Evolving Animal Welfare: Science, Ethics, and Innovation

April George:
Our industry is not only ethically passionate about animal welfare, but we also have a lot of guided principles from society and regulatory expectations. So a couple of examples of this, the Animal Welfare Act, which is a federal law that regulates the treatment of animals in various capacities as well as the five freedoms of animal welfare.

Mary Parker (00:07):
I am Mary Parker, and welcome to this episode of Sounds of Science. The 3Rs's principles of replacement reduction and refinement were developed over 60 years ago to provide a framework for performing animal research. Since then, there have been significant advancements in animal welfare initiatives and standards. Here to lend their expertise are three Charles River scientists, Carly O'Malley, A 3Rs Scientist, Judy Murray, director, animal Welfare Training, and April George Manager for learning and Development for Discovery and Safety Assessment, global operations at Charles River. Welcome everyone.

April (01:09):
Thank you so much, Mary.

Mary (01:13):
I really appreciate you all being here. This is a really cool topic and I'm excited to learn more. Can we do a quick round table to tell our listeners about your backgrounds, your education, and your roles at Charles River? Carly, want to start with you?

Carly O'Malley (01:31):
Sure. Thank you Mary. My name is Carly O'Malley and I'm a 3Rs scientist with global animal welfare and training. My background is I have a PhD in Animal Behavior and Welfare and I've been with Charles River since 2020. In my role, I conduct research primarily focused on refinements with research animals such as housing and handling practices and overall behavioral management. I also promote 3Rs-related topics within quarterly behavior calls, company-wide media productions, 3Rs workshops and welfare working groups. I also develop and manage our species welfare assessment tools.

Mary (02:07):
That's awesome. How did you get interested in this area of science?

Carly (02:14):
I think just through exposure at different conferences and in my work in animal behavior and welfare through just looking at what opportunities were available and just becoming really interested in the idea of animals and humans working together for a common goal of improving science.

Mary (02:40): 
I love that. Judy, how about you? What's your role at Charles River and how'd you get started?

Judy Murray (02:46): 
Hi. Well, I'm Judy Murray. I'm the director of animal welfare training. I have a degree in psychobiology and that kind of got me started in the animal world. I am responsible for leading the evaluation and implementation of our company-wide Animal Care and Welfare and other associated trainings. And I actually learned very early in my career the importance of providing humane animal care by focusing on their welfare and their overall wellbeing. So being part of a group that focuses on this really provides me the opportunity to have a positive impact on the lives of millions of animals.

Mary (03:33): 
Thank you. And I have never heard the term psychobiology.

Judy (03:40): 
It's a combination. It's kind of mind body. So the impact that our psychological wellbeing has actually on our physiology and we are learning more and more about that all every day I believe. And as we look at wellness and wellbeing, the work that's coming out of the pandemic now is exciting in this area as well. So we'll learn more about it.

Mary (04:04): 
Last but not least, April, take it away.

April George (04:11): 
Hello, my name is April George and I currently work with the Charles River Safety Assessment Learning and Development Team. I have been with Charles River since 2013. I began at that point as a clinical veterinarian and I've been very fortunate to be able to follow my passion for learning and development in animal welfare to my current role. I work with an amazing team and we're tasked with improving training processes and efficiencies. And then we're also working to identify alternative training or simulation training methods.

Mary (04:47): 
That's awesome. I'm glad to hear we've got a veterinarian's perspective. So like we said, the 3Rs principles were established kind of a long time ago as an industry-wide roadmap to conducting ethical animal research. So why is animal welfare important? It is important from a scientific perspective, not just a moral one. Carly, can you give us your thoughts?

Carly (05:18): 
Yeah. Animal welfare is at the center of all the work we do within Charles River. When we talk about animal welfare, we are referring to the physical and mental state of the animal, how it's coping with its environment, the quality of the life of the animal, and ethical considerations over the animal's care and use.

Mary (05:38): 
Excellent. Anyone have anything to add to that?

April (05:42): 
Yeah. I'd also like to add our industry is not only ethically passionate about animal welfare, but we also have a lot of guided principles from society and regulatory expectations. So a couple of examples of this, the Animal Welfare Act, which is a federal law that regulates the treatment of animals in various capacities as well as the five freedoms of animal welfare. This was introduced from Britain's Farm Animal Welfare Council, and this is the freedom from hunger and thirst, freedom from discomfort, freedom from pain and injury and disease, the ability to express normal behaviors as well as freedom from fear and distress.

