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Sounds of Science is a monthly podcast about beginnings: how a molecule becomes a drug, how a rodent elucidates a disease pathway, how a horseshoe crab morphs into an infection fighter. The podcast is produced by Eureka, the scientific blog of Charles River, a contract research organization for drug discovery and development. Tune in and begin the journey.
Mary Parker:
I'm Mary Parker and welcome to this episode of Eureka's Sounds of Science. Today we are joined by veterinarian Adrian Smith, who is the secretary of the Norwegian organization Norocopa. Noricopa works to advance the three Rs of ethical lab animal use, replacement, reduction, and refinement. Although funded mainly by the Norwegian Ministry of Agriculture and Food, their research and resources are used around the world as a gold standard for lab animal care. I'm also joined by Liz Nunemaker, Executive Director, Global Animal Welfare and Training for Charles River, who will help me to understand the global impact of Noricopa. Welcome Adrian and Liz.
Liz Nunamaker:
Thank you.
Adrian Smith:
Thank you.
Mary Parker:
Thank you both so much for being here. This is obviously a very important topic so I'm happy to have you both. Adrian, can we start with your background? When did you first develop an interest in veterinary medicine?
Adrian Smith:
I've always had a great interest in animals. There were two heroes in my life. One was my mother who was a biology teacher and kept a lot of pets herself when she was young and we had a lot of pets in my childhood home as well. And the other was David Attenborough. I worked all his films and read his books and wanted to do something like that when I grew up. So when I had to choose a career path, veterinary medicine was quite an obvious choice really. My ambition was to be a small animal surgeon, but like most of the vets in my generation who ended up in laboratory animal science, it was basically pure chance that they ended there. And I've been there for the last 45 years.
Mary Parker:
I'm just curious that when you were studying to be a veterinarian, was lab animal science even something that people thought about or was it just kind of something that you happened to fall into later? Nowadays, it seems like there are classes dedicated to lab animal science, but I'm not sure if that was the case when you were in school.
Adrian Smith:
No, we had two hours of lectures on lab animal science. So it certainly wasn't considered an important topic by any of our students and that it didn't sort of create any particular interest in me at that stage.
Mary Parker:
So can you tell us about Norocopa and how you got involved?
Adrian Smith:
Yeah, sure. I moved to Norway in 1980 and I had to be registered as a veterinarian in Norway and had to take a course at the veterinary school. After I'd done that, still had to learn the language properly. So I thought apply for a job at the veterinary school where I could learn these things under relatively easy conditions. And that was the way I got basically involved in animal research. At that time, three R centers were beginning to be established in Europe and at any rate, by the 1990s, about 15 centers in Europe. And by then I was head of the lab animal unit at the vet school in Oslo. And we wanted to see a center like that established in Norway. The Ministry of Agriculture appointed a working group, which I was the head of to see whether we needed a center. We concluded that we did and this got written into a governmental report on animal welfare that was published in 2002.
And to cut a long story short, we ran a temporary three-hour platform for a couple of years and then NORICOPA was finally established in 2007. The only problem was that they only gave us money for one position and that is a position I've had since then. We've managed to persuade Parliament over the years to give us a bit more money, but the big breakthrough was actually not until just before Christmas in 2025 when we were given half a million dollars to establish a much larger 3R center in Norway.
Mary Parker:
That's fantastic. Congratulations.
Adrian Smith:
Thanks.
Mary Parker:
Liz, when did Norcopa get on your radar? How are their resources useful for your team?
Liz Nunamaker:
Yeah, so I've actually known about Norocopa for quite a while. I was first introduced to it when I was a vet student because I knew I wanted to go into Lab Animal back then and my mentors were very into sharing about the various 3R centers in Europe. And so I began relying more and more and more on their website all through residency and beyond just it's always been a great resource for what's going on globally, the links to other resources out there. And then especially because of their resource that I know we're going to talk a little bit more about Norina. I was really interested in non-animal training methods and this was a place where I could go to learn more and find out about different options that were available so that I wasn't having to reinvent the wheel all by myself.
