S5E5: Animal Testing and its Alternatives with Thomas Hartung

Claudia talks to Thomas Hartung about animal testing in pharmacology and toxicology. They discuss how animal testing involves a weighing of values as well as some of the disruptive technologies that are providing alternatives to animal testing – including stem cell technologies and artificial intelligence.  

Date Recorded: 5 October 2022

Thomas Hartung, MD PhD, is the Doerenkamp-Zbinden-Chair for Evidence-based Toxicology in the Department of Environmental Health and Engineering at Johns Hopkins Bloomberg School of Public Health, Baltimore, with a joint appointment at the Whiting School of Engineering. He also holds a joint appointment for Molecular Microbiology and Immunology at the Bloomberg School. He is adjunct affiliate professor at Georgetown University, Washington D.C.. In addition, he holds a joint appointment as Professor for Pharmacology and Toxicology at University of Konstanz, Germany; he also is Director of Centers for Alternatives to Animal Testing (CAAT) of both universities. CAAT hosts the secretariat of the Evidence-based Toxicology Collaboration and manages collaborative programs on Good Read-Across Practice, Good Cell Culture Practice, Green Toxicology, Developmental Neurotoxicity, Developmental Immunotoxicity, Microphysiological Systems and Refinement. As PI, he headed the Human Toxome project funded as an NIH Transformative Research Grant and the series of annual Microphysiological Systems World Summits starting in 2022 by 52 organizations. He is Field Chief Editor of Frontiers in Artificial Intelligence. He is the former Head of the European Commission’s Center for the Validation of Alternative Methods (ECVAM), Ispra, Italy, and has authored more than 620 scientific publications with more than 41,000 citations (h-index 105). His toxicology classes on COURSERA had more than 15,000 active learners. Connect with Thomas on Twitter (@ToxmasHartung). 

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• Toxicology for the twenty-first century by Thomas Hartung
• A Roadmap for the Development of Alternative (Non-Animal) Methods for Systemic Toxicity Testing By David Basketter et al 
• Study Illustrates A Quicker And Less Expensive Way To Explore Gene-Plus-Environment Causes Of Autism Spectrum Disorder And Other Conditions via John Hopkins
•  A Johns Hopkins collaboration has demonstrated that the novel coronavir

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Transcript

00:00:00  This is another iROAR podcast.

00:00:04 Thomas Hartung: We cannot deny there was medical progress with the best and only tool we had at hand. But we're not seventy kilograms rats. This is my mantra. And if you can study things which are closer to human, you, you will have better hits. You will have better medicines. You will find the side effects not only after many years of use of a drug, but you can anticipate many things. And this is what is coming into reach.

00:00:43 Claudia Hirtenfelder: Welcome back to season five of The Animal Turn, where we are focusing in on animals and biosecurity. I can't believe that we are halfway now halfway, which is pretty, pretty awesome. And before I get into today's episode, I just wanted to flag that you might start hearing an ad or two in the show buzzsprout, where I host the show. I started a new initiative that makes it really easy for podcast hosts to insert adverts into their show. And these are normally adverts done by other podcasters on on buzzsprout. I'm testing it out. I want to see how this works and what it feels like. And if it's too disruptive or jarring, I'll remove it. But this is all kind of part of my initiative to continue building and expanding the podcast and ensuring its longevity and hopefully making a little bit more money so that I can start to pay the graduate students who help me, as well as friends like Kristian, who assist me with kind of editing and stuff. So the animal turn is growing and I'm figuring it out. And this is, you know, a new testing measure. And if you have any views, if you are one of the people that has heard an advert in the show and you have some ideas, or you think it was too loud or too soft, I'd really appreciate a message or an email info at the animal turn. There are other ways you can help the animal turn as well if you're interested. Don't forget to share it with your friends and your family and anyone who you think is into podcasts. And if you are a student at a university or you're teaching at a university, consider including it in your course or telling a professor or a teacher about it. I think that these work really well alongside kind of extra reading, and they make for a really good pedagogical tool. So don't forget to do that kind of stuff. And also, if you've got the time to leave a trustee review, reviews really do go a super, super long way. I like Podchaser because I've got easy access to Podchaser, and I'm able to kind of read those reviews and share them in a, in a kind of efficient and nice way. But you can leave a review anywhere, anywhere where you listen. And that would be really, really wonderful. But let me get back to the season. As you know, season five has been focusing on animals and biosecurity. And so far in the season, we've discussed many of the ways in which animals and diseases are interrelated. And this has included some thoughts on ethics, most notably the conversation with Jeff Sebo, as well as a couple of hints at the ways in which animals are included in biosecurity measures and, importantly, a key way in which animals are included is they themselves can kind of get sick from diseases and diseases spread through animals. But another really important way that animals are included and should be thought of when thinking about biosecurity is because they are tested on. So that is, animals are not only impacted by the spread of disease, but they are also tested on in labs and, and they're researched with. And this is something that we need to pay attention to. So in this episode, we are going to talk about animal testing, but we're also going to speak about some of the alternatives to animal testing. It's very easy to kind of be outraged that animal testing is happening. But what are the other options? What else is out there? And my guest today is a perfect person for answering that question. So Thomas Hartung is the the Duren camp chair. I'm sorry for evidence based toxicology in the Department of Environmental Health and Engineering at the Johns Hopkins Bloomberg School of Public Health. He's got a joint appointment at the Whiting School of Engineering. He also holds a joint appointment for molecular microbiology and immunology at the Bloomberg School, and is an adjunct affiliate professor at Georgetown University. In addition, he holds a joint appointment as professor for pharmacology and toxicology at the University of Konstanz in Germany. And importantly, for our purposes today, Thomas is the director for the center for Alternatives to Animal Testing at both universities, and he is a wealth of knowledge in terms of, you know, some of the practices that have been used on animals, but also the many, many alternatives that are available. He's co-authored and authored over six hundred and twenty scientific publications and has more than forty one thousand citations. So needless to say, he's an expert in the field. And throughout the interview, we speak about why animals are tested on. And he is clear that many of the methods that are still in use are outdated. And if we're going to take biosecurity seriously and develop better medicines for responding to disease, there is massive room for innovation. And that doesn't necessarily rely on animals. So it's fascinating. There's some really mind bending stuff that goes on in this episode. Thomas is talking about some technology that I really have to do, some like mental gymnastics to try and understand. And yeah, you might have to do some googling after this episode. Not, not because I think it's understandable, but because you're going to want to see what some of this stuff looks like. It's wild. Anyway, if after hearing this conversation with Thomas, you're keen to learn more about his work, think about joining the fifteen zero zero zero active learners in his toxicology course on Coursera. We rush a little bit towards the end of the interview. I'm sorry about that. Thomas had another meeting that he had to get to, and he ended up keeping his tax ban man waiting because our conversation was so good. And yeah, it really was so, so good. And I hope you enjoyed too. Hi, Thomas. Welcome to the Animal Town podcast.

