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“Research Ethics Reimagined” is a podcast created by Public Responsibility in Medicine and Research (PRIM&R), hosted by Ivy R. Tillman, PRIM&R's executive director. Here, we talk with scientists, researchers, bioethicists and some of the leading minds exploring new frontiers of science. This season, we are going examine research ethics in the 21st century -- and learn why it matters to you.
I am happy to welcome our special guest to the podcast today. Earlier this year, the Premier Board meeting was held in Atlanta, Georgia at Emory University. During our time, we toured the Emory National Primate Research Center where the leaders and staff graciously gave us a tour. Joining me today are two of the people who make that work possible. Doctor Paul Johnson who leads the center and Doctor Joyce Cohen who oversees the health and welfare of the animals at the heart of this research.
Ivy Tillman:Together, they represent an intersection of scientific discovery, veterinary medicine, and ethical leadership that is central to advancing research responsibly. So I wanna take a moment to welcome Paul and Joyce to the podcast. Thank you for joining us.
R. Paul Johnson, MD:Ivy, thank you for having us. We're looking forward to the conversation.
Ivy Tillman:So first, can you each take a moment to share a little bit about your career path? We appreciate having the chance to learn from our guests about how they develop the expertise that they have.
R. Paul Johnson, MD:I can go first. Sure. So I am a infectious disease physician scientist. My area of interest has been AIDS research. I did not go to medical school intending to be a monkey doctor.
R. Paul Johnson, MD:That that was not my planned career path. I went to medical school. I graduated in eighty nineteen eighty four and then did internship and residency in the mid eighties and then my infectious disease fellowship in the late eighties. That was when the HIV AIDS epidemic was first taking off in The US. And it was time before we had effective antiretroviral treatment.
R. Paul Johnson, MD:And so we were still figuring out a lot about the virus, what type of immune cells that infected, how it damaged the immune system. We were working on trying to develop effective antivirals and working on trying to see if a vaccine was possible. And so my initial work started off in in HIV infected people in in Bruce Walker's laboratory at Mass General Hospital. We're looking at a particular type of cell called a killer T cell cytotoxic T cell. And we we learned a lot about those cells, but there were a lot of questions, fundamental questions we couldn't address in people and looking at things like what happens early on in infection.
R. Paul Johnson, MD:That was a period a really critical period of infection that was very difficult to study in humans. What would happen if you had a candidate vaccine? We weren't ready to test anything in humans yet, and so we needed an animal model. Fortunately, there there was work ongoing at the New England primate center at that time by Rhonda Rosier and Norm Lutvan that established an incredibly valuable nonhuman primate model of AIDS that has spread throughout the world and models what happens in people very, very well from what cells it infects, course of disease, which is a little more rapid in monkeys than in people, and its susceptibility to to vaccines and antivirals. And so I started working doing some work part time at the primate center, trying to extend some of the work that we had some of the skills that we had in looking at immune responses in HIV infected people, translating those to nonhuman primates.
R. Paul Johnson, MD:And then it sort of took off from there. And so we really recognized I was trying to split my time going back and forth between Mass General Hospital and the New England Primate center and and then, you know, being a clinician as well. And that that was that was hard.
Ivy Tillman:I bet.
R. Paul Johnson, MD:And and so as time went on through the nineties, I spent more and more time at Primate Center and then eventually focused my career there. Sort of fast forward to 2014, the longtime director of the emory primate center, Stuart Zola decided to retire, and I was lucky enough to be selected to be the director of the emory primate center. So I got here in 2014 and have been having a wonderful time since then.
Ivy Tillman:Absolutely. Joyce, tell us about your career path.
Joyce Cohen, VMD, DACLAM:Sure. First, I just have to say that I've worked with you for twelve years, Paul, and I've never actually heard that story. So that was really interesting to to learn that. My my career path was also not said. It took a little bit of a convoluted path, but I mean, I was definitely not one of those people who grew up knowing I wanted to be a vet.
Joyce Cohen, VMD, DACLAM:I was pre med all the way, is definitely my plan, started college pre med. And it was actually a conglomeration of two things that sort of changed my path. So one, I was taking psych 101, and the professor was a renowned primatologist, Robert Safarth. And he talked a lot about animal behavior and a lot about behavioral primatology. And I became super fascinated with that and really interested, excited.
