 Our next session is titled, Communicating about NAMS with Dr. Lisa Herr 11, and I will note that the title of this session refers intentionally to the acronym NAMM, because as Sally said this morning, it addresses the concept for which by my count, there are at least 15 possible terms that those letters could stand for, including non-animal model and new alternative methodology and various combinations of those terms. So what we wanted to focus on in this session was the overall concept rather than the specifics of any one term, so we just left it as the acronym. We invited Dr. Levin to participate in this workshop because of her role in encouraging the development of NAMS and in defining the criteria for research that's better done with NAMS and the criteria for research for which currently available NAMS are still inadequate. As a veterinarian, she has helped leadership positions in animal sheltering systems and worked in animal advocacy as well as working to promote high quality biomedical research efforts. We asked her to share with us in this workshop what she considers important for scientists to keep in mind about NAMS when we try to communicate effectively with the general public. Dr. Levin. Well, thank you very much for that kind introduction. I have so much enjoyed listening to the presentations today and I hope that mine brings at least as much value to this part of our day and thank you very much to National Academies. This really is a privilege and a pleasure to be able to be among you and speak. So let's see, sorry, working with somebody else's in control of my slides. Okay, so before we begin, this is my disclaimer, the views that are expressed in this presentation are only mine and they may not represent those of Caridia, my past employers, colleagues, people with whom I am or have been acquainted or the boroughs welcome fund to which I am very grateful for the support of my work in this area. My day job involves trying to find alternatives to the traditional use of whole animals in cardiovascular, neuroscientific and renal research and my exit strategy from that position involves trying to demystify the role of animals and non-animal methods, new approach methods, NAMS, whatever your preference is to call them and research drug development, a little bit of safety testing, but what I'm most interested in is how NAMS development regulatory approval and broad implementation in these areas can be accelerated. I don't want this announcement at about a minute into my presentation to have you scratching your heads about why is this person participating in a workshop about improving scientist communication with the public but I'll tell you, if I can get this to advance, I began my veterinary career as a postdoctoral research fellow at Johns Hopkins and that was after veterinary school summers there as a research student that was during that time I was very much impressed by the level of attention paid to animal welfare by an excellent laboratory animal veterinarian, the late Frank Lowe and by the time I became a research fellow and highly invasive neuroscience investigator, I'd already been exposed to many of yous from scientists and also from those individuals trying to secure rights for animals and I wasn't alone. Maybe that had something to do with the postdoc vintage to which I belonged and it certainly wouldn't have been unusual to find a copy of New England Journal and the Pita magazine, one of us found some place sharing space on the end tables in any of our homes. So what I'm saying is there was quite a few factors that went into providing me with an unusually good front row seat on the conduct of research in a top tier medical institution before, during and after what I consider to be the most significant amendments to the animal welfare act. I also developed a good appreciation which I still have for the work that's performed by the folks in animal protection. I don't want to leave this slide without saying that front most in my mind and that of the investigators that I knew and know was animal welfare. One of my present colleagues has at her own expense and it's a considerable sum, sent two of her non-human primates from her laboratory to Sanctuary and they may already be there and they've left from a laboratory where although they were research subjects, they received a tremendous amount of attention by a very large group of caring individuals and that's the sort of enrichment and investment in welfare that every laboratory should be doing. We're here to share our thoughts. Can everybody hear me okay? All right, I want to make sure. We're here to share our thoughts about how best to speak with the public about the confluence of scientific investigation, animal welfare and healthcare outcomes. On this slide and I would like to get the purpose of this is I really like listening to good music through some outstanding sound systems and every one of these fits that bill. I want to emphasize the importance of finding the sweet spot in doing that. So on the slide from left to right or loud speaker, loud speaker amplifier and I'm not advertising for anybody so I'm just going to reference them by their place on the screen. The one speaker on the left is very warm sounding and it's accurate. The one in the center is very accurate, not as warm sounding. Let us say a lot less forgiving. You will hear every mistake. These are amplifiers on the right. These are stack of amplifiers. I don't go to rock concerts but if you do there will be stacks of them across the room and up to the ceiling where the idea is get loud, loud the sound back to reach everybody in the place. Where I'm trying to go with this is it's important that we find a comfortable volume and the tone for truth telling. I'd like to recommend the discovery and communication model that I had the privilege of piloting with some members from the NAMS, the animal research and some other stakeholder communities. Again, many thanks to the boroughs welcome fund for underwriting the support of those round tables. But before I do that, I want to preface it with a few statements. Science is hard. I think we've we stated that conclusion at least several times today. We all understand that in this room but I don't know that the public fully understands just how hard it is. Dr. Trappicar is a new friend and colleague of mine. He works with micro physiological systems in the laboratory of human biomimetics at the Johns Hopkins all Children's Hospital. And his statement really is quite extraordinary. Don't