00:06:11 Thomas Hartung: Hello, Claudia. Thanks for having me.

00:06:13 Claudia Hirtenfelder: I'm excited to talk to you because as you know, this season of the Animal Town podcast, we're looking at animals and biosecurity. And so far, I've spoken to a range of guests who, you know, we've spoken about health, we've spoken about kind of the ways in which disease is thought about some of the history with regards to rats, and how rats kind of got caught up in thinking about biosecurity. And in some of these conversations, it's become clear to me that something that's missing is talking about how animals are tested on in trying to secure biosecurity. Animal testing is something that's kind of happening always in the background of, of biosecurity conversations. So I'm hoping that today we can bring kind of animal testing more to the foreground. What is animal testing? But also what are some of the alternatives to animal testing? And I know that you're an expert in both of those fields. So I'm looking forward to talking to you about that. But before we get into that, perhaps you could tell us a little bit about yourself, your kind of institutional background and what you're focused on and how you came to be interested in in animal testing.

00:07:16 Thomas Hartung: Actually, I'm not interested in animal testing. I'm interested in its alternatives, though I did my share of animal experiments, I have to say, because, I mean, I love animals, but I did make choices in my life which brought me to pharmacology and toxicology, which are certainly the areas where animals are used and where it is a challenge to replace these. But I like challenges. So I'm I'm an MD, PhD by training, so I did biochemistry, but also study mathematics informatics. So in the end, as a physician, I know the problems and I try to solve them with these tools. I've been become a professor first at the University of Konstanz in Germany, where still a professor of pharmacology joined. Then the European Commission. For seven years there was heading the center for the Validation of Alternative methods. So exactly. Trying to promote but also to quality assess what we can do instead of animals. Interestingly, for a year then, I was responsible for security issues. Among others, I developed a strategy for the European Commission's Joint Research Centre for A, B and C threat agents and how to handle this. So when I joined Johns Hopkins and got a chair for toxicology, it met was really just the ideal moment to join a National Academies of Science panel, where we discussed animal models for countermeasures for bioterrorism and the threat agents. So I've been around this quite a bit. And here in Baltimore. We are close to the Aberdeen Proving Grounds. So this for the chemical threat agents, there's a lot of interactions with respective programs.

00:08:55 Claudia Hirtenfelder: So I think a lot of folks that maybe listen to this podcast are not familiar with many of the kind of concepts that you said there, or at least I myself found my like googling to just try and, you know, you hear words like pharmacology and toxicology and you think, oh, you know, you just kind of assume you know what they are, but maybe you could just give us a quick snapshot of what? What do you mean when you say toxicology and pharmacology? What are we what are we actually talking about?

00:09:18 Thomas Hartung: So pharmacology is the type of science which tries to understand how substances we apply to. In the end, the human body, but also obviously animals we want to treat in order to improve the outcomes of certain diseases. So drugs, the all these medicines, they're getting more diverse by the hour, but it is trying to help the organism, especially in disease states or to prevent diseases. Toxicology does the opposite. It is trying to understand what is harmful, what is threatening our life, our well-being, and in order to take decisions on how to manage these threats. Also possibly how to treat them. So there's clinical toxicology as well. But we are trying really to understand what is driving disease because in principle there's only three ways to to, to get ill. There's your genes are promoting diseases, infections are promoting diseases and exposure and exposure is a lot is chemicals. It's not only chemicals, there's also radiation. There's lifestyle factors. But chemicals are a big part of this. So you have only these three. And if you want to live longer and live longer, better, you have to get this under control.

00:10:34 Claudia Hirtenfelder: In the first episode for the season, I spoke to Stephen Hinchcliffe and he kind of said, biosecurity is about making life safe. And I think in many ways, what you're saying here with pharmacology and toxicology are doing that they're trying to make life safe by either keeping you healthy, existing, healthy, or preventing you from getting sick in the first place. So how is it that animals are caught up in these in these kinds of industries? What I call them industries or disciplines, sorry, disciplines. How are they? How are animals caught up in these disciplines?

00:11:04 Thomas Hartung: I mean, disciplines, if you see it academically and big industries behind it, which are developing drugs and want to have safe drugs or want to develop drugs to help also with biosecurity issues, for example. I mean, we we only started about one hundred and thirty years ago to synthesize drugs and also only for since the First World War, we actually were looking into chemical threat agents, at least more systematically. On the biosecurity side, biological warfare has been used. Historically, there was infected animals thrown on to infect your. your, your, your enemies. But also, again, this is pretty new discipline because I was a pharmacologist in infectious diseases, mainly, there was a natural fit for me to understand. How can you change the odds if you're being infected? How can you make it more? Probably survive an infection by trying to understand how infections work. So I'm really bringing in a lot of this mix, which is relevant to biosecurity because of my infectious disease background. So when we started synthesizing drugs at the very first one, which still is in use is aspirin, by the way. So and there was no model, nobody was using animal models really systematically. And this only started with safety concerns when first drugs were marketed and we noticed people were dying, children were dying from from drugs. And there was a cough syrup in the thirties of the last century, which killed almost a hundred kids. And this substance elixir, it was called, led to the. In the end, the creation of the FDA and a lot of the safety testing we are doing. The problem was the antibiotic was harmless, but instead of using it as a pill, they wanted to give it as a syrup to children. And they used an unsuitable solvent which killed children. Yeah. And the Food and Drug Act of the of, I think, nineteen thirty six or seven. Yeah. It was really the, the starting point for a lot of our safety thinking. And this has really developed over time. You know, we don't have not done animal experiments forever. Animal experiments really came up in the twenties of the last century before nobody would have believed, you can use a mouse, you can use a rat to to protect humans or so. But starting with these small animals, which are cheap, you can grow them fast. You can breed them, can quickly run experiments. People started using these technologies, and when the problems came up a few years later, they said, oh, let's use this now to solve our problem of, of kids being harmed by, by new drugs. So this is a, this was the starting point really for life sciences using animal experiments as their main tool, because it's typically not possible to test on humans. It is very difficult to conclude something on observing humans because we we take in so much stuff. So it's extremely difficult to to conclude something is problematic. I mean, imagine it took us fifty years to prove that smoking is causing lung cancer. So it is it is really not easy to just observe something in humans and come to a conclusion. And this is why the animal experiment was the only out. Cell culture did not exist. Computers did not exist to to make any predictions. So the technologies which are disruptive in the life sciences, which change the way we are doing science at the moment, they were not around. And this is why we have this very, very strong role of animal experiments, whether it is in developing drugs, finding out what is what is safe for us, what is not, studying infectious diseases.