Joyce Cohen, VMD, DACLAM:I added in anthropology as a second major because I was so interested in it, you know, but still continuing my pre med path. And it was actually one summer in college when I was putting together my resume for looking for a summer job. And I looked at it when I was done, and I was like, everything I've ever done has been with animals. I haven't done any human medicine thing. I shadowed a vet at Ocean World.
Joyce Cohen, VMD, DACLAM:I worked at the Wild Bird Center. I followed the vet clinic. I'm like, maybe that's the path I want to take. And then it was in consultation with another primatologist at school that was telling me about a potential career path given my background with medicine to consider going into research, where I'd still get to work with nonhuman primates. So I decided to start exploring the animal research path.
Joyce Cohen, VMD, DACLAM:And when I finished college, I went to work in a research lab at Columbia in Visual Neuroscience with nonhuman primates, and made my decision about whether or not at this point it was either vet school or PhD in primatology. And I decided to go the vet school path, knowing that I wanted to work with nonhuman primates and work research environment. That was my goal and here I am.
Ivy Tillman:It's always interesting to hear the paths because it's rare that we've had guests or even like in our professions that had the straight path, right? And I think it's those experiences that make your career richer and what you bring to where you are now, which is at the Primate Research Center. The center has been advancing biomedical science for nearly a century. It serves as one of only seven NIH supported national primate research centers in our country. For listeners who may not be familiar with the center or even the network of primate research centers throughout The US, could you, either one of you, describe your role, the center's role, and how the work comes together to support the center's mission?
R. Paul Johnson, MD:It's a great question. Thank you, Ivy. So I'll start off. So the the system, the NIH supported primate centers were founded in the nineteen sixties, and their charge was to support nonhuman primate models that ultimately improved and advanced human health. Mhmm.
R. Paul Johnson, MD:And so they were they were all about establishing models. There's some primatology for primatology sake that that's really important. There's some work on conservation. But the primary charge is help people conduct better research in nonhuman primates to advance NIH supported research that that improves human health. So they've gone through a number of evolutions.
R. Paul Johnson, MD:They were initially when founded, they were the regional primate research centers. In the early two thousands, there was a a reevaluation of the network, and they decided to rebrand themselves as national primate research centers to emphasize the importance of supporting a national network of researchers, which is something that we do here and that all the primate centers do. About about half of the research that we support here is research that is led by by researchers outside of emory. That's that's a very important charge. And then we're we continue to evolve.
R. Paul Johnson, MD:Over the past year, a number of the centers have evolved to become national biomedical research centers. And so that's been an official change at Tulane and the at Washington. And just last month, the our primate center has officially renamed as the Emory National Biomedical Research Center. Oh, wow. And so the the intention of that is to indicate that we we support a wide range of research projects.
Ivy Tillman:Right.
R. Paul Johnson, MD:Nonhuman primate is our research is our sweet spot, an area of expertise. It takes considerable expertise and specialized resources, and Joyce can talk more about those to to support high quality top notch nonhuman primate research. And so that's that's sort of our our central charge. But on the other hand, we also support a wide range of research projects. We did a survey earlier this year on our of our researchers to look how many researchers are using new approach methodologies, NAMS
Ivy Tillman:Mhmm.
R. Paul Johnson, MD:Using the broad NIH definition, including organoids in in silico modeling, etcetera. Right. And, basically, 70% of our researchers are currently employing NAMS in their research
Ivy Tillman:Mhmm.
R. Paul Johnson, MD:In addition to nonhuman primates. And and similarly, about 70% of our researchers use human samples. Mhmm. And so I think it's important to think of us as centers of excellence that use a whole range of research models going from in vitro studies, NAMS, rodents, nonhuman primates, and human samples. So we have the complete arc of biomedical research that's designed to, again, ultimately advance human health.
R. Paul Johnson, MD:And so that's our charge. There are seven centers across the country. We work quite closely together to make sure that we have are using best practices in our line. But and we work very closely with our colleagues at the NIH to make sure that we're supporting a national group of of biomedical researchers.
Ivy Tillman:Right. Thank you for that that overview because it clarifies also the work that's done and being done and the impact that it's having on our citizens here in The United States. So, Joyce, can you describe the work that you do at the National is it Biomedical Research Center now?
R. Paul Johnson, MD:Yes. We're still we're still work we're we're still getting used to the name. But yes. And I I think just for clarity, when we say primate centers, there there are a lot of primate centers. But when we, in this conversation, say primate centers because not everybody has changed over, we're we're referring to the group of seven NIH supported centers.
