Hi, I’m Anjli Venkateswaran, senior director of marketing at Biomere. And it is my pleasure to introduce Dr. Kevin Schwartz, who will be joining me today. Kevin is the manager of behavior and acclimation at Biomere’s site in Worcester, and he is focused on advancing our behavior enrichment and training programs. Prior to joining Biomere, Kevin worked as a research assistant, NHP colony manager, program development lead behaviorist, and behavioral consultant at multiple biotech and contract research companies. He received his bachelor’s degree from Rockhurst University and a doctoral degree from the University of Kansas Medical Center.
Biomere is a CRO with locations in Worcester, Mass., Richmond, California, and multiple sites in China. Biomere’s portfolio includes comprehensive discovery and GLP toxicology services. You can learn more about Biomere’s service offering at www.biomere.com. Let’s get into today’s topic on primate behavior programs at Biomere. Kevin, thank you so much for joining me.
Kevin: Hi, Anjli. I appreciate the invitation and thank you for the kind introduction. As you mentioned, I am the manager of our large animal behavior and acclimation groups here at Biomere. Our behavior group focuses on the well-being of these incredible animals and encourages them to live and express species-typical behaviors. Enrichment is one way that we encourage our animals to express themselves, and it goes much deeper than just providing toys, food, and produce items, that kind of thing. A real thoughtful and effective enrichment program requires attention to each individual animal’s needs and addresses those needs with a proactive and dynamic mindset. However, if the animals are exhibiting abnormal behaviors despite comprehensive enrichment efforts, fast identification of the root cause and an appropriate response are paramount for us.
The other group I currently manage is our acclimation team. The acclimation team is responsible for the bulk of the hands-on training received by most primates on our campus. We implement a thorough training protocol tailored for each animal to effectively communicate our training goals and prepare them for the amazing research they are contributing to.
Anjli: That’s amazing. You know, it’s funny, when we were talking about this topic, animal enrichment is not something that you think about, right? You think, “Okay, I’m going to be doing a study. I need X number of NHPs. I’m going to be dosing them and I’m going to be doing this.” But why do enrichment at all? And how does it impact the studies and the outcome? Because there’s a lot of work that goes into building and executing an enrichment program, right?
Kevin: Yeah, and it really comes down to running your study and getting the highest quality data that you can. Enrichment really contributes to making the monkeys the most monkey that they can be. Working with primates, that’s really my specialty, particularly macaques. And, you know, by having a comprehensive enrichment program, we’re addressing not only physical drivers, but also psychological and social needs that the animals have.
Anjli: Which is really true. We think about it because we think physiological, right? Like, I’m going to dose, I’m going to dose intrathecal or something, whatever. But it’s true, because when the animals are psychologically and mentally stimulated properly, and they’re psychologically healthy, that has a direct impact on their physiology. Is that the right way of thinking about it?
Kevin: Oh, yes, absolutely. And just from a physiological standpoint, especially if you are operating in a more sensitive physiological space such as you’re doing things that involve the immune system, if you are, for example, a transplant study, or if you’re testing vaccines or anything like that, any added stressors can really come in and potentially cloud your data.
Anjli: Right, right, right. And this can even vary between animals in a cohort, right? Because like humans, primates, you know, some primates are probably a little more jittery, they exhibit anxiety more than another animal. There’s animal-to-animal variation. Do you see that? Do you see a lot of differences within individual animals, and do you have to tailor the programs to the individual animal level?
Kevin: Yeah, absolutely, we do. You know, there’s been a lot of amazing work done by some big-name primatologists, just off the top of my head, like John Capitanio, looking into each animal’s specific temperament and how that really affects how they develop and what really helps them thrive in the times that they’re in. We are looking at integrating some neat things to assist our animals to get through the training they need to perform the research they’re doing, but also do it in a way that eases those steps for them at an individual level.
Anjli: Right, right. And I know we’re going to touch on the 3R’s. But I’m just curious, on personal individual animals, do you see any gender and age-specific differences for enrichment? For example, are younger, like, say, juvenile animals, or are some adults more in need of enrichment compared to older animals? Or is it all kind of the same across all animals, sexes?
Kevin: You know, honestly, the best thing that we can do for the animals that are here is ensure that their social needs are being met, particularly when it comes to establishing pairs or trios. It’s really one of the main focuses of my groups here at Biomere, which is ensuring that, let’s say an animal does lose its partner because of, you know, stuff happens in research occasionally, or it’s designed to happen that way, that we are taking proactive steps to have that animal’s needs addressed as soon as possible.
