Digestion Rumiantes

I'm Aina Garten, welcome to Be My Guest, the podcast. One of the best gifts you can give friends is spending time together, but what's even better than that? Cooking with them. Unbe My Guest, the podcast. New friends and old stop on my barn for some conversation and great cooking. We talk about food, life, and everything in between. Listen to Be My Guest, the podcast with me, Aina Garten, and Join us, wherever you get your podcasts. Hey, team. Sam here with a quick note before we get into the episode. You know, sharing and reviewing Curiosity Weekly really helps us keep everything running smoothly behind the scenes. So tell us what you think. Send in some science questions with a review section on your favorite podcast platform. We would love to hear from you. All right, now onto the episode. Animal testing. If the thought of it brings up big feelings, you're not alone. It's one topic that's been so hotly debated for a really long time. How do we balance safety and innovation with animal welfare? To help answer that difficult question, we'll chat with veterinarian and bioethicist Dr. Lisa Moses. Before we get into that, there's some exciting news for our friends suffering from sleep apnea. And later, we'll look into a study that may have found a new path for diabetes treatment. Welcome to Curiosity Weekly. My name's Dr. Samantha Amin. Let's get into it. Roughly 1.4 billion people globally suffer from obstructive sleep apnea. Based on that number, chances are that you probably know someone with the condition. My pops just started on a CPAP machine and it's been amazing for him. But it takes an adjustment and it's not the most convenient. So I'm really excited to learn that there are new treatment discoveries on the horizon that could mean big changes for our sleep-deprived friends and loved ones. Researchers at the University of Goldenberg in Sweden just published Phase 2 of a clinical trial where they found that a drug cults a theame reduced breathing interruptions and people with moderate to severe sleep apnea. Obstructive sleep apnea is a sleep-related breathing disorder where the throat muscles relax a bit too much while you're asleep, which blocks the airway. This causes breathing pauses, loud snoring, and a choking feeling. People with sleep apnea often wake up throughout the night to regain control of their breathing. While that may not seem like such a big deal in the short term, small sleep disruptions over time can increase the risk of a ton of different health issues, like heart disease, high blood pressure, and even stroke. Plus, there's this general feeling of exhaustion from waking up so often in the night. But CPAP machines, which stands for continuous, positive airway pressure, CPAP, do just that. Manually keep the airways open while someone's asleep. Though the CPAP machine is helpful, it's a bit of a bulky setup, which ironically makes it even more difficult for some people to sleep. Even when people agree to start using the machine, about one-third of them stop over time. Sultiame is the first pharmacological option developed that's been shown to help keep the airway open during sleep. In the trial, participants were either given a placebo or different doses of sultiame. The higher the dose, the more improvements they saw in oxygen levels during sleep, breathing interruptions throughout the night, and daytime sleepiness. The drug works by boosting the upper airway muscle activity, so it's less likely to collapse, and that stabilizes the body's control of breathing throughout the night. The medication inhibits an enzyme called carbonic and hydrates, which causes the body to go into state of mild metabolic acidosis. That just means that our blood pH goes a little at a whack. This alerts the brain to increase our respiratory drive to get more oxygen and balance out the pH, keeping it more vigilant to disruptions while we're asleep, and keeping the airway muscle flex so it doesn't collapse. The brain has to work to keep blood pH at regular levels because if things get too acidic or too basic, then the body can experience some serious repercussions like organ damage or metabolic failure. The drug is already available for epilepsy, so we already have a ton of safety data on it. This was a phase two dosing trial to figure out the effective dose for sleep apnea. The next steps before it hits any shelves would typically be a phase three trial in more people. Whether we like it or not, animal testing has played an important role in modern science. From your cleaning supplies to makeup to pesticides, a ton of products that make up our everyday lives have some sort of connection to animal testing for safety purposes. And that's not even getting into the research on diseases, genetics, and medical treatments that often require testing on animals. It's been a hotly debated topic for a while, but with the rise of lab-grown tissues and tech-based alternative research methods, there are new layers to add to the conversation. Here to speak with me about the past, present, and future of animal testing is Dr. Lisa Moses. Dr. Moses is a veterinarian