Joyce Cohen, VMD, DACLAM:My role as a veterinarian here, I love my job. I love being a part of it. So we get to be a part of cutting edge research. In our roles, we get to consult with investigators and help them create their research models and figure out the best path forward, as well as be a part of the hands on work with the research using the animals as well. However, I also in my role get to have oversight and ensure animal welfare, which is critically important.
Joyce Cohen, VMD, DACLAM:And our mission as the veterinarians is we are the advocates for the animals and looking out for them while facilitating and supporting critical research. So we get to do that in many forms, whether that's grant writing and figuring out the experimental model or IACUC review and being a part of that process and refinement. But it also stretches beyond that with how we get to care for the animals. And that's why I love being at a primate center, because here we get the luxury of having so many animals that we have dedicated support staff in many different areas just for the animals, whether that's our colony management group who manages the large social groups at the field station and our breeding colonies, or our behavioral management team that's looking out welfare of every animal from a behavioral perspective. And one of the things I get to do in my role is to work on the housing and the facilities that they live in.
Joyce Cohen, VMD, DACLAM:And that's whether that's designing new caging, bigger caging with better features, geared for what the nonhuman primate needs are specifically to more social housing and to constructing new housing buildings to improve animal welfare. And that's how we work together to support all of the missions. And the last thing, while our central mission is to support human health, I always have to mention that this circles back around to support veterinary animal health as well, because all of the medical discoveries are even though their start in animals go to human, they're translated back to use in veterinary medicine for treatment for your companion or farm animals as well.
Ivy Tillman:I think that's really important to bring up because oftentimes when we're having these conversations, particularly in public spaces, we don't always think about the impact of the work that you're doing on our companion animals. My companion animal is sitting right next to me as I'm recording this broadcast. So that matters for her care as well. And you touched on the oversight and the infrastructure support that you have. Can you, either one of you, talk about the role of the Ayah Cook, particularly for individuals for whom this may be a new term.
Ivy Tillman:What is an IACUC and what role do they play in this research process and in strengthening the quality of research in animal welfare?
Joyce Cohen, VMD, DACLAM:Do you want me to start on that, Paul?
R. Paul Johnson, MD:Yeah. Why don't you?
Joyce Cohen, VMD, DACLAM:So just to to define for the public, for anyone who might not be aware, IACUC stands for Institutional Animal Care and Use Committee, and this is a group that is mandated by law under the Animal Welfare Act and under OLAW PHS guidance for using animals in research that you have to have this group. And this group consists of researchers, veterinarians, and a member of the public and non scientific member. And constitution of the committee again is expressly mandated by law. So having said that, our IACUC here at Emory mandated to have the five representation, we probably have over 50 people on our IACUC committee, we have an extremely large one, because we're combined with the primate center with the school of medicine. So we we have a lot of participants in the IACUC.
Joyce Cohen, VMD, DACLAM:And this is the group that reviews every animal research protocol that's happening at the institution. And so we look at every procedure that's going to be done. We look at the goals of the research, the animal numbers, and justification for why they're doing what they're doing and making sure that they're using standards that the institution will support.
Ivy Tillman:So you talked about different roles within the center and staff, right? How do you or how does the center encourage investigators, the researchers, the veterinarians, the technicians and the staff to ask difficult questions and look for ways to continually improve? Talking about like that culture that's created. Right?
R. Paul Johnson, MD:That's a great question, and I I think we can Joyce and I can ping pong on
Joyce Cohen, VMD, DACLAM:that. Sure.
R. Paul Johnson, MD:I think first is to have a culture of collaboration. And open communication. And it's just we we are a large community of diverse people that's required to run a primate center. We have we just within animal resources to the choice has there. There are people with a range of responsibilities, researchers similar.
R. Paul Johnson, MD:You've got sort of different operations, a principal investigator, a lab manager and technicians. Then we've got research administrators and facilities people, etcetera. So I I think one thing is just just to make sure that there are several different opportunities for open exchange of information that don't just go filter up to the top and then filter down. You have to have that communication within the in the hierarchy, in the pyramid. And in it, people need to be comfortable in expressing honest opinions.
R. Paul Johnson, MD:And and sometimes they're difficult, honest opinions. But that's really critical. And so and and having people say, hey, this line of communication is not working.
Ivy Tillman:Mhmm.