Since coming to Charles River, Nora Copa is continued to be an amazing resource for all the same reasons. We use their website to stay abreast of what's going on globally and we share that information out through our newsletters, directing others within the Charles River family to their website. Since we're a global organization, it's nice to be able to point them to one place and be like, "Okay, you're in France. If you go to Nora Copa's website, you can find out what your three hours resources are in France or Finland or Germany or the US." And so it's a really nice one-stop shopping, if you will. We've also been very into supporting the NARINA database in collaboration with the DSA Gold Training Group to promote the use of non-animal training methods here at Charles River as well.
Mary Parker:
Yeah. Before we get into Norina, it's just worth highlighting that as competitive as the pharmaceutical industry is and everybody's trying to get drugs and have that next blockbuster big moneymaker, when it comes to the 3Rs, it's a lot more collaborative. Everybody wants the same goal and everybody has the same kind of thought processes of adhering to the 3Rs. So a global resource like this is obviously super valuable. So Adrian, can you tell us about Narina, the Norwegian inventory of alternatives? What is it?
Adrian Smith:
Yeah, sure. This is the first database that we produced around the end of the 1980s, early 1990s, people were starting to use our own personal computers and simple computer simulations were being developed within education and training. I was working at the vet school where we used quite a lot of animals in the preclinical subjects, physiology and pharmacology in particular and people worldwide were starting looking at alternatives to using these animals to teach basically knowledge that you could have got from a textbook anyway. So there was a lot of debate about whether we still needed to use animals in those subjects. I had a colleague in Bergen, Richard Foster, also a liberty animal veterinarian who had started making a little database of computer simulations he'd heard about and we agreed that we should take over the work of collecting information about these simulations, the vet school.
And my wife Corina, who is a nurse, was roped into start developing Norina from 1991 as we started looking around for alternatives worldwide, this snowballed really. We found more and more resources out there and we decided to cover the whole area of use of animals in education and training, right from junior school through high school university to the needs of technicians and scientists who would be using animals in animal research. And as I'm sure you know, in the US there was a lot of discussion about school dissections using animals. In all these years, we've had a lot of interest from people in the US looking for alternatives to use of frogs, for example, intersection schools. So that's also part of the Norina database. We now have about three and a half thousand items in this database. We don't supply any of them ourselves. We just tell people where they can go to buy them themselves or loan them because there's some loan systems as well.
So it covers everything about animal use from, as I say, schools right up to university and research. And we also came across a lot of books and manuals that were also relevant to this. So we started another database which we call textbase with information on books, manuals, handbooks within lab animal science and welfare. And there are about 2,200 books in that database. So these two databases, what we started with, we've produced other databases since and also expanded the Norocorpa website to include a lot of webpages with links to other resources.
Mary Parker:
That's fantastic. What are some of the most interesting or promising new alternatives for replacing animal models? Adrian, I'll have you go first, but Liz, feel free to chime in.
Adrian Smith:
Yeah. So I've already mentioned the alternatives within education and training and this is really getting very sophisticated now. The models are getting a lot more realistic. We're seeing the use of virtual reality and augmented reality as well. And then we have all the ones within research, the use of cell culture, organ culture, organs on a chip, or not least the use of databases and computer simulations where we're now seeing big databases of chemicals that we know the effect of and which we can then use to predict the likely effect of new chemicals that we construct on the computer before they even put into an animal. So there are a lot of really interesting alternatives now. A bit later, maybe we can talk about the public's view of this and how realistic it is to start using these alternatives, but the science is certainly there now and the opportunities are incredible.
Now the main challenge I think is often the validation process within regulatory toxicology for example, making sure that we don't spend longer than absolutely necessary getting these new methods validated for use instead of all animals.
Mary Parker:
It's funny you should mention public perception because I think that is also important to talk about there are some, from my understanding, there are just some safety precautions that we take when we have a new drug that is about to hit the market that are just too complex to be done with an alternative model. I'm thinking of things like reproductive toxicology where there's just at the moment, no way to successfully mimic that on a chip or an organoid or virtually, but that's not to say that there haven't been a lot of advances in other ways that have proved extremely valuable and as good if not better than some of the animal models that have traditionally been used.