Mary (06:26): 
I mean, it also makes sense because something like any unnecessary stress could affect the outcome of an experiment and give you results that aren't accurate. So reducing unrelated stress as much as possible would seem to be a high priority for scientists.

April (06:40): 
Absolutely.

Mary (06:43): 
Speaking of which, so animal welfare for 60 years of 3Rs is obviously an eternity in modern science. So how have animal welfare standards evolved in that time?

Judy (06:57): 
Well, the care and use of animals in biomedical research really has a very long and somewhat complex history. And as science has advanced and our understanding of the animal's needs, the interactions between an animal's ability to perform natural behaviors, their overall emotional state and their optimal biological functioning continue to evolve really. So have the standards of care and regulations for working with them in research

Carly (07:28): 
And to add on what Judy was mentioning, previous discussions of animal welfare have also focused on minimizing pain and distress for research animals, but more modern discussions of animal welfare focus on not just minimizing those negative experiences, but providing positive experiences for the animals as well. So in other words, ensuring that the animals have a life worth living, this is reflected in contemporary definitions of the 3Rs that provide more proactive considerations for how the 3Rs should be considered for animal research. And these definitions have been provided by the NC 3Rs or the National Center for the Replacement Refinement and Reduction of Animals and Research, which is a UK-based organization. But this is also reflected in more modern frameworks of animal welfare, such as the five domains model that incorporates positive experiences for the animals. As a major consideration,

Mary (08:24): 
It seems like the 3Rs are incredibly flexible. They provide an excellent baseline to guide your motivations for doing these experiments, but they can be kind of redefined and rethought in different ways as our understanding of how the animals think and feel gets more sophisticated.

Judy (08:48): 
Yes, and you really can see that in the more modern definitions through the NC 3Rs.

Mary (08:53): 
What are some of the challenges associated with animal welfare?

Carly (09:11): 
Well, one primary challenge of animal welfare is that there is no clear cut definition or criteria of what animal welfare is and how to measure it. People in different roles are from different backgrounds, education, experience, cultures, et cetera. They'll have different definitions of what animal welfare is and how to assess animal welfare, or they'll have different priorities for approaching animal welfare. For example, veterinarians might prioritize the biological functioning or physical health of the animals as a primary measure of animal welfare, whereas behaviorists like myself might prioritize the animal's effective state or their overall behavioral phenotypes. There are also studies showing that the public prioritizes the naturalness of the animal or their ability to show natural behaviors. And the second challenge is that animals cannot simply tell us what they're experiencing. We have to infer the animal's experience by observing the animal's behavior or taking different measures of the animal's physical response to the environment. Or by looking at management practices of an organization to infer what the animals may experience.

Mary (10:16): 
This seems like where it would be important to have extremely competent and observant vet techs who take care of the animals because they're going to notice any slight changes in their behavior before it might even register on any kind of test.

Carly (10:31): 
Yes, the people working directly with the animals every day, or the most important part of this equation is like you said, they know the animals best and any small changes and their input is invaluable for welfare assessment.

Mary (10:44): 
So as a contract research organization, what steps are we taking to mitigate those challenges and advance animal welfare?

Carly (10:54): 
Well, within Charles River, we are developing species specific welfare assessment tools as a primary way to harmonize how we discuss, define, and measure animal welfare. With these tools, we take a holistic approach to welfare. We focus on six categories, including physical, behavioral, environmental training, procedural and culture of care. Our tools are unique in that we incorporate culture of care, which assesses the wellbeing, training, resources and experiences of the personnel working with the animals as well as animals experiences. The tool uses room based assessment, which observe animals in their environment. We also look at self-site level assessments, which look at the protocols and management, and we use personnel surveys to assess that culture of care piece. So with these tools, the sites assess their programs every six months, and then they receive a report with the trends of their scores over time. And then sites will look at these results and use that data to develop goals based on what priorities and resources they have available to them.

(11:57): 
But additionally, within Charles River, we also promote a behavioral management approach to our animal programs, which promotes species specific natural behaviors and assesses program success through outcomes of observing behaviors that we hope to promote rather than the inputs which is assessing what we provide the animals. Another way we address challenges with animal welfare is we've developed an animal welfare and 3Rs certificate program for Charles River employees. With this program, we hope to provide another avenue to harmonize discussions and efforts around animal welfare in the 3Rs, so that as a company, we have a common language and understanding of these topics, and this will aid in empowering employees to advance these concepts within their own roles, allowing Charles River to maintain a leader in these areas.

Mary (12:45): 
That's amazing. Oh, go ahead Judy.