R. Paul Johnson, MD:And and I have to give Joyce credit here. Joyce has has often come to me in the twelve years to work together and say, hey, this line of communication isn't working. How about if we change it? She says it very nicely. And she's she's been right every time, actually.
R. Paul Johnson, MD:But we needed to rethink the way we had a a a constituted committee to loop in the appropriate people at the table. Mhmm. And that doesn't, again, just go to the top of the pyramid. It's lots of lines crossing the pyramid where people can provide information and have those conversations and express ideas. Then within that, you also have to have a common value.
R. Paul Johnson, MD:We can't say there's one North Star for primate center, but I think our two, three North Stars are provide outstanding care for the animals, support outstanding science and take care of our people. Those are sort of a I'm mixing the metaphor by coming up with three north stars, but we have to agree on where we wanna go. And as we go through those conversations of how do we achieve it operationally, we have to rely on on those points, taking care of our animals, supporting the science and supporting our people. But I'm sure Joyce can add to that.
Joyce Cohen, VMD, DACLAM:I mean, a lot of times you might hear there's a dichotomy between the scientists and, you know, the animal resources, veterinary staff, you know, have being opposing forces, but that's not the culture here. We work together. I mean, occasionally, have differences of opinion, but overall, we all want to move the science forward. We all want it to be meaningful and important research with good results. And we all care tremendously about the animals and their welfare.
Joyce Cohen, VMD, DACLAM:And with those main principles, we can always come to some resolution. I mean, probably the the most controversy or difference we might have might be in the finances side of it, with making sure we have enough money to run the center still and they have enough money to do their science, which can be a conflict. But we we do all work together. We we wanna invest in the animals. We all wanna see them in the best housing.
Joyce Cohen, VMD, DACLAM:You know. And at a primate center, we have such experts with some of the hands on work, especially in infectious disease that maybe sometimes the researchers aren't actually working hands on with the animals. We'll bring them into the animal facility to see the animals that they're working with. Oh, I mean, you can't not love the monkeys when you see them. They're amazing animals.
Joyce Cohen, VMD, DACLAM:And so we we work really hard to make sure that we're all talking the same language and seeing the same things so that we can, you know, all agree on plans forward.
Ivy Tillman:I like that. I heard words like collaboration and transparency and like the three like the three North Stars. I was actually envisioning them. I like that concept and it's clear what your priorities are. Like you said, Joyce, it's about moving the science forward.
Ivy Tillman:And so if we think about the scientific need for the research that's done at the center, I want us to talk about what the center has contributed particularly. Are there specific advancements or discoveries on scientific questions that have been answered during your time there or even in the history of the center?
R. Paul Johnson, MD:Sure. There are there are so many. There's there's scores. And so I we'll make a start. And we'll I think if it's okay, I'd like to highlight not just what happened here at Emory, which we will certainly emphasize.
R. Paul Johnson, MD:But Sure. Since we are a consortium of seven centers, what what's happened at all the centers? Writ large, we do studies in nonhuman primates when they can't be done in another model. Mhmm. If it can't be done in rodents, it can't be done in humans.
R. Paul Johnson, MD:And you need a model that accurately models closely as possible what goes on in humans. And so that down selects to a couple of to a handful of specific general topics of infectious disease, neuroscience, transplantation, regenerative medicine and stem cell therapy, and metabolic diseases. That that doesn't cover everything, but those are sort of the big five. Since my background's infectious disease, the contributions for HIV AIDS, for primate models have just been among the centers have just been spectacular. It's contributed a huge body of knowledge to where we are now, which is having an effective viral therapy and having antiviral regimens that can prevent infection with with essentially one hundred percent efficacy, which is remarkable.
Ivy Tillman:The
R. Paul Johnson, MD:initial studies at the New England Primate center establishing the SIV AIDS model in rhesus macaques were fundamental in providing rigorous evidence that primary lentiviruses can cause immunodeficiency. We accept that as a given right now. But in the mid eighties, just after the identification of these viruses, there are still a lot of questions swirling around. So you identify these viruses. That's good.
R. Paul Johnson, MD:But do they really cause AIDS or are there other causes? And the animal models provided rigorous evidence for that. Yeah. They taught us a lot of things about how the virus damages the immune system, in particular, how the the virus, both initially in monkeys and then it was validated in people, particularly affects the gut associated lymphoid tissue. We we often don't think about our gut, but in fact, most of our immune cells are in our gut.