you think coming from an MPS scientist? But I think he has an excellent rationale for it. Maybe it's just that we don't understand enough yet about the diseases that we're studying. In the same breath, I think we can all agree that there are some reproducibility and translatability problems with many animal models. But science is hard. Yes. I know Dr. Barrage a much longer time. Some of you may know him from his pharma days or from National Toxicology program or his current work as the principal for B2 pathology solutions. And his statement is supremely practical. I can count on him for that sort of thing. And it really should be one of those communications of science is hard that we share with lay people. So what we're trying to figure out what's the best way? Or what's the best science? Is it an animal model? Is it NAMS? Is it a combination of both? We also need to figure out the best way to explain the use of animals and the use of NAMS with the public, which really needs to be much better educated about these things than it is at present. We can start by expanding, optimizing the conversational input. Too often, the animal research controversy is painted as science and animal protection in this very painful struggle. And we know that's not the whole picture. And it's certainly not a table for two. The dialogue would be much better served if we recognize and accept the reality that this is a multi stakeholder involvement and get these folks involved into the conversation. That's the model that I advocate. And this is how we did it at the Burroughs Welcome Fund roundtables. On the left side of the screen are the eight stakeholder groups that I consider most closely associated with the development, the regulatory approval, and the implementation of NAMS. Coincidentally, they're also the eight stakeholder groups who are most attached to animal research matters. Now going forward, I would like to include the groups on the right. I think it's a much greater, a better collective to do that. The first series of roundtables deeply explored the pain points each stakeholder had with NAMS and included conversations about creating action items that would help us develop an evidence base, the well reasoned path toward integrating them as partial and or full animal replacements and all the areas that I mentioned. I consider the roundtables to be a success because a group of very engaged individuals committed to sitting in one place and talking about what was going to be best science. Now we focused on NAMS, but the same thing could be said for animal research. The core beliefs and the present actions of each of these stakeholder groups need to be clearly understood across all of the demographics. At the beginning of my presentation, I said that I like to be able to demystify the role that NAMS and animal use have played in research drug development and safety testing. To that end, I'm going to recommend a course for public engagement that first will let scientists pursue science with the aid of animal protection. Now that's something new. That first step is going to require a very strong accord. What I mean by that is there has to be an initial agreement what the animal protectionists and what the scientists see as each other's plan for the animals being used as experimental subjects. Second, animal protection really should receive some durable proof from the science community that replacements are being developed while animals are still being used. And when I say do speed, that do speed I think is going to be primarily tied to the level of funding. Third, all communities, I'm going to go beyond both communities, all communities, it's beyond the initial science and animal protection conversation must be provided with every assurance that any animal who is used as an experimental subject does receive the full attention of the three Rs, the reduction, refinement and replacement strategies in terms of animal use. And I think it would probably be helpful if institutions might provide some proof of that action. I mean by that maybe some sort of statement, particularly why we are not foxes watching the hen house statement. Because I think that's in a lot of people's minds unfortunately. And last, all of the stakeholders, I don't know why I focused on the general public news because of this, but everybody, in fairness everybody deserves to receive this information. Everybody needs to be provided with an understandable trajectory of this transition. But how's that going to happen? And from whom is this map from here to there going to be delivered? I know this is problematic and in the next few slides I'll discuss that and it certainly requires attention. Well let's start here. I don't know anyone who would disagree with this statement, right? No one likes to use animals as experimental subjects. During my fellowship I was asked by a faculty member from another group, would I please and sanitize the male dog who he was going to use for a study. And he said to me, I can't look into his eyes. So it really was only because this fella was so unnerved and I felt that his venopuncture, the accessing vein to inject the anesthetic solution was going to go so poorly and cause pain to this animal that I agreed. And I told him don't look in the dog's eyes, look in mine. Because he needed to see that this was hard for every investigator. And had I euthanized that animal, he certainly would have seen in my eyes the pain that I would have felt while I was watching the light of life go out and out of the dogs. So I don't know if Mr. McKellips is still attending with us, but if you are, sir, I can assure you that those eight seconds would have been the most impactful and important nonaudible message of my day. Science is hard. It is hard here and it is hard here. Ken Gordon, who is the incoming CEO for the Washington State Veterinary Medical Association, is a new friend and colleague of mine and he very graciously provided me with this nice graph of gallop polling between 2001 and 2023 about the moral correctness of using animals in research. You can see by 2025 the lines are approaching an equivalence of foreign against opinion, but whether it's a gallop poll or some other indicator of societal view about animal use, the true metric is going to be human action. There's been no popular vote in this country against the use of animals in research. However close, and this is in my opinion, however close an opposition comes, even to 100%, holding their use is going to involve a vote more likely