So you said your career was was taking off. Was there any sort of particularly particular landmark or was it one or two years, or was it a much longer period that when you felt that your career began to take off? How did you know that your career was taking off?

Well, I I worked very hard and I felt like we were doing really important work. We were isolating single rotavirus-specific B cells from the gut of babies and children's and biopsies. And that was at the very front end of human monoclonal work and not doing it with phase display, but doing it out of individual cells from tissues. I thought it was pretty stunning, but I couldn't seem to get traction with journals at high levels. And I felt sort of frustrated. But I had a benchmark moment. We invited Max Cooper to visit as a visiting professor who was at the UAB and you know, now Emory. And he he's just a seminal scientist in terms of B cell discovery of B cells and their biology, and a really lovely man and incredibly accomplished. So I had dinner with him, and I was sort of complaining, like, I work so hard and I can't seem to get this B cell work forward. And he just reassured me said, I think you should just do what you love and ask the questions you want to ask and just pursue that, and just let all this sort of climbing into journals or that sort of the status idea of it let it go. Just let that worry go. And honestly, Dennis, I think it was about six months later we had a paper in Nature on 1918 influenza responses in a hundred-year-old people, where we isolated, you know, B cells at least 60 years later for the 1918 flu. And I think the same month I had a paper in PNAS on cell biology of RSV infection using you know confocal microscopy and a lot of protein biochemistry. So I had two fields going in my lab, and they both sort of had good papers in one month. And and then I I sort of relaxed. I felt like Max is right. I should just do what I want to do and not worry about what other people think about it. And then it it just sort of felt easier and it it started clicking, and the funding came, the papers came, people joined the lab, and it's been a fun ride, really.

So clearly, very important people to you, Bob Chanock, Max Cooper. I mean, Max is amazing. I mean, really um Nobel Prize should be there. But Bob, Max, anyone else in if you sit down now and say who yeah, if you have to say three people that are really influenced you, would can you think of a third one or it's a good question.

I mean, uh a lot of mentors have been important to me. Uh I I I mean, it's awkward to say on this podcast, but I think my relationship with you and Carlos Barbas in the early 90s when human antibodies were just becoming possible, the fact that we all came together and had this dream that we could that we could obtain human monoclonal antibodies and turn them into something for good. I remember that was so heady, just the fact that we could get them. And I distinctly remember Chanock had he and his friends, sometimes Maurice Hilleman, and you know, a lot of the people from the 50s of the vaccine world had a Cold Spring Harbor meeting on vaccines, and it was kind of their club, but they would invite all the people doing important stuff in the field. And I remember we showed up with FABs for RSV that we'd done together. And uh, I remember someone in the audience said that will never work. Everyone knows FABs will not inhibit a virus, and yet we had on the slide neutralizing activity and protection of a mouse. So the things that were going on with you, and and also Carlos was amazing, right? He was just so technologically gifted and so humble, and uh, it was just fun. I I remember just the the fun and excitement of working with you. And of course, Chanock was friends with Lerner, who was the head of Scripps. So Chanock and Lerner made the connection, but then working with you and Carlos was was sort of a thrilling beginning of my antibody career. So I think that that whole couple of years was very inspiring to me. You know. Sure, sure, it

AHEAD 100 Antibody Index Fund

was.

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Moving on then to your antibodies to pathogens, take us through some of that. You know, Zika, Ebola, SARS CoV 2. How how yeah, how How did that go? Because you built up a large team over this time and invited a lot of uh and and and gained a lot of funding. So give us a bit of the history of how that's happened.