R. Paul Johnson, MD:HIV and SIV in the first two weeks of infection wipe out fifty percent or more of the helper T cells in the gut. And that's a huge opening salvo in in in the course of immunodeficiency that then plays out over years to come. But those initial steps were only discovered in monkeys because you could do the studies that you can't do in people. Going on to antivirals, the Washington Primate Center did initial studies with a drug called tenofovir that had been put on a back burner, frankly, because it was difficult to administer. But the results in monkeys were so dramatic that the the drug was pulled off the shelf and said, we have to use this drug.
R. Paul Johnson, MD:They figured out a way to modify it, give it orally, and it's now a mainstay of antiretroviral therapy for tens of million people tens of millions of people worldwide. The ability of antibodies to prevent infection in infants and in in adults has been fundamentally altered by results in nonhuman primates. And then very recently, there's a really very provocative and exciting study done from investigators, both at the California Primate Center and Tulane Primate Center, looking at giving a basically a gene therapy, but an antibody that's encoded by a virus called the AAV that can deliver the gene for that antibody given to infants that could provide lifelong, apparently, protection against mother to child transmission. So one shot could prevent could one shot could, in theory, prevent mother to child transmission. And just in this past week, there are studies from the emory primate center that have been led with scientists at the Scripps Institute in California that have been able to show that using the right combination of of immunizations, you can lead the immune system down the path to generate antibodies that are able to neutralize a substantial number of diverse HIV isolates.
R. Paul Johnson, MD:The the elusive, broadly neutralizing antibodies, which have been really difficult to to produce by vaccination.
Joyce Cohen, VMD, DACLAM:Mhmm.
R. Paul Johnson, MD:With a very promising result. So that again, this is my background, so I'm a little bit biased. But arguably, the contributions of nonhuman primates to HIV AIDS research have been have really been remarkable. And that's looking in the rearview mirror going forward as we look towards trying to really get these vaccines over the line to being effective and developing less complicated regimens for people, for prospects for an HIV cure, for developing better antivirals, better means to prevent infection. Results of studies in nonhuman primates are going to continue to be essential for the for the near future, for the foreseeable future, for us to end the HIV AIDS epidemic.
R. Paul Johnson, MD:So that that's just one area. Right. Right. It's and all the centers, you can go to each of the the seven centers and see fundamental substantial contributions that each of the centers have made in in the HIV AIDS arena.
Joyce Cohen, VMD, DACLAM:Do you wanna mention transplant here for every specific
R. Paul Johnson, MD:I was about transplant. That was next up. There are really some great advances in in transplantation. To transplant an organ from an unrelated or unrelated individual to a person who needs a kidney transplant or another organ transplant, the immune system will reject it as foreign. And so you need to use immunosuppressive agents in order for that organ to not be rejected.
R. Paul Johnson, MD:And historically, those immunosuppressive drugs have been sort of blunt instruments. And while they maintain the kidney, kept the kidney from being rejected or the liver or the heart from being rejected, they also made people more susceptible to to infection. And in some cases, they have significant toxicity. So for instance, for kidney transplantation, somewhat ironically, one of the mainstay immunosuppressants is called cyclosporine. And cyclosporine suppresses the immune system very well, but it can also affect the kidney.
R. Paul Johnson, MD:So you could, you know, ironically suppress the immune system and then have the drug suppressing the immune system damage the organ that it's trying to protect. Mhmm. And so there is a really very well known transplant surgeon here, Chris Larson at Emory, who is interested in a more precise way to suppress the immune system using designer molecules that block specific pathways that activate T cells. He identified a promising strategy that worked in mice, tried it in monkeys, didn't work in monkeys. And then he had to go back working with the pharmaceutical company to refine the candidate drug, found one that worked very well, worked in monkeys, worked in people, and then ultimately was went on to FDA approval and then is now given to every patient at Emory University Hospital who has who undergoes a kidney transplant.
R. Paul Johnson, MD:The drug's called belatacept. And it was the first new immunosuppressive drug, I think, approved in ten to twenty years. And ultimately, a follow on comprehensive phase three study found that people treated with belatacept versus cyclosporine had better kidney retention rates and better survival. So it affected overall mortality. It's a great example of this arc of research where you start off with an idea, you test it in rodents, you test it in monkeys.