and bioethicist at the Center for Bioethics at Harvard Medical School. Thank you so much for joining me, Lisa. Welcome to the show. Oh, thanks for having me. I really love to talk about the subject with people. Can you explain for our listeners just how common animal testing is in modern science and why it's necessary? Sure. So animal testing is really kind of the bedrock of modern biomedical science, in particular and biological science. And I think people might be quite surprised to know how much information we have gotten out of doing tests on animals over the last, oh, wow, hundreds and hundreds of years. And can you give us a sense like the types of questions that necessitate an animal versus the alternative, let's say, being a cell line or something more theoretical? Well, you know, that's a question that is rapidly changing. If you had asked me that question 20 years ago, I would give you a very different answer. We have a lot of new stuff now that is changing the answer to that question. But there are still things that we know we are far away from being able to not use animals for. And those are things that generally require the use of a integrated body. So for example, an immune system that works with your kidneys. So animal testing, it's very closely regulated. Researchers need to propose any experiments using animals to an animal welfare committee haven't approved. They have to justify whites necessary beforehand. But from a biopathetic perspective, what are the major things welfare committees are looking for and how much can we mitigate concerns through that review process? Like what's the behind the curtain of that? Sure. So if you don't mind, I want to back up just a little bit. And I want to make sure that everybody understands that there's a difference between thinking about the ethics of using animals as research subjects and the regulation of using animals as research subjects. Yes. There are lots and lots of regulations. I've covered the way we decide how exactly we use animals and how animals are cared for in the research process. And the majority of what those committees that you mentioned do is talk about whether or not the regulations are being followed. That's really different from what an ethicist thinks about, talks about, looks at. What an ethicist is really concerned about is not just the regulatory part of it, but the part about what's right, what's wrong, what are our values, what are our values, what are other people's values about the subject and how do we honor other people's values about that subject. So it's a different kind of a thing to look at. That's a great point. So can you tell us more perhaps than on the ethics side, some examples of things that you might be considering that maybe our great areas on the regulatory or just things that you think are interesting ethically? I teach lots of different groups of students about this subject and nearly everybody has a pretty strong feeling about it. But what I find often is that people really know very, very little about the way animal research actually happens. The uses of animals in research are so broad and huge that it is very hard to say we shouldn't do it at all. We should do it without any concern or something on those lines. We really need to think about which uses do we think are justifiable ones, which ones might we decide are not justifiable from a moral standpoint and why. One thing I think that people think a lot about is cosmetic testing. And in lots of places in the world, cosmetic testing on animals has already been banned. And truly in most cases, it's not done very much anymore. And that might be an area where people would say you know what? I think I feel okay about us saying we should not test cosmetics on animals for human safety. On the other hand, for example, I work a lot or a little bit in xenotransplantation research where we are doing research to use tissues or organs from one species of animals to transplant into another. Most of the time these days we are talking about transplanting kidneys and hearts from pigs into human beings. And in that case, people who are desperately waiting for a kidney transplant might feel really, really different about how important it is. important or necessary it is to do that kind of research. Now it used to be a requirement in many countries to test on animals in preclinical studies. So before something went to a clinical trial, phase one, two, three, etc., they would have to do a preclinical study in animals. Right now we're seeing some shifts there. So regulators around the world are starting to make pledges to try and develop alternative methods that we don't need to rely on animal testing for preclinicals. I'd love to hear your perspective on that. But that's that you have there. And then let's talk about what some of those new approaches are. Sure. I think COVID was a time that really showed us what some of the new approach methodologies could do, especially when we're looking at specific toxicity of therapeutic studies or when we are looking at efficacy studies. It was really exciting that we were able, for example, to