Well, when I in the late 90s, the US US and the Soviets had a treaty pinned out that they were gonna sign to eradicate smallpox by it was only left in certain labs and they were gonna autoclave it and it would be gone. And I think certain scientists said, wait, we don't even know the sequence of these things. We we know very little, and we're gonna eliminate the research opportunity. So the Clinton administration put $50 million into smallpox research before the autoclaving was done. And I think maybe you, you and I got the two antibody grants for that. And I showed up in Washington at a meeting on biodefense agents, including smallpox, and I was just blown away about all the bad things that can happen in the world and all of the uh biowarfare and bioterrorism concerns, and I just got really intrigued by it. So I was working on vaccinia, smallpox, monkeypox, cowpox, antibodies. That was the idea. But then I realized, wow, there's so many families in which you could see a danger, and very few people were working on these things. Some virologists were, but in terms of making a solution, there were so few people. So we started trying to work on them one by one, especially when an outbreak occurred. So H5 flu in Asia, and we made H5 flu antibodies. And then as each outbreak occurred, whether it was Zika or Ebola or Chikungunya, we were responding to the outbreak and trying to go fast, fast, fast. And back in those days, fast was like two years. So by the time we were done with one campaign, and and I literally, the moment I decided to do the Ed 100 program was we had just published a paper on a set of antibodies for one pathogen in cell, and we were pretty excited about the work and the antibodies and the paper. And a journalist, local journalist, wanted to do a TV interview on the next epidemic, which was just happening that week. And I realized they don't care. This one happened two, two years ago. They want to know what we're doing about the one that's happening this week. I decided, well, we have to go faster than this. And, you know, we started learning how to go fast, fast, fast. And it just never was fast enough. And so then I thought, well, the only way to be faster than about a month, which is where we got, was to do it ahead of time. And so then I said, well, we're just going to make antibodies for all the infections that can occur, and we're going to do it ahead of time. That's it. We're done. That's what the goal is going to be. And frankly, that is what we're doing. So we made a list of 100. I think we have six or seven that have gotten into human beings in the clinic. One of them was a full-blown drug in you know, 70 countries. So we are executing on making 100 drugs and stockpiling them. And we're seven or eight into it. And uh in terms of lab work, we've already done 30 or 40 of them. So it it really came from not being fast enough to doing them all. And then why 100? Well, the problem is you can't predict the next one. If you knew what the next one was, you would work on it. But if you work on one to ten of them, which is what the funding bodies like you know, NIH or CEPI or Wellcome and all these people, they they try to they they have limited resources, they try to predict the next one. And I just decided that's like stock picking. Stock pickers in general don't do well financially, whereas index fund investors, their stuff goes up 7% a year and they make money. So I thought, well, we're just gonna do index fund investing in research on emerging infections. And so the AHEAD 100 program is essentially an index 100, you know, investment. And any outbreak that occurs, it's gonna be on my list. And if I've already done it, which has played out this year because measles outbreak, well, we already had measles antibodies, Andes hantavirus on a cruise ship. Yeah, we already had that. Bundibugyo outbreaks going on right now, yeah. We did that 10 years ago. We already have these antibodies in hand, and we've already done non-human primate studies and so on. So it's starting to work. It's just we don't have the clinical grade material usually to move forward. So I'm sort of doubling down on this idea of AHEAD 100, and we're just looking for sponsors to help us fund it at this point.

So who is funding it now?

Well, we've been very diligent to put in family-by-family grants, basically. So there is a prototype pathogens program that was envisioned by Barney Graham and others at the NIH, and that rolled out from NIH funding in a program called ReVAMPPs. And we're participating in three different ReVAMPP consortia, one of which we lead. So that covers coronaviruses, arenaviruses, bunyaviruses, alpha viruses, flaviviruses, filoviruses, and paramyxoviruses are in our ReVAMPP. So we've got specific funding for those families. And then we've participated in the NIH B- cell epitope mapping contracts for a very long time. We're doing influenza studies there, including avian influenzas. And then we also have shifted, I think unusual for academics, but we've shifted to the Department of War entities. So we have funding from CPE, which used to be called JPO, and we've had funding from DARPA and DITRA and various agencies that are more on the military side. And that's also been helpful because a lot of those allow some more translational and even some manufacturing activities. So pushing things farther along. So a combination of HHS and NDOW funding is really how we're we're pulling it off right now.

So are there pathogens that you don't yet have antibodies to that that maybe keep you awake at night?

Well, it's interesting. The ones that are the most lethal generally are pretty easy to work on because we can find individuals who survive those infections. And if you've had something like Ebola virus in your body for three months circulating around, you typically are going to have a lot of B cells, and you at some point will have affinity-matured some of those clones to be extremely good antibodies, avid and neutralizing. But it's actually harder to get antibodies to some of the viruses that in most cases are less lethal. So, for instance, we're doing rhinovirus C discovery program for several years now. And it's proven to be very difficult because rhinovirus C can cause severe pneumonia, especially in immunocompromised people. So it is a significant target for us. But most people get an upper restroom infection, like a common cold. And that doesn't seem like it's a very immunizing event. And so the convalescent individuals will have very low B cell frequencies. And also the antigen has some quirkiness that it's very difficult to reproduce the antigen. And so we've really struggled with rhinovirus C. I think we're getting a little bit of traction, but you know, it it's not difficult to get the hemorrhagic fever ones and these viruses that cause a lot of viremia. It's harder to do the ones that only infect the mucosa, get in and out, and have very little viremia. I think it's not that they keep me up at night in terms of worrying about a pandemic or something, it's more about just the technical difficulty of meeting our goal of getting antibodies for it.