R. Paul Johnson, MD:Sometimes it's recursive. Sometimes you find a problem. You have to go back, try again and eventually go, well, you know, go on to human trials. But again, if we look at what would have happened if you didn't have nonhuman primates
Ivy Tillman:Mhmm.
R. Paul Johnson, MD:The likely story would have been that they would have gone forward with something that didn't work
Ivy Tillman:Right.
R. Paul Johnson, MD:In human trials and failed, and that could have been the end of the story.
Joyce Cohen, VMD, DACLAM:Mhmm.
R. Paul Johnson, MD:And instead, we have this arc of a of a drug that is very successful, better than the standard of what was the standard of care Mhmm. To help in in kidney transplantation.
Ivy Tillman:Wow. I like the illustration and the arc from the conception, like thinking about it to actually the impact on human health. And the fact, like you said, sometimes you have to go back and fix again. That's a part of the scientific process.
R. Paul Johnson, MD:That's research.
Ivy Tillman:Yeah. Yes. And we want people to understand that process.
R. Paul Johnson, MD:It's not a straight linear path.
Ivy Tillman:It is not. It is not so remarkable. So I'm gonna shift this a little bit and think about as we're talking about, you know, scientific progress and a lot of accomplishments that have already been made. Paul, actually mentioned new approach methodologies earlier when we began this conversation and we're seeing that we call them NAMS are increasingly a part of the public conversation. How do you think about NAMS?
Ivy Tillman:Like where do they show promise and where do nonhuman primate models remain essential in ways that the alternatives just cannot replicate?
R. Paul Johnson, MD:Yeah. Great great question and something, as you noted, is being, really front of mind for all of us these days as as it should be.
Ivy Tillman:Mhmm.
R. Paul Johnson, MD:A couple of overarching points to make first. One is that the primate centers and and researchers at primate centers have used NAMS for decades. Right. We didn't call them that. But, in fact, thirty years ago, I published a technique for for taking basically thymic tissue and forming what it was essentially a thymic organoid.
R. Paul Johnson, MD:Because for for early precursor bone marrow cells to mature into T cells, they need a specialized environment. You can't just plop them in a petri dish in the lab and have them turn into T cells. They need special signals, special environment. And so we we developed something like this 30 ago that allowed us to study T cells that matured in a thymic environment, but outside of a monkey. And that was a very valuable model for us to test and down select things before we did in vivo experiments.
R. Paul Johnson, MD:Unfortunately, there's been, in some conversations, a false dichotomy between NAMS or nonhuman primates.
Ivy Tillman:Right.
R. Paul Johnson, MD:It's the wrong way to think about it. Again, we use a range of research models to answer questions, to answer biomedical questions. And so it should be an you know, the the the usual, you know, and Right. It's it's the and thing. It's NAMS and nonhuman primates.
R. Paul Johnson, MD:And so I think the the current emphasis on NAMS is really critical. They they're helpful, I think, at this stage in mainly refining and reducing nonhuman primate usage. Mhmm. I would also say that another confounding factor of the NAMS debate is our our focus of our conversation here today has been on what we'll call discovery or foundational research on trying to identify how systems work and then how therapies or vaccines could improve human health. There's there's a other note.
R. Paul Johnson, MD:There's a whole nother conversation related to toxicology and use of animal models and toxicology. That's not my area of expertise. And and in some ways, I think in many ways, the appropriate use of NAMS for toxicology experiments is is advanced. Many cases because they're they're asking a specific question. Does this compound irritate skin?
R. Paul Johnson, MD:Does this compound cause toxicity to X? So they're they're asking a specific targeted question.
Ivy Tillman:Right.
R. Paul Johnson, MD:And names are often very again, that's not my area of expertise, but names are often very, very helpful there for us figuring out, Okay, how does this virus affect a whole organism with multiple organ systems, multiple immune cell types? That's we can begin to dissect that out in a in a petri dish with a name with the names and the names can give us very helpful information. But we're not at the point yet where we can synthesize that information to replace in any case that I'm aware of for discovery research for a nonhuman primate test. So it's the conversation should be like, how do we work together?
Ivy Tillman:Right.