just Congress making it an illegal activity. So with all of this said, as objectionable or as favorable, the majority position is at this very moment of polling about animal use. We operate in an environment that permits it and that's the point from where to continue the remainder of what I call the eight step program. We all know this book, Russell and Birch has their three R's doctrine in there, the reduction, the replacement and the refinement of animals in research. And the purpose of that right is to bring humane performance to scientific investigation. We can also talk about the Animal Welfare Act and its amendments and how helpful or how toothless it is and the usual criticisms are there aren't enough inspectors or there's infrequent inspections and of course there's the guide with its key concepts of animal care and use and I hope that some of my good and learned colleagues in this room and elsewhere will be participating in the revision of that soon. Moving from animal use to replacement, oh wow, okay, sorry, that was fast. Okay, I guess we're there already or at least in this dimension. That's going to require some work and they need to be proven reliable. It's the pinnacle of the three R strategy, yeah, but they need to be proven reliable before they can be deployed as such. But what defines reliable? At the Burroughs Welcome Fund Roundtable I talked about the big book of the new language to which each stakeholder would contribute some vocabulary and that vocabulary needs to be precise because without that precision there's really no reasonable way to evaluate an animal or a non-animal method much less make comparisons between them. I think we need to be prepared to hear a lot of what's that. Most people have not been exposed to NAMS. They're not going to know what the limitations were. The advantages are in vitro and silico or in chemical work. I wasn't trained as a bench scientist. I needed to read plenty of material and listen to many lectures and webinars before I felt comfortable about having a meaningful conversation with a NAMS scientist. I still feel like a neophyte. There's a lot that I need to learn. I have been so fortunate and I hope I continue to be that way by the grace of their patience to remain receiving such tremendous tutelage from such bright people. I don't want all of this to sound like, oh well now this is a disincentive to educate the public with what you're going through. Well I don't think the public needs to attain the level of knowledge about NAMS that I aspire to. I'm doing it for a different purpose. I say this from a different position because I think about something I do know about animal models of disease. I can explain to a layperson why an animal model at this time and in some cases will provide much more information than a very incomplete NAM. I can also say why this animal model is better than that animal model and sometimes say you know what there's just no good animal model for this at all at all at all. So I think the level of conversation can be simplified. I'm not saying these are simple simple people. I'm saying it can be simplified whether this is a NAM scientist or someone using animals having the conversation. And the first move toward understanding and consensus is identifying members of the science community who are willing to speak the language of diplomacy with members of the public who are deeply concerned about animal protection. Americans for medical progress encourages institutions to host an annual biomedical research awareness day. That's a wonderful opportunity for the public to go and speak with individuals who are working in research. And I hope that many of them continue to speak with the investigators and others and staff afterward and perhaps the institutions maintain some sort of communication portal for that. I know this can be difficult and that difficulty I think is based on distrust but these are conversations that need to be encouraged because if they're not and I may sound a bit like the late Yogi Barra about this if there's no conversation about this there's going to be no conversation about this right. And in fairness to the scientists the lay persons who they're speaking with need to have a sufficient educational level and that does not require a doctoral degree to understand and to ask questions about animal use or what are the challenges about making a scientifically satisfactory very complex biological system in the form of an animal replacement. Nam scientists and those using animals must be able to explain why their models are helpful and maybe one superior to the other in terms that are understandable to the lay people in both cases the scientists need to recognize and I think most do that these concepts are not a first language for the lay people and patience is going to need to be demonstrated and questions must be anticipated and the need for these people to verify trust have it verified in the presented material. I use this lollipop to teach the rationale for preemptive analgesia that's administering pain medication before procedure to veterinary students and to the one lay person who asked me we all understand at least one reason for anesthesia in a surgical setting and that's so the patient is rendered insensible to pain but that doesn't mean that the patient will awaken pain free that's going to require some pain medication being on board. So an anesthesiologist before the first incision is made will administer preemptive analgesia the pain injection pain medication injection so wherever the on the periphery of that lollipop which is the spinal cord this is the central nervous system by the way of a dog sheep pig horse cat goat non-human primate and some other animals the stick is the spinal cord the lollipop head is the brain and as those nasty pain messages come through nerves that plug into that spinal cord the preemptive analgesia will act as a blockade now ideally none of the pain messages go up to the brain the reality is that some do but it's a mitigated response so they go up to the brain which translates the message we're doing mostly okay in terms of pain if the patient does not receive the preemptive analgesia and let's just take any post-operative pain medication out of this then those nasty pain messages travel up to a brain which registers out out out the patient's going to be awfully miserable upon awakening and that's not a good result okay well we in this room and veterinary students who I use this to teach to them can have a much more sophisticated