So, you know, some folks would worry, for example, about filoviruses and you know, a pandemic. What what would your thoughts be on that? I mean, do you think that some of those most, if you call them spectacular viral infections, some of them producing hemorrhagic fevers, do you think those are real pandemic or or yeah, pandemic threats?

Well, they they clearly cause significant epidemics. And the last, you know, the last Ebola West African one killed 10,000 people or something. So, I mean, it depends on whether you consider that significant or not. The pandemic risk, in my opinion, you know, stems from the R naught, the likelihood that one case will infect how many other people. And once you get over an R naught of two or something like that, then you're gonna get a very large outbreak if you have susceptible individuals. And so it's gonna be uh, you know, if I had to guess, which I don't like guessing, the whole point of AHEAD 100 is to do them all, but if I had to guess, and influenza viruses in general, they're gonna keep causing pandemics. So they're just well suited to that and they transmit well in respiratory and fomite transmission. Coronavirus is the same. Some of the paramyxoviruses, you know, a lot of them have respiratory spread. So measles is is obviously proving its metal as highly transmissible and it transmits by small particle aerosols. I think we're gonna see a lot of measles, but the big, big pandemic's probably gonna be flu and coronaviruses still, even though people already know about them.

How To Run A 50-Person Lab

So switching gears a little bit, how how many folks do you have in your in your lab at the moment?

Yeah, it's funny. Generally, I don't know, but I had to we're doing a personnel review this week. So I actually do know it's uh 49 people at present. So we run around 45 or 50 typically. But you know, it's it's interesting because I uh running a larger group is not something you learn typically in scientific training. So I done a lot of executive coaching with local coaches in Nashville, and I'm also in a a national program with Stephen Cotler, who's a major New York Times bestselling author and coach about you know how to get stuff done that's aspirational. And so we've we've designed our group in special ways, like we have a lot of project managers who are not scientists, but they're experts in project management, MTAs, CDAs, IP, and shipping and federal regulations, export control, biosafety, chemical safety, human society, all that kind of stuff. So we have program people who do that, and they're sort of the glue. And then we have a really good administrative team, we have several lab managers, we have IT people who do programming, and they built us our own bespoke laboratory information system. And so when you boil it down, I think we have a and we have a lot of technical staff as well. So we have about a dozen people who I would say are sort of project leads, maybe 12 or 15. So each person's doing two or three projects, probably, and collaborating with others, and they're the point person, but that one person can pull along the other 50 to support them. And it it's kind of based on military models where you have a special forces person and you drop them behind enemy lines, and it's just one person with a bunch of equipment on them, but behind them are all the communications people, the supply chain, and all that. So, so we have a relatively small group of about a dozen people doing projects, but supported by the other 40 or so, and that's the model. And I came up with that, you know, through executive coaching because I used to have 50 direct reports, and believe me, that doesn't work very well because you just can't do that. So now I have a more organized system and it's good. The it sort of works like a clock.

So let me ask you about uh mentoring. So Bryan Briney, who in uh you know very well did a PhD with you, came to me, did a post document, he's now a full professor at scripts, you know, huge, hugely successful. I mean, how do you feel about mentoring within the kind of framework that you have, which is, you know, in some ways more like a biotech setup than than maybe a classical academic lab. How do you deal with the mentoring? Where where do the most of the people that uh work with you, where do they go or do they stay with you?

Yeah, well, mentoring's been a big part of my you know life as a lab head and also the lab culture we like doing it. The people who work in our lab generally like training young people for new careers. I think it's evolved over time. There were there used to be a mix of people who would come and then go into public health careers at the CDC, FDA, NIH. Lots of our grads are in US government labs like that. And then some were going into industry, and then some wanted to do a traditional academic route. I've had an intellectual property law grad, etc. Over time, I think the goals have shifted more toward industry, and maybe that is because our lab looks like a mid-sized biotech now. I mean, we have millions of dollars equipment and robotics, and there's a lot of automated stuff. So at this point, when we're recruiting, so the graduate students all show up in in August. So this is about to happen for me. And, you know, 25 of the 75 students will show up and say, hey, I won't I might want to be in your lab. And we sort of send them all away and say, no, you don't want to work here because it's too big and fast and chaotic, and you'll get lost in the shuffle. And some of them will come back and say, Well, no, I worked in a big lab, I know what you're talking about, or I worked in industry. So there are people who are still going to grad school who have some experience of working in larger groups or in industry, and those people are a better fit for us. So we sort of vet them and we only take in trainees who can work horizontally with lots of different people with different skill sets. And um, also, I used to do all the interviewing and accepting of trainees, and now they don't even let me do that. We have a whole process in the lab where people are vetted and they have to interview with 12 individuals in the lab. And if anybody vetoes them, then probably that person's not getting in. So we have we have sort of a group hiring process, and at the very end, I I accede to the group will. But I I want to be excited about training the person, but I'm just saying it it has to be a good fit for us for them to succeed. And that's been a good process because we have students now who I mean, I have a student who trained with me maybe five years ago, went to a biotech startup in California and already has a drug that she made in the biotech in the clinic. So to see that kind of rapid success in any of these fields, uh, industry, government, academia, it's very fulfilling. And I and I can see our it's not just me, our team's impact is sort of propagating out into the world. And yeah, I love to see it. It's great.