R. Paul Johnson, MD:To use nonhuman primate NAMS, to use human NAMS in concert with nonhuman primate models to advance human health? It should be an and question and not a an or question. And so the areas that you mentioned, so there's work in infectious disease to try to see whether there's specific molecules that can reactivate virus that the that's latent, that's not for HIV cure research. And, the the NAMS models are helpful in doing initial screening and down selection, but there's very clear data that there are big differences between what goes on in vitro in in a test tube, even in an AMS, and what happens in people or monkeys. And so right now, we can do if you're trying to screen 20 compounds, you can do some initial down selection with AMS, but you're not going to get the final answer of what you would need to to go forward.
R. Paul Johnson, MD:With a human clinical trial in the vast majority of cases, there's some really work neat work that's going on with respiratory, with with trying to model the lung and developing names that have combinations of respiratory epithelial cells and immune cells. The California Center is doing a lot in this regard. Again, those are in early stage there. It's very promising research. It should absolutely be supported.
R. Paul Johnson, MD:But it's these are early days. And right now, to know if those results in the names are relevant to what goes on in a in a whole organism, we need to do the comparative studies in nonhuman primates to see if they model biology appropriate. So this is this is a very active area of research where we have investigators here who involve, as I mentioned, who about 70% of our investigators are using NAMS in one way or another. Really important line of research. But this should be a big conversation about working together to to advance human health rather than having arbitrary timelines, saying that science doesn't work generally by arbitrary timelines.
R. Paul Johnson, MD:Those don't saying that we're going to end nonhuman primate research in some arbitrary timeframe. Science doesn't work that way. We should start from the bottom up. Okay. How do we develop better systems that we can study and see whether they are able to to reduce, refine or replace nonhuman primate models?
R. Paul Johnson, MD:But it it needs to be a conversation. And sometimes the conversation has gotten a little divisive, but we wanna have this be a big tent conversation.
Ivy Tillman:Exactly. Exactly. And, Joyce, when we're considering as methods evolve and as we have the and conversation, not the either or, how do you think research oversight is evolving or will evolve to support innovation and animal welfare?
Joyce Cohen, VMD, DACLAM:I think research oversight has always done a pretty good job of supporting both and trying to move the needle with animal welfare. But honestly, so much of that change has been driven internally by the lab animal community setting their own new goals and pushing regulatory bodies to change what they're asking for because it's all something that we wanna see ourselves. But it's definitely complimentary. I as Paul was indicating, I think right now and in the near future, DAMPs can certainly help reduce the number of nonhuman primates by prescreening and asking some early questions on to refine what we're doing in the nonhuman primate model. So I think absolutely that can start helping with reduction of animal use.
Ivy Tillman:I wanna talk about, as we're discussing NAMS and the public discourse around NAMS and honestly the interest associated, a broader conversation that we at Premier are having and continue to have with the public as well as Research Ethics and Oversight professionals. That's around trust and transparency and bringing the public along in our work. And so the broader questions are, what do you wish people understood more about your work and how do you build and maintain public trust?
Joyce Cohen, VMD, DACLAM:I feel that in the last ten to twenty years, we've been really working to improve communication and openness to gain public trust because there had been a lot of risk avoidance before that and not maybe sharing enough information with the public to allow a different narrative to be driven into people's minds. I think we're really made a lot of strides in improving sharing information and getting accurate information out there, and I think that does help. If I wanted to impart one thing to the public to understand is I wish they understood how much the people here working with the animals care about what we do and how much compassion there is. And we have relationships with the animals we work with, whether that's a monkey or a mouse. We're here doing the hands on work because we love the animals and because we believe in the importance and value of what we do.
Joyce Cohen, VMD, DACLAM:So we wanna be here to make sure it's done right and look out for the animals. I wish people knew that and also realize the incredible regulatory oversight
R. Paul Johnson, MD:Right.
Joyce Cohen, VMD, DACLAM:That we have seeing what we do. There's more law, rules, regulation, inspections, oversight on what we're doing every day than there is in many other animal situations like shelters, things along those lines. I mean, we we are very carefully managed, and we live up to it because we really, really care about
Ivy Tillman:the animals. It's really important. I can attest to going to the center and, you know, seeing interaction with the animals and leaving different. I did not expect to I'd been in this world for a long time as far as biomedical research, right? More so with human, but worked at universities that had animal research, but to see the animals understand some of the research and understand some of the behavioral research that was being done and the impact that it was having on the animals, but also the long term impact on human health.
Ivy Tillman:But to actually see them and the interaction remarkable. It actually really impacted me greatly. I'm sorry, Paul, you were going to say?