00:15:03 Claudia Hirtenfelder: And we use them in a variety of ways. I'm guessing so. So I, you know, as someone who's never really been in a lab or a lab setting with animals, the only kind of idea I have of what's happening to animals and labs is being, I think, fed to me from, you know, movies and also the work of activists kind of saying that this is what, what is happening to animals, industries showing like rabbits having things put in their eyes, or monkeys having their heads bolted so that their brains can be looked at. Is this the type of stuff that's happening to animals and how and how efficient is it actually in developing drugs? In creating new drugs and telling us about toxicity. So so it's happening and it's widespread. And as I think you've just given us a really good kind of historical understanding of how animals came to be positioned here, but is it is it actually useful? Has it been useful?

00:15:59 Thomas Hartung: This is something which we cannot answer. Black or white, yes or no? Because there's no doubt we make scientific progress which helps save lives. We have done so over the last one hundred and fifty years. Every year which is born lives three months longer than the one before, since eighteen fifty. And this was hygiene. But about sixty percent people have calculated came from medical innovation. Yeah. Sixty percent of this gain in life expectancy at the beginning was mainly about infectious diseases and kids. In the meantime, it is about prolonging our life with cardiovascular diseases, with cancer. There are many people who have already survived one cancer. Yeah. So this is really something where we cannot deny there was medical progress with the best and only tool we had at hand, but we're not seventy kilogram rats. This is my mantra. And if you can study things which are closer to human, you, you will have better hits. You will have better medicines. You will find the side effects not only after many years of use of a drug, but you can anticipate many things and this is what is coming into reach. Very simple. I'm focusing a lot on safety sciences nowadays. I'm almost sixty years old now. Most of the animal tests which we are still using have been introduced when I was not yet born or in kindergarten. There has been a rough estimate that every seven years we double our knowledge in the life sciences. So we have now more than a thousand times more knowledge than we had when we introduced these animal tests. So there must be must be something in the box. So there's no other area of science where we continue doing the same experiment for sixty years, sometimes even eighty years.

00:17:55 Claudia Hirtenfelder: So why the attachment? Why? Why the need to if if these are somewhat outdated practices, why? Why is there still just this deep attachment to, to testing on animals to develop these drugs and, and prevention methods?

00:18:11 Thomas Hartung: There's, first of all, this attitude of, we have always done it like this and not risking anything. So many people in this field are happy to add to these basic tests, but not to replace them. There's there's many reasons for this. On the one hand, we are happy about the state of things. Not too many chemicals and drugs are showing up to harm us. You might argue whether we would find them because it's so difficult to make a cause effect relationship. I mentioned lung cancer as an example. It is almost impossible to take conclusions on many substances. There's this big discussion on bisphenol A you might have heard. Yeah, out of baby bottles. Is this endocrine disruptor. Is it a problem? Twelve thousand plus scientific papers have been written on this substance, and we don't come to a conclusion. Yeah. So it is not easy in science often to to draw an ultimate conclusion on, on a given substance. And, and part of this is that we, we produce a lot of noise versus a little bit of signal. And we are not good in identifying the signal. And, and there's also a big problem that science is not self-critical. This sounds odd, but, um, we you have no incentive to critically review the model systems you are working with. Because when I write a scientific paper, I will always make clear I used the best possible tool. When I write a grant application, I have to write. Yeah, this is state of the art whether it is or not, because otherwise I don't get the money and we hand our awards to each other between the people who are using the same models. Most of these animal tests have never really gone undergone critical evaluations. And if somebody who has experience in a model really turns against the model, it is typically because they really got frustrated about the results or they have something better, and then they have a conflict of interest because they want to sell the thing, which is better. It is it is really a pretty perverse situation, but I think this contributes to the fact that around ninety five percent of the drugs which go into human trials do not work.

00:20:32 Claudia Hirtenfelder: So they've been tested on animals already. And so thousands or hundreds of thousands of animals have been tested on and been through the system. But then it goes to humans. And then ninety five percent don't work on humans.

00:20:45 Thomas Hartung: Yes, I would guess there's not really good numbers, but that a typical drug has been tested on ten to twenty thousand animals before it is being going into humans or around the time it going into humans.

00:20:58 Claudia Hirtenfelder: It is how many fail. Sorry to interrupt you. How many fail. So we know how many fail once they get to the humans. Do we know how many? Because I know that there's something of a like a positive bias that we tend to publish when we've been successful with something, but are there a lot of tests happening on animals where, you know, things haven't worked, they haven't failed? So we know that ninety five percent of the tests that were successful on animals fail on humans. Do we know how many have been Unsuccessful on on animals?

00:21:30 Thomas Hartung: Not really. Also because it's a moving target. I can give you a rough estimates. Yeah. The first thing is you should understand a drug which goes into humans has already caused the company roughly nine hundred million dollars in development costs.

00:21:45 Claudia Hirtenfelder: So one drug, one drug.

00:21:46 Thomas Hartung: Yeah. So these are the latest figures I have seen. And then the clinical part is, uh up to one point five billion. So it's a, it's really expensive to, to produce a drug. And so the company is really interested in only putting their money on the best. And then then they succeed in five to ten percent of cases. Depends a bit on how you calculate. Yeah. Which is not not good. Yeah. I mean if you see it as a crystal ball, animals are not really extremely helpful. Companies are trying to get out of the animal part of testing, not only because of public pressure, but because they see the limitations. And they also see how long it takes to get the information and. But mainly it's about productivity. That's. That's not doing a proper job. The classical traditional way of thinking was you need to test about ten thousand structures to find one medicine, which makes it to the market.

00:22:45 Claudia Hirtenfelder: What is a structure?

00:22:47 Thomas Hartung: Ten, ten thousand different chemicals. Yeah. So this was the way we were producing chemicals in the nineties, early two thousand really synthesized them starting testing. And in a in a process, about ten of them would make it into clinical trials and one out of them would make it to the market. This was the rule of thumb. Yeah. Ten thousand. And in these ten thousand, you start sorting out in simple systems, cellular systems typically. And let's say a hundred of them would make it into into some type of animal testing, perhaps two hundred. And then ten of them go into clinical trials and one makes it. So this is the process. This has changed a lot. Companies have started now testing instead of tens of thousands substances, millions of. Because we can now use robots and. But it's only. The funnel is bigger and very quickly reducing it to the same. Similar numbers of which go into the different phases of clinical development.

00:23:47 Claudia Hirtenfelder: You've flagged us now to maybe speak a bit about some of the alternatives to animal testing. So based on our conversation so far, animals are tested on in great numbers in order to secure human life in a variety of ways. And, and I think Covid nineteen was quite an interesting moment because for exactly what you're talking about here, all of a sudden people were trying to produce drugs and vaccines at a speed that wasn't conducive to testing on animals. So I think if I, if I'm not mistaken, Covid nineteen, there was a big, a big skip, like a whole bunch of people just skipped that, that, that step in order to produce vaccines, which was quite an interesting, I think, moment. So perhaps you could tell us a little bit about that situation with regards to Covid and what you think happened there. And then maybe we could talk about thereafter some of the some of what you're doing with regards to alternatives to, to animal testing.