conversation we can talk about anxiolytics and regional anesthesia and analgesia but I must tell you this was a very suitable um and a satisfactory according to the layperson explanation and maybe I said something about uh we can bring other modalities and uh to aid with the pain medication so I think the the same sort of approach can be taken with NAM scientists and with those using animals to explain their work ultimately uh an assurance and this is going to be one of the first diplomatic milestones that we reach an assurance between the science community public members and the whole large group of stakeholders jointly issue an assurance about everything we've been talking about to their communities and once it's decided on the physical format it takes and who is the way who is creating and delivering this message then there really is going to be a solid serious and thoughtful policy about the development of NAMs accompanying the three years guided use of animals in research safety testing and uh drug development the predictable next step after an assurance is reached is the stakeholders asking about a timeline are we there yet that's not a question that's limited to youngsters who are traveling in a car uh I believe we voice it with a lot more insistence as as we get older timeline was very dirty word at the roundtables one individual said no timeline science develops organically now there's mm-hmm we need to have timelines let's us have goals and it informs policymakers about the direction in which science is heading third said you know we ought to get the lawmakers into this conversation because they'll set expectations they'll remove the exaggerations you know sometimes they're kind of good at finding support for some of our our new projects so the map from here to there is probably going to incorporate the best parts of those and probably some other views the best I think we can hope for right now is that the stakeholders and this is going to take some time would jointly approve a metric system to estimate a timeline for partial and or full replacements but the fact is dams dams nams are a dynamic enterprise and that dirty word timeline is is going to reflect that dynamism I'm going to riff a little bit on a phrase from a 1950 sitcom uh called I love Lucy we have a lot of explaining to do we need to move beyond ourselves we need to move beyond the science and animal protection conversation the dialogue needs to include this larger constellation of stakeholders who really should be involved we need to do that now and we need to do it well thank you for your attention this really has been a pleasure does anyone have questions thank you very much Lisa um this has given us a lot to think about I don't see questions in the the Q&A yet but wanted to ask you about say you're you're emphasizing the importance of stakeholder conversations and I wanted to ask you what you see as the primary obstacles to allowing those conversations promoting those conversations from happening people are fearful people don't like being rejected do you want to play with me now okay do you want to listen to my opinion about animal research not really do you want to hear what I have to say about nams really could care less okay so these are some major obstacles the truth and and I'm I'm thinking that Simmar put up what you you didn't have background for you I think you were just for kicks and giggles at the bell curve but there's truth to it you're going to have the Flat Earth Society on either side of this bell curve and now you can't use animals and yes you can use animals and you know you know very absolutist and it's the middle the that is going to be communicative sorry I have one I may need to go last because of our timing but what what are do you have any ethical concern for the use of nams by that what I mean is some of them can be of human origin right organoids chimera you know at what point do you feel that review of nams might lead more to an IRB review or is your commentary not human-based if you will no I it's it's human it's animal-based I think certainly IRBs if they're not already involved in this are going to be involved in this I showed on one of the slides the original late stakeholder groups now I'm getting older analyzer and I realize that we need to include other stakeholder groups which include medical ethicists patient advocacy groups institutional administrators and committees so yes we have ethicists in there I don't have that level of sophistication and that's the reason for obviously having the stakeholder input and they're going to be they're going to be critical on that thank you so much my pleasure I think we have to close up for today we've had quite a full day I have very much appreciated all the input from our speakers and presenters and questioners we started off with a survey of of what our current opinions and what might influence those opinions and then we've heard from three different pairs of presenters and scientists trying to hash out the difficult parts and also heard from some very interesting speakers about issues that we all need to think more about and think about how we're going to talk about so I think we're all ready for this day one to end and take a break and then come back tomorrow for more good afternoon again everyone as we draw to a close for the first day of our workshop I want to express my gratitude to everyone for your active participation and the insightful contributions that you have brought to our discussions today today has been a remarkable day of learning sharing and building connections the diversity of perspectives experiences in this room is inspiring and I am confident that the second day of our workshop will be equally as enriching before we part ways for today let me reiterate the importance of the principles that underpin our gathering our commitments of fostering a respectful and inclusive environment remains unwavering I encourage you all to continue engaging in discussions with an open mind embracing the opportunities for collaboration for all that lie ahead as a reminder you can scan the QR code that is located at the top of the first page of our meeting book this will take you to the national academy's workshop web page where you will be able to access a tab that lists all of the resources that we have compiled regarding effective communication this tab will help you to access the different resources and different ways of effective communication I want to thank you all for your time and your attendance today