R. Paul Johnson, MD:Yeah. I wanted to echo Joyce's point because I had exactly the same response to that question framed slightly differently. But I think the the big surprise would be how much our our researchers and staff really care for the animals. And and that's that's key in terms of openness. Again, I think it's an ongoing issue.
R. Paul Johnson, MD:We we get public funds from the NIH to do our research. We have an ethical responsibility in in doing work with animals. But openness and transparency is is key. And so we have two campuses. The one where you visited when you on your tour is is out in Lawrenceville about 30 miles from our main campus.
R. Paul Johnson, MD:That's where our breeding colonies are. And we have open houses twice a year there to bring in members from the immediate neighborhoods and the community to see the animals to and to hear from our staff and to hear from our scientists about why the research is important, how we take care of the animals, and the types of research that we do. I think another surprise would be for for many people would be that the sort of behavioral research that we talked about at that takes place out at the primate center and the opportunity to study the incredibly complex behavioral relationships that take place with rhesus macaques in a large group Mhmm. And how you can use that as as a model for stress. And and and in fact, there's so much we can learn from that work about how stress affects the immune system, how it affects diet, how specific biomarkers that are can be affected by stress.
R. Paul Johnson, MD:And so that's another area of research that I suspect many people are unaware of. So I think that that we have to continue to work every day, earn and maintain the public trust on on the work we do here because it is important. We take it very seriously, but it can't end there. We have to be able to demonstrate to the greater public about the high standards that we have for our for animal research and why we do animal research.
Ivy Tillman:Absolutely. So as we begin to conclude our conversation, which, I'm really enjoying, by the way, so thank you, Moe. I'm well aware of the next generation and having conversations about like, what are we preparing for the next generation of oversight professionals and scientists and researchers? And so if you had to give someone advice, someone entering into the fields in various ways about biomedical research today and the work that you do, what type of advice would you give them?
Joyce Cohen, VMD, DACLAM:That's tough. I'd be honest. This is a challenging time to be in science and research. We're really passionate about the importance and value of what we do, but it's a little challenging because some of the administrative decisions being made right now devalue all the work that we have done, and we are working to move forward. So I would say that people need to still feel that drive and passion and still come into the field.
Joyce Cohen, VMD, DACLAM:I'm worried about the next generation of people in research and if people are gonna continue to go forward, but we're leaders in innovation and creativity and science, and we have the infrastructure set up here. We shouldn't lose it. We should move forward. We need to take the lead also in animal welfare and in enhancements and changing how we do things. And we need people to come into the field to continue to make a difference.
Joyce Cohen, VMD, DACLAM:And that's what I would encourage people to strive to
Ivy Tillman:do. Paul?
R. Paul Johnson, MD:I think two things. One is I think if from a scientific perspective, the the opportunities that we have now in science across all the disciplines are just unparalleled. We have the research tools that we have now are incredible. We can you know, when I first started studying the immune system, two color flow cytometry was really exciting, and now we have 40 or more colors. We can study expression of thousands of genes in millions of cells.
R. Paul Johnson, MD:Mhmm. For neuroscience research, there's the ability to to acquire very complex datasets and analyze them at scale to take video social coding of behavior. They're they're just incredible opportunities we have right now. And and, yes, there are challenges, but we shouldn't be blind to that. But the the scientific opportunities are really just remarkable.
Ivy Tillman:Mhmm.
R. Paul Johnson, MD:And then I think it's most of us, as we talked about at the beginning, you're not gonna follow a linear path.
Joyce Cohen, VMD, DACLAM:Right.
R. Paul Johnson, MD:But you have to find something that you're passionate about and that you really care about. And it helps if you're good at it, but it's most important thing is to be passionate about it. And then and then you follow the path, and the path is not always straight. So find an area that you're excited about. Find a great mentor who is as passionate about it as you are and then provides a supportive lab environment that fosters excitement and creativity.
Ivy Tillman:I think those are really important words of wisdom and advice from both of you. And as we conclude, I just wanna say thank you. This conversation, I was so looking forward to it after our visit to the center, but also making sure that the public and our professions, we serve both animal research oversight and human research oversight professionals that they are privy to these types of conversations and that we have these conversations about the importance of the work that's being done at the center, at this center and others within our country. So thank you both. Thank you for your time, and thank you for joining us today on the podcast.
Joyce Cohen, VMD, DACLAM:Thank you.
R. Paul Johnson, MD:Thank you, Ivy. It's been a pleasure.