00:24:40 Thomas Hartung: Covid nineteen is certainly a moment where you can see science at work, how science has taken up this challenge. And this is really most remarkable. In the first year after we learned about Covid nineteen, two hundred and forty thousand scientific articles have been published on the topic. Yeah. So you can imagine everybody who could write Covid nineteen wrote at least a review paper. And, but, but also we try to just do what we could to help in these things. But they were really miracles happening, Developing a drug is a twelve year process. On average, developing a vaccine is a ten point seven year process on average. And if you just take the vaccines. Yeah, we had vaccines roughly a year after the pandemic in the clinic. So this is an absolute miracle. And of these of a vaccine project, companies have on average a six percent success rate. So six percent of the things they're developing are, in the end, successfully making it to the market. To the best of my knowledge, the nine vaccines which are around worldwide. Last time I counted this is tremendous success rate. I did not hear about many which did not make it didn't make the cut. Yeah, many were simply stopped, simply stopped the development because the competition was already on the market and made no sense to compete with the BioNTech and Moderna's of the world. Yeah. But in essence, we have seen something unprecedented high success rates in clinical trials and very short development times. So now you have to ask how was this possible this short development times? It was not possible without animal tests. So not to be misunderstood here. But most of the animal tests came when we already were in clinical trials. They just did secure that. They did not overlook something they could not observe. We have exact data for the Moderna vaccine, for example. It is amazing if you see this, on the twelfth of January of twenty twenty, the sequence of the virus has been published. On the fifteenth of January, Moderna started producing a vaccine based on this sequence. Three days later and eight weeks later, then on the fifteenth of of of March, they injected the first human with their vaccine eight weeks. The experiments they used later to say yes, animal experiments show that there's antibodies produced in response to this vaccine, which are neutralizing not the virus, but the pseudovirus. But is neutralizing structures of the of the virus itself was an eight week experiment. So it was certainly not a decision point for going into humans. They produced it. They started these experiments. If they start production, they probably took them days or weeks to to get enough material to get the animals aligned. So the data on animals came late. They came when we were already in human trials and already could tell. Yeah, it is, it is having an effect in humans. Certainly important before you use it broadly for for many people, but definitively not something which some animal per animal groups at the moment are doing and saying Pro-animal testing groups. To be clear to say we saved the world because of animal experiments. We have vaccines now. No, it was development, which is the most important parts, by choosing the right thing, were not optimized in any animal model. They were just going into humans and then showed some safety aspects while they were already testing in humans. It is not the normal process. I can tell you, normally you really optimize your formulation, how you dose it in animal models of disease. I would argue we still, until today, don't have a good animal model for Covid nineteen.

00:28:54 Claudia Hirtenfelder: You know, I'm I'm very much in the animal ethics realm of things. So I hear, hear, and then part of me immediately starts to say, well, you know, if you take into consideration the animals who are used in the experiments, how, how we justify using them to begin with, you know, we wouldn't we wouldn't, we would definitely have protocols and measures in place in terms of how we include humans in these and the speed and the speed with which we decide to use animals just seems to me a massive problem. You know, do you imagine a world in which we could have a future where there is no testing on animals? Or is it always going to be a matter of we use animals to try and find advances or health for, for humans, because it just seems as though we put human health above that. Yeah, I don't know. Like it's, it's hard for me to kind of grapple with a little.

00:29:43 Thomas Hartung: I mean, it is obviously a weighing of values. And these values are, on the one hand, our goal to understand, understand bodies, animal bodies and human bodies. This is a value. Yeah. And what is it against the suffering, the consumption of animals. We also have to say that lab animals are not necessarily the worst treated animals. What we do in our slaughterhouses, what we do with farm animals, I think is outrageous. Very often you see terrible animal experiments, but these are few. Many are harmless. Yeah. Are not really producing any effects there. To ensure the safety of something, not the not demonstrating the problem of something. And it is very important that we treat animals well in order to get good scientific results. I think the compromise then there's other reasons to test on animals. The goal of producing a drug saving us from the pandemic or so is certainly something you can argue. It is better to test on these animals than to go in humans, directly or broadly use something to find out possible risks. We will also need in the future testing on animals, simply because you want to develop veterinary medicines like a human drug has to be tested on human patients. You will need to test on animals for this purpose. And there's also things which are very difficult to to replace. If you want to study behavior, you cannot go for cell culture. There's also drugs to change behavior from all the psychotropic drugs and whatever. So there is, there is things which are difficult to to replace. This is why a consensus was developed, which is to to use as few animals as possible. So as we can, as long as we can strive for replacing them wherever we can, as long as we can say, yeah, we use less and less animals for a given purpose. We define strategies where animals don't need to be killed at every time point in my study, but I just use the same animal throughout by less invasive type of measurements, for example, and by giving them optimal treatment, reduce their suffering, not giving them painkillers. Humans also get painkillers when they are getting a medicine in a disease where. Which is painful. Doing experiments under anaesthetics and under anesthesia. So these are things which we can commit to. And this is a social compromise between the people who say for me it is ethically difficult to support animal testing. And these are these are more and more people. Yeah. I mean, in the US, it's about fifty percent now who say, no, I don't really want animal experiments to take place in Europe. It's ten percent higher. And in some areas it's even more. If you ask for cosmetics, it's seventy percent in the US who object to animal testing, eighty percent in Europe. Okay. So so society pushes, pushes us. Yeah. So we really have to very good find good justifications, um, in order to still continue doing experiments. And by committing to this what is known as the three R's of replacing if we can, reducing their number if we if we can. And by refining our experiments to make less suffering. So this is this is really the strategy, I think, where the societal compromise lies.

00:33:23 Claudia Hirtenfelder: And I think you you were pointing to some of this a bit earlier. So I obviously I object to animals being tested, but I hear that you're saying currently based on how the the models are set up and the structures are placed in order to generate knowledge. Animals have been positioned as the best model. But I think where you're coming in with some of your alternatives is you're saying to some extent, we're not really reducing the sound, kind of vague. If if scientists are not being self-critical of their work, if they're not, if they're constantly saying that animals are the best model and the only model, then they're not really propelling any sort of efforts to reduce, at the very least, to reduce, replace or refine their methods. But you're doing some of that work with your your organoids. Organoids? Is that how you say it? Organoids. That's a very fun word. Organoids. And I was reading about some of these alternatives to animal testing and it's quite exciting. So perhaps we could shift now from focusing on what's done to animals in, in these kind of biosecurity measures to talking about what the alternatives are. So could you give us a rundown of, of some of the work you're doing and some of the alternatives there are to animal testing and the ways in which you think they they perform.