use some organ on a chip technology to very accurately predict whether or not certain medications to treat some of the impacts of COVID would work or not in people and do it fast. And bypass a lot of the multi-stage, many-year, very expensive kind of system that we have in place for testing those kinds of therapeutic. So I think it's really exciting that we have speeded this up. You know, I think those of us who have been thinking about this for a long time are of two minds. In one hand, we've been talking about alternatives to animal research forever almost. And people have been doing research on the non-animal models or the new approach methodologies, however you want to say it, for a long, long time, you know, 50 years or more. So it's great to see that there is some new momentum and maybe, maybe, maybe, there will be more money because a lot of what's happened is that we didn't actually devote very much intellectual power or money to those approaches for a long time. And there's a lot more interest now. There are still some big obstacles that would actually be fairly easy to change that we don't yet seem willing to change. So that part is a little discouraging. Like what? Are you able to sure things like the way people get grants? You know, we have a very well entrenched system of which animal models are used for which kinds of research. And we really haven't changed that. So people have to, you know, there's a lot of talk about validation of the new model systems. And that definitely needs to happen because we need to be able to say that there at least is good for particular approaches as the old ones. But on the other hand, there's a lot of things that we never validated that we've used forever. So there's that. The other thing that we have to think about is that right now it's actually cheaper to use animals in many, many cases. And that is going to be a big obstacle to overcome. But in terms of replacing the use of animal models, I think the one that is already showing the most benefit is the computational one. That's fair. And how do you see it minimizing animal use? Can you walk us through for people who are less familiar? So I am very fortunate to work with folks at the Broad Institute of MIT and Harvard and the Comparative Genomics Lab. So what they do is they are sequencing complete genomes of a lot of different animals that we don't have complete genomes for. And a big reason why they do that is because we know that certain species of animals have adaptations that would be hugely beneficial to human health. Like for example, fruit bats walk around and live their lives with a blood glucose level in the 6 to 800 range, which for human being is essentially lethal. You know, that's what uncontrolled diabetes is. So if we could figure out how fruit bats are able to live and be healthy with that kind of a blood sugar level, we could learn a lot. And we're doing that through computational modeling. Do you see like any perhaps like risks or rewards for phasing out animal testing or decreasing it? People might not be thinking about like what are we risk losing or gaining I guess? Well, you know, one of the big arguments about why we can't get rid of animal research is the entire endeavor of science is sort of unknown. We don't know what we're going to find when we start doing science, right? So I think there is a real fear that we will lose the opportunity to learn things that we might have that is we have an opportunity to learn things we never would have learned to. Yeah, true. What kind of responses do you see from the scientific community when it comes to this? They're all over the place. You know, I think there is a lot of fear because we have been doing science in a certain kind of way for a long time. We have very, as you know, very entrenched systems of publication of education of promotion, tenure, all kinds of things that are part of the way science happens and the culture of science that are built on animal research. So I think the unknown of what it would look like without that is very scary. I get that. But I also think that there are a lot of people who have struggled with their own feelings and their own moral distress surrounding the use of animals in their work and are very much welcoming the potential for changing that. Because there has been a lot of backlash over the treatment of animals and scientific settings over the years, it's caused this enthusiasm we're talking about to embrace alternative methods. It's also forced, I don't want to say secrecy, but there's a lot of hesitancy talking about having done animal research even in the media. I know the way that we talk about it has to be really particular. You could say there's, we've had to kind of be more protective about it. And there's a transparency thing there. I think it's no secret that there is some degree of fear and paranoia even. There is a lot of a culture of secrecy. But one thing that has been fascinating to me as an ethicist in this work in the last 15, 20 years is there's a whole faction of people who do this work who are calling for essentially radical transparency so