Judy (12:48): 
I was saying, as you had mentioned, the human piece to it.

Judy (12:53): 
There's the role of the animal caretakers. You have veterinarians, you have scientists, you also have members of oversight bodies. And their whole job really is to ensure the best care and use of the animals that we work with. And part of that nature of that work can be difficult. And so what we want to do is be sure that because the animals can't tell us what they're experiencing, that people really are focused on their animals and they do notice those subtle changes. So we work very hard to encourage a strong human animal bond, and that really benefits both the caretaker and the animal. It helps to promote empathy and compassionate care, which directly impacts on their welfare. And to do this, Charles River has developed a compassion science program, and it's really focused on reducing compassion related stresses and providing tools for building resiliency across the organization. And this helps employees cope with that emotional challenge that comes with their work. And the concepts of compassion, stress, and resiliency are also part of the animal welfare and 3Rs certificate program. So again, we continue to reinforce that interconnectedness of animal and human welfare and wellbeing.

Mary (14:14): 
That makes perfect sense because the care provided is only going to be as good as the carers who are involved. And if they're burned out, then that's going to negatively affect the animals as well.

Mary (36:34): 
So Charles River's Humane Care imperative includes establishing industry best practices to increase awareness around the importance of humane care and to foster animal welfare worldwide. So can you tell us more about the Humane Care Imperative and its primary focus?

Judy (00:01): 
The Humane Care imperative is just one way that Charles River supports a strong culture of care within our company.

Judy (14:46): 
It's one of the first things that our new hires learn about, and that's no matter their position within the company. And it starts with really their understanding of the essential role that animal welfare and the 3Rs play in our work and what the expectations are that each employee actually has a role in supporting animal welfare. And if you then have a role that is animal related, there is additional reinforcement trainings that are provided within their first 90 days of onboarding. And this training focuses on key areas related to the ethics of working with animals and research and its connection to the company's values and expectations for working with animals. There's also additional trainings that speak to animal sentience, and this is their ability to experience positive and negative feelings such as pleasure, joy, pain and distress and indicators of the animal's health and psychological wellbeing.

(15:51): 
So again, kind of pulling in that piece about really understanding your animals. And so it just reinforces again that we are all responsible for assuring their good health welfare and the safety of their animals. We have additional trainings, again, if you're in that animal role. Each year we have a training that's focused on a different kind of hot topic related to animal care and welfare. And we also have, in addition to these, we produce multiple workshops that Carly had alluded to. And we do this throughout the year. And the goal is to share knowledge and ideas really across this global organization. And we target certain audiences. So for instance, we have some species specific workshops and they highlight research as well as internal 3Rs efforts. And we also have a global trainer workshop that promotes development of a trainer's abilities and discusses refined techniques, and they also share use of non-animal alternative training models. And we also keep going with training.

Judy (17:01): 
Currently certificate programs are amazing, and they're the first for our company, and they're both, there's two now in the works, we have the one that's the animal welfare and 3Rs, and that looks at applied ethics and the ethical framework for what we do behavior at all and behavior at all aspects. So we have another one coming up, which is our animal behavioral management certificate. And that really does look holistically at behavioral management, including social behavior training, welfare assessments, and that human animal connection. So I think we do quite a bit actually through the Humane Care imperative to constantly reinforce the company's dedication to the welfare and each person's responsibility to that.

Mary (17:49): 
Yeah. Carly, it sounds like you're really involved in these. Can you tell me a little bit about these workshops and the kind of reception they've had? Are people pretty engaged in them?

Carly (17:59): 
Yes, absolutely. We have great attendance at these workshops. We start our workshop planning by thinking of what learning outcomes we hope users or attendees will get out of the workshops. As Judy mentioned, we also think of what hot topics are there related to that species or that topic that need to be addressed if there's certain trends going on within lab animal science or other issues that we think need to be brought up or discussed. But we really try to make it kind of a celebration of what the company's doing. So we invite people from the site level to share what they're working on at their site, if there's excellent advancements in their refinements or reduction practices at their site, we really want them to share that with everyone. And we always have great attendance and great engagement at those. And yet people like sharing their work and having those discussions and they take things back that they learn to their own site and they'll implement some of these practices that they learn about. So yeah, it's a great opportunity for us to just share everything that's going on within Charles River.

Judy (19:11): 
And this is actually a nice, well, the nice by-product of COVID in that we are really utilizing the virtual space to do this. So our reach has really grown exponentially across the company. So if you have to look at brightside from the pandemic, that is one of the benefits.