00:34:36 Thomas Hartung: Let me say one thing first before we move to exactly this. Yeah. I think a key message from the discussion is animal experiments are overestimated in their value by far too many colleagues. And by giving them their rightful place, we already overcome a lot of the animal testing. And there's a lot of reasons why people don't like to open the discussion about the shortcomings of animal tests. You are challenging what you have been doing. You cannot sleep well anymore. If you see that the decisions you took on the safety of a substance is not really certain that your tools are only seventy eighty percent correct. And this is what you get as soon as you start looking into the quality of animal tests. They have a value, but they are not the tool which helps us to solve a problem definitively, which allows us to close the book and say, this substance is safe. This one is not okay. There's alternatives. Yes, because it makes no sense to lament about something. If you cannot offer an alternative and you don't want to tell society, stop developing new drugs and let grandma die. This is because this is this is what what the question is. And it's not only about grandma, it's also about children and your spouses who need who need drugs or have at the moment not, well, curable diseases. So what is there? There is, in principle, from my point of view, two disruptive technologies which have in very recent times changed the landscape of biomedical research. And these are the bioengineering of cellular systems fueled by stem cells and artificial intelligence. And the computational consequences of this. These are very recent developments. We can now create in our laboratories what we call organoids, or organ and chip systems, which are using stem cells from humans, which are not ethically problematic because we no longer use embryonic stem cells, but we use so-called induced pluripotent stem cells, which means you take some skin, you take a bit of urine or whatever from a human, and you reprogram these few cells, which you get, and you produce Material you can use like an embryonic stem cells and produce essentially any type of tissue. This development was made in two thousand and six. It got a Nobel Prize for Yamanaka already in twenty twelve because it was such an important contribution. And this opening everything, we have not really found a good terminology yet, one which is used throughout. As I said, it's fairway. It is organoids.

00:37:33 Claudia Hirtenfelder: Yeah. The organ organ on a chip. I had to look that up. I imagined, I imagined like a bag of crisps. And then you like just pulling out your organ on a chip. Someone's going to make someone's going to make that at some point. But I saw a picture of one of them. So it's kind of, again, for someone who's completely outside of this world, it looks to me kind of the organ on a chip looks a little bit like a small here. It's like a USB sized plastic ish type thing that's got these connections, these bio connections of sorts happening. I'm not doing a very good description. Perhaps you can do a bit better. What is an organ on a chip?

00:38:07 Thomas Hartung: It really comes in many flavors. Um, there's there, there's not, there's not really any standardization yet, neither of how we call it nor how we technically do it. Because you have to imagine, let's say, let's start with the cell culture was in the past. If you wanted human cell culture until about twenty years ago, you had to, with very few examples, exceptions, uh, you can get a little bit of skin, you can get blood cells, but you cannot get cells of humans except when the person is dead. Yeah. I'm working on the brain. Uh, let me ask somebody, can I have a bit of brain for my research? I will not get a lot of enthusiasm.

00:38:51 Claudia Hirtenfelder: No, I don't think so. Although that's what Covid testing felt a bit like. Like, maybe if you tried that, you'd get a bit of brain.

00:38:57 Thomas Hartung: No, no, I tell you, you don't reach the brain, but it's. But the important point is really, we opened the gates for for research on human materials with stem cell technologies. And this is really the game changer. And this then started to change the way before cell culture was really tumor cell lines, mainly. So tumor materials. But the tumor is not an organ. Otherwise you would transplant somebody in need of a liver with a liver tumor of somebody else. Yeah. We used really materials which were had a lot of compromises. They showed a bit of function still of a liver. Our liver cell lines. But they're not really doing the trick. And this has changed dramatically. It's not perfect yet, but it has changed really dramatically. Before we we cultured our cells in a petri dish like pan fried eggs, sunny side up. That's how they look. They have hardly any cell cell contacts. They're just sitting there. And you see this nucleus like the egg yolk, and they touch some two percent is cell cell contacts in a tissue. It's one hundred percent cell cell contact. They are a thousand times less dense than a tissue. Yeah. So there's really a lot of shortcomings in classical things. But stem cells really allowed us, first of all, to produce something which looks like tissue. It's a clump of cells. These were the first type of organoids. We were producing spheres of cells. Then these programs allow us to get the different cells of a, of a, of an organ together. If you take a lung, a lung has more than forty different cell types. Before we were culturing, one cell was just one cell. This is not giving you the function. And then with more and more bioengineering over the last decade, we are recreating now architecture and functionality of an organ. So suddenly you really get something which is working like like a little, little tiny organ. Our brains are just visible. Yeah. We're producing. We called in the beginning. We call them mini brains, but we changed our own wording. We call them now brain organoids because they're not brains. They don't have a lot of the functionality and architecture. But but still it is it is a more a scientific selling thing here.

00:41:15 Claudia Hirtenfelder: So it's not like it's not like you're growing, you know, like you have a box somewhere and you've grown a whole liver or a whole, it's a small device that's kind of functioning or operating and is making the the same kind of biological connections that's allowing you to test on it or to test ideas on it in a way that's moving away from animals. So you're getting these cultures or these stem cells and you're able to, if I'm understanding correctly, kind of create some of these structures in these, these chips or these organoids, and then you're testing on that. And because it's, I'm assuming somewhat cheaper to produce or, and more readily available, you don't have to keep it alive for long periods of time. It offers a whole bunch of opportunities for for testing. Exactly.

00:42:01 Thomas Hartung: You've summarized in a wonderful way. No, I mean.

00:42:04 Claudia Hirtenfelder: It's a testament. It's a testament to your explanation, I think.

00:42:07 Thomas Hartung: I didn't answer your question. So just to to I will start this with the with our own work. We were the third group to produce brain organoids. So mini brains only twenty sixteen. But we were the first to mass produce them. So what are we doing. We use such stem cells and within a three month protocol we produce tiny, tiny little balls. They are just visible. They have less neuronal cells or brain cells than a fruit fly, just about thirty zero zero zero per thing. But they have all the different cell types and they show activity. They are electrophysiologically active, so you can test tons of things on them. And they do cost us far less than a dollar a piece, so much less than any animal. And for most experiments, one of them is sufficient. And this is why many, many collaborators are using our brain organoids. And we are we are just supplying them.

00:43:02 Claudia Hirtenfelder: And you were instrumental in finding out using these. You were instrumental in finding out how Covid nineteen impacted brains. Like, I know that this was a big.

00:43:09 Thomas Hartung: That was a big hit. Yeah, because we wanted to make our contribution when the pandemic hit and when we saw that patients are showing neurological symptoms, uh, en mass, we asked, is the brain infected by the virus? There is no animal model until today to show this, but clinical data are absolutely clear. There is a certain fraction of patients which shows brain infection by Covid could be linked to some of the long term Covid symptoms we are seeing. This is bad news and using our brain organoids, we were the first to show already in May of twenty twenty, so just four months after the pandemic started to show that human neurons are infected, that the virus replicates, destroys the neuron and affects neurons. And this has been, in the first year, reproduced by ten other groups who are working the same or similar systems and who published on. Yeah, we can infect them too. And this has led really to a quite rich literature and has changed the view. We see the infection because we have to look for what are the consequences, what are the consequences of a pregnant woman where the possibly the fetus is being infected and living a life with a virus. And many of the viruses which are found in the brain are not good news. They are increasing risk for autism. They're increasing risk for Alzheimer at later stages. So virus infection of the bread of the brain is not something you would like to have. The problem of organoid research is that after a certain size, you cannot grow them any bigger because oxygen and nutrients don't reach the center, and then the whole thing is rotting from the inside. And this is why you need to find ways of perfusing these. And this is the organ on chip technologies. So you need to find ways that you can pump. In some ways, fluid like blood is flowing through your organs, that you can get nutrients and oxygen to the center of such organoids. This is why the chip on chip technology is necessary.