Anjli: That’s a really good point. And you know, that probably segues right into the 3 R’s. I mean, there’s a huge commitment, right? And this is true for Biomere and any other ethical CRO, it’s like an ethical concern to make sure that the 3R’s are met. And from a 3R’s perspective, I think animal enrichment is critical because of the whole idea of managing animal use and being very thoughtful about the number of animals and things like that. Tell me a little bit more about how we are tying in the enrichment programs with the 3R’s? I mean, some of it is obvious, but I’d love to hear you summarize it for us.
Kevin: Yeah, absolutely. And for those who aren’t familiar, the 3R’s of research are replacement, reduction, and refinement. Replacement involves substituting non-animal methods, like an artificial intelligence computer model, or testing in tissue culture or other in vitro methods instead of using animal models. It could also include using lower phylogenic animals such as fruit flies instead of primates. The second, Reduction, requires that we use the minimum number of animals for the studies to be scientifically robust. That also includes potentially being able to share a control group between similar studies that are happening at the same time so that we don’t have two control groups going at the same time unnecessarily. The third R is really where my group jumps in even more so in that sense for Refinement. This is what really addresses the animal’s actual experience when they’re in the scientific process, and all aspects of their lives in the laboratory, from husbandry to enrichment to training to the scientific procedures that they undergo, should be persistently and critically evaluated to reduce unnecessary burdens that are placed on these animals. Not only is it our ethical duty to fulfill these, but it’s also our legal obligation.
Anjli: Yes, federal, international, and the scientific community at large demand diligent care and scientific rigor when working with researchers, and rightly so. You know, you’re absolutely right. The 3R’s is such an important concept. And it’s awesome to see pharma, biotech, the whole community, and academia, everybody embracing it and being very thoughtful about it. However, balancing that is always the dollar for the money, right? And these studies are not cheap, as we know, and the budget can get pretty big pretty quickly. In this era of cost consciousness, and people are just watching the dollars a little bit carefully, how do we continue to explain to our listeners and the community that animal enrichment and primate enrichment programs are going to help you manage your budget and they are very important? So cutting corners on that is bad science but also has a negative economic impact as well down the road. So absolutely.
Kevin: Yeah, and you know, appropriate behavioral management and training protocols are essential for us to produce highly accurate and quality data sets. At a very base level, the animals must be trained for research procedures and actual data collections, whether that be various blood collections, body weights, dosing routes, whatever the study dictates. But above that is where superior animal enrichment programs really efficiently generate reliable data. One of my primary approaches to effectively manage our NHPs and also service our clients is to identify some natural primate behavior drives and incorporate them into our basic operations. A lot of this research into primates in general comes from incredible primatologist researchers. I mentioned John Capitanio before, but also some other ones who have been influential for me would be Nancy Caine, Steve Schapiro, Melanie Graham, and Linda Novak, just to name a few of them. I don’t have enough time today to discuss all their amazing work, but I have to shout out my colleagues. I’m a very proud member. And even though I’m not technically a primatologist because I don’t study primates, by reading the research, it really allows me to learn in-depth about the creatures that I’m working with to increase the level of care that they’re getting and also increase efficiencies for our clients as well.
Anjli: Yes, no, I agree, and maybe this is a bit of a segue, but I’ll confess, I don’t know much about primatology, and I’m not sure how many of our listeners do, but are a lot of the primatology studies done within a controlled lab environment, or are they done in the wild, or is it a mixture? Can you give us a very high-level introduction into how primatology works? I know you could go into tons of detail, but for somebody who’s not super familiar with the space, it might be good to get an understanding, just out of curiosity.
Kevin: Yeah, absolutely. So, primatology revolves typically in, I would say, three major worlds. The first would be like the conservation world, so that would be studying primates in their natural habitats. The second would be primates at the primate centers, for instance, the California National Primate Research Center or the Oregon National Primate Research Center. There are seven national primate research centers around the country, and they house large numbers of animals. They have large breeding colonies; they can study group dynamics and a bunch of stuff like that. And then the third group is the group that we more fall into, which is the industry use for most of them.
Anjli: The lab animal setting.
Kevin: More of a lab animal type setting. It’s trying to take a lot of information that comes from those first two groups and distill it in a way that is usable and applicable to our situation.
Anjli: Right, right, right. You know, switching gears a little bit, one of the reasons why the NHP, the non-human primate, has become the model of choice for a lot of human diseases is that translational aspect, right? Because mice have always been a rodent model, especially mouse models have been used forever and ever, but there are a lot of limitations. The first thing that pops into my mind is CNS studies. I mean, the mouse brain and human brain are very different, and the primate is a very good model with high translational potential. As I understand, primates are very cognitive, they’re very intelligent animals. So I think, do these enrichment programs help enhance complex studies and the translational value of complex studies? What I’m trying to get at is you have limitations with mice in terms of what you can get them to do cognitively, whereas with a primate you can do a lot more. So how do these enrichment programs boost that even further?