April (21:28): 
So externally, we definitely use the guide, we call it affectionately, it's the guide for the care and use of laboratory animals, and this is likely one of the most utilized guides we use for the overall care of our animals. In addition to that, we've got a lot of proactive and informative organizations. Carly talked about the NC 3Rs. We've also got the American Association for Laboratory Animal Sciences, or Alas. So both of these organizations amongst others, put out a number of really valuable concepts and resources. They've put out things like the grimace pain scores, behavioral assessment tools, and then definitely a lot of journals that we use to keep up with some of the most up-to-date concepts and practices.

(22:30): 
And then we've talked a little bit about the laws and regulations a little bit, but we definitely have a lot of regulatory bodies that we utilize and that help guide us through our animal welfare procedures and policies. So we've got the United States Department of Agriculture, the Food and Drug Administration, and the Environmental Protection Agency. And then we do have an elective organization. The primary one is going to be the Association for Assessment and Accreditation of Laboratory Animal Care International. And then internally, a lot of us have probably heard of the IACUC. This is our Institutional Animal Care and Use Committee. They're a group at each of our sites that review animal related procedures and protocols, and they're going to review them for scientific justification in areas for 3Rs'S implementation, animal welfare improvements. And then as we talked about earlier, probably our most critical and impactful ways to ensure animal welfare is our staff. Our staff love their animals and are constantly identifying and advocating opportunities to improve our practices and enhance their lives

Mary (23:47): 
Excellent. I do love that there are so many outside governing bodies who are all overseeing each other. I think that level of, I mean, it might seem like a bureaucratic onion, but I think in cases like these, it's actually quite important and valuable.

April (24:05): 
Absolutely. Definitely guides what we do and keeps us all on the same plane and make sure we're all communicating the same way and expecting the same level of care.

Mary (19:30): 
Have any suggestions come out of these workshops that were brought up by one of the workshop attendees that turned out to be a good idea that got implemented later?

Judy (00:02): 
These events are opportunities for individuals to share their work with colleagues across the globe. So for instance, these are just a few examples of refinements that have had some pretty good uptake. Following these workshops and webinars, we have the use of a common blood volume calculating tool that's used on studiesensuring that they're getting their best care and use of enriched social environments

(01:12): 
We also have implementation of a tool called the technical assessment of skills and knowledge or task that's used across business units. So as we have said, the employee's connection to the animals and their level of knowledge and skill directly contributes to the animal's welfare. So providing feedback to trainees to help improve their skills, assessing those skills based on specific criteria and documenting their achievements provides an organized approach to new hire training across the company. We also have refinements and handling techniques such as low stress handling. This was a huge undertaking for Charles River, and we are currently at 87% of all sites having implemented low stress handling in 2024, with the goal to be at 100% by the end of 2025. From a trainer's perspective, sharing resources, websites, image repositories, gamification tools and more helps to ensure that trainers are staying current with the industry and provides for professional development of our trainers.

(02:23): 
And lastly, we see increase in hosting of biomedical Research Awareness Day events. These provide an opportunity to educate students and the public about the importance of biomedical research and the humane care and use of animals. We have a global network of sites that host these events. They share ideas for engagement and materials that the sites can use. We have seen involvement in this event grow from 10 sites in the US in 2019 to 32 sites in the US, Canada, UK, and EU in 2024.

Judy (19:53): 
April, actually, you have a lot with the alternative methods that I think have filtered down into the site level.

April (20:16): 
Yeah, it's been a lot of information sharing in regards to what we call art methods or alternative replacement training methods. And this is things from basically incorporating training documents that outline a procedure and guide you through the process to videos and images, to training models. Everybody always knows about the CPR model, so items like that that they can actually get some muscle memory and practice, get comfortable with the equipment before they actually go into the lab and actually perform the procedure. So it's a lot of conversation around that and how to incorporate those options and how to develop them, where to find them, things like that.

Mary (24:19): 
We are seeing a progressive shift in the industry with the pursuit of non-animal alternative methods to responsibly replace or reduce the need for animals in research—so two of those 3Rs. How is Charles River implementing replacement models?