that people who fund this research know what actually happens, know the way the animals are cared for and what happens to them and that we talk openly about this work because essentially it is done for public service. Yeah, that's a great point. There are vet techs who are keeping an eye on the animals every single day, intending to them, which is, it's important work. I think them in my thesis acknowledgments because the question for you, did you think the animals? A lot more people are doing that. Yeah, good call. I don't think I did. That's a good point. You know, I don't, I don't mean to call you out on the spot, but I, but I think people are doing more and more of that. There are more monuments to the animals used in research. But again, they're generally hidden away. The medical students that I teach, I work primarily with physicians, of course, at the medical school. Lots of them, even though they do research, really don't know very much about the animals that they do research on. And many, many people don't know that there are veterinarians who their entire job and their actual specialty is to take care of lab animals. I think that's fascinating that physicians don't realize that there are veterinarians who are essentially mice veterinarians. I want to hear from you as an ethicist, a veterinarian, in your ideal world, how does the scientific community move forward in this balancing act between scientific innovation and animal welfare? How do these two things coexist? What do you want to see it looking like? Well, I think the first thing I want to see is the easy stuff to fix gets fixed. You know, there's so many millions of animals that are involved in the pursuit of research, millions, literally, globally, that the very first thing I would want to happen is that we change some of the stuff that would be easy to change. Like, for example, we don't actually count the number of animals that we use. It's pretty hard. I mean, we're a data-driven universe. We don't have data. So we don't even know how many animals we use. We don't know what species, we don't know what we're doing to them. That is not entirely true in other countries, and there's no global report. So, could we at least start with knowing how many animals lives are part of this? That would be great. I'd love that to happen today. Fascinating. Dr. Liza Moses is a veterinarian biopathasist at the Center for Biopathics at Harvard Medical School. Thank you so much for joining us on the show and speaking openly about this really important topic in science. Thank you so much for asking. We need to talk more about it. Scientists may have cracked the longstanding medical mystery of why people who live at high altitudes are less likely to get diabetes. It turns out, the red blood cells act like glucose sponges in low oxygen conditions, which lowers blood sugar and may help protect against diabetes. Red blood cells transfer oxygen from the lungs to the rest of our tissues. Since there's naturally less oxygen in high altitudes communities, people who live there usually have more red blood cells than people who live closer to sea level. Diabetes happens when blood sugar or glucose is too high. So, a team, led by researchers from the Gladstone Institute, did some experiments on mice. Thank you to the mice for your assistance. They wanted to understand more about the relationship between their blood, glucose, and low oxygen environments. They found that when they housed the mice in a low oxygen environment and fed them sugar, the sugar all but disappeared from their bloodstream. They also saw a near doubling in red blood cell count. The researchers tested whether red blood cells were using up that glucose. First, they removed red blood cells from mice that had been living in low oxygen conditions. The mice's blood sugar bounced back up. Then, they transfused red blood cells from donor mice at either low or high oxygen into mice living at normal oxygen levels. And then, the blood sugar dropped. In both of these experiments, more red blood cells meant more glucose was taken up and then lowered the blood sugar. But beyond that, the humble red blood cell, previously thought of as a passive oxygen carrier, also reacts differently to glucose when the body is experiencing low oxygen. Not only are more red blood cells produced in low oxygen, but the new cells also act as a sort of glucose sponge, taking it in faster and using it to generate a molecule that helps release more oxygen where it's needed. In tissues around the body. The researchers tested a drug they recently developed that mimics low oxygen exposure and found that that medication completely reversed high blood sugar in mice with diet induced diabetes. Now, we're still far from a cure, but this study opens a fresh avenue for treatments. For Warner Bros. Discovery, Curiosity Weekly is produced by the team at Wheelhouse DNA. The senior producer and editorial correspondent is. Teresa Carey. Our producer is. Kiaranoni. Our audio engineer is. Nick Currismi. And head of production for Wheelhouse DNA is. Cassie Berman. And I'm Dr. Samantha Yween. Thanks for listening.