Adrian Smith:
Yeah, because a lot of the animal models have actually never been validated. We've been used to using them for years. What worries me a bit is that people are often rather careless in their use of terms. We talk about research and testing as if they were two identical areas. The potential for implementing alternatives is very, very different from between, for example, regulatory testing on the one hand and blue sky research where we don't really even know what we're going to be finding at the end of the day.
Liz Nunamaker:
I think just with this talk about the three Rs and with a heavy emphasis on replacements and NAMS, I think it's really important that we really focus on using both replacements and animal models and especially as we start using computer simulations and silico and even some of the MPS work that we're doing, the information that we gather from animal studies can help inform our NAMs and make them better. And then what we learn from the NAMs, we can turn around and refine our animal models. And so the two can work together to allow us to do more informed, better scientific research and ultimately testing so that we can ultimately minimize the number of animals that we're using and maximizing the science that we're doing.
Mary Parker:
Absolutely. I mean, we've kind of hit all the three Rs, replacement obviously with an alternative, but also reduction. Maybe you don't need to use as many if you supplement with a non-animal model and refinement. So it kind of hits all three.
Adrian Smith:
I wonder whether we should just spend a couple of seconds explaining what NAMS are and because this says something about the way we try and replace our research. We often talk about NATS and NAMS, NAT, NAT, non-animal technology, where we are looking for a specific replacement for a specific animal experiment. NAMS new approach methodologies where we're often thinking outside that box and using things that aren't replacements for animals, but are new technologies that are giving us the answers we want often using human material, for example, use of the human placenta. That's not a replacement for an animal experiment, but it's a new methodology which we can use instead of animals. So we're working on two tracks at the same time. We're trying to replace animal research using NATS and we're also thinking outside the box, how can we advance science? What is the best model for looking at this problem?
And then that is often NAMS, these new approaches.
Mary Parker:
That's an excellent distinction. Thank you.
Adrian Smith:
One thing I'd like to mention in connection with the debate about animal research and testing and the potential for replacing animal use is that I get the distinct impression there's quite a lot of oversal from people on both sides, both those who are very against the use of animals altogether and those researchers who've built their career on an animal model.
And I think we need what I like to call a responsible and respectful dialogue between these two groups and that was one of the purposes of starting NORACOPA. We call it NORICOPA because it's the Norwegian platform of an organization called ECOPA, which was started at the end of the 1990s. ACOPA stands for a European consensus platform on alternatives. And the idea behind ACOPA was that they would approve national consensus platforms that had all the four major stakeholders in their governing body. That's representatives for regulators, industry, research and animal welfare to get everybody around the table and try and get a good respectful dialogue going about the potential for implementing the three Rs because at that time at the end of the 1990s, there was a lot of overt aggression against animal research. I remember going to meetings with people when we were establishing COPA who said, "I have a mobile phone up in the attic of my house and in case I have to call for armed response because somebody's threatening me or they used to check underneath their cars before they went to work to see if there was a bomb place there." And we were trying to do something to reduce disegration, get people around the table to talk about the way ahead.
Liz Nunamaker:
And Adrian, I think that's something that you've done really well over the years. I've seen you multiple times encourage the lab animal community to engage in respectful dialogue with both sides to not just go to our lab animal meetings and speak to each other. We're basically all preaching to the choir, but getting out to the primary scientist meetings where they maybe don't talk about these things as explicitly and they are either entrenched in their NAM model or they are entrenched in their old school animal research approaches, but trying to engage everyone in respectful dialogue so that we can move forward.
Mary Parker:
It's important to consider the human element in research. So can you explain the culture of care network and how it helps laboratory veterinarians as well as the animals in their care?
Adrian Smith:
Yeah. This is a concept that's becoming more and more fashionable worldwide. There have been big initiatives both in the US and in Europe. The three hours collaborative have been working hard on this in North America and we at Nori Corpora have started hosting the website of an international network of people interest in culture and of care. And by that we are trying to help those who feel challenged emotionally in lab animal science. So the network, which I'm involved in and I'm sure the three ask collaborative does the same, it collects and provides resources to help individual institutions improve their culture of care at their local workplace. We also have a discussion forum where members of it can discuss the challenges that arise and this is empowering technicians in particular at all levels, even the most junior technicians to feel that they have the confidence to raise a concern without risking reprisals or ridicule.