00:45:15 Claudia Hirtenfelder: So an organoid and an on chip are not the same. The organoid is the putting together of the cells. And the on chip is trying to facilitate the like blood flow. So putting those organoids in a chip so they're not okay. So that helps me. So they're not one and the same.

00:45:29 Thomas Hartung: No. Exactly. So it's a it is a second component which allows us then also to combine different organoids, like through the bloodstream. You can put several of these systems together to reach human on chip type of systems or patient on chip type of systems.

00:45:45 Claudia Hirtenfelder: Yeah, I see, okay. I mean, you can definitely see why that would be useful. I know in one of your presentations, you spoke about how these you can almost end up with a more personalized ability to look at disease and infection, where if I'm looking at my own cells, I might be able to get a better sense of how I would respond to specific treatments or cancer treatments, a virus. So is that is that correct?

00:46:12 Thomas Hartung: Exactly. Yeah. That's a that's that's what it's all about. To really come closer and closer to showing aspects of the complexity of an organism. Organ organ interactions are critical. Getting an immune system insight to have also the inflammatory components of a of a disease. And so many substances are metabolized by the liver and then act on another organ. So it's really about combining these elements with a better liver model and a better brain model. I have the liver brain axis. Yeah. And and you can study them. It's still a system which is reductionistic in principle, you reduce it to the components you you want to study, and it's much more accessible than an entire organism. But it is much more complex than anything we had in the past.

00:47:00 Claudia Hirtenfelder: Incredible. And it speaks more to how humans actually respond to and how different humans respond to these diseases. So it actually has the potential to move away from treating humans as a kind of singular species. But speaking more to, as you said at the beginning of the interview, different environmental pressures that are faced in different geographies, different physiological pressures that are faced by different humans, whether it be age, you know, gender, these all impact how we respond to diseases and risks. So it sounds to me like this just seems a lot more variable than what a single kind of rat who's been bred to have some differences. You know, it just sounds to me like this would be more responsive, like you say, closer to the mark of what different humans are facing as as health threats.

00:47:46 Thomas Hartung: And this is exactly the point. The, you know, we we do animal testing on inbred twins, which are typically three to four months old. Yeah. That's the type of standardized animal which have never had any disease, which get standardized food and lived their entire life in a cage with twelve hours light, twelve hours dark. So this is how meaningful the setting is for the two of us. Yeah. With weight differences, our history of diseases, all of the components which influence our life. It helps us to come to some conclusions with a relatively small numbers of animals, but it is not a very well predictor of what we would do if we have such a drug. And if you just take Covid, if you see the variety of reactions. Yeah. How many people have nothing at all with the same infection? Some others are dying, but some are dying from the lung infection. Some are dying from the brain complications and so on and so on. Yeah, we are so diverse and even something which is relatively standardized, which is the droplet infection via which we inhaled. Yeah. And this is and, and the new technologies allow us to produce our brain organoids from anybody's material. If I get a little bit of your skin, tiny, tiny, nobody sees it. I can produce brain organoids and can discuss with you whether certain drugs work on you and better than than others. Yeah. Wow. So there's really a lot.

00:49:21 Claudia Hirtenfelder: Of it really does sound revolutionary.

00:49:23 Thomas Hartung: It is. It is. And this is why we brought this community together now and organized the First World Summit. These technologies have an umbrella term used by the FDA of Microphysiological systems because they produce physiology in a microenvironment and systems. So it's really interactive, allowing interactions of different components. So we just did in New Orleans in June of this year, the First World Summit, the next one will be next year in Berlin. And I'm proud that we brought fifty two organizations behind us for the first one and created a society. But disruptive technologies. There's another thing which is happening, which is changing all of our lives every day. And this is artificial intelligence. And people have not not everybody notices the acceleration of this development because artificial intelligence has been around since nineteen fifty six when this term was coined. And we saw hype and then disappointment and so on. But real artificial intelligence, which does the trick we have since twenty twelve only. So it's very recent because then deep learning was invented, which essentially is the computer programs itself again and gets better and better changes the program. That's the deep learning in a nutshell. and since then we have seen this enormous progress. If you recall Moore's Law. Moore's law said fifty years ago, computers get better by doubling their capabilities every second year at half the price. This. This holds true for fifty years. Artificial intelligence is doubling its potency for the last ten years, every three months.

00:51:10 Claudia Hirtenfelder: When you were speaking about artificial intelligence, you said deep learning. I think when many of us hear artificial intelligence, we're maybe thinking about like iRobot and robots that are having sentient conversations with us. That's not what you're talking about here. When you. Are you meaning just the capacity of computers to to process information?

00:51:31 Thomas Hartung: Yes. And, you know, the computer is agnostic. It doesn't care what what type of data they are consuming. Yeah. The, the principle of AI Is making big sense of big data, and you can feed in essentially what you want, and the computer tries to make sense of it. So natural language processing is one of the aspects where AI is used. So understanding what people write and what people say and do. The GPT three is one of the big natural language processing programs of last year. It was trained on the entire internet. So all of the billions of pages which we have as internet, it used all of this as base information to produce one model. It's very difficult to grasp, but if you see something like this in action, ask any question. And there's models now which are producing images. You can talk and create something which even did win an art award recently, where people, I think, were not aware that the computer created the artwork and not and not the human being. So it's, it is really incredible what is happening here with a speed unprecedented and and obviously you can also use it to combine the information which we get now from other computer models, from the data from the past of all of these technologies. And you feed it in and you're blown away what these models can do. In twenty eighteen, we built built a model just based on information of the past. We used ten million chemicals and we created with these ten million chemicals, a map of the chemical universe where these ten million chemicals were placed. The two, which are similar, are very close to each other, and those which are further apart. They are different in their structures and the groups and all of the things at the time. Did this cost us five thousand dollars because we needed an Amazon Cloud server with one hundred and eighty cores for two days. And today my computer at home could do this in a few hours. Yeah. Ten million structures is pretty good. Sample of the chemical universe. One hundred and eighty thousand have been. Have been. One hundred eighty million have been synthesized and have been synthesized so far. This map allows us now to place any chemical into its environment within a millisecond. Just saying, what is the chemicals which are close to you? And then we found for six hundred thousand of these chemicals we found data properties, chemical, physical properties, this toxicity, that toxicity. And in the end, we had a model which allowed us to make predictions. And we tested this for one hundred and ninety thousand examples where we had a chemical either in the map, not in the map, where we knew that a risk assessment has said this is a dangerous property, nine different properties, and we were eighty seven percent correct in predicting them. This is the biggest validation ever for for something one hundred and ninety thousand tests. Yeah. And eighty seven percent has to be compared to the reproducibility of an animal experiment, which is only around eighty one percent, because it is not taking just the information on this one substance, it also takes into consideration. Yeah, there's another substance, which is which is very similar. But for this one we know it is carcinogenic. So better set a flag for carcinogenic. Yeah. Even if no property of the substance itself is is saying so.