Yeah. So switching

Where AI Actually Helps Antibodies

gears again. So one quote that I've seen from you was that pattern recognition is a big part of how science is done. And you know, I'd agree with that. And of course, one of the most powerful tools now for pattern recognition is AI. Are you using AI? What what what what are your views on on AI?

Yeah, every person in every business field has to deal with how to integrate AI into the workflow and deal with the existential angst about it. What I would say is there's a conversation going on in the antibody field. I I feel like right now that there's sort of a hype cycle. AI and and designing antibodies de novo on a computer is completely replaced lab scientists, and we won't need that anymore. And then the lab scientists like me are saying, well, I can make a million, and we have. We've made a million monoclonals from a single sample. How many more do you need? And ours are naturally occurring, they're not engineered, so actually, we probably don't need AI. And and that kind of black and white dualistic thinking is not helpful. I think we need to not be defensive or hype cycle about our fields and just think what are the benefits of each thing. So I think what's evolving for me is we are working with people who are fully computational, and that stuff moves so fast. Every two weeks it's moving. I mean, Claude Science just came out maybe 10 days ago, and that alone is going to revolutionize how science is done. So AI is giving us new tools, but I also tell back to the purely computational people using liquid handlers and scale, we can also can very rapidly make hundreds of thousands or millions of candidate molecules, and we have them in our hand and we can validate their activity. So the real question is how to integrate these two, where the laboratory people like us are generating enormous data sets and then using AI to interrogate those and making the lab work more efficient. So what I predict that the lowest hanging fruit in our field right now is the fact that people like us can make broad and potently neutralizing antibodies for viruses, but then we hand them to a manufacturer and they say, Oh, we don't like that one. It has liabilities for manufacturing, and I don't think I can develop it. What else you got? And that's a fail if we find out at the end that we can't make it. So I think the AI tools are probably gonna be really good if they're watching large data sets of lots of sequences being expressed and looking at the expression level and aggregation and stability of those molecules. We're gonna be able to predict based on sequence developability and manufacturability in a pretty short order, I think. So if we can bring that all the way into discovery, when we discover a million monoclonals from a sample, we'll down select out the ones that are not developable before we even touch them. We won't even see them. And what comes out the discovery pipeline will be broad, potent, and developable. So I think that's what's going to happen the next year or two, even. And then, you know, we'll get better and better at using AI and lab things together. And the way I've explained this to myself, I was thinking the other day, I was walking from my parking lot to my lab and I was dictating an email on my phone. So then by the time I got to work, I realized I wrote 10 emails by walking and talking. Then I thought, well, AI just did voice recognition of my voice to put the text down. And then a grammar checking program read through that text and found typographic errors and grammar errors and fixed them automatically. And I thought, I didn't even really think I was using AI. I was just talking into my phone and it all fixed itself. So I think that's what's going to happen with antibody engineering. It'll just become seamless. We won't be thinking, oh, we're using AI. Look how cool it is. It'll just be part of the workflow, just like the high throughput, you know. I don't think I don't tell people now I do high throughput liquid handling. That's not what I do. I do antibody discovery, you know, and underneath the hood, there's single-cell RNA-seq and liquid handlers, but those are just tools. They're not the essence of it. So I think it's gonna be fine. I think we're gonna weave them together, and I'm excited about

Vaccines Versus Long-Acting Protection

it.

So, you know, you've expressed quite strong views about vaccines and antibodies. I think you you view them as as in the future equal partners. I mean, at the minute you would say that vaccines are are, you know, far more universal, far more, far cheaper, and uh you know, have done a lot more for human health than have antibodies. So talk talk talk a little bit about how how you view antibodies and vaccines, particularly neutralizing antibodies for viruses, but also you know, antibacterial antibodies given the emergence of uh resistance bacteria resistant bacteria.