And this of course improves both the quality of the research and the atmosphere of the facility of everybody feels happy and feels able to take part in the discussions about the way forward for better animal research.
Liz Nunamaker:
Something that I really appreciate about the Culture of Care Network is, especially like the event that you did at Philosoph this past summer was having everyone that's a member of the network share about their program. I think no two programs are exactly the same and we can learn a lot from each other. And I really like that sharing of ideas and putting things into practice and seeing how it works at different institutions. I found that really valuable.
Mary Parker:
Can both of you give me an example of some recent exciting research or breakthroughs that have come with the help of NORACOPA? Liz, why don't you start?
Liz Nunamaker:
So something that I think NORACOPA has done a really great job of recognizing recently is this increased interest in systematic reviews. This is a really nice 3Rs tool that allows us to extract additional information about a given topic from the animal literature without using additional animals. And this is a skillset not many people have. And so NORACOPA has done a really nice job of partnering with individuals who are experts in doing systematic reviews to train others so that we can build this skillset and really help maximize the amount of data that we are able to get from the animal-based literature that's
Mary Parker:
Out there. Adrian, do you have an example of something exciting, some research that has come from NoraCopa that you are really proud of?
Adrian Smith:
Yeah. We haven't had anything that sort of happened yesterday that's made an enormous breakthrough, except the fact that we've just managed to get half a million dollars from Parliament to start a bigger 3R center, but we worked systematically for several years to increase the availability of the PREPARE guidelines, which are now available in 37 languages. We've produced a refinement wiki so that people, including technicians who don't want to spend the time or effort to write a proper scientific paper about refinements can publish that information in a Wiki in a far easier way. We also do a lot of work to make what we hope and consider as the most comprehensive and up-to-date webinars and meetings calendar worldwide. Spend a lot of time doing that and that's, I think, one of our success stories as well. And we write pretty comprehensive newsletters as well about seven times a year with the latest news internationally.
And this I think is important to mention that the philosophy in Oracle is to spread information about three hour advances over the whole world. We're certainly not just talking about what's going on in Norway or at Norical, but we are trying to disseminate information about three hours. The three hour advances worldwide.
Mary Parker:
So we kind of talked about this a litle bit, but to bring it back up again to close out. So as animal research gains attention from the public and from regulatory, what would both of you like people to know about the importance of the 3Rs? Adrian, why don't you go ahead.
Adrian Smith:
Yeah. First thing is we certainly are working on it and everybody is interested in introducing the 3Rs. We're trying to do in the correct order as well, replacement, reduction, refinement. There are challenges because you can't compare research with testing. The potential for replacement of animals is very different depending on what we're talking about and that I think is something the public have to appreciate that if you want the standard of healthcare that you're used to, then you're going to have to accept some animal research and testing for the foreseeable future. Also that we need to avoid too much hype about these new methods. They are very exciting, but a lot haven't been validated yet. A lot are still at the experimental stage and we need to be realistic about the possibility of implementing particularly within the regulatory field where there are very strong conditions for uptake of alternative methods quite naturally.
So we avoid side effects like the thalidomide tragedy, for example.
Mary Parker:
Absolutely. Liz, anything to add to that?
Liz Nunamaker:
No, I completely agree with everything that Adrian just said. I think that the three Rs are more important than ever. There's a lot of focus and hype surrounding replacement technologies about NAMs and these are to some extent very dependent on high quality animal studies also being performed. And we really need to continue to pursue all three Rs, replacement, reduction, and refinement to ensure the highest quality science and appropriate and humane use of animals.
Mary Parker:
Well, thank you both so much for taking your time to be with me and talk to me about this important topic. I really appreciate the insight that your booth can offer.
Liz Nunamaker:
Thank you so much.
Adrian Smith:
Thank you for having us.