Kevin: Yeah, a lot of it comes down to just the animals’ well-being and what they’re willing to do as well, when it comes to training them to do things. If you have an animal-centric, welfare-first mindset, the animals will be much more willing to participate in the training that you’re doing. And then with an effective training protocol on top of that, you can really start working on some elegant study designs to really analyze the topic that you’re researching. A good example of that would be how non-human primates have been utilized in the neuroscience-based field. With my Ph.D., we were studying motor systems research and precision step movements, and the primate is an amazing model for that just because they are so similar to us physiologically that it really gives insight that no other species can.
Anjli: So I’m going to dig a little bit deeper. When you say, “really,” you were talking about fine motor skills, right? You’re talking about very small movements, not gross movements, but more like the fine. Can you give us an example that you’ve either worked on or read about? What are we talking about here? What does that mean?
Kevin: Yeah, so a lot of my Ph.D. work revolved around how the primary motor cortex generates initial and corrective sub-movements, particularly when it comes to reaching. If I’m reaching for something small, that large movement of reaching to get that thing is actually broken down into an initial, you know, several corrective sub-movements if necessary. The primate brain, very similar to ours, has areas for the hand. Their limbs are constructed similar to how ours are. So we can get a good idea of the neural representation in the motor cortex in the primate brain, much more so than we would see with a rodent.
Anjli: Right, right, right. And as you were talking about motor stuff, I was thinking, gosh, things like motor neuron disease or losses. I don’t know if Parkinson’s is an application, but you definitely have movement issues with Parkinson’s. This could be a really interesting way to look at those fine movements and be able to see other small changes in these fine movements. Yeah, absolutely.
Kevin: And, you know, to bring it back home to your initial question, a comprehensive and quality enrichment program means your animals are going to be much more likely to participate voluntarily in that. You should have much more reliable and accurate data.
Anjli: Well, you shouldn’t be forcing animals to do actions they’re not comfortable with and not willing to do, right? Because wouldn’t that skew the data, not to mention the welfare part of it? But when they are willing to do it, then the stress levels are probably lower, so it would be absolutely cleaner data. So it seems to me, what I’m getting out of this is that it makes a ton of sense, not only from a welfare point of view, that’s absolutely clear, but within the three R’s, refinement, and I do believe that there is a reduction component, because if you can use smaller cohorts that are enriched and well-trained, you’re not going to have crazy changes in your data, which would be a challenge to analyze. But if you have tighter data sets with less variation, you could potentially get away with using smaller cohorts. Is that true?
Kevin: Yeah, absolutely. If you are getting quite a bit of variability in your data, I mean, that could be the setting itself telling you something. But you need to do your best to control for those variables.
Anjli: Yes, truly.
Kevin: The worst-case scenario is having to rerun a study for analysis. That not only goes against the three R’s, as you mentioned, and ethical research practices in general, but it also has a significant cost to the clients and their patients. We work in the biomedical field. These are medications, or devices, or potential processes or medical treatments that are potentially going into patients. These mistakes can result in inaccurate results, future study design flaws, test formulations, and timeline delays. Proper animal training and behavioral management are major tools that we have to prevent having to pay these costs.
Anjli: Yes, and I’ll add one more point, because the truth remains that animal sourcing continues to be a challenge. So when you do have a study, and you do have the animals, you want to make sure that you get the best, cleanest, tightest data set because, as you said, rerunning studies is not just about cost. Sometimes timelines get blown out and it’s hard to ethically source high-quality animals, especially if you’re looking for certain ages or genders, it could really upend an entire drug development timeline if you’re not careful.
Kevin: Yeah, especially if a client is looking to submit for approval or if they are being fast-tracked. Any kind of delay is extremely detrimental to that, not only financially but to the patients as well.
Anjli: Right, right. And a lot of our folks in the drug development space are biotechs, right? And their funding depends on getting to a milestone. It’s always a race against time, whether it’s for money, whether it’s for getting to the FDA. This has been wonderful. I’ve learned a ton. And it really brings home the fact that people don’t think about animal enrichment as much as they should, but it’s so important. I find it’s something that underpins the entire study. I’m really glad that you’re with us at Biomere. Thank you so much for enriching, for educating us rather, enriching us on animal enrichment, educating us. I think this is something that our listeners are going to find very, very useful. Thank you so much, Kevin.
Kevin: Thank you, Anjli. I appreciate the opportunity to discuss the importance of behavioral management and quality training of non-human primates in biomedical research. It really is a privilege to work with these amazing animals and participate in the research that they’re helping advance.
Anjli: I absolutely could not agree more. I mean, we owe so much to these animals. I’m so glad that you and your team care about these animals and make sure that they’re living in a really good environment. With that, I will say thank you. And to our listeners, I will say if you’re interested in learning more about Biomere, our services, and what we do, please do email bd@biomere.com or check out our website, www.biomere.com. Thank you.