April (24:38): 
Yeah, there's definitely a lot of momentum in this area for sure. In 2024, so just last year, Charles River launched its Alternative Methods Advancement Project or AMAP. This is in an effort to reduce reliance on animals in the drug development process. Within this overall initiative, there's efforts such as organ on a chip, in vitro assays, animal free endotoxin testing, rodent pathogen detection systems, and the start of a virtual control group. So all of these initiatives reduce animal requirements for study. But another example of the evolution of animal welfare and the 3Rs is that we're actually starting to look at the entire experience of the animal. So my group in particular has been focusing on identifying alternatives for training animals, specifically, how can we minimize their needs and how can we leverage alternative replacement training methods more within our training programs? So examples of this is it can start with simple training documents or SOPs that outline a procedure, but then it can advance to training models like the CPR models that can simulate training and build up practice and muscle memory to building up shadowing and mentorship opportunities for our staff to some of the more exciting technologies such as virtual reality, digital 3D images, there's really a lot of opportunity to improve knowledge without the requirement for animals.

(26:14): 
So both AMAP and alternative training are areas that I personally am really excited to see, expand and look forward to see how it unfolds in the future.

Mary (26:24): 
I would have to say that virtual control groups are one of my favorites. That just seems like such a cool thing that's almost a no-brainer and is one of the things that AI is actually useful for in this context.

April (26:41): 
A great initiative.

Mary (27:14): 
So what impact do these scientific advancements in alternatives have on animal welfare? I mean, besides the obvious of reduction in replacement?

April (27:38): 
Yeah. They each have an independent contribution, as you mentioned. Some of them are going to reduce or eliminate the needs for animals, whether it's for study or for training. While others may not eliminate the animal requirements, but they're definitely going to improve the animal experience. And I'm also going to advocate for our employees. It'll improve their experience as well by refining our current processes and improving our animal welfare care.

Mary (28:06): 
Anybody else have an opinion and want to add into that one?

Judy (28:12): 
From my perspective, I believe just that increase in muscle memory, that increase in confidence, that it really does help the person that's caring for the animal and it helps move them through their training, I think in a more effective way, as well as it's benefit to the animal that may ultimately be there to training with. They have a lot more confidence when they're working with them, and that's the piece that I think is really important too.

Mary (29:56): 
So animals are essential to our understanding of disease progression, biological mechanisms, as well as drug safety and efficacy. The industry and regulatory environment have come a long way in terms of prioritizing animal welfare. But when we think about the next 50 years, how will animal welfare continue to be prioritized in a research setting?

Carly (30:35): 
I think over the next 50 years, I think there will continue to be a strong focus on animal welfare and how to incorporate these new technologies and priorities within the 3Rs. I think in terms of refinement and animal care, there'll be a focus on cooperative care or training with the animals as well as promoting natural behaviors through behavioral management programs. I also think newer technologies and innovative thinking will lead to more alternatives being used in research for drug development and for training personnel working with animals. As April was talking about

Mary (31:11): 
April final thoughts?

April (31:14): 
Yeah, I think definitely incorporating more alternatives within study design within training is something that is definitely going to advance. I think we're going to continue to learn and grow so much over the next few years. And as we learn about the animal's behavioral needs preferences, physiologic needs, our thoughts on welfare and 3Rs is going to evolve as it has in the past. So we've come such a long way thus far and I anticipate it's just going to continue and hopefully our industry will refuse to settle for the status quo and continue to grow and evolve with it.

Mary (31:52): 
I think that's probably a given considering the people that work in our industry and how hard they work. Judy, what do you think?

Judy (34:08): 
.So I think that with the FDA modernization act allowing for certain alternatives to animal testing including cell-based assays, computer models, really into the drug development process is going to improve translational medicine and increase that reproducibility of animal-based studies in human clinical trials. And this will really speed up, I think, our drug development in the pipeline to getting them to the patients. This will also lead to further growth in those non-animal alternative methods with greater acceptance by regulatory bodies. However, I do still think that animal models will remain an essential component of scientific and medical advancements and laws and regulations need to continue to evolve to address species specific needs and increasing overall animal wellbeing. I also am beginning to see more and more research into understanding vertebrate and invertebrate sentinence that this is going to lead to policy and regulatory changes as well related to these species.

Mary (35:20): 
That's an important consideration. Thank you. And thank you Carly, Judy, and April for being part of Sounds of Science. It's been a real pleasure having all three of you.

Carly (35:29): 
Thank you for the opportunity. Thank you for having us.

Mary (35:33): 
Thank you for being here. Carly O'Malley is a 3Rs scientist. Judy Murray is director animal welfare training, both with global animal welfare and training. And April George is manager learning and development for Discovery and Safety Assessment global operations at Charles River. Stay tuned for the next episode of Sounds of Science. Until then, you can subscribe to Sounds of Science on Apple Podcasts, Spotify, Stitcher, or wherever you get your podcasts. Thanks for listening.