00:55:11 Claudia Hirtenfelder: So if I just want to make sure I understand again, you're in a in a world, I really struggle sometimes to open my email. So this is like mind bending for me now. So you've got a compute, a computational model where you're feeding data into it. This is what a particular hazard is. This is how this particular hazard or chemical response to this environment or these these circumstances, and you can insert a new condition into that and see what happens.

00:55:41 Thomas Hartung: So we can take any substance, even one which the chemist only wants to synthesize. Now we can take this structure and say, where is it in our map? And then it will inform you. This is the probability of of being, let's say, a skin irritant, which you don't want for this use. And then the chemist can decide ninety percent probability. It is irritating, only produces costs. I don't even synthesize it.

00:56:09 Claudia Hirtenfelder: I see. So there could be a new drug or a new idea, and you insert it into this. And based on all of the data that you've collected, it would position it closer or further to other drugs because we've got so many drugs already. And then you would have a higher understanding of what its impacts and effects could be.

00:56:28 Thomas Hartung: Exactly. And at the moment we are expanding this to many more properties. And It is incredible what you can fit in and and other developments of AI help us. So we are close to computers being able to read the scientific papers of the past and take out the essence. They're almost as good as a PhD student in reading a scientific paper, but my PhD students read at best one paper per week because they do mostly experiments. A computer can read millions of papers in a day.

00:56:59 Claudia Hirtenfelder: Incredible.

00:57:01 Thomas Hartung: The art is to produce the right experiments and report them in a proper way. But they are becoming extremely important tools to help you understand. We have the human in the loop. It is the. But we get on the silver platter the information which is out there. And this is the. This is the disruptive part of this technology that we can be much better informed in our decisions, whether it's a decision to run an experiment, to synthesize a certain substance, to develop something further, we can inform this.

00:57:32 Claudia Hirtenfelder: And we're not producing redundant knowledge where we're just testing the same experiment a bazillion times. When you've you've got proof and evidence here that it's been done. It's been done enough. And, and also that you're not just feeling your way in the dark, you're not just like, oh, could this happen? Or could this happen? You're, you're pinpointing a closer idea of where there might be issues.

00:57:53 Thomas Hartung: You can put your money on the right horse. And it's also helping you just to retrieve the data by amassing all of this information. The easiest question is, do I have information on this already? And then the second information is do I can I predict this reasonably from all of the information I have? That's it.

00:58:12 Claudia Hirtenfelder: Awesome. So you've got a quote for us.

00:58:15 Thomas Hartung: Yeah. I mean, one quote, which I usually used to end my presentations. So most of my presentations have the same slide at the end. It's, uh, not from a scientist, but from an economist, John Maynard Keynes, known to many of you. And he said the problem lies not with the new ideas, but in escaping from the old ones. And I think this is really the problem. It's not new ideas. I think I've told you AI organoids, all of this, there's tons of new ideas. But the problem is to escape from the old concepts and really give the new things the right place. And this is my main message to you.

00:58:53 Claudia Hirtenfelder: That's a fantastic message. And thank you so much for the work you do, I really do. I'm excited by these organoids and these organ chips and these big data. I don't fully understand things, but just based on what you're saying here, it sounds like there's a lot of there's a lot here to help us move away from animal testing and to think about biosecurity in ways that are probably more effective and efficient for us as humans, and probably nicer for animals if they're not being tested on as much. So thank you for the work you're doing, and I'm really excited to see where it goes. And if you like, perhaps you could just tell us quickly where folks can get in touch with you.

00:59:31 Thomas Hartung: The center for Animal Testing at Johns Hopkins exists for forty one years already. It was the first institution of this kind in the US and is still certainly the largest. We are trying to promote alternatives to animal testing. It is easy to find us. C a t at Johns Hopkins. There's a newsletter to subscribe to so to stay tuned. There's. For each and every level of education, there's opportunities to engage and to learn and to get get in contact with us.

01:00:01 Claudia Hirtenfelder: Wonderful. Well, thank you so much for your time. Hi, Mandy. Welcome back to the Animal Highlight.

01:00:13 Speaker 4: Hi, Claudia.

01:00:14 Claudia Hirtenfelder: So this week we were talking to. I spoke to Thomas Harting about animal testing and it was a really good episode. So I'm interested to hear who who you've got for us in the animal highlight.

01:00:23 Speaker 4: Well, it's probably unsurprising that today I'm actually going to revisit rats who were highlighted, I think, back in season three.

01:00:31 Claudia Hirtenfelder: Yeah, I think I did. It was one of my first like, the highlights were still quite new. And I think I remember I read an excerpt from Dawn Des Bella's book about rats in the city, and she just had this beautiful kind of excerpts about how they, how they navigate the city in like the early morning or the late night to find food. And it was really quite beautiful. But anyway. Yeah. Yes, rats are always welcome.