Yeah, I've I find it very ironic that in the late 19th century antibodies emerged as one of the first things we could do about infections using horse serum to treat rabies and diphtheria and tetanus. Uh, the the antibody principle was established very early for infectious diseases. The first Nobel Prize was given for anti toxins, which became the word antibodies. And yet now we have closing in on 200 antibodies, and they're mostly for cancer and autoimmunity, which I feel jealous of that. Why are the cancer people getting all the fun with antibodies when they really were their their origin and their origin stories out of infectious disease? So I feel encouraged and optimistic that we're finally going to bring antibodies back to the infectious disease field, and we're at a tipping point in history right now where it's actually happening, where antibodies are gonna become as important or in some instances more important than vaccines for preventing infection and disease. And there's several reasons for that. One is investigators have found long-acting variants or mutations in the FC region. So now antibodies, instead of having one to three or four weeks half-life, they can have three or four months half-life. The other is with our techniques, we get very high potency antibodies now. You just need a little bit of antibody to do the job. So we have some Rift Valley fever antibody that are already in the clinic, have been tested in humans, that have an IC50 of 0.01 nanogram per ml IC50 neutralization. So you could almost skin prick a person to give enough antibody to treat their whole body. So the lowering of the doses needed enabled by high potency discovery programs and the long half-life is going to allow us to protect people for a year or two or three from a single injection of antibody. And that is comparable to or better than some vaccines, like uh current flu subunit vaccines or mRNA vaccines where COVID antibodies are outperforming those formats. And it's actually happened in the clinic twice. So we made some antibodies that became the drug EV-shelled with AstraZeneca. That was the first long-acting. And the PK predicted a year of protection against COVID from a single IM injection event. And then now for RSV, you can have a choice. Either the mother gets an active immunization while pregnant, or the child gets passive administration of an antibody that's long-acting. So right there, you can see they're being used equivalently. You can get the vaccine or the antibody. And I think that's going to happen more and more, especially in epidemics and outbreaks. So I'm not vaccine or antibody thinker. Again, let's not be black and white. Let's say let's use vaccines when that's the best choice. But increasingly we're going to have the opportunity to use long-acting antibodies for prevention in a vaccine-like way because of all the innovations. And I think there's some cultural resistance in science and medicine to antibodies still. I run into this. And I think that's just people have been working on vaccines for so long, they're in a mindset. But I keep telling people we're not about the technology of a vaccine or an antibody. What we are about is making people immune and healthy. So really the goal is to make people immune, not to vaccinate people. And whether we use it with an active vaccine or passive administration is we should be agnostic about that because the end point is the same of keeping people immune and healthy.

Ultramarathons And Clear Thinking

Let me ask you about ultramarathons. We know that you um at least in the past you've you've you've run quite a lot of those. Tell tell us about ultramarathons and what um and what they've done for you.

Yeah, it's been an important part of my life. In fact, I'm going to Namibia in about 10 days to run 250K in the Namib desert with a backpack, all this stuff on your back. So I still do this stuff. Uh, you know, there was a period of time when I was very busy with all my grandmother's papers and so on, and I still had more energy. I was like, what am I going to do with this energy? And the things that we do are knowledge work, right? It's all in our head, and we're kind of sitting around. And I just felt the urge or need to do something embodied, use my body to do something, and not just my brain. And so I got into running, biking, I did Iron Man triathlon for a while, and then that's like 12 or 13 hours, and then I wanted something longer than that. Well, that takes you to 100 mile ultramarathons, and now I'm doing weeklong races. So, you know, my experience is after a few hours of running, your mind sort of settles down and becomes much more clear. And at some point, you can just sort of completely clear your mind of all the noise and just be present, you know, breathe, drink, salt, sunscreen. Don't fall down. That's sort of the level of function that you have. And I find it very meditative and refreshing. And uh sometimes problems I'm dealing with, either scientific problems or maybe they're administrative problems or something like that. When I'm running, it just feels like my mind is letting go and not gripping these problems and try to force a solution. And all of a sudden, in that relaxation, an insight comes, oh, that's the way forward. It's easy. How come I didn't think of that? So somehow the the running for a very long distance changes the neurochemistry and allows me to sort of relax into good solutions. So it's it's really important, and I'm gonna do it as long as I can.

Great, thanks, Jim. Thanks, Jim Crow, uh, for a very uh interesting and illuminating informative hour. Thank you, Jim.

Yeah, thanks for having, Dennis. Thanks for everyone for listening.