01:00:53 Speaker 4: And just to say, I love that excerpt, it was so poetic and evocative. I really loved that highlight. I'm gonna sort of, I guess, add to it today. And before I get going, for those who are interested, as always, I've drawn a lot from the books Pleasurable Kingdom by Jonathan Balcombe, a frequent. He makes frequent appearances in my references The Emotional Lives of Animals by Mark Beckhoff, rat by Jonathan Burtt, and Lisa Fawcett's chapter in Animal Subjects two point oh. So I want to revisit rats today because as this season's guests have already pointed out, they're deeply impacted by dominant biosecurity discourses and practices. These dominant biosecurity narratives simultaneously regard rats as these disease infested vermin and as sacrifices for scientific and medical advancement. They're strongly associated with disease, most notably the bubonic plague. And they've long been targeted by eradication campaigns in the name of public health. So, for example, in Alberta, Canada, which is where I was born and grew up, they've achieved, quote, rat free status through anti-rat campaigns and legislation that ultimately call for the prevention, surveillance and killing of rats. And at the same time, rats are among the most exploited creatures in laboratories. It's impossible to know exact numbers. But just to give you a sense of the sheer magnitude of exploitation, a twenty twenty one article by Larry Carbone estimates that in the United States, one hundred and eleven point five million rats and mice were used in animal experimentation between twenty seventeen and twenty eighteen. And of these rats and mice, Carbone estimates that forty four point five million underwent potentially painful experiments. And these staggering numbers, they're more than just statistics. They represent thinking, feeling complex individuals who are profoundly impacted by experimentation. So in laboratories, rats can be forced to endure distressing and painful experiments. For example, in twenty thirteen, rats at Queen's University in Canada, which is the school that I attend was subjected to two months of solitary confinement, psychotic drugs and food restrictions, and recently Queen Mary University in England conducted sepsis experiments, which are not uncommon and under anesthesia. Rats have their intestines punctured to create fecal and bacterial leaks, and then, upon regaining consciousness, these rats experience intense pain, multiple organ failure and hypothermia. It's, er, it's disgusting and heartbreaking. And even even if these rats weren't experimented on, the laboratory environment is woefully insufficient to meet the really dynamic needs. According to the American Anti-Vivisection Society, lab rats are often housed in shoebox sized plastic containers that slide onto these vertical stacking racks. And in these barren, small and largely isolated environments, rats suffer. Marc Bekoff notes that it isn't uncommon for laboratory rats to begin sleeping excessively, pacing repeatedly, chasing their own tails, biting themselves or behaving aggressively and fearfully. Laboratory environments are so at odds with rats intense social sociality. Rats thrive with companionship and community. For example, wild brown or Norway rats who. There. The rats that. Who. Albino rats are actually mutated and selectively bred from the albino lab. Rats. These brown rats live in large colonies that can house as many as one hundred and fifty individuals. Jonathan Balcombe discusses how rats take great pleasure in social touch. Many seek out being petted and tickled by familiar humans or other rats and let out these really joyful chirps and even laughter in response. One of my absolute all time favorite things about rats is what is known as bruxing and boggling. So Bruxing refers to when a rat grinds their front incisors together, and boggling as a side effect of this, where rat's eyes bulge in and out of their sockets and in the right context. So, for example, imagine a rat is snuggling with their best buddy after a tasty meal. This can be a sign of them feeling really content and happy. And it is so heart melting to watch. Rats can also be really empathetic and helpful. In a series of unethical experiments, rats were found to act to free their trapped and distressed companions, and also to share chocolate chips with each other when they didn't have to. Wild and domesticated rats will often help each other groom hard to reach Places. They'll sound alarm calls to warn other rats of nearby danger. There's also arguably a cultural component to rat sociality. So in an article by Schweinfurth, it's outlined how rats show local differences in their hunting techniques, where some, for example, will raid birds nests while others might fish for small fish. Others still will dive to collect mussels. So just incredible cultural worlds that we don't even really give any attention to.

01:06:53 Claudia Hirtenfelder: I mean, sorry to interrupt there, but I think that's so remarkable because we, you know, a couple of times I think I've mentioned at least to friends and certainly on the podcast about the how dynamic and beautiful whales are because they have these different cultural dynamics, right? They speak different languages. Killer whales have different strategies of hunting in the wild, depending on which pod you're part of. And everyone's like, wow. Yeah, that's amazing because I think we all most of us agree, that whales are just remarkable, right? They're charismatic. But then this idea that rats also have these kinds of localized cultural practices. And why should that be surprising? They're mammals, and that's really native rats that are muscle diving. And yeah, quite remarkable.

01:07:37 Speaker 4: No, it's totally remarkable and I think humbling to sort of realize just how insufficient it is to say that they're social like they have. Not only are they social, but there are textures and layers to their like, to their cultural fabrics that we don't even know about. But yeah, in addition to all of this and in addition to community, rats need play. They need enrichment, they need variety, all things which are denied to lab rats. And of course, rats are individuals, so what kinds of play and enrichment they enjoy will vary widely depending on their different personalities and contexts. Jonathan Balcombe discusses how the three rats who he adopted, Veronica, Rachel and Lucy each have different play preferences. So, for example, Veronica takes great pleasure in running on an exercise wheel, while Rachel really prefers to play hide and go seek under this old curtain that she loves. Meanwhile, Lucy views the running wheel not as a device for play, but rather as the perfect toilet. All three of them love peanut butter cookies, though they experience eating this treat in their own unique ways. And Veronica, Rachel, and Lucy get bored of eating the same foods. They'll eagerly eat peas or banana slices if those peas and banana slices break up the monotony of having the same repeated meal over the past several days. And then can you imagine how kind of distasteful and monotonous it might be to eat these same formulated pellets in a lab every day?

01:09:30 Claudia Hirtenfelder: That's a really good point, because we often think of rats as a, you know, we realize that they've been bred to kind of be standardized. But I think what you're pointing to here is also just the standardization of their lives, right? The standardization of what they can eat, where they can move all in service of an experiment as well, because these are all these are all factors or what's the word like science. They're all variables, right? That need to be accounted for.

01:09:54 Speaker 4: And variability is one of the pleasures of life. It certainly can have stressful aspects to it sometimes, but it can also be incredibly enriching. And yeah, I can't imagine eating the same meal, even a meal I love every day for the rest of my life. In closing, I just want to reiterate by paying attention to rats, it becomes really clear that they're profoundly harmed when they're denied opportunities to be social, to build community, to engage in their cultures, to relish and touching and being touched, to play, to explore, to enjoy variety. If you're just as delighted by these creatures as I am, and if you think that you can meet their needs, you might want to consider adopting some. So animal rescues are always looking for humans to provide caring and enriching homes for rescued rats. So, for example, at least at the time of this recording, Lady Bird Sanctuary in Hamilton, Ontario, Canada, is looking for someone to adopt Addy and Kendra, who are described as very active and happy rats. Despite enduring a lot of human neglect and harsh conditions prior to rescue or the Liberty Foundation in Australia will adopt out former research animals, including rats.

01:11:17 Claudia Hirtenfelder: Thank you so much. And yeah, I've heard rats are fantastic pets who, like you've said, love to cattle, enjoy to play. I've met a couple of people who kind of were foster parents and have now fallen in love and converted entire like rooms of their house to like rat oases. So no, thank you so much. And thank you for pointing out. So often when we talk about animal testing, I think we focus on. And we think of these really extreme experiments that are carried out on on rats and similarly other animals in these experiments. But there is something to be said about the kind of monotony, mundane, sterile environments that even if they weren't violently intervened on, you know, corporately or with their bodies, there's something to be said about being imprisoned and caged in that way that really is deficient of the ways in which they experience their lives. So thank you. Thank you so much for another incredible highlight. Thank you so much to Thomas for being an engaging guest, for dealing with all of my questions where I didn't quite understand what was going on. To animals and philosophy. Politics. Law and ethics. Apple for sponsoring this podcast. To the Biosecurity and Urban Governance Research Collective for sponsoring this season. To Gordon Clark for the bad music. Jeremy John for the logo. To Christian Manes for his editing work. And Amanda Benton Wahlberg for all of the amazing work that she's doing with the animal highlights. This is the animal. Turn with me, Claudia Guttenfelder.

01:13:00 Speaker 1: For more Great Irish podcasts, visit iReport dot com. That's I